Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy.

OBJECTIVE: Patients with hypertension have a risk of depression. Morinda officinalis oligosaccharides (MOOs) have anti-depressant properties. In this study, we aimed to determine whether MOOs can improve the symptoms of depression in individuals with hypertension. METHODS: Dahl salt-sensitive rats fed with a high-salt diet were stimulated by chronic unpredictable mild stress to mimic hypertension with depression. Primary astrocytes and neurons were isolated from these rats. Astrocytes underwent LPS stimulation to simulate the inflammatory astrocytes during depression. MOOs were administrated at 0.1 mg/g/day in vivo and 1.25, 2.5, and 5 mg/mL in vitro. Mitophagy was inhibited using 5 mM 3-methyladenine (3-MA). Astrocyte-mediated neurotoxicity was detected by co-culturing astrocytes and neurons. RESULTS: MOOs decreased systolic pressure, diastolic pressure, and mean arterial pressure, thereby improving depression-like behavior, including behavioral despair, lack of enthusiasm, and loss of pleasure during hypertension with depression. Furthermore, MOOs inhibited inflammation, astrocytic dysfunction, and mitochondrial damage in the brain. Then, MOOs promoted autophagosome and lysosome enriched in mitochondria in LPS-stimulated astrocytes. MOOs suppressed mitochondrial damage and the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß in astrocytes undergoing LPS stimulation. Importantly, MOOs rescued the impaired neurons co-cultured with astrocytes. The effects of MOOs on LPS-stimulated astrocytes were reversed by 3-MA. Finally, MOOs upregulated LPS-downregulated Mfn2 expression in astrocytes. Mfn2 inhibition partly reversed the effects of MOOs on hypertension with depression. Intriguingly, Mfn2 suppression activated PI3K/Akt/mTOR pathway during MOOs treatment. CONCLUSIONS: Astrocytes develop neuroinflammation in response to mitochondrial damage during hypertension with depression. MOOs upregulated Mfn2 expression to activate the PI3K/Akt/mTOR pathway-mediated mitophagy, thereby removing impaired mitochondria in astrocytes. HIGHLIGHTS: 1. MOOs have anti-hypertensive and anti-depressive properties. 2. MOOs inhibit inflammation and injury in astrocytes during hypertension with depression. 3. MOOs induce mitophagy activation in inflammatory astrocytes with mitochondrial damage. 4. MOOs upregulate Mfn2 expression in astrocytes. 5. Mfn2 activates mitophagy to resist mitochondrial damage in astrocytes.

Antidepressants and Risk of Liver Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous results regarding the association between the antidepressants use and risk of liver cancer are controversial. OBJECTIVE: This study aimed to assess whether antidepressants use increases liver cancer risk. METHODS: We systematically searched several English and Chinese databases, including the Cochrane Library, MEDLINE, Embase, PsycINFO, Web of Science, CNKI, CQVIP database, Wanfang database, and SinoMed, and 3 clinical trial registration platforms through May 2022. Observational studies evaluating liver cancer risk in patients on antidepressants use were included, and the quality of studies was assessed using the Newcastle-Ottawa scale. A random-effects model was used to calculate the pooled effect estimates and 95% confidence intervals (CIs). RESULTS: We included 11 studies with a total of 132 396 liver cancer cases. The meta-relative risk (RR) for liver cancer associated with antidepressants use was 0.72 (95% CI 0.59-0.86). In subgroup analyses, only selective serotonin reuptake inhibitors were negatively correlated with risk of liver cancer (RR 0.64, 95% CI 0.51-0.79); both dose subgroups ≤365cDDD (RR 0.77, 95% CI 0.69-0.85) and >365cDDD (RR 0.57, 95% CI 0.40-0.81) were associated with lower liver cancer risk; only in patients with chronic viral hepatitis, the use of antidepressants reduced liver cancer risk (RR 0.70, 95% CI 0.54-0.90). CONCLUSIONS AND RELEVANCE: The result of the current meta-analysis shows antidepressants use is not associated with increased risk of liver cancer and appears to be correlated with decreased risk. However, the observed association needs to be verified by more powerful evidence from prospective, methodologically rigorous studies.

