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Trace amines are endogenous molecules distributed in the central nervous system and peripheral tissues that resemble common biogenic amines in terms of subcellular localization, chemical structure, and metabolism. Trace amine-associated receptor (TAAR) is a kind of evolutionarily conserved G-protein-coupled receptors in vertebrates, in which TAAR1 is a functional regulator of monoamine transmitters such as dopamine and serotonin. TAAR1 is widely considered as a potential therapeutic target for schizophrenia, depression and drug addiction. Moreover, TAAR1 is also expressed in peripheral tissues. The homeostasis imbalance of trace aminergic system can induce over-activation of peripheral immune system and central immune inflammatory response. TAAR1 modulators are becoming potential emerging drugs for the treatment of immune-related illnesses, because they may play a major role in the activation or modulation of immune response.
Subject(s)
Animals , Humans , Receptors, G-Protein-Coupled/metabolism , Biogenic Amines , Dopamine , Substance-Related DisordersABSTRACT
Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Subject(s)
Animals , Mice , Corticotropin-Releasing Hormone/metabolism , Nucleus Accumbens/metabolism , Receptors, Corticotropin-Releasing Hormone/metabolism , Sleep , Sleep Wake Disorders , Stress, Psychological/complicationsABSTRACT
@#Objective To investigate the effects of Niuhuang (Bovis Calculus, BC) and Shexiang (Moschus) (BC-Moschus) on human hepatocellular carcinoma (HCC) cells SMMC-7721 and a nude mouse model of subcutaneous xenografts, and to explore its anti-HCC mechanism. Methods The BC-Moschus combination was applied to two liver cancer models in vivo and in vitro. SMMC-7721 was divided into the BC-Moschus group and the control group, and different doses (rude drug dosage 0.625, 1.25, 2.5, and 5 mg/mL) of BC-Moschus extract were used for the intervention. The proliferation ability of HCC cells was detected using the Cell Counting Kit-8 (CCK-8) assay, and the migration ability was detected by a wound healing assay. A subcutaneous xenograft model was prepared using nude mice with human HCC. Specific pathogen-free-grade BALB/c nude mice (5-week-old) were randomly divided into the following groups (n = 6 per group): control (0.9% physiological saline 0.2 mL/d), BC-Moschus [BC 45.5 mg/(kg·d)+ Moschus 13 mg/(kg·d)], and cisplatin (DDP, intraperitoneal injection 5 mg/kg per week) groups. All groups were administered for 14 d. The volume and mass of the subcutaneous xenografts in nude mice were observed. The expression levels of phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, apoptosis-associated factor p70 S6 Kinase (S6K), Bax, Bcl-2, caspase-3, and caspase-9 in nude mice subcutaneous xenografts were measured by real-time quantitative PCR (RT-qPCR) and Western blot. Terminal Deoxynucleotidy Transferase-Mediated dUTP Nick-End Labeling (TUNEL) was used for quantitative analysis of apoptotic cells. Results The CCK-8 assay demonstrated that the BC-Moschus combination inhibited HCC cell proliferation in a superior manner to the use of BC and Moschus alone, and the inhibition effect was dose- and time-dependent (P < 0.01). The wound healing assay showed that the BC-Moschus combination inhibited HCC cell migration (P < 0.01). In the subcutaneous xenograft model of nude mice with human HCC, we found that the tumor volume and weight of the BC-Moschus group were lower than those of the control group (P < 0.01). The levels of the PI3K/AKT/mTOR signaling pathway and S6K protein in the BC-Moschus and DDP groups were significantly decreased (P < 0.01). The expression level of the anti-apoptotic gene Bcl-2 was downregulated (P < 0.05), and the expression of the pro-apoptotic gene Bax and apoptosis-related factors caspase-3 and caspase-9 were significantly upregulated (P < 0.01). The TUNEL assays further confirmed that the combination of the BC-Moschuas could promote HCC (P < 0.01). Conclusion The BC-Moschus combination inhibited the proliferation and migration ability of HCC cells SMMC-7721 and effectively inhibited the growth of subcutaneous xenografts in nude mice. The mechanism may be closely related to the downregulation of the PI3K/AKT/mTOR pathway, regulation of apoptosis-related protein caspase-3, caspase-9, Bcl-2, and Bax expression, and promotion of apoptosis.
