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.

Selenium deficiency exacerbates ROS/ER stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus.

Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

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]

Efeitos do treinamento físico supervisionado na ansiedade, estresse e depressão após a Covid-19 / Effects of supervised physical training on anxiety, stress and depression after Covid-19 / Efectos del entrenamiento físico supervisado en la ansiedad, el estrés y la depresión después de la Covid-19

Objetivo: avaliar ansiedade, estresse e depressão antes e após o treinamento físico em acometidos pela Covid-19. Método: estudo quase-experimental realizado em Goiânia com pacientes que tiveram Covid-19 moderada a grave, após internação. Investigou-se ansiedade, estresse e depressão por meio da DASS-21. Os participantes realizaram dezoito sessões de treinamento físico, três vezes/semana composto por exercícios aeróbios, resistidos e de flexibilidade. Utilizou-se teste Shapiro Wilk para distribuição e os testes t pareado e Wilcoxon com nível de significância de p<0,05 para comparações. Resultado: participaram dezessete indivíduos com 55,59(±5,20) anos, predominantemente mulheres (64,7%), média de dezessete dias internados, maioria obesos (52,9%) com alguma doença prévia à Covid-19 (76,5%). Houve redução da ansiedade (mediana de 9,0 para 2,0 [p=0,001]), estresse de 10,0 para 2,0 (p=0,001) e depressão de 6,0 para 2,0 (p<0,001) após treinamento físico. Conclusão: o treinamento físico foi eficaz para melhora da ansiedade, estresse e depressão após dezoito sessões.

Objective: to assess anxiety, stress and depression before and after physical training in people affected by Covid-19. Method: a quasi-experimental study carried out in Goiania with patients who had moderate to severe Covid-19 after hospitalization. Anxiety, stress and depression were investigated using the DASS-21. The participants underwent eighteen physical training sessions, three times a week, consisting of aerobic, resistance and flexibility exercises. The Shapiro Wilk test was used for distribution and the paired t-test and Wilcoxon test with a significance level of p<0.05 were used for comparisons. Results: seventeen individuals took part, aged 55.59 (±5.20) years, predominantly women (64.7%), an average of seventeen days in hospital, the majority obese (52.9%) with some illness prior to Covid-19 (76.5%). There was a reduction in anxiety (median from 9.0 to 2.0 [p=0.001]), stress from 10.0 to 2.0 (p=0.001) and depression from 6.0 to 2.0 (p<0.001) after physical training. Conclusion: physical training was effective in improving anxiety, stress and depression after eighteen sessions.

Objetivo: evaluar la ansiedad, el estrés y la depresión antes y después del entrenamiento físico en afectados por la Covid-19. Método: estudio cuasi-experimental realizado en Goiânia con pacientes que tuvieron Covid-19 moderada a grave, tras hospitalización. Se investigó la ansiedad, el estrés y la depresión mediante el DASS-21. Los participantes realizaron dieciocho sesiones de entrenamiento físico, tres veces por semana compuesto por ejercicios aeróbicos, de resistencia y de flexibilidad. Se utilizó la prueba Shapiro Wilk para distribución y las pruebas t pareada y Wilcoxon con nivel de significancia de p<0,05 para comparaciones. Resultado: participaron diecisiete individuos con 55,59 (±5,20) años, predominantemente mujeres (64,7%), media de diecisiete días hospitalizados, mayoría obesos (52,9%) con alguna enfermedad previa a la Covid-19 (76,5%). Hubo reducción de la ansiedad (mediana de 9,0 a 2,0 [p=0,001]), estrés de 10,0 a 2,0 (p=0,001) y depresión de 6,0 a 2,0 (p<0,001) tras el entrenamiento físico. Conclusión: el entrenamiento físico fue eficaz para mejorar la ansiedad, el estrés y la depresión después de dieciocho sesiones.

Rates and psychological stress predictors of problematic internet use (PIU) during the COVID-19 pandemic in a racially diverse sample of young adults.

