Rhythm Alterations Research Articles

Unveiling the novel role of circadian rhythms in sepsis and septic shock: unexplored implications for chronotherapy

Circadian rhythms are critical to coordinating body processes to external environmental cues, such as light and feeding, to ensure efficiency and maintain optimal health. These rhythms are controlled by ‘clock’ transcription factors, such as Clock, Bmal1, Per1/2, Cry1/2, and Rev-erbs, which are present in almost every tissue. In modern society, disruptions to normal circadian rhythms are increasingly prevalent due to extended lighting, shift work, and long-distance travel. These disruptions misalign external cues to body processes and contribute to diseases such as obesity and non-alcoholic fatty liver disease. They also exacerbate pre-existing health issues, such as depression and inflammatory bowel disease. The normal inflammatory response to acute infection displays remarkable circadian rhythmicity in humans with increased inflammatory activity during the normal night or rest period. Severe bloodborne infections, exemplified in sepsis and the progression to septic shock, can not only disrupt the circadian rhythmicity of inflammatory processes but can be exacerbated by circadian misalignment. Examples of circadian disruptions during sepsis and septic shock include alteration or loss of hormonal rhythms controlling blood pressure and inflammation, white blood cell counts, and cytokine secretions. These changes to circadian rhythms hinder sepsis and septic shock recovery and also increase mortality. Chronotherapy and chronopharmacotherapy are promising approaches to resynchronise circadian rhythms or leverage circadian rhythms to optimise medication efficacy, respectively, and hold much potential in the treatment of sepsis and septic shock. Despite knowledge of how circadian rhythms change in these grave conditions, very little research has been undertaken on the use of these therapies in support of sepsis management. This review details the circadian disruptions associated with sepsis and septic shock, the influence they have on morbidity and mortality, and the potential clinical benefits of circadian-modulating therapies.

Clock system disruption in male Fischer 344 rats fed cafeteria diet and administered sweet treats at different times: The zeitgeber role of grape seed flavanols.

Current lifestyles include calorie-dense diets and late-night food intake, which can lead to circadian misalignment. Our group recently demonstrated that sweet treats before bedtime alter the clock system in healthy rats, increasing metabolic risk factors. Therefore, we aimed to assess the impact of the sweet treat consumption time on the clock system in rats fed a cafeteria diet (CAF). Moreover, since flavanols have demonstrated beneficial effects in metabolic disorders and clock gene modulation, we also investigated whether these phenolic compounds can restore the circadian disruption caused by these altered dietary patterns. For this, 64 Fisher rats were fed CAF for 9 weeks. In the last 4 weeks, animals were daily administered a low dose of sugar (160 mg/kg) as a sweet treat at 8 a.m. (ZT0) or 8 p.m. (ZT12). Two other groups received 25 mg/kg of grape seed flavanols in addition to sweet treats. Finally, the animals were sacrificed at different time points (9 a.m., 3 p.m., 9 p.m., and 3 a.m.). The results showed that metabolic and circadian disturbances by CAF may be influenced by the time of sugar administration, slightly reinforcing the alterations in diurnal rhythmicity of serum biochemical parameters, hormones, and hypothalamic genes with bedtime snacking. Flavanols improved metabolic health and restored the oscillation of biochemical parameters, hormones, and clock and appetite-signaling genes, showing greater effects at ZT12. These results highlight the importance of meal timing in influencing physiological and metabolic outcomes, even under calorie-dense diets. Moreover, they also suggest the zeitgeber role of flavanols, modulating the clock system and contributing to an improved metabolic profile under different feeding pattern conditions.

Changes in Circadian Rhythm in Chronically-Starved Mice Are Associated With Glial Cell Density Reduction in the Suprachiasmatic Nucleus.

