There is increasing evidence that COVID-19 induces endothelial dysfunction that may precede thrombotic and cardiovascular complications. The aim of this study is to evaluate the endothelial function using peripheral arterial tonometry (EndoPAT). The primary endpoint is the hyperemic vascular response index (LnRHI) at two months post-discharge. Secondary endpoints include the LnRHI during hospitalization and at six months follow-up, the proportion of patients with endothelial dysfunction (LnRHI≤0.51), and the incidence of thrombotic events, cardiovascular complications, and mortality during the follow-up period. The study included 23 COVID-19 patients and 22 healthy matched controls. The patients exhibited a significant reduction in the LnRHI at two months post-discharge compared to the controls (median=0.55 [IQR: 0.49-0.68] vs median=0.70 [IQR: 0.62-0.83]; p=0.012). The difference in the LnRHI between patients and controls was evident from hospitalization and persisted at two and six months without significant temporal changes. The proportion of COVID-19 patients with endothelial dysfunction (LnRHI≤0.51) was 61% during hospitalization, and 55% at six months. There was no significant difference in thrombotic or cardiovascular events, nor in mortality. This study demonstrates that COVID-19 adversely affects endothelial function, as evidenced by a reduction in the hyperemic vascular response index, and the endothelial dysfunction may also persist.

Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (> 100 mg/L) and signs of respiratory failure were treated with CRP apheresis. 2-12 CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest x-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. All patients had comorbidities. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation require-ments. Our clinical observations regarding the here presented seven patients support the hypoth-esis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.

INTRODUCTION: The purpose of the study was to determine (a) the overall preclinical character; (b) the cumulative cutoff values and the risk ratio, and (c) the factors associated with severity by a unidimensional and multidimensional analysis on 2173 Sars-Cov2 patients. METHODS: The machine learning study population consisted of 2173 patients (1587 mild and non symptoms patients, 377 moderate patients, 209 severe patients). The status of the patients was recorded from September 2021 to March 2022. RESULTS: The Covid19 Severity directly links with a significant correlation to Age, Score index of the chest X-ray, percentage and quantity of neutrophils, Albumin, C reactive protein, and ratio of Lymphocytes. Their important cut off values (from regression analysis) respectively are: 77.56 years old (the mild-moderate group), 5.53 (the mild-moderate group) and 10.51 (the moderate-severe group), 84.80% (the mild-moderate group) and 87.74%(the moderate-severe group), 11.77G/L (the moderate-severe group), 29.73g/L (the moderate-severe group), 7.46mg/dL (the mild-moderate group), 6.32% (the moderate-severe group). Their significant (p<0.0001) R score correlation with the severity of Covid19, are: 0.44, 0.52 and 0.52, 0.33 and 0.44, 0.42, -0.43, 0.40, -0.41. Their significant risk ratio (p<0.00001) from the meta-analysis, respectively are: 4.19 [3.58-4.95], 3.29 [2.76-3.92] and 3.03 [2.4023;3.8314], 3.18 [2.73-3.70] and 3.32 [2.6480;4.1529], 3.15 [2.6153;3.8025], 3.4[2.91-3.97], 0.46 [0.3650;0.5752] (p<0.00001), 0.34 [0.2743;0.4210]. The pair ALT – Leucocytes and Transferrin – Anion Chloride get the most important correlation shift. ALT – Leucocytes show the important negative link (R=-1, p<0.00001) in the mild group to the significant positive correlation in the moderate group (R=1, p<0.00001). Transferrin–anion Chloride has an important positive association (R=1, p<0.00001) in the mild group with a significant negative correlation in the moderate group (R=-0.59, p<0.00001). The network map and HCA show that in the mild-moderate group, the closest neighbors with the Covid19 severity are ferritins, Age. Then there is C-reactive protein, SI of X-ray, Albumin, and Lactate dehydrogenase, which are the next close neighbors of these three factors. In the moderate-severe group, the closest neighbors with the Covid19 severity are Ferritin, Fibrinogen, Albumin, the quantity of Lymphocytes, SI of X-ray, white blood cells count, Lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: Complete multidimensional study in 2173 Covid19 patients in Vietnam shows the whole picture of all the preclinical factors, which may become the clinical reference marker for surveillance and diagnostic management

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

Evidence suggests that COVID-19 infection increases the risk of type 1 (T1D) and type 2 diabetes (T2D). Diabetes, in turn, increases COVID-19 susceptibility and contributes to increased COVID-19 morbidity and mortality. Oxidative stress (OxS) has emerged as a common factor driving the pathogenesis of diabetes and COVID-19 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The mechanistic links between OxS, T2D, and COVID-19 have primarily been studied in adults and will be summarized in this review. However, we suggest that studying these interconnections in children and young adults is critical since early intervention is optimal for improving outcomes. At the height of the pandemic, COVID-19 was a leading cause of death in children and young people, and people in this age group are as susceptible to COVID-19 as adults and the elderly. Glutathione (GSH) is the primary water-soluble intracellular antioxidant and can be deficient in both diabetes and COVID-19. GSH is a tripeptide containing cysteine (CYS), glutamic acid (GLU), and glycine (GLY). Strategies to increase GSH levels may be beneficial in helping to manage COVID-19-induced diabetes as well as diabetes-induced COVID-19 risk. Dietary supplementation with GlyNAC may be optimal since it contains two metabolic GSH precursors, i.e., n-acetyl-l-cysteine (NAC) and GLY.

The oxidative stress is one of the main cause for cardiovascular diseases (like Hypertension) also one of the results of these diseases. This study involved 56 subjects matched ages and sex divided into two groups; 28 hypertensive subject and 28 healthy subject as control group. The following analysis was done: 4-Hydroxy-2-nonenal(4HNE) and albumin. The results show that there is a significant increase in (4HNE) between patients group and control group. The increase in 4HNE which is a product of lipid peroxidation is attributed to destruction in body cell caused by due to the increase in stress events. It has been concluded that is important nappy on ideal weight, because obesity considered main factors for heart disease and hardening of the arteries. The aim of this study was to investigate the relationship between of some oxidative stress markers and cardiovascular diseases.

COVID-19 has become a severe global public health concern. The critical illness has a mortality rate of 61.5%, and thus, reducing the severity and mortality is top priority. Currently, inflammatory storms are considered as the cause of critical illness and death due to COVID-19. However, After systematical review of the literature, we proposed that cross-reactive antibodies-associated antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies of the virus, we speculate that the ADE can be avoided and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such conditions. We recommend that pharmaceutical companies conduct clinical trials urgently.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

The clinical relationship between diabetes and inflammation is well-established. Various branches of science independently have confirmed that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with Type 2 diabetes mellitus (T2DM). Under diabetic condition, hyperglycemia, especially inflammation, and increased reactive oxygen species generation are bidirectionally associated. Inflammation, oxidative stress and tissue damage are believed to have a role in the development of diabetes. Although the exact mechanism underlying the oxidative stress and its impact on diabetes progression remains uncertain, the hyperglycemia-inflammation-oxidative stress interaction clearly plays a significant role in onset and progression of vascular disease, kidney disease, hepatic injury, pancreas damage and, therefore holds promise as a therapeutic target. Evidence strongly indicates that the use of multiple antidiabetic medications therapy fails to achieve the normal range for glycated hemoglobin target, signifying treatment resistant diabetes. Antioxidants with polyphenols are considered useful as adjuvant therapy for their potential anti-inflammatory effect and antioxidant activity. We aimed to analyze the current major points reported in preclinical in vivo and clinical studies of antioxidants in the prevention or treatment of inflammation in T2DM. Then, we will share our speculative vision of the future diabetes clinical trials.

Background: Acute pancreatitis is a common emergency. Morbidity control requires early detection of disease severity. METHODS: A total of 131 AP patients were analyzed retrospectively. Patients were divided into two groups mild AP (MAP: Ranson score <3) and severe AP (SAP: Ranson score ≥3), according to Ranson’s criteria. Demographic data, hospitalization duration, PNI, CRP, and RDW levels were compared. Any p-value below 0.05 (p<0.05) was accepted as statistically significant. RESULTS: Study included 67 (51.15%) males and 64 (48.85%) females. The age average was 59.74 (19-90) years. 95 (72.52%) patients had MAP, and 36 (27.48%) patients had SAP. Mean hospitalization time, PNI, and CRP differed significantly between the two groups (p=0.010, p<0.05, p<0.05, respectively). The RDW (p=0.380) level difference was insignificant. For SAP prediction; the sensitivity, specificity and cut-off value according to Ranson code cut-off point for PNI were determined as 80.0% (95% CI:54.8-85.8), %72.2 (95% CI:70.5-87.5) and ≤45.6 (gr/L) + (mm3), respectively, and 94.7% (95% CI:57.8-87.9), %75.0 (95% CI:88.1-98.3) and >105,1 mg/L, respectively for CRP. CONCLUSION: PNI and CRP values (but not RDW values) were compatible with the disease severity determined by the Ranson criteria.

