Composite healthy lifestyle, socioeconomic deprivation, and mental well-being during the COVID-19 pandemic: a prospective analysis.

The adverse psychological and social impacts of COVID-19 pandemic are well characterized, but the role of composite, modifiable lifestyle factors that may interact to mitigate these impacts is not. The effect of socioeconomic deprivation on these lifestyle risks also remains unclear. Based on a nationally representative, longitudinal cohort, we assessed the association between a combination of pre-pandemic lifestyle factors and mental health conditions during pandemic, and the contribution of deprivation to it. Composite lifestyle factors included BMI, smoking status, alcohol consumption, physical activity, sedentary time, sleep duration, and fruit and vegetable intake, with lifestyle scores and lifestyle categories calculated for each participant. Symptoms of depression and anxiety, and personal well-being were assessed by validated scales during the pandemic. Socioeconomic deprivation was characterized by both individual-level (income, wealth, and education) and group-level factors (Index of Multiple Deprivation). Of the 5049 eligible participants (mean [SD] age, 68.1 [10.9] years; 57.2% were female) included in the study, 41.6% followed a favorable lifestyle, 48.9% followed an intermediate lifestyle, and 9.5% followed an unfavorable lifestyle. Compared with favorable lifestyle category, participants in the intermediate and unfavorable lifestyle category were at increased risk of mental health conditions, with the hazard ratio (HR) for trend per increment change towards unfavorable category of 1.17 (95% CI 1.09-1.26) for depression, 1.23 (1.07-1.42) for anxiety, and 1.39 (1.20-1.61) for low well-being. A significant trend of lower risk for mental health conditions with increasing number of healthy lifestyle factors was observed (P < 0.001 for trend). There were no significant interactions between lifestyle factors and socioeconomic deprivation for any of the outcomes, with similar HRs for trend per one increment change in lifestyle category observed in each deprivation group. Compared with those in the least deprived group with favorable lifestyle, participants in the most deprived group adherent to unfavorable lifestyle had the highest risk of mental health outcomes. These results suggest that adherence to a broad combination of healthy lifestyle factors was associated with a significantly reduced risk of mental health conditions during the COVID-19 pandemic. Lifestyle factors, in conjunction with socioeconomic deprivation, independently contribute to the risk of mental health issues. Although further research is needed to assess causality, the current findings support public health strategies and individual-level interventions that provide enhanced support in areas of deprivation and target multiple lifestyle factors to reduce health inequalities and promote mental well-being during the ongoing COVID-19 pandemic.

Mitochondrial damage-associated molecular patterns: A new insight into metabolic inflammation in type 2 diabetes mellitus.

The pathogenesis of diabetes is accompanied by increased levels of inflammatory factors, also known as "metabolic inflammation", which runs through the whole process of the occurrence and development of the disease. Mitochondria, as the key site of glucose and lipid metabolism, is often accompanied by mitochondrial function damage in type 2 diabetes mellitus (T2DM). Damaged mitochondria release pro-inflammatory factors through damage-related molecular patterns that activate inflammation pathways and reactions to oxidative stress, further aggravate metabolic disorders, and form a vicious circle. Currently, the pathogenesis of diabetes is still unclear, and clinical treatment focuses primarily on symptomatic intervention of the internal environment of disorders of glucose and lipid metabolism with limited clinical efficacy. The proinflammatory effect of mitochondrial damage-associated molecular pattern (mtDAMP) in T2DM provides a new research direction for exploring the pathogenesis and intervention targets of T2DM. Therefore, this review covers the most recent findings on the molecular mechanism and related signalling cascades of inflammation caused by mtDAMP in T2DM and discusses its pathogenic role of it in the pathological process of T2DM to search potential intervention targets.

Quinoa alleviates osteoporosis in ovariectomized rats by regulating gut microbiota imbalance.

