Mass cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in scientific literature and is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptides and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

Immune checkpoint inhibitors (ICI) are currently use in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. Aim of our study was to find predictive biomarkers of ICI treatment. We analyzed by immunohistochemistry various cell subsets, including CD3+ cells, CD8+ cells, CD68+ cells, CD20+ cells, FoxP3+ cells, and molecules as LAG-3, IDO1, TGfβ. Comprehensive genomic profiles were analyzed. Correlation of various biomarkers with efficacy of ICI treatment in patients with advanced solid tumors was evaluated. We evaluated 56 patients treated with ICI monotherapy. Longer median progression-free survival (PFS) was found in tumors negative for nuclear FoxP3 (P = 0.002, HR 0.14) and in TMB-high tumors (P = 0.024, HR 0.38). Longer overall survival (OS) was found in patient with intraepithelial CD8 negativity (P = 0.045, HR 0.47). In malignant melanoma CD68 negativity, FoxP3 negativity and PDL TPS ≥ 1 was associated with longer PFS. In NSCLC FoxP3 was associated with longer PFS and OS. We found that absence of expression of several biomarkers such as CD68 and FoxP3 is associated with better survival. TMB-high and PD-L1 expression not universally but in certain disease could predict response.

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

Epilepsy is a chronic neuronal disorder characterized by periodic, unpredictable, and recurrent seizures due to either a genetically determined or an acquired brain disorder. Although many anti-epileptics drugs (AEDs) are developed to control epilepsy, 30% of patients still need additional drugs or experience recurrent seizures and psychiatric and behavioral side effects. Thus, the need for medical care for patients with uncontrolled epilepsy remains unmet. The Genus Artemisia L. is one of the largest genera in the Asteraceae family with more than 500 species widely distributed in Europe, Asia, and North America. Many Artemisia species have been used in various treatments since ancient times as folk remedies. They demonstrated strong antioxidant, anti-inflammatory, antimicrobial, antimalarial, and antitumor activity. Recent studies reveal that some species of Artemisia demonstrated a therapeutic benefit for epilepsy by its anti-oxidant, anti-inflammatory, neuroprotective, and anticonvulsant properties. In this review, we investigate the current state of the literature regarding the neuroprotective and antiepileptic potentials of the genus Artemisia and its possible underlying mechanisms.

Argulus is an ectoparasite that frequently infects goldfish, with severe effects and a high death rate. The use of plant extracts has been widely reported to have antiparasitic activities, including one of the solasodine compounds in sour eggplant extracts. This research evaluated the antiparasitic activities of Compositions A (Solanum ferox and Zingiber zerumbet extract at 400 and 200 ppm, respectively), B (SFE and Boesenbergia pandurata at 900 ppm), and C (single Solanum ferox at 400 ppm). The research stages comprised 1) isolation and analysis of solasodine content in sour eggplant extracts and its extract composition, 2) in vitro antiparasitic activities on Argulus sp. at doses of 50 and 100 ppm with a testing time of 60–240 minutes, and 3) in vivo antiparasitic activities on Argulus sp. on goldfish at a dose of 100 ppm and observation for 2–12 hours of medication. The results showed that sour eggplant extracts had a solasodine concentration of 7.151 mg/L, whereas the derivative compositions A, B, and C were 656, 485, and 295 ppm, respectively. The in vitro testing demonstrated that composition A was effective for killing approximately 80–100% of Argulus, whereas compositions B and C killed 80–90% and 60–70%, respectively. Viewed from the effectiveness for killing parasites, the result was excellent (above 50%). The in vivo medication test was continued using three extract compositions at a dose of 100 ppm. Compositions A, B, and C were found to be capable of releasing 81.33, 75.67, and 71.00 arguli, respectively, per fish. We concluded that the single SFE extract and a concoction with BPE and ZZE had reasonable antiparasitic activity, whereas the concoction of SFE and ZZE killed more Argulus parasites at a higher rate.

Neocarya macrophylla (Sabine) Prance (Nm, Chrysobalanaceae) is used traditionally as food, for medicinal spiritual and industrial purposes. It is also used as soap, dye, glue, fodder, termite repellent, firewood and for structural materials. Few studies on the physicochemical, nutritional contents, phytochemical and pharmacological activities have validated the benefits of Nm to humanity as food, in cosmetics and pharmaceutical products. The major bioactive constituents identified in the plant so far are steroids and flavonoids (such as stigmasterol, quercetin, catechin and its related glycosides). Extracts of the plant have shown good antivenom, antimicrobial, analgesic, anti-inflammatory, antimycobacterial, anthelmintic and antioxidant activities. Acute toxicity studies conducted have confirmed the plant to be toxic. More studies on the plant are required in order to exploit other biological activities as claimed by traditional healers and also to isolate more bioactive compounds. In addition, the safety and tolerability assessment of Nm should be undertaken due to its widespread usage.

Total 219 countries and territories globally suffering from the recent pandemic COVID-19 is now in its second wave with more brutality, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . It has several symptoms like as persistent fever; respiratory illnesses; cough; fatigue; shortness of breath; loss of appetite; persistent pain or pressure in the chest; dysgeusia; acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19 in both peoples who had died of due to acute respiratory distress syndrome (ARDS) or those who survived. Due to COVID-19, dysregulated immune response and wound repair mainly in elderly patients causes this secondary pulmonary fibrosis. Thus using anti-fibrotic agents could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article you will get to know about the lung fibrosis generation due to COVID-19 infection, about anti-fibrotic agents and the currents challenges of this field.

In recent years, intelligent fault diagnosis algorithms using deep learning method have achieved much success. However, the signals collected by sensors contain a lot of noise, which will have a great impact on the accuracy of the diagnostic model. To address this problem, we propose a one-dimensional convolutional neural network with multi-scale kernels (MSK-1DCNN) and apply this method to bearing fault diagnosis. We use a multi-scale convolution structure to extract different fault features in the original signal, and use the ELU activation function instead of the ReLU function in the multi-scale convolution structure to improve the anti-noise ability of MSK-1DCNN; then we use the training set with pepper noise to train the network to suppress overfitting. We use the Western Reserve University bearing data to verify the effectiveness of the algorithm and compare it with other fault diagnosis algorithms. Experimental results show that the improvements we proposed have effectively improved the diagnosis performers of MSK-1DCNN under strong noise and the diagnosis accuracy is higher than other comparison algorithms.

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

Functional ZnO nanostructured surfaces are important in a wide range of applications. Here we report facile fabrication of ZnO surface structures at near room temperature with morphology resembling that of sea urchins, with densely packed, μm-long, tapered nanoneedles radiating from the urchin centre. The ZnO urchin structures were successfully formed on several different substrates with high surface density and coverage, including silicon (Si), glass, polydimethylsiloxane (PDMS), and copper (Cu) sheets, as well as Si seeded with ZnO nanocrystals. Time-resolved SEM revealed growth kinetics of the ZnO nanostructures on Si, capturing the emergence of “infant” urchins at the early growth stage and subsequent progressive increase in the urchin nanoneedle length and density, whilst the spiky nanoneedle morphology was retained throughout the growth. ε-Zn(OH)₂ orthorhombic crystals were also observed alongside the urchins. The crystal structures of the nanostructures at different growth time were confirmed by synchrotron X-ray diffraction measurements. On seeded Si substrates, a two-stage growth mechanism was identified, with a primary growth step of vertically aligned ZnO nanoneedle arrays preceding the secondary growth of the urchins atop the nanoneedle array. The antibacterial, anti-reflective, and wetting functionality of the ZnO urchins—with spiky nanoneedles and at high surface density—on Si substrates was demonstrated. First, bacteria colonisation was found to be suppressed on the surface after 24 h incubation in Gram-negative E. coli culture, in contrast to control substrates (bare Si and Si sputtered with 20 nm ZnO thin film). Secondly, the ZnO urchin surface, exhibiting superhydrophilic property with a water contact angle ~0°, could be rendered superhydrophobic with a simple silanization step, characterised by a water static contact angle θ of 159° ± 1.4° and contact angle hysteresis ∆θ < 7°. The dynamic superhydrophobicity of the surface was demonstrated by bouncing-off of a falling 10 μL water droplet, with a contact time of 15.3 milliseconds (ms), captured using a high-speed camera. Thirdly, it was shown that the presence of dense spiky ZnO nanoneedles and urchins on the seeded Si substrate exhibited a reflectance R < 1% over the wavelength range λ = 200–800 nm. The ZnO urchins with unique morphology via a facile fabrication route at room temperature, readily implementable on different substrates, may be further exploited for multifunctional surfaces and product formulations.

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

White spot lesions (WSLs), a side effect of orthodontic treatment, can result in reversible and unaesthetic results. Graphene oxide (GO) with a bioactive glass (BAG) mixture(BAG@GO) was added to Low Viscosity Transbond XT(LV) in a ratio of 1, 3, 5%. The composite’s characterization and its physical and biological properties were verified with scanning electron microscopy(SEM) and X-ray diffraction(XRD); its microhardness, shear bond stress (SBS), cell viability, and adhesive remnant index (ARI) were also assessed. Efficiency in reducing WSL was evaluated using antibacterial activity of S. mutans. Anti-demineralization was analyzed using a cycle of the acid-base solution. Adhesives with 3 or 5 wt.% of BAG@GO showed significant increase in microhardness compared with LV. The sample and LV groups showed no significant differences in SBS or ARI. The cell viability test confirmed that none of the sample groups showed higher toxicity compared to the LV group. Antibacterial activity was higher in the 48-hour group than in the 24-hour group; the 48-hour test showed that BAG@GO had a high antibacterial effect, which was more pronounced in 5 wt.% of BAG@GO. Anti-demineralization effect was higher in the BAG@GO-group than in the LV-group; the higher the BAG@GO concentration, the higher the anti-demineralization effect.

Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.

Butanol extracts from leaves, twigs and fruits of Elaeagnus rhamnoides (L.) A. Nelson (sea buckthorn, SBT) were fractionated into phenolic and non-polar lipid components. Their chemical composition was analyzed using the Thermo Ultimate 3000RS chromatographic system, equipped with a diode array detector, a corona-charged aerosol detector, and coupled with a (Q-TOF) mass spectrometer. Assuming that an effect on natural microbiotaand host epithelial cells needs to be assessed, regardless of the purpose of using SBT formulations in vivo, the MIC/MBC/MFC of the fractions and reference phytocompounds were screened involving 17 species of Gram-positive and Gram-negative bacteria and Candida species. The impact of the fractions (subMIC) on the important in vivo persistence properties of S. aureus and C. albicans strains was evaluated. Tests for adhesion and biofilm formation on an abiotic surface and the surfaces conditioned with fibrinogen, collagen, plasma or artificial saliva showed the inhibitory activity of the fractions. The effects on FITC-labeled staphylococci adhesion to fibroblasts (HFF-1) and epithelial cells (Caco-2), and on fungal morphogenesis, indicated that SBT extracts have high anti-virulence potential. Cytotoxicity tests (MTT-reduction) on the standard fibroblast cell line showed variable biological safety of the fractions depending on their composition and concentration.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant anti-TB activity with an MIC₉₀ value of 1.5 μM.

Tea (Camellia sinenesis) is a health beneficial beverage and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of hetero-polysaccharides bounded with proteins. There were tests showing that TPS had various bioactivities, such as antioxidant, antitumors, antihyperglycemia, anti-inflammation and improving immunity. However, inconsistent results concerning chemical composition and bioactivity of TPS were published in recent years. The advances in chemical composition and bioactivities of TPS were reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS were also discussed.

(1) Background: Eosinophils importance as T2 inflammation markers is known to be fundamental in asthma, chronic sinusitis, vasculitis. In cancer, despite their potential antiproliferative effect, their role remains unclear. Our purpose was to describe the relation between baseline blood eosinophil count (EOS) and overall survival in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We have analyzed retrospectively the data of 137 adult patients, who underwent surgical treatment of PDAC between years 2012-2019 with no history of systemic steroid use directly before surgical treatment and no metastases found intraoperatively. (3) Results: EOS&lt;0,1 G/l (vs. ≥0,1 G/l) was an independent prognostic factor for OS both the uni- and multivariate Cox regression (respectively: HR=1,48, p=0,035 and HR=1,57, p=0,021). According to EOS and PDAC stage, median OS were: in stage I-III, EOS ≥0,1 G/l group: 14,5 months, in stage I-III, EOS &lt;0,1 G/l group: 8,0 months, in stage IV, EOS ≥0,1 G/l group: 7,0 months, in stage IV, EOS &lt;0,1 G/l group: 5,0 months. (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that T2 inflammation may be the factor directly or indirectly lengthening survival of PDAC patients.

Skin cancers, including melanoma, and non-melanoma- cutaneous basal cell carcinoma and cutaneous squamous cell carcinoma, are a diverse group of malignancies characterized by variations in their molecular and cellular features. Melanoma is a highly heterogenous tumor characterized by the dysregulation of a myriad of cell-cycle associated signaling pathways. In the non-melanoma skin cancers, such as cutaneous basal and cutaneous squamous cell carcinoma, the role of cyclin-dependent kinases and cyclins remains poorly understood with relatively limited investigation. Although revolutionary therapies against diverse molecular targets have been introduced over the last decade leading to significant prognostic benefit, advanced stages of melanoma remain exceptionally difficult to treat. The three cancers are united by evidence of stem-like, cancer initiating cell populations which dictate highly dynamic microenvironments and rely on disrupted cell cycle signaling to support treatment resistance and cancer progression. Potential of cell cycle targeting in skin cancer in underexplored in terms of identification of specific mechanisms supporting the maintenance of skin cancer stem cell pools and could offer potential targets to advance the therapy in these malignancies. In this review, we comprise the existing data on major cell of cell cycle regulators in skin cancer, the regulation of cancer stem cells and most recent developments and limitations surrounding cell cycle-targeted therapies, with a focus on the application of CDK inhibitors.

Cancer, a complex group of diseases marked by uncontrolled cell growth and invasive behavior, is characterized by distinct hallmarks acquired during tumor development. These hallmarks, first proposed by Douglas Hanahan and Robert Weinberg in 2000, provide a framework for un-derstanding cancer's complexity. Targeting them is a key strategy in cancer therapy. It includes inhibiting abnormal signaling, reactivating growth suppressors, preventing invasion and me-tastasis, inhibiting angiogenesis, limiting replicative immortality, modulating the immune sys-tem, inducing apoptosis, addressing genome instability, and regulating cellular energetics. Usnic acid (UA) is a natural compound found in lichens that has been explored as a cytotoxic agent against cancer cells of different origins. Although the exact mechanisms remain incom-pletely understood, UA presents a promising compound for therapeutic intervention. Under-standing its impact on cancer hallmarks provides valuable insights into the potential of UA in developing targeted and multifaceted cancer therapies. This article explores UA activity in the context of disrupting hallmarks in cancer cells of different origins based on articles that emphasize the molecular mechanisms of this activity.

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of tri-ple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs, so that the distinct pH of tumor cells, would stimulate the release of the drug and/or genetic materi-al. The current revision summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

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.

Cancer, a globally prevalent and often deadly disease, holds promise for improved treatment through the integration of innovative medical technologies and interdisciplinary collaborations. Despite advancements, current cancer therapies lack a specific focus on addressing recurrence and targeting cancer stem cells (CSCs), known contributors to relapse. In this study, we utilized three types of cancer cells and generated three types of CSCs derived from them to conduct proteomic analysis and identified shared cell surface biomarkers as potential targets for a comprehensive treatment strategy. The selected biomarkers underwent evaluation through shRNA treatment, revealing contrasting functions in cancer and CSCs. Knocking down the identified protein showed promising results in regulating epithelial-mesenchymal transition (EMT) and stemness via the ERK signaling pathway. This led to a reduction in resistance to anticancer agents, ultimately enhancing the overall anticancer effects. Additionally, the biomarker's significance in clinical patient outcomes was confirmed using bioinformatics. Our study suggests a novel cancer treatment strategy that addresses existing limitations in current anticancer therapies.

Introduction: Skin cancer is the 5th most common cancers in western countries with surge in the cases of occurrence with the passing time making it a global burden on health care system. In this present study, the cancer preventive activities of Argemone mexicana Linn (AM), which has been widely used by folklores to treat different ailments. Aim: The experiment advocates the cancer preventive activity of ethanolic extract of AM and to against DMBA/TPA induced skin cancer in mice model. Materials and Methods: Experimental animals were divided into doses group,100mg/kg B.W, 250mg/kg B.W, 500mg/kg B.W and 1000mg/kg B.W and subjected to toxic dose determination. The DMBA/TPA method was followed to induce the skin cancer in mice along with the feeding of non-toxic doses of 100mg/ kg, 250mg/kg, 500mg/kg mice were given as a pretreatment and 500mg/kg as a separate post treatment group as per body weight. The anti-cancerous activity was determined by different parameters on 0day, 30th day and 60th day including change in incidence of tumour induction, haematological parameters, histopathology and changes in pattern of TNF-α secretion and NF-kB (p65 subunit) signaling pathway in the blood serum. Results: The 1000 mg/kg BW was found to exhibit sub-acute toxicity. It was observed that the 500mg/kg BW pretreated group resisted and delayed the tumour formation for up to 8 weeks as compared to the Negative Control group where growth was seen in 4 weeks. The tumour burden was also found to be varying in a dose-dependent where on 60th day, Negative Control group and 100mg/kg BW was found to possess significantly high (p&lt;0.001) tumour burden in comparison to the 500mg/kg BW group where tumour burden was not found till 60th day. The study was validated by body weight, blood parameters, histopathology and altered pattern in regulation of TNF-α and NF-kB signaling pathway which play an important role in cancer progression. The expression of TNF-α and p65 subunit of NF-kB signaling pathway was found to be reduced significantly in a dose dependent manner and found to be highly reduced in 500mg/kg BW group (p&lt;0.001) as compared to Negative control. Conclusion: The 500mg/kg BW pretreated group was found to have significant results in comparison to 500mg/kg BW post treatment group. The study revealed effective cancer preventive activity of Argemone mexicana Linn leaves (AML) in the mice model and paved a pathway for molecular approaches which could be explored more in future studies.

Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL is involved in tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, PODXL has been considered as a promising target of monoclonal antibody (mAb)-based therapy. However, PODXL also plays an essential role in normal cells such as vascular and lymphatic endothelial cells.Therefore, cancer-specificity or selectivity is required for the reduction of adverse effects on normal cells. Here, we developed an anti-PODXL cancer-specific mAb (CasMab), PcMab-6 (IgG₁, kappa), by immunizing mice with soluble PODXL ectodomain derived from a glioblastoma LN229 cell.PcMab-6 reacted with the PODXL-positive LN229 cells, but not with PODXL-knockout LN229 cells in flow cytometry. Importantly, PcMab-6 recognized pancreatic ductal adenocarcinoma (PDAC) cell lines (MIA PaCa-2, Capan-2, and PK-45H), but did not react with normal lymphatic endothelial cells (LECs). In contrast, one of the non-CasMabs, PcMab-47 showed high reactivity to both the PDAC cell lines and LECs. Next, we engineered PcMab-6 into a mouse IgG_2a type (PcMab-6-mG_2a) and a humanized IgG₁-type (humPcMab-6) mAbs, and further produced the core fucose-deficient types (PcMab-6-mG_2a-f and humPcMab-6-f, respectively) to potentiate the antibody-dependent cellular cytotoxicity (ADCC). Both PcMab-6-mG_2a-f and humPcMab-6-f exerted ADCC and complement-dependent cellular cytotoxicity in the presence of effector cells and complements, respectively. In the PDAC xenograft model, both PcMab-6-mG_2a-f and humPcMab-6-f exhibited potent antitumor effects. These results indicated that humPcMab-6-f could apply to antibody-based therapy against PODXL-expressing pancreatic cancers.

