Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Estudiar y trabajar como factores de riesgo en estudiantes de enfermería, Universidad Nacional Formosa, 2022 / Study and work as risk factors in nursing students, National University of Formosa,2022

Objetivo: Correlacionar la variable principal sostén del hogar con las variables género, edad, horas de trabajo, horas de sueño y factores de riesgo cardiovascular (índice de masa corporal, hipertensión arterial, dislipemia y diabetes mellitus), en estudiantes de 3º, 4 y 5º año de la Licenciatura en Enfermería, Universidad Nacional de Formosa. Metodología: estudio descriptivo, correlacional, transversal realizado en 214 estudiantes, durante el año 2022, utilizándose un cuestionario on-line autoadministrado, estructurado y medición de peso y talla. Resultados: el 76% fueron mujeres; 64%, principal fueron principal sostén del hogar, 57% refirió dormir menos de 6 horas al día, 15 % trabaja más de 41 horas semanales; 67% tuvo respuestas no saludables a la variable estrés, para la variable actividad física este valor ascendió a 71% y el 53,8% presentó exceso de peso. Se encontró asociación significativa entre ser el principal sostén del hogar con exceso de peso, trabajar 41 horas o más semanalmente, dormir menos de 6 horas al día y con la presencia de 3 o más factores de riesgo cardiovascular. Conclusiones: Las condiciones de vida que afrontan los estudiantes que de manera simultánea estudian, trabajan y son principal sostén del hogar pueden generar estrés, el cual es un factor de riesgo para las enfermedades cardiovasculares[AU]

Objetive: to correlate the main variable of primary income earner or primary breadwinner with gender, age, working hours, sleep hours, and cardiovascular disease risk factors (body mass index, hypertension, dyslipidemia, and diabetes mellitus) in 3rd, 4th, and 5th-year nursing students at the Nursing Program at the National University of Formosa. Methodology: The study was a descriptive, correlational, cross-sectional, conducted with 214 students during 2022 using a self-administered structured online questionnaire and measurement of weight and height. Results: 76% were women, 64% were the main breadwinner, 57% reported sleeping less than 6 hours a day, 15% working more than 41 hours per week; 67% had unhealthy responses to the stress variable, this value rose to 71% for the physical activity variable, and 53.8% were overweight. A significant association was found between the main variable of primary breadwinner and being overweight, working 41 or more hours weekly, and the presence of 3 or more cardiovascular risk factors. Conclusions: The living conditions faced by students who simultaneously study and work, and being the main breadwinner in the household can generate stress, which is a risk factor for cardiovascular diseases[AU]

Objetivo:: correlacionar a variável principal de sustento econômico do lar com as variáveis gênero, idade, horas de trabalho, horas de sono e fatores de risco cardiovascular (índice de massa corporal,hipertensão arterial, dislipidemia e diabetes mellitus) em estudantes do 3º, 4º e 5º ano do curso de graduação em Enfermagem, Universidade Nacional de Formosa. Metodologia: O estudo foi descritivo, correlacional e transversal, realizado em 214 estudantes durante o ano de 2022. Foi utilizado um questionário online autoadministrado e estruturado, e a medição de peso e altura dos estudantes foi realizada. Resultados: 76% dos estudantes eram mulheres; 64% eram o principal sustento econômico do lar; 57% relataram dormir menos de 6 horas por dia, 15% responderam que trabalham mais de 41 horas por semana; em relação aos fatores de risco cardiovascular, 67% tiveram respostas não saudáveis para a variável estresse, para a variável atividade física esse valor aumentou para 71% e 53,8% apresentaram excesso de peso. Foi encontrada uma associação significativa entre a variável principal de sustento econômico do lar com as variáveis excesso de peso, trabalhar 41 horas ou mais por semana, dormir menos de 6 horas al día e a presença de 3 ou mais fatores de risco cardiovascular. Conclusões: As condições de vida enfrentadas pelos estudantes que simultaneamente estudam, trabalham e são o principal sustento do lar podem gerar estresse, que é um fator de risco para doenças cardiovasculares[AU]