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Objective:To explore the effects of low-calorie diet intervention and aerobic exercise intervention on insulin levels and body composition in obese patients with type 2 diabetes.Methods:A total of 300 obese patients with early type 2 diabetes who were diagnosed and treated in the Department of Endocrinology, Xuanwu Hospital of Capital Medical University from July 2016 to July 2019 were selected as the research objects. According to the random sampling method, they were divided into a control group and an observation group with 150 cases each. Calorie diet intervention was given to control group, while the observation group was given low-calorie diet intervention and concentrated aerobic exercise intervention. Observation and evaluation of fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), body fat percentage, body weight, triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were conducted.Results:After 4 weeks of intervention, FBG, FINS, HOMA-IR, BMI, body fat percentage, body mass, TG, TC, HDL-C, LDL-C indicators of the observation group were (6.15±0.92) mmol/L and (14.12±1.11) mU/L, 2.67±0.32, (25.01±1.75) kg/m 2, (27.45±1.92)%, (70.01±3.56) kg, (3.01±0.30) mmol/L, (5.25±0.88) mmol/L, (2.25 ±0.42) mmol/L, (3.15±0.41) mmol/L. The control group were (8.18±1.28) mmol/L, (16.78±1.85) mU/L, 3.78±0.78, (27.36±2.45) kg/m 2, (29.78±2.39)%, (72.98±5.62) kg, (3.49±0.52) mmol/L, (6.23±1.08) mmol/L, (1.88±0.30) mmol/L, (3.98±0.89)mmol/L. The difference between the two groups was statistically significant ( t values were 5.47-16.13, all P<0.05). After 8 weeks of intervention, FBG, FINS, HOMA-IR, BMI, body fat percentage, body mass, TG, TC, HDL-C, LDL-C indicators of the observation were (5.06±0.45) mmol/L, (12.78±0.69) mU/L, 2.01±0.12, (23.25±1.18) kg/m 2, (25.05±1.19)%, (66.02±2.45) kg, (2.21±0.12) mmol/L, (4.03±0.41) mmol/L, (3.08 ±0.72) mmol/L, (2.65±0.15) mmol/L,while in the control group were (6.07±0.88) mmol/L, (14.09±1.05) mU/L, 2.95±0.45, (26.98±2.08) kg/m2, (27.18±2.06)%, (70.98±4.02) kg, (2.98±0.28) mmol/L, (5.16±0.71) mmol/L, (2.41±0.51) mmol/L, (3.29±0.39) mmol/L. The difference between the two groups was statistically significant ( t values were 5.47-30.96, all P<0.05). Conclusions:Low-calorie diet intervention combined with concentrated aerobic exercise intervention is more conducive to improving patients′ blood sugar and blood lipid levels, as well as reducing body weight.
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Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. Methods Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. Results A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. Conclusion A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.
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Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of cystic echinococcosis (CE), so as to provide insights into the research and development of therapeutic drugs targeting CE. Methods Female Kunming mice at ages of 6 to 8 weeks were randomly assigned into the CE group and the control group. Mice in the CE group were intraperitoneally infected with 2 000 Echinococcus multilocularis protoscoleces, while mice in the control group were injected with the same volume of physiological saline. All mice in both groups were sacrificed after breeding for 350 d, and the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the CE group and the normal liver specimens (the normal group) were sampled from mice in the control group for data independent acquisition (DIA) proteomics analysis, and the differentially expressed proteins were subjected to Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results A total of 26 differentially expressed proteins were identified between the lesion group and the normal group and between the peri-lesion group and the normal group, including 8 up-regulated proteins and 18 down-regulated proteins. GO term enrichment analysis showed that these differentially expressed proteins were predominantly enriched in endoplasmic reticulum membrane (biological components), oxidoreductase activity (molecular function) and oxoacid metabolic process and monocarboxylic acid metabolic process (biological processes). KEGG pathway enrichment analysis revealed that the differentially expressed protein Acyl-CoA oxidase 1 (Acox1), which contributed to primary bile acid biosynthesis during the fatty acid oxidation, was involved in peroxisome signaling pathway, and the differentially expressed protein fatty acid binding protein 1 (Fabp1), which contributed to fatty acid transport, was involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Conclusion Differentially expressed proteins are identified in the liver specimens between mouse models of CE and normal mice, and some differentially expressed proteins may serve as potential drug targets for CE.
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OBJECTIVE@#To evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP).@*METHODS@#From January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D'Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated.@*RESULTS@#In total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 μg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462, P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group.@*CONCLUSION@#RARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.