BRCA1 and 2 pathogenic variants increase lifetime risks of breast (50-75%) and ovarian cancer (15-20%). Guidelines recommend breast screening (MRI and mammogram) or risk-reducing mastectomy with salpingo-oophorectomy for ovarian cancer prevention. We sought to 1) characterize the population of BRCA1/2 carriers in Newfoundland and Labrador (NL) 2) evaluate risk-reducing interventions 3) identify factors influencing screening and prevention adherence. Methods: This is a retrospective study from a population-based provincial cohort of BRCA1/2 carriers. Eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommended screening or prevention. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. Results: 276 BRCA1/2 carriers were identified; 156 living NL females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 y versus 51.7 y; p=0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0% and 75.7% of patients underwent MRI, mammogram, risk-reducing mastectomy, and risk-reducing salpingo-oophorectomy, respectively. Individuals with breast cancer were more likely to have risk-reducing mastectomy (64.7% versus 35.3%; p<0.001), and those who attended specialty hereditary cancer clinic were more likely to be adherent with breast/ovarian cancer recommendations (73.2% versus 13.4%; p<0.001) and to undergo risk-reducing salpingo-oophorectomy(84.1% versus 15.9%; p<0.001). Conclusions: Nearly 40% of female BRCA1/2 carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic breast and pelvic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian health care systems and have the potential to reduce the burden of disease country-wide.

Pain is frequently reported during cancer disease, and still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Thereby, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discuss the different options currently available to manage pain in (former) cancer patients in the light of progress made in the last decade. Major progress in the field are recent development of a chronic cancer pain taxonomy now included in International Classification of Diseases (ICD-11) and update of WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, opioids being considered as mainstay. The opioids crisis has prompted the reassessment of opioids use, both in cancer patients and cancer survivors. The review focuses on the current utilization of opioids, on the neuropathic pain component often neglected and on techniques and non-pharmacological strategies available which help to personalize patient’s treatment. Cancer pain management is now closer to the management of chronic non-cancer pain i.e. “an integrative pain care” aiming to improve patient’s quality of life.

In the present study, we have followed the hydrothermal path for the synthesis of gold nanoparticles (Au NPs) from the biomaterial Elaeocarpus ganitrus seeds extract, which is a rapid, eco-friendly, non-chemical way. The prepared NPs were thoroughly analyzed by PXRD & HR-TEM studies and also tested for photocatalytic dye degradation and anticancer studies. Besides, antioxidant, antibacterial and anticancer properties of Au NPs were studied. In vitro studies revealed the dose-dependent cytotoxic effect of Au NPs. The prepared nanoparticles showed good cytotoxic impact against Prostate cancer (PC-3) cells line. The results of the present study could contribute to synthesize new and cost-effective drugs from Elaeocarpus ganitrus seeds extract by using bio approach.

Cachexia is a complex metabolic syndrome characterized by loss of skeletal muscle, leading to a significant weight loss that impacts patient morbidity and mortality. Given the complexity of gene regulatory networks that control gene expression, our objective was to perform an integrative mRNA and miRNA profiling to identify genetic programs that capture essential mechanistic details that promote muscle atrophy in cancer cachexia. Here, we used RNA sequencing to analyze miRNAs and mRNAs expression profiles in tibialis anterior (TA) muscles of the Lewis lung carcinoma model of cancer cachexia. In addition, we compared these findings with RNA-Seq data from C2C12 myotubes treated in vitro with the cachectic factors tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Extracellular matrix (ECM) alterations were validated by picrosirius staining, western blot, and fractal dimension analyses. We found 1,008 mRNAs and 18 miRNAs differentially expressed in cachectic mice. This set of genes was associated with the ECM, proteolysis, and inflammatory response. Enrichment analysis of transcriptional factor binding sites revealed activation of the atrophy-related transcriptional factors: NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and miRNA expression profiles identified post-transcriptional regulation by miRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and FoxO signaling pathway. C2C12 myotubes treated with TNF-α and IFN-γ similarly down-regulate subsets of ECM genes, including collagens. Our integrative analysis of miRNA-mRNA co-profiles comprehensive characterized regulatory relationships of molecular pathways and revealed miRNAs targeting ECM-associated genes in cancer cachexia. We also confirmed in C2C12 myotubes that changes in ECM-associated genes are dependent on inflammatory signaling of the cytokines TNF-α and IFN-γ.

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes’ and Wilson’s diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

Circular RNA (circRNA) vaccines are emerging as a revolutionary strategy in cancer immunotherapy, offering novel mechanisms for inducing robust and durable immune responses. Unlike traditional linear mRNA vaccines, circRNAs exhibit exceptional stability, enhanced translational efficiency, and resistance to exonuclease degradation, making them ideal candidates for vaccine development. This review delves into the fundamental principles underlying circRNA biology, highlighting their unique structural advantages and translational potential. We examine recent advancements in circRNA vaccine design, focusing on their application in oncology. As the circRNA-based cancer vaccine is a relatively novel approach, accounts of all the major studies describing the efficacy have been discussed. To maximize the anti-cancer effects of circRNA vaccines, we also investigate their combination with other immunotherapeutic modalities such as immune checkpoint inhibitors and adoptive cell therapies. Large-scale manufacturing, immunogenicity optimization, delivery systems, and other challenges and future directions in the sector are also discussed. This study aims to thoroughly analyse the state-of-the-art and potential future applications of circRNA vaccines in cancer immunotherapy, highlighting them as exciting possibilities for next-generation cancer therapies.

Purpose: Testicular cancer (TC) is a rare cancer but due to early age at diagnosis and excellent cure rates, there is a big cohort of survivors. Recent studies have highlighted the late side effects of treatments of TC especially cisplatin based chemotherapy. These complications make the survivorship care challenging with detrimental effects on health and prognosis of TC survivors. In this study we provide a snapshot of common late side effects in TCS and a possible care pathway with nurse-led specialised clinic. Methods: We invited TCS in one of the cancer centre in Ireland for a comprehensive screening using questionnaires, examination and blood tests. Further investigations were performed as indicated. Mortality was assessed through retrospective chart reviews. Results: We recruited 78 TCS to participate in study. 3 patients who had died in survivorship phase were assessed through retrospective chart review. Second malignant neoplasms accounted for all three mortalities. Most common conditions in TCS after 5 years of diagnosis were hypertension (40%), dyslipidaemia (55.6%), hypogonadism (~45%) and high body mass index (52%). Majority of underlying conditions were diagnosed during screening in our clinic including two cases of coronary artery disease and one case of transient ischaemic attacks. Chemotherapy and age more than 30 years at the time of TC diagnosis were associated with a higher incidence of the late side effects. Conclusions: TC is a highly curable cancer but survivorship phase is marred by a range of late side effects. As we lack clear guidelines and care pathways for survivorship, this remains a challenge for patients and healthcare workers. A nurse-led, specialised, screening clinic can improve the care and prognosis of TC survivors.

: Optical coherence tomography is a non-invasive imaging technique that provides three-dimensional visualization of subsurface tissue structures. OCT has been proposed and explored in literature as a tool to assess oral cancer status, select biopsy sites, or identify surgical margins. Our endoscopic OCT device can generate widefield (centimeters long) imaging of lesions at any location in the oral cavity – but it is challenging for raters to quantitatively assess and score large volumes of data. Leveraging a previously developed epithelial segmentation network, this work develops quantifiable biomarkers that provide direct measurements of tissue properties in three-dimensions. We hypothesize that features related to morphology, tissue attenuation, and contrast between tissue layers will be able to provide a quantitative assessment of disease status (dysplasia through carcinoma). This work retrospectively assesses seven biomarkers on a lesion-contralateral matched OCT dataset of lateral and ventral tongue (40 patients, 70 sites). Epithelial depth and loss of epithelial-stromal boundary visualization provide the strongest discrimination between disease states. The stroma optical attenuation coefficient provides distinction of benign lesions from dysplasia and carcinoma. The stratification biomarkers visualize subsurface changes which provides potential for future utility in biopsy site selection or treatment margin delineation.

Identifying the primary site of origin of metastatic cancer is vital for guiding treatment decisions, especially for patients with cancer of unknown primary (CUP). Despite advanced diagnostic techniques, CUP remains difficult to pinpoint and is responsible for a considerable number of cancer-related fatalities. Understanding its origin is crucial for effective management and potentially improving patient outcomes. This study introduces a machine learning framework ONCOfind-AI that leverages transcriptome-based gene set features to enhance the accuracy of predicting the origin of metastatic cancers. By ensuring compatibility between RNA-sequencing and micro-array data, we were able to construct a more comprehensive training dataset. Integrating data from different platforms improved the accuracy of our machine learning models for predicting cancer origins. Our method was validated using external data from clinical samples collected through Kangbuk Samsung Medical Center and the Gene Expression Omnibus. The external validation results demonstrated a top-1 accuracy ranging from 0.80 to 0.86, with a top-2 accuracy of 0.90. This study highlights that incorporating biological knowledge through curated gene sets can merge gene expression data from different platforms, enhancing the compatibility needed for more effective machine learning prediction models.

Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

Abstract: Cervical cancer, which is the fourth most common malignancy and the fourth greatest cause of cancer-related deaths in women globally, continues to be a serious issue for global health. Despite advancements in treatment techniques, particularly the implementation of concomitant chemoradiation therapy, predicting the prognosis of locally advanced cervical cancer, especially for stage III, remains challenging. In recent years, neoadjuvant chemotherapy (NACT) has gained interest as a viable treatment strategy. The objective of this review paper is to scrutinize the clinical data and outcomes associated with NACT in the management of stage 3 cervical cancer. Electronic databases were used to perform a comprehensive literature search, and research up to 2023 were included. The findings suggest that NACT followed by irradiation may have advantages such as lowering tumor size, pelvic architectural distortion, and subclinical distant metastases, therefore enhancing radiation delivery. However, several studies have produced conflicting findings, raising questions regarding toxicity and finding no appreciable survival benefit over radiation alone. NACT followed by radical surgery has demonstrated more promising outcomes compared to surgery alone in terms of increasing rates of overall survival (OS) and progression-free survival (PFS). Additionally, NACT has been associated with decreased tumor growth, parametrial infiltration, nodal, metastases, and vascular space invasion. These findings suggest adjuvant radiation treatment. Although the overall survival rate has been markedly increased by concomitant chemoradiation treatment, metastatic disease continues to be a major factor in the death rate from cervical cancer. Therefore, improving outcomes in locally advanced cervical cancer requires investigating novel systemic treatments, such as NACT. The study also emphasizes how crucial it is to research factors like cisplatin dose-intensity and cycle lengths in order to maximize NACT's efficacy. To prevent the need for subsequent treatments and cumulative toxicity, more study should concentrate on patient selection for NACT followed by surgery.

Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was identification of serum biomarkers of early response to NAC. Methods: We conducted this prospective study in the MSCNRIO, in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers signed informed consent. Complete blood count, blood chemical tests, carcinoembryonic antigen (CEA) carcinoma antigen 125 (CA125), carcinoma an-tigen 19.9 (CA19.9), d-dimer, fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Results: Of all the measured parameters, only IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in complete pathological re-sponse (pCR) vs non-pCR group (3.71 pg/mL vs 7.63 pg/mL, p=0,004). In all patients with IL-6 levels below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs ypN0 (7.69 pg/mL vs 2.89 pg/mL, p=0.022). Conclusions: The trial showed that elevated level of IL-6 prior to treatment and C2 might be a predictor of pathologic response to NAC.

The cancer burden is increasing worldwide with contrasting national patterns. Therefore, providing national estimations is necessary to understand and control this health issue. Herein, we comparatively describe incidence, mortality, and disability-adjusted lived years (DALYs) due to 29 groups of cancer in Mexico from 1990 to 2019 by sex and age. Using public data from the Global Burden of Disease Study 2019, we assessed the national burden of cancer using counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and their trends using the annual percentage of change from 1990 to 2019. In 2019, cancer caused 222,060 incident cases, 105,591 deaths, and 2,86,054 DALYs in the general population. Nonmelanoma skin cancer, prostate cancer, and breast cancer had the highest incidence, and six groups of cancer (lung, colorectal, stomach, prostate, breast, and pancreatic) caused 53% of the deaths in 2019. From 1990 to 2019, incidence and mortality showed an increasing trend that varied between 10% and 436% among the groups of cancer, whereas the crude and age-standardized rates showed cancer-specific sex disparities. Our results demonstrate a substantial growth of the national burden of cancer with sex-specific patterns of change. These results may guide national efforts toward reducing health loss due to cancer.

The genome sequencing technologies reveal the molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing (WGS) data. We analyzed sequencing data from 1076 unrelated individuals, released openly for academic and clinical research as The Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort (our study) was compared to the frequency estimated for the non-Finnish European population, obtained from the gnomAD database (gnomad.broadinstitute.org). Statistically significant variants included 23 genes. Even though the Polish population is genetically similar to other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as RET, CHECK2, BRCA1, SLC26A4 or TERT. Further studies are needed to identify genomic variants associated directly with DTC.

Savolitinib is a highly selective small molecule inhibitor of the mesenchymal epithelial transition factor (MET) tyrosine kinase, primarily developed for the treatment of non-small cell lung cancer (NSCLC) with MET mutations. It is also being investigated as a treatment for breast, head and neck, colorectal, gastric, pancreatic, and other gastrointestinal cancers. In both preclinical and clinical studies, it has demonstrated efficacy in lung, kidney, and stomach cancers. Savolitinib is an oral anti-cancer medication taken as a 600 mg dose once daily. It can be used as a monotherapy in patients with non-small cell lung cancer with MET mutations, and in combination with epidermal growth factor receptor (EGFR) inhibitors for patients who have developed resistance to them. Furthermore, savolitinib has shown positive results in gastric cancer treatment, particularly in combination with docetaxel. As a result, this review aims to validate its efficacy in NSCLC and suggests its potential application in other gastrointestinal cancers, such as pancreatic cancer, based on related research in gastric and renal cancer.

Blood-based circulating cell free DNA(cfDNA) detection offers a non-invasive and easily accessible way for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to develop the clinical biomarkers. For example, cfDNA with genetic alterations often compose a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from health population will be important for the cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in small amount of cfDNA-based cancer test. We hypothesize that, the combination of diverse types of cancer studies on cfDNA can provide us a new insight to identify low-frequency genetic variant across cancer types for early clinical detection of cancers. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritize 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting to membrane, some of which are tumor suppressor, oncogene and related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as the common biomarkers in early cancer diagnosis.

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnosis. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NAT) from TCGA repository, and proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D-cells and EVs, but barely expressed in NAT. Moreover, 20 tRFs were expressed in 3D-cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and cell-substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-EV derived samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.

Two related tumor suppressor genes, Brca1 and Brca2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanism(s) of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on mechanisms of DNA damage repair where these proteins are involved in and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also propose a hypothesis that explains why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss perspectives of novel therapeutic approaches for treating BRCAness cancers.

Pancreatic cancer represents one of the difficult problems of contemporary medicine. The development illness evolves very slowly, takes place in special sake (stroma) and manifests clinically close to a final stage. Another feature of this pathology is a coexistence (symbiotic) effect between cancer cells and normal cells inside stroma. All these aspects make it difficult to understand the pathogenesis of pancreatic cancer and develop a proper therapy. The emergence of pancreatic pre-cancer and cancer cells represents a branching stochastic process engaging populations of 64 cells differing in the number of acquired mutations. In this study we formulate and calibrate the mathematical model of pancreatic cancer using the quasispecies framework. The mathematical model incorporates the mutation matrix, fineness landscape matrix and the death rates. Each element of the mutation matrix presents the probability of appearing a specific mutation in the branching sequence of cells representing the accumulation of mutations. The model incorporates the cancer cell elimination by effect CD8 T cells (CTL). The down-regulation of the effector function of CTLs and exhaustion are parameterized. The symbiotic effect of coexistence of normal and cancer cells is considered. The computational predictions obtained with the model are consistent with empirical data. The modelling approach can be used to investigate other types of cancers and examine various treatment procedures.

Cancer is the second leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. Although traditional molecular profiling techniques, i.e., bulk sequencing, can identify common mutations and gene expression patterns in cancer cells, they cannot detect tumour heterogeneity. However, single-cell technology has provided an ample opportunity to overcome this difficulty. Since this technology allows us to detect the heterogeneous properties of all cancer cells, this can further our knowledge of the signaling pathways in cancer cells. Indeed, single-cell transcriptomics technology has paved the road for identifying novel biomarkers and signaling pathways, which can serve as targets. This study aims to review the current knowledge about pathways involved in developing cancer cells and shed light on single-cell studies as promising therapeutic approaches.

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) of Minnesota, “Sage”, provides breast cancer screening to uninsured women. We introduce a novel mapping technique, spatially adaptive filters (SAFs), to estimate utilization of Sage screening in Minnesota. Sage screenings (N = 74,712) were geocoded. The eligible population was modeled with the RTI synthetic population dataset. Between 2011 and 2015, 36,979 women a year were Sage eligible. Utilization was highly variable across Minnesota (M = 37.2%, range 0% - 131%, SD = 18.7%). This replicable approach modeled utilization rates to the neighborhood-level, allowing Sage to prioritize locations and engage communities.

Young women with breast cancer represent 15% of cancer cases in Latin America. Genomic studies have found that early-onset breast-cancer cases exhibit a higher genetic susceptibility and a specific genomic signature as compared to their older counterparts. The aim of this study was to describe clinically relevant germline mutations in a cohort of young women with breast cancer. To achieve this, we analyzed hereditary-cancer genes from whole-exome sequencing data in 108 unrelated women with an extreme phenotype of breast cancer (≤40 years of age), diagnosed and treated at the National Cancer Institute of Mexico; 11% of the patients carried a pathogenic variant. BRCA2 comprised 46% of the mutations, followed by BRCA1 with 23%; PALB2 with 15%; and TP53 and RAD51C with 8 % each. This article describes a novel pathogenic mutation in RAD51C c.519dupT. The median age at diagnosis was 35 years overall; however, it was six years younger in patients with mutations. Age at diagnosis (OR=0.82, CI 95% 0.71-0.94; P= 0.008) and first-degree family history of cancer (OR=8.26, CI95% 1.35-50; P= 0.022) were the only epidemiological variables associated with mutational status. We found no differences in disease-free survival (p=0.403) or overall survival (p=0.735) among mutational status subgroups.

Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that in turn promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report, we analyzed clinical dataset of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We thus developed a new therapeutic approach to inhibit EGFR and hypoxia by combination of metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic, this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.