Association between mitochondrial DNA levels and depression: a systematic review and meta-analysis.

BACKGROUND: Mitochondrial dysfunction leading to disturbances in energy metabolism has emerged as one of the risk factors in the pathogenesis of depression. Numerous studies have identified alterations in the content of mitochondrial DNA (mtDNA) in peripheral blood and cerebrospinal fluid of individuals with depression. Researchers have sought to establish a clear association between mtDNA and depression. Consequently, we conducted a comprehensive meta-analysis to assess the existing evidence regarding the impact of mtDNA on depression. METHODS: This study conducted a thorough search of the following databases up to March 13, 2023: PubMed, Embase, the Cochrane Library, the Web of Science, Wanfang Database, SINOMED, the China Science and Technology Journal Database, and China National Knowledge Infrastructure. The meta-analysis was carried out using RevMan (version 5.4) and Stata (version 16.0) software. In addition, publication bias was assessed with funnel plots, Begg's test and Egger's test. RESULTS: Our analysis included data from 10 articles, including 12 studies for further examination. A total of 1400 participants were included in this study, comprising 709 (including 300 males and 409 females) patients with depression and 691 (including 303 males and 388 females) healthy controls. The average age of depressed patients was (42.98 ± 2.55) years, and the average age of healthy people was (41.71 ± 2.6) years. The scales used to assess outcomes are Hamilton-rating scale for Depression(4 articles), Montgomery-Asberg Depression Rating Scale(3 articles), and Mini-Internatioal Neuropsychiatric Interview (1 articles). The meta-analysis revealed significantly higher levels of mtDNA in circulating blood samples and skin fibroblasts of individuals with depression in comparison to healthy controls [standardized mean difference(SMD) = 0.42, 95% confidence intervals(CI): 0.16, 0.67]. CONCLUSIONS: Our study concludes that there is a significant (p < 0.05) increase in mtDNA levels in serum, plasma, and cerebrospinal fluid in individuals with depression. These findings suggest that mtDNA could serve as a potential biomarker for diagnosing depression. REGISTRATION NUMBER: PROSPERO CRD42023414285.

Lactobacillus cell envelope-coated nanoparticles for antibiotic delivery against cariogenic biofilm and dental caries.

BACKGROUND: Due to their prevalence, dental caries ranks first among all diseases endangering human health. Therefore, the prevention of caries is of great significance, as caries have become a serious public health problem worldwide. Currently, using nanoscale drug delivery systems to prevent caries has received increased attention. However, the preventive efficacy of these systems is substantially limited due to the unique physiological structure of cariogenic biofilms. Thus, novel strategies aimed at combating cariogenic biofilms to improve preventive efficiency against caries are meaningful and very necessary. Herein, inspired by cell membrane coating technology and Lactobacillus strains, we coated triclosan (TCS)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TCS@PLGA-NPs) with an envelope of Lactobacillus (LA/TCS@PLGA-NPs) and investigated their potential as a nanoparticle delivery system against cariogenic biofilms and dental caries. RESULTS: LA/TCS@PLGA-NPs were successfully prepared with favorable properties, including a coated envelope, controllable size, negative charge, sustained drug-release kinetics and so on. The LA/TCS@PLGA-NPs inherited native properties from the source cell surface, thus the LA/TCS@PLGA-NPs adhered to S. mutans, integrated into the S. mutans biofilm, and interfered with the biofilm formation of S. mutans. The nanoparticles significantly inhibited the activity, biomass and virulence gene expression of S. mutans biofilms in vitro. Additionally, LA/TCS@PLGA-NPs exhibited a long-lasting inhibitory effect on the progression of caries in vivo. The safety performance of the nanoparticles is also favorable. CONCLUSIONS: Our findings reveal that the antibiofilm effect of LA/TCS@PLGA-NPs relies not only on the inheritance of native properties from the Lactobacillus cell surface but also on the inhibitory effect on the activity, biomass and virulence of S. mutans biofilms. Thus, these nanoparticles could be considered feasible candidates for a new class of effective drug delivery systems for the prevention of caries. Furthermore, this work provides new insights into cell membrane coating technology and presents a novel strategy to combat bacterial biofilms and associated infections.