Background: The predictive value of changes in C-reactive protein (CRP), procalcitonin and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. This study aims to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of patients admitted to the intensive care unit (ICU) with a diagnosis of pneumosepsis and pneumonia-related septic shock, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Methods: The study analyzed the demographic data, Charlson Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65 years), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores of 230 patients admitted to the ICU with a diagnosis of pneumosepsis and pneumonia-related septic shock between April 1, 2022, and December 31, 2023. The levels of CRP, procalcitonin, and leukocytes were also recorded and analyzed to assess their impact on 1-month and 3-month mortality outcomes. Results: According to multivariate logistic regression analysis, low BMI, male gender, high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p<0.05). An elevated SOFA score was associated with 1-month mortality, while advanced age was related to 3-month mortality (p<0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both 1-month and 3-month mortality cases (p<0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared to those who survived (p=0.004). Discussion: Although PCT, CRP, and leukocyte values measured at the time of admission were not significantly associated with 1-month mortality in patients with pneumosepsis or pneumonia-related septic shock, the persistent elevation and concurrent increase of these values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, impaired epidermal barrier function and unbalanced inflammatory response. The pathophysiology involves immune dysregulation, with a predominance of T-helper 2 cells. AD is triggered by many known and unknown factors, including oxidative stress. Reactive oxygen species (ROS) contribute to AD pathogenesis by causing cellular damage and inflammation. Moreover, increased oxidative stress in AD leads to hyperactivation of the MAP kinase pathway, extracellular signal-regulated kinase (ERK) and p38, with DNA damage and subsequent skin barrier dysfunction. This narrative review provides a comprehensive overview of the role of natural antioxidant compounds, highlighting their potential therapeutic value in AD management. They include vitamin D, vitamin E, pyridoxine (vitamin B6), Vitamin C, carotenoids and melatonin, in AD. Despite some studies have shown an association between vitamin D, vitamin E, vitamin C and carotenoids levels and AD course, conflicting results exist. Pyridoxine supplementation has shown mixed results, and melatonin has demonstrated antioxidant and anti-inflammatory properties in AD; in fact, melatonin treatment resulted in a decrease in symptoms in patients with AD, although no significant correlation with changes in sleep latency was reported. In addition, iron and zinc (Zn) supplementation can also improve AD symptoms. Further research is needed to elucidate the optimal use of these natural antioxidants in AD treatment

Although a slight imbalance between oxidative and antioxidative mediators is part of normal physiology that enables cell aging and the removal of dead cells, burns disturb this equilibrium locally and systemically. Topical burn dressings may attenuate local and systemic oxidative stress and positively influence the post-burn clinical course. This review integrated knowledge regarding the impact of burn dressings on oxidative stress. Using keywords and in-text searches, literature was identified from PubMed, Google Scholar, and Google articles, and studies on local or topical applications of wound dressings and associated oxidative stress were selected. As im-balances between oxidative mediators and antioxidative agents significantly contribute to organ dysfunction and healing disturbance, we investigated oxidative stress on organs, metabolic changes, clinical results, and oxidative parameters influenced by applied dressings. We found positive local and systemic effects of external burn dressings in laboratory and animal tests; however, such studies were rare in humans. Nevertheless, we identified successful cases of semi-occlusive, occlusive, and biologically active dressings that reduce oxidative stress in hu-man burns. In particular, we highlight promising clinical and laboratory results from lac-tate-releasing dressings. Our review provides an invaluable resource for future development and clinical applications of burn dressings.

Background: Bloodstream infections (BSIs) pose a major health risk to hemodialysis patients, significantly contributing to morbidity and mortality. This study aimed to identify the bacterial pathogens responsible for BSIs in this population, analyze clinical and laboratory profiles, and identify risk factors associated with poor outcomes. Methods: This retrospective study was conducted at Sohar Hospital, Oman, analyzing cases from January 2018 to December 2022. Data were obtained from e-health records, focusing on patient demographics, bacterial etiology, antibiotic susceptibility, and clinical outcomes. Statistical analysis included t-tests, Mann-Whitney tests, chi-square, and Fisher’s exact tests, with univariate odds ratios calculated for mortality associations using the R package GTSUMMARY. Results: Among 1332 hemodialysis patients, 148 (11.1%) developed a BSI, with an average age of 60.43±14.46 years. Infections were more common among females (54%) and those over 60 years. The predominant comorbidities were hypertension (86%) and diabetes mellitus (74%). The main causative agents were coagulase-negative staphylococci (29.7%), Staphylococcus aureus (20.3%), Pseudomonas aeruginosa (12.2%), and Klebsiella pneumoniae (8.8%). Gram-negative bacteria showed high susceptibility (80-100%) to carbapenems and piperacillin-tazobactam, while Gram-positive bacteria exhibited 80-100% susceptibility to amoxicillin-clavulanic acid and universal sensitivity to linezolid and vancomycin. Conclusions: BSIs in hemodialysis patients at Sohar Hospital are associated with high morbidity and mortality rates, underscoring the need for prompt empirical antibiotic therapy and targeted treatment adjustments based on culture results. This study highlights critical mortality-associated factors, offering valuable insights for improving patient management and survival outcomes in this vulnerable population.

Thalassemia is a heterogeneous congenital hemoglobinopathy common in the Mediterranean region, Middle East, Indian subcontinent, and Southeast Asia with increasing incidence in Northern Europe and North America due to immigration. Iron overloading is one of the major long-term complications in patients with thalassemia and can lead to organ damage and carcin-ogenesis. Hepatocellular carcinoma (HCC) is one of the most common malignancies in both transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). The incidence of HCC in patients with thalassemia has increased over time, as better chelation therapy confers a sufficiently long lifespan for the development of HCC. The mechanisms of iron overloading-associated HCC development include the increased　reactive oxygen species (ROS), inflammation cytokines, dysregulated hepcidin, and ferroportin metabolism. The treat-ment of HCC in patients with thalassemia was basically similar to those in general population. However, due to the younger age of HCC onset in thalassemia, regular surveillance for HCC development is mandatory in TDT and NTDT. Other supplemental therapy and experience of novel treatment for HCC in thalassemia population were also reviewed in this article.

Background: C-reactive protein (CRP) is a predictive biomarker of colorectal surgery (CRS) complications but has not been evaluated by comparing patients undergoing CRS with intracorporeal anastomosis (IA) or extracorporeal anastomosis (EA). Therefore, we aimed to describe postoperative CRP values between two groups of patients who underwent laparoscopic right hemicolectomy for right-side colon cancer with IA or EA. Methods: We retrospectively reviewed the data of patients affected by right-side colon cancers who underwent laparoscopic right-hemicolectomy with ileo-colic IA or EA between January 2016 and December 2022. Results: A total of 340 patients underwent laparoscopic right hemicolectomy. EA was performed in 238 (70%) and IA in 102 (30%) cases. Patients with IA showed significantly higher values of CRP in the second, third and fourth postoperative days (15.2 mg/dL vs 9.5 mg/dL p=

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine).is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), in vitro. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n=3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

Osteoporosis, often linked to increased osteoclast activity due to menopause or aging, was the focus. In this study, the inhibitory effects of Salicornia europaea L. (SE) water extract of desalted SE (WSE) were investigated on osteoclast differentiation and bone loss in ovariectomized mice. The findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as evidenced by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. Gene expressions related to osteoclast differentiation, including NFATc1, TRAP, cathepsin K, and DC-STAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoyl quinic acids (DCQAs) and saponins in WSE were detected, with 3,4-, 3,5-, and 4,5-DCQA isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQA, as preventive or therapeutic agents against osteoporosis and related conditions.

C-reactive protein to lymphocyte ratio (CLR) has been shown to be associated with diseases characterized by chronic, low-grade inflammation. Since type 2 diabetes (T2DM) is also associated with inflammation, we aimed to study the association between CLR and T2DM. Patients with T2DM who presented to internal medicine outpatient clinics of our institution were divided into 2 groups according to their glycosylated hemoglobin (HbA1c) levels as well-controlled (HbA1c&lt;7%) and poorly controlled (HbA1c≥7%) T2DM groups. Subjects assigned as healthy in routine check-up were included as control group. CLR values of the well and poorly controlled diabetics and control cases were compared. CLR of T2DM group (3.51 (0.03-21.78)) was significantly higher than that of the controls (0.65 (0.02-2.92)) (p&lt;0.001). CLR was found to have a sensitivity of 63.2% and a specificity of 97.3% in predicting T2DM. The CLR value of patients with poor diabetic control was 4.76 (0.06-21.78), while the CLR value of patients with well controlled disease was 2.53 (0.03-12.07) (p&lt;0.001). The sensitivity and specificity of the CLR in demonstrating poor diabetic control was 41.2% and the 86.1%, respectively. In conclusion, elevated CLR in T2DM patients and even more increased levels in poorly controlled diabetics suggest that CLR could be a useful additional diagnostic tool in treatment follow-up of the T2DM population.

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants – primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction, to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are in order, a viral infection, a metabolic disorder, an ischemic event, and a neurodegenerative disorder. OS may be an early initiator or a significant promotor of their progressive pathophysiologic processes. Consequently, addressing initial OS-related pathology may avoid subsequent severe and irreversible complications. Early intervention would modulate multiple factors, including cytokine stimulation, complement dysregulation, immuno-thrombosis, fibrosis, and autoimmunity. Past clinical studies that addressed OS have had equivocal results. It may be due to the use of ineffective antioxidants, an untimely delay in their use, or an inefficient delivery system. Experimental studies have used antioxidants that are not available for clinical trials. Although GSH can significantly reduce OS, its exogenous use is hampered by the lack of an effective delivery system. By incorporating GSH into cyclodextrin (CD) through nanotechnology, there is recent evidence that exogenous GSH can be delivered more effectively to prevent or mitigate injury from OS [1]. Future studies using the GSH/cyclodextrin (GC) complex will be needed to confirm its effectiveness and, hopefully, offer a path to treat many sub-optimally managed or currently untreatable illnesses.

Medical ozone is a redox regulator with beneficial effects in oxidative etiology diseases such as rheumatoid arthritis (RA). The aim of this study was to conduct a holistic review from different pharmacological trials involving ozone in model diseases as well as the clinical response of RA patients. The ROS involved in RA and its relationship to the main pathological pathways of this autoimmune disease were here considered. The integrator analysis of experimental results from animals with clinical findings have revealed that both methotrexate (MTX) and medical ozone share common mechanisms via adenosinergic regulation. This finding has enabled us to propose a new pharmacological mechanism in the treatment of RA. We concluded that MTX + medical ozone combined therapy reduces ROS overproduction and the generation of proinflammatory cytokines, and decreases anti-cyclic citrullinate peptide levels by a mutual mechanism involving adenosine A1 receptors.

The manufacture of SiC-based composites is quite widespread, and currently different methods are employed for to produce them. The most efficient method, taking into account the cost/performance ratio, is reactive melt infiltration. It consists in infiltrating liquid silicon into a porous preform that must contain carbon, so that SiC is produced during infiltration. This chemical reaction is, in fact, the driving force of the process. In the present work, the synthesis of two SiC-based composite materials with very different applications and microstructures has been studied and optimized. In both cases, materials have been obtained with suitable properties for the selected applications. One of the materials studied is SiCp/Si for protection systems such as armor jackets, and the other one is Cf/SiC for use in braking systems. For the optimization, the dwell time and the atmosphere (Ar or primary vacuum) were used as variables. It has been found that in both preforms the optimum conditions are 1 hour dwell time and a vacuum atmosphere at 1450 °C. The effect of these parameters on microstructure and infiltration kinetics are discussed.

