Protective Role Research Articles

Associations between plasma metabolism associated proteins and future development of giant cell arteritis: results from a prospective study.

To investigate the relation between biomarkers associated with metabolism and subsequent development of giant cell arteritis (GCA). Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30447), who were subsequently diagnosed with GCA, were identified in a structured process. Matched GCA-free controls were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics metabolism panel (92 metabolic proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, Adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated (odds ratio (OR) per standard deviation (SD) 1.67; 95% CI 1.08-2.57), and Fructose-1,6-bisphosphatase 1 (FBP1) negatively associated (OR per SD 0.59; 95% CI 0.35-0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled <8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those sampled closest to diagnosis with a decreasing trend with longer time to GCA (p= 0.03). In the hypothesis generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.

Investigating the Role of 17-Beta Estradiol in the Regulation of the Unfolded Protein Response (UPR) in Pancreatic Beta Cells.

Diabetes mellitus is clinically defined by chronic hyperglycemia. Sex differences in the presentation and outcome of diabetes exist with premenopausal women having a reduced risk of developing diabetes, relative to men, or women after menopause. Accumulating evidence shows a protective role of estrogens, specifically 17-beta estradiol, in the maintenance of pancreatic beta cell health; however, the mechanisms underlying this protection are still unknown. To elucidate these potential mechanisms, we used a pancreatic beta cell line (BTC6) and a mouse model of hyperglycemia-induced atherosclerosis, the ApoE-/-:Ins2+/Akita mouse, exhibiting sexual dimorphism in glucose regulation. In this study we hypothesize that 17-beta estradiol protects pancreatic beta cells by modulating the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. We observed that ovariectomized female and male ApoE-/-:Ins2+/Akita mice show significantly increased expression of apoptotic UPR markers. Sham operated female and ovariectomized female ApoE-/-:Ins2+/Akita mice supplemented with exogenous 17-beta estradiol increased the expression of adaptive UPR markers compared to non-supplemented ovariectomized female ApoE-/-:Ins2+/Akita mice. These findings were consistent to what was observed in cultured BTC6 cells, suggesting that 17-beta estradiol may protect pancreatic beta cells by repressing the apoptotic UPR and enhancing the adaptive UPR activation in response to pancreatic ER stress.

The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study.

Accumulating evidence shows that dysregulation of intestinal flora is associated with inflammatory skin diseases, specifically atopic dermatitis (AD), psoriasis (PSO), and rosacea (ROS). However, the causality is still unclear. To study the underlying causality between gut microbiota (GM) and AD, PSO, and ROS, a bi-directional two-sample Mendelian randomization (2SMR) analysis was conducted. Summary statistics of gut microbiota, AD, PSO, and ROS were extracted from large-scale genome-wide association studies (GWASs). In 2SMR analysis, in addition to the inverse variance weighted as the principal method for evaluating causal association, four different methods were also used. Sensitivity analysis and reverse 2SMR study were implemented to evaluate the robustness of 2SMR results or reverse causal relationship, respectively. A total of 24 specific gut microbiota species related to AD, PSO, and ROS were identified by 2SMR analysis. After using the Bonferroni method for multiple testing correction, family FamilyXIII (ID: 1957) [OR = 1.28 (1.13, 1.45), p = 9.26e-05] and genus Eubacteriumfissicatenagroup (ID: 14373) [OR = 1.20 (1.09, 1.33), p = 1.65e-04] were associated with an increased risk for AD and PSO, respectively. The genus Dialister showed a negative association, suggesting a protective role against both atopic dermatitis and rosacea. Our reverse 2SMR analysis indicated no reverse causality between these inflammatory skin diseases and the identified gut microbiota. In summary, this study provided evidence for the causality between GM and inflammatory skin diseases. These findings suggested that supplementing specific bacterial taxa may be an effective therapy for AD, PSO, and ROS.

