Mechanism of HDAC1 Regulating Iron Overload-Induced Neuronal Oxidative Damage After Cerebral Hemorrhage.

Iron overload is associated with brain edema in the context of intracerebral hemorrhage (ICH). Here, we investigated the role of histone deacetylase 1 (HDAC1) in mediating oxidative damage induced by iron overload after ICH. Utilizing ICH mouse models and FeCl2-induced HT-22 cell models, we assessed HDAC1 expression and its impact on iron overload and oxidative damage. We examined the levels of Kruppel like factor 4 (KLF4), RAN binding protein 9 (RANBP9), as well as the acetylation levels of HDAC1 and histones H3 and H4 in the KLF4 promoter, and the KLF4 level in the RANBP9 promoter. Additionally, we investigated the binding relationships between KLF4 and the RANBP9 promoter, HDAC1 and miR-129-5p. Our results demonstrated elevated HDAC1 expression in ICH mice and FeCl2-induced HT-22 cells. HDAC1 silencing improved neurological function in mice, reduced brain edema, and alleviated iron overload and oxidative damage in vitro. HDAC1 downregulated KLF4 expression by reducing acetylation levels in the KLF4 promoter, leading to decreased KLF4 enrichment in the RANBP9 promoter and increased RANBP9 expression. Furthermore, upstream miR-129-5p inhibited HDAC1, and the downregulation of miR-129-5p mitigated the protective effect of HDAC1 silencing. Collectively, our findings highlight the significant role of HDAC1 in exacerbating iron overload-induced oxidative damage following ICH and its regulation by miR-129-5p.

Cognitive and motor profiles as prodromal markers in predicting phenoconversion and phenotype in isolated REM sleep behavior disorder.

OBJECTIVE: To determine the clinical markers based on cognitive and motor profiles in predicting phenoconverion and phenotype in isolated rapid eye movement sleep behavior disorder (iRBD). METHODS: 45 iRBD patients and 25 healthy controls were included in the follow-up study. All participates received comprehensive evaluations of cognitive, motor and autonomic function at baseline. Positive phenoconversion were identified according to standard diagnostic criteria during follow-up. RESULTS: 21 iRBD patients displayed phenoconversion in a mean follow-up of 2.9 ± 1.6 years, with 14 presenting motor phenotype and 7 cognitive phenotype. In iRBD, visuospatial, memory, attention-executive function, information processing speed, and motor function predicted phenoconversion, with the combination of Trail Making Test (TMT) and Alternate-tap Test (ATT) performing best (sensitivity = 95.0 %, specificity = 75.0 %); attention-executive function, information processing speed, and motor function predicted motor phenotype conversion, with the combination of TMT and ATT performing best (sensitivity = 100 %, specificity = 66.7 %); visuospatial, memory, and attention-executive function predicted cognitive phenotype conversion, with TMT performing best (sensitivity = 83.3 %, specificity = 91.7 %). Furthermore, individuals with lower z-scores of TMT, Symbol Digit Modalities Test, and ATT than the established cutoff values in iRBD exhibited a significantly higher risk for phenoconversion at follow-up (HR = 2.98, 9.53, 11.68; respectively). CONCLUSIONS: In iRBD, the attention-executive and motor function served as optimum combined markers in predicting phenoconversion and motor phenotype, whereas the attention-executive function performed best in predicting cognitive phenotype. Poor attention-executive function, information processing speed and motor function in iRBD independently increased the risk of phenoconversion.

Mood Disorders are Correlated with Autonomic Nervous Function in Chronic Insomnia Patients with OSA.