Background: Although lower extremity revascularization is commonly performed in hemodialysis patients, poor prognosis remains a major problem. Protein-energy wasting is reportedly associated with chronic inflammation and advanced atherosclerosis in hemodialysis patients. We investigated the association between the geriatric nutritional risk index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in the prediction of amputation and/or mortality. Methods: We enrolled 800 patients successfully underwent lower extremity revascularization. Patients were divided into low, middle and high tertile (T1, T2 and T3) according to GNRI and CRP levels, respectively. Results: Amputation-free survival rates for 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI, and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p<0.0001 for both). Declined GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p=0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95%CI 1.30-2.70, p=0.0007 for T3 vs. T1) were independent predictors of amputation and/or mortality. In the combined setting of both variables, the risk was 3.77-fold higher (95% CI 1.97-7.69, p<0.0001) in the T1 of GNRI with T3 of CRP than in the T3 of GNRI with T1 of CRP. Conclusions: Patients with pre-procedural decreased GNRI and elevated CRP levels frequently experienced amputation and/or mortality, and a combination of both variables could more accurately stratify the risk.

Background/Aim: Performing emergency surgery for bowel obstruction continues to place a significant strain on the healthcare system. Conventional assessment methods for outcomes in bowel obstruction cases often concentrate on isolated factors, and the evaluation of results for individuals with bowel obstruction remains poorly studied. This study aimed to examine the risk factors associated with major postoperative complications. Methods: We retrospectively analyzed 99 patients undergoing surgery from 2015 to 2022. We divided the patients into two groups: 1) benign related obstruction (n=68), 2) cancer related obstruction (n=31). We used logistic regression, KNN and XGBOOST. We calculated the receiver operating characteristic curve, and accuracy of the model. Results: Colon obstructions were more frequent in the cancer group (p=0.005). Operative time, intestinal resection and stoma were significantly more frequent in the cancer group. Major complications were 41% for the cancer group vs. 20 in the benign group (p=0.03). Uni-and multivariate analysis shows that significant risk factors for major complication were cancer related obstruction and CRP. The best model was KNN with an accuracy of 0.82. Conclusion. Colonic obstruction is associated with a tumor-related blockage. Malignant cancer and an increase in C-reactive protein (CRP) are significant risk factors for patients who have undergone emergency surgery due to major complications. KNN could improve the process of counseling and the perioperative management of patients with intestinal obstruction in emergency settings.

Nonalcoholic fatty liver disease (NAFLD) is a liver metabolism-associated steatohepatitis caused by non-alcoholic factors. NAFLD is currently the most prevalent liver disease in the world, affecting one-fourth of the world's population, and its prevalence increases with age. There are no approved drugs specifically for the treatment of NAFLD, and one important reason hindering drug development is the lack of effective biomarkers. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. Coincidentally, hepatocytes are responsible for the major CRP production, and the levels of CRP increase with age. Therefore, CRP is not only a potential marker, but also acts as a key factor driving liver aging and NAFLD. Herein, we reviewed the biological function and production mechanism of CRP and the relationship between CRP and NAFLD. We also comprehensively described the potential molecular mechanisms of CRP-mediated signaling in aging-associated NAFLD. Finally, we proposed possible therapeutic approaches based on the mechanism of CRP signaling in the pathogenesis of NAFLD. We hope this study can provide new insights into the development of aging associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

The brain's unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain vascular tone vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or presenting acute brain injuries. The brain's high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, with a potential impact on cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. Reactive nitrogen species (RNS), particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone during high oxidative stress conditions. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, as well as to explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.

Background: Strong indicators of inflammation, such as C-reactive protein (CRP), hypersensitive CRP (hs-CRP), and a series of hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and red blood cell distribution width (RDW), are regarded related with the incidence of contrast induced nephropathy (CIN) closely. Whereas, it remains unclear whether they can function as predictors of CIN onset. The objective of this meta-analysis was to determine the relationship between above indicators and CIN incidence among patients receiving coronary intervention. Methods: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to June 3rd, 2020. Meta-analysis was performed on pool eligible studies. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 26 studies involving 29,454 patients were included in the meta-analysis. Pooled analysis results revealed that patients with higher CRP (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.01–1.12, P=0.02), hs-CRP (OR=1.03, 95% CI: 1.01–1.06, P=0.004), NLR (OR=1.11, 95% CI: 1.01–1.20, P=0.02), RDW (OR=1.35, 95% CI: 1.19–1.53, P<0.00001), and lower HCT (OR=0.94, 95% CI: 0.92–0.97, P=0.0003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR=1.12, 95% CI: 0.99–1.26, P=0.07). Conclusion: The meta-analysis reported here demonstrates that pre-angiography CRP/hs-CRP and some hematological indices are associated with CIN.

Neurodegenerative diseases like Alzheimer’s disease (AD) are poised to become a global health crisis, and therefore understanding the mechanisms underlying the pathogenesis is critical for the development of therapeutic strategies. Mutations in genes encoding presenilin occur in most familial Alzheimer’s disease but the role of PSEN in AD is not fully understood. In this review, the potential modes of pathogenesis of AD are discussed, focusing on calcium homeostasis and mitochondrial function. Moreover, research using Caenorhabditis elegans to explore the effects of calcium dysregulation due to presenilin mutations on mitochondrial function, oxidative stress and neurodegeneration is explored.

Schizophrenia is a spectrum of neuropsychiatric deformities, characterized by hallucination, delusion, mood disorders, speech pathology, and neurocognitive deficits. Among various clinical manifestations, hallucination has been recognized as a core psychotic symptom that occurs more frequently in schizophrenia. A significant number of subjects with neurocognitive disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and other neurological diseases like stroke and epileptic seizure also experience hallucinations. While aberrant neurotransmission has been linked to the neuropathogenic events of schizophrenia, the specific cellular mechanism contributing to hallucinations remains ambiguous. Neurodegeneration in the hippocampus of the brain has been identified as a predominant pathogenic determinant of dementia. While the scientific proof for the neurodegeneration in schizophrenia is limited, the occurrence of dementia in schizophrenia has become increasingly evident. To note, both neurodegenerative, neurodevelopmental, and neuropsychiatric disorders display impaired neurogenesis in the brain. Impaired neurogenesis in the hippocampus has been linked to dementia and mood disorders. Notably, the early phase of many neurodegenerative disorders has been characterized by reactive neuroblostosis and aberrant cell cycle activation in mature neurons leading to the fluctuation in neurogenic processes leading to abnormal synaptogenesis and neurotransmission in the brain. Thus, this article emphasizes a hypothesis that aberrant neurogenic processes could be an underlying mechanism of hallucination in schizophrenia and other neurological diseases.

It is now well accepted that most chronic diseases have a common feature which is “low-grade” inflammation. Whether inflammation is causal or rather consequent to these diseases is still a matter of debate. A key factor of inflammation is considered to be “oxidative stress”, which is the result of an alteration of redox homeostasis which is critical for the regulation of physiological cell and organ metabolism and proliferation. The term “oxidative stress” is how-ever often used in an inappropriate manner as the primary target of the initial oxidative radical, superoxide ion, is nitric oxide which, being in large excess, acts as a “buffer”, yielding reactive nitrogen species. It is only once the superoxide fluxes exceed the nitric oxide fluxes that true “oxidative stress” occurs. Nitro-oxidative stress is a more appropriate term which takes into account the evolving generation of reactive nitrogen and oxygen species and their effects on cell and organ pathophysiology. The molecular bases of redox homeostasis and nitro-oxidative stress will be presented and discussed using obesity-linked inflammation as a path-ophysiological example.

Background: Macrophage inflammatory protein-1 alpha (MIP-1α) and C-reactive protein (CRP) are pro-inflammatory biomarkers that quantify clinical and subclinical inflammation in cardiac ischemia in cardiac inflammation and disease. Adiponectin is an anti-inflammatory marker associated with good health. The susceptibility of periodontitis patients to cardiovascular events needs to be evaluated. Objective: This study aims to assess the levels of biomarkers in periodontitis patients with and without acute myocardial infarction (AMI) compared to controls. Material and methods: Pro-inflammatory and anti-inflammatory analytes were examined by collecting unstimulated saliva from three groups (n = 20/each): healthy individuals, individuals with stage III periodontitis, and post-myocardial infarction patients with stage III periodontitis. The samples were collected within 48 hours of AMI. Results: Adiponectin levels were significantly lower in patients with periodontitis with and without AMI compared to controls, while CRP and MIP-1α were significantly higher in patients with periodontitis with and without AMI compared to controls. The highest titers for MIP-1α and CRP were detected among patients with periodontitis with and AMI. Conclusion: Our study provides evidence of the association between periodontitis and salivary analytes that occur in tandem with cardiovascular disease. The lower levels of Adiponectin and higher levels of CRP and MIP-1α in patients with periodontitis indicate that this condition is a potential risk factor for cardiovascular disease. The findings emphasize the importance of early detection and intervention for periodontitis patients to prevent cardiovascular events.

Reactive oxygen species and reactive nitrogen species in semen are both essential for fertilization process; however, they become harmful at excessive levels, causing oxidative stress and nitrosative stress, respectively. Recently, oxidation–reduction potential (ORP) has been used as a marker for measuring oxidative stress, and this study investigated the possibility of comprehensively evaluating nitrosative stress. The correlation between standardized ORP (sORP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) and NOx per unit sperm was tested. Based on the previously reported cutoff value, samples were classified into oxidative stress-positive and negative groups. Thereafter, a receiver operating characteristic curve was drawn on 8-OHdG and NOx, and each optimal cutoff value was determined. Both standardized 8-OHdG and NOx significantly correlated with sORP. Although both correlated significantly with sORP in the oxidative stress group, no correlation was found in the nonoxidative stress group. The optimal standardized 8-OHdG level to determine oxidative stress status was 0.52 ng/106 spermatozoa, and the standardized NOx was 0.17 µM/106 spermatozoa/mL. The ORP is a simpler and quicker assay that can comprehensively assess oxidative and nitrosative stresses. Optimal cutoff values for both stresses were established in this study.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Magnesium hydroxide continuous coagulation process was used for treating simulated reactive orange wastewater in this study. Effects of mixing conditions and retention time on the coagulation performance and floc properties of magnesium hydroxide were based on the floc size distribution (FSD), zeta potential and floc morphology analysis. Floc formation and growth in different reactors were also discussed.The results showed that increasing rapid mixing speed led to a decrease in the final floc size. Floc formation process was mainly carried out in rapid mixer, rapid mixing speed of 300rpm was chosen according to zeta potential and removal efficiency. Reducing retention time caused relatively small floc size in all reactors. When influent flow is 30 L/h (retention time of 2min in rapid mixer), the average floc size reached 8.06μm in rapid mixer, through breakage and re-growth, the floc size remained stable in flocculation basin. After growth, the final floc size reached to 11.21μm in sedimentation tank. The removal efficiency of reactive orange is 89% in magnesium hydroxide coagulation process.