Evaluation of antisense oligonucleotide therapy targeting Hsd17b13 in a fibrosis mice model

Human genetic evidence suggests a protective role of loss-of-function variants in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) for liver fibrotic diseases. Although there is limited preclinical experimental data on Hsd17b13 antisense oligonucleotide (ASO) or siRNA in a fibrosis model, several ASO and siRNA approaches are being tested clinically as potential therapies for nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the therapeutic potential of Hsd17b13 ASO in a preclinical advanced NASH-like hepatic fibrosis in vivo model. In vitro testing on primary hepatocytes demonstrated that Hsd17b13 ASO exhibited strong efficacy and specificity for knockdown of the Hsd17b13 gene. In choline-deficient, L-amino acid-defined, HFD (CDAHFD)-induced steatotic and fibrotic mice, therapeutic administration of Hsd17b13 ASO resulted in a significant and dose-dependent reduction of hepatic Hsd17b13 gene expression. The CDAHFD group exhibited considerably elevated liver enzyme levels, hepatic steatosis score, hepatic fibrosis, and increased fibrotic and inflammatory gene expression, indicating an advanced NASH-like hepatic fibrosis phenotype. Although Hsd17b13 ASO therapy significantly affected hepatic steatosis, it had no effect on hepatic fibrosis. Our findings demonstrate, for the first time, that Hsd17b13 ASO effectively suppressed Hsd17b13 gene expression both in vitro and in vivo, and had a modulatory effect on hepatic steatosis in mice, but did not affect fibrosis in the CDAHFD mouse model of NASH.

Selenium and mercury concentration, Se/Hg molar ratio and risk–benefit assessment of marine fish consumption: Human health risks and protective role of Se against Hg toxicity

This study aimed to explore the concentrations of Se and Hg in marine fish along the Gulf of Mannar (southeast coast of India) and to assess related risks and risk-based consumption limits for children, pregnant women, and adults. Se concentrations in pelagic and benthic fish ranged from 0.278 to 0.470 mg/kg and 0.203 to 0.294 mg/kg, respectively, whereas Hg concentrations ranged from 0.028 to 0.106 mg/kg and 0.026 to 0.097 mg/kg, respectively. Se and Hg contents in demersal fish (Nemipterus japonicus) were 0.282 and 0.039 mg/kg, respectively. The lowest and highest Hg concentrations in pelagic fish were found in Scomberomorus commersoni and Euthynnus affinis whereas the lowest and highest Se concentrations in benthic fish were found in Scarus ghobban and Siganus javus. Se concentrations in marine fishes were found in the following order: pelagic > demersal > benthic whereas Hg concentrations were found in the following order: pelagic > benthic > demersal. The presence of Se in fish was positively correlated with trophic level (TL) and size whereas that of Hg was weakly correlated with TL and habitat and negatively correlated with size. Se risk–benefit analysis, the AI/RDI (actual intake/recommended daily intake) ratio was > 100 % and the AI/UL (upper limit) ratio was < 100 %, indicating that all fish have sufficient levels of Se to meet daily requirements without exceeding the UL. Hg level was below the maximum residual limit (MRL) of 0.5 mg/kg for most fish but it was 1 mg/kg in E. affinis and Lethrinus lentjan. The target hazard quotient (THQ < 1) and hazard index (HI < 1) imply that the consumption of fish poses no noncarcinogenic health risks. However, all examined fish had a mean Se/Hg molar ratio > 1, indicating that human intake of fishwas rather safe relative to Hg content. Health benefit indexes (Se-HBV and HBVse) with high positive values in all fish supported the protective effect of Se against Hg toxicity, suggesting the overall safety of fish consumption. The high Se/Hg ratio in fish could be attributed to the replacement of Se bound to Hg, thereby suppressing Hg toxicity and maintaining normal selenoprotein synthesis. This insight is useful for a better understanding of food safety analysis.

METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke

BackgroundStroke is a major medical problem, and novel therapeutic targets are urgently needed. This study investigates the protective role and potential mechanisms of the N6-methyladenosine (m6A) RNA methyltransferase METTL3 against cerebral injury resulting from insufficient cerebral blood flow.MethodsIn this study, we constructed mouse MCAO models and HT-22 cell OGD/R models to mimic ischemic stroke-induced brain injury and neuronal damage. We generated NEDD4L knockout and METTL3 overexpression models and validated therapeutic effects using infarct volume, brain edema, and neurologic scoring. We performed qRT-PCR, western blotting, and co-immunoprecipitation to assess the influence of NEDD4L on ferroptosis markers and TFRC expression. We verified the effect of NEDD4L on TFRC ubiquitination by detecting half-life and ubiquitination. Finally, we validated the impact of METTL3 on NEDD4L mRNA stability and MCAO outcomes in both in vitro and in vivo experimental models.ResultWe find NEDD4L expression is downregulated in MCAO models. Overexpressing METTL3 inhibits the iron carrier protein TFRC by upregulating the E3 ubiquitin ligase NEDD4L, thereby alleviating oxidative damage and ferroptosis to protect the brain from ischemic injury. Mechanistic studies show METTL3 can methylate and stabilize NEDD4L mRNA, enhancing NEDD4L expression. As a downstream effector, NEDD4L ubiquitinates and degrades TFRC, reducing iron accumulation and neuronal ferroptosis.ConclusionIn summary, we uncover the METTL3-NEDD4L-TFRC axis is critical for inhibiting post-ischemic brain injury. Enhancing this pathway may serve as an effective strategy for stroke therapy. This study lays the theoretical foundation for developing m6A-related therapies against ischemic brain damage.

Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.

Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish-Mycobacterium marinum infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and the tsc1a and cxcl12a/ccl2/ccr2 signalling axes resulting in the suppression of non-tnfa expressing macrophage accumulation at early M. marinum granulomas. Mechanistically, we found a detrimental effect of tsc1a expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by the cxcl12a/ccl2/ccr2 signalling axis was at the expense of the recruitment of classically activated tnfa-expressing macrophages and increased cell death around granulomas. Together, our results delineate putative pathways by which infection-induced miR-126 may shape an effective immune response to M. marinum infection in zebrafish embryos.

Chishao (Paeoniae Radix Rubra) alleviates intra-hepatic cholestasis by modulating NTCP in rats.

Background: Cholestasis is a common pathological manifestation dominated by accumulation of potentially toxic biliary compounds. Na+-taurocholate cotransporting polypeptide (NTCP) plays a critical role in protection from cholestasis and can be targeted therapeutically. Chishao (Paeoniae Radix Rubra) is a clinically efficacious agent for treating cholestasis, but the underlying mechanism has not been fully clarified. Objective: To evaluate the effects of Chishao on the expression of NTCP in rats with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. Methods: Chishao extracts were obtained by water decoction. Cholestasis model induced by ANIT in rats were established. Thirty rats were divided into five groups: control group (C), ANIT model group (M), 10g/kg Chishao group (LD), 20g/kg Chishao group (MD) and 40g/kg Chishao group (HD). The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP) and total bile acid (TBA) were detected. The mRNA and protein expression of NTCP, multidrug resistance associated protein 2 (MRP2) and bile salt export pump (BSEP) were detected by reverse transcription qPCR and Western blotting respectively. To assess the effects of Chishao on NTCP, MRP2 and BSEP localized at the membrane of hepatocytes, an in vitro experiment involving primary hepatocytes was conducted via the utilization of laser scanning confocal microscopy. Results: The extracts of Chishao significantly improved serum ALT, AST, ALP, TB, DB and TBA (p < 0.05), especially ALP in the HD group (p < 0.01). The histological pathological findings were also reversed in LD, MD and HD groups. The mRNA level of MRP2 was significantly downregulated after treatment with ANIT, whereas it was reversed in MD and HD groups (p < 0.05). The mRNA expression of NTCP was significantly downregulated after ANIT treatment, but dramatically upregulated in the HD group. The expressions of BSEP and MRP2 were similar, but that of NTCP decreased after ANIT treatment, which was reversed significantly by Chishao extracts in a dose-dependent manner. The expression of NTCP in hepatocytes from rats increased dose-dependently after Chishao treatment in vitro. Conclusion: Chishao extracts can improve the serum and histological performances of intra-hepatic cholestasis caused by ANIT, probably by working on transport proteins in liver cell membranes.

