Hypoxia-inducible factor-1α in myocardial infarction.

Hypoxia-inducible factor 1 (HIF1) has a crucial function in the regulation of oxygen levels in mammalian cells, especially under hypoxic conditions. Its importance in cardiovascular diseases, particularly in cardiac ischemia, is because of its ability to alleviate cardiac dysfunction. The oxygen-responsive subunit, HIF1α, plays a crucial role in this process, as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival, angiogenesis, and metabolism. Furthermore, HIF1α expression induced reperfusion in the ischemic skeletal muscle, and hypoxic skin wounds in diabetic animal models showed reduced HIF1α expression. Increased expression of HIF1α has been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction. Genetic variations in HIF1α have also been found to correlate with altered responses to ischemic cardiovascular disease. In addition, a link has been established between the circadian rhythm and hypoxic molecular signaling pathways, with HIF1α functioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light. This editorial analyzes the relationship between HIF1α and the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia. Understanding the changes in molecular signaling pathways associated with diseases, specifically cardiovascular diseases, provides the opportunity for innovative therapeutic interventions, especially in low-oxygen environments such as myocardial infarction.

Comparative Analysis of Sleep Hygiene and Patterns among Adolescents in Two Russian Arctic Regions: A Pilot Study.

PURPOSE: The circumpolar habitat stands as one of the most vulnerable environments for human activity and health. The primary study objective was to compare sleep-related factors, light exposure, social cues, and potential confounding variables among schoolchildren residing in the European Arctic region from two settlements situated below and above the Polar Circle using validated self-reported questionnaires. MATERIALS AND METHODS: We recruited 94 children aged 13-15 years (40.4% males), matched by sex and age, from public educational institutions in two circumpolar settlements located below (Kem', Republic of Karelia; 64.6 NL) and above the Polar Circle (Apatity, Murmansk Region; 67.3 NL). Participants completed several surveys, including the Pediatric Daytime Sleepiness Scale, the Insomnia Severity Index, the Adolescent Sleep Hygiene Scale, and the Munich ChronoType Questionnaire, to evaluate sleep parameters and chronotype. The χ2 test was used to test for differences between proportions. Linear regression and multiple regression models with co-factors were applied to assess the relationship between studied indicators. RESULTS: A noteworthy increase in physical activity was observed in children residing in Kem' compared to those in Apatity. Children from Apatity showed higher alcohol consumption than their counterparts from Kem'. The overall rate of excessive daytime sleepiness in the sample was 17.1%. Moderate insomnia symptoms were reported in 18.4% of adolescents living in Kem' and in 25% of respondents living in Apatity, respectively. Notably, participants from Kem' attained higher academic scores and had longer exposure to sunlight on schooldays. On the other hand, children from Apatity tended to have later bedtimes and sleep-onset times on schooldays. According to the Munich ChronoType Questionnaire data, a reliance on alarm clocks on schooldays, and a higher Sleep Stability Factor based on the Adolescent Sleep Hygiene Scale. DISCUSSION: Our study indicating that higher physical activity and longer sunlight exposure among Kem' children on schooldays are associated with earlier wake-up times during schooldays, earlier bedtime whole week, reduced dependence on alarm clocks, and higher academic achievements. The results of older schoolchildren differ from many works published previously in the USA, Argentina, and Japan, which could be explained by the season when the study was performed. Here, we observed a negative impact on school performance and sleep parameters in children living in high latitudes, namely in circumpolar regions. CONCLUSIONS: Our study points out that adolescents living above the Polar Circle tend to have sleep problems, e.g., late sleep-onset times, higher excessive daytime sleepiness, and insomnia-related symptoms, because of experiencing reduced exposure to natural light. Future research encompassing assessments across all four seasons will provide a more comprehensive understanding.

Circadian Factors in Stroke: A Clinician's Perspective.

Stroke remains one of the leading causes of mortality and long-term and permanent disability worldwide despite technological innovations and developments in pharmacotherapy. In the last few decades, the growing data have evidenced the role of the circadian system in brain vulnerability to damage, the development and evolution of stroke, and short-term and long-term recovery. On the other hand, the stroke itself can affect the circadian system via direct injury of specific brain structures involved in circadian regulation (i.e., hypothalamus, retinohypothalamic tracts, etc.) and impairment of endogenous regulatory mechanisms, metabolic derangement, and a neurogenic inflammatory response in acute stroke. Moreover, the disruption of circadian rhythms can occur or exacerbate as a result of exogenous factors related to hospitalization itself, the conditions in the intensive care unit and the ward (light, noise, etc.), medication (sedatives and hypnotics), and loss of external factors entraining the circadian rhythms. In the acute phase of stroke, patients demonstrate abnormal circadian variations in circadian biomarkers (melatonin, cortisol), core body temperature, and rest-activity patterns. The approaches aimed at the restoration of disrupted circadian patterns include pharmacological (melatonin supplementation) and non-medication (bright light therapy, shifting feeding schedules, etc.) interventions; however, their effects on short- and long-term recovery after stroke are not well understood.

Social Jetlag and Excessive Daytime Sleepiness from a Sample of Russian Children and Adolescents.

