Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator capable of promoting wound healing and regenerative functions of mesenchymal stem cells (MSCs), en-dothelial cells, and macrophages. The third-degree (3o) burn healing and regenerative functions of MSCs are also enhanced by ACgel1, an arginine and chitosan-based protein-mimic hybrid hy-drogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporates PreM1 and MVFs into ACgel1 via optimal design and fabrication is capable of delivering PreM1 to 3o burn wounds at least up to 7 days post-burn (dpb), and of scaffolding and delivering MVFs, which promoted 3o burn the healing in mice, including vascularization and collagen formation. The re-epithelization and closure of 3o burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s) while PreM1-MVFs-ACgel1 was most effective. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of the 3o burns. These PreM1- and/or MVFs- functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapies for overcoming the drawbacks of current skin grafting or substituting for treating severe deep burns.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

The effective integration of aerial remote sensing data and ground multi-source data has always been one of the difficulties of quantitative remote sensing. A new monitoring mode is designed which installs the hyperspectral imager on the UAV and places a buoy spectrometer on the river. Water samples are collected simultaneously to obtain in situ assay data of total phosphorus, total nitrogen, COD, turbidity and chlorophyll during data collection. The cross correlogram spectral matching (CCSM) algorithm is used to match the data of the buoy spectrometer with the UAV spectral data to reduce the UAV data noise significantly. An absorption characteristics recognition algorithm (ACR) is designed to realize a new method for comparing UAV data with laboratory data. This method takes into account the spectral characteristics and the correlation characteristics of test data synchronously. It is concluded that the most accurate water quality parameters can be calculated by using the regression method under five scales after the regression tests of multiple linear regression method (MLR), support vector machine method (SVM) and neural network (NN) method. This new working mode of integrating spectral imager data with point spectrometer data will become a trend in water quality monitoring.

The inclusion of spent hemp biomass (SHB), an extracted byproduct from industrial cannabidiol (CBD) production, in the diets of dairy cows and lambs appear to be safe with minor effects on the metabolism, including a decrease of circulating cholesterol and increase bilirubinemia, both associated with liver metabolism. Those effects could be consequence of the presence of cannabinoids, particularly Δ9-tetrahydrocannabinol (THC) and CBD in the SHB. This study aimed to study the transcriptional profile of the liver of dairy cows and lambs fed SHB. Dairy cows received SHB or alfalfa pellet for four weeks of intervention (IP) and four weeks of withdrawal periods (WP). Finishing lambs were fed a control diet (CON), 10% (LH2) or 20% (HH2) SHB for 2 months or 1 month followed by 1-month SHB withdrawal (LH1 and HH1, respectively). RNA sequencing was performed, and the mRNA was annotated using the latest reference genomes. The RNAseq data were filtered, normalized for library size and composition, and statistically analyzed by DESeq2. The bioinformatic analysis was performed by using DAVID, Gene Set Enrichment (GSE) analysis, and the Dynamic Impact Approach. Using a 0.2 FDR cut-off, we identified only ≤24 differentially expressed genes (DEG) in the liver by feeding SHB in dairy cows and a larger number of DEG in lambs (from 71 in HH1 vs. CON to 552 in LH1 vs. CON). The KEGG analysis demonstrated that feeding SHB in dairy cows and lambs had relatively minor to moderate metabolic alterations in dairy cows and lambs mainly associated with amino acids and lipid metabolism whereas cholesterol synthesis was overall activated in lambs. GSE analysis identified activation of PPAR signaling pathway only in dairy cows. We found an opposite effect on activation of metabolism of drug and xenobiotics by cytochrome P450 enzymes in dairy cows and lambs receiving less SHB but an inhibition in HH2 lambs. Immune system-related pathways were inhibited by feeding SHB in lambs, but the impact was minor. Cumulatively, inclusion of SHB containing cannabinoids in dairy and lambs demonstrate very little effects on the alteration of transcriptomic profile of the liver.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Type 1 diabetes (T1D) is associated with hyperglycaemia-induced hypoxia and inflammation. The study assessed the effects of a single high-intensity interval exercise (HIIE) on glycaemia (BG) and serum level of pro-inflammatory cytokines and an essential mediator of adaptive response to hypoxia in T1D patients. The macronutrients intake was also evaluated. Nine patients suffering from T1D for about 12 years and nine healthy individuals (CG) were enrolled and completed one session of HIIE at the intensity of 120% lactate threshold and duration of 4 x 5 min intermittent with 5 min rest after each bout of exercise. Capillary and venous blood was withdrawn at rest, immediately after and at the 24 h post-HIIE for analysis of BG, hypoxia-inducible factor alpha (HIF-1α), tumour necrosis factor alpha (TNF-α) and vascular-endothelial growth factor (VEGF). Pre-exercise BG was significantly higher in the T1D compared to the CG (p = 0.043). HIIE led to a significant decline in T1D patients’ BG (p = 0.027) and to a tendency for a lower BG at 24-h post-HIIE vs pre-HIIE. HIF-1α was significantly elevated in the T1D compared to CG and there was a trend for HIF-1α to decline, and VEGF, TNF-α to increase in response to HIIE in the T1D group. Both groups consumed higher and lower than recommended amounts of protein and fat, respectively. In T1D group, a tendency for a higher digestible carbohydrate intake and more frequent hyperglycaemic episodes on the day after HIIE were observed. HIIE was effective in reducing T1D patients’ glycaemia and improving the short-term glycaemic control. HIIE has the potential to improve adaptive response to hypoxia by elevating the serum level of VEGF. Patients’ diet and level of physical activity should be screened on a regular basis, and they should be educated on the glycaemic effects of digestible carbohydrates.

BACKGROUND Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. METHODS A total of 394 samples collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing-Bablok regression and Bland-Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. RESULTS The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Method comparison yielded an area under the curve of 0.976, with a standard error of 0.009. Passing-Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. Regarding internal validation, calculated cholesterol with our regression line did not differ from serum cholesterol analysis, while significant differences were observed in calculated cholesterol levels using the external formula. CONCLUSIONS Total cholesterol analysis in dot blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection.

In this paper, carbon nanotubes modified screen-printed electrode (CNTs/SPE) was prepared and the CNTs/SPE was employed for the electrochemical determination of antioxidant substance Chlorogenic acids (CGAs). A pair of well-defined redox peak of CGA was observed at the CNTs/SPE in 0.10 mol∙L^-1 acetic acid-sodium acetate buffer (pH 6.2) and electrode process is adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method for the determination of CGA were proposed based on the CNTs/SPE. Under the optimal conditions, the proposed method exhibited linear ranges from 4.73×10^-7 to 4.45×10^-5 mol∙L^-1, the linear regression equation was Ipa(µA) = 4.1993 C (mol∙L^-1)+1.1039 (r = 0.9976) and the detection limit for CGA could reach 3.25×10^-6 mol∙L^-1. The recovery of matrine was 94.74~106.65% (RSD = 2.92%) in coffe beans. The proposed method is quick, sensitive, reliable, and can be used for the determination of CGA.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.

Breast cancer in patients with prior breast augmentation poses unique challenges for detection, diagnosis, and management. Mastectomy rates are increasing, and patients with prior augmen-tation often have a lower body mass index, making autologous techniques unsuitable. This study aims to assess the best reconstructive option in patients with a history of subglandular or dual plane breast augmentation. Materials and methods: a prospective analysis was conducted on pa-tients who underwent breast reconstruction after mastectomy. Patients with subglandular or dual plane breast augmentation were included. Patients were divided into submuscular breast recon-struction (group 2) or prepectoral breast reconstruction (group 1) groups. Demographic and sur-gical data were collected. Results: A total of 47 patients were included, with 23 in Group 1 and 24 in the Group 2. Complications occurred in 11 patients (23.4%), with significant differences be-tween groups. The most common complication was seroma formation. Implant loss occurred in 4.3% of cases in the Group 1, while no implant loss was observed in the Group 2. Patient-reported satisfaction scores were similar between groups at 12 months postoperatively. Conclusions: sub-pectoral breast reconstruction with a tissue expander seems a safer and effective technique for pa-tients with prior breast augmentation. It resulted in fewer complications. This approach should be considered as an option for breast reconstruction after mastectomy in this cohort of patients.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression; notably, decreased expression of Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. It demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress play also role in frailty (frail) and metabolic syndrome (MetS). Methods: 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n=19), NonMetS-frail (n=20), MetS-Nonfrail (n=17), and MetS-frail (n=10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggests that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome.

Microglial cells are highly specialized central nervous system (CNS) cells that can promote the inflammation and neurodegeneration seen in Multiple Sclerosis (MS). MS is a neurodegenerative autoimmune disease characterized by inflammation, demyelination, and axonal degeneration. In MS patients, demyelination is associated with activated microglia. Endothelin-1 (ET-1) is a potent vasoconstrictor that induces severe and prolonged cerebral vasoconstriction and inflammation. However, the mechanism of how ET-1 activates a proinflammatory response in the CNS is unknown. To investigate ET-1’s role in microglia activation, HMC3 cells were treated with ET-1 in the presence or absence of endothelin receptor B antagonist, BQ788. TNFα and IL-6 levels were measured using ELISA. Nitric Oxide (NO) production was measured using Griess Reagent. Reactive oxygen species (ROS) production was measured using the MUSE Oxidative Stress kit. ET-1 increases TNFα levels by 56% (p= 0.0003) and IL-6 levels by 86% (p= 0.0111) in HMC3 cells, and it was decreased to basal levels in the presence of BQ788. NO and ROS production is induced by ET-1 (p<0.05), and treatment with BQ788 was able to decrease them. ET-1 increases STAT-1 activation by 3.5 folds compared to control (p <0.0001) in microglia cells. Moreover, to study ET-1 levels in MS, we used C57BL/6 mice brains with or without induced experimental autoimmune encephalomyelitis (EAE). The brain ET-1 levels were measured by qPCR and ELISA. We found that the ET-1 gene and protein were upregulated by 1.5 folds (p= 0.0199) in EAE mice compared to the control. These data suggest that in vitro administration of ET-1-activated microglia significantly increased inflammatory cytokine levels and NO and ROS formation. This novel mechanism of microglial cell activation will provide key information to understand MS pathogenesis.