Effect of Natural Plant Products on Alzheimer's Disease.

Plants and their extracts like ginger, garlic, Curcuma, Salvia, and Ginkgo are best known for their anti-oxidative and anti-inflammatory responses. These plants have shown their anti-Alzheimer's properties in various in vivo and in vitro studies. Their diverse phytochemicals play a protective role against amyloid-beta-induced neurotoxicity and improve cognitive and learning impairments. These plants have a wide range of bioactive compounds, including alkaloids, flavonoids, phenols, glycosides, terpenoids, coumarins, and saponins. These chemicals scavenge the free radicals, lower the amyloid burden, improve memory dysfunction, and inhibit acetylcholinesterase activity. Some of the clinical trials and animal-based studies suggested the protective role of these plants and their extract mentioned in the literature. The articles for this review were majorly searched from popular search engines, viz, Google Scholar, PubMed, and Scopus. Medicinal plants improve cognitive and memory impairments by inhibiting acetylcholinesterase activity and scavenging free oxygen species by activating superoxide dismutase, catalase, and GSH activity. The plant extracts reduce amyloid insult by inactivating the beta-site amyloid precursor protein cleaving enzyme (BACE). The inactivation of Caspase 3 and 9 reduces apoptosis. Furthermore, the stimulation of microglial cells and astrocyte reduce inflammation by lowering chemokines and interleukins. The medicinal plants help to reduce AD pathogenesis by controlling different pathways and could be used as a therapeutic agent against the symptoms.

Longitudinal Examination of the Relationship Between Virtual Companionship and Social Anxiety: Emotional Expression as a Mediator and Mindfulness as a Moderator.

As the interweaving of human interaction and Artificial Intelligence (AI) intensifies, understanding the psychological impact, especially regarding social anxiety, of engaging with AI-driven virtual companionship becomes crucial. While a substantial body of research on social anxiety has concentrated on interactions between individuals, both online and offline, there is a noticeable deficit in explorations concerning how human-computer interactions influence social anxiety. This study offers a comprehensive, longitudinal examination of this underinvestigated relationship, intricately dissecting the roles of emotional expression and mindfulness within the context of AI-based interactions. We use social support theory and emotion regulation theory as our theoretical foundation. Data were collected from 618 undergraduate students in Eastern China over two intervals (May 15, 2023 and September 15, 2023). We utilized SPSS 26.0 to conduct descriptive statistics, while AMOS 25.0 facilitated multi-group confirmatory factor analysis (CFA) and the cross-lagged panel modeling. Our findings indicate that as the frequency of virtual companionship use increases, there's a decline in online social anxiety but a rise in offline social anxiety. Emotional expression emerges as a significant mediator, with heightened emotional expression leading to reduced social anxiety in both contexts. Mindfulness serves as a potent moderator, suggesting its protective role against the potential pitfalls of frequent virtual interactions. This research not only deepens our theoretical understanding of the dynamics between virtual interactions and social anxiety but also serves as a cornerstone for future endeavors aimed at optimizing AI and devising therapeutic interventions tailored for the digital generation.

Vitamin D as a Modulator of Neuroinflammation: Implications for Brain Health.