Social media uses amongst adolescents: motives, minority stress and eudaimonic well-being / Uso de redes sociales en adolescentes: motivación, estrés de minorías y bienestar eudaimónico

Introduction: The scientific evidence regarding the effects of online social media use on the well-being of adolescents is mixed. In gen-eral, passive uses (receiving, viewing content without interacting) and more screen time are related to lower well-being when compared with active uses (direct interactions and interpersonal exchanges). Objectives:This study ex-amines the types and motives for social media usage amongst adolescents, differentiating them by gender identity and sexual orientation, as well as its effects on eudaimonic well-being and minority stress. Method: A cross-sectional study was conducted with 1259 adolescents, aged 14 to 19 (M= 16.19; SD= 1.08), analysing the Scale of Motives for Using Social Net-working Sites, eudaimonic well-being, the Sexual Minority Adolescent Stress Inventory, screen time and profile type. Results:The results found that longer use time is related to finding partners, social connection and friendships; that gay and bisexual (GB) adolescents perceive more distal stressors online;and that females have higher levels of well-being. Discus-sion: The public profiles of GB males increase self-expression, although minority stress can be related to discrimination, rejection or exclusion. Dif-ferentiated socialization may contribute to a higher level of well-being in females, with both active and passive uses positively effecting eudaimonic well-being in adolescents.(AU)

Introduction: The scientific evidence regarding the effects of online social media use on the well-being of adolescents is mixed. In general, passive uses (receiving, viewing content without interacting) and more screen time are related to lower well-being when compared with active uses (direct interactions and interpersonal exchanges). Objectives: This study examines the types and motives for social media usage amongst adolescents, differentiating them by gender identity and sexual orientation, as well as its effects on eudaimonic well-being and minority stress. Method: A cross-sectional study was conducted with 1259 adolescents, aged 14 to 19 (M = 16.19; SD = 1.08), analysing the Scale of Motives for Using Social Networking Sites, eudaimonic well-being, the Sexual Minority Adolescent Stress Inventory, screen time and profile type. Results: The results found that longer use time is related to finding partners, social connection and friendships; that gay and bisexual (GB) adolescents perceive more distal stressors online; and that females have higher levels of well-being. Discussion: The public profiles of GB males increase self-expression, although minority stress can be related to discrimination, rejection or exclusion. Differentiated socialization may contribute to a higher level of well-being in females, with both active and passive uses positively effecting eudaimonic well-being in adolescents.(AU)

Peroxiredoxin 6 Protects Pulmonary Epithelial Cells From Cigarette-related Ferroptosis in Chronic Obstructive Pulmonary Disease.

Peroxiredoxin 6 (PRDX6) has a protective effect on pulmonary epithelial cells against cigarette smoke (CS)-induced ferroptosis. This study investigates the role of PRDX6 in the development of chronic obstructive pulmonary disease (COPD) and its possibility as a target. We observed that PRDX6 was downregulated in lung tissues of COPD patients and in CS-stimulated cells. The degradation of PRDX6 could be through the lysosomal pathway. PRDX6 deficiency exacerbated pulmonary inflammation and mucus hypersecretion in vivo. Overexpression of PRDX6 in Beas-2B cells ameliorated CS-induced cell death and inflammation, suggesting its protective role against CS-induced damage. Furthermore, PRDX6 deficiency promoted ferroptosis by adding the content of iron and reactive oxygen species, while iron chelation with deferoxamine mitigated CS-induced ferroptosis, cell death, and inflammatory infiltration both in vitro and in vivo. The critical role of PRDX6 in regulating ferroptosis suggests that targeting PRDX6 or iron metabolism may represent a promising strategy for COPD treatment.