Anorexia nervosa (AN) is an eating disorder characterized by severe weight loss and associated with hyperactivity and circadian rhythm disruption. However, the cellular basis of circadian rhythm disruption is poorly understood. Glial cells in the suprachiasmatic nucleus (SCN), the principal circadian pacemaker, are involved in regulating circadian rhythms. We hypothesize that the circadian rhythm disruption in AN patients is associated with glial cell changes in the SCN. In the starvation-induced hyperactivity mouse model, mice had free access to a running wheel and received a restricted amount of food once a day, until a 25% body weight loss was reached and maintained their weight loss for two weeks. This was followed by a refeeding phase. Different daily periods of running wheel activity were defined, such as food anticipatory activity up to 4 h before feeding. Circadian rhythmicity was analyzed using the cosinor method. Gene expression was evaluated using real-time polymerase chain reaction. Immunohistochemistry was used to quantify astrocytes, microglia, and oligodendrocytes. Starvation induced changes in circadian rhythm, as indicated by changes in cosinor-based characteristics. Refeeding reversed these effects. Additionally, there was an increase in cryptochrome circadian regulator 1 expression and a decrease in the density of astrocytes and oligodendrocytes in the SCN after chronic starvation. Starvation-induced alterations in circadian rhythms are associated with molecular, and cellular changes in the hypothalamus. Reduced astrocytes and oligodendrocytes in the SCN in a mouse model of AN suggest that glial pathophysiology may play a role in circadian rhythm disruption.

Maternal high-fat diet alters the transcriptional rhythm in white adipose tissue of adult offspring.

A maternal high-fat diet (HFD) deteriorates the long-term metabolic health of offspring. Circadian rhythms are crucial for regulating metabolism. However, the impact of maternal HFD on the circadian clock in white adipose tissue (WAT) remains unexplored. This study aimed to identify transcriptional rhythmic alterations in inguinal WAT of adult male offspring induced by maternal HFD. To this end, female mice were fed an HFD and their male offspring were raised on a standard chow diet until 16 weeks of age. Transcriptome was performed and the data was analyzed using CircaCompare. The results showed that maternal HFD before and throughout pregnancy significantly altered the circadian rhythm of inguinal WAT while slightly modifying the WAT clock in adult male offspring. Specifically, maternal HFD contributed to gaining rhythmicity of Cry2, resulted in the elevated amplitude of Nr1d2, and led to increased midline estimating statistic of rhythm (MESOR) of Clock and Nr1d2. Furthermore, maternal HFD changed the rhythmic pattern of metabolic genes, such as Pparγ, Hacd2, and Acsl1, which are significantly enriched in metabolic regulation pathways. In conclusion, a maternal HFD before and throughout pregnancy altered the circadian rhythm of inguinal WAT in adult offspring. These alterations may play a significant role in disturbing metabolic homeostasis, potentially leading to metabolic dysfunction in adult male offspring.

Comparative Electrocardiographic Analysis Between Physical Exercise Practitioners and Athletes: A Cross-Sectional Study.

The trained heart adapts through geometric changes influenced by concentric and eccentric hypertrophy, depending on the predominance of the isometric or dynamic components of the exercise performed. Additionally, alterations in heart rhythm may occur due to increased vagal system activity. Cardiological evaluation with an electrocardiogram (ECG) aims to identify cardiac conditions that could temporarily or permanently disqualify an athlete from competition. This study sought to compare electrocardiographic findings in regular exercisers with those observed in athletes and to correlate these findings with training duration and load. A cross-sectional study was conducted with 154 participants divided into two groups: exercisers (EG) and athletes (AG). Data were collected on exercise type, weekly training time and practice duration. Each participant underwent a resting ECG, analyzed by two independent physicians, with a third review in case of disagreement. The Seattle criteria were applied to categorize ECG changes as physiological, borderline or abnormal. The findings revealed that 75% of athletes exhibited ECG changes, with left and/or right ventricular hypertrophy and incomplete right bundle branch block (IRBBB) being the most prevalent. Age (PR = 0.92; p = 0.004) and exercise duration (PR = 1.00; p = 0.004) significantly influenced the observed electrocardiographic changes. The majority of both regular exercisers and athletes displayed ECG alterations, with the prevalence increasing with age and training duration.

Mitochondrial dynamics: molecular mechanism and implications in endometriosis.

Endometriosis affects about 10% of women of reproductive age, leading to a disabling gynecologic condition. Chronic pain, inflammation, and oxidative stress have been identified as the molecular pathways involved in the progression of this disease, although its precise etiology remains uncertain. Although mitochondria are considered crucial organelles for cellular activity, their dysfunction has been linked to the development of this disease. The purpose of this review is to examine the functioning of the mitochondrion in endometriosis: in particular, we focused on the mitochondrial dynamics of biogenesis, fusion, and fission. Since excessive mitochondrial activity is reported to affect cell proliferation, we also considered mitophagy as a mechanism involved in limiting disease development. To better understand mitochondrial activity, we also considered alterations in circadian rhythms, the gut microbiome, and estrogen receptors: indeed, these mechanisms are also involved in the development of endometriosis. In addition, we focused on recent research about the impact of numerous substances on mitochondrial activity; some of them may offer a future breakthrough in endometriosis treatment by acting on mitochondria and inhibiting cell proliferation.