Submucosal invasion is a critical step in gastric cancer (GC) progression, which greatly enhances metastasis risk. Cancer stem cells are responsible for invasion, metastasis, and tumor growth. To identify stem cell-related markers associated with submucosal invasion in GCs, we investigated the expression of candidate cancer stem cell (CSC) markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs with submucosal invasion. Remarkably, expression of all ISC markers and CD133 was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer. The proportion of stem cell marker-positive cells substantially increased during submucosal invasion. Given that ISC markers are restricted to the crypt base of the normal intestinal mucosa, these findings suggest that many early GCs may retain hierarchical characteristics. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. RSPO2 from muscularis mucosa seem to be partly responsible for the increased expression of ISC markers in GC cells at the basal areas. We also found that ISC markers were correlated with CDX2 expression in GCs, indicating that ISC markers are involved in the intestinal differentiation in GCs. Interestingly, ISC markers (EPHB2 and OLFM4) and CD133 showed a positive impact on clinical outcomes. In particular, the prognostic value of EPHB2 was significant for intestinal-type GCs in a multivariate analysis. In summary, ISC markers and CD133 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs. EPHB2 was an independent prognostic marker in intestinal-type GCs.

Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Lung cancer remains the leading cancer killer worldwide. Early diagnosis can effectively increase the patient cure rate but existing diagnostic methods limit early lung cancer diagnosis. Therefore, development of a simple but efficient lung cancer screening method is important to improvement of both the diagnosis rate and the survival rate of lung cancer patients. In this study, ten photosensitive materials with high sensitivity and high specificity were screened accurately to construct a microarray sensor that can rapidly identify six types of lung cancer biomarkers in exhaled breath. Results from hierarchical cluster analysis (HCA), principal component analysis (PCA) and difference maps showed that the classification of the analytes agreed with structure similarity laws. The detection results from parallel experiments and structurally similar analytes, in turn, cluster into a group; the fingerprints of the different analytes have specific response regions. The well-screened sensor chip fabrication workload and cost were both reduced by approximately two thirds, while the microfluidic device sensitivity and stability increased by approximately 1.3 times their corresponding values before optimization. The dual-channel device also offers real-time contrast detection and synchronous parallel detection functions and has potential application prospects for use in extensive screening of high-risk populations for lung cancer.

BACKGROUND: Endoscopic placement of Self Expandable Metal Stents to relieve malignant colorectal obstruction has become a common therapeutic advancement in clinical practice. MATERIAL: In a 16 year period 167 patients had endoscopic placement of a Self Expandable Metal Stent in a center where gastroenterologists and surgeons cooperate in a daily basis, discussing indications. RESULTS: There was no operative mortality and no major complication in placement of the stent. Technical and clinical success was respectively 95.1% and 92.9%. Consultation among specialists changed the preoperative indication in 60 patients, during the same time period. CONCLUSIONS: Self expandable metal stents placement represents an important tool to treat patients with obstructing colorectal cancer and complications after colorectal resection . A proper training is required, and this training in operative endoscopy is not always available and possible. In this scenario, a close collaboration among specialists in selecting the most appropriate operative procedure is essential and brings to better results.

Coordinated sets of extremely numerous digital data, on a given social or economic event, are treated by Artificial Intelligence tools to obtain reasonably accurate, valuable predictions. The same approach, applied to biomedical issues, as how to choose the right drug to completely cure a given cancer patient, does not reach satisfactory results. It is the “organized biological complexity”, which requires a different systems approach, to integrate, in an Augmented Intelligence strategy, statistical computations of digital data, network construction of “omics” findings, well-designed mathematical models and new experiments in an iterative pathway to reconstruct the “logic” beneath the “organized complexity”, as shown here for Systems Metabolomics of cancer. On this basis new diagnostic approaches, able to identify precision drug treatments, as well as new discovery strategy for more effective anti-cancer drugs are described.

Mutations in the “guardian of the genome” TP53 predominate in solid tumors. In addition to loss of tumor suppressor activity, a specific subset of missense mutations confers additional oncogenic properties. These “gain-of-function” (GOF) mutations portend poor prognosis across cancer types regardless of treatment. Our objective in this study was to identify novel therapeutic opportunities to overcome the deleterious effects of GOF TP53 mutants. Using gynecologic cancer cell lines with known TP53 mutational status, we established that treatment with a proteasome inhibitor induced cell death in cells with two recurrent GOF TP53 mutations (R175H and R248Q), and addition of a histone deacetylase inhibitor (HDACi) enhanced this effect. By contrast, p53-null cancer cells were relatively resistant to the combination. Towards understanding the mechanism, we found that proteasome inhibition promotes apoptosis of cells with TP53 GOF mutations, potentially through induction of the unfolded protein response. In line with the reported hyperstabilization of GOF p53 protein, cells treated with HDACi exhibited reduced levels of p53 protein. Together, these data form the basis for future clinical studies examining therapeutic efficacy in a preselected patient population with GOF TP53 mutations.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

Several evidences suggest that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometime inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: PhIP, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline: MeIQx, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene: (B(a)P) and “meat derived mutagenic activity”: MDM) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR=1.20; 95%CI:1.13,1.28; p<0.001), MeIQx (OR=1.14; 95%CI:1.05,1.23; p=0.001), DiMeIQx (OR=1.13; 95%CI:1.05,1.21; p=0.001), B(a)P (OR=1.10; 95%CI:1.02,1.19; p=0.017) and MDM (OR=1.17; 95%CI:1.07,1.28; p=0.001). A linear and curvilinear trend was observed in dose-response meta-analisis between CRA risk in association with PhIP and MDM, MeIQx, respectively. CRC risk (21344 cases) was increased by uptake of MeIQx (OR=1.14; 95%CI:1.04,1.25; p=0.004), DiMeIQx (OR=1.12; 95%CI:1.02,1.22; p=0.014) and MDM (OR=1.12; 95%CI:1.06,1.19; p<0.001). No publication bias could be detected whereas heterogeneity was in some cases rather high. Mutagenic compounds formed during cooking of meat at high temperature may be responsible of its carcinogenicity.

Gut dysbiosis and an inflamed bowel are growing concerns in mammals, including dogs. Probiotic supplements have been used to restore the natural microbial community and improve gastrointestinal health. Biofilm formation, antimicrobial activities, and immunological responses of probiotics are crucial to improving gut health. Thus, we tested a commercial probiotic blend (LabMAX-3), a canine kibble additive comprising Lactobacillus acidophilus, Lacticasibacillus casei, and Enterococcus faecium for their ability to inactivate common enteric pathogens; their ability to form biofilms, epithelial cell adhesion and anti-inflammatory response on Madin-Darby Canine Kidney (MDCK) cell line. Probiotic LabMAX-3 blend, or individual isolates, showed a strong inhibitory effect against Salmonella enterica, Listeria monocytogenes, enterotoxigenic Escherichia coli, and Campylobacter jejuni. LabMAX-3 formed biofilms comparable to Staphylococcus aureus. LabMAX-3 adhesion to the MDCK cell line (with or without lipopolysaccharide, LPS) pretreatment showed comparable adhesion and biofilm formation (p < 0.05) to L. casei ATCC 334 used as a control. LabMAX-3 had no cytotoxic effects on the MDCK cell line during 1 h exposure. The IL-10 and TNFα ratio of LabMAX-3, compared to the L. casei control, showed a significant increase (p < 0.05), indicating a more pronounced anti-inflammatory response. The data show that LabMAX-3, a canine kibble supplement, can improve gastrointestinal health.

We provide representations for the generalized Drazin inverse of an anti-triangular matrix of the form $\left( \begin{array}{cc} a&b\\ 1&0 \end{array} \right)$ in a Banach algebra $\mathcal{A}$, under the condition that $ab=ba$. Specifically, we present the representation of Drazin inverse for these types of anti-triangular matrices in Banach algebras.

Abstract: Conventional antibiotic and multidrug treatments become less and less effective and a discovery of new effective and safe antibacterial agents got a global priority. The returning to the natural antibacterial product is relatively new current trend. Terrestrial biota is a rich source of biologically active substances whose antibacterial potential was not fully utilized. Aim of this review is to present the current state-of-the art of terrestrial biota-derived antibacterial agents and inspired by nature treatments. It is a summary of the most important sources and new identified or modified antibacterial agents and treatments during the last 5 years. It focuses on the significance of plants- animals- and bacteria-derived biologically active agents as powerful alternatives to antibiotics as well as on the advantages of utilizing natural antibacterial molecules alone or in combinations with antibiotics. The main conclusion is that the terrestrial biota derived antibacterial products and substances open variety of new ways to modern improved therapeutic strategies. New terrestrial sources of known antibacterial agents and new antibacterial agents from terrestrial biota were discovered during the last 5 years, which are under investigation together with some long ago known but now surviving their renaissance for the development of new medical treatments. Use of natural antibacterial peptides as well as combinational therapy by commercial antibiotics and natural products outlines as the most promising for treating of bacterial infections. In vivo testing and clinical trials are necessary to reach clinical application.

Glucocorticoids (GCs) are widely used in blood cancer treatment despite their multiple adverse effects. Biological response to GCs is mediated by glucocorticoid receptor (GR) by transactivation (TA), associated with side effects, and transrepression (TR), mediating anticancer effects. Selective GR agonists (SEGRAs) preferentially activating GR TR could be better option for cancer treatment. One of well-characterized SEGRAs is 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium-chloride (CpdA), demonstrated anticancer activity in vitro and in vivo, however its translational potential is limited due to chemical instability. CpdA derivatives CpdA-01-08 were designed by two synthetic strategies. Derivative CpdA-03 demonstrated superior GR affinity and stability compared to CpdA. Analysis of CpdA-03 ligand properties in lymphoma Granta and leukemia CEM cell lines revealed its SEGRA profile: it induced GR TR without triggering GR TA, as evidenced by changes in expression of GR target genes. Effects of CpdA-03 on cell viability, growth, and apoptosis were similar to reference GR ligand, dexamethasone (Dex), and the proto-type compound CpdA. In vivo testing of CpdA-03 anti-lymphoma activity in transplantable P388 murine lymphoma model showed that CpdA-03 reduced tumor volume threefold, outperforming Dex and CpdA. In conclusion, this work introduces CpdA-03 as promising new SEGRA with potential for further development as anti-lymphoma drug with fewer side effects.