BACKGROUND: Postmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota. RESULTS: Quinoa significantly improved osteoporosis-related biochemical parameters of OVX rats and ameliorated ovariectomy-induced bone density reduction and trabecular structure damage. Quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to estrogen signaling pathway, secondary and primary bile acid biosynthesis, benzoate degradation, synthesis and degradation of ketone bodies, NOD-like receptor signaling pathway and biosynthesis of tropane, piperidine and pyridine alkaloids. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis. CONCLUSION: Quinoa could significantly reverse the high intestinal permeability and change the composition of gut microbiota in OVX rats, thereby improving bone microstructure deterioration and bone metabolism disorder, and ultimately protecting the bone loss of OVX rats. © 2024 Society of Chemical Industry.

Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN. METHODS: Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected. RESULTS: CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs. CONCLUSIONS: CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.

Association of longitudinal trajectories of general and abdominal adiposity during middle age with mental health and well-being in late life: A prospective analysis.

Single measures of adiposity markers, such as body mass index (BMI) and waist circumference (WC), are associated with adverse mental health outcomes; however, long-term patterns of adiposity and their health effects remain unclear. The current study assessed adiposity trajectories during a 14-year span beyond middle age and their relevance to mental well-being in late life, and the contribution of genetic and lifestyle factors to the trajectories. Based on a nationally representative sample with longitudinal anthropometric measures, adiposity trajectories were identified by latent mixture modeling, and logistic regression model was used to estimate their associations with mental well-being, with adjustment for confounders. Of the 3491 eligible participants included (mean [SD] age, 69.5 [8.9] years), five discrete BMI and four WC trajectory patterns were identified over 14 years. Compared with the low-stable BMI group (range, 22.8 to 22.9 kg/m²; representing stable healthy body weight), the high-stable group (range, 34.3 to 35.4 kg/m²; stable obese) was associated with increased risk of depression (odds ratio [OR], 1.63; 95 % CI, 1.28-2.07) and low subjective well-being (OR, 1.35; 95 % CI, 1.02-1.79). Compared with the low-stable WC group (range, 75 to 79 cm healthy WC), the high-increasing group (range, 114 to 121 cm) was associated with increased risk of depression (odds ratio [OR], 1.64; 95 % CI, 1.19-2.25) and low well-being (OR, 1.48; 95 % CI, 1.01-2.16). The adiposity trajectories, especially the high-stable/increasing groups, were driven by genetic factors in a dose-response manner, whereas the high/moderate-increasing groups were also behaviorally related. This longitudinal cohort study reveals that stably high trajectory patterns of central and general adiposity during middle age were associated with higher risk of depression and low well-being in late life. The findings indicate the importance of weight management beyond middle age, such as adherence to a healthy lifestyle, in promoting mental health and well-being.

Establishment of a chronic insomnia rat model of sleep fragmentation using unstable platforms surrounded by water.

Chronic fragmented sleep is a very common type of insomnia that affects the daily lives of numerous people around the world. However, its pathogenesis is not very clear and a corresponding rat model has not been reported for this purpose at present. The present study aimed to establish a rat model of chronic insomnia with sleep fragmentation using self-made multiple strings of unstable platforms surrounded by shallow water. During the establishment of the models, changes in body weight and differences in food and water intake in the daytime and at night were acquired. The rat models were assessed using several tests, including the Morris water maze test, pentobarbital sodium-induced sleep, infrared monitoring and electroencephalogram/electromyography during sleep. The expression levels of certain inflammatory factors and orexin A were detected in the serum and brain tissues using ELISAs, immunohistochemistry and immunofluorescence. The expression levels of orexin 1 receptor (orexin 1r) were also detected in the brain. Polysomnography indicated that the model rats were successfully prepared with reduced non-rapid eye movement (non-REM) sleep in the daytime, which was increased at night, and considerably lower REM duration during the day and night. The number of instances of sleep arousals were also increased in the day and at night, and the average duration of each sleep bout was decreased in the daytime. The body weights of the model rats increased at a normal rate. However, the reduction of body weight in the daytime and increased in body weight at night were significantly less than those of the control rats. The daytime food and water consumption of the model rats increased significantly compared with that of the control rats, but was similar to that of the control group at night. The Morris water maze test indicated that the model rats were slow to learn to escape the platforms and performed a lower number of target crossings. The pentobarbital-induced sleep experiment confirmed that the model rats exhibited a longer sleep latency and shorter sleep time. The serum IL-1ß, IL-6, TNF-α and orexin A levels of the model rats were significantly increased, whereas their serum IL-10 levels were significantly decreased compared with those of the control rats. The expression levels of IL-1ß, IL-6, orexin A and orexin 1r in the brain tissues of the model rats were also significantly increased. In conclusion, these data indicate that learning and memory function, sleep time, arousal times, diurnal and nocturnal body weight changes, food and water intake, and expression levels of the specific inflammatory factors orexin A and orexin 1r were altered in the model rats. This suggests the chronic insomnia rat model with sleep fragmentation was successfully established using multiple strings of unstable platforms surrounded by water.