Subject(s)
Aged , Humans , Male , Prostatectomy , Prostatic Neoplasms/surgery , Recovery of Function , Robotics , Treatment Outcome , Urinary Incontinence/etiologyABSTRACT
Objective:To explore the potential targets and mechanism of action of "Clematis Radix et Rhizoma-Trichosanthis Radix" based on network pharmacology. Method:Chinese Medicine System Pharmacology Analysis Platform（TCMSP） was used to screen out active ingredients and corresponding target proteins of Clematis Radix et Rhizoma and Trichosanthis Radix according to oral bioavailability（OB） and drug likeness（DL），cancer disease targets were screened out using GeneCards and OMIM databases，R language software was used to screen out common targets of clematis，trichosanthin and cancer diseases， Cytoscape 3.7.2 software was used to construct a network map of "drug-active ingredient-disease-target"， STRING database was used to draw protein protein interaction（PPI）of common target proteins， R language software was used to perform enrichment analysis of gene ontology（GO） functions and Kyoto encyclopedia of genes and genomes（KEGG） channels on effective targets. Result:A total of 9 effective active ingredients were obtained from Clematis Radix et Rhizoma-Trichosanthis Radix powder pair. A total of 31 target genes were searched，and 814 relevant target genes were searched from cancer diseases. The two kinds of relevant target genes were matched to obtain 9 common target genes，which mainly involved endopeptidase，cysteine-type endopeptidase activities involving in the apoptosis process and cancer necrosis factor receptor superfamily binding and other biological processes，and played a role in the treatment of cancers by regulating apoptosis，measles，hepatitis B，kaposi sarcoma-associated herpesvirus infection，p53，interleukin-17（IL-17），tumor necrosis factor（TNF） and many other pathways. Conclusion:The mechanism of Clematis Radix et Rhizoma-Trichosanthis Radix in the treatment of cancer is preliminarily studied. Clematis Radix et Rhizoma-Trichosanthis Radix has multiple active ingredients and can play a role in treating cancer through multiple targets and multiple pathways.
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Objective:The Meta-analysis was used to systematically evaluate the clinical efficacy of traditional Chinese medicine in treating Late onset hyponatremia （late onset hyponatremia，LOH）. Method:Pubmed，Web of Science，China Knowledge Base Database （CNKI），Wanfang Database （WanFang），Weipu Full-text Periodical Database（VIP），Chinese Biomedical Literature Database （CBM）were retrieved to collect randomized controlled trials of traditional Chinese medicine（TCM） for treatment of LOH. Two researchers independently screened out the literatures， extracted the data， conducted quality assessment by Cochrance bias risk assessment tool，and made Meta-analysis by RevMan 5.3.5 software. Result:Nine eligible documents were finally included. Meta-analysis results showed that the test group was superior to the control group in improving patient's physical fitness/cardiovascular score ［mean deviation（MD）=-1.42，95% CI（-2.39，-0.45），<italic>P</italic>=0.004］ and psycho-psychological score［MD=-0.74，95% CI（-1.26，-0.22），<italic>P</italic>=0.005］，with no statistically significant difference between test group and control group in sexual function score ［MD=-0.68，95% CI（-1.38，-0.03），<italic>P</italic>=0.06］，serum testosterone （TT） concentration［MD=-0.68，95% CI（-1.38，-0.03），<italic>P</italic>=0.06］ and effective rate ［odds ratio（OR）=1.57，95% CI（0.64，3.88），<italic>P</italic>=0.33］. Conclusion:TCM is equivalent to western medicine（testosterone undecanoate）in the treatment of late onset hypogonadism， and better than western medicine in improving patients' physical fitness/cardiovascular score and mental and psychological score.
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Intestinal Peyer's patches （PPs） are local immune tissues of the intestine， which are considered to be the main induction site of the intestinal mucosal immune response， and closely related to immune-related refractory enteropathies， such as ulcerative colitis and Crohn's disease. In recent years， more and more scholars have tried to find a new breakthrough for treating refractory enteropathies with a limited efficacy of clinical interventions through in-depth study of the relationship between PPs and enteropathy. Traditional Chinese medicine （TCM） polysaccharides are considered to be a key component for immune regulation with TCM. Modern studies show that TCM polysaccharides have a significant positive intervention effect on the structure and function of PPs， with good development prospects. Based on this， this paper focuses on PPs and intestinal-related diseases， and systematically introduces the physiological structure of PPs and their drug delivery mechanism， and summarizes the interactions of PPs with effect on immune-related enteropathies， analyze of current studies and prospects of effect of TCM polysaccharides in intervening intestinal disease and its dysfunction by regulating PPs， with the aim to provide new strategies for basic studies and clinical treatment of immune-related refractory enteropathies from the perspective of PPs， and new ideas for basic studies and clinical studies on effect of TCM polysaccharides in intervening enteropathies.