PURPOSE: Insufficient nocturnal sleep is a primary source of excessive daytime sleepiness. Most previous research has focused on the disparity between sleep demands and study start times in adolescents. Fewer studies have focused on elementary schoolchildren. We hypothesize that late sleep timing is connected to excessive daytime sleepiness in a sample of Russian children and adolescents. The major goals of our study were to evaluate excessive daytime sleepiness in Russian schoolchildren and adolescents using the Russian version of the Pediatric Daytime Sleepiness Scale (PDSS) and to estimate its relationship with sleep-wake parameters using the Munich Chronotype Questionnaire (MCTQ). MATERIALS AND METHODS: Student subjects were from public educational facilities in the Republic of Karelia. They completed both the PDSS and the Munich Chronotype Questionnaire to estimate sleep parameters and chronotype (MSFsc). Five hundred and eleven students provided data for the PDSS and sleep-wake variables, and 479 for the full MCTQ data. RESULTS: The overall prevalence of Excessive Daytime Sleepiness (EDS) in our sample was 18%. The total PDSS score was inversely correlated with sleep length on school nights and was independent of respondents' sex. Higher PDSS scores were associated with later bedtimes on school days and free days, and shorter sleep duration on school days. Late chronotype and more pronounced social jetlag were both positively correlated with high PDSS scores. A negative correlation was found between chronotype and the duration of the sleep period on weekdays (p < 0.001) and a positive correlation was found on weekends (p < 0.001). Longer average sleep duration was positively related to less daytime sleepiness. CONCLUSION: This study suggests that excessive daytime sleepiness is chronotype-dependent. School start times could be shifted to a later hour to prolong sleep and reduce EDS.

Sleep characteristics, chronotype and winter depression in 10-20-year-olds in northern European Russia.

The purpose of this work was to examine the relationships between geographical coordinates and the prevalence of winter depression (SADW ), and to compare the sleep characteristics and chronotype of youths with and without SADW . We conducted a cross-sectional study of self-reported sleep characteristics, chronotype and winter depression in northern European Russia. Two questionnaires, the Munich Chronotype Questionnaire (MCTQ) and the Seasonal Pattern Assessment Questionnaire (SPAQ), were administered to a total of 3435 adolescents aged 10-20 years (1517 males and 1918 females). The prevalence of SADW in the study population was 8.4% and sub-SADW 11.8%. Four variables predicted the likelihood of SADW in youths: sex [higher in females: odds ratio (OR): 1.87, P < 0.0001], age (increases with age: OR: 1.09, P < 0.001), latitude (higher in the North: OR: 1.49, P < 0.029) and position in the time zone (higher in the West: OR: 1.61, P < 0.001). Later sleeping and waking, longer sleep latencies, more severe sleep inertia, shorter total sleep times and lower sleep efficiencies were observed in both males and females with SADW . The influence of SADW on sleep characteristics was more pronounced on school days. Significant phase delays of the sleep-wake rhythm and severe social jetlag (the difference between the mid-point of sleep phase at weekends and on workdays) were observed in females with SADW , but not in males. There are significant differences in sleep characteristics and chronotype between people with SADW and no-SAD. We demonstrate that both latitude of residence and location within the time zone are significant predictors of SADW in young inhabitants of the North.

Distinct signaling pathways of microtubule inhibitors--vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively.

Vinblastine and paclitaxel (Taxol) are widely used chemotherapeutic drugs that inhibit the normal function of microtubules causing mitotic arrest and cell death. Despite these similarities, the signaling pathways that mediate and regulate cell death induced by these agents remain incompletely understood. The purpose of this study was to directly compare the two drugs in terms of their ability to activate components of the c-Jun N-terminal protein kinase (JNK) pathway, and to establish the importance of these signaling events in apoptosis induced by these agents. We show that both drugs induce mitotic arrest and subsequent apoptotic cell death with highly similar kinetics and that both activate JNK and induce c-Jun protein and c-jun mRNA expression. Surprisingly, vinblastine induced c-Jun phosphorylation and c-jun transcriptional activation, although Taxol failed to do so. However, inhibition of JNK or an absence of JNK protected against both vinblastine- and Taxol-induced cell death. These results suggest that although JNK activation plays an important role in cell death induced by both agents, vinblastine and Taxol differ markedly with respect to signaling downstream of JNK, with AP-1-dependent and -independent mechanisms, respectively. In addition, these results show, contrary to popular belief, that JNK activation is not necessarily accompanied by c-Jun activation, and thus c-Jun is not an obligate substrate of JNK.

Induction of apoptosis by vinblastine via c-Jun autoamplification and p53-independent down-regulation of p21WAF1/CIP1.

Vinblastine treatment in all cell lines examined causes a robust increase in c-Jun protein expression and phosphorylation and a corresponding increase in activator protein-1 (AP-1) transcriptional activity. We show in KB-3 carcinoma cells that this is due to a strong autoamplification loop involving the proximal AP-1 site in the c-Jun promoter, resulting in highly increased c-Jun mRNA and c-Jun protein. Inhibitors of RNA transcription and protein translation blocked both vinblastine-induced c-Jun expression and apoptotic cell death, suggesting that apoptosis is dependent, at least in part, on transcription/translation. Small interfering RNA (siRNA) to c-Jun was used to interrupt the amplification cycle and was found to be highly effective, reducing vinblastine-induced c-Jun expression at both the mRNA and protein levels by 90%. Apoptosis and caspase-3 activation were significantly inhibited in c-Jun siRNA-treated cells. To uncover potential mechanisms of c-Jun-mediated cell death and protection by c-Jun siRNA, candidate target genes were examined. Chromatin immunoprecipitation revealed preferential association of c-Jun with the p21 (cyclin-dependent kinase inhibitor) gene promoter after vinblastine treatment. In KB-3 cells, which have compromised p53 function, and in p53-null cells but not in p53 wild-type cells, vinblastine caused down-regulation of p21 expression concomitant with increased c-Jun expression, suggesting a role for c-Jun in negative regulation of the p21 promoter independent of p53. These results provide strong evidence that c-Jun induction in response to vinblastine plays a proapoptotic role in part via down-regulation of p21, promoting cycling and subsequent cell death of mitotically impaired cells.