Neuroinflammation represents a critical immune response within the brain, playing a pivotal role in defense against injury and infection. However, when this response becomes chronic, it can contribute to the development of various neurodegenerative and psychiatric disorders. This bibliographic review delves into the role of vitamin D in modulating neuroinflammation and its implications for brain health, particularly in the context of neurological and psychiatric disorders. While vitamin D is traditionally associated with calcium homeostasis and bone health, it also exerts immunomodulatory and neuroprotective effects within the central nervous system. Through comprehensive analysis of preclinical and clinical studies, we uncover how vitamin D, acting through its receptors in glial cells, may influence the production of proinflammatory cytokines and antioxidants, potentially mitigating the cascade of events leading to neuronal damage. Clinical research has identified vitamin D deficiency as a common thread in the increased risks of multiple sclerosis, Parkinson's disease, Alzheimer's, and depression, among others. Furthermore, preclinical models suggest vitamin D's regulatory capacity over inflammatory mediators, its protective role against neuronal apoptosis, and its contribution to neurogenesis and synaptic plasticity. These insights underscore the potential of vitamin D supplementation not only in slowing the progression of neurodegenerative diseases but also in improving the quality of life for patients suffering from psychiatric conditions. Future clinical studies are essential to validate these findings and further our understanding of vitamin D's capacity to prevent or alleviate symptoms, opening new avenues for therapeutic strategies against neuroinflammation-related pathologies. Neuroinflammation is a crucial immune response in the brain against injuries or infections, but its persistence can lead to diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and depression. Cholecalciferol (Vitamin D3) emerges as a regulator of neuroinflammation, present in brain cells such as astrocytes and microglia, modulating immune function. Vitamin D's mechanisms of action include cytokine modulation and regulation of nuclear and mitochondrial genes. It adjusts inflammatory mediators and antioxidants, resulting in neuroprotective effects. Additionally, vitamin D impacts neurotransmitter synthesis and brain plasticity. This positions vitamin D as a potential adjunct in treating diseases like Alzheimer's and Parkinson's. Lastly, its role in intestinal microbiota and serotonin synthesis contributes to psychiatric disorders like schizophrenia and depression. Thus, vitamin D presents a novel therapeutic approach for neuroinflammatory, neurodegenerative, and neuropsychiatric diseases.

Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.

The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.

The deubiquitinase USP40 preserves endothelial integrity by targeting the heat shock protein HSP90β

Endothelial cell (EC) barrier disruption and inflammation are the pathological hallmarks of vascular disorders and acute infectious diseases and related conditions, including the coronavirus disease 2019 (COVID-19) and sepsis. Ubiquitination plays a critical role in regulating the stability, intracellular trafficking, and enzymatic activity of proteins and is reversed by deubiquitinating enzymes (DUBs). The role of DUBs in endothelial biology is largely unknown. In this study, we report that USP40, a poorly characterized DUB, prevents EC barrier disruption through reductions in the activation of RhoA and phosphorylation of myosin light chain (MLC) and cofilin. Furthermore, USP40 reduces EC inflammation through the attenuation of NF-ĸB activation, ICAM1 expression, and leukocyte-EC adhesion. We further show that USP40 activity and expression are reduced in response to endotoxin challenge. Global depletion of USP40 and EC-targeted USP40 depletion in mice exacerbated experimental lung injury, whereas lentiviral gene transfer of USP40 protected against endotoxin-induced lung injury. Using an unbiased approach, we discovered that the protective effect of USP40 occurs through the targeting of heat shock protein 90β (HSP90β) for its deubiquitination and inactivation. Together, these data reveal a critical protective role of USP40 in vascular injury, identifying a unique mechanistic pathway that profoundly impacts endothelial function via DUBs.

The protective roles of coping self-efficacy and social support for posttraumatic stress during the COVID-19 pandemic.