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Rhei Radix et Rhizoma was first recorded in Shennong Ben Cao Jing, with a wide range of pharmacological activities. Autoimmune disease is a kind of disease that damages the tissue structure and function of immune cells and their components due to the impairment of immune tolerance function, including atherosclerosis, multiple sclerosis, gout, rheumatoid arthritis, autoimmune thyroiditis, ulcerative colitis, type 1 diabetes and IgA nephropathy. In recent years, clinical and experimental studies show that Rhei Radix et Rhizoma has potential therapeutic effects on autoimmune diseases. Under the guidance of the theory of traditional Chinese medicine, this paper reviews therapeutic and intervening effects of Rhei Radix et Rhizoma and its main active ingredient anthraquinone on autoimmune diseases. It also puts forward new study directions in view of the existing problems in studies of rhubarb and its anthraquinone, with the aim to provide reference for clinical treatment and scientific studies of effect of Rhei Radix et Rhizomaon autoimmune diseases.
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Animals , Anthraquinones , Autoimmune Diseases/drug therapy , Drugs, Chinese Herbal , Rheum , RhizomeABSTRACT
Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain (especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses, but the underlying molecular mechanisms remain unclear. Here, we investigated how synaptic cell adhesion molecules (e.g., nectin3) are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex (mPFC). Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77. One week later, the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory, simplified dendritic structure, and reduced spine density in the mPFC. Membrane localization of nectin3 was also altered, and was significantly correlated with behavioral performance. Furthermore, knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology. These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.
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BACKGROUND@#Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD.@*METHODS@#This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0-52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study.@*DISCUSSION@#The tACS applied in this trial may have treatment effects on MDD with minimal side effects.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.
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Objective::To explore the pharmacological mechanism of Xiao Xianxiongtang in treating type 2 diabetes mellitus (T2DM) by network pharmacology. Method::The main active ingredients, corresponding targets and target genes of Xiao Xianxiongtang were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) website. Relevant target genes of T2DM were obtained through Gene Cards. The targets of drug active ingredients were mapped to the targets of T2DM, and the intersection targets were obtained as the predictive targets of Xiao Xianxiongtang on T2DM. Cytoscape 3.7.1 software was used to construct the drug active ingredient-intersection target network model and select the key active ingredients. Interactive protein-protein interaction network (PPI) was constructed by STRING website, and key target genes were selected. Gene function analysis (GO) and enrichment analysis based on the Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed on the intersecting targets using DAVID6.8 online tool. Result::Xiao Xianxiongtang had 30 active ingredients, 156 relevant targets, 14 key active ingredients and 18 key target genes on T2DM. GO analysis showed that the biological functions of Xiao Xianxiongtang in the treatment of potential genes of T2DM mainly involved transcriptional regulation, oxidative stress, protein binding and inflammatory reaction. KEGG pathway enrichment showed that the main pathways of Xiao Xianxiongtang in the treatment of T2DM were hypoxia inducible factor-1 (HIF-1) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway and thyroid hormone signaling pathway, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hepatitis B, hepatitis C, tyrosine kinase receptor2(ErbB) signaling pathway, calcium signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway. Conclusion: Xiao Xianxiongtang is a multi-component, multi-target and multi-pathway process in the treatment of T2DM. It plays an important role in the treatment of T2DM by regulating transcription, oxidative stress, protein binding and inflammatory reaction. Conclusion::The mechanism of Xiao Xianxiongtang in treating T2DM may alleviate insulin resistance, increase insulin sensitivity and reduce blood sugar by inhibiting the secretion of inflammatory factors, participating in anti-inflammatory response, reducing oxidative stress, increasing intracellular calcium concentration, blocking glucagon signaling pathway and activating PI3K/Akt pathway.
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Objective::To study the chemical constituents in Baihe Dihuangtang by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). Method::The separation was performed on an ACQUITY UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm) by a gradient elution of acetonitrile-0.1%formic acid solution. The flow rate was 0.4 mL·min-1 and the column temperature was 30 ℃, the injection volume was 5 μL. Electrospray ionization was applied and the data were collected via positive and negative ion modes. By using SCIEX OS 1.4 software, the chemical constituents were analyzed based on the retention time, excimer ion peak and fragment ion peak of the compounds, as well as comparison with reference substances and literature data. Result::A total of 49 chemical constituents in Baihe Dihuangtang were identified, including 5 phenolic glycerides, 15 phenylethanoid glycosides, 11 iridoids, 8 lonones, 3 phenylpropanoids, 2 nucleosides, 1 organic acid, and 4 other compounds. Among them, phenolic glycerides belonged to Lilii Bulbus, and other components mainly belonged to Rehmanniae Radix. Four chemical constituents (acteoside, isoacteoside, ferulic acid and caffeic acid) were identified by comparison of reference substances. Conclusion::The established detection method can quickly and accurately analyze the chemical constituents of Baihe Dihuangtang. The information of chemical constituents in Baihe Dihuangtang is comprehensively expounded. The study establishes a foundation for the research of quality control, material foundation of efficacy and the development of compound preparations of Baihe Dihuangtang.