BACKGROUND: Problematic internet use (PIU), which includes social media misuse (SMM) and gaming misuse (GM), is uncontrollable and associated with significant psychological impairment. PIU is a coping behavior for COVID-19-related stress. We explored distress-related predictors of PIU in a young adult racially diverse sample during the pandemic. METHODS: Analyses used cross-sectional survey data (N = 1956). Psychological diagnoses, financial distress, COVID-19-related emotions, psychological distress, distress tolerance, social support, loneliness, SMM and GM were measured. Hierarchical multiple regressions identified predictors of PIU. Race-stratified exploratory analyses sought to understand if predictors held true across racial groups. RESULTS: Low distress tolerance was associated with SMM and GM, as were depression symptoms, with racial differences observed. SMM was associated with younger age, and GM was associated with male gender. PTSD symptoms predicted more GM. SMM and GM rates varied between racial groups. COVID-19-related adjustment challenges and stress predicted SMM and GM respectively, with racial differences observed. CONCLUSION: Individual psychological distress and low distress tolerance markedly increased PIU risk. Clinicians should screen for stress-related PIU risk factors and bolster distress tolerance in vulnerable patients. Comparing PIU to different forms of coping in a larger sample would further clarify groups differences in stress coping behaviors.

Vaccinia virus F1L blocks the ribotoxic stress response to subvert ZAKα-dependent NLRP1 inflammasome activation.

Inflammasomes are essential for host defense, recognizing foreign or stress signals to trigger immune responses, including maturation of IL-1 family cytokines and pyroptosis. Here, NLRP1 is emerging as an important sensor of viral infection in barrier tissues. NLRP1 is activated by various stimuli, including viral double-stranded (ds) RNA, ribotoxic stress, and inhibition of dipeptidyl peptidases 8 and 9 (DPP8/9). However, certain viruses, most notably the vaccinia virus, have evolved strategies to subvert inflammasome activation or effector functions. Using the modified vaccinia virus Ankara (MVA) as a model, we investigated how the vaccinia virus inhibits inflammasome activation. We confirmed that the early gene F1L plays a critical role in inhibiting NLRP1 inflammasome activation. Interestingly, it blocks dsRNA and ribotoxic stress-dependent NLRP1 activation without affecting its DPP9-inhibition-mediated activation. Complementation and loss-of-function experiments demonstrated the sufficiency and necessity of F1L in blocking NLRP1 activation. Furthermore, we found that F1L-deficient, but not wild-type MVA, induced ZAKα activation. Indeed, an F1L-deficient virus was found to disrupt protein translation more prominently than an unmodified virus, suggesting that F1L acts in part upstream of ZAKα. These findings underscore the inhibitory role of F1L on NLRP1 inflammasome activation and provide insight into viral evasion of host defenses and the intricate mechanisms of inflammasome activation.

Fumonisin B1 induces endoplasmic reticulum damage and inflammation by activating the NXR response and disrupting the normal CYP450 system, leading to liver damage in juvenile quail.

Fumonisin B1 (FB1) is a mycotoxin affecting animal health through the food chain and has been closely associated with several diseases such as pulmonary edema in pigs and diarrhea in poultry. FB1 is mainly metabolized in the liver. Although a few studies have shown that FB1 causes liver damage, the molecular mechanism of liver damage is unclear. This study aimed to evaluate the role of liver damage, nuclear xenobiotic receptor (NXR) response and cytochrome P450 (CYP450)-mediated defense response during FB1 exposure. A total of 120 young quails were equally divided into two groups (control and FB1 groups). The quails in the control group were fed on a normal diet, while those in the FB1 group were fed on a quail diet containing 30 mg/kg for 42 days. Histopathological and ultrastructural changes in the liver, biochemical parameters, inflammatory factors, endoplasmic reticulum (ER) factors, NXR response and CYP450 cluster system and other related genes were examined at 14 days, 28 days and 42 days. The results showed that FB1 exposure impaired the metabolic function and caused liver injury. FB1 caused ER stress and decreased adenosine triphosphatease activity, induced the expression of inflammation-related genes such as interleukin 6 and nuclear factor kappa-B, and promoted inflammation. In addition, FB1 disrupted the expression of multiple CYP450 isoforms by activating nuclear xenobiotic receptors (NXRs). The present study confirms that FB1 exposure disturbs the homeostasis of cytochrome P450 systems (CYP450s) in quail liver by activating NXR responses and thereby causing liver damage. This study's findings provide insight into the molecular mechanisms of FB1-induced hepatotoxicity.

Copeptin as a surrogate marker for arginine vasopressin: analytical insights, current utility, and emerging applications.

Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable in vitro. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimated glomerular filtration rate and a greater risk of new-onset chronic kidney disease. Furthermore, copeptin is associated with disease severity in patients with autosomal dominant polycystic kidney disease. Copeptin predicts the development of coronary artery disease and cardiovascular mortality in the older population. Moreover, the predictive value of copeptin was found to be comparable with that of N-terminal pro-brain natriuretic peptide for all-cause mortality in patients with heart failure. Whether the measurement of copeptin in these conditions alters clinical management remains to be demonstrated in future studies.