Advanced sleep phase syndrome: Role of genetics and aging.

Advanced sleep phase (ASP) is seldom brought to medical attention because many individuals easily adapt to their early chronotype, especially if it emerges before the age of 30 and is present in a first-degree relative. In this case, the disorder is considered familial (FASP) and is mostly discovered coincidentally in the presence of other sleep disorders, mainly obstructive sleep apnea syndrome (OSAS). The prevalence of FASP is currently estimated to be between 0.21% and 0.5%. Autosomal dominant mutations in circadian clock genes like PER2, CK1, PER3, CRY2, TIMELESS, and DEC2 have been linked to FASP, some with pleiotropic effects influencing other health aspects like migraine and depression. Early morning awakening is, instead, more common among older individuals, occurring in almost 4% of cases, without considering associated comorbidities. Advanced sleep-wake phase disorder (ASWPD) is characterized by a consistent and distressing anticipation of sleep-wake timing, affecting almost 1% of middle-aged individuals. On average, women have a shorter circadian period than men, making them more susceptible to ASWPD, albeit no significant gender discrepancies have been observed. Age-related alterations in circadian rhythms are exacerbated and compounded by neurodegenerative disorders, impacting the suprachiasmatic nucleus (SCN), sensitivity to light, and light responsiveness in those affected. Conflicting data has surfaced regarding the protective or detrimental effects of ASWPD in studies on aging, mild cognitive impairment (MCI), and diverse dementia conditions.

Endothelial BMAL1 decline during aging leads to bone loss by destabilizing extracellular fibrillin-1.

The occurrence of aging is intricately associated with alterations in circadian rhythms that coincide with stem cell exhaustion. Nonetheless, the extent to which the circadian system governs skeletal aging remains inadequately understood. Here, we noticed that skeletal aging in male mice was accompanied by a decline in a core circadian protein, BMAL1, especially in bone marrow endothelial cells (ECs). Using male mice with endothelial KO of aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), we ascertained that endothelial BMAL1 in bone played a crucial role in ensuring the stability of an extracellular structural component, fibrillin-1 (FBN1), through regulation of the equilibrium between the extracellular matrix (ECM) proteases thrombospondin type 1 domain-containing protein 4 (THSD4) and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), which promote FBN1 assembly and breakdown, respectively. The decline of endothelial BMAL1 during aging prompted excessive breakdown of FBN1, leading to persistent activation of TGF-β/SMAD3 signaling and exhaustion of bone marrow mesenchymal stem cells. Meanwhile, the free TGF-β could promote osteoclast formation. Further analysis revealed that activation of ADAMTS4 in ECs lacking BMAL1 was stimulated by TGF-β/SMAD3 signaling through an ECM-positive feedback mechanism, whereas THSD4 was under direct transcriptional control by endothelial BMAL1. Our investigation has elucidated the etiology of bone aging in male mice by defining the role of ECs in upholding the equilibrium within the ECM, consequently coordinating osteogenic and osteoclastic activities and retarding skeletal aging.