[Expert consensus on clinical application of Compound Congrong Yizhi Capsules in treatment of vascular dementia].

Compound Congrong Yizhi Capsules is widely used in clinic for the long-term treatment and synergistic treatment of vascular cognitive impairment. After years of clinical observation, it has an obvious curative effect on the treatement of vascular cognitive impairment and has been recommended by multiple guidelines, consensuses, and series. This consensus was formulated for the treatment of vascular dementia. On the basis of summarizing the application experience of clinicians, and combined with the existing evidence-based evidence, 11 recommendations/consensus recommendations were finally reached through the nominal group method. The indications, usage and dosage, course of treatment, medication time, concomitant medication, and precautions of Congrong Yizhi Capsules in the treatment of vascular dementia were proposed, and the safety of the clinical application was described. This consensus is applicable to the use of Compound Congrong Yizhi Capsules in the treatment of patients with vascular dementia, and can be used by clinicians from the departments of encephalopathy(neurology), geriatrics, and traditional Chinese medicine in general hospitals. This consensus has been approved by China Association of Chinese Medicine, with the number of GS/CACM 298-2022.

Public Mental Health in Post-COVID-19 Era.

Transmission of the 2019 novel coronavirus (COVID-19) has now rapidly spread around the world, which has alarming implications for individuals and communities, in particular for public mental health. Significant progress has been made in the prevention and control of the COVID-19 pandemic in China, but the psychological crisis caused by the epidemic is still not over and may continue to exist. The public mental health in the post-COVID-19 era should not be ignored. This article provides early warning for the public's mental health in the post-COVID-19 era by listing the characteristics and duration of the public mental health crisis following the SARS outbreak. In addition, based on the current situation, specific methods and measures are proposed in order to provide effective reference for the prevention and control of psychological crisis caused by the COVID-19 epidemic.

[Systematic review and Meta-analysis of efficacy and safety of Compound Congrong Yizhi Capsules on vascular cognitive impairment].

To analyze the efficacy and safety of Compound Congrong Yizhi Capsules in treatment of vascular cognitive impairment. Databases, such as CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, ClinicalTrials were electronically retrieved for relevant randomized controlled trials about the effect of Compound Congrong Yizhi Capsules in treatment of vascular cognitive impairment. Two researchers independently screened the literatures and extracted data according to the inclusion criteria, and used the risk of bias assessment tool in the Cochrane evaluation manual for quality assessment. The Cochrane systematic evaluation software RevMan 5.3 was used for data analysis. Totally 12 articles including 1 279 patients were included. The intervention measure was Compound Congrong Yizhi Capsules used alone or combined with Western medicine, and the control measure was the Western medicine alone or the blank control. According to the findings, for patients of vascular cognitive impairment no dementia, Compound Congrong Yizhi Capsules was better than the blank control in improving MoCA scale score and serum NO levels and reducing serum ET-1 levels. For vascular dementia patients, Compound Congrong Yizhi Capsules combined with Western medicine was better than Western medicine alone in improving MMSE and MoCA scale score. Five studies reported adverse events, but no significant adverse reaction was found. In conclusion, Compound Congrong Yizhi Capsules alone could alliviate early cognitive impairment in patients of vascular cognitive impairment no dementia; Compound Congrong Yizhi Capsules combined with Western medicine is superior to Western medicine alone in improving cognitive impairment. No obvious adverse reaction was found. Compound Congrong Yizhi Capsules can be recommended in clinical use. This conclusion needs to be further confirmed in high-quality clinical trials in the future.

[Expert consensus on Injection of Breviscapine in clinical practice].