Bite hard: Linking cranial loading mechanics to ecological differences in gnawing behavior in caviomorph rodents.

The mammalian skull is very malleable and has notably radiated into highly diverse morphologies, fulfilling a broad range of functional needs. Although gnawing is relatively common in mammals, this behavior and its associated morphology are diagnostic features for rodents. These animals possess a very versatile and highly mechanically advantageous masticatory apparatus, which, for instance, allowed caviomorph rodents to colonize South America during the Mid-Eocene and successfully radiate in over 200 extant species throughout most continental niches. Previous work has shown that differences in bite force within caviomorphs could be better explained by changes in muscle development than in mechanical advantages (i.e., in cranial overall morphology). Considering the strong bites they apply, it is interesting to assess how the reaction forces upon the incisors (compression) and the powerful adductor musculature pulling (tension) mechanically affect the cranium, especially between species with different ecologies (e.g., chisel-tooth digging). Thus, we ran finite element analyses upon crania of the subterranean Talas' tuco-tuco Ctenomys talarum, the semi-fossorial common degu Octodon degus, and the saxicolous long-tailed chinchilla Chinchilla lanigera to simulate: (A) in vivo biting in all species, and (B) rescaled muscle forces in non-ctenomyid rodents to match those of the tuco-tuco. Results show that the stress patterns correlate with the mechanical demands of distinctive ecologies, on in vivo-based simulations, with the subterranean tuco-tuco being the most stressed species. In contrast, when standardizing all three species (rescaled models), non-ctenomyid models exhibited a several-fold increase in stress, in both magnitude and affected areas. Detailed observations evidenced that this increase in stress was higher in lateral sections of the snout and, mainly, the zygomatic arch; between approximately 2.5-3.5 times in the common degu and 4.0-5.0 times in the long-tailed chinchilla. Yet, neither species, module, nor simulation condition presented load factor levels that would imply structural failure by strong, incidental biting. Our results let us conclude that caviomorphs have a high baseline for mechanical strength of the cranium because of the inheritance of a very robust "rodent" model, while interspecific differences are associated with particular masticatory habits and the concomitant level of development of the adductor musculature. Especially, the masseteric and zygomaticomandibular muscles contribute to >80% of the bite force, and therefore, their contraction is responsible for the highest strains upon their origin sites, that is, the zygomatic arch and the snout. Thus, the robust crania of the subterranean and highly aggressive tuco-tucos allow them to withstand much stronger forces than degus or chinchillas, such as the ones produced by their hypertrophied jaw adductor muscles or imparted by the soil reaction.

Curvilinear relationship was found between visceral adiposity index and stress urinary incontinence among US adult women: A cross-sectional study.

AIMS: The purpose of this study was to find out the relation between visceral adipose index (VAI) levels and stress urinary incontinence (SUI) in adult women. METHODS: From the National Health and Nutrition Examination Survey (NHANES) 2007-2020, females aged 20 or above were identified for this study. Visceral adiposity was determined using the VAI score, and the assessment of urinary incontinence was carried out through a correlation questionnaire. Logistic regression models and restricted cubic spline (RCS) regression were employed to analyze the relationship between VAI levels and SUI. RESULTS: Among the 6522 participants, 2672 (41.0%) were reported SUI. Multivariate logistic regression revealed significantly higher odds of SUI with increasing VAI levels (Q4 vs. Q1), adjusted odds ratio (aOR) = 1.53 (CI: 1.29-1.81, p < 0.001). RCS regression indicated a curvilinear relationship between VAI and SUI (p = 0.003). In threshold analysis, aOR for developing SUI was 1.18 (CI: 1.11-1.26, p < 0.001) for participants with VAI < 4.73, suggesting an 18% increased risk of SUI with each unit increase in VAI. No association between VAI and SUI was observed when VAI was ≥4.73. CONCLUSIONS: Our study has revealed a significant curvilinear relationship between VAI and SUI within a large and representative sample of women. Future research is necessary to evaluate the relationship between the two and explicate the underlying mechanisms of this relationship.

Psychosomatic complaints are indicative of stress in young individuals: findings from a Swedish national cohort study.