1

Background. Regional anesthesia has become widely used in routine anesthesiology practice, it is considered a safer method of anesthesia in older patients and those with concomitant pathology. Nevertheless, both general and regional anesthesia have side effects on the cardiovascular system. The cardiotoxic effect of anesthesia in one way or another is present with any variant of anesthesia. One of the most transparent signs is rhythm alterations on the ECG. These changes can occur not only intraoperatively, but also in the early postoperative period, have an asymptomatic clinical course. But the presence of these signs can have a negative impact on the patient’s prognosis. That is why we performed daily Holter monitoring for patients undergoing trauma surgery. The purpose of the study was to compare regional and general anesthesia as a risk factor for perioperative rhythm disturbances. Materials and methods. It was a 2-group observational study that included 120 trauma patients undergoing surgery using general (group GA) or regional anesthesia (group RA). Postoperative Holter monitoring lasted 24 hours. Further analysis of the recording included the assessment of the presence of ischemic changes or extrasystoles. Results. The incidence of ST-depression episodes within 24 perioperative hours was 10 % in the GA group compared to 3 % in the RA group. In the GA group, the percentage of extrasystole was significantly higher compared to the RA group: 1.5 ± 2.1 % versus 0.7 ± 1.3 % (p = 0.0145). An increase in Qtd was significantly higher in the GA group 15 minutes after the start of anesthesia (51.31 ± 23.09) compared to the RA group (40.70 ± 19.97; p = 0.008). At the same time, QT dispersion was statistically significantly higher in the RA group 1 hour after the start of anesthesia compared to the GA group — 38.22 ± 12.30 versus 50.1 ± 19.5 (p = 0.04). The QT interval was significantly longer in the GA group 15 minutes after the start of anesthesia: 440.00 ± 33.09 versus 400.70 ± 23.18 in the RA group (p = 0.04). One hour after the start of anesthesia, QTt was longer in the RA group: 390.22 ± 23.60 versus 410.1 ± 30.1 in the GA group (p = 0.05). Conclusions. Regional anesthesia has less hemodynamic effects and is the method of choice in patients with cardiovascular comorbidity. However, given the risk of cardiotoxicity due to the resorptive effect of the local anesthetic, in older patients and with existing risk factors, it is crucial to account for the arrhythmogenic effects of local anesthetics and adjust the dosage accordingly.

Circadian rhythm and epilepsy: a nationally representative cross-sectional study based on actigraphy data.

The study aims to assess the relationship between epilepsy and circadian rhythms. This study included a cohort of 7,410 participants sourced from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) database. The investigation focused on the comparative analysis of seven nonparametric indices associated with circadian rhythms (Interdaily Stability (IS), Intradaily Variability (IV), Relative Amplitude (RA), L5, M10, L5 start time, and M10 start time) between the overall population and patients with epilepsy. Logistic regression analysis was utilized to assess the potential correlation between the rest-activity circadian rhythm patterns and the presence of epilepsy within the cohort. Compared to the general population, individuals with epilepsy exhibited lower values of IS and M10. Multivariable logistic regression analysis, when IS, RA, and M10 were categorized into four groups based on quartiles, revealed that the odds ratio (IS: OR = 0.36, 95% CI: 0.13, 0.89; RA: OR = 0.25, 95% CI: 0.06, 0.77; M10: OR = 0.24, 95% CI: 0.06, 0.73) for the highest quartile was lower than that for the lowest quartile. Furthermore, after adjustment for confounding factors, participants in the highest quartile compared to those in the lowest quartile of IV and M10 start time demonstrated a higher prevalence of epilepsy. Individuals with epilepsy demonstrate significant alterations in circadian rhythms.

Intermittent fasting triggers interorgan communication to suppress hair follicle regeneration.

Intermittent fasting has gained global popularity for its potential health benefits, although its impact on somatic stem cells and tissue biology remains elusive. Here, we report that commonly used intermittent fasting regimens inhibit hair follicle regeneration by selectively inducing apoptosis in activated hair follicle stem cells (HFSCs). This effect is independent of calorie reduction, circadian rhythm alterations, or the mTORC1 cellular nutrient-sensing mechanism. Instead, fasting activates crosstalk between adrenal glands and dermal adipocytes in the skin, triggering the rapid release of free fatty acids into the niche, which in turn disrupts the normal metabolism of HFSCs and elevates their cellular reactive oxygen species levels, causing oxidative damage and apoptosis. A randomized clinical trial (NCT05800730) indicates that intermittent fasting inhibits human hair growth. Our study uncovers an inhibitory effect of intermittent fasting on tissue regeneration and identifies interorgan communication that eliminates activated HFSCs and halts tissue regeneration during periods of unstable nutrient supply.

Revealing the Bioactivities of Physalia physalis Venom Using Drosophila as a Model.

Physalia physalis, commonly known as the Portuguese Man o' War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila melanogaster. The venom administered orally revealed dose- and time-dependent mortality, with an LD50 of 67.4 μg per fly. At sublethal doses, the treated flies displayed uncoordinated movement and fell when attempting to climb. Real-time analysis of flies exposed to the venom revealed hyperexcitability followed by paralysis, with phenotypes similar to those observed in vertebrate models. The venom was shown to be non-thermolabile, as no significant differences in behavior and locomotion were observed between flies exposed to untreated or thermally treated venom. The circadian rhythm alterations, the enhanced light attraction, and the reduction in heat avoidance suggest altered neuronal function. This abnormal behavior indicates that the venom contains bioactive molecules, opening avenues for discovering new compounds with potential for pharmacological applications.