Natural cytokinins are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of novel cytokinin analogs with alkyl substituents at various positions of the aromatic moiety, as well as with oxygen-containing groups, and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Two amino-linked compounds were anti-proliferative with the ability to act synergistically with doxorubicin, and two carbamate-based ones were cytoprotective. According to the molecular docking data, anti-proliferation was based on the A2AR and APRT inhibition and cytoprotection on the CDK2 inhibition. The obtained results are promising for the development of novel anti-cancer therapeutics.

This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax China L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads to skin inflammation, we developed a fermented product, MB-2006, and compared its effects to those of heat-killed probiotics, Lactobacillus acidophilus (LAC) and Lac-tobacillus rhamnosus (LRH). Our experiments focused on elucidating the mechanism of action of MB-2006 in AD-like HaCaT keratinocyte cells, particularly its impact on the NF-kB pathway, a pivotal regulator of inflammation. MB-2006 proved more effective in reducing inflammation markers such as IL-4 and thymic stromal lymphopoietin (TSLP), and in inhibiting NF-kB activation, compared to LAC and LRH. Significantly, MB-2006 also reduced the expression of thymus- and activation-regulated chemokine (TARC), highlighting a synergistic effect that enhances its thera-peutic potential. These results suggest that the combined fermentation of Smilax china L. extract with lactic acid bacteria enhanced both the anti-inflammatory and immunomodulatory effects, pre-senting a promising integrative approach to treating conditions like AD. Further studies are needed to validate these results in clinical settings and fully explore the potential of this synergistic fer-mentation process.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, that is managed by using non-steroidal anti-inflammatory drugs (NSAIDSs). Information is limited about how NSAIDSs affect the therapeutic potential of stem cells. Therefore, we investigated the effects of ibuprofen and diclofenac in low and high therapeutic doses on the properties of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro. Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Our results suggest that concomitant use of the NSAIDSs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, which can affect the efficacy of stem cell therapy.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

Shigellosis is a pathological condition that affects the digestive system to possibly cause diarrhoea. Shigella species, which are responsible for this disease, are highly contagious and spread through contaminated food and water. The increasing development of resistance by Shigella species necessitate the urgent need to search for new therapies against shigellosis causing diarrhoea. The scientific validation of medicinal plants, such as Diospyros gilletii, which is used for the traditional treatment of diarrhoeal conditions is worthwhile. The present study aims to investigate the antibacterial activity of extracts from D. gilletii against selected Shigella species. Extracts from D. gilletii stem bark were prepared by maceration using various solvents. An-tibacterial activity of D. gilletii extracts was evaluated on Shigella dysenteriae, S. flexneri, S. boydii, and S. sonnei using a microdilution method, whereas cytotoxicity test was performed on Vero and Raw cells using resazurin-based colorimetric assay. Bacterial membrane permeability studies were evaluated using pro-pidium iodide (PI) and 1-N-phenylnaphthylamine (NPN) uptake assays, whereas inhibition and eradica-tion tests on bacterial biofilms were carried out by spectrophotometry. As a result, methanol, ethanol and hydroethanol extracts of D. gilletii inhibited the growth of S. boydii, S. flexneri and S. sonnei with MIC values ranging from 125 to 500 µg/mL, without toxicity to Vero and Raw cells. Time kill kinetics revealed bacteri-cidal orientation at 2MIC and 4MIC, and bacteriostatic outcome at 1/2MIC. The mechanistic basis of anti-bacterial action revealed that D. gilletii extracts inhibited and eradicated Shigella biofilms, and promoted the accumulation of NPN and PI within the inner and outer membrane of bacteria to increase membrane per-meability, thereby causing membrane damage. This novel contribution toward the antibacterial and mech-anisms of action of D. gilletii extracts against Shigella species substantiate the use of this plant in the tradi-tional treatment of infectious diarrhoea.

A new biodegradable paper-based film is a hot research topic in the development of green agriculture. In this paper, a black paper base film coated with cooked tung oil with excellent mechanical properties, hydrophobic surface, high heat transfer and strong weather resistance was prepared by spraying high pigment carbon black solution on the surface of base paper. The results showed that the surface solidified oil film with rough structure was made by the brush coating process of cooked tung oil, and the base film of black paper was given hydrophobic structure, and the contact angle reached 98.9 °. Cooked tung oil permeates into the inside of the paper base, and after curing, it forms a multi-dimensional network film structure. The maximum tensile stress of the black paper base film is about 123% higher than that of the original paper base film. The coloring of carbon black makes the black paper base film have heat conduction effect, and the average heat transfer rate reaches 15.12 °C/s. Cooked tung oil is combined with the paper-based fiber high-toughness layer to form a stable system. The existence of the cured film improves the basic mechanics and hydrophobicity, and the resistance to ultraviolet radiation and hot air is greatly improved. This study provides a feasible scheme for the application of a black paper base film coated with cooked tung oil.

The enhancement of human living conditions has resulted in an increase in average life expectancy, giving rise to a novel social and medical challenge: aging, which diminishes the overall quality of human life. The aging process of the body begins through the activation of effector signaling pathways of aging in cells, loss of their normal functions and deleterious effects on the microenvironment, which leads to chronic inflammation and similar transformation of neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated mortality risk. Among the most encouraging methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. The review explores the strategies and advancements in the field of anti-aging therapies that are currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches.

Streptococcus thermophilus is widely used as a starter culture in the dairy industry and has garnered attention as a beneficial bacterium owing to its health-promoting functionalities in humans. In this study, the probiotic potential of S. thermophilus MCC0200, isolated from a dairy product, was investigated through a combinatorial approach of in-vitro and in-silico studies. MCC0200 demonstrated the ability to survive harsh gastro-intestinal transit (GIT), adhere to intestinal mucosa and exert health-promoting traits in in-vitro studies. These findings were corroborated with in-silico evidence, wherein MCC0200 genome harboured genes associated with tolerance to GIT conditions, intestinal adhesion and colonization. Genome mapping also highlighted the ability of MCC0200 to produce compounds advantageous for host (folate, bacteriocins), to release enzymes that can reinforce the host ability (antioxidative enzymes), to metabolize food components that can be harmful to sensitive people (lactose). MCC0200 also demonstrated a positive effect on reducing cholesterol levels, proving to be a potential candidate for food and pharmaceutical applications. Absence of transmissible antibiotic resistance genes and virulence genes underscored the GRAS nature of MCC0200. This study explored the potential of Streptococcus thermophilus for its probable applications as a probiotic beyond the dairy industry.

Background: Retinal diseases such as neovascular age related macular degeneration (nAMD), diabetic macular edema (DME) or branch-/central retinal vein occlusion (B/CRVO) have significant implications for patients' social and psychological well-being. To gain a comprehensive understanding of patients' backgrounds and attitudes, we developed an exploratory questionnaire, the Basic Care and Patient Satisfaction Questionnaire (BPZ-9). Methods: The ALBATROS study aimed to assess the care situation of treatment-naïve patients diagnosed with either nAMD, DME or B/CRVO. The data collection took place at the beginning of treatment and after twelve months of anti-VEGF (vascular endothelial growth factor) therapy. The BPZ-9 instrument comprises nine questions to evaluate patients’ psychological and social situation and their satisfaction with treatment. Results: Data were collected from 1.478 nAMD (mean 78 years), 445 DME (67 years), 233 BRVO (70 years) and 144 CRVO (71 years) patients at 102 study centers throughout Germany. Approximately one third of the patients was living alone and six percent were in organized care. One in four patients had difficulties to walk and one in five needed accompany for treatment. Anxiety to lose vision was present in three out of four patients at the beginning and slightly decreased to two out of three over the 12-month treatment preriod. The distress of having a retinal disease was generally higher than the distress related to treatment. Most patients reported high treatment satisfaction (73%) and felt well informed (81%). Conclusion: Patients receiving anti-VEGF therapy commonly experience impaired mobility, dependency on others, distress and the fear of vision loss.

Diabetes mellitus is a chronic disease, commonly associated with unhealthy habits and obesity, and it is becoming a serious health issue worldwide. As a result, new approaches to treat diabetes are required, and a movement towards more natural ones is emerging. Consuming fruit and vegetables is advised to prevent diabetes since they contain several bioactive compounds. A simple and ef-fective strategy to include them in the diets of diabetic and obese people is through beverages. This review aimed to report the anti-diabetic potential of different vegetable and fruit beverages. These functional beverages demonstrated in vitro potential to inhibit α-glucosidase and α-amylase en-zymes, and to improve glucose uptake. In vivo, the beverage consumption showed a reduction of blood glucose, increase of insulin tolerance, improvement of lipid profile, control of obesity, and reduction of oxidative stress. This suggests the potential of vegetable and fruit-based functional beverages to be a natural innovative therapy for the management of diabetes.