Ginkgolic acids (GA) have been reported to exhibit anticancer properties, however, the mechanisms remain unclear. This study aims to investigate the mechanisms of GA C13:0 that was isolated from Ginkgo biloba exocarp (GBE) for anti-proliferation, pro-apoptosis and anti-migration effects in human MCF-7 and mouse 4T-1 breast cancer cells. The cytotoxic effect, apoptosis induction and migration inhibition were measured using MTT, TUNEL and Wound healing assays. The expression of mRNA and protein were determined using qPCR and Western blot. Our results showed that no cytotoxicity was found at concentrations of C13:0 below 100µM. The effects of GA C13:0 was further demonstrated by up-regulation of the Bax/Bcl-2 apoptosis pathway and the expression of Apaf-1 protein in the mitochondria. In addition, GA C13:0 also suppressed cell migration and epithelial to mesenchymal transition (EMT) with the increase of E-cadherin expression accompanied by the decrease of Snail, MMP-2, MMP-9 and Vimentin expression. Moreover, GA C13:0 induced cytochrome P450 (CYP) 1B1 expression in aryl hydrocarbon receptor (AhR) pathway. Notably, the up-regulation of CYP1B1 also might play a pivotal regulatory role in mitochondrial and EMT pathways in MCF-7 and 4T-1 cells. Our results may have implications for the development of anticancer agents containing GA as functional additives.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Introduction: Polycystic Ovary Syndrome (PCOS) is an endocrinologic disorder that affects 5-15 % of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, a characteristic multi-follicular morphology of the ovary, an elevated ratio of LH/FSH, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. Inflammatory processes consist of the acute inflammatory response and resolution processes initiated concomitantly. "Classical" pro-inflammatory lipid mediators like prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. SPM biosynthesis starts from the essential polyunsaturated fatty acids DHA, DPA, or EPA via certain hydroxylated intermediates (18-HEPE, 17-HDHA, 14-HDHA). The present study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Blood samples were taken (20 ml), separated into plasma and serum, and analyzed by HPLC/MS-QQQ. Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as comparator group, were recruited for the study. The main outcome measures were: Pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA; SPMs (Resolvins, Maresins, Protectins, Lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). Ratio [(sum of pro-inflammatory molecules)/sum of SPMs]. Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio [(sum of pro-inflammatory molecules) / (sum of SPMs plus hydroxylated intermediates)] reflecting the inflammatory state was significantly lower in the group of healthy women. Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

This study is based on the fatty acid and amino acid profile of 7 edible insect species: Acheta domesticus, Alphitobius diaperinus, Blaptica dubia, Galleria mellonella, Locusta migratoria, Tenebrio molitor and Zophobas morio. The fatty acid distribution within lipid classes (neutral lipids, glycolipids and phospholipids) was studied, while the amino acid profile was used to calculate the species-specific nitrogen-protein conversion factor (Kp). The profiles were used to evaluate the nutritional quality of the lipids and proteins. Oleic acid was the predominant fatty acid in all insects except for A. domesticus, in which a larger percentage of linoleic acid was found. The majority of the lipids were neutral lipids. L. migratoria showed a remarkably high content of α-linolenic acid in its phospholipid fraction, while T. molitor phospholipids were the only fraction in which a measurable amount of docosahexaenoic acid was found. Overall, in most insects, the phospholipid fraction had the highest polyunsaturated fatty acid content compared to the other classes, which may be protective in terms of autoxidative stability. Kp values in the range of 4.17 to 6.43 were obtained. Within the nutritional quality indices, all insects showed healthy fatty acid and high quality amino acid profiles.

(R)-2-Amino-1-hydroxyethylphosphonic acid 2 was prepared by hydrolytic kinetic resolution of rac-diethyl oxiran-2-ylphosphonate followed by reaction with benzylamine, acid hydrolysis, catalytic hydrogenolysis and anion exchange chromatography. Recrystallization from water-ethanol gave 2, which was characterized by IR, 1H NMR, 13C NMR, 31P NMR, polarimetry, elemental microanalysis, high-resolution mass spectrometry and single-crystal X-ray diffraction. The acid 2 crystallized in the orthorhombic chiral space group P212121 with cell constants a = 6.303(2) Å, b = 7.104(2) Å, c = 11.627(3) Å. The X-ray crystal structure confirmed the (R)-configuration of 2 and revealed that 2 is zwitterionic in the solid state, with extensive intermolecular hydrogen bonding between the hydroxyl, ammonium cation and phosphonate anion groups.

Stormwater runoff from large roads is a major source of pollutants to receiving waters. Porous pavements have been shown to substantially reduce many of these pollutants, but studies are lacking on arterial roads. We sampled typical stormwater pollutants in runoff from sections of an arterial road 9-16 years after installation of three pavement types: control with conventional asphalt, porous asphalt overly, and full-depth porous asphalt. Both types of porous pavements substantially reduced most of the stormwater pollutants measured. Total suspended solids, turbidity, total lead, total copper, and 6PPD-quinone were all reduced by >75%. Total nitrogen, ammonia, total phosphorus, biochemical oxygen demand, total and dissolved copper, total mercury, total zinc, total polycyclic aromatic hydrocarbons, and di-2-ethylhexyl phthalate were all reduced by >50%. Reductions were lower or absent for nitrate, orthophosphate, E. coli, dissolved lead, and dissolved zinc. Most reductions were statistically significant. Many pollutants exceeded applicable water quality standards in the control samples but met them with both types of porous pavement. This study demonstrates that porous overlays and full-depth porous asphalt can provide substantial reductions of several priority stormwater pollutants on arterial roads for many years after installation.

By introducing environmental mediator, for avoiding randomness in selecting indicators and subjectivity in deciding interaction path coefficients to reveal interaction mechanism among forest industry, ecology and environmental capacity, structural Pressure–State–Impact–Response (PSIR) and quantitative Structural Equation Modeling (SEM) are utilized with data on thirty–one provinces of China. We can find that: (i) forest industry has a negative influence on ecology, whereas ecology has a positive influence on industry; (ii) the destructive influence that industry has on ecology is much greater than the positive effect ecology has on industry; and (iii) environmental capacity plays a partial mediating role between industry and ecology. According to these results we can conclude that: (i) forest industry and ecology are not in a symbiotic relationship and have not reached a level of ecological security; (ii) the interaction between industry and ecology is in a period of transition from antagonistic to beneficial; and (iii) industry dominates ecology. However, we prospect the following advice: (i) methods of forest industry should be changed; (ii) new modes of industrial integration and circular economy should be developed; and (iii) the ability of the environment to sustain itself should be enhanced. The level of forest ecological security to discuss the symbiotic mechanism of industry and ecology will propose to be measured in future.

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Objective: To determine the effect of sandblasting before and after sintering on the surface roughness of zirconia and the micro-tensile bond strength of a pressable veneering ceramic to zirconia. Methods: Pre-sintered zirconia blocks (IPS e.max ZirCAD, Ivoclar Vivadent) were divided into a control group (CTR, no surface treatment) and four test groups of three specimens each: Pre-S-30, Pre-S-50, Pre-S-110 were sandblasted with 30µm SiO2, 50µm Al2O3 and 110µm Al2O3 particles respectively, before sintering, Post-S-30 was sandblasted with 30µm SiO2 after sintering. For each treatment, the surface roughness was measured (Ra, Perthometer M4P, Mahr Perthen). After sintering the zirconia blocks, a liner and a pressable ceramic (IPS e.max ZirPress, Ivoclar Vivadent) were fired. Sixteen micro-bars were obtained from each block and submitted to the micro-tensile bond strength (µTBS) test. Data were analyzed with one-way ANOVA. Any correlation between Ra and µTBS was evaluated (Sperman test). Results: Sandblasting before sintering with 110µm Al2O3 (Ra=3.44±0.44µm), 50µm Al2O3 (Ra=2.32±0.46µm), and 30µm SiO2 (Ra=1.22±0.22µm) resulted in significantly higher roughness than sandblasting after sintering with 30µm SiO2 (Ra=0.46±0.11µm). The highest µTBS was measured when the sintered zirconia was sandblasted with 30μm SiO2 (26.79±14.80 MPa), which was significantly different from that of specimens that were sandblasted before sintering (Pre-S-30=20.90±11.70; Pre-S-50=21.27±15.19; Pre-S-110=23.99±16.83) or were not treated (CTR=17.44±14.03). Conclusions: Sandblasting zirconia before sintering enhances the surface roughness proportionally to the particle size of the sand used. Sandblasting with 30µm SiO2 after sintering appeared to improve bonding between the veneering ceramic and zirconia. Clinical Significance: Sandblasting with 30µm SiO2 after sintering may improve bonding between veneering ceramics and zirconia, thus reducing ceramic fractures/chippings.

Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this study was to further evaluate the influence of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38±15 years/age and 7 females at 34±18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 grams of EAAS twice/day (BID)) or high dose (HD: 13 grams of EAAS BID). Both groups consumed the supplement for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual energy x-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at P<0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p=0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407±141 ng/ml and HD at 429±196 ng/ml, indicating chronic and excess alcohol consumption. Based on these results, we conclude that 13 grams of proprietary EAAS consumed BID lowers IHL in individuals with mild to moderate AUD.

