To explore the anti-depression effect of Suanzaoren Decoction(SZRD), the regulatory effects on endogenous metabolites in the liver of rats with depression induced by chronic unpredictable mild stress(CUMS) were analyzed by using LC-MS metabolomics. The rats were randomly divided into normal control group, model group, low-dose SZRD group, high-dose SZRD group, and positive drug group. The CUMS depression model was replicated by applying a variety of stimuli, such as fasting and water deprivation, ice water swimming, hot water swimming, day and night reversal, tail clamping, and restraint for rats. Modeling and treatment were conducted for 56 days. The behavioral indexes of rats in each group, including body weight, open field test, sucrose preference test, and tail suspension test, were observed. Plasma samples and liver tissue samples were collected, and the contents of 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) in plasma were measured using enzyme-linked immunosorbent assay(ELISA). Meanwhile, the regulatory effects of SZRD on the liver metabolic profile of CUMS model rats were analyzed by the LC-MS metabolomics method. The results show that SZRD can significantly improve the depression-like behavior of CUMS model rats and increase the neurotransmitter levels of 5-HT, DA, and NE in plasma. A total of 24 different metabolites in the rats' liver are identified using the LC-MS metabolomics method, and SZRD can reverse 13 of these metabolites. Metabolic pathway analysis indicates that nine metabolic pathways are found to be significantly associated with depression, and in the low-dose SZRD group, four pathways can be regulated, including pentose phosphate pathway, purine metabolism, inositol phosphate metabolism, and sphingolipid metabolism. In the high-dose SZRD group, two metabolic pathways can be regulated, including sphingolipid metabolism and glycerol glycerophospholipid metabolism. Sphingolipid metabolism is a metabolic pathway that can be regulated by SZRD at different doses, so it is speculated that it may be the primary pathway through which SZRD can alleviate metabolic disturbances in the liver of CUMS model rats.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Depression/metabolism* ; Male ; Liver/drug effects* ; Rats, Sprague-Dawley ; Antidepressive Agents/administration & dosage* ; Serotonin/blood* ; Humans ; Disease Models, Animal ; Behavior, Animal/drug effects*

Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM_2.5 and PM₁₀, carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM_2.5 (8.53 µg/m³) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM_2.5 and survival time to newly onset depressive disorder. CONCLUSION PM_2.5 is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1.
Humans ; Particulate Matter/analysis* ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Incidence ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Taiwan/epidemiology* ; Receptors, Tumor Necrosis Factor, Type I/blood* ; Proportional Hazards Models ; Biomarkers/blood* ; Depression/epidemiology* ; Aged, 80 and over ; Depressive Disorder/chemically induced* ; Risk Factors ; Air Pollution/adverse effects*

OBJECTIVE: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism. METHODS: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization. RESULTS: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05). CONCLUSIONS XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Animals ; Tryptophan/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/blood* ; Male ; Stress, Psychological/drug therapy* ; Behavior, Animal/drug effects* ; Rats ; Chronic Disease ; Hippocampus/drug effects*

OBJECTIVE: To investigate the effect of Zuogui Jiangtang Jieyu Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression. METHODS: Diabetic rat models with depression were randomly divided into model group, positive drug (metformin + fluoxetine) group, and low-, medium-, and high-dose ZJJ groups (n=16), with normal SD rats as the control group. The positive drugs and ZJJ were administered by gavage, and the rats in the control and model groups were given distilled water. After the treatment, blood glucose level was detected using test strips, and behavioral changes of the rats were assessed by forced swimming test and water maze test. ELISA was used to examine the serum level of leptin; The expressions of nestin and Brdu proteins in the dentate gyrus of the rats were detected using immunofluorescence assay, and the expressions of self-renewal marker proteins and Shh signaling proteins were detected using Western blotting. RESULTS: The diabetic rats with depression showed significantly increased levels of blood glucose and leptin (P < 0.01) and prolonged immobility time in forced swimming test (P < 0.01) and increased stage climbing time with reduced stage seeking time and stage crossings in water maze test (P < 0.01). The expressions of nestin and Brdu in the dentate gyrus, the expressions of cyclin D1, SOX2, Shh, Ptch1, Smo in the hippocampus and the nuclear expression of Gli-1 were decreased (P < 0.01) while hippocampal Gli-3 expression was increased significantly (P < 0.01) in the rat models. Treatment of rat models with high-dose ZJJ significantly reduced the blood glucose (P < 0.01) and leptin level (P < 0.05) and improved their performance in behavioral tests (P < 0.01). The treatment also obviously increased the expressions of nestin, Brdu, cyclin D1, SOX2, Shh, Ptch1, and Smo and the nuclear expression of Gli-1 in the dentate gyrus (P < 0.01) and reduced hippocampal expression of Gli-3 (P < 0.05) in the rat models. CONCLUSION ZJJ can significantly improve the self-renewal ability of neural stem cells and activate Shh signaling in dentate gyrus of diabetic rats with depression.
Animals ; Rats ; Blood Glucose ; Bromodeoxyuridine ; Cell Self Renewal ; Cyclin D1 ; Dentate Gyrus ; Depression ; Diabetes Mellitus, Experimental ; Hippocampus ; Leptin ; Nestin ; Rats, Sprague-Dawley