Keriorrhea, una entidad poco común

Keriorrhea is the emission of an orange oily fluid in the feces that can appear after eating some species of fish, like butterfish. Symptoms can appear between 1 hour and 3 days after fish intake. Keriorrhea consists of orange oily fluid emission (like mussel oil) in the feces without depositional rhythm alteration and does not need any treatment.

The genetically programmed rhythmic alteration of diurnal gene expression in the aged Arabidopsis leaves.

The circadian clock regulates the daily pattern of temporal gene expression. In Arabidopsis, aging is associated with a shortening of the endogenous period of circadian rhythms under circadian conditions. However, the functional link between the circadian clock and aging under diurnal conditions and its physiological relevance remain elusive. In this study, we investigate and characterize the effect of aging on the waveforms of rhythmic gene expression patterns under light/dark cycles. Our analysis revealed that the diurnal rhythmic patterns of core clock genes undergo significant rhythmic alteration with phase shift and change of waveforms in aged plants compared to younger plants. Transcriptomic analysis indicated that this age-dependent rhythmic alteration occurs not only in core clock genes but also globally. Due to the rhythmic alteration patterns of the diurnal rhythmic gene expression, aged plants experience subjectively a shorter day and longer night. We also observed that genetic mutants of core clock component genes exhibited broadly yet distinctively altered changes in diurnal rhythmic gene expression patterns as aging progresses. Collectively, our findings support that age-dependent rhythmic alteration of diurnal gene expression rhythms reprograms the timetable of daily gene expression, leading to the physiological changes required for plant senescence.

Exposure to nicotine and withdrawal in Wistar rats: an electrophysiological study.

Throughout the world, smoking is one of the principal causes of preventable death. Nicotine, the primary active component of tabacco, acts as a psychostimulant and modulates the electrical activity of a number of the areas of the brain involved in addiction. Abstinence from nicotine will also impact the functional state of the brain, which is reflected in symptoms of craving and susceptibility to relapse. In addition, given the increase in the sympathetic tone of the heart and pulse rate promoted by nicotine, its consumption can contribute to tachyarrhythmia. The present study investigated the electroencephalographic (EEG) and electrocardiographic (ECG) patterns of Wistar rats submitted to acute or chronic exposure to nicotine, followed by withdrawal for 24 or 48 hours, and the re-administration (or not) of nicotine, to simulate episodes of relapse. The EEG data revealed an increase in all types of brainwaves, with emphasis on high-frequency (alpha, beta, and gamma) brain oscillations following both acute and chronic exposure to nicotine (14 days), whereas in withdrawal, there was a predominancy of delta waves. When exposure to nicotine was reinstated after withdrawal, the observed EEG profile was similar to that found in chronic exposure. The electrocardiogram reads showed that both acute and chronic exposure to nicotine caused abnormalities in the atrioventricular conduction and that, while these changes improve with substance withdrawal, relapse can worsen these parameters. The results of this study indicate that high-frequency brainwaves are correlated with nicotine dependence, while slow brain oscillations are consistent with drug craving, and episodes of nicotine relapse can reproduce brain activity patterns linked to dependence. Finally, exposure to nicotine predisposes the individual to heart rhythm abnormalities, which are attenuated by withdrawal, but may nevertheless be restored rapidly with re-exposure to the substance. This study demonstrated that nicotine increases high-frequency brain oscillations, which is associated with addiction, whereas withdrawal elevates the delta wave power, suggesting craving. Re-exposure to nicotine following withdrawal restores rapidly the EEG profile of chronic dependence. In addition, nicotine has deleterious impacts on cardiac activity, which are linked to fatal arrhythmias. This implies that stopping smoking is beneficial for the amelioration of the alterations in heart rhythm caused by nicotine addiction. This study elucidates the functional states of the brain and heart during both sporadic and chronic nicotine use, and the electrophysiological explanation for substance dependence and drug relapse after craving episodes.

Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.

Circadian Rhythm Disruption in Cancer Survivors: From Oncogenesis to Quality of Life.