Preclinical antidiabetic and antioxidant effects of Erythrophleum africanum (benth.) harms in streptozotocin-induced diabetic nephropathy.

OBJECTIVES: This study investigated the antidiabetic effects of the methanolic extract of E. africanum (MEEA) stem bark on streptozotocin (STZ)-induced diabetic nephropathy (DN) in Wistar rats. METHODS: The in vitro enzyme (α-amylase) inhibitory activity of MEEA was measured using a standard procedure. Diabetic rats with fasting blood glucose above 250 mg/dL were considered diabetic and were divided into the following groups: control (distilled water-treated), diabetic-control, diabetic metformin (100 mg/kg), diabetes + MEEA (150 mg/kg), and diabetes + MEEA (300 mg/kg) via oral gavage once daily for 14 days. At the end of the experimental period, kidney tissues were collected for biochemical and histological analyses. Kidney apoptosis and marker gene expression were measured by real-time quantitative PCR. RESULTS: MEEA exhibited α-amylase inhibitory effects. MEEA significantly (p<0.05) reduced the STZ-induced increases in blood glucose, serum urea, serum creatinine, uric acid, alanine aminotransferase, alkaline phosphatase, and malondialdehyde and increased the STZ-induced decreases in superoxide dismutase, catalase, and reduced glutathione. In addition, MEEA protects against DN by significantly downregulating the mRNA expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response binding protein (CREB), and cFOS and upregulating B-cell lymphoma 2 (Bcl-2), suggesting that the nephroprotective ability of MEEA is due to the modulation of the cAMP/PKA/CREB/cFOS signaling pathway. Furthermore, MEEA treatment protected against histopathological alterations observed in diabetic rats. CONCLUSIONS: The data from this study suggest that MEEA modulates glucose homeostasis and inhibits redox imbalance in DN rats.

Mechanical Stress-induced Connective Tissue Growth Factor Plays a Critical Role in Intestinal Fibrosis in Crohn's-like Colitis.

Crohn's disease (CD) is an inflammatory bowel disease characterized by transmural inflammation and intestinal fibrosis. Mechanisms of fibrosis in CD are not well understood. Transmural inflammation is associated with inflammatory cell infiltration, stenosis, and distention, which present mechanical stress (MS) to the bowel wall. We hypothesize that MS induces gene expression of pro-fibrotic mediators such as connective tissue growth factor (CTGF), which may contribute to fibrosis in CD. A rodent model of CD was induced by intracolonic instillation of TNBS to the distal colon. TNBS instillation induced a localized transmural inflammation (site I), with a distended colon segment (site P) proximal to site I. We detected significant fibrosis and collagen content not only in site I, but also in site P in CD rats by day 7. CTGF expression increased significantly in sites P and I, but not in the segment distal to the inflammation site. Increased CTGF expression was detected mainly in the smooth muscle cells (SMC). When rats were fed exclusively with clear liquid diet to prevent mechanical distention in colitis, expression of CTGF in sites P and I was blocked. Direct stretch led to robust expression of CTGF in colonic SMC. Treatment of CD rats with anti-CTGF antibody FG-3149 reduced fibrosis and collagen content in both sites P and I and exhibited consistent trends towards normalizing expression of collagen mRNAs. In conclusion, our studies suggest that mechanical stress, by up-regulating pro-fibrotic mediators i.e. CTGF, may play a critical role in fibrosis in CD.

The effects of ACE inhibitor Enalapril on Mytilus galloprovincialis: Insights into morphological and functional responses.