This study used machine learning techniques combined with routine blood cell analysis parameters to build preliminary prediction models, helping differentiate patients with depression from healthy controls, or patients with anxiety. A multicenter study was performed by collecting blood cell analysis data of Beijing Chaoyang Hospital and the First Hospital of Hebei Medical University from 2020 to 2021. Machine learning techniques, including support vector machine, decision tree, naïve Bayes, random forest and multi-layer perceptron were explored to establish a prediction model of depression. The results showed that based on the blood cell analysis results of healthy controls and depression group, the accuracy of prediction model reached as high as 0.99, F1 was 0.975. Receiver operating characteristic curve area and average accuracy were 0.985 and 0.967, respectively. Platelet parameters contributed mostly to depression prediction model. While, to random forest differential diagnosis model based on the data from depression and anxiety groups, prediction accuracy reached 0.68 and AUC 0.622. Age, platelet parameters, and average volume of red blood cells contributed the most to the model. In conclusion, the study researched on the prediction model of depression by exploring blood cell analysis parameters, revealing that machine learning models were more objective in the evaluation of mental illness.
Humans ; Depression ; Bayes Theorem ; Machine Learning ; Support Vector Machine ; Blood Cell Count

This study used machine learning techniques combined with routine blood cell analysis parameters to build preliminary prediction models, helping differentiate patients with depression from healthy controls, or patients with anxiety. A multicenter study was performed by collecting blood cell analysis data of Beijing Chaoyang Hospital and the First Hospital of Hebei Medical University from 2020 to 2021. Machine learning techniques, including support vector machine, decision tree, naïve Bayes, random forest and multi-layer perceptron were explored to establish a prediction model of depression. The results showed that based on the blood cell analysis results of healthy controls and depression group, the accuracy of prediction model reached as high as 0.99, F1 was 0.975. Receiver operating characteristic curve area and average accuracy were 0.985 and 0.967, respectively. Platelet parameters contributed mostly to depression prediction model. While, to random forest differential diagnosis model based on the data from depression and anxiety groups, prediction accuracy reached 0.68 and AUC 0.622. Age, platelet parameters, and average volume of red blood cells contributed the most to the model. In conclusion, the study researched on the prediction model of depression by exploring blood cell analysis parameters, revealing that machine learning models were more objective in the evaluation of mental illness.
Humans ; Depression ; Bayes Theorem ; Machine Learning ; Support Vector Machine ; Blood Cell Count

OBJECTIVE: To evaluate the effectiveness and possible mechanism of acupuncture treatment for negative emotion in patients with polycystic ovary syndrome (PCOS). METHODS: A total of 40 PCOS patients were randomly divided into an observation group and a control group, 20 cases in each one. Both groups received lifestyle interventions (exercise and diet guidance) on the 5th day of menstruation. On the basis of above treatment, the patients in the observation group received acupuncture at Guanyuan (CV 4), Zhongwan (CV 12), Guilai (ST 29), Futu (ST 32), Liangqiu (ST 34), Sanyinjiao (SP 6), Zusanli (ST 36), Hegu (LI 4), Shenmen (HT 7), Baihui (GV 20) as the main acupoints, and connected the electroacupuncture (continuous wave, 2 Hz, 30 min), once every other day, 3 times a week. The treatment for 1 month was as one course and 4 courses were required totally in both groups. Before and after treatment, the body mass index (BMI), ferriman-gallway (F-G) score, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score, PCOS health-related quality of life questionnaire (PCOSQ) score were observed, meanwhile, serum sex hormone, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E), progestin (P), prolactin (PRL), testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) levels, and serumβ-endorphin levels were detected. RESULTS: Compared with before treatment, the BMI, F-G score, SAS score, SDS score and serum FAI level were decreased and the PCOSQ score and the levels of serum SHBG andβ-endorphin were increased in the observation group after treatment (all <0.05). Compared with before treatment, the SDS score was decreased in the control group after treatment (<0.05). Compared with the control group, the F-G score, SDS score, SAS score, and serum FAI level were lower, and the PCOSQ score and serumβ-endorphin level were higher in the observation group after treatment (all <0.05). CONCLUSION Applying acupuncture to the treatment of patients with PCOS can effectively relieve anxiety and depression, and the mechanism may be related to the regulation on the levels of serumβ-endorphin and androgen.
Acupuncture Points ; Acupuncture Therapy ; Anxiety ; therapy ; Depression ; therapy ; Emotions ; Female ; Gonadal Steroid Hormones ; blood ; Humans ; Polycystic Ovary Syndrome ; psychology ; therapy ; Quality of Life

BACKGROUND: Albuminuria is an indicator of renal impairment in patients with diabetes or hypertension. Studies on the effect of sleep duration on albuminuria in hypertension patients are limited. Hence, the purpose of this study was to investigate the association between sleep duration and albuminuria in Korean hypertension patients.METHODS: In this cross-sectional study, data on hypertensive patients were obtained from the fifth Korean National Health and Nutrition Examination Survey (2011–2012). Participants were classified into five groups according to self-reported sleep duration. Multiple logistic regression analyses were performed to determine the association between sleep duration and albuminuria.RESULTS: When the sleep duration was shorter than 5 hours or longer than 9 hours, the odds ratio (OR) for albuminuria was significantly higher. After adjusting for age, sex, diabetes, hemoglobin A1c, systolic blood pressure, depressive symptom, stress status, smoking status, drinking habit, triglycerides, estimated glomerular filtration rate, and body mass index, ORs (95% confidence interval) for sleep durations of ≤5 hours and ≥9 hours were 1.69 (1.14–2.51) and 2.00 (1.22–3.26), respectively.CONCLUSION: This study showed that a sleep duration of ≤5 hours or ≥9 hours was associated with the high prevalence of albuminuria in Korean hypertension patients.
Albuminuria ; Blood Pressure ; Body Mass Index ; Cross-Sectional Studies ; Depression ; Drinking ; Glomerular Filtration Rate ; Humans ; Hypertension ; Logistic Models ; Nutrition Surveys ; Odds Ratio ; Prevalence ; Smoke ; Smoking ; Triglycerides