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BACKGROUND@#Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.@*METHODS@#Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate.@*RESULTS@#Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs. 631.33 ± 34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs. 723.54 ± 39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs. 89.39 ± 12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P < 0.001).@*CONCLUSION@#Early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the NAc.
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BACKGROUND@#Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.@*METHODS@#Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV)- and calretinin (CR)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala).@*RESULTS@#Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs. 43.11 ± 2.85%, t(22) = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs. 33.14 ± 5.95 s, t(25) = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV, not CR, inter-neuron density in the mPFC (F(1, 39) = 19.30, P 10.09, all P < 0.004), which suggests stress-induced hypoexcitability in these regions.@*CONCLUSIONS@#Chronic stress during adolescence increased depression-like behaviors in aged mice, which may be associated with the E/I imbalance in stress-sensitive brain regions.
ABSTRACT
Background@#Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.@*Methods@#Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)- and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala).@*Results@#Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs. 43.11 ± 2.85%, t(22) = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs. 33.14 ± 5.95 s, t(25) = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV+, not CR+, inter-neuron density in the mPFC (F(1, 39) = 19.30, P < 0.001), and hippocampus (F(1, 42) = 5.823, P = 0.020) and altered the CR+, not PV+, inter-neuron density in the amygdala (F(1, 28) = 23.16, P < 0.001). The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09, all P < 0.004), which suggests stress-induced hypoexcitability in these regions.@*Conclusions@#Chronic stress during adolescence increased depression-like behaviors in aged mice, which may be associated with the E/I imbalance in stress-sensitive brain regions.
ABSTRACT
Background@#Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.@*Methods@#Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate.@*Results@#Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs. 631.33 ± 34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs. 723.54 ± 39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs. 89.39 ± 12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P < 0.001).@*Conclusion@#Early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the NAc.
ABSTRACT
Objective:To establish the HPLC fingerprint test method for the medicinal materials, decoction pieces and substance benchmarks of Shaoyao Gancaotang for investigating the quality transmitting of substance group in preparation process of the medicinal materials-decoction pieces-substance benchmarks, then to evaluate the scientificity and rationality of preparation process of substance benchmarks of Shaoyao Gancaotang by combining with yields of dry extract, transfer rates of effective components and other indexes. Method:Substance benchmarks of Shaoyao Gancaotang was prepared according to the method recorded in ancient medical books, fingerprints of 15 batches of medicinal materials, decoction pieces and substance benchmarks were detected by HPLC, and the contents of effective ingredients were determined. At the same time, the correlation analysis of quality transmitting of substance group during the preparation of substance benchmarks was carried out by combining the yields of dry extract and transfer rates of effective components. Result:The established HPLC fingerprint method has good precision, repeatability and stability, it can be used for the simultaneous determination of fingerprint of medicinal materials, decoction pieces and substance benchmarks. In the fingerprint of substance benchmarks, 16 common peaks were determined by taking liquiritin as the reference peak, of which 6 chromatographic peaks belong to Paeoniae Radix Alba and 11 chromatographic peaks belong to Glycyrrhizae Radix et Rhizoma, 7 major chromatographic peaks were identified. The similarities of fingerprints of 15 batches of medicinal materials, decoction pieces and substance benchmarks of Shaoyao Gancaotang were good by comparing with their respective reference fingerprints(≥ 0.90), the average dry extract rate of 15 batches of substance benchmarks was 24.81%, and no discrete data were found; the average transfer rates of paeoniflorin, liquiritin and glycyrrhizic acid from decoction pieces to substance benchmarks were 79.68%, 63.70% and 51.20%, respectively, and no discrete data were found. Conclusion:In this paper, a scientific and reasonable method for evaluating the process of substance benchmarks of Shaoyao Gancaotang is established by means of the fingerprint method controlled by the whole substance group, the research idea of quality transmitting of substance group in the preparation process, and the evaluation of technical and economic indicators. It can be used as a reference for the evaluation and research of material benchmarks in other famous classical formulas.