In the last decades, pharmaceuticals have emerged as a new class of environmental contaminants. Antihypertensives, including angiotensin-converting enzyme (ACE) inhibitors, are of special concern due to their increased consumption over the past years. However, the available data on their putative effects on the health of aquatic animals, as well as the possible interaction with biological systems are still poorly understood. This study analysed whether and to which extent the exposure to Enalapril, an ACE inhibitor commonly used for treating hypertension and heart failure, may induce morpho-functional alterations in the mussel Mytilus galloprovincialis, a sentinel organism of water pollution. By mainly focusing on the digestive gland (DG), a target tissue used for analysing the effects of xenobiotics in mussels, the effects of 10-days exposure to 0.6 ng/L (E1) and 600 ng/L (E2) of Enalapril were investigated in terms of cell viability and volume regulation, morphology, oxidative stress, and stress protein expression and localization. Results indicated that exposure to Enalapril compromised the capacity of DG cells from the E2 group to regulate volume by limiting the ability to return to the original volume after hypoosmotic stress. This occurred without significant effects on DG cell viability. Enalapril unaffected also haemocytes viability, although an increased infiltration of haemocytes was histologically observed in DG from both groups, suggestive of an immune response. No changes were observed in the two experimental groups on expression and tissue localization of heat shock proteins 70 (HSPs70) and HSP90, and on the levels of oxidative biomarkers. Our results showed that, in M. galloprovincialis the exposure to Enalapril did not influence the oxidative status, as well as the expression and localization of stress-related proteins, while it activated an immune response and compromised the cell ability to face osmotic changes, with potential consequences on animal performance.

Racism and alcohol-related problems among black adults: The role of negative emotionality to experiencing racism.

INTRODUCTION: Although Black Americans tend to consume less alcohol than non-Hispanic/Latine White Americans, Black Americans who do drink alcohol appear at especially high risk for negative alcohol-related problems. This alcohol-based health disparity indicates a need to identify psycho-sociocultural factors that may play a role in drinking and related problems to inform prevention and treatment efforts. Minority stress-based models posit that stressors such as racism increase negative emotions, which may be associated with using substances such as alcohol to cope with negative emotions. Yet, little research has directly assessed emotional reactions to racism and whether it plays a role in drinking-related behaviors. METHOD: Participants were 164 Black American undergraduates at a racially/ethnically diverse university who endorsed current alcohol use 18-48 (M = 21.7, SD = 4.3). Participants completed an online survey regarding their experiences with racism and alcohol-related behaviors. RESULTS: Experiencing more frequent racism was related to greater negative emotions experienced in response to racism (i.e., negative emotional reactivity to racism) and alcohol-related problems. More frequent racism was related to more alcohol-related problems via the sequential effects of negative emotional reactivity to racism and coping motivated drinking. CONCLUSIONS: These data indicate that the experience of negative emotions that occur after experiencing racism and attempts to cope with those negative emotions by consuming alcohol play important roles in drinking behaviors among Black Americans.

Are Differences Evident in the Ways Boys and Girls Appraise and Interpret Their Traumatic Experiences? A Qualitative Analysis of Youth Trauma Narratives.

The purpose of this study was to explore potential similarities and differences in the ways boys and girls appraise and interpret their traumatic experiences, and better understand how gender roles, performance, and socialization processes may impact trauma experiences, appraisals, and narratives within the context of trauma-focused treatment. We used thematic analysis to analyze the trauma narratives of youth (N = 16) ages 8-16 who had experienced multiple types (M = 5.38) of child maltreatment and who were receiving Trauma-focused Cognitive Behavioral Therapy to address clinically elevated posttraumatic stress symptoms. Four themes emerged: variations in the content of negative cognitions, differences in relational emotion, adoption of socially prescribed gender roles, and symptom differences. Although many similarities existed in youth's trauma narratives, differences emerged that point to the importance of social context and the ways gender role expectations and socialization processes influence youth's appraisal of and responses to traumatic events. Findings indicate the importance of considering distress tolerance, relational emotion, gender identity development, and role socialization within the treatment milieu.

Cannabinoid 2 receptor activation protects against diabetic cardiomyopathy through inhibition of AGE/RAGE-induced oxidative stress, fibrosis, and inflammasome activation.