With the advancement of the aging process, cerebrovascular disease has become China's first cause of death. Injection of Breviscapine is a type of traditional Chinese medicine injections published in the Chinese Pharmacopoeia of 2015 Edition and the National Basic Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drug Catalogue, and used to treat ischemic cerebrovascular disease in clinic. In order to further improve clinicians' understanding of the drug and guidance of its rational clinical use, we gave full consideration of clinical research evidences and expert experience, followed the procedures developed based on expert consensus of Chinese Academy of Traditional Chinese Medicine, and then offered recommendations for clinical problems summarized by clinical first-line investigations and evidence-based clinical problems according to internationally accepted evidence grading and recommendation standards, i.e. Grade. As for clinical problems without evidence, we reached through nominal group method, and formed consensus recommendations. Safety issues of Injection of Breviscapine, such as indication, syndrome, dosage, course of treatment, precautions, suggestions and contraindications, were defined to improve clinical efficacy, promote rational drug use and reduce drug risks. This consensus needs to be revised in the future based on emerging clinical issues and evidence-based updates in practical applications.

Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress.

BACKGROUND: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven't been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. MATERIALS: The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR. RESULTS: The results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY. CONCLUSION: The results indicated that XPJY can improve depression and related learning and memory and the effect of XPJY is partly exerted through the cAMP-PKA-CREB-BDNF signaling pathway.

Differentially disrupted functional connectivity of the subregions of the amygdala in Alzheimer's disease.

The amygdala is an important brain area involved in cognitive procession and emotional regulation. Previous studies have typically considered the amygdala as a single structure, which likely masks contribution of individual amygdala subdivisions. Actually, the amygdala is heterogeneous and composed of structurally and functionally distinct nuclei, which may present different connectivity patterns and predict to relevant cognitive deficits in Alzheimer's disease (AD). However, little is known about functional connectivity of amygdala subregions in the resting state in AD subjects. Here, we employed resting-state functional MRI (fMRI) to examine functional connectivity changes of subregions comparing the AD patients with the age-matched control subjects. Thirty-two AD and 38 control subjects were analyzed. We defined three subregions of the amygdala according to probabilistic cytoarchitectonic atlases and mapped the whole-brain resting-state functional connectivity for each subregion: The central medial nucleus (CM) of amygdala exhibited connections with the lentiform nucleus, parahippocampus and lateral temporal gyrus; the lateral basal nucleus (LB) of amygdala functionally connected with the parahippocampus, lateral temporal gyrus, middle occipital gyrus and medial prefrontal cortex; and the superficial nucleus (SF) of amygdala had connection with the parahippocampus, lentiform nucleus, lateral temporal gyrus, insula, middle occipital gyrus, precentral and postcentral gyrus. Comparing with the controls, the AD patients presented disrupted connectivity patterns in the LB of amygdala, which predicted disconnection with the left uncus, right insula, right precentral gyrus, the left superior temporal gyrus and right claustrum. These findings in a large part supported our hypothesis and provided a new insight in understanding the pathophysiological mechanisms of AD.

Exploration of the mechanism of Traditional Chinese Medicine for anxiety and depression in patients with diarrheal irritable bowel syndrome based on network pharmacology and meta-analysis.

Background: The efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy. Methods: By conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM's effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database. Results: Twenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I2 = 0%] Additionally, treatment for depression [SMD = -1.08, 95% CI (-1.30, -0.86), p < 0.00001, I2 = 68%; SDS: SMD = -1.69, 95% CI (-2.48, -0.90), p < 0.0001, I2 = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, -0.91), p < 0.00001, I2 = 89%; SAS: SMD = -1.75, 95% CI (-2.55, -0.95), p < 0.00001, I2 = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), p < 0.00001, I2 = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance. Conclusion: Chinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM's therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.

Diagnostic value of MicroRNAs for depression: A systematic review and meta-analysis.