Purpose: To evaluate the correlation between sleep microstructure, autonomic nervous system activity, and neuropsychological characteristics in chronic insomnia (CI) patients with obstructive sleep apnea (OSA). Patients and Methods: Forty-five CI-OSA patients, forty-six CI patients and twenty-two matched healthy control subjects (HCs) were enrolled. CI-OSA patients were then divided into two groups: mild OSA and moderate-to-severe OSA. All participants completed neuropsychological tests, which included the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Mini-mental State Examination (MMSE). The autonomic nervous system activity and sleep microstructure were examined by the PSM-100A. Results: The CI-OSA patients exhibited higher scores on the PSQI, ESS, ISI, HAMA, and HAMD than HCs and CI patients (all p < 0.01). The CI-OSA patients had a lower proportion of stable sleep, REM sleep and a higher proportion of unstable sleep ratio (all p < 0.01) than HCs and CI patients (all p < 0.01). The CI-OSA patients had higher ratios of LF and LF/HF, and lower ratios of HF and Pnn50% (all p < 0.01) than HCs and CI patients (all p < 0.01). Compared to CI-mild OSA patients, the CI-moderate-to-severe OSA patients presented with a higher ESS scores, higher ratios of LF and LF/HF, and lower ratios of HF (all p < 0.05). In CI-OSA patients, higher HAMD scores were correlated with decreased MMSE scores (r=-0.678, p < 0.01). A higher LF ratio was correlated with higher HAMD and HAMA scores (r=0.321, p=0.031, r =0.449, p =0.002), and a higher HF ratio was correlated with lower HAMD and HAMA scores (r=-0.321, P =0.031, r =-0.449, p =0.002). Conclusion: OSA exacerbates the abnormalities of sleep microstructure and the autonomic nervous dysfunction in CI patients. Dysfunction of the autonomic nervous system could contribute to mood deterioration in CI with OSA patients.

Role of IGF-1 in neuroinflammation and cognition deficits induced by sleep deprivation.

Sleep deprivation negatively influences cognition, however, the regulatory mechanisms to counteract this effect have not been identified. IGF-1 has been shown to be anti-inflammatory and neuroprotective in CNS injury models. In this study, we determined the impact of IGF-1 on brain injury and inflammation while modeling sleep deprivation. We found that IGF-1 was downregulated in human peripheral blood and in mice subjected to sleep deprivation for 5 days, with reduced activation of the downstream PI3K/AKT/GSK-3ß pathway in mice brains. In addition, we found reduced levels of the anti-apoptosis enzyme Bcl-2 and increased levels of pro-apoptosis enzyme Caspase-9 expression, together with increased pro-inflammatory factors. The administration of IGF-1 after sleep deprivation induced activation of the PI3K/AKT/GSK-3ß pathway, reversed changes in Bcl-2, Caspase-9, and pro-inflammatory factors, and alleviated cognitive impairment. Notably, IGF-1 also induced activation of the PI3K/AKT/GSK-3ß pathway, and displayed anti-apoptosis and anti-inflammatory properties under normal sleep conditions,while IGF-1 did not improve the cognition under normal sleep conditions. These results suggest that the IGF-1/PI3K/AKT/GSK-3ß pathway is involved in the regulation of cognitive function after sleep deprivation through modulation of apoptosis and inflammatory response. IGF-1 could be a viable therapeutic target, though further investigation is required to better understand its role in sleep deprivation.

Positive impacts of e-aid cognitive behavioural therapy on the sleep quality and mood of nurses on site during the COVID-19 pandemic.

OBJECTIVE: To investigate the positive impact of e-aid cognitive behavioural therapy on the sleep quality, anxiety, and depression of nurses on site during the COVID-19 pandemic. METHODS: Nurses on site at the Tianjin Medical University General Hospital Airport Site experiencing insomnia, anxiety and depression during the COVID-19 prevention and control period, from February 2020 to April 2021, were selected and divided into either an e-aid cognitive behavioural therapy (eCBT-I) group or a control group using a randomized grouping method. The eCBT-I group was given standard eCBT-I for 6 weeks; the control group did not get any intervention. The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) were used to evaluate the sleep quality of the subjects. The Generalized Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire (PHQ-9) were used to assess the subjects' anxiety and depression. Changes in sleep quality, anxiety and depression before and after treatment were compared between the two groups. RESULTS: Of 118 nurses randomized, the PSQI and ISI scores within the eCBT-I group (n=60) were significantly lower after treatment (5.9 ± 3.9, 6.7 ± 4.5) than before treatment (10.4 ± 3.5, 12.4 ± 4.7) (p <0.05). Compared to the scores of the control group (n=58) (9.1 ± 3.9, 10.6 ± 4.1), the PSQI and ISI scores in the eCBT-I group (5.9 ± 3.9, 6.7 ± 4.5) were lower after treatment (p <0.05). The GAD-7 and PHQ-9 scores in the eCBT-I group were all lower after treatment (3.7±3.4, 4.2±4.1) than before treatment (6.7±4.9, 7.7±5.1) (p <0.05). Compared with subjects in the control group (7.1±5.6, 7.3±5.1), subjects in the eCBT-I group (3.7±3.4, 4.2±4.1) had lower scores on the GAD-7 and PHQ-9 scales after treatment (p <0.05). CONCLUSION: eCBT-I improved the sleep quality of frontline nurses during the COVID-19 prevention and control period and relieved anxiety and depression.