Oxidative stress, fibrosis, and inflammasome activation from AGE-RAGE interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of ß-caryophyllene (BCP) on activating CB2 receptors against diabetes complications and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding high-fat diet with streptozotocin injections. After the development of diabetes, the animals received a 12-week oral BCP treatment at a dosage of 50 mg/kg/body weight. BCP treatment showed significant improvement in glucose tolerance, insulin resistance, and enhanced serum insulin levels in diabetic animals. BCP treatment effectively reversed the heart remodeling and restored the phosphorylated troponin I and SERCA2a expression. Ultrastructural examination showed reduced myocardial cell injury in DCM mice treated with BCP. The preserved myocytes were found associated with reduced expression of AGE/RAGE in DCM mice hearts. BCP treatment mitigated oxidative stress by inhibiting expression of NOX4 and activating PI3K/AKT/Nrf2 signaling. BCP suppressed cardiac fibrosis and endothelial-to-mesenchymal transition (EndMT) in DCM mice by inhibiting TGF-ß/Smad signaling. Further, BCP treatment suppressed NLRP3 inflammasome activation in DCM mice and alleviated cellular injury to the pancreatic tissues evidenced by significant elevation of the number of insulin-positive cells. To demonstrate CB2 receptor dependent mechanism of BCP, another group of DCM mice were pretreated with AM630, a CB2 receptor antagonist AM630 and AM630 was observed to abrogate the beneficial effects of BCP in DCM mice. Taken together, BCP showed the potential to protect the myocardium and pancreas of DCM mice mediating CB2 receptor dependent mechanisms. Significance Statement 1. ß-caryophyllene (BCP), a cannabinoid type 2 receptor (CB2R) agonist. 2. BCP attenuates diabetic cardiomyopathy via activating CB2R in mice 3. CB2R activation by BCP shows strong protection against fibrosis and inflammasome activation 4. It regulates AGE/RAGE and PI3K/Nrf2/Akt signaling in mice.

Determinants of work stress among emergency department nurses in Sleman, Yogyakarta, Indonesia.

BACKGROUND: The nursing field is the fourth most stressful occupation in the health sector. Emergency department nurses often face crises and unpredictable situations that can negatively affect their quality of life and the quality of care. This study aimed to investigate the determinants of work stress among ED nurses in Sleman, Yogyakarta, Indonesia. METHODS: A descriptive cross-sectional study was conducted. Participants (n = 122) were emergency nurses recruited through convenience sampling from four EDs in Sleman District, Yogyakarta, Indonesia. Data were gathered using an online self-administered survey consisting of the workload, self-efficacy, and work stress questionnaires. Hierarchical linear regression analysis with the entry method was used to examine the main determinants of work stress. RESULTS: The average work stress (38.29 ± 8), workload (30.83 ± 9.21), and self-efficacy (32.47 ± 3.61) scores were at a moderate level. Hierarchical linear regression showed that workplace, being a head nurse, and workload were the main determinants that contributed to 25.4 % of work stress among ED nurses. CONCLUSIONS: The study results confirm that having a high workload, working in a private hospital, and being a head nurse are the main determinants of work stress among ED nurses in Sleman, Indonesia.

Prevalence of depressive and anxiety symptoms and perceived stress in hospitalised patients with COVID-19.

BACKGROUND: COVID-19 infection is associated with significant depressive and anxiety symptoms and stress. We examined the prevalences of depressive and anxiety symptoms and perceived stress among patients with COVID-19. METHODS: Clinically stable patients with COVID-19 aged 18 to 60 years who were admitted between April 2021 and September 2021 to the MES Medical College in Kerala, India were prospectively recruited. They were assessed using the Montgomery-Asberg Depression Rating Scale, the Hamilton Anxiety Scale, and the Perceived Stress Scale. RESULTS: Of 112 patients screened, 103 were included in the analysis. Depression scores were higher in patients of lower socio-economic status (p = 0.04), of unemployed (p = 0.01), and with longer hospital stays (p < 0.001). Anxiety scores were higher in patients aged 31 to 40 years (p = 0.04), of lower socio-economic status (p = 0.01), with a history of psychiatric illness (p = 0.006), and with a history of self-harm (p = 0.019). Perceived stress scores were higher in patients of lower socio-economic status (p = 0.02), with a history of psychiatric illness (p = 0.001), and with a history of self-harm (p = 0.022). CONCLUSION: Socio-economic status, employment status, a history of psychiatric illness, and duration of hospital stay are associated with depression, anxiety, and stress among patients with COVID-19.