BACKGROUND: Currently, depression is diagnosed on the basis of neuropsychological examinations and clinical symptoms, and there is no objective diagnostic method. Several studies have explored the application of microRNAs as potential biomarkers diagnostic for depression. This study aims to determine the diagnostic value of microRNAs for depression. METHODS: PubMed, Embase, the Cochrane Library, the Web of Science, Wanfang Database, SINOMED, China Science and Technology Journal Databaseand China National Knowledge Infrastructure were searched up to 11 January 2022. Stata (version 16.0) and RevMan (version 5.3) software were used for meta-analysis. The pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) were calculated; the summary receiver operating characteristic (SROC) curve was plotted, and the area under the curve (AUC) was calculated. Moreover, meta-regression analyses were performed to determine the source of heterogeneity. Deeks' funnel plot test was used to assess publication bias. RESULTS: In total, 677 patients were enrolled, including 364 patients with depression and 313 healthy controls. Meta-analysis results showed that the pooled sensitivity, specificity, and DOR of microRNAs for the diagnosis of depression were 0.82 [95% confidence intervals(CI): 0.76, 0.87], 0.70 (95% CI: 0.62, 0.77), and 11 (95% CI: 6, 20), respectively, and the AUC of the SROC was 0.84 (95% CI: 0.80, 0.87). CONCLUSIONS: MicroRNAs have high sensitivity and specificity in diagnosing depression and are potential diagnostic biomarkers for depression. REGISTRATION NUMBER: PROSPERO CRD42022303616.

Efficacy and safety of the Chinese herbal medicine Xiao Yao San for treating anxiety: a systematic review with meta-analysis and trial sequential analysis.

Introduction: The effectiveness and safety of the Chinese herbal medicine (CHM) Xiao Yao San (XYS) used for treating anxiety disorders are still unknown. Thus, we conducted this systematic review with meta-analysis and trial sequential analysis (TSA) to determine its safety and efficacy. Methods: We searched 12 databases for relevant studies from the inception of each database till 10 August 2023. We selected randomized controlled trials to compare the efficacy and safety of XYS (including XYS only and XYS + anxiolytics) to those of anxiolytics in patients with anxiety. Results: We found 14 trials with 1,256 patients in total that met the requirements for inclusion. We assessed the majority of studies (8 out of 14) as being at high risk of bias; 6 were assessed as having a moderate risk of bias. Three trials compared oral XYS to anxiolytic medication, and 11 trials compared oral XYS plus anxiolytics to anxiolytic treatment alone. The pooled results showed that the efficacy of treatment in the XYS + anxiolytics groups was significantly higher than that of the anxiolytics alone group (RR = 1.19; 95% CI: [1.13, 1.26]; p < 0.00001; I2 = 0) and the adverse event rates in the XYS + anxiolytics groups were significantly lower than those in the anxiolytics alone group (RR = 0.44; 95% CI: [0.28, 0.82]; p = 0.001 < 0.05; I2 = 13). The efficacy of treatment in the XYS alone groups was also significantly higher than that of the anxiolytics alone groups (RR = 5.41; 95% CI: [2.23, 13.11]; p < 0.0001; I2 = 0). However, there was no statistical difference between the adverse events of the XYS alone group and the anxiolytics alone group, although the incidence of adverse events in the XYS alone group was lower than that in the anxiolytics alone group. The results of the TSA confirmed the above findings. Conclusion: The use of XYS combined with anxiolytics for treating anxiety was found to be safe and effective. However, although XYS alone is effective in the treatment of anxiety disorder, more large-scale research is needed to investigate adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=350358, identifier CRD42022350358.

Antidepression of Xingpijieyu formula targets gut microbiota derived from depressive disorder.