Revealing the mechanism of quinoa on type 2 diabetes based on intestinal flora and taste pathways.

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high-fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway.

B serum proteome profiles revealed dysregulated proteins and mechanisms associated with insomnia patients: A preliminary study.

Background: Insomnia is a clinical problem of significant public health importance; however, the underlying pathogenesis of this disorder is not comprehensively understood. Methods: To identify potential treatment targets and unfold one of the gaps that were involved in insomnia pathological mechanisms, we employed a tandem mass tag-based (TMT) quantitative proteomics technology to detect differentially expressed proteins (DEPs) in serum from patients with insomnia and controls. DEPs were further analyzed by bioinformatics platforms. In addition, parallel reaction monitoring (PRM) was used to verify the TMT results. Results: Patients with insomnia had poorer sleep quality compared with healthy controls. A total of 106 DEPs were identified among patients with insomnia and controls. They were mainly enriched in immune and inflammation-related biological functions and signaling pathways. Using the protein-protein interaction network, we screened the 10 most connected proteins as key DEPs. We predicted that four key DEPs were subject to targeted regulation by natural compounds of herbs. Eight key DEPs were validated using PRM in an additional 15 patients with insomnia and 15 controls, and the results also supported the experimental findings. Conclusion: We identified aberrantly expressed proteins in insomnia that may be involved in the immune-inflammatory response. The 10 key DEPs screened may be potential targets for insomnia, especially FN1, EGF, HP, and IGF1. The results of this study will broaden our understanding of the pathological mechanisms of insomnia and provide more possibilities for pharmacotherapy.

Proteomics Reveals Molecular Changes in Insomnia Patients with More Dreams.

Background: Insomnia is a sleep disorder and the cause of many healthy problems. However, there are few studies on patients with insomnia and dreaminess at present. Therefore, this study is aimed at exploring the pathological molecular mechanisms and potential diagnostic and therapeutic targets related to insomnia patients with more dreams. Methods: Sleep characteristics of 36 primary insomnia patients with more dreams and 36 well sleeping participants were assessed using polysomnography (PSG) and Pittsburgh Sleep Quality Index (PSQI). Serum samples from 9 insomnia patients and 9 controls were randomly selected for proteomic detection. Differentially expressed proteins (DEPs) between the two groups were identified; enrichment analysis and PPI network were performed. The top 10 most connected proteins in the PPI network were subjected to targeted drug prediction and screened key proteins. Proteins with targeted drugs were recognized as key proteins and subjected to ELISA detection. Results: Insomnia patients had a distinct REM behavior disorder signature compared with controls. Proteomic sequencing identified 76 DEPs. Enrichment analysis found that DEPs were significantly enriched in the complement and coagulation cascades. Metabolic responses were also activated in insomnia patients. Among the hub proteins screened in the PPI network, APOA1, APOB, F2, and SPARC may be targeted by many herbal medicines and considered as key proteins. ELISA assays validated their differential expression between insomnia and controls. Conclusion: In this study, we identified the potential key proteins of insomnia patients with more dreams. The pathological process may associate with inflammation and metabolic response. These results provide molecular targets for diagnostic and therapeutic targets. The results of our analysis suggest that the expression changes of key proteins have a good predictive diagnostic role for the occurrence of insomnia with more dreams in patients.