Rivastigmine for treatment-refractory posttraumatic stress disorder: a systematic review.

We conducted a systematic review evaluating the efficacy of rivastigmine augmentation for treatment-refractory posttraumatic stress disorder (PTSD). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The databases Ovid MEDLINE, PubMed, CINAHL, and EMBASE were searched using key words: 'rivastigmine' OR 'Exelon' OR 'rivastigmine augmentation' OR 'Exelon augmentation' AND 'posttraumatic stress disorder*' OR 'post-traumatic stress disorder*' OR 'PTSD' OR 'combat disorder*' OR 'post-traumatic symptoms'. The asterisk specified plural forms of the relevant word. Four papers were identified, comprising one double-blind randomised controlled trial, one non-controlled open trial, one case series (presenting three case studies), and one paper with two case studies. The randomised controlled trial found no statistically significant difference in efficacy, using the PTSD CheckList-Military Version as the relevant outcomes measure, between the active add-on rivastigmine interventions and placebo or treatment as usual. The open trial, although reporting relatively positive outcomes, had a weak study design and lacked reporting of key information, including participant sex and age and pre-rivastigmine PTSD measures. The assessment of efficacy was based on participants' reporting of subjective benefits, and clinician-rating using a Clinical Global Impression, rather than established PTSD assessments scales. Although the five case studies reported improvement in PTSD symptoms, there were confounding factors and limitations in clinical and demographic data, warranting caution regarding attributed benefits. There is a lack of methodologically robust evidence supporting the efficacy of add-on rivastigmine for the treatment of refractory PTSD. Additional research may help in further evaluating its possible clinical efficacy.

Hidradenitis suppurativa and psychosocial well-being: a cross-sectional survey analysis from the All of Us research program.

Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease that often leads to decreased quality of life. Prior research assessing stress and discrimination related to stigmatization of those with HS is limited. The aim of this study was to examine the association between HS and the following factors related to psychosocial well-being: stress, discrimination, and loneliness. We performed secondary analysis of participants 18 years and older registered in the National Institutes of Health's All of Us Research Program in March 2024. The study sample was limited to individuals who had completed ≥ 1 of 4 psychosocial well-being surveys. Among 1,352 individuals with HS, 135 were included in the sample. Among 208,290 individuals without HS, 56,902 were included. The following surveys assessed loneliness, stress, perceived discrimination in everyday settings, and perceived discrimination in medical settings, respectively: the UCLA Loneliness Scale, Cohen Perceived Stress Scale, Everyday Discrimination Scale, and Discrimination in Medical Settings Scale. The association between HS and survey scores was modeled using multivariable linear regression adjusted for self-reported sex, self-reported race and ethnicity, age, and income. In an unadjusted model, those with HS reported a significantly higher degree of stress (MeanHS (SD) = 21.5 (4.74); Meannon-HS (SD) = 19.8 (3.98); p < 0.001), discrimination in everyday settings (MeanHS (SD) = 18.9 (8.16); Meannon-HS (SD) = 16.0 (7.06); p < 0.0001), and discrimination in healthcare settings (MeanHS (SD) = 1.77 (0.64); Meannon-HS (SD) = 1.56 (0.62); p < 0.001). After adjusting for sex, race, age, and income, the association between HS and discrimination in healthcare settings was non-significant; however, associations between HS and increased levels of perceived stress and everyday discrimination remained significant. Low survey completion rates and demographic differences between those who did and did not complete the study surveys may limit generalizability of results. Findings suggest that those with HS may benefit from regular screening for psychosocial well-being and provision of support resources.