Nowadays a recognized need for accurate observations of atmospheric aerosols (AEs) and reactive gases (RGs) exists in the framework of regional, national and global near-surface networks based on permanent or mobile measurement stations. In this context, a paramount and not-trivial issue is related to the correct execution of continuous sampling of ambient air and its subsequent distribution to measurement analyzers hosted inside the stations. Sampling artifacts must be minimized for obtaining reliable pictures of ambient air composition. To respond to this need, a suite of novel “smart” and relatively low-cost systems for the continuous sampling of ambient air was developed in the framework of the Project I-AMICA (2012 – 2015, www.i-amica.eu). These systems were designed to execute AE and RG measurements according with WMO/GAW and ACTRIS recommendations and standard operation procedures. A particular attention was dedicated to the stabilization and control of the sampling flow rates and temperatures. The analysis of one full year of operations at the WMO/GAW regional station of Capo Granitola (GAW ID: CGR, Italy), allowed to conclude that these systems are effective in meeting the technical requirements for correct execution of AE and RG measurements

Background and aim: Apigenin (API), a dietary flavone subclass of flavonoid found in herbs, fruits, and vegetables, exhibits various pharmacological effects. However, its role in triggering oxidative stress- induced apoptosis in uterine cells remains unclear. This study aimed to evaluate the oxidative stress-mediated apoptosis induced by apigenin in rat uterine leiomyoma ELT3 cells. Material and methods: ELT3 cells were treated with 50 and 100 µM API for 48 hours. We assessed oxidative stress markers (reactive oxygen species, malondialdehyde), antioxidant defense (glutathione reductase activity), cell proliferation, and apoptotic gene expression (p53, Bax, Bcl-2, caspase-3, caspase-9) using relevant assays and real-time PCR. Results: API treatment decreased cell proliferation and glutathione reductase activity in ELT3 cells. This coincided with increased levels of reactive oxygen species, malondialdehyde, and lactate dehydrogenase activity, indicating oxidative stress and cell damage. Furthermore, apigenin upregulated pro-apoptotic genes (p53, Bax, caspase-3, caspase-9) and downregulated the anti-apoptotic gene Bcl-2, suggesting activation of the intrinsic apoptotic pathway. Conclusion: API induces apoptosis in rat uterine leiomyoma cells through a mechanism involving oxidative stress-mediated activation of the intrinsic apoptotic pathway.

SiC is a material with excellent mechanical and thermal properties, but with a high production cost. Obtaining SiC by reactive infiltration is an attractive method and at a much lower cost than the traditional sintering process. However, the reactive infiltration process presents a serious problem, which is the high residual silicon content, which decreases its range of application. The replacement of silicon with silicides is a widely used alternative. The present investigation shows the good mechanical properties of the SiC/IrSi₃ composite material obtained by reactive infiltration of SiC/C preforms with Ir-Si alloys. The thermomechanical analysis shows a high compatibility of silicide with SiC. The presence of the silicide shows a substantial improvement against the oxidation of the SiC/Si composites.

This paper updates earlier thoughts by the author on a putative propulsion system. The concept was based around static electromagnetic momentum, as expounded in the “Feynman Disk” and experimentally verified by Graham and Lahoz. That said, naïve static electromagnetic momentum schemes to achieve linear translation are defeated by “hidden momentum” mechanisms, so too are simple arrangements just cycling the fields; we shall survey the flaws in their arguments. It may however be possible to achieve linear translation by means of arrangements of torques with a novel mechanism to break the symmetry of forces (or torques) on the second half of the cycle as the field is switched off. At the time of earlier presentation no mechanism could be found to explain the momentum balance for the process but it was believed that momentum was being given to the zero-point of the field. We show that it is possible to dump angular momentum and thence linear momentum to the ground state by standard quantum analysis of the EM field. None of this violates the conservation of momenergy.

The aim of this cross-sectional study was to assess the influence of the maturity status on speed, explosive power and change of direction (COD) in 13-year-old football players. Ninety-eight male players (age: 13.1 ± 1.0 y) were divided into late, average, and early maturation groups. Physical fitness testing included the following variables: 10 and 30-meter sprint time and maximum speed in the 20-30 m segment of the 30-meter sprint test, the T-test time, countermovement jump height and horizontal distance in the triple jump. The data showed a significant effect of maturity status on performance in three parameters: in maximum speed in the 20-30 m section (p = 0,024), however, the only significant differences were found between the early-maturation group and average-maturation group (p = 0.033); in the COD (p = 0.024), where significant differences were confirmed between the late-maturation group and the average-maturation group (p = 0.033); in the unilateral triple jump distance of the dominant and non-dominant (p = 0,007 and p = 0.001, respectively) lower limb. For both limbs, significant differences between the late-maturation group and average maturation group (p = 0.005 and p = 0.013, respectively) as well as the late-maturation group and early-maturation group (p = 0.007 and p = 0.045, respectively) were proved. These results indicate that maximal speed, COD speed and unilateral lower limb reactive strength are moderated by biological age in football players aged 13 years.

Nonalcoholic fatty liver disease (NAFLD) has become a widely studied subject due to its increasing prevalence and links to diseases such as type 2 diabetes and obesity. It has severe complications, including nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and portal hypertension that can lead to liver transplantation in some cases. To better prevent and treat this pathology, it is important to understand its underlying physiology. Here, we identify three main factors that play a crucial role in the physiopathology of NAFLD: oxidative stress, insulin resistance, and the key role of carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1). We discuss the pathophysiology linking these factors to NAFLD pathophysiology.

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyse the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week during 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week during 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

Cold stress is a major environmental factor affecting the growth, development, and productivity of various crop species. With the current trajectory of global climate change, low temperatures are becoming more frequent and can significantly decrease crop yield. Wheat (Triticum aestivum L.) is the first crop to be domesticated and is the most popular cereal crop in the world. Due to a lack of systematic research on cold response pathways and gene regulatory networks, the underlying molecular mechanisms of cold signal transduction in wheat are poorly understood. This study reviews recent progress in wheat, including the ICE-CBF-COR signaling pathway in cold stress and the effects of cold stress on hormonal pathways, reactive oxygen species (ROS), and epigenetic regulation. This review also highlights outstanding issues that are crucial for understanding the interactions between wheat and low-temperature conditions.

Erastin (ER) induces cell death by utilizing the process of ferroptosis via generation of reactive oxygen species (ROS). Ferroptosis is characterized by accumulation of ROS within the cell, leading to an iron-dependent oxidative damage-mediated cell death. Here, we have examined ferroptosis-dependent mechanism(s) of cytotoxicity of ER in K-RAS mutant human ovarian tumor OVCAR-8 and NCI/ADR-RES cell lines. We used these cell lines to decipher the mechanisms of ER as NCI/ADR-RES cells express higher activities of SOD, glutathione peroxidase and transferases than OVCAR-8 cells. We found that ER was equally cytotoxic to both cells; ER formed more ROS in OVCAR-8 cells than in NIH/ADR-RES cells. Ferrostatin-1, an inhibitor of ferroptosis, inhibited ER-induced cell death in both cell lines. In contrast, RSL3 (RAS-selective lethal 3), an inducer of ferroptosis, significantly enhanced cell death in both cell lines. ER induced significant lipid peroxidation only in OVCAR-8 cells. We found that RSL3 was more cytotoxic to NCI/ADR-RES cells and significantly enhanced ER-induced lipid peroxidation in both cells, indicating GPX4 was involved in the process of ER-mediated ferroptosis. ER treatment also differentially modulated several ferroptosis related genes (e.g., HMOX1/OH1, and CHAC1) in these cells, indicating ER-induced cell death may be mediated differently in OVCAR-8 and NCI/ADR-RES ovarian cells. Our studies suggest that combinations of ER and RSL3 may contribute significantly to the treatment of ovarian cancers, including those that are resistant to other therapeutic agents due to the presence of P-gp or tumors with Ras mutation in the clinic. ER induced ferroptosis may also be an important treatment modality for resistant tumors expressing MDR1 in the clinic.

Salinity stress affect plant growth and development by causing osmotic stress, and nutrient imbalances through excess Na+, K+ and Cl- ion accumulations that induce toxic effects during germination, seedling development, vegetative growth, flowering, and fruit set. However, the effects of salt stress on such processes, especially in polyploidised leguminous plants remains unexplored and scantly reported compared to their diploid counterparts. This paper discusses the physiological and molecular response of legumes towards salinity stress based osmotic and ionic imbalances in plant cells. A multigenic response involving various compatible solutes, osmolytes, ROS, polyamines and antioxidant activity, together with genes encoding proteins involved in the signal transduction, regulation and response mechanisms to this stress were identified and discussed. This discussion reaffirms polyploidisation as the driving force in plant evolution and adaptation to environmental stress constraints such as drought, feverish temperatures, and in particular, salt stress. As a result, thorough physiological and molecular elucidation of the role of gene duplication through induced autopolyploidisation and possible mechanisms regulating salinity stress tolerance in grain legumes must be further studied.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. The data show that the impact of YFV on ZIKV replication is cell line dependent. In differentiating embryoids, the presence of YFV antibodies enhanced ZIKV infection. Since viral pathogenesis, and the impact of antigenic cross-reactive antibodies, is cell line specific at the maternal-fetal axis, this suggests there may be discreet mechanisms that impact congenital ZIKV infections.

The article concerns problems related to the assessment of reactive power in power networks with non-linear, fast-varying loads, such as electric arc furnaces, rolling mill drives, etc. The operation of this type of loads is characterized by the introduction of interharmonic currents (including higher harmonics) into the power supply network and a relatively low power factor. Rapid changes in the RMS value of the current also cause voltage fluctuations and the related phenomenon - flicker. Therefore, there is a need to evaluate the selection of power of compensating devices taking into account the random nature of load changes and the distortion of current and voltage waveforms, in particular interharmonic components, the impact of which has not been fully investigated so far. To analyze the random nature of load changes, autocorrelation functions were used, which allowed for the estimation of the expected values of the arc furnace current distortion coefficient (based on the recorded waveforms). In order to determine the parameters of reactive power compensating devices, and in particular capacitor banks, an autocorrelation function in the exponential-cosine-sine form was used, which meets the conditions of differentiation. The article contains comparative results of calculations of the reactive power of capacitor banks determined using different methods.