Wheat is widely grown in the Mediterranean region, where plants frequently face water shortages. Recently, more attention to rationalizing irrigation water has been increased due to the adoption of sustainable agricultural systems. Therefore, two field trials were conducted at the Agriculture Research Station of Nubaria, Egypt, in two consecutive seasons (2017/2018 and 2018/2019) to examine three irrigation regimes' effects, i.e., 60, 80, and 100% of crop evapotranspiration (ETc) combined with foliar ascorbic acid (AsA) or vitamin B2 (VB2) on yield and water productivity of wheat in two separate experiments. A split-plot design was used with three replicates. Irrigation treatments occupied the main plots, while the subplot in the first experiment was placed by ascorbic acid (AsA) and vitamin B2 in the second experiment. Results indicated that 100% ETc produced higher wheat yield and its attributes and insignificantly surpassed 80% ETc. Compared to the unsprayed plots, the foliar application of 6 mM ascorbic acid or 2.0 mM vitamin B2 significantly increased grain yield, components, and water use efficiency. The interaction between irrigation regimes (100% ETc or 80% ETc) and foliar application of 6.0 mM ascorbic acid or 2.0 mM vitamin B2 resulted in the highest values with no significant difference. Foliar application of ascorbic acid or vitamin B2 saved 20% of irrigation water while yielding a reduction that did not exceed 10%. The biplot graph of treatments x traits (TT) was a useful statistical tool for examining the impact of treatments on yield and its characteristics and identifying the links between these factors. Results suggest that riboflavin or ascorbic acid may have a potential role as an effective antioxidant for enhancing the tolerance for drought stress in wheat.

Background: Systemic autoimmune rheumatic diseases (SARDs), including Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), are characterized by chronic inflammation and autoimmunity. Identifying reliable biomarkers is crucial for enhancing diagnosis, monitoring disease progression, and evaluating therapeutic responses. This study explores the potential of serum Syndecan-1 (SDC-1) as a biomarker for these conditions and concurrently examines its relationship with free light chain (FLC) expression levels in the same patients. Methods: A retrospective analysis was performed on serum samples from 120 patients (60 RA, 60 SLE), alongside 50 healthy donors (HD). Serum levels of κ and λ FLCs were determined by turbidimetric assay, while SDC-1 levels were measured using ELISA. Statistical analyses, including the Kruskal-Wallis test, Wilcoxon-Mann-Whitney U test, multivariable linear regression and Spearman’s correlation, were employed to compare biomarker levels across groups and to explore correlations among them. Results: Significantly increased levels of SDC-1, κ-FLC, and λ-FLC were observed in patients diagnosed with RA and SLE compared to HD (p < 0.001), while no significant differences in the κ/λ ratio were noted among the groups (p = 0.4). A statistically significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE statuses are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age. Conclusion: Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared to healthy controls underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cells activation, supporting the SDC-1 role in the pathogenesis of these conditions.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Abstract Peripartum depression (PPD) is a major complication of pregnancy and many risk factors have been associated with its development, including dysfunctional coping strategies and insecure attachment styles, both during pregnancy and postpartum. The aim of our study was to investigate the role of coping strategies in mediating the relationship between women’s attachment style and PPD in pregnancy, and one week after childbirth, in a large cohort of women. We hypothesized that the relationship between anxious and avoidant attachment and PPD would be mediated by use of maladaptive coping strategies. The assessment instruments were Edinburgh Postnatal Depression Scale (EPDS), Brief Coping Orientation for Problem Experiences (COPE), Experiences in Close Relationship Scale (ECR). The results indicated that the effect of insecure attachment styles (anxious and avoidant attachment) on antepartum depressive symptomatology was partially mediated by dysfunctional coping styles. Anxious attachment has also an indirect significant effect on postpartum depression through emotional coping; however, avoidant attachment does not seem to be significantly related to postpartum depression. Our findings revealed that not only it is important to consider attachment in understanding PPD but also that coping plays an important role in these relationships. These findings would help a preventive coping-based intervention strategy to enhance the capacity of women with insecure attachment styles to use more adaptive coping during and after pregnancy.

Several types of guided bone regeneration materials are available with various properties and clinical indications. Among them, dentin-derived matrix from extracted teeth is an excellent alternative to traditional graft materials, such as allografts and xenografts. Different clinical preparation protocols exist: block form versus powder form, demineralized versus non-demineralized form. Out of these methods, demineralization protocols for dentin-derived matrix from extracted teeth have been noted for a wide range of successful clinical outcomes. The purpose of this animal study was to find out the most effective method of demineralizing dentin-derived matrix to result in the highest regenerative ability in the bone graft material in rabbit calvaria. The study conducted a comparative histomorphometric analysis of four groups in distinguished matrix conditions: a control group without graft placement, a non-demineralized dentin-derived matrix graft placement group, a 15-minute demineralized dentin-derived matrix graft placement group, and a 30-minute demineralized dentin-derived matrix graft placement group. Regenerative processes were evaluated three times at 2, 4, and 8 weeks post-graft placement. These groups of rabbits were evaluated randomly in a blinded setting to prevent bias. Among the four groups compared, the group with a 15-minute demineralized dentin-derived matrix graft showed the most efficient bone regeneration in the histomorphometric analysis. Based on this animal study, it was apparent that a 15-minute demineralization of dentin-derived matrix is the preferred preparation protocol to maximize the regenerative potential in the matrix.

Micro plasma devices (MPD) with power gains are of interest in applications involving operations in the presence of ionizing radiations, in propulsion, in control, amplification of high power electromagnetic waves, and in metamaterials for energy management. Here we review and discuss MPDs with an emphasis on new architectures that have evolved during the past 7 years. Devices with programmable impact ionization rates and programmable boundaries are developed to control the plasma ignition voltage and current to achieve power gain. Plasma devices with 1-10 μm gaps are shown to operate in the sub-Paschen regime in atmospheric pressures where ion-assisted field emission results in a breakdown voltage that linearly depends on the gap distance in contrast to the exponential dependence dictated by the Paschen curve. Small gap devices offer higher operation frequencies at low operation voltages with applications in metamaterial skins for energy management and in harsh environment inside nuclear reactors and in space. In addition to analog plasma devices, logic gates, digital circuits, and distributed amplifiers are also discussed.

An electrochemical bioassay based on the rotating droplet electrochemistry by using electron transfer mediator was developed for the evaluation of a wide variety of pollutants such as antibiotics, heavy metals and pesticides in the water environment. Ferricyanide was used as electron transfer mediator for obtaining the catalytic response of Escherichia coli. The electrochemical response of E.coli was measured via hydrodynamic chronoamperometry in a microdroplet on a screen-printed carbon electrode (SPCE). The constructed electrode system successfully evaluate the catalytic response of E.coli solution in presence of ferricyanide. The assay for antibiotic toxicity on E.coli was carried out. The EC50 for ampicillin, sulfamonomethoxine, chlorotetracycline, tetracycline and oxytetracycline valuated by the pre-incubation method were 0.26, 0.77, 5.25, 18.5, 19.0 µM, respectively. The toxicity order was ampicillin &gt; sulfamonomethoxine &gt; chlorotetracycline &gt; tetracycline&gt;oxytetracycline. The proposed method can be used to evaluate the antibiotic toxicities in different real sample, such as pond water, powder and raw milk. Recoveries were found in the range 90 and 99%. The developed methods do not require additional incubation time to evaluate toxicity.

(S)-1-Methyl-2-oxoimidazolidine-4-carboxylic acid 1 is an analog of (S)-pyroglutamic acid, a key component of naturally occurring peptide hormones and synthetic pharmaceutical candidates. Reaction of (S)-2-amino-3-(methylamino)propionic acid with COCl2 and aqueous NaHCO3 followed by ion exchange afforded 1, which was recrystallized from acetonitrile and then characterized by IR, 1H NMR, 13C NMR, polarimetry, elemental microanalysis, high resolution mass spectrometry and single crystal X-ray diffraction. The acid 1 crystallized in the orthorhombic chiral space group P212121 with cell constants a = 6.2275(4) Å, b = 8.3963(5) Å, c = 24.9490(14) Å. The X-ray crystal structure reveals that two distinct conformers of 1 occur at alternating positions within helices which are supported by hydrogen-bonding. Each molecule of 1 is linked to its two neighbors in the helix by a total of three hydrogen bonds and four molecules of 1 are contained within each turn of the helix. The pattern of hydrogen bonds illustrates a preference for the carboxylic acid group to act as a hydrogen bond donor and for the urea unit to be a hydrogen bond acceptor.

In green chemistry, filamentous fungi are regarded as a kind of robust microorganism for the biotransformation of natural products. Nonetheless, the screening of microorganisms is crucial for the effective biotransformation of natural products such as phenazine compounds. The precursor metabolite of most phenazine derivatives in Pseudomonas spp. is phenazine-1-carboxylic acid (PCA), the key constituent of shenqinmycin, widely used to control rice sheath blight in southern China. In this study, a new fungus strain Aspergillus sclerotiorum was isolated, which can efficiently convert PCA into 3-hydroxy-phenazine 1-carboxylic acid (3-OH-PCA). Moreover, an effective whole cells biotransformation system was constructed by screening optimal reaction conditions and carbon sources. Hence, Aspergillus sclerotiorum exhibited desirable adaptation by consumption of different carbon sources and maximum whole cell biomass (10.6 g/L DCW) was obtained as a biocatalyst from glucose. Optimal conditions for whole-cell biocatalysis of PCA were evaluated, including PCA concentration of 1120 mg/L, pH 7.0, temperature of 25°C, rotation rate 200 rpm and dry cell weight 15 g/L for 60 h, thus 1060 mg/L of 3-OH-PCA was obtained and the conversion efficiency of PCA was 94%. Hence, the results of repeated batch mood revealed that the biotransformation efficiency of fungus pellets reduced with each subsequent cycle but remained stable in all five cycles with the provision of glucose supplement. These findings open the prospective of using filamentous fungi for the whole cell biocatalysis of phenazine in enormous amount and efficient production of 3-OH-PCA. Moreover, these results laid the foundation for further research to disclose the genetic based mechanism of the strain responsible for PCA biotransformation.

Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms in evaporative cooling water systems, but these agents can adversely affect the environment and human health. Alternatively, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years with excellent results. The tower water chemistry method concentrates natural salts in highly-softened water to produce elevated pH and dissolved solids, with low calcium and magnesium. This practice conserves water while generating only a small volume of non-toxic natural salt concentrate for cost efficient separation and disposal if required. This review presents a novel perspective of natural antimicrobial chemistry for inhibiting parasitic microbiome functional relationships within the bio-triad of Legionella outbreaks, "Trojan Protozoans" and biofilms. The review further examines practical application and function of polyvalent metal ions in the inhibition of biofilms. Reducing global dependence on toxic antibacterial agents discharged to the environment is an emerging concern due to their impact on the natural microbiome, plants, animals and humans. Discharge of antibacterial agents also contributes to development of pathogen resistance. Use of natural antibacterial chemistry can play a key role in managing the cooling water environment in a more ecologically sustainable manner.

In this paper, we extend the KdVSKR equations in (1+1)-dimension and (2+1)-dimension to fractional KdVSKR equations with modified Riemann-Liouville derivative. The (2+1)-dimensional KdVSKR equation, which is a recent extension of (1+1)-dimensional KdVSKR equation, can model the resonances of solitons in shallow water. By means of the Hirota bilinear method, finite symmetry group method and consistent Riccati expansion method, many new interaction solutions have been derived. Soliton-cnoidal interaction solution of the (1+1)-dimensional fractional KdVSKR equation has been derived for the first time. For the (2+1)-dimensional frac-tional KdVSKR equation, two-wave interaction solutions and three-wave interaction solutions, including dark-soliton-sine interaction solution, bright-soliton-elliptic interaction solution, and lump-hyperbolic-sine interaction solution, have been derived. Impact of the fractional order on the shapes of these solutions has been illustrated by figures. Three-wave interaction solutions of fractional systems have not been reported in the existing references. The research idea in this paper can be applied to other fractional differential equations.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

Background: Ventilator-associated pneumonia (VAP) is among the most common healthcare-associated infections in Pediatric Intensive Care Units (PICUs). Because of the lack of a gold-standard diagnostic test, early diagnosis of VAP is challenging. We investigated whether bronchial biomarkers interleukin-4 (IL-4), plasminogen activator inhibitor-1 (PAI-1) and soluble receptor for advanced glycation end products (RAGE) could contribute in early VAP diagnosis through their fluctuation in time in critically ill pediatric patients. Methods: Bronchial secretions were collected from PICU patients with VAP on days 1 and 6. PAI-1, RAGE and IL-4 levels were measured by ELISA. Protein concentrations between high and low VAP suspicion patients were compared using unpaired Student’s t or Mann–Whitney U tests. Results: Twenty PICU patients, with median age 7.75yrs (range 0.5-15.3), mechanically ventilated for ≥48hrs with increased oxygenation requirements and VAP clinical/laboratory signs were enrolled. They were divided in VAP high-suspicion (n=12) or low-suspicion (n=8) groups based on Clinical Pulmonary Infection Score (cutoff:6). ΡΑΙ-1 και RAGE levels did not differ between high- or low-VAP suspicion groups the 1st or 6th days (p-value&gt;0.05). IL-4 was not detected in bronchial secretions. Conclusion: Bronchial concentrations of IL-4, PAI-1 and RAGE in critically ill children are not correlated with high- or low-VAP suspicion.

Introduction Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced the search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease, it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndrome, which includes, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) in improving lipid profile parameters in 1-year follow-up. Material and Methods Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in 1-year observation were analyzed. Results Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL levels decrease were observed along with the increase of high-density lipoprotein (HDL) cholesterol level. Conclusions Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

During pregnancy, profound physiological changes occur in the maternal body, including those affecting oral health. Dental stem cells (DSCs) have emerged as promising candidates for regenerative therapies in dentistry. This manuscript delves into the intricate interplay between DSC behavior and maternal oral health during pregnancy. We provide an overview of current knowledge concerning the impact of pregnancy on DSCs, highlighting their potential roles in maintaining oral homeostasis and responding to pathological conditions. Additionally, we identify key research gaps and propose future directions for investigating novel therapeutic strategies leveraging DSCs to improve maternal and fetal oral health outcomes. By elucidating this relationship, we aim to pave the way for innovative approaches in preventive and regenerative dentistry tailored to the unique needs of pregnant women.

This paper proposes the recycling of plates from spent car batteries by the melt quenching method and the incorporation of NiO or Co3O4 contents in order to improve the electrochemical performance of new materials for applications as electrodes on batteries. The analysis of X - ray diffractograms indicates the gradual decrease of the sulfated crystalline phases, respectively 4PbO•PbSO4 and PbO•PbSO4 phases until their disappearance for higher dopant concentrations. IR data show a decreasing trend in the intensity of the bands assigned to sulfate ions and a conversion of [PbO3] pyramidal units into [PbO4] tetrahedral units by doping with high dopant levels yielding to the formation of the PbO2 crystalline phase. The EPR data indicate three resonance lines centered on the gyromagnetic factor, g ~ 2, 2.2 and 8, which are dependent on the NiO level. The first two resonance lines are assigned to nickel ions in higher oxidation states and the last signal centered at g ~ 8 corresponds to nickel metal nanoparticles. This compositional evolution can be explained by considering a process of drastic reduction of nickel ions in oxidation states superior to metallic nickel. The linewidth and the intensity of resonance lines situated at about g ~ 2, 2.17, 4.22 and 7.8 corresponding to the Co+2 ions from EPR spectra depend very strongly on the Co3O4 concentration. The best reversibility of the cyclic voltammograms was highlighted for the samples with x = 8 mol% NiO and 10 mol% Co3O4, which are recommended as suitable in applications as electrode for renewable batteries.

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P&lt;0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P&lt;0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

Mastocytosis is characterized by pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

Cancer is one of the leading causes of death, and latest predictions indicate that cancer- related deaths will increase over the next few decades. Despite significant advances in conventional therapies, treatments remain far from ideal due to limitations such as lack of selectivity, non-specific distribution, and multidrug resistance. Current research is focusing on the development of several strategies to improve the efficiency of chemotherapeutic agents and, as a result, overcome the conventional therapies challenges. In this regard, combined therapy with natural compounds and other therapeutic agents, such as chemotherapeutics or nucleic acids, has recently emerged as a new strategy for tackling the drawbacks of conventional therapies. Taking this strategy into consideration, the co-delivery of the above-mentioned agents in lipid-based nanocarriers provide some advantages by improving the potential of the therapeutic agents carried. This review encompassed different strategies associated with combined therapy, at the same time highlighting the most recent advances and outstanding advantages of lipid-based nanocarriers for achieving a promising combination therapy that may overcome cancer treatment challenges.

Carotenoids are common and diverse organic compounds with various functional roles in ani-mals. Except for certain aphids, mites, and gall midges, all animals acquire necessary carotenoids only through their diet. The House fly (Musca domestica) is a cosmopolitan pest insect that populates diverse habitats. Its larvae feed on organic substrates that may vary in carotenoid composition according to their specific content. We hypothesized that the carotenoid composition in the adult House fly’s body would reflect its composition in the larval feed. We reared house fly larvae on substrates that differed in carotenoid composition and characterized the carotenoid composition of the emerging adults. Our results indicate that the carotenoid composition of adult House flies is related to the carotenoid composition in its natal substrate, but does not directly reflect it. We suggest that these findings may be developed to identify sources of House fly in-festations. We also recommend that care should be taken when considering the rearing substrates of House fly larvae used for animal feed.

Probiotics are living microbes that provide benefits to the host. The increasing data on health promotion following probiotics administration triggered growing interest among researchers and pharmaceutical companies looking for novel therapeutic or preventive tools. Infections of the lower genital tract in females are caused by a wide range of pathogens, they are widespread, and represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women in their reproductive age at least once during their lifetime. Of these women 5-8% develop the recurrent form (RVVC). The disease onset is triggered by the overgrowth of Candida species on the vaginal mucosa. Here, we evaluated the beneficial properties of the Bacillus coagulans spore-producing LMG S-24828 against C. albicans and C. parapsilosis. Our results show that both alive B. coagulans and its Cell-Free-Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, alive B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells and showed co-aggregation capacity. Overall, B. coagulans LMG S-24828 exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies. Traditional pharmacological treatments aimed at slowing degeneration are ineffective in the long-term. Orthobiologics, regenerative agents derived from the patient’s own tissue, are a promising emerging therapy for degenerative disc disease. This review first outlines the pathophysiology of degenerative disc disease, highlighting the limitations of existing treatments and explores the orthobiologic tools for treating degenerative disc disease (platelet-rich plasma, mesenchymal stem cells). Their history in regenerative medicine is outlined, demonstrating how in vitro evidence informed preclinical animal studies on their efficacy in treating degenerative disc disease. Finally, clinical trials utilizing these treatment options are reviewed and directions for future research are outlined. Although the current clinical evidence available is limited to propagate their routine clinical usage the field holds immense potential in the management of DDD. There is room for these treatments to be optimized for effective consistent clinical outcomes in DDD.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic dis-orders frequently associated with iron accumulation in the basal nuclei of the brain. Among NBIA subtypes, β -propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate autophagic defects and secondary pathological con-sequences in cellular models derived from two patient harboring WDR45 mutations. Both protein and mRNA expression levels of WDR45 were decreased in patient-derived fibro-blasts. In addition, the increase of LC3B upon treatments with autophagy inducers or inhibitors was lower in mutant cells compared to control cells, suggesting decreased autophagosome formation and impaired autophagic flux. Transmission electron microscopy (TEM) analysis showed mitochondrial vacuolization associated with accumulation of lipofuscin-like aggregates containing undegraded material. Autophagy dysregulation was also associated with iron ac-cumulation and lipid peroxidation. In addition, mutant fibroblasts showed altered mitochon-drial bioenergetics. Antioxidants such as pantothenate, vitamin E and α-lipoic prevented lipid peroxidation and iron accumulation. However, antioxidants were not able to correct the ex-pression levels of WDR45 neither the autophagy defect nor cell bioenergetics. Our study demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism and cell bioenergetics. Antioxidant partially improved cell physiopathology, however autophagy and cell bioenergetics remained affected.