Cognitive deficit is correlated with sleep stability in insomnia: A cardiopulmonary coupling study.

OBJECTIVES: To assess the correlation of cognitive function with sleep stability and depressive-anxious symptoms in insomnia patients. METHODS: Twenty-two insomnia patients with cognitive impairment (insomnia-CI), 21 insomnia patients with normal cognition (insomnia-CN), and 15 matched healthy control subjects (HCs) were enrolled and completed neuropsychological tests, the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index (PSQI),the Insomnia Severity Index (ISI), and the cardiopulmonary coupling (CPC) examination. Ratios of high-frequency coupling (HFC), low-frequency coupling (LFC), and very low-frequency coupling (VLFC) measured by CPC analysis represent stable sleep, unstable sleep, and wake/rapid eye movement (REM) sleep, respectively. RESULTS: The HAMD, HAMA, PSQI, and ISI scores were higher in the insomnia-CN patients than in the HCs (all p < .01). However, no differences were found in the HFC, LFC, and VLFC ratio between the HCs and insomnia-CN groups. Compared with the insomnia-CN patients, insomnia-CI patients exhibited higher scores on the HAMD, HAMA (all p < .01), and PSQI (p < .05), performed worse on the Auditory Verbal Learning Test, Trial Making Test B, and Stroop Test B (all p < .01), had a lower HFC ratio, and had a higher LFC ratio in the CPC analysis (all p < .01). Furthermore, in the insomnia patients, poorer cognition was correlated with a decreased HFC ratio and an increased VLFC ratio (r = .356, p = .019; r = -.339, p =.026, respectively) and increased HAMD and HAMA scores (r = -.507, p < .001; r = -.561, p < .001, respectively); a higher VLFC ratio was correlated with an increased ISI score (r = .346, p = .023). CONCLUSIONS: Cognitive deterioration in insomnia patients was associated with a decreased stable sleep ratio, an increased wake/REM sleep ratio and more severe symptoms of depression and anxiety. CPC analysis can reflect the severity of insomnia.

Risk Factors of Acute Gastrointestinal Failure in Critically Ill Patients With Traumatic Brain Injury.

OBJECTIVE: To assess the risk factors associated with acute gastrointestinal failure (AGF) in critically ill patients with traumatic brain injury (TBI). METHODS: Prospective, observational study was conducted in NanFang Hospital, Southern Medical University. All patients admitted to the Department of Critical Care Medicine and Department of Neurosurgery from June 1, 2017 to December 1, 2018 with TBI were enrolled. RESULTS: Overall, 199 patients were enrolled. About 62 episodes (31%) of AGF were diagnosed. In the multivariate analysis, women, severe Glasgow Coma Scale (GCS) classification, frontal lobe injury, abnormal serum sodium, pulmonary infection, and intracranial infection are significantly associated with developing AGF, independent of other prognostic factors. CONCLUSION: The AGF occurs frequently in intensive care unit patients who are suffering from TBI. In critically ill patients with TBI, women, severe GCS classification, frontal lobe injury, abnormal serum sodium, pulmonary infection, and intracranial infection are independent risk factors for AGF.

Long Noncoding RNA UCA1 Is Related to Autophagy and Apoptosis in Endometrial Stromal Cells.