OBJECTIVE: This investigation aims to determine the antidepressant role of Xingpijieyu formula (XPJYF) mediated via gut microbiota (GM)-brain axis. METHODS: We collected fecal microbiota from patients with depressive disorder (DD) and cultured microbiota in vitro. Some of microbiota were transplanted into germ-free rats with the intragastric administration of XPJYF grain at the dose of 1.533 g/kg/day. The behaviors were studied by forced swimming test, open field test, sucrose preference test, and body weight. Products of hypothalamus-pituitary-adrenocortical (HPA) axis, neurotransmitter, and serum cytokines were investigated by enzyme linked immunosorbent assay. Glial fibrillary acidic protein (GFAP), a biomarker of astrocyte, was quantified using immunofluorescence. Microbiota culturing in vitro after XPJYF treatment was analyze by 16 s RNA sequencing technology. We used lipopolysaccharide (LPS) to mimic activated rat primary astrocyte in vitro. Brain-derived neurotrophic factor (BDNF), cytokines, and oxidative stress factors were determined by western blotting, and glycometabolism in astrocyte was investigated by 2-deoxy-D-glucose (2-DG) uptake, adenosine triphosphate (ATP), and glucose-1-phosphate (G1P) kits. RESULTS: Microbiota composition during 8 mg/ml of XPJYF (H12-8) for 12 h showed the more consistency. Lactococcus is enriched in DD-derived microbiota composition, and Biffdobacterium and Lactobacillus in H12-8 group. GLUCOSE1PMETAB-PWY and PWY-7328 of which biofunctions were dominantly encoded by Biffdobacterium were the top two of altered pathways. XPJYF improved behaviors and repressed astrocyte activation in depression rats. XPJYF elevated 2-DG uptake, ATP, glucose-1-phosphate, and brain-derived neurotrophic factor (BDNF), and inhibited cytokines and oxidative stress in LPS-induced astrocyte. CONCLUSION: XPJYF treatment targets inflammation, activation, and glycometabolim in astrocyte via gut microbiota modulation, thereby improve animal behaviors, HPA axis dysfunction, and neurotransmitter synthesis in depression rats.

To explore the regulatory effect of Buyang Huanwu Decoction on cerebral infarction based on quantitative proteomics.

Buyang Huanwu Decoction (BYHW) contains chemical components such as ligustrazine, oxypaeoniflora, chlorogenic acid, and others. To explore the neuroprotective effect and potential target protein of BYHW in cerebral infarction (CI). A double-blind, randomized controlled trial was established and patients with CI were divided into the BYHW group (n = 35) and the control group (n = 30). To evaluate the efficacy by TCM syndrome score and clinical indicators, and to explore the changes of serum proteins by proteomics technology, so as to explore the mechanism of BYHW and potential target proteins. The study found that compared with the control group, the TCM syndrome score, including Deficiency of Vital Energy (DVE), Blood Stasis (BS), and NIHSS in the BYHW group decreased significantly (p < 0.05), and the Barthel Index (BI) score was significantly higher. A total of 99 differential regulatory proteins were identified by proteomics, which act on lipids and atherosclerosis, complement and coagulation cascade, and TNF-α signaling pathway. In addition, Elisa verified the results of proteomics and found that BYHW can reduce the neurological impairments focus on IL-1ß, IL-6, TNF-α, MCP-1, MMP-9, and PAI-1. Significance: In this study, quantitative proteomics was used in combination with liquid chromatography-mass spectrometry (LC-MS/MS) to study the therapeutic effect of BYHW on cerebral infarction (CI) and potential changes in serum proteomics. In addition, the public proteomics database was used for bioinformatics analysis, and Elisa experiment verified the results of proteomics, further clarifying the potential protection mechanism of BYHW on CI.

Neuroprotective effect of Astragali Radix on cerebral infarction based on proteomics.

Objective: Astragali Radix (AR, Huangqi in Chinese) has a neuroprotective effect on cerebral infarction (CI). In order to explore the biological basis and therapeutic mechanism of AR in CI, a double-blind randomized controlled trial was established in this study, and proteomics analysis was carried out on serum samples of patients. Methods: The patients were divided into the AR group (n = 35) and the control group (n = 30). The curative effect was evaluated by the traditional Chinese medicine (TCM) syndrome score and clinical indicators, and the serum of the two groups was analyzed by proteomics. Based on bioinformatics analysis methods, the changes in differential proteins between two groups of samples were explored, and the key proteins were validated through enzyme-linked immunosorbent assay (ELISA). Results: The results of this study showed that the scores of deficiency of vital energy (DVE), blood stasis (BS), and NIH Stroke Scale (NIHSS) decreased significantly (p < 0.05), while the scores of the Barthel Index (BI) increased, indicating that AR could significantly improve the symptoms of CI patients. In addition, we found that compared with the control group, AR upregulated 43 proteins and downregulated 20 proteins, especially focusing on anti-atherosclerosis and neuroprotective effects. Moreover, ELISA indicated the levels of IL-6, TNF-α, VCAM-1, MCP-1, and ICAM-1 were significantly decreased in the serum of the AR group (p < 0.05, p < 0.01). Conclusion: This study found that AR can significantly recover the clinical symptoms of CI. Serum proteomics research results show that AR may act on IL-6, TNF-α, VCAM-1, MCP-1, and ICAM-1, and play anti-atherosclerosis and neuroprotective roles. Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT02846207].