RIP3 orchestrates oxidative stress and pyroptosis in doxorubicin-induced cardiotoxicity through regulation of AKT/Nrf2 signaling cascade.

This study was designed to explore the role of RIP3 in DOX-induced cardiotoxicity and its underlying molecular mechanisms. Our results demonstrate that RIP3 exacerbates DOX-induced cardiotoxicity through promoting oxidative stress and pyroptosis by regulating the AKT/Nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway. Inhibition of RIP3 using GSK-872 attenuated DOX-induced cardiac remodeling and contractile dysfunction. Moreover, using GSK-872 in vivo, the results revealed that inhibition of RIP3 alleviated DOX-induced cardiotoxicity by the resulting inhibition of oxidative stress and pyroptosis. In addition, inhibition of RIP3 increased the protein levels of AKT and Nrf2 in DOX-treated mouse hearts. Furthermore, the AKT inhibitor LY294002 lessened RIP3 reduction-offered protection against DOX-induced H9c2 cell injury by moderating oxidative stress and pyroptosis. Taken together, these data demonstrate that RIP3 activation orchestrates DOX-induced cardiotoxicity through elevated oxidative stress and pyroptosis in an AKT/Nrf2-dependent manner. Those findings highlight the clinical relevance and therapeutic potential of targeting RIP3 for the treatment of DOX-induced cardiotoxicity.

Potential Role of Dipeptidyl Peptidase-4 in Regulating Mitochondria and Oxidative Stress in Cardiomyocytes.

Oxidative stress causes mitochondrial damage and bioenergetic dysfunction and inhibits adenosine triphosphate production, contributing to the pathogenesis of cardiac diseases. Dipeptidyl peptidase 4 (DPP4) is primarily a membrane-bound extracellular peptidase that cleaves Xaa-Pro or Xaa-Ala dipeptides from the N terminus of polypeptides. DPP4 inhibitors have been used in patients with diabetes and heart failure; however, they have led to inconsistent results. Although the enzymatic properties of DPP4 have been well studied, the substrate-independent functions of DPP4 have not. In the present study, we knocked down DPP4 in cultured cardiomyocytes to exclude the effects of differential alteration in the substrates and metabolites of DPP4 then compared the response between the knocked-down and wild-type cardiomyocytes during exposure to oxidative stress. H2O2 exposure induced DPP4 expression in both types of cardiomyocytes. However, knocking down DPP4 substantially reduced the loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular reactive oxygen species production, and reducing apoptosis-associated protein expression. These findings demonstrate that inhibiting DPP4 improves the body's defense against oxidative stress by enhancing Nrf2 and PGC-1α signaling and increasing superoxide dismutase and catalase activity. Our results indicate that DPP4 mediates the body's response to oxidative stress in individuals with heart disease.

More efficient adaptation of cardiovascular response to repeated restraint in spontaneously hypertensive rats: the role of autonomic nervous system.