A twin-screw extruder was used to fabricate poly(butylene succinate) (PBS)/high density polyethylene (HDPE) blends (7:3 weight ratio) and blend-based nanocomposites. Carbon nanotubes (CNTs), graphene nanoplatelets (GNPs) and organoclays (15A and 30B) served as the nanofiller, while maleated HDPE (PEgMA) acted as an efficient compatibilizer for the blend. In the composites, individual nanofillers were mostly localized in HDPE domains, but some fillers were also observed at PBS-HDPE interfaces. The sea-island morphology of compatibilized blend evolved into a pseudo-co-continuous morphology in the composites. Differential scanning calorimetry results confirmed that PEgMA with HDPE evidently accelerated the crystallization of PBS in the blend. The possible nucleation effect of added fillers on PBS crystallization was obscured by the formation of quasi-connected HDPE domains, causing less PBS nucleation sites. The presence of nanofillers improved the thermal stability and burning anti-dripping behavior of the parent blend. The anti-dripping efficiency of added fillers followed the sequence: CNT>15A>30B>GNP. Rigidity of the blend was increased after formation of nanocomposites. In particular, adding GNP resulted in 31% increase in flexural modulus. Development of a pseudo-network structure in the composites was confirmed by measurement of rheological properties. Electrical resistivity of the blend was reduced by more than 6 orders of magnitude at 3 phr CNT loading, demonstrating the achievement of double percolation morphology.

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. In this study, we investigated the protective effects of tocotrienol-rich fraction (TRF) on BL-induced oxidative stress and hyperpigmentation in B16-F1 melanocytes. Alpha-tocopherol (αTP) was used as a comparator. Our results showed that TRF effectively suppressed the formation of reactive oxygen species, and preserved the mitochondrial membrane potential. Additionally, TRF exhibited anti-apoptotic properties by reducing the activation of p38 mitogen-activated protein kinase molecule and downregulating the expression of cleaved caspase-3. Moreover, TRF modulated tyrosinase activity, resulting in a lowered rate of melanogenesis and reduced melanin production. In contrast, αTP did not exhibit the significant protective effects against skin damages and pigmentation in BL-induced B16-F1 cells. Therefore, this study indicates that TRF may offer superior protective effects over αTP against the effects of BL on melanocytes. These findings demonstrate the potential of TRF as a protective natural active against BL-induced skin damages and hyperpigmentation via its antioxidative and anti-melanogenic properties.

We performed a retrospective, observational study for 51 eyes of 51 treatment-naive patients with polypoidal choroidal vasculopathy (PCV), whose lesion ranged within the 6x6mm scope of optical coherence tomography angiography (OCTA). Patients were divided into two groups based on the pattern of branching vascular network (BVN) on OCTA: ill-defined group and well-defined group. BVN morphology was not related to baseline best-corrected visual acuity (BCVA). But the BCVA in the ill-defined BVN group (-0.18 [interquartile range: -0.40 to 0.00]) was significantly improved after anti-vascular endothelial growth factor (VEGF) injections, compared with that (0.00 [interquartile range: -0.18 to 0.00]) in the well-defined group (z=2.143, p=0.032). Multiple logistic regression analysis showed that male sex, smaller number of injections, and presence of polypoidal lesions on OCTA images at baseline predicted a poor prognosis of polypoidal lesions on OCTA images after anti-VEGF therapy (all p&lt;0.05). Finally, BCVA at baseline and the number of injections were protective factors for BCVA after anti-VEGF therapy (all p&lt;0.05). In contrast, history of hypertension and macular edema at baseline were risk factors for BCVA after anti-VEGF injections (all p&lt;0.05). Our results revealed the visual and morphological prognosis of patients with active subfoveal circumscribed PCV after anti-VEGF therapy.

Anastatica hierochuntica L. (Brassicaceae) has been claimed to treat various conditions including complicated childbirth. The principal objective of this research was to provide scientific evidence on the contractile effect of the aqueous and hydroethanolic extracts of the whole plant from A. hierochuntica during labor. Qualitative and quantitative methods helped identify and quantify the phytoconstituents in both extracts. The antioxidant activity was studied using four standard methods. The inhibitory power of the extracts on pro-inflammatory enzymes such as 15-lipoxygenase and phospholipase A2 was determined. The contractile effects of the extracts were evaluated using isolated pregnant mice uteri. Steroids, triterpenoids, flavonoids, tannins, coumarins, and reduced compounds were identified in both extracts. The extracts demonstrated the ability to reduce oxidative stress. The hydroethanolic extract displayed the most significant anti-lipoxygenase activity with an IC50 value of 55.82 ± 1.15 µg/mL. The lethal dose (LD50) of extracts was estimated to be superior to 2000 mg/kg bw. The ability of the samples to produce one cm amplitude of contraction at 50% effective concentrations (EC50) was 1.51 ± 0.08 mg/mL for aqueous extract and 3.57 ± 0.61 mg/mL for hydroethanolic extract. These findings could provide evidence for using Anastatica hierochuntica to augment labor.

Alzheimer’s disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders have proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured by passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured by ELISA kits, Western blotting, and immunostaining techniques. Data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p &lt; 0.05 ~ p &lt; 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg. p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments, ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue Considering the data obtained, DTZ exhibited a potential neuroprotective anti-dementia role in ICV-STZ-induced SAD-type conditions in rats and might be repurposed as a potential therapeutic agent in the treatment and management of AD and related dementia pathologies.

Suffocation syndrome is the leading cause of hypoxia and mortality in the most common lung diseases, asthma and COVID-19. Inhaled corticosteroids (ICSs) have been shown to be the main-stay of critical care in these diseases. Meanwhile, mortality from strangulated hypoxia is highest in low-income countries because ICSs are not currently available to many patients. Warm alkaline hydrogen peroxide solutions (WAHPSs) have reportedly been invented in recent years to urgently turn thick sputum, mucus, pus, serous fluid, blood clots and many other biological masses con-taining the enzyme catalase into a fluffy oxygenated foam. It has been shown that the mechanism of action of WAHPSs consists in alkaline saponification of lipid and protein-lipid complexes of bi-ological masses and their transformation into oxygen foam, because hydrogen peroxide is urgently decomposed into water and oxygen gas under the action of the biological masses catalase enzyme At that excess oxygen is absorbed into blood through lungs and increases blood oxygen saturation. Based on the described mechanism of action of WAHPSs and the high availability of their ingre-dients, it is suggested that mortality from choking and hypoxia in asthma and COVID-19 can be reduced by combining ICSs with inhaled WAHPSs, especially in poor countries. The essence of the inventions underlying the formation of WAHPSs is given.

Secondary metabolites such as flavonoids are considered to be promising in the treatment of NAFLD, which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated with regard to their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from STZ-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose-dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver TG levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.

Accumulation of extra fats in the body results in disturbance in homeostasis causing obesity. The pathophysiology of obesity has been associated with various genetic, epigenetic factors and the disturbed lifestyles of an individual. One of the outcomes is disturbance in the sleep cycle which leads to sleep disorders. The evolutionary significance of sleep lies in the fact that it saves energy and is crucial for adjustment of an individual to ecological and environmental factors, and thus maintains homeostasis. Sleep has an anabolic function and replenishes the wakefulness-associated loss of glycogen stores. However, the modern lifestyle is well known to disrupt sleep behavior and patterns affecting human health negatively. Alteration in homeostasis leads to several acute and chronic pathophysiological conditions like obesity and related metabolic morbidities being one amongst them. Shorter sleep duration and poor sleep quality are important risk factors associated with the development of obesity and have more adverse effects on energy homeostasis. Consequently, it is crucial to comprehend the obesity and sleep relationship and its therapeutic strategies, given that strong crosstalk exists between energy balance that favors obesity and sleep apnea. It is therefore highly recommended to the people with a high risk of obesity to maintain sleep discipline and good sleep hygiene in our daily life. Interventions are required to improve both sleep quality and quantity, and associated obesity. More focused research is needed for uncovering the pieces of evidence that determine whether such interventions can improve obesity-related health consequences. The present review discusses the important findings on the therapeutic and neuroendocrine mechanisms regulating sleep and obesity.

The bridge crane is often used in a complex environment, often subject to interference of all loads. Some uncertainties factors often have an inevitable impact on its swing. So the force situation of the bridge crane during a working cycle is analyzed, and a three-dimensional dynamic mathematical model of the bridge crane is built. Through the simulation analysis of the model under the action of driving force and wind load, the change law of the swing angle of the bridge crane is studied. Then, the fuzzy control theory is used to determine the control parameter in the anti sway control process. The position, swing angle deviation and deviation rate of the bridge crane are taken as the input, and the parameter correction is obtained after the fuzzification by using the center of gravity method, the anti sway fuzzy control system of the bridge crane is designed and simulated. The research results show that the fuzzy PID anti sway controller can not only improve the adaptability of the control system, but also overcome the large overshoot, quickly restrain the swing, and effectively realize the anti sway function of the bridge crane.

Four previously undescribed highly oxygenated diterpenoids (1–4), zeylleucapenoids A–D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of Leucas zeylanica. Their structures were elucidated primarily by NMR experiments. The absolute configuration of 1 was established by theoretical ECD calculations and X-ray crystallographic analysis, whereas those for 2−4 were assigned by theoretical ORD calculations. Zeylleucapenoid D (4), with an IC₅₀ value of 38.45 μM in RAW264.7 macrophages and nontoxic activity for zebrafish embryo, and obviously inhibited pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. Compound 4 inhibited of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated the possible mechanism of action for 4 may be bind to targets by hydrogen- and hydrophobic- bond interactions.

Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury, pain, as well as acute and chronic diseases. Since long-term uses of steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly-crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) were found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E2 (PGE2) production. In an air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells including neutrophils, monocytes and lymphocytes, and tumor necrosis factor-α and interleukin-1β concentrations, as achieved with dexamethasone (a steroid). Notably, PVRE also inhibited PGE2, similar to dexamethasone and indomethacin (an NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS ― NO and COX-2 ― PG pathways, and that PVRE could be a promising anti-inflammatory material for diverse issue injuries.