This study examined the roles of social support and coping self-efficacy (CSE) in attenuating posttraumatic stress (PTS) symptoms during the COVID-19 pandemic among a nonclinical university student sample. Participants (n = 610; 59% female) completed questionaries assessing psychological distress (Kessler Psychological Distress Scale) at baseline and 6-month follow-up, and social support (Interpersonal Support Evaluation List-12), CSE Scale, and PTS symptoms (Impact of Event Scale-Revised) at 6 months. A path analysis was conducted using SPSS Amos to examine the direct and indirect pathways from psychological distress to PTS symptoms that are accounted for by social support and CSE, controlling for gender. All direct effects in the path analysis were significant except for the relationship between social support and PTS symptoms. Notably, CSE was directly related to PTS symptoms (CSE: β = -.30, p < .001). There was a significant indirect effect of early psychological distress on PTS symptoms 6 months into the pandemic through social support and CSE (β = .14, p < .001). Individuals with higher levels of social support are more likely to have greater confidence in their coping capabilities, which helps to explain PTS symptom severity after controlling for initial levels of psychological distress and gender. These findings suggest that following a potentially traumatic event, CSE may be one factor to screen for to better identify individuals who are at higher risk for significant psychological difficulties and may benefit from interventions that bolster protective factors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Benzydamine hydrochloride ameliorates ethanol-induced inflammation in RAW 264.7 macrophages by stabilizing redox homeostasis

Objective: To evaluate the protective effect of benzydamine hydrochloride against ethanol-induced oxidative stress and inflammation in RAW 264.7 macrophages. Methods: RAW 264.7 macrophages were treated with ethanol (100 mM) and benzydamine hydrochloride (7.5 μM). The inflammatory status was confirmed by measuring pro-(TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines through ELISA and RT-PCR assays. Reactive oxygen species generation and mitochondrial membrane potential were investigated to study the protective role of benzydamine hydrochloride against ethanol-induced oxidative stress. Apoptosis detection was also investigated using flow cytometry and acridine orange/ethidium bromide staining. Results: Benzydamine hydrochloride significantly decreased the secretion of TNF-α and IL-6, as well as the generation of reactive oxygen species inside the cells, thereby stabilizing the mitochondrial membrane potential and reducing DNA fragmentation. The ethanol-induced cellular necrosis was also reversed by the administration of benzydamine hydrochloride. Conclusions: Benzydamine hydrochloride ameliorates ethanol-induced cell apoptosis and inflammation in RAW macrophages.

Supplemental Material for The Protective Roles of Coping Self-Efficacy and Social Support for Posttraumatic Stress During the COVID-19 Pandemic

Supplemental Material for The Protective Roles of Coping Self-Efficacy and Social Support for Posttraumatic Stress During the COVID-19 Pandemic

Secondary Modification of S100B Influences Anti Amyloid-β Aggregation Activity and Alzheimer's Disease Pathology.

Proteinaceous aggregates accumulate in neurodegenerative diseases such as Alzheimer's Disease (AD), inducing cellular defense mechanisms and altering the redox status. S100 pro-inflammatory cytokines, particularly S100B, are activated during AD, but recent findings reveal an unconventional molecular chaperone role for S100B in hindering Aβ aggregation and toxicity. This suggests a potential protective role for S100B at the onset of Aβ proteotoxicity, occurring in a complex biochemical environment prone to oxidative damage. Herein, we report an investigation in which extracellular oxidative conditions are mimicked to test if the susceptibility of S100B to oxidation influences its protective activities. Resorting to mild oxidation of S100B, we observed methionine oxidation as inferred from mass spectrometry, but no cysteine-mediated crosslinking. Structural analysis showed that the folding, structure, and stability of oxidized S100B were not affected, and nor was its quaternary structure. However, studies on Aβ aggregation kinetics indicated that oxidized S100B was more effective in preventing aggregation, potentially linked to the oxidation of Met residues within the S100:Aβ binding cleft that favors interactions. Using a cell culture model to analyze the S100B functions in a highly oxidative milieu, as in AD, we observed that Aβ toxicity is rescued by the co-administration of oxidized S100B to a greater extent than by S100B. Additionally, results suggest a disrupted positive feedback loop involving S100B which is caused by its oxidation, leading to the downstream regulation of IL-17 and IFN-α2 expression as mediated by S100B.