AIMS: Psychosomatic complaints are common in youth and are often assumed to indicate stress. Although several studies have confirmed that a cross-sectional association exists, few have empirically investigated whether or not perceived stress influences psychosomatic complaints. The objective of the present study was to build upon previous research by exploring whether changes in perceived stress over time are associated with corresponding changes in psychosomatic complaints. This analytical approach takes unmeasured time-invariant confounding into account, thereby offering more robust evidence for a causal association between the variables under study. METHODS: Data was derived from the Swedish national cohort study Futura01, with information from 2,708 participants aged 17-18 in 2019 and 20-21 in 2022. Perceived stress was measured by Cohen's Perceived Stress Scale. Psychosomatic complaints were measured by questions on the frequency of stomach aches, headaches and difficulties falling asleep, which were added to an index. Information on gender, parental education, and parental country of birth was derived from registries. Linear regression analyses were conducted and the first difference (FD) approach was used. RESULTS: Perceived stress and psychosomatic complaints exhibited cross-sectional associations at both time points. The FD analyses showed that increases in perceived stress were associated with increases in psychosomatic complaints, and this was the case irrespective of sociodemographic characteristics. CONCLUSIONS: This study provides further empirical support for the assumption that psychosomatic complaints can be partially attributed to stress. Societal efforts aimed at reducing stressors and strengthening coping resources and strategies among young people may help mitigate perceived stress and, consequently, the likelihood of developing psychosomatic complaints.

Neurobiology and Treatment of Posttraumatic Stress Disorder.

The recent worldwide surge of warfare and hostilities exposes increasingly large numbers of individuals to traumatic events, placing them at risk of developing posttraumatic stress disorder (PTSD) and challenging both clinicians and service delivery systems. This overview summarizes and updates the core knowledge of the genetic, molecular, and neural circuit features of the neurobiology of PTSD and advances in evidence-based psychotherapy, pharmacotherapy, neuromodulation, and digital treatments. While the complexity of the neurobiology and the biological and clinical heterogeneity of PTSD have challenged clinicians and researchers, there is an emerging consensus concerning the underlying mechanisms and approaches to diagnosis, treatment, and prevention of PTSD. This update addresses PTSD diagnosis, prevalence, course, risk factors, neurobiological mechanisms, current standard of care, and innovations in next-generation treatment and prevention strategies. It provides a comprehensive summary and concludes with areas of research for integrating advances in the neurobiology of the disorder with novel treatment and prevention targets.

Targeting the redox vulnerability of acute myeloid leukaemia cells with a combination of auranofin and vitamin C.

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by complex molecular and cytogenetic abnormalities. Pro-oxidant cellular redox status is a common hallmark of AML cells, providing a rationale for redox-based anticancer strategy. We previously discovered that auranofin (AUF), initially used for the treatment of rheumatoid arthritis and repositioned for its anticancer activity, can synergize with a pharmacological concentration of vitamin C (VC) against breast cancer cell line models. In this study, we observed that this drug combination synergistically and efficiently killed cells of leukaemic cell lines established from different myeloid subtypes. In addition to an induced elevation of reactive oxygen species and ATP depletion, a rapid dephosphorylation of 4E-BP1 and p70S6K, together with a strong inhibition of protein synthesis were early events in response to AUF/VC treatment, suggesting their implication in AUF/VC-induced cytotoxicity. Importantly, a study on 22 primary AML specimens from various AML subtypes showed that AUF/VC combinations at pharmacologically achievable concentrations were effective to eradicate primary leukaemic CD34+ cells from the majority of these samples, while being less toxic to normal cord blood CD34+ cells. Our findings indicate that targeting the redox vulnerability of AML with AUF/VC combinations could present a potential anti-AML therapeutic approach.

Defining and distinguishing early life stress, trauma, adversity, toxic and chronic stress and allostatic load: a descriptive review.

AIMS: Various concepts are used to study the impact of stress on childhood development. These concepts are often used inconsistently or interchangeably. Our main objectives were to determine how selected stress concepts (chronic stress, toxic stress, allostatic load, early life stress, childhood adversity, childhood trauma and adverse childhood experiences; ACEs) are defined, operationalized and described, and to provide a theoretical context to aid the choice for a preferred concept in public health research. METHODS: For this descriptive review, we systematically searched for literature published before 4 August 2021, on PubMed, Embase and PsycInfo. Two independent reviewers included studies. Exclusion criteria were: no systematic review, not peer reviewed, not published in English, selected stress concepts were no predetermined variable or a substantial topic in the discussion, full text was unobtainable or study described non-human or non-childhood populations. Data extraction forms were used. Descriptives were gathered, publication fields were identified through Journal Citation Reports categories, and verbatim descriptions were ordered in text and Venn diagrams. RESULTS: Of 264 screened studies, 124 were included. ACEs, childhood adversity and childhood trauma were used most. ACEs were the main concept used most frequently (47.6%). A total of 11 of 14 public and environmental health journals used ACEs. All concepts refer to prolonged, repeated, interpersonal stress from 0 to 18 years, that can alter physiological systems. Four concepts were stressor oriented, two concepts focused on stress response and effect and one on the state of challenged homeostasis. CONCLUSIONS: ACEs seem most fitting for public health setting, due to their operationalizability, large set of core experiences and widespread use.