Smart manufacturing encompasses a category of manufacturing that employs computer-integrated capabilities and technologies to enhance supply chain optimization, production efficiency, and recyclability. Yet limited studies have been conducted to optimize these prospects from the perspective of low resource countries where such innovative studies have not been adequately explored. This paper aims to examine the implications of smart manufacturing practices (Smart Procurement, Smart Supply Chain, Smart Production Planning and Control, Automation and Industrial Robot, and Supply Chain Configuration) on pro-environmental behaviour and develop a baseline moderated mediation model to explain the relationship between smart manufacturing and pro-environmental behaviour with a role of green dynamic capability, and environmental orientation. This study is anchored on quantitative research approach, deductive reasoning, and explanatory design. Cross – sectional survey data have been obtained from 382 manufacturing companies in Ghana. Our hypotheses have been tested using Structural Equation Modelling and SMART-PLS version 3.8.9. The study has revealed that smart manufacturing practices significantly and positively relate to pro-environmental behaviour. Moreover, green dynamic capability and environmental orientation moderate the relationship between smart manufacturing and pro-environmental behaviour. The implications of the study include the emergence of a baseline model to guide policymakers, practitioners, and academicians to explain the relationship between smart manufacturing and sustainable manufacturing in the context of developing countries. Again, the social implication of the study includes the realisation of decent job and economic growth, responsible consumption and production as well as actions taken to combat climate change.

Exposure to cadmium sulfate (CdSO4) can lead to neurotoxicity. Nevertheless, the precise molec-ular mechanisms underlying this phenomenon remain unclear, and effective treatment strategies are scarce. This study explored the protective effects of ellagic acid (EA), a natural polyphenolic compound, against CdSO4 exposure-induced neurotoxicity in HT22 cells. Additionally, the inves-tigation sought to elucidate the molecular mechanisms underlying this phenomenon. Our findings demonstrated that exposure of HT22 cells to CdSO4 resulted in apoptosis, which was effectively reversed by EA supplementation. EA supplementation also decreased reactive oxygen species (ROS) and mitochondrial ROS productions, reduced malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, EA supplementation at 5–20 μM significantly counteracted Cd-induced mitochondrial membrane potential and ATP losses and reduced the ratio of Bax/Bcl-2 and cleaved-caspase-3 protein expression. Furthermore, EA supplementation upregulated Nrf2 and HO-1 protein expression while downregulating the phosphorylation of JNK and p38 proteins. Pharmacological inhibition of JNK partially inhibited CdSO4-induced Nrf2/HO-1 activation and exacerbated its cytotoxicity. In conclusion, our results indicate that EA supplementation provides protection against CdSO4-induced cell apoptosis in HT22 cells by inhibiting oxidative stress and activating the Nrf2 pathway. Activation of the JNK pathway plays a protective role in CdSO4-induced cell apoptosis in HT22 cells.

The efficacy and safety of organic UV-filters could benefit from their incorporation into lipid nanoparticles because of the ability of such carriers to reflect solar radiations, thus acting synergically as physical sunscreens. In this work, bemotrizinol (BMTZ), a broad-spectrum UV-filter, was loaded into nanostructured lipid carriers (NLC) whose lipid matrix contained different oils to assess the effects of the lipid core composition on the properties of the resulting NLC. Subsequently, the effects of incorporating different concentrations of optimized BMTZ-loaded NLC on the technological properties of O/W emulsions (pH, viscosity, spreadability, occlusion factor, in vitro BMTZ release and skin permeation, in vitro sun protection factor) were assessed. Optimized BMTZ-loaded NLC showed mean size=190.6±9.8 nm, PDI=0.153±0.013, ζ-potential=-10.6±1.7 mV, loading capacity=8% w/w. The incorporation of increasing concentrations of optimized BMTZ-loaded into emulsions provided slight increase of spreadability, lower viscosity and no change of pH, occlusion factor and BMTZ release compared to the control. No BMTZ skin permeation was observed from all formulations. About 20% increase of sun protection factor values was obtained for vehicles containing BMTZ-loaded NLC. Therefore, BMTZ-loaded NLC incorporation into emulsions could be a promising strategy to develop safer and more effective sunscreen formulations.

Interactions between human immunodeficiency virus type 1 (HIV-1) and the host factors or restriction factors of its target cells determine the cell’s susceptibility to, and outcome of, infection. Factors intrinsic to the cell are involved at every step of HIV-1’s replication cycle, contributing to productive infection and replication, or severely attenuating HIV-1’s chances of success. Furthermore, factors unique to certain cell types contribute to the differences in infection between these cell types. Understanding the involvement of these factors in HIV-1 infection is a key requirement for the development of anti-HIV-1 therapies. As the list of factors grows, and the dynamic interactions between these factors and the virus are elucidated, comprehensive and up-to-date summaries that recount the knowledge gathered after decades of research are beneficial to the field, displaying what is known so that researchers can build off the groundwork of others to investigate what is unknown. Herein, we aim to provide a review focusing on protein host factors, both well-known and relatively new, that impact HIV-1 replication in a positive or negative manner at each stage of the replication cycle, highlighting factors unique to HIV-1’s various target cell types where appropriate.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

By using Modified simple equation method, we study the Cahn Allen equation which arises in many scientific applications such as mathematical biology, quantum mechanics and plasma physics. As a result, the existence of solitary wave solutions of the Cahn Allen equation is obtained. Exact explicit solutions interms of hyperbolic solutions of the associated Cahn Allen equation are characterized with some free parameters. Finally, the variety of structure and graphical representation make the dynamics of the equations visible and provides the mathematical foundation in mathematical biology, quantum mechanics and plasma physics.

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

Abstract: Measures to counteract AMD generation need to start at the mineral surface, inhibiting mineral-oxidizing, acidophilic microbes. Laboratory and long-term field tests with pyrite-containing mining wastes, where Carbonaceous Phosphate Mining Waste (CPMW) was added, resulted in low acidity, and near neutral drainage. The effect was reproducible, nd confirmed by several independent research groups. This was shown to involve an organic coating, likely a biofilm. The biofilm formation was confirmed when CPMW was added to lignite coal waste with an initial pH of 1. Forty five days after the addition, the coal waste was dominated by heterotrophic microorganisms in biofilms. A review of the scientific literature supports that CPMW has physical and chemical characteristics which are capable of inducing a strong inhibitory effect on sulphide oxidation by forming an organic coating over the mineral surface. CPMW characteristics appear to provide the cornerstone of a new technology for the reduction of sulphide oxidation in mine wastes. An hypothesis for testing this technology is presented which could result in an economical and sustainable approach to mine waste and water management.

This study presents an innovative method for producing thermosensitive bio-ink from chitosan hydrogels saturated with carbon dioxide and agarose. It focuses on a detailed characterization of their physicochemical properties and potential applications in biomedicine and tissue engineering. The ORO test approved rapid regeneration of the three-dimensional structure of chitosan-agarose composites in the unidirectional bench press simulation test. The diffusion of dyes through chitosan-agarose hydrogel membranes strongly depended on the share of both polymers in the composite and the molecular weight of the dyes. Glucose, as a nutrient marker, also diffused through all membranes regardless of composition. Biocompatibility assessment using MTT tests on 46BR.1N fibroblasts and HaCaT keratinocytes confirmed the safety of the bioink. The regenerative potential of the bioink was confirmed by efficient cell migration, especially HaCaT. Long-term viability studies showed that chitosan-agarose scaffolds, unlike the agarose ones, support cell proliferation and survival, especially 14 days after bioink extrusion. Experiments in a skin wound model in mice confirmed the biocompatibility of tested dressing and the beneficial action of chitosan on healing. Studies on vessel formation in chicken embryos highlight the potential of the chitosan-agarose composition for enhancing proangiogenic effects. This composition meets all entry criteria and possesses excellent biological properties.

Vertical and horizontal bone augmentation is one of the most challenging techniques in bone engineering. The use of barrier membranes and scaffolds in guided bone regeneration (GBR) procedures is a common approach for the treatment of lost bone around teeth and dental implants. The aim of this study was to estimate the barrier effects of a synthetic poly (lactic acid/caprolactone) [P(PA/CL)] bilayer membrane for GBR, compared to a porcine collagen bilayer membrane, in the vertical augmentation model on 10–12-months old rat skull without periosteum. The HAp block (diameter: 4 mm, height: 3 mm, porosity:75%, average pore size:150 μm) was placed on the rat skull without a periosteum. The P(LA/CL) membrane (solid layer: 25 μm, porous layer: 175 μm) or the collagen membrane (solid layer, porous layer) was applied onto the HAp block. At 3, 6, and 12 weeks after the surgery, the incised tissues were fixed, decalcified, and stained with hematoxylin and eosin for histological evaluation. The P(LA/CL) membrane remained until 12 weeks and could achieve barrier effects to inhibit cellular invasion from the repositioned soft tissues. Local bone formation occurred in the interconnected pores of HAp at 6 weeks. On the other hand, the collagen membrane did not inhibit cellular invasion for its expansion until 3 weeks, and was absorbed until 6 weeks. The results indicated that the P(LA/CL) membrane might be effective in GBR as occlusive absorbable membrane.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipozyme, or lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the non-polar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by collections of small, nonpolar or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two phase octanol-water system with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol was then replaced with DOPC added to the water in the form of vesicles, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence which revealed catalytic turnover numbers on a scale of 10−4s−1 for each system, which is comparable to some slow enzymes. The reaction product was characterized by 1H-NMR measurements which were consistent with ester hydrolysis. The implications of thinking about lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology and synthetic biology.