Curcuma longa is only a rich source of curcumin (1) and its major analogues demethoxycurcumin (2) and bisdemethoxycurcumin (3) among the Curcuma species. The content ratio of these three curcumins in turmeric is depended on the varieties and growing environment. Recently, curcumin (1) has been reported as potential inhibitor of hepatic and enzymatic protein tyrosine phosphatase 1B (PTP1B) and its related disorders such as hypertriglyceridemia, hyperlipidemia and liver steatosis. Thus, we further purified curcumins (1–3) from C. longa and investigated their inhibitory effects against PTP1B and α-glucosidase enzymes. As the result, curcumins (1–3) exhibited potential PTP1B inhibition with IC50 values of 37.8 ± 1.4, 45.3 ± 0.7, and 72.6 ± 1.1 μM, respectively, and α-glucosidase inhibition with similar manner (IC50 values of 78.2 ± 0.2, 82.4 ± 0.6, and 90.6 ± 1.0 μM, respectively). These results reveal a key role of methoxylation in the variation of PTP1B and α-glucosidase inhibitory activity for these curcumins. In addition, density functional theory (DFT) was used accompanying with molecular docking (MD) to analyze the ligand stability and the interaction of curcumins (1–3) with PTP1B and glucoside hydrolase proteins. Assay-based results and the MD data obtained are highly correlation suggesting that the deterioration of the enzyme activity caused by the distortion of structural conformation of PTP1B and glucoside hydrolase may be related to the arrangement of amino acids in protein structure. This reported for the first time that inhibitory effects of curcumins (1–3) against PTP1B and glucoside hydrolase have been examined in vitro and in silico as well.

Introduction: Periodontitis is a severe oral infection that can contribute to systemic inflammation. A large body of evidence suggests a role for systemic inflammation in the initiation of neurodegenerative disease. This systematic review synthesized data from observational studies to investigate the association between periodontitis and neuroinflammation in adults. Methods and materials: A systematic literature search of PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed for studies published from the date of inception up to September 2021. Search terms for the exposure “oral disease” and outcome “dementia”, “neuroinflammation” and “cognitive decline” were used. Study selection and data extraction were independently undertaken by two reviewers. The final eligible articles were included only if the exposure is periodontitis and the outcome is cognitive impairment or dementia or a topic related to this condition, and if the study was conducted in an adult population. The quality and risk of bias were assessed by Newcastle Ottawa Scale (NOS). Qualitative synthesis was used to narratively synthesize the results. Six cohort studies, three cross-sectional studies, and two case-control studies met the inclusion criteria. These eleven studies were only narratively synthesized. Meta-analysis was not performed due to the methodological heterogeneity of the studies. Results: All the included studies show evidence of an association between periodontitis and cognitive im-pairment or dementia and Alzheimer’s disease pathology. Conclusion: Nonetheless, the mechanisms responsible for the association between periodontitis and dementia are still unclear.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Multiple biological pathways manifest and latent, meant for human survival, become a liability in cancer cure. With an increasing understanding of innumerable complex paths, cancer progression and development of resistance is no surprise. For the three “vasculature-immune-phenotypic” fundamental changes, hypoxia is the maestro orchestrating the whole gamut of changes (through the master manipulator - HIF-1 α), simultaneously transactivating hundreds of pro-angiogenic genes. Such a complex molecular bio-network begs the question, “Is our cancer research caught in such a tangled web that we have lost sight of the Spider?”. Hypoxia is this Spider weaving compensatory webs with every intervention/ obstruction. Anti-angiogenic (AAG) research has been conducted mainly in silos – exploring independent paths. This review conceptualizes a convergence of a multitude of research worldwide to a single theme of normalizing vasculature as a primary baseline for overcoming resistance to AAGs or their combinations.

Citrus flavonoids are well-known for beneficial effects at the cardiovascular and cardio-metabolic level, but often the encouraging in vitro results are not confirmed by in vivo approaches; also clinical trials are inconsistent. The limited bioavailability of them can be, at least in part, the reason of these discrepancies. Therefore many efforts were performed towards the improvement of their bioavailability. Hydrodynamic cavitation methods were successfully applied to the extraction of byproducts of the Citrus fruits industry, showing high process yields and affording stable phytocomplexes, known as IntegroPectin, endowed with great amounts of bioactive compounds and high water solubility. Cardioprotective effects of grapefruit IntegroPectin were evaluated by an ex vivo ischemia/reperfusion protocol. A further pharmacological characterization was carried out to assess the involvement of mitochondrial potassium channels. Grapefruit IntegroPectin, where naringin represented 98% of flavonoids, showed anti-ischemic cardioprotective activity, better than pure naringenin (the bioactive aglycone of naringin). On cardiac isolated mitochondria, this extract confirmed that naringenin/naringin were involved in the activation of mitochondrial potassium channels. The hydrodynamic cavitation-based extraction confirmed a valuable opportunity for the exploitation of Citrus fruits waste, with the end product presenting high levels of Citrus flavonoids and an improved bioaccessibility that enhances its nutraceutical and economic value.

Sesamum indicum is considered an underutilized oil-bearing seed in the semi-arid regions of Ghana. Nonetheless, it is a promising source of food with both nutritional and therapeutic benefits. The aim of the present study was to evaluate the antioxidant properties S. indicum seeds using different extraction solvents. The seeds were obtained from the local farmers and prepared for analysis. The bioactive compounds present in the seeds were extracted using hexane, ethyl acetate, ethanol and water and their yields quantified. Total phenolic content (TPC), Condensed tannin content (TTC) and Total antioxidant capacity (TAC) , and DPPH radical scaveging assay were analyzed using standard methods. Antinutrients such as saponins, alkaloids, phytates and oxalates were also analyzed from the powdered seeds. Two chemometric methods; hierarchical cluster analysis (HCA) and Pearson correlation were employed to evaluate the interdependence of the various parameters to result in their antioxidant properties. The re-sults revealed that the solvents utilized had a significant impact on the extraction yield, phyto-chemical component concentration, and antioxidant activities. Hexane extracts of S. indicum seeds significantly exhibited the highest antioxidant activity (p &lt; 0.05). It was marked with the highest TAC value of 232.6 ± 6.267 mg/g AAE and a strong DPPH scavenging activity with an IC50 of 52.81 ± 2.30 µg/mL. Correlations (p &lt; 0.05) was established between TPC,CTC, TAC and DPPH radical scavenging activity) of the extracts. Antinutrients such as; phytate, oxalate, saponins and alkaloids were found to be 7.691 ± 0.8576, 1.501 ± 0.1375, 21.33 ± 4.619 and 317.33 ± 30.29 mg/g respectively. Data obtained suggest that S. indicum possess rich bioactive compounds that can be used in neutraceuticals and food products.

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

Abstract: This work is part of the interest of solving the problems of water contamination with last generation pollutants, for which a novel and in an aqueous medium FeBTC material incorporated with magnetite nanoparticles was proposed. That material was synthesized by in situ solvothermal method, the Fe3O4 nanoparticles were added during the Fe-BTC MOF synthesis and used in the drug’s adsorption. The materials were characterized by XRD, FTIR and Raman spectroscopy, and N2-physisorption at 77 K. Fe3O4-FeBTC material showed a maximum adsorption capacity of 357.1 mg g−1 for diclofenac sodium, 70.9 mg g−1 for naproxen sodium, and 122.9 mg g−1 for Ibuprofen. A pseudo-second-order kinetic model can describe the adsorption process, and the thermodynamic study revealed that the adsorption of the three drugs was a feasible, spontaneous, and exothermic process. The incorporation of magnetite nanoparticles in the FeBTC considerably increased the adsorption capacity of pristine FeBTC. Also, hybridization of the FeBTC with magnetite nanoparticles reinforced the most vulnerable part of the MOF, increasing its thermal and aqueous media stability. The electrostatic interaction, H-bonding, and interactions in the open-metal sites played a vital role in drug adsorption. The competition of sites in the multicomponent mixture's adsorption showed selective adsorption at diclofenac sodium and naproxen sodium.

Pathological vessel growth harms vision and may finally lead to vision loss. Anti-angiogenic gene therapy with viral vectors for ocular neovascularization has shown great promise in pre-clinical studies. Most of the studies has conducted with different adeno-associate serotype vectors. In addition, Adeno and lentivirus vectors have been used. Therapy has targeted to block vascular endothelial growth factors or other pro-angiogenic factors. Clinical trials of intraocular gene therapy for neovascularization have shown the treatment to be safe without severe adverse events or systemic effects. Nevertheless, clinical studies have not proceeded phase 2 trials further.

IgA vasculitis is a hypersensitivity vasculitis, which is usually self-limiting. Renal involvement is the most damaging long-term complication of IgA vasculitis, happening in 20% - 100% of cases. Some factors have been reported to be associated with renal involvement in IgA vasculitis; however, no biomarker has been proved as a risk factor for renal involvement and its severity yet. We followed 48 patients with a confirmed diagnosis of IgA vasculitis for six months. We checked these patients for renal involvement by microscopic urine examination. We checked aPL antibodies in all patients on admission and 12 weeks later. Urinalysis showed renal involvement in 14 of 48 patients with IgA vasculitis (29.16%). Antiphospholipid antibodies were positive in 9 patients with IgA vasculitis and renal involvement (9 out of 14, 64.28%), while they were positive in only six patients with IgA vasculitis without renal involvement (6 out of 34, 17.64%), showing a moderate correlation between positive aLP and renal involvement in patients with IgA vasculitis, with a kappa index of 0.457. Serum aPL antibodies, as a tool to predict renal involvement in IgA vasculitis, show a sensitivity of 64.3%, a specificity of 82.4%, PPV of 60.0%, and NPV of 84.8%, demonstrating that a positive serum aPL antibody can be used to positively predict the renal involvement, while a negative result is not strong enough to rule out future renal involvement.