Ginsenoside Rb1 protects hippocampal neurons in depressed rats based on mitophagy-regulated astrocytic pyroptosis.

BACKGROUND: Astrocytes play a vital role in offering functional support for neurons, which are related to the pathogenic mechanism of depression. Ginsenoside Rb1 (GRb1) is demonstrated with antidepressant-like activities. PURPOSE: We aimed to investigate whether GRb1 can inhibit mitophagy-mediated astrocytic pyroptosis to protect neurons in depression. STUDY DESIGN: Model rats were subjected to chronic unpredictable mild stress (CUMS) for determining the in vivo antidepressant activity of GRb1. METHODS: The mitophagy-mediated antipyroptosis role of GRb1 was assessed in lipopolysaccharide (LPS) + ATP-stimulated astrocytes. The mechanism by which GRb1 protects synaptic plasticity was investigated using hippocampal neurons incubated in an astrocyte medium. The rat depressive-like behaviors were determined through sucrose preference, forced swimming, and the open-field tests. Escitalopram was used in the anti-depression control of GRb1. Cyclosporin A (CsA), a mitophagy inhibitor, and interleukin (IL)-1ß were used to reverse the role of GRb1 in mitophagy and pyroptosis, respectively. RESULTS: GRb1 inhibited LPS-induced inflammation and activation in the astrocytes and repressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Also, GRb1 repressed LPS + ATP-promoted astrocytic pyroptosis. During GRb1 treatment, the activation of mitophagy with a decrease in ROS was observed in LPS + ATPs-stimulated astrocytes. CsA enhanced GRb1-decreased ROS and promoted astrocytic pyroptosis. The GRb1-treated astrocyte medium suppressed neuron death and increased neuron viability and synaptic density. Escitalopram and GRb1 improved the depressive-like behaviors of the rats. GRb1 activated mitophagy and inhibited astrocytic activation and pyroptosis in rats with depression. It also reduced impairments in synaptic structures and increased synaptic density in depressive-like rats. IL-1ß increased astrocytic pyroptosis and reversed GRb1-enhanced synaptic plasticity in the rats exposed to CUMS. There were no statistical changes in depressive-like behaviors between GRb1 and Escitalopram groups. CONCLUSION: GRb1 modulates mitophagy and the NF-κB pathway to inhibit astrocytic pyroptosis, thereby maintaining neurological homeostasis by repressing inflammation and enhancing synaptic plasticity.

Metronidazole-loaded polydopamine nanomedicine with antioxidant and antibacterial bioactivity for periodontitis.

Aim: This study focused on treating periodontitis with bacterial infection and local over accumulation of reactive oxygen species. Materials & methods: Polydopamine nanoparticles (PDA NPs) were exploited as efficient carriers for encapsulated metronidazole (MNZ). The therapeutic efficacy and biocompatibility of PDA@MNZ NPs were investigated through both in vitro and in vivo studies. Results: The nanodrug PDA@MNZ NPs were successfully fabricated, with well-defined physicochemical characteristics. In vitro, the PDA@MNZ NPs effectively eliminated intracellular reactive oxygen species and inhibited the growth of Porphyromonas gingivalis. Moreover, the PDA@MNZ NPs exhibited synergistic therapy for periodontitisin in vivo. Conclusion: PDA@MNZ NPs were confirmed with exceptional antimicrobial and antioxidant functions, offering a promising avenue for synergistic therapy in periodontitis.