Immune disorders, characterized by dysregulation at cellular and inflammatory levels, result from a complex interplay of genetics and environmental factors that lead to an abnormal immune response against autoantigens, triggering tissue damage. Recent research highlights reactive antibodies as key players in autoimmune diseases and graft rejection, but the complexity of their determination limits their use in clinic. Hence, we studied the specific binding profile of serological antibodies against a panel of cellular membranes in order to determine whether this antigenic panel could be used to diagnose specific immune disorders in humans. For this purpose, cell membrane microarrays of spleen, liver, and kidney tissues of monkey, rat, and human were developed, and human sera were analyzed, including healthy controls, patients with autoimmune disorders, and kidney transplant patients. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and Human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in the serum of patients as potential biomarkers of immune disorders.

Activity of the Nox1 centered NADPH oxidase complex depends on the activator NoxA1 and the organizer NoxO1. NoxO1 itself is not involved in electron transfer for superoxide formation. Instead, by creating proximity of all components in the right place NoxO1 enables a constitutive formation of reactive oxygen species by that complex. All subunits should form the complex in a 1:1:1 ratio. When analyzing different cell lines in this study, we found an unequal expression of the component on mRNA level with an excess of NoxO1. Even with plasmid-based overexpression of individual components of Nox1 centered NADPH oxidase complex results in different expression of their mRNA, with NoxO1 mRNA being best expressed. Despite an unchanged high level of NoxO1 mRNA over a wide range of transfected plasmid, protein expression is increased with accelerating plasmid concentrations. We thought to analyze the ability of NoxO1 to induce ROS formation, when present in different ratio to Nox1 and NoxA1. To this end, we used Hek293 cells with constitutive expression of Nox1 and NoxA1 transfected with increasing concentrations of NoxO1. Our results suggest that ROS formation by the Nox1 centered NADPH oxidase strongly depends on the level of NoxO1 and a surplus of NoxO1 further increases the activity of the complex.

The present study evaluated the effect of Prosthechea karwinskii leaves extract on antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in a model of obese rats with insulin resistance to know its nutraceutical potential on insulin resistance and oxidative stress. Obesity and insulin resistance were induced in rats by administering 40% sucrose in water. Once the model was established, four groups were evaluated (control, obese, obese administered with extract, and obese administered with metformin), and the indices of insulin resistance and the activity of antioxidant enzymes were measured. In addition, compounds in the extract were identified with UHPLC-ESI-qTOF-MS/MS. The glucose, insulin, triglycerides, and insulin resistance indicators (HOMA-IR and TyG) increased in obese rats. The activity of the antioxidant enzymes evaluated increased in the obese group, apparently as an adaptive response to oxidative stress to inhibit reactive oxygen species formed by hyperglycemia. Administration of P. karwinskii extract and metformin reduced glucose, insulin, triglyceride levels, insulin resistance indicators and antioxidant enzymes to values like those of the control group. This study shows the nutraceutical potential of P. karwinskii extract as an ingredient in the formulation of food supplements or functional foods to help treat diseases related to insulin resistance and oxidative stress.

Sputtered reactive multilayers applied as a heat source in electronic joining processes are an emerging technology. Their use promises low-stress assembly of components while improving the thermal contact and reducing the thermal resistance. Nanostructured surface modifications can significantly enhance adhesion and reliability of joints between different materials. This work examines reactive multilayer of nickel and aluminum, directly sputtered on nanostructured black silicon surfaces and compares their phase transformation with reference samples deposited on pristine silicon surface. The investigation of the quenched self-propagating reaction reveals a clear influence of the nanostructured surface on the prolongation of the phase transition. Rapid thermal annealing tests result in the formation of Al_1.1Ni_0.9 phase. The nanostructured interface seems to hinder the full transformation of the parent material. The surface modification improves the adhesion of the formed alloy on silicon surfaces and can possibly increase the reliability of joints based on reactive aluminum/nickel multilayer. The use of black silicon, a nanostructured surface modification, is thus a promising approach to realize reliable multi-material joints in complex systems.

In modern materials science and surface engineering, Reactive Plasma Spraying (RPS) occupies a key po-sition due to its ability to create high quality coatings with unique properties. However, the efficiency of this process is highly dependent on the physicochemical characteristics of the starting powder materials. Mechanical activation, as a pretreatment, can have a significant effect on the structure and reactivity of powders, thereby modifying and improving the RPS process. The present study focuses on analysing the changes that occur to powder materials after mechanical activation and their subsequent effects on the quality and performance of coatings produced by the RPS process. The study of these changes is of key importance for optimising the spraying process as well as developing new materials with improved methods. This is important not only to improve the efficiency of reactive plasma spraying technologies, but also to expand their applications in various industrial and scientific fields. Improved materials can be a decisive factor in increasing the productivity and prevalence of products, as well as creating new opportunities for innovation and development in various industries.

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adher-ence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity mediated by the production of reactive oxygen species. This study investigates the in vitro effect of the combination of blue light (448 nm) and red light (645 nm) with terbinafine on the cell viability of human keratinocytes and the production of reactive ox-ygen species. The combination of terbinafine and blue light exhibits a synergistic effect on the production of reactive oxygen species and a significant increase in the expression of superoxide dismutase (SOD), an enzyme involved in the reduction of superoxide ions (O2-) and the genera-tion of hydrogen peroxide (H2O2). Such effect could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity, and shorten their duration.

Febrile infections are a common cause of presentation to the emergency department (ED) in chil-dren. While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; the better understanding of immunochemical pathways has nowadays led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models combining them for serious bacterial infections (SBI) diagnosis in febrile children. Litera-ture analysis showed that inflammatory response is a complex mechanism in which many bio-chemical and immunological factors contribute to host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined and for this reason it is reasonable to take them both into consideration in the evaluation of a febrile children. The potential of machine learning tools, who represent a real novelty in medical practice, in conjunction with routine clinical and biological in-formation, may improve accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pe-diatric precision medicine still uncertain. More data from further researches are needed to improve clinical practice and decision making using these new technologies.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function with neuronal damage. Although the precise pathobiology of AD is still elusive, accumulating evidences suggest that mitochondrial dysfunction is one of the underlying causes of AD. Mutations of mitochondrial or nuclear DNA that encode mitochondrial constituents may cause mitochondrial dysfunctions. In particular, dysfunction of electron transport chain complexes along with interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunctions in AD. Mitochondrial dysfunction causes an imbalance in reactive oxygen species, leading to oxidative stress (OS) and vice-versa. Neuroinflammation is another potential contributory factor to induce mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense system, and thereby protect against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Pharmacological intervention through neuroprotective phytochemicals can, therefore, be a potential strategy to combat mitochondrial dysfunctions as well as AD. This review focuses on the role of phytochemicals to mitigate mitochondrial dysfunction in the therapy of AD pathogenesis.

Reactive energetic plasticizers (REPs) coupled with hydroxy-telechelic poly(glycidyl azide-co-tetrahydrofuran) (PGT)-based energetic polyurethane (PU) binders for use in solid propellants and plastic-bonded explosives (PBXs) were investigated. The generation of gem-dinitro REPs along with a terminal alkyne stemmed from a series of finely designed approaches to not only satisfy the common demands as conventional energetic plasticizers but prevent the migration of plasticizers. The miscibility and rheological behavior of a binary mixture of PGT/REP with various REP fractions were quantitatively determined by differential scanning calorimetry (DSC) and rheometer, respectively, highlighting the promising performance of REPs in the formulation process. The kinetics on the distinct reactivity of propargyl vs. 3-butynyl species of REPs towards the azide group of the PGT prepolymer in terms of Cu-free azide-alkyne 1,3-dipolar cycloaddition (1,3-DPCA) was studied by monitoring 1H nuclear magnetic resonance spectroscopy and analyzing the activation energies (Ea) obtained using DSC. The thermal stability of the finally cured energetic binders with the incorporation of REPs indicated that the thermal stability of the REP/PGT-based PUs was maintained independently of the REP content. The tensile strength and modulus of the PUs increased with increasing the REP content. In addition, the energetic performance and sensitivity of REP and REP triazole species was predicted.

Covalent drugs can offer significant advantages over noncovalent drugs, in terms of pharmacodynamics (i.e. target-binding properties). However, the development of covalent drugs is sometimes hampered by pharmacokinetic limitations (e.g. low bioavailability, rapid metabolism, and toxicity due to off-target binding). Polymeric nanoparticles offer a potential solution to these limitations. Delivering covalent drugs via polymeric nanoparticles provides myriad benefits in terms of drug solubility; permeability; lifetime; selectivity; controlled release; and the opportunity for synergistic administration alongside other drugs. In this short review, we examine each of these benefits in turn, illustrated through multiple case-studies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and memory loss. Oxidative stress (OS) has emerged as a central element in the pathophysiology of AD, linking various pathological features including amyloid-β (Aβ) plaque formation, tau hyperphosphorylation, and synaptic dysfunction. This review comprehensively examines the role of OS in AD, focusing on the mechanisms of reactive oxygen species (ROS) production, mitochondrial dysfunction, and their impact on neuronal integrity. Additionally, the review highlights recent advances in antioxidant therapy. Elevated ROS levels in the aging brain exacerbate oxidative damage to lipids, proteins, and DNA, contributing to neuronal atrophy and synaptic loss. Mitochondrial dysfunction further amplifies OS, disrupting cellular energy metabolism and promoting neurodegeneration. Despite the strong association between OS and AD, antioxidant therapies have shown inconsistent clinical outcomes. Emerging strategies targeting offer promising avenues for therapeutic intervention. This review highlights the need for a multifaceted approach in understanding and mitigating OS-related damage in AD, aiming to pave the way for more effective treatments and improved patient outcomes.

Photoacoustic imaging is attracting a great deal of interest owing to its distinct advantages over other imaging techniques such as fluorescence or magnetic resonance image. Availability of photoacoustic probes for reactive oxygen and nitrogen species (ROS/RNS) could shed light on a plethora of biological processes mediated by these key intermediates. Tetramethylbenzidine (TMB) is a non-toxic and non-mutagenic colorless dye that develops a distinctive blue color upon oxidation. In this work we have investigated the potential of TMB as photoacoustic probe for ROS/RNS. Our results indicate that TMB reacts with hypochlorite, hydrogen peroxide, singlet oxygen and nitrogen dioxide to produce the blue oxidation product, while ROS such as the superoxide radical anion, sodium peroxide, hydroxyl radical or peroxynitrite yield a colorless oxidation product. TMB does not penetrate Escherichia coli cytoplasm but is capable of detecting singlet oxygen generated in its outer membrane.