RESEARCH QUESTION: The expression of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in embryonic tissues is higher than that in most cancer tissues, such as bladder cancer, indicating that RNA is a carcinoembryonic antigen. However, there are no published reports on the role of UCA1 in endometriosis (EMS). Therefore, to address this gap in knowledge, we assessed the potential role of lncRNA UCA1 in the pathogenesis and progression of EMS. DESIGN: To verify the expression of UCA1 in EMS, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used. RNA interference (siRNA) was used to study the biological function of UCA1 in EMS in vitro. RESULTS: qRT-PCR analysis showed that the expression of lncRNA UCA1 in EMS was increased (P<0.01). Knockdown of UCA1 in vitro significantly inhibited the proliferation of endometrial stromal cells (ESCs) and induced autophagy and apoptosis. CONCLUSION: UCA1 is highly expressed in EMS and promotes the proliferation of ESCs but suppresses autophagy and apoptosis. In EMS, UCA1 may be a prognostic marker and therapeutic target.

Nicotinic Mitigation of Neuroinflammation and Oxidative Stress After Chronic Sleep Deprivation.

Sleep deprivation negatively influences all aspects of health. Oxidative stress and inflammatory responses induced by sleep deprivation participate in its adverse effects but the regulatory mechanisms to counteract them remain poorly understood. In mice subjected to sleep deprivation for 7 days, we found activation of microglia and astrocyte accompanied by down-regulation of α7 nicotinic acetylcholine receptor (α7-nAChR) and reduced activation of downstream PI3K/AKT/GSK-3ß. These changes occurred with an increase of pro-inflammatory factors, together with reduced levels of anti-inflammatory factors, transcriptor Nrf-2, and anti-oxidant enzyme HO-1. Administration of an α7-nAChR agonist PHA-543613 induced activation of PI3K/AKT/GSK-3ß, and reversed changes in pro-inflammatory and anti-inflammatory factors, Nrf-2 and HO-1. These results suggest that stimulation of α7-nAChR reduce neuroinflammation and oxidative stress after chronic sleep deprivation.

Sleep deprivation inhibits proliferation of adult hippocampal neural progenitor cells by a mechanism involving IL-17 and p38 MAPK.

Sleep deprivation impairs hippocampal neurogenesis, but the underlying mechanisms are inadequately understood. Sleep deprivation is associated with an increased production of pro-inflammatory factors. In this study, we demonstrate that acute rapid eye movement (REM) sleep deprivation in mice for 3 days leads to increased expression of interleukin (IL)-17A, IL-17F and activation of p38 MAPK pathway in the hippocampus, together with suppressed cell proliferation in the dentate gyrus. Similarly, activation of p38 MAPK and suppressed cell proliferation in the dentate gyrus were observed after administration of recombinant IL-17 in mice without sleep deprivation. Pharmacological blockade of the p38 MAPK after sleep deprivation mitigates sleep deprivation-induced ablation of cell proliferation in the dentate gyrus with unaltered expression of IL-17A and IL-17F. In addition, hippocampal neural progenitor cells express IL-17 receptor A (IL-17RA) and IL-17 receptor C (IL-17RC). These findings suggest that acute REM sleep deprivation suppresses proliferation of adult hippocampal neural progenitor cells by a mechanism involving IL-17 and p38 MAPK signaling.

Emerging role of SIRT3 in mitochondrial dysfunction and cardiovascular diseases.

As a nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylase, SIRT3 is highly expressed in tissues with high metabolic turnover and mitochondrial content. It has been demonstrated that SIRT3 plays a critical role in maintaining normal mitochondrial biological function through reversible protein lysine deacetylation. SIRT3 has a variety of substrates that are involved in mitochondrial biological processes such as energy metabolism, reactive oxygen species production and clearance, electron transport chain flux, mitochondrial membrane potential maintenance, and mitochondrial dynamics. In the suppression of SIRT3, functional deficiencies of mitochondria contribute to the development of various cardiovascular disorders. Activation of SIRT3 may represent a promising therapeutic strategy for the improvement of mitochondrial function and the treatment of relevant cardiovascular disorders. In the current review, we discuss the emerging roles of SIRT3 in mitochondrial derangements and subsequent cardiovascular malfunctions, including cardiac hypertrophy and heart failure, ischemia-reperfusion injury, and endothelial dysfunction in hypertension and atherosclerosis.