We hypothesized that sympathetic hyperactivity and parasympathetic insuficiency in spontaneously hypertensive rats (SHR) underlie their exaggerated cardiovascular response to acute stress and impaired adaptation to repeated restraint stress exposure compared to Wistar-Kyoto rats (WKY). Cardiovascular responses to single (120 min) or repeated (daily 120 min for 1 week) restraint were measured by radiotelemetry and autonomic balance was evaluated by power spectral analysis of systolic blood pressure variability (SBPV) and heart rate variability (HRV). Baroreflex sensitivity (BRS) was measured by the pharmacological Oxford technique. Stress-induced pressor response and vascular sympathetic activity (low-frequency component of SBPV) were enhanced in SHR subjected to single restraint compared to WKY, whereas stress-induced tachycardia was similar in both strains. SHR exhibited attenuated cardiac parasympathetic activity (high-frequency component of HRV) and blunted BRS compared to WKY. Repeated restraint did not affect the stress-induced increase in blood pressure. However, cardiovascular response during the post-stress recovery period of the 7th restraint was reduced in both strains. The repeatedly restrained SHR showed lower basal heart rate during the dark (active) phase and slightly decreased basal blood pressure during the light phase compared to stress-naive SHR. SHR subjected to repeated restraint also exhibited attenuated stress-induced tachycardia, augmented cardiac parasympathetic activity, attenuated vascular sympathetic activity and improved BRS during the last seventh restraint compared to single-stressed SHR. Thus, SHR exhibited enhanced cardiovascular and sympathetic responsiveness to novel stressor exposure (single restraint) compared to WKY. Unexpectedly, the adaptation of cardiovascular and autonomic responses to repeated restraint was more effective in SHR.

Microbe-induced coordination of plant iron-sulfur metabolism enhances high light stress tolerance of Arabidopsis.

High light stress in subtropical and tropical regions strongly limits agricultural production due to photo-oxidative damage, decreased growth and yield. Here, we investigated whether beneficial microbes can protect plants under high light stress. We found that Enterobacter sp. SA187 (SA187) supports Arabidopsis thaliana growth under high light stress by reducing the accumulation of reactive oxygen species (ROS) and maintaining photosynthesis. When subjected to high light stress, SA187 triggers dynamic changes in Arabidopsis gene expression related to fortified iron metabolism and redox regulation thereby enhancing the plant anti-oxidative glutathione/glutaredoxin redox system. Genetic analysis shows that SA187-enhanced iron and sulfur metabolism are coordinated by ethylene signaling. In summary, beneficial microbes could be an effective and inexpensive means for enhancing high light stress tolerance in plants.

Molecular Mechanisms Underlying the Therapeutic Potential of Plant-Based α-Amylase Inhibitors for Hyperglycemic Control in Diabetes.

BACKGROUND: Diabetes mellitus (DM), arising from pancreatic ß-cell dysfunction and disrupted alpha-amylase secretion, manifests as hyperglycemia. Synthetic inhibitors of alphaamylase like acarbose manage glucose but pose adverse effects, prompting interest in plantderived alternatives rich in antioxidants and anti-inflammatory properties. OBJECTIVE: The current review investigates plant-based alpha-amylase inhibitors, exploring their potential therapeutic roles in managing DM. Focusing on their ability to modulate postprandial hyperglycemia by regulating alpha-amylase secretion, it assesses their efficacy, health benefits, and implications for diabetes treatment. METHOD: This review examines plant-derived alpha-amylase inhibitors as prospective diabetic mellitus treatments using PubMed, Google Scholar, and Scopus data. RESULTS: Plant-derived inhibitors, including A. deliciosa, B. egyptiaca, and N. nucifera, exhibit anti-inflammatory and antioxidant properties, effectively reducing alpha-amylase levels in diabetic conditions. Such alpha-amylase inhibitors showed promising alternative treatment in managing diabetes with reduced adverse effects. CONCLUSION: The current literature concludes that plant-derived alpha-amylase inhibitors present viable therapeutic avenues for diabetes management by modulating alpha-amylase secretion by regulating inflammatory, oxidative stress, and apoptotic mechanisms involved in the pathogenesis of diabetes. Further investigation into their formulations and clinical efficacy may reveal their more comprehensive diabetes therapeutic significance, emphasizing their potential impact on glucose regulation and overall health.

The ß2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury.

BACKGROUND: Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that ß2-adrenergic receptor (ß2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome. OBJECTIVES: The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy. METHODS: Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours. RESULTS: The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of ß2-AR agonist formoterol (50 µg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels. CONCLUSION: Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the ß2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.