The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational-parent/fetal exchange and ultimately fetal development and growth. Not surprisingly, in cases of placental dysfunction - where aspects of placental development or function become compromised - adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero-placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

Abstract: Ovarian cancer (OC) ranks as the fifth most common cancer among women in the United States and globally, posing a significant health threat. Reactive oxygen species (ROS) have emerged as critical factors in the pathophysiology of this malignancy. ROS, characterized by their instability due to an unpaired electron, are involved in essential cellular functions and play a crucial role in the immune response under normal physiological conditions. However, an imbalance in ROS homeostasis, leading to excessive ROS production, results in oxidative stress (OS), which can cause indiscriminate damage to cellular structures and contribute to the pathogenesis of specific diseases, including OC. OC is primarily classified based on the originating cell type into epithelial, stromal, and germinal tumors, with epithelial tumors being the most prevalent. Despite advancements in medical technology, early detection of OC remains challenging, often leading to delayed treatment initiation. Current therapeutic approaches include surgical excision of tumor tissue, radiotherapy and chemotherapy. While these treatments are effective in early-stage OC, high mortality rates and frequent relapse underscore the urgent need for novel diagnostic and therapeutic strategies. This review aims to elucidate the role of ROS in OC, emphasizing the potential for developing innovative diagnostic tools and treatments that target ROS-mediated pathways. Given the critical impact of early detection and effective treatment, advancing our understanding of ROS in the context of OC could significantly enhance patient outcomes.

The excellent properties of nanomaterials have been confirmed in many fields, but the effects on plants are still unclear. In this study, we have found that bismuth vanadium promoted the growth of taproots and the development of lateral roots, increased the roots activity by regulating the expression of polyamine or hormone-related genes and reducing the accumulation of reactive oxygen species in Arabisdopsis thaliana. Meantime, BV had higher antimicrobial effect than that of graphene oxide (GO). These results showed us a new perspective possibility of nanomaterials assisting the development of plants and crops, which is expected to become one of the ways to solve the problem of controlling and promoting the development of plants and crops.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions and biomarkers, such as c-reactive protein (CRP) and adiponectin. Recently, marine algal biomaterials have been investigated extensively due to their health benefits. We report on associations between metabolic markers and bioactive nutrients from diet and Sujiaonori algal biomaterial (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of ulvan-rich fiber, in a sample of Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m² [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Background: Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coro-nary heart disease. We investigated the relationship of CRP with findings from myocardial per-fusion imaging (MPI). Methods: In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) that underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6mg/L) within 1 month from MPI, were included. Patients had no infection or recent acute coronary syndrome. Results: the median CRP level was 4mg/L (2,10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (P = 0.006) and summed rest score (SRS) (P = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, P = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (P = 0.027 and P = 0.005 respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). Conclusion: A high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

The objective of this study was to synthesize 9-/13-position substituted berberine derivatives and evaluated their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e) and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in compare with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at 9-/13-position of berberine may have facilitated its penetration into test cell and hence enhanced its photocytotoxicity on human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e and 7e induced HepG2 cells to arrest at S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine (1) and its derivatives 5e, 6e and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e and 7e greatly enhanced photocytotoxicity. Taking together, the test data led us to conclude that berberine derivatives with a dodecyl group at 9-/13-position could be great candidates for the anti-liver cancer medicines developments.

Viral infections induce exosomes containing viral material and inflammatory factors. During respiratory tract infection, exosomes can easily cross the blood-brain barrier and transmit the inflammatory signal to the brain; however, such a hypothesis has no experimental evidence. The study investigated whether exosomes from virus mimetic poly (I:C)-primed airway cells enter the brain and interact with brain immune cells microglia. Airway cells were isolated from Wistar rats and BALB/c mice; microglial cell cultures - from Wistar rats. Exosomes from poly (I:C)-stimulated airway cell culture medium were isolated by precipitation, visualised by transmission electron microscopy, and evaluated by nanoparticle analyser; exosomal markers CD81 and CD9 were determined by ELISA. For in vitro and in vivo tracking, exosomes were loaded with Alexa Fluor 555-labelled RNA. Intracellular reactive oxygen species (ROS) were evaluated by DCFDA fluo-rescence and mitochondrial superoxide - by MitoSOX. The exosomes from poly (I:C)-primed airway cells entered the brain within an hour after intranasal introduction, were internalised by microglia, and induced intracellular and intramitochondrial ROS production. There was no ROS increase in microglial cells was after treatment with exosomes from airway cells untreated with poly (I:C). The data indicate that virus-primed airway cell exosomes might enter the brain and induce the activation of microglial cells.

Early Endosomes represent first line sorting compartments or even organelles for internalized molecules. They enable the transport of molecules or ligands to other compartments of the cell, such as lysosomes for degradation or recycle them back to the membrane by various mechanisms. Moreover, early endosomes function as signaling and scaffolding platform to initiate or prolong distinct signaling pathways. Accordingly, early endosomes have to be recognized as either part of a degradation or recycling pathway. The physical proximity of many ligand-binding receptors with other membrane bound proteins or complexes such as NADPH oxidases may result in an interaction of second messengers like reactive oxygen species (ROS) and early endosomes that promote correct recognition of individual early endosomes. In fact, redoxosomes comprise an endosomal subsection of signaling endosomes. One example of such potential interaction is epidermal growth factor receptor (EGFR) signaling. Here we summarize recent findings on EGFR signaling as a well-studied example for receptor trafficking and trans-activation and illustrating the interplay between cellular and endosomal ROS.

Reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) manifest in individuals facing attachment system chal-lenges, particularly observed in minors under protective measures. The lack of standardized tools for assessing these difficulties and uncertainty about the most effective instruments from a psychometric perspective prompted this study. Using the COSMIN checklist, we systematically reviewed instruments assessing RAD, adhering to PRISMA and COSMIN guidelines. Examined tools included the Disturbance Attachment Inter-view, Preschool Age Psychiatric Assessment, Relationship Patterns Questionnaire, Assessment of RAD and DSED, Development and Well-Being Assessment, and Reactive Attachment Disorder Question-naire. Of the 11 articles analyzed, results highlight a research emphasis on internal consistency, structural and construct validity, sidelining other properties. While the instruments demonstrate strong structural validity, excellent internal consistency, and generally satisfactory error measurement results, the study concludes a dearth of investigations into psychometric properties for children and adolescents under protective measures.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions, c-reactive protein (CRP) and adiponectin. We report on associations between targeted metabolic markers and active nutrients from diet and Sujiaonori algal supplement (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of bioactive ulvan-rich fiber, in Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m2 [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Many medicinal plants and their essential oils are used to treat or prevent diseases without the risk of mutagenicity, carcinogenicity, or teratogenicity. Eucalyptus essential oils are commonly used as preservatives, flavoring agents, and in various consumer goods. Eucalyptus leaves are being widely studied due to their volatile essential oils, including 1,8-cineole, p-cymene, α and β-pinene, limonene, citronellal, citral, eudesmol, terpinen-4-ol, terpineol, α–phellanderene, and 9β-sitosterol. Among these compounds, 1,8-cineole is the most abundant. Eucalyptus leaves are rich in flavonoids and phenolic compounds and are thus a great source of antioxidants. 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays are used to measure antioxidant capacity. The antioxidant activity of Eucalyptus essential oil is stronger than that of standard antibiotics like Erythromycin, Cefixime, and Gentamicin due to the presence of significant terpenoids in addition to phenolic chemicals and flavonoids. The lower the IC₅₀ value, the higher the antioxidant potential. Phenolic compounds and flavonoids are often associated with beneficial health outcomes, including anti-inflammatory and antioxidant effects, anti-cancer properties, reduced risk of cardiovascular diseases, prevention of age-related neurodegenerative diseases, and prevention of Alzheimer’s disease. Flavonoids also play an essential role in plants, including protecting against reduction, fertility, reproduction, and infection. Due to their anti-inflammatory, anti-oxidative, and immune-modulatory properties, flavonoids are crucial for pharmacological, medical, and nutraceutical applications.

Polymers' controlled pyrolysis is an economical and environmentally friendly solution to prepare activated carbon. However, due to the experimental difficulty in measuring the dependence between tissues and pyrolysis parameters at high temperatures, the unknown pyrolysis mechanism hinders access to the target products with desirable morphologies and performances. In this study, we investigate the pyrolysis process of polystyrene under different heating rates and temperatures employing reactive molecular dynamics (ReaxFF-MD) simulations. A clear profile of the generation of pyrolysis products determined by the temperature and heating rate is constructed. It is found that the heating rate affects the type and amount of pyrolysis intermediates and their timing, and low-rate heating helps yield more diverse pyrolysis intermediates. While the temperature affects the pyrolytic tissues of the final equilibrium products, either too low or too high a target temperature is detrimental to generating large areas of graphitized tissue. The established theoretical evolution process matches experiments well, thus contributing to preparing target activated carbons by referring to the regulatory mechanism of pyrolytic tissues.

From oxidative eustress and distress, to bioenergetic metabolism, and cell death, the reactive species interactome (RSI) and mitochondria are two connected metabolisms that require further investigation improving redox medicine. The step before, finding new clues needs a comprehensive discussion of the two metabolisms, and their relationship. Here, the review focuses on the RSI-mitochondria axis, from mitochondrial roles to crosstalk between mitochondria and other organelles, and the major implication of the RSI in mitochondrial roles. Specifically, the review discussed the apoptosis-necroptosis-ferroptosis death traingle, mitochondrial protein quality control system, calcium homeostasis, and mitochondrial metabolome. Through mitochondrial diseases, and mitochondrial dysfunction associated with diseases, the RSI-mitochondria axis is proposed as a brand-new perspective, including with the involvement of bacterial microbiota, on redox signaling, and redox medicine.

Each year, the global population and agriculture suffer critical agricultural output losses as a result of severe drought devastation. Physiological drought occurs when plants are unable to extract water from the soil, even though it is available in the root zone. Apart from having a significant effect on plant physiology, drought stress has the effect of reducing crop yield. Drought stress influences plant metabolism both directly and indirectly. Drought stress alters the morpho-anatomical, physiological, and biochemical composition of plants, thereby decreasing transpiration water loss and increasing the efficiency with which plants use their water. Constant water loss through transpiration, combined with previously lost water, results in leaf water deficits. Nonetheless, drought stress has a wide variety of effects, ranging from lesions to confusion. Plant health is harmed when their ability to absorb water and nutrients, interact with their environment, and breathe is harmed. Apart from oxidative damage to plants, it may also result in cell death, which can occur under certain conditions when cells are exposed to their environment. Drought induces a plethora of physiological and molecular changes in plants, the majority of which assist them in adapting to the harsh environment. To mitigate drought's adverse effects, we must first gain a better understanding of how drought affects plant physiology. The purpose of this research is to better understand how drought affects plant development by examining the causes and effects of drought stress.