Mental Health and Related Factors of Adolescent Students During Coronavirus Disease 2019 (COVID-19) Pandemic.

OBJECTIVE: Adolescents are at a special stage of physical and mental development, which is a susceptible period for mental disorders. Since the outbreak of coronavirus pneumonia in December 2019, long term stress may have negative effects on the mental health of the adolescents. In the context of the coronavirus disease 2019 (COVID-19), the study was designed to investigate the mental and psychological health of adolescents in China and its possible related factors. METHODS: A cross-sectional study design was adopted using a structured questionnaire which were distributed through the Internet to measure depression, anxiety, life events and stress related factors. Descriptive statistics and multiple regression analyses were conducted to process the data. RESULTS: The final sample comprised 795 adolescents. The total detection rate of depression was 76.48% and the total detection rate of anxiety was 33.08%. ANOVA showed that there were significant differences in depression scores in terms of gender, anxiety scores, history of mental disorders, COVID-19 knowledge reserve, family and social contradictions (p<0.05). And there were significant differences in anxiety scores in terms of gender, depression scores, mental health knowledge reserves, family and social contradictions (p<0.05). Multiple regression analysis showed that anxiety score, health status and COVID-19 knowledge reserve were positively associated with depression score (p<0.01), and history of psychosocial disorders was negatively associated with depression score (p<0.05); depression score, family and social contradictions were significantly positively correlated with anxiety score (p<0.01), and history of mental disorders was significantly negatively correlated with SDS score (p<0.01). CONCLUSION: During the outbreak of COVID-19, adolescent students with better understanding of the pandemic, more complete knowledge of mental health, and better family and social relationship had less impact on their mental health. Therefore, to ensure a sound social support system, elaborate health instruction, and family communication and mutual understanding are conducive to alleviating the psychological stress caused by the epidemic, and it is positive for adolescent students to maintain a good mental health.

Shugan granule contributes to the improvement of depression-like behaviors in chronic restraint stress-stimulated rats by altering gut microbiota.

AIM: The investigation aims to evaluate the potential effect of Shugan Granule (SGKL) on the gut, brain, and behaviors in rats exposed to chronic restraint stress (CRS). METHODS: The fecal microbiota and metabolite changes were studied in rats exposed to CRS and treated with SGKL (0.1 mg/kg/day). Depressive behaviors of these rats were determined through an open-field experiment, forced swimming test, sucrose preference, and weighing. Moreover, LPS-stimulated microglia and CRS-stimulated rats were treated with SGKL to investigate the regulation between SGKL and the PI3K/Akt/pathway, which is inhibited by LY294002, a PI3K inhibitor. RESULTS: (i) SGKL improved the altered behaviors in CRS-stimulated rats; (ii) SGKL ameliorated the CRS-induced neuronal degeneration and tangled nerve fiber and also contributed to the recovery of intestinal barrier injury in these rats; (iii) SGKL inhibited the hippocampus elevations of TNF-α, IL-1ß, and IL-6 in response to CRS modeling; (iv) based on the principal coordinates analysis (PCoA), SGKL altered α-diversity indices and shifted ß-diversity in CRS-stimulated rats; (v) at the genus level, SGKL decreased the CRS-enhanced abundance of Bacteroides; (vi) Butyricimonas and Candidatus Arthromitus were enriched in SGKL-treated rats; (vii) altered gut microbiota and metabolites were correlated with behaviors, inflammation, and PI3K/Akt/mTOR pathway; (viii) SGKL increased the LPS-decreased phosphorylation of the PI3K/Akt/mTOR pathway in microglia and inhibited the LPS-induced microglial activation; (ix) PI3K/Akt/mTOR pathway inactivation reversed the SGKL effects in CRS rats. CONCLUSION: SGKL targets the PI3K/Akt/mTOR pathway by altering gut microbiota and metabolites, which ameliorates altered behavior and inflammation in the hippocampus.