Regulatory macrophages (Mregs) are unique in that they have anti-inflammatory and immunosuppressive properties. Thus, treating inflammatory diseases using Mregs is an area of active research. Human Mregs are usually generated by culturing peripheral blood monocytes stimulated by macrophage colony-stimulating factor with interferon (IFN)-. Here, we generated Mregs with an elongated cell morphology from THP-1 cells stimulated with phorbol 12-myristate 13-acetate and cultured with arginylglycylaspartic acid and vitamin D3. These Mregs regulated macrophage function, and respectively downregulated and upregulated the expression of pro-inflammatory and immunosuppressive mediators. They also expressed Mregs-specific marker, such as dehydrogenase/reductase 9, even when exposed to inflammatory stimulants such as IFN-, lipopolysaccharide, purified xenogeneic antigen, and xenogeneic cells. The Mregs also exerted anti- inflammatory and anticoagulatory actions in response to xenogeneic cells and immunosuppressive effects on mitogen-induced Jurkat T-cell proliferation. Our method of generating functional Mregs in vitro without cytokines is simple and cost-effective.

Stem cells can be used in cellular therapy. This happended in order to replace damaged cells or having aim to regenerate organs. The definition of stem cells can be extended. From this point of view, we can mention taking in consideration the idea in which it is known that these cells form the base of the building body. More than, we can mention that stem cells are characterized by two knowing properties namely differentiation and self renewal. Based on the observation that differentiation of adult stem cells into specific derivative scan be controlled by laboratory techniques, it is anticipated that adult stem cells may become the basis of therapies for many, and various types of medical conditions. Taking on stem cells, regenerative medicine (RM) it is known as being one of the hottest topics in biotechnology nowadays. From this purpose, stem cells can be used in regenerative medicine (RM). The principles of regeneration are found in different types of cultures, from long time ago. As an interdisciplinary field of research, regenerative medicine, play a great role in tissues and organs damaged reparation with a higher potential in transplantation if necessary.

Peri-implant diseases are defined as pathological inflammatory reactions in the tissue surrounding the osseointegrated implants. They are classified into two categories: mucositis - defined as peri-implant soft tissue inflammation and peri-implantitis - bone loss in the peri-implant region. A clinical case of a 61-years-old woman with an implant in the 46 anatomical position and a 5-year follow-up is presented. A probe depth of 5mm and a bone defect length of 35% was observed. The Implacure® Protocol was applied, with the main objective of eliminating the biofilm present on the exposed implant surface. There are multiple approaches to treat peri-implant diseases. While non-surgical treatment is essential for mucositis control, the treatment of peri-implantitis surgical treatment should be considered. Regenerative bone reconstruction promotes bone repair in the defect area and reduces bleeding during probing. To achieve that, autologous fibrin combined with Cerasorb M® was used. The proposed approach in the exposed clinical case involves the application of Implacure® Protocol, whose combination of the physical decontamination technique, together with the use of chlorhexidine and orthophosphoric acid, added with the combination Piperacillin + Tazobactam together with hyaluronic acid, provide a base that allows to regenerate bone using platelet-rich fibrin with Cerasorb M® and increase the survival time of the implant.

Objectives: 1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world in Rehabilitation Setting; 2) to evaluate clinical effectiveness by Visual Analog Scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study run from January 2018 to September 2021. Inclusion criteria: a) patients 18 years or older; b) with knee OA KL 2º or more; c) biochemical analysis before-and-after treatment; d) pain more than 3 on VAS. Exclusion Criteria: a) previous knee surgery; b) favism; c) pregnancy; d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: a) IL-6; b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: a) CRP, b) ESR, c) uric acid, d) VAS pain, e) WOMAC pain, function and stiffness. Ozone protocol consisted of 4 sessions (once a week) of an intra-articular infiltration of 20 mL (20µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus ®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.7 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p<0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in real world Rehabilitation Setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone downregulates pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

HIV-1 transcribes only one kind of transcript – the full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must splice but not completely. Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all. HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full length genomic RNA and has a dramatic fitness cost. Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 has to circumvent this cell policing mechanism to allow some splicing while suppressing most. Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev. There is still much work to be done to clarify the combinatorial effects of these splicing regulators. These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and also present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

المستخلص تصنيع لقاح مكون من الحمض النووي الريبوزي الرسول الخاص بالبروتينات المسئولة عن انتاج البروتينات نيورامنيديز والهيم اجليوتونين لفيروسي الانفلونزا الخنازير والطيورمحاط بجزيئات دهنية بحجم النانوميتر عدوى انفلونزا الخنازير وانفلونزا الطيور مشكلة خطيرة تؤرق العالم كله هذه الايام خصوصا انها مميتة لكثير من اطفال العالم . بعد فترة التعافي من الاصابة تتكون المناعة المكتسبة ضدها لمدة عام تقريبا. هذه الانفلونزا تسبب تسمم فيروسي في الدم بالاضافة للالتهاب الرئوي وهذامن بين اكبرالاسباب للوفاة بين الاطفال قبل سن عامين عالميا بشكل مباشر. الهدف من الدراسة هو انتاج لقاح الحمض النووي الريبوزي الرسول من نوع الام بالنانوتكنولوجي لبروتينات الهيم اجليوتونين والنيورامنيديز الموجودة على سطح هذه الفيروسات التي تساعدتها في الاتصاق بالعائل الذي ستتكاثر داخل خلاياه بالجهاز التنفسي. هذه الدراسة دراسة استكشافية ومن خلالها استطاعنا تصميم هذا اللقاح باستعمال نظام توصيل للقاح بالنانوتكنولوجي حجم جزيئاته 70نانوميمتر. اللقاح الجديد اظهر فاعلية بنسبة 60% واظهر فاعلية حيوية مقاربة واثار جانبية اقل بالمقارنة باللقاحات المتوفرة حاليا بالسوق الدوائي ضد هذا النوع من الفيروسات الوبائية. ABSTRACT Background: Worldwide, Swine and Avian influenza, or the H1N1 and H5N1 serotypes of the Influenza A virus, is a highly contagious illness. In recent years, the global incidence of mortality rate has surpassed 284,000 fatalities. Aim of the study: The production of mRNA vaccine lipid nanoparticles (LNP) to combat the deadly strains of Avian and Swine influenza (H1N1 and H5N1 of the influenza A serotype). Methodology: Polymerase chain reaction (PCR) was used to clone genes of interest encoding Haemagglutinin (HA) and Neuraminidase (NA) of Influenza A virus strains (H5N1 and H1N1) known as Avian flu and Swine flu, respectively. The genes were then inserted using the EcoR1, BAM Hind II restriction endonuclease type II, and Ligase enzyme into the pET-21(+) transcription vector plasmid. On the other hand, the hybrid transcription vectors were mixed with T7 RNA polymerase and ribonucleotides within a test tube after being linearized using EcoR II. Following their purification via reversed-phase high-performance liquid chromatography (RP-HPLC), the mRNAs of the HA and NA were encased in 70 nm LNPs and subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). Lastly, immunogenicity studies were performed in stages 1/2 of randomized human and preclinical clinical trials. Results: The bivalent vaccination had around 63% efficacy in preclinical studies and approximately 60% efficacy in randomized human clinical trials. As shown by the ELISA test, strong neutralizing antibodies against HA were prevalent. Conclusion: The current study is a promising effort because of the development of the novel LNP-mRNA vaccine, which could lower the incidence of Avian and Swine flu infectious disorders.

Background: Chronic kidney disease (CKD) is a significant cardiovascular (CV) risk factor, with dialysis-dependent CKD (DD-CKD) patients facing high mortality rates. Hypercholesterolemia is another crucial CV risk factor, typically managed with lipid-lowering therapy, though its efficacy in DD-CKD remains uncertain. Evidence shows mixed results regarding the benefits of statins in these patients. Citrate-based dialysates are known to reduce inflammatory biomarkers compared to acetate-based ones, potentially impacting lipid profiles and immune responses. This study aimed to determine the effects of citrate versus acetate dialysate on lipid profiles and immunophenotypes in DD-CKD patients. Methods: This unicentric, cross-over, prospective study included 21 hemodialysis patients (10 males, 11 females, average age 62.25 years). Each patient underwent 24 dialysis sessions (12 with each dialysate) and acted as their own control. Lipid profiles, immunological parameters, and nutritional and inflammatory markers were measured before the last session with each dialysate. Results: Compared to acetate dialysate (AD), citrate dialysate (CD) resulted in significantly higher LDL (75.71 vs. 67.05 mg/dL, p=0.042) and HDL (51.19 vs. 47.14 mg/dL, p=0.013), and lower TG (97.86 vs. 110.38 mg/dL, p=0.046). CD also led to higher NK cells (19.24 vs. 16.95%, p=0.035), higher complement C3 levels (115.14 vs. 107.81 mg/dL, p=0.009) and lower CD3+ CD8+ and CD16+56+ lymphocytes. Finally, total lymphocytes were lower with AD than with CD. We found no difference in predialysis nutritional nor inflammatory parameters (IL-6 and hs-CRP) except for ESR, which was higher when subjects used CD than AD. Conclusion: There are significant differences in lipid and immunophenotypic profiles that should increase the CV risk of patients who use CD. However, numerous studies have shown no differences, or even a benefit in mortality in certain HD subpopulations that use CD. Further studies are needed to understand if the observed changes may be counterbalanced by other mechanisms potentially provided by citrate (e.g., reducing vascular calcification).