Circadian rhythms are approximately 24-hour cycles in physiological and behavioral processes. They are entrained to the external solar day via blue wavelength light. Disruptions in these intrinsic rhythms can lead to circadian dysfunction, which has several negative implications on human health, including cancer development and progression. Here we review the molecular mechanisms of circadian disruption and their impact on tumor development and progression, discuss the interplay between circadian dysfunction and cancer in basic scientific studies and clinical data, and propose the potential clinical implications of these data that may be used to improve patient outcomes and reduce cost of treatment. Using scientific literature databases, relevant studies were analyzed to draw overarching conclusions of the relationship between circadian rhythm dysruption and cancer. Circadian disruption can be mediated by a number of environmental factors such as exposure to light at night, shift work, jetlag, and social jetlag which drive oncogenesis. Tumor growth and progression, as well as treatment, can lead to long-term alterations in circadian rhythms that negatively affect quality of life in cancer survivors.

Kaempferol Extends Male Lifespan Under Blue Light Irradiation in Drosophila.

Short-wavelength blue light is ubiquitous in daily life and has a lasting destructive influence. Its potential harm to biological health is significant. This study used Drosophila as a model organism to investigate the protective effects of kaempferol, a flavonoid, against the toxicity of blue light. It also examined its physiological effects on Drosophila under blue light irradiation. In this experiment, fruit flies were fed with three different concentrations of kaempferol solutions (0.1, 0.01, and 0.001 mol/L) dissolved in food. The survival rate and physiological indexes of Drosophila were investigated under blue light irradiation of 2500 lux. The results showed that 0.1 mol/L kaempferol increased the activity of male flies during the day and significantly extended the male survival time under blue light irradiation. However, the study found that kaempferol did not significantly prolong the survival time of Drosophila in the oxidative stress experiment, and no significant difference was observed in the feeding experiment. In summary, our research found that kaempferol, at the concentration of 0.1 mol/L, has a protective effect on Drosophila under blue light irradiation, potentially achieved through alterations in circadian rhythm.

Late Bedtime and Altered Diurnal Axial Length Rhythms of the Eye

Purpose Affecting one-third of the population worldwide and increasing, the sight-threatening condition myopia is causing a significant socio-economic burden. To better understand its etiology, recent studies investigated the role of ocular and systemic rhythms, yet results are conflicting. Here we profiled 24-h variations of axial length of the eye and salivary melatonin concentration in young adults with and without myopia and explored the potential impacts of bedtime on these rhythms. Methods A total of 25 healthy young adults (age 25.0 ± 4.8 years, 13 females) completed this study, including 13 myopes (mean spherical equivalent refractive error −2.93 ± 1.46 diopters) and 12 non-myopes (0.14 ± 0.42 diopters). Saliva sample collection and axial length measurements were repeated for seven times over 24 h starting from 8 am. Information on sleep and chronotype was collected at first visit with the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire. Results Significant diurnal rhythms of axial length and salivary melatonin concentration were identified in both refractive groups (both p < 0.001), with no myopia-related rhythm difference (interaction of measurement time-point × myopia, p = 0.9). Late bedtime was associated with altered rhythms (p = 0.009) and smaller diurnal change (p = 0.01) in axial length. Elevated melatonin levels were observed in myopes (p = 0.006) and in late sleepers (p = 0.017). Conclusions These findings suggest that sleep/wake cycles may be involved in the regulation of axial length rhythms. Further research is needed to determine if there exists a causal relationship between the two.

Inflammatory pain in mice induces light cycle-dependent effects on sleep architecture.

As a syndrome, chronic pain comprises physical, emotional, and cognitive symptoms such as disability, negative affect, feelings of stress, and fatigue. A rodent model of long-term inflammatory pain, induced by complete Freund's adjuvant (CFA) injection, has previously been shown to cause anhedonia and dysregulated naturalistic behaviors, in a manner similar to animal models of stress. We examined whether this extended to alterations in circadian rhythms and sleep, such as those induced by chronic social defeat stress, using actigraphy and wireless EEG. CFA-induced inflammatory pain profoundly altered sleep architecture in male and female mice. Injection of the hind paw, whether with CFA or saline, reduced some measures of circadian rhythmicity such as variance, period, and amplitude. CFA increased sleep duration primarily in the dark phase, while sleep bout length was decreased in the light and increased in the dark phase. Additionally, CFA reduced wake bout length, especially during the dark phase. Increases in REM and SWS duration and bouts were most significant in the dark phase, regardless of whether CFA had been injected at its onset or 12 hours prior. Taken together, these results indicate that inflammatory pain acutely promotes but also fragments sleep.