Future, flexible thermal energy conversion systems require new, demand-optimized high-performance materials. The High performance Ferritic (HiperFer) stainless steels, under development at the Institute of Microstructure and Properties of Materials (IEK-2) at Forschungszentrum Jülich GmbH in Germany, provide a balanced combination of fatigue, creep and corrosion resistance at reasonable price. This paper outlines the scientific background of alloy performance development, which resulted in an age-hardening ferritic, stainless steel grade. Furthermore, technological properties are addressed and the potential concerning application is estimated by benchmarking versus conventional state of the art materials.

Lymphadenomegaly is well described in dogs with neoplastic diseases, but it can also reflect in-flammation. However, its role in assessments of inflammation is little reported in the veterinary literature. Lymph nodes are most easily assessed superficially through palpation, but computed tomography (CT) enables evaluation of deep lymph nodes. Accordingly, we investigated associ-ations between maximal lymph node diameter and plasma concentrations of C-reactive protein (CRP), a sensitive inflammatory marker, targeting three deep lymph nodes (sternal, cranial me-diastinal, and internal iliac). We evaluated data from small dogs with non-neoplastic diseases that underwent synchronous CT and blood biochemistry at our institution. We found that cranial mediastinal lymph node diameter was significantly greater in dogs with clinically elevated CRP than those with clinically unremarkable CRP (CRP 0.7-7.0< mg/dL vs.

Prolonged exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody, sedentary with antineutrophil antibody, exhaustive exercise with control antibody, and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered intraperitoneally to the mice prior to their running on a treadmill. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using quantitative reverse transcriptase-polymerase chain reaction. Furthermore, nicotinamide adenine dinucleotide phosphate oxidase activity and hydrogen peroxide concentration in the kidneys were measured. The pathologic changes were manifested as congested and swollen glomeruli, tubular dilatation, and nuclear infiltration after exhaustive exercise. These changes were suppressed by the administration of the 1A8 antibodies. KIM-1 concentration increased after exhaustive exercise but were reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and reactive oxygen species levels.

This study aimed to obtain and characterize extracted hemp oil enriched in cannabidiol (CBD) by decarboxylation of cannabidiolic acid (CBDA) and to give new insights into its antioxidant and anticancer effects. Optimization of CBDA decarboxylation in hemp oil was performed, and CBD and CBDA contents and purities were determined by “flash chromatography”, 1H- and 13C-NMR. The antioxidant properties of CBD-enriched oil were investigated by Fe2+ chelating activity, Fe3+ reducing antioxidant power assay, O2− scavenging activity, HO− scavenging ability and lipid peroxidation inhibitory assay and its cytotoxicity, apoptosis- and oxidative stress-inducing effects on NHDF, MeWo, HeLa, HepG2 and HOS cells were determined. The CBD concentration in hemp oil was increased by CBDA soft decarboxylation optimized at 90°C, for 1 h and resulted oil was capable of reducing iron, scavenging free radicals, and inhibiting lipid peroxidation in cell-free oxidative conditions. CBD-enriched oil promoted NHDF proliferation at up to 15 µg CBD/mL, while inducing apoptosis and ROS production and modulating antioxidant enzymes’ gene expression in cancer cells, being selective for osteosarcoma cells and induced apoptosis by p53- and ROS-independent mechanisms. CBD-enriched hemp oil demonstrated antioxidant properties in oxidative conditions and promoted normal fibroblasts’ proliferation, while inducing apoptosis and ROS production in cancer cells.

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at our hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6–62.4, p=0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (p=0.009) and that at week 8 (p=0.005) were significantly associated with clinical remission at week 48. The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, antibiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and catecholaminergic metabolism due to its capability as a pro-oxidant and other harmful molecules, versus its involvement in oxidative stress and aberrant immune response, which it is highly dependent on NM saturation state and its extracellular release.

Wheat blast caused by the hemibiotroph fungal pathogen Magnaporthe oryzae Triticum (MoT) pathotype, is a destructive disease of wheat in South America and Bangladesh. Generation of reactive oxygen species (ROS) is one of the defense responses in plants during the infection process by a pathogen. However, empirical evidence on regulation of ROS in wheat and other host and non-host plants towards MoT is limited. This study aimed to determine the susceptibility of some major cereals and weeds of Bangladesh and compare the antioxidant enzyme activities in host and non-host plants in response to artificial inoculation by MoT. Seedlings of wheat, maize, barley and swamp rice grass were susceptible to MoT and produced considerable number of conidia on infected leaves (host). Rice seedlings showed a resistant response in our laboratory conditions (non-host). The activities of ROS-detoxifying enzymes; catalase (CAT), ascorbate peroxidase (APX), Glutathione peroxidase (GPX), Glutathione S-transferase (GST), Peroxidase (POX) increased in all plants after inoculation by MoT with a few exceptions. Interestingly, an early and very high accumulation of CAT was observed within 24 hours of inoculation (hai) in wheat, barley, maize and swamp rice grass while H2O2 concentration was low during that time and immediately after that (24-48 hai). In contrast, an early and high accumulation of H2O2 was observed in rice at 48 hai with little CAT activity only at a late stage. The APX, GST and POD activity was also increased due to the inoculation of MoT at the early stage of infection in rice but were very high at the disease progression stage in wheat, barley, maize and swamp rice grass. GPX activity gradually decreased with the increase of time in rice. Taken together, our results suggest that a robust and late induction of most of the antioxidant enzyme activities occurs in susceptible/host plants whereas an early induction of antioxidant enzyme activities occurs in resistant/ non-host plant but with slow kinetics.

Acid in-situ leaching (ISL) is a common approach to the recovery of uranium in the subsurface. As some toxic and harmful substances might be produced by the chemical reactions among the injected sulphuric acid, the groundwater, and the porous media during leaching processes, the pollution control of the mining plan for ISL is important. In this study, a three-dimensional reactive transport modeling (3DRTM) was applied to decide the pollution control mining plan, considering the partial penetration through wellbore in confined aquifer and complex chemical reactions between main minerals. Based on the 3DRTM, different pumping ratio and non-uniform injection schemes were compared. The results show that the preferential pollution control mining plan is non-uniform injection ratio equal 0.1. By analyzing the characteristics of water table and streamline, it is concluded that the scheme has a strong hydraulic capture effect. In this scheme, the concentration of UO22+, H+, SO42- obtained by 3DRTM is lower. The inner well injection rate is 194.09 m3/d, the outer well injection rate is 158.89 m3/d, and the pumping rate is 264.00 m3/d. A reasonable suggestion is to adopt non-uniform injection mining mode in ISL.

Background: Schizophrenia is a mental disorder associated with inflammatory and oxidative stress markers such as lactate; in addition, the rate of physical inactivity in this population is very high, which leads to physical and metabolic alterations. Aims: This study measured the effect of assisted physical exercise over lactate levels in schizophrenia. Methods: Stable outpatients with schizophrenia and a group of Healthy controls received two different programs of Physical exercise (Aerobic and Functional) in a clinical trial. Results: Patients had higher lactate compared to healthy controls before and after intervention, and had higher rate of lactate increase after activity. The finding of increased lactate in schizophrenia detected before and after physical exercise deserve further attention in biomarker studies and in the development of physical rehabilitation in schizophrenia, suggesting different profile of oxidative metabolism after physical exercise. Basal increased lactate may reflect mitochondrial dysfunction or metabolic dysregulation, and the higher rate of increase may reflect a different metabolic and oxidative process. Conclusion: The finding is in line with recent studies as surrogate of mitochondrial dysfunction in schizophrenia and points to the need of additional studies on mitochondrial activity in schizophrenia, and to additional care in the design of physical interventions in schizophrenia.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a term that covers a range of hepatic disorders involving fat deposits in the liver. NAFLD begins with simple steatosis and progresses into non-alcoholic steatohepatitis (NASH) characterised by inflammation, fibrosis, apoptosis, oxidative stress, lipid peroxidation, mitochondrial dysfunction and release of adipokines and pro-inflammatory cytokines. Oxidative stress and antioxidants are known to play a vital role in the pathogenesis and severity of NAFLD/NASH. A number of oxidative stress and antioxidant markers are employed in the assessment of the pathological state and progression of the disease. In this article, we review several biomarkers of oxidative stress and antioxidants that have been measured at clinical and experimental levels. The levels/ activity in various models reviewed are also included. Also included is a comprehensive description of oxidative stress, sources and contribution to the pathogenesis of NAFLD/NASH

Prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the aging cognitive decline and mood changes are not completely understood. In order to improve our knowledge, we integrated transcriptomic data of four studies of human PFC from old people -58-80 years old- compared with young people -20-40 years old- using a meta-analytic approximation combined with molecular signature analysis. We identified 1816 differentially expressed genes -561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of SHH pathway and up-regulation of metallothioneins I and genes of the family EZR -ezrin, radixin, and moesin-. The main conclusions of our study are the confirmation that in aged PFC there is a global dysfunction of the synapses and we reported for the first time opposite phenotypes of astrogliosis because of brain aging.

Ferroptosis is an iron-dependent cell death pathway that involves depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of Glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IP3R) channel plays a role in this process. We show that inhibition of GPx4 by RAS Selective Lethal Compound 3 (RSL3) generated an increase in reactive oxygen species (ROS), increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, an inhibitor of the ER-resident IP3R calcium channel, by decreasing IP3R levels with carbachol and by IP3R1 knock-down. The intracellular calcium chelator BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IP3R-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which in turn stimulate the production of ROS and induce lipid peroxidation and ferroptotic cell death in a noxious positive feedback cycle.