The Impact of Physical Activity on the Outcomes of Active Surveillance in Prostate Cancer Patients: A Scoping Review

Introduction: Active surveillance has emerged as a valid therapeutic option in patients with low-risk prostate cancer, allowing for the deferral of definitive treatment until the time of possible disease progression. Although it is known that physical activity plays a protective role in the onset and progression of this tumor, its impact on patients with low-risk disease who are managed with active surveillance remains unclear. Our scoping review aims to summarize the existing evidence on this subject. Evidence Acquisition: On 9 April 2023, a systematic search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: (“prostate cancer” OR “prostate tumor”) AND (“active surveillance”) AND (“physical activity” OR “physical exercise” OR “physical intensive activity” OR “intensive exercise”) AND (“lifestyle”). Out of the 506 identified articles, 9 were used for the present scoping review, and their results were reported according to the PRISMA-ScR statement. Evidence Synthesis: We discovered a lack of uniformity in the assessment of PA and its stratification by intensity. There was no consensus regarding what constitutes cancer progression in patients choosing expectant management. In terms of the impact of PA on AS outcomes, conflicting results were reported: some authors found no correlation, while others (six of total studies included) revealed that active men experience smaller increases in PSA levels compared to their sedentary counterparts. Additionally, higher levels of exercise were associated with a significantly reduced risk of PCa reclassification. Conclusion: Due to the heterogeneity of the methodologies used in the available studies and the conflicting results reported, it is not possible to draw definitive conclusions concerning the role physical activity may play in the risk of prostate cancer progression in men managed with active surveillance.

Síndrome de burnout, ansiedad y depresión en residentes de dermatología: un estudio transversal

Background and objectiveBurnout syndrome is a mental health disorder due to chronic occupational stress. Both burnout and associated comorbidities are prevalent among health care professionals, being medical residents a vulnerable group. Despite this, the scientific medical literature currently available on this issue in dermatology residents is scarce. The aim of this study was to analyze the prevalence of the burnout syndrome, anxiety, and depression in dermatology residents, and the associated risk factors. Material and MethodThis was a cross-sectional trial designed to include dermatology residents from Spain (from December 2022 through June 2023). A self-administered form was sent via online messaging applications, including validated scales to study professional quality of life, burnout syndrome, anxiety, and depression. ResultsA total of 48 dermatology residents were included in the study, 50% of whom (24/48) were women, with a mean age of 27 years (1.25). A total of 58.33% (28/48) of the residents had some degree of anxiety, 22.9% (11/48) some degree of depression, and 23.4% a moderate risk of burnout (11/48). Workload was the main risk factor associated with the 3 disorders studied, while managerial support or intrinsic motivation seem to play a protective role. ConclusionsBurnout syndrome and its comorbidities are both prevalent in dermatology residents in Spain and closely related to each other.

Pretreatment with platelet-rich plasma protects against ischemia–reperfusion induced flap injury by deactivating the JAK/STAT pathway in mice

BackgroundIschemia–reperfusion (I/R) injury is a major cause of surgical skin flap compromise and organ dysfunction. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, with tissue regenerative potential. PRP has shown promise in multiple I/R-induced tissue injuries, but its effects on skin flap injury remain unexplored.MethodsWe evaluated the effects of PRP on I/R-injured skin flaps, optimal timing of PRP administration, and the involved mechanisms.ResultsPRP protected against I/R-induced skin flap injury by improving flap survival, promoting blood perfusion and angiogenesis, suppressing oxidative stress and inflammatory response, and reducing apoptosis, at least partly via deactivating Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signalling pathway. PRP given before ischemia displayed overall advantages over that given before reperfusion or during reperfusion. In addition, PRP pretreatment had a stronger ability to reverse I/R-induced JAK/STAT activation and apoptosis than AG490, a specific inhibitor of JAK/STAT signalling.ConclusionsThis study firstly demonstrates the protective role of PRP against I/R-injured skin flaps through negative regulation of JAK/STAT activation, with PRP pretreatment showing optimal therapeutic effects.