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Background: Interleukins play dual roles in breast cancer, acting as both promoters and 11 inhibitors of tumorigenesis within the tumor microenvironment, which is shaped by their 12 inflammatory functions. This study analyzed the subtype-specific prognostic significance 13 of anti-inflammatory and pro-inflammatory signatures using microarray-based gene ex- 14 pression analysis. Correlations between these interleukin signatures and immune cell 15 markers (CD8, IgKC, CD20) and immune checkpoints (PD-1) were also evaluated. 16 Materials and Methods: The study investigated the prognostic significance of an anti- 17 inflammatory interleukin signature (IL-12, IL-21, IFN-γ) and a pro-inflammatory interleu- 18 kin signature (IL-4, IL-5, IL-10, IL-13, IL-17, CXCL1) for metastasis-free survival (MFS) 19 using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with 20 early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coef- 21 ficient. 22 Results: Kaplan-Meier curves revealed that the prognostic significance of the anti-inflam- 23 matory signature was specifically pronounced in the basal-like subtype (p=0.004, Log 24 Rank). This signature retained independent prognostic significance in multivariate Cox 25 regression analysis (HR 0.463, 95% CI 0.290-0.741; p=0.001). Higher expression of the anti- 26 inflammatory interleukin signature was associated with longer MFS. The pro-inflamma- 27 tory interleukin signature showed a significant prognostic effect in the whole cohort, with 28 higher expression associated with shorter MFS (p=0.034). Strong correlations were found 29 between the anti-inflammatory signature and CD8 expression (ρ=0.391; p<0.001) and be- 30 tween the pro-inflammatory signature and PD-1 expression (ρ=0.627; p<0.001).

Latin America and the Caribbean offer the most favorable natural and social conditions for the emergence of cattle ranching that regenerate and maintains the ecosystem services on which life on Earth depends, that is energy efficient and that contributes to meeting fundamental human food needs. Unlike other major global producers, cattle farming in Latin America and the Caribbean is fundamentally based on pasture. Therein lies both its strength (due to the regenerative potential of well-managed pastures) and its vulnerability (due to the pervasive link between deforestation and pasture formation, especially in the Amazon, where 40% of the Brazilian herd is concentrated). The diversification of pastures (today marked by impressive monotony, with brachiaria accounting for 85% of the species in Brazil), the introduction of legumes and tree plantations within them, and the proper management of herds, open the way to the possibility of drastically reducing the area currently occupied by the activity (especially in the Amazon) while maintaining the supply of its products. Agricultural research has disseminated forms of moderate intensification of cattle ranching, which represent a low opportunity cost of animal feed and, at the same time, regeneration of ecosystem services that have so far been destroyed by the prevailing methods of farming.

Infections are a common post-operative ailment for patients who have received a dental implant or device and can be attributed to biofilm formation in tissue or on the implant. Many current solutions for oral hygiene have side effects and affect the natural oral microbiome. 2-heptylcyclopropane-1-carboxylic acid (2CP) is a medium-chain fatty acid and synthetic diffusible signaling factor that can prevent and disperse biofilm. The purpose of this work was to evaluate an immersion strategy for coating hydroxyapatite (HAp) with 2CP to prevent biofilm attachment on and around natural teeth and dental implants. The release profile of 2CP-loaded and 2CP+oral rinse-loaded HAp coupons (n=6) was assessed by a 3-day exposure to phosphate buffered saline (PBS). Antimicrobial properties against Porphyromonas gingivalis and cytocompatibility of 2CP-loaded HAp coupons (n=4) were also assessed alone and in combination with 0.12% chlorhexidine gluconate oral rinse. The majority of 2CP is released by 12 hours. 2CP, oral rinse, and 2CP+oral rinse significantly reduced P. gingivalis viability, though direct contact assay demonstrates a significant reduction in Saos-2 viability for oral rinse and 2CP+oral rinse coupons. Immersion or rinsing hydroxyapatite with 2CP could inhibit biofilm-associated dental infections and prevent further complications including caries, gingivitis, and peri-implantitis.

Long intergenic noncoding (LINC)01270 is a 2278 bp transcript belonging to the intergenic subset of long noncoding (lnc)RNAs. Despite increased reports of LINC01270’s involvement in different diseases, evident research on its effects on inflammation is yet to be achieved. In the present study, we investigated the potential role of LINC01270 in modulating the inflammatory response in the human monocytic leukemia cell line THP-1. Lipopolysaccharide treatment upregulated LINC01270 expression, and siRNA-mediated suppression of LINC01270 enhanced NF-kB activity and the subsequent production of cytokines IL-6, IL-8, and MCP-1. Interestingly, the knockdown of LINC01270 downregulated expression of leucine zipper downregulated in cancer 1 (LDOC1), a novel NF-kB suppressor. An analysis of the LINC01270/micro-RNA (miRNA)/protein interactome profile identified miR-326 as a possible mediator. Synthetic RNA agents that perturb the interaction among LINC01270, miR-326, and LDOC1 mRNA mitigated the changes caused by LINC01270 knockdown in THP-1 cells. Additionally, a luciferase re-porter assay in HEK293 cells further confirmed that LINC01270 knockdown enhances NF-kB activation, while its overexpression has the opposite effect. This study provides insight into LINC01270’s role in modulating inflammatory responses to lipopolysaccharide stimulation in THP-1 cells via miR-326/LDOC1 axis which negatively regulates NF-kB activation.

Agroforestry is increasingly being recognized as a holistic food production system that can have numerous significant environmental, economic, and social benefits. This growing recognition is paralleled in the U.S. by the budding interest in regenerative agriculture and motivation to certify regenerative practices. Current efforts to develop a regenerative agriculture certification offer an opportunity to consider agroforestry’s role in furthering regenerative goals. To understand this opportunity, we first examine how agroforestry practices can advance regenerative agriculture’s five core environmental concerns: soil fertility and health, water quality, biodiversity, ecosystem health, and carbon sequestration. Next, we review a subset of certification programs, standards, guidelines, and associated scientific literature to understand existing efforts to standardize agroforestry. We determine that development of an agroforestry standard alongside current efforts to certify regenerative agriculture offers an opportunity to leverage common goals and strengths of each. Additionally, we determine that there is a lack of standards with measurable criteria available for agroforestry, particularly in temperate locations. Lastly, we propose a framework and general, measurable criteria for an agroforestry standard that could potentially be implemented as a standalone standard or built into existing agriculture, forestry, or resource conservation certification programs.

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

The color of carcass fat is an important factor in meat quality. To investigate the characteristics and changes in lipid metabolism of SAT in Mongolian cattle at 34 M of age compared with the control group, we evaluated the color, relative expression of genes associated with browning, and profiles of lipid metabolites by using qPCR and non-targeted lipidomics techniques. Overall, the yellowness value and relative expression of mitochondrial biogenesis–specific markers, thermogenic, UCP2, and beige adipocyte marker genes in the SAT of 34 M cattle were higher than those control (p &lt; 0.05). Using multivariate analysis, 172 significantly different lipids (SDLs) were identified. Triacylglycerols (TGs) and phosphatidylcholines (PCs) had high relative contents with abundant unsaturated fatty acids. The upregulation of TGs observed in the SAT of 34 M cattle mainly consisted of medium- and long-chain fatty acids. Pathway analysis demonstrated that 172 SDLs were primarily involved in glycerophospholipid, glycerolipid, ether lipid, and sphingolipid metabolism. In summary, yellow fat of naturally grazed cattle was impacted by many factors such as lipid metabolism, browning genes expression and age. These findings provide new insight into the characteristics and metabolic pathways of adipose tissue in natural grazing Mongolian cattle.

In this study dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [18F]GE180 and the amino acid [18F]FET were acquired and normalized to healthy background (TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

Sea urchins are long-living invertebrates with a complex immune system which includes extended families of immune receptors. A central immune gene family in the sea urchins encodes for the Transformer (Trf) proteins. The Trf family was so far studied mainly in the purple sea urchin Strongylocentrotus purpuratus. In this study, we explored this protein family in the Mediterranean Sea urchin Paracentrotus lividus. The PlTrf genes and predicted proteins were found to be highly diverse and showed a typical Trf size range and structure. We found that P. lividus coelomocytes and hemolymph contain different PlTrf protein repertoires with a shared subset which specifically bind E. coli bacteria. Using FACS, we identified five different P. lividus coelomocyte sub-populations with cell surface Trf protein expression. The relative abundance of the Trf-positive cells sharply increased following immune challenge with E. coli bacteria, but not following challenge with LPS or sea urchin pathogen V. penaeicida. Finally, we demonstrated that the phagocytosis of E. coli bacteria by P. lividus phagocytes is mediated through the hemolymph and is inhibited by blocking Trf activity with anti-Trf antibodies. Together, our results suggest collaboration between cellular and humoral Trf-mediated effector arms in the P. lividus specific immune response to pathogens.

The therapeutic, attenuative, and morphological effects of proprietary neural stem cell-derived extracellular vesicles (NSC EVs, AB126) produced by Aruna Bio, Inc. were assessed in a range of in vitro and in vivo models of stroke. We emphasize that modulation of neuroinflammation is a key target and suggest further studies to advance our understanding of the mechanisms of action and ultimately how best to dose and monitor the benefits of AB126 in stroke patients.