Changes in epitranscriptome with N6‐methyladenine (m6A) modification could be involved in the development of multiple diseases, which might be a prevalent modification of messenger RNAs (mRNAs) in eukaryotes. The m6A modification might be performed through the action of methyltransferases, demethylases, and methylation-binding proteins. Importantly, the m6A methylation may be associated with various neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), depression, aging related diseases, and/or aging itself. In addition, the m6A methylation might functionally regulate the eukaryotic transcriptome by influencing splicing, export, subcellular localization, translation, stability, and decay of mRNAs. Neurodegenerative diseases may possess a wide variety of phenotypes depending on the neurons that degenerate at occasions. Interestingly, increasing number of evidences have indicated that m6A modification could modulate the expression of autophagy-related genes and promote autophagy in neuronal cells. Oxidative stresses such as reactive oxygen species (ROS) could stimulate the m6A RNA methylation, which may be also related to the regulation of autophagy and/or the development of neurodegenerative diseases. Both m6A modification and autophagy could also play critical roles in regulating health condition of neurons. Therefore, a comprehensive understanding of the m6A and autophagy relationship in human diseases may benefit in developing therapeutic strategies in the future. This paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of neurodegenerative diseases and/or aging, discussing the possible therapeutic procedures related to mechanisms of m6A RNA methylation and autophagy.

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&lt;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 &lt;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.

Background and Objectives: Obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis resistant obese individuals. Materials and Methods: Thirty-nine, periodontally healthy subjects were enrolled. Based on BMI scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were assessed for interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A) and CRP. Results: GCF CRP levels were significantly higher in obese than lean individuals. No statistically significant differences were noted between the two groups in both GCF and blood on any of the inflammatory cytokine levels. IL-17A was not detected in GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, the association tended to be stronger in obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels positively associated with multiple GCF inflammatory cytokines (e.g., IL-1β, IL-6, IL-8 and TNF-α) in all subjects, the associations tended to be weaker in obese individuals (e.g., IL-1β, IL-6, TNF-α). Furthermore, the levels of GCF inflammatory cytokines IL-6 and TNF-α were depressed in obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a dysregulated inflammatory cytokine response in the gingival tissues of obese individuals.

Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.

In this work, oligoesters with terminal hydroxyl groups were obtained by directed glycolytic degradation of polyethylene terephthalate. The possibility of obtaining bifunctional reactive oligomers with an average molecular weight of 865 g mol-1 by directed glycolytic destruction via a dissolution-degradation strategy in dimethyl sulfoxide at a low concentration of ethylene glycol (32.3 mass parts per 100 mass parts of polyethylene terephthalate) was shown. This process allows us to partially solve the urgent problem of recycling post-consumer polyethylene terephthalate.

Background and Objective: Although whole body-electromyostimulation (WB-EMS) has been shown to favorably improve body composition in several research studies, it has not been confirmed how it affects adipose tissue-derived biomarkers and circumferences of the abdomen and thighs. Materials and Methods: Twenty participants of obese elderly women were randomly classified into an EMS group (EMSG; n = 10) or a non-EMS group (CON; n = 10). The WB-EMS suits used in this study enabled the simultaneous activation of 8 muscle groups with selectable intensities for each phase. Stimulation frequency was selected at 85 Hz, impulse-width at 350 μ seconds, and impulse-rise as a rectangular application. Impulse duration was 6 seconds with a 4-second break between impulses. The EMS sessions were combined with aerobic dancing 3 times a week for 12 weeks. Both groups received the same program; however, the CON did not receive electrical stimuli. Biomarkers and body composition including circumferences of the abdomen and thighs were measured on Week 0 and Week 12. Results: Compared with the CON, 1) a significant effect of the EMS-intervention concerning decreased body weight (p = 0.032) and increased basal metabolic rate (p = 0.029) were evident. The thigh subcutaneous fat and total fat of EMSG were not significantly changed, but those of CON were significantly increased after 12 weeks. 2) The biomarkers of CON either increased or showed no change, although the interleukin (IL)-6 was significantly (p = 0.028) decreased in EMSG. Specifically, C-reactive protein (CRP; p = 0.005) and alpha-fetoprotein (p = 0.050) of CON were significantly increased after 12 weeks. In addition, the IL-6 (p = 0.034), CRP (p = 0.001), carcinoembryonic antigen (p = 0.017), and low density lipoprotein (p = 0.005) of EMSG were lower than those of CON in the end of experiment. 3) Conclusions: The results indicate that EMS intervention improved body composition and reduced negative biomarkers, thus highlighting its effectiveness.

Photodynamic inactivation (PDI) combines the nontoxic photosensitizer (PS) and visible light to generate reactive oxygen species (ROS), which can cause oxidative damages in (on) microbial organisms. Previously, we have shown that chitosan can augment the bactericidal efficacy mediated by PDI against bacteria and Candida. In this study, we showed that the antimicrobial action of chitosan to augment PDI relates to the enlargement of cell surface destruction. The microbial cell surfaces exhibit severe irregular shapes after PDI in the presence of chitosan. Furthermore, increase in the concentrations or incubation time of chitosan significantly reduce the amounts of photosensitizers TBO required, indicating that chitosan could be a synergistic agent with PDI against human pathogens. A prolonged lag phase was found in PDI surviving microbial cells, in which chitosan can act to synergistically eradicate the cells. Once the impaired cells rebuild their cellular functions from PDI-induced damage, the increased cytotoxic effect of chitosan disappeared. Together, our results suggest that chitosan with an augmented bactericidal activity after PDI is to inhibit the rehabilitation of PDI surviving cells, leading to microbial death.

Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2’-FL and its potential mechanisms in a mouse model of ischemic stroke. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

In this paper an overview of waste materials in underground coal mines is presented, whereas waste materials can be of anthropogenic or geogenic origin. Complex interactions with mine water and waste materials take place, especially during mine water level rebound. Bearing in mind that under the increasing societal pressure most, if not all underground coal mines are going to be closed rather sooner than later, it is important to understand these interactions and to predict the composition and dynamics of mine water lever rebound in underground coal mines to prevent adverse effects to the environment, especially receiving waters and drinking water resources. The second part of this article focusses on the experiences gained in the Ruhr area, a closed underground coal mining region in Western Germany, where mine water rebound has been ongoing for decades. In this regard, the modelling program DMT-Boxmodel has been developed and applied to predict the hydrodynamics and hydrogeochemical development of the water rebound. As an example, simulation results of water rebound as well as solute and PCB transport in central province of Ruhr mining area are compared to the monitoring data, and predictions over 3 decades are given. The experiences gained in the mine water management in Ruhr area can be applied in mining areas worldwide.

Control of oxidation/antioxidation homeostasis is important for cellular protective functions, and disruption of the antioxidation balance by exogenous and endogenous ligands can lead to profound pathological consequences of cancerous commitment within cells. Although cancers are sensitive to antioxidation drugs, these drugs are sometimes associated with problems including tumor resistance or dose-limiting toxicity in host animals and patients. These problems are often caused by the imbalance between the levels of oxidative stress induced reactive oxygen species (ROS) and the redox efficacy of antioxidants. Increased ROS levels, because of abnormal function, including metabolic abnormality and signaling aberrations, can promote tumorigenesis and the progression of malignancy, which are generated by genome mutations and activation of pro-oncogene signaling. This hypothesis is supported by various experiments to show that the balance of oxidative stress and redox control is important for cancer therapy. Although many antioxidant drugs exhibit therapeutic potential, there is a heterogeneity of antioxidation functions, including cell growth, cell survival, invasion abilities, and tumor formation, as well as the expression of marker genes including tumor suppressor proteins, cell cycle regulators, nuclear factor erythroid 2-related factor 2, and Jun dimerization protein 2; and their effectiveness in cancer remains unproven. Here, we summarize the rationale for the use of antioxidative drugs in preclinical and clinical antioxidant therapy of cancer, and recent advances in this area using cancer cells and their organoids, including the targeting of ROS homeostasis.

In organisms that use reduced sulfur compounds as alternative or additional electron donors to organic compounds, transcriptional regulation of genes for enzymes involved in sulfur oxidation is needed to adjust metabolic flux to environmental conditions. However, little is known about the sensing and response to inorganic sulfur compounds such as thiosulfate in sulfur-oxidizing bacteria. In the Alphaproteobacterium Hyphomicrobium denitrificans, one strategy is the use of the ArsR-SmtB-type transcriptional regulator SoxR. We show that this homodimeric repressor senses sulfane sulfur and that it is crucial for the expression not only of sox genes encoding the com-ponents of a truncated periplasmic thiosulfate-oxidizing enzyme system but also of several other sets of genes for enzymes of sulfur oxidation. DNA binding and transcriptional regulatory activity of SoxR are controlled by polysulfide-dependent cysteine modification. The repressor uses the formation of a sulfur bridge between two conserved cysteines as a trigger to bind and release DNA and can also form a vicinal disulfide bond to orchestrate a response to oxidizing conditions. The importance of the sulfur bridge forming cysteines was confirmed by site directed mutagen-esis, mass spectrometry and gel shift assays. In vivo, SoxR interacts directly or indirectly with a second closely related repressor, sHdrR.

Huntington’s disease (HD) is a late-onset; progressive, dominantly inherited neurological disorder marked by an abnormal expansion of polyglutamine (poly Q) repeats in Huntingtin (HTT) protein. The pathological effects of mutant Huntingtin (mHTT) are not restricted to the nervous system but systemic abnormalities including immune dysregulation have been evidenced in clinical and experimental settings of HD. Indeed, mutant huntingtin (mHTT) is ubiquitously expressed and could induce cellular toxicity by directly acting on immune cells. However, it is still unclear if selective expression ofmHTT exon1 in neurons could induce immune responses and hemocyte function. In the present study, we intended to monitor perturbations in the hemocytes population and their physiological functions in Drosophila, caused by pan-neuronal expression of mHTT protein. We found that pan-neuronal expression of mHtt significantly alters crystal cells and plasmatocyte count in larvae and adults with disease progression. Interestingly, plasmatocytes isolated from diseased conditions exhibit a gradual decline in phagocytic activity ex vivo at progressive stages of the disease as compared to age-matched control groups. We also observed an increased production of reactive oxygen species (ROS) in plasmatocytes at advanced stages of the disease. In addition, diseased flies displayed elevated reactive oxygen species (ROS) in circulating plasmatocytes at the larval stage and in sessile plasmatocytes of hematopoietic pockets at of disease. All the parameters were monitored progressively, targeting the circulation at larvae stage and hematopoietic pockets in adults at different disease stages, and many alterations were documented in the early stage itself. These findings strongly implicate that neuronal expression of mHtt alone is sufficient to induce non-cell-autonomous immune dysregulation in vivo. Based on these findings, we propose that further insight into the mechanisms through which neuronal expression of mHtt might be inflicting the innate immune responses would facilitate therapeutic inventions aimed at amelioration of HD pathology and improving the quality of life of the patients.