The potential protective effect of propolis on diabetic nephropathy induced by streptozotocin in adult albino rats.

Diabetes mellitus is a common metabolic disorder. It is associated with serious life-threatening complications if not properly managed. The current study aimed at investigating the possible protective role of propolis on streptozotocin-induced diabetic nephropathy. A diabetic rat model was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin. After 4 days, the diabetic rats received oral propolis (300 mg/kg/day) via gastric gavage for 28 days. Biochemical, histopathological and ultrastructural evaluations were performed. The results showed that: streptozotocin-induced diabetes was associated with a marked decrease in the serum high-density lipoproteins and antioxidant enzymes. However, a significant elevation in the levels of serum creatinine, blood urea nitrogen, uric acid, cholesterol, triglycerides and low-density lipoproteins was detected. Furthermore, streptozotocin treatment induced histopathological alterations of the renal cortex; in the form of distorted glomerular capillaries, widened Bowman's space and signs of epithelial tubular degeneration. Ultra-structurally, thickening and irregularity of the glomerular basement membrane and podocytes foot processes effacement were observed. The tubular epithelial cells showed swollen vacuolated mitochondria, scarce basal infoldings and loss of microvilli. Conversely, propolis partially restored the normal lipid profile, antioxidant biomarkers and renal cortical morphology. Propolis exhibited a sort of renoprotection through hypoglycemic, anti-hyperlipidemic and antioxidant effects.

PTSD and mood disorders in implantable cardioverter defibrillator patients: is more psychological assessment needed?

INTRODUCTION: The aim of this review is to identify common mood concerns in ICD patients and suggest brief psychological screeners essential for early detection and monitoring in patient care. AREAS COVERED: Reliable and valid psychological assessment tools are reviewed, including those specifically designed for ICD patient populations. EXPERT OPINION: Psychological assessment, in combination with cardiologic standard of care, can help overcome many barriers associated with poor implantable cardioverter-defibrillator (ICD) management and related cardiovascular outcomes. Earlier identification and treatment of mood concerns in ICD patients has been shown to improve quality of life (QOL) and patient outcomes. At this time, however, logistical challenges and time restraints, in addition to knowledge of appropriate treatment plans or referral options, remain central barriers to providing integrated, patient-centered care. Ultimately, all cardiology clinics would benefit from a collaborative care team that includes a mental health consultant or in-house psychologists who can provide consultations or referral services. Additionally, all patients that come to the clinics should complete proactive screening measures as routine component of care to assess the presence of mood concerns to improve patient outcomes and aid in treatment planning.

CIPK11 phosphorylates GSTU23 to promote cold tolerance in Camellia sinensis.

Cold stress negatively impacts the growth, development, and quality of Camellia sinensis (Cs, tea) plants. CBL-interacting protein kinases (CIPK) comprise a pivotal protein family involved in plant development and response to multiple environmental stimuli. However, their roles and regulatory mechanisms in tea plants (Camellia sinensis (L.) O. Kuntze) remain unknown. Here we show that CsCBL-interacting protein kinase 11 (CsCIPK11), whose transcript abundance was significantly induced at low temperatures, interacts and phosphorylates tau class glutathione S-transferase 23 (CsGSTU23). CsGSTU23 was also a cold-inducible gene and has significantly higher transcript abundance in cold-resistant accessions than in cold-susceptible accessions. CsCIPK11 phosphorylated CsGSTU23 at Ser37, enhancing its stability and enzymatic activity. Overexpression of CsCIPK11 in Arabidopsis thaliana resulted in enhanced cold tolerance under freezing conditions, while transient knockdown of CsCIPK11 expression in tea plants had the opposite effect, resulting in decreased cold tolerance and suppression of the C-repeat-binding transcription factor (CBF) transcriptional pathway under freezing stress. Furthermore, the transient overexpression of CsGSTU23 in tea plants increased cold tolerance. These findings demonstrate that CsCIPK11 plays a central role in the signaling pathway to cold signals and modulates antioxidant capacity by phosphorylating CsGSTU23, leading to improved cold tolerance in tea plants.