Aims: This study aims to evaluate the impact of family-centered empowerment on Jordanian adolescents with type 1 diabetes (T1DM), focusing on their HbA1c levels, self-efficacy, and quality of life (QOL). Background: Poor glycemic management in adolescents with type 1 diabetes increases complications. Improved control is linked to various variables, but few studies focus on Middle Eastern populations. Methods: An experimental study involved 68 adolescents with T1DM visiting Jordanian Royal Medical Services' clinics. Two sets of participants were created: control (n = 34) and intervention (n = 34). Data was collected through face-to-face interviews and medical records. Results: The study found significant differences in self-efficacy scores between the intervention and control groups, with the intervention group experiencing a significant decrease in HbA1c readings and a significant difference in QOL between pre-program and post-program phases. Discussion: Family empowerment can significantly improve the lives of Jordanian teenagers with type 1 diabetes. This strategy leads to improved glycemic management, increased self-efficacy, and improved quality of life. Future treatments and health policies should recognize and value the critical role families play in the care of this population. Conclusion: The study suggests that patients with T1DM should receive continuous care education sessions, including self-care training, to improve their health. Nurses should also incorporate these training into treatment plans and educational programs for adolescents to enhance their QOL.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Background: CCL11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL11 plays a role in brain disorders as well. Aims: This paper reviews the associations between CCL11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders.Methods: Electronic databases were searched for original articles examining CCL11 in neuropsychiatric disorders.Results: CCL11 is rapidly transported from the blood to the brain through the brain-blood barrier. Age-related increases in CCL11 are associated with cognitive impairments in executive functions, episodic and semantic memory and, therefore, this chemokine was described as an “endogenous cognition deteriorating chemokine” (ECDC) or “accelerated brain-aging chemokine” (ABAC). In schizophrenia, increased CCL11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL11 levels. In diseases of old age, CCL11 is associated with lowered neurogenesis and neurodegenerative processes and, as a consequence, increased CCL11 increases risk towards Alzheimer's Disease. Polymorphisms in the CCL11 gene are associated with stroke. Increased CCL11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL11 may protect against nigrostriatal neurodegeneration. Increased production of CCL11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies.Conclusion: Increased CCL11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL11 production is a new drug target in the treatment and prevention of those disorders.

In the last decades, studies on the inflammatory signaling pathways in multiple pathological contexts revealed new targets for novel therapies. Among the family of G-protein-coupled Proteases Activated Receptors, PAR2 was identified as a driver of the inflammatory cascade in many pathologies, ranging from autoimmune disease to cancer metastasis. For this reason, many efforts have been focused on the development of potential antagonists of PAR2 activity. This work focuses on a small molecule, 1-Piperidine Propionic Acid (1-PPA), previously described to be active against inflammatory processes, but whose target is still unknown. Stabilization effects observed by cellular thermal shift assay coupled to in-silico investigations, including molecular docking and Molecular Dynamics simulations, suggested that 1-PPA binds PAR2 in an allosteric pocket of the receptor inactive conformation. In addition, this compound was found able to inhibit platelet aggregation, a process mediated by PAR family members, including PAR2. Since the allosteric pocket binding 1-PPA is highly conserved in all the members of the PAR family, the evidence reported here suggests that 1-PPA could represent a promising new small molecule targeting PARs with antagonistic activity.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, has potency to prevent pathological mitochondrial fission by inhibiting protein-protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca2+ channel blocking action of cilnidipine, prevent the palmitic ac-id-induced Drp1-filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high fat diet-fed mouse livers. These results propose that targeting Drp1-filimin interaction becomes a new strategy for the prevention or treatment of fatty liver disease.

Stress during a pandemic increased the risk of alcohol consumption, which may require pharmacological management. The characteristics of emergency calls for alcohol-related issues for patients pharmacologically treated, admitted to, or not admitted to the emergency department (ED) were analyzed. An observational single-center retrospective study was conducted from January 1, 2018 to December 31, 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the EDs of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ES) who were either admitted or not admitted, due to their refusal. A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, a reduced rate of pharmacological treatment for calls coded green (non-critical), and an increase in calls coded yellow (fairly critical) and red (very critical) were recorded. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

In recent decades, reports of deforestation, mass extinctions, biodiversity loss, and emergencies like floods and droughts have clearly highlighted the impact of human activities on these outcomes. This underscores the need for significant lifestyle changes to mitigate this impact. Pro-environmental behavior (PEB) change involves adopting actions that protect the environment and reducing environmentally harmful activities. While qualitative research may provide unique insights into PEB barriers that are challenging to capture through quantitative methods, reports of qualitative studies are scattered across different literatures with little integration. With the present review, we bring together insights from qualitative studies on PEB barriers and examine whether those studies reveal barriers compatible with existing barrier frameworks from environmental psychology. We identified 38 qualitative studies on barriers to PEB change. Our analysis revealed that most of the barriers to individual pro-environmental action identified in qualitative studies align with environmental psychology frameworks. These barriers were experienced not only by individuals in their role as consumer or citizen, but also by community-level actors (e.g., seeking to implement pro-environmental policies) and industrial decision-makers (e.g., aiming to reduce the ecological footprint of their business activities). Our findings underscore the multifaceted nature of barriers to PEB change and emphasize the importance of addressing structural and institutional factors alongside individual-level interventions.

This paper presents a Cartesian model of sustainability by a novel integration of Circular Economy principles and ESG (Environmental, Social, and Governance) criteria to explicitly establish a clear path for closing the loops of negative social and environmental externalities. As global sustainability transformations accelerate, they bring both opportunities and inherent financial risks and social uncertainties. Historically, economic development has often been achieved at the expense of environmental balance. The contemporary challenge is to attain a dynamic equilibrium between natural and socio-economic systems. We introduce an integrated, multidisciplinary, and dynamic framework for studying and managing sustainability transitions. Our innovative 4-quadrant framework utilizes a Cartesian coordinate system to map the impacts of various business models on natural and socio-economic systems, spanning from linear open-loop to circular closed-loop ESG models. The framework is data-driven, employing normalized coordinates (-1 to 1) to facilitate empirical analysis and the establishment of temporal Key Performance Indicators. By integrating the Human Development Index within ecological limits, our model targets regenerative development that harmonizes human progress with planetary boundaries. This versatile and robust framework serves as a practical tool for businesses, households, organizations, and policymakers to navigate the complexities of sustainable development, promoting innovation and fostering a just transition towards regenerative practices. Our approach provides a comprehensive roadmap for achieving high human development within the planet's ecological limits, contributing significantly to the broader discourse on sustainability science and management.

Breast cancer (BC) ranks among the most prevalent cancers diagnosed in women. Its treatment necessitates precision tailored to the cancer's genetic makeup for enhanced efficacy. Research has been directed towards natural compounds for their anti-BC properties, aiming to augment existing treatment modalities. Chromolaena tacotana (Klatt) R.M. King and H. Rob, commonly referred to as Ch. tacotana, is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant's inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from Ch. tacotana inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in Luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between the chalcone and various anti-apoptotic proteins, including the mTOR protein. The chalcone was identified as 2',4-dihydroxy-4',6'-dimethoxy-chalcone (DDC), also known as Flavokavain C (FKC). This compound demonstrated selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study observed the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in MCF-7 and MDA-MB-231 cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents like the hydroxy-methylated flavonoids from Ch. tacotana.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSIL) but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3-month supplementation with 600 mg of ALA on antioxidant- and lipid status param-eters in 100 patients with LSIL were investigated in randomized placebo-controlled study. Obtained results were discussed in terms of patients’ initial metabolic status and diet quality (particularly nutritional intake of antioxidants). Obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted with small but statistically significant increase of serum low density lipoprotein (LDL) and observed effect was significantly affected by the initial lipid status of participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Cyanobacterial mass developments in eutrophic ponds and lakes are a major concern for lake management, as many cyanobacteria produce a huge variety of toxic secondary metabolites, e.g. microcystins. The aim of this research was to culture a strain of the cyanobacterium Microcystis sp strain BM25, to observe its biomass production and to isolate and purify protease inhibitors from this cyanobacterial biomass. Different secondary metabolites were isolated following a standard bioassay-guideline. Isolation was performed, with an enzymatic protease assay as bioassay. High performance liquid chromatography was used to identify different fractions of secondary metabolite from the strain BM25. Moreover, protease homogenates were isolated from Daphnia magna in order to test the inhibitors against naturally occurring major digestive proteases trypsin and chymotrypsin. It was measured that 60% MeOH and the 80% MeOH C18-SPE fraction inhibits chymotrypsin activity 98% (6 nmol pNA min^-1 mg^-1) and 99 % (4 nmol pNA min^-1 mg^-1), respectively. In contrast, trypsin activity was not inhibited by methanolic extracts of this cyanobacterium strain.

Based on research data from the renovation of old residential areas in Chengdu, China, this study provides empirical evidence regarding the causal relationship between urban renewal and the transformation of residents' pro-environmental behaviors. The research findings demonstrate a significant enhancement in residents' engagement in pro-environmental behaviors due to the renovation of old residential areas. Robustness tests based on replacement samples and two-stage difference-in-difference models also confirm the reliability of the conclusions. The preliminary mechanism test indicates that the mechanism of the impact of renovation of old residential areas on the transformation of residents' pro-environmental behaviors can be attributed to two main factors. Firstly, the improvement of environmental infrastructure provides residents with better conditions for participating in pro-environmental activities. Secondly, there is an elevation in residents' environmental protection awareness, prompting a more voluntary engagement in pro-environmental behavior. This study suggests that decision-makers should fully recognize that urban renewal activities nationwide are not only a process of improving urban hardware and functionality, but also a realistic and vivid "environmental education" course for the whole nation. Taking urban renewal as an opportunity to enhance citizens' awareness of environmental protection will effectively promote the transformation of pro-environmental behaviors among residents.