Modern technology-based exploration of mechanism of traditional Chinese medicine in prevention and treatment of gastric cancer

This review comments on the article“To explore the mechanism of Yigong San anti-gastric cancer and immune regulation”.We are interested that the article applied network pharmacology and bioinformatics techniques to elucidate the mechanism of action of Yigong Sang,a traditional Chinese medicine(TCM),in the treatment of gastric cancer(GC).The mechanism of action of Yigong Sang in the treatment of GC has not yet been elucidated because it is composed of multiple Chinese medicines with multiple components and multiple targets.The emergence of network pharmacology and bioinformatics analysis helps explain the mechanism of action of TCM in preventing and treating GC,and provides a possibility for TCM to transform from empirical to evidence-based medicine.This is of great significance for the application of TCM in oncology,new drug development,formula optimization,and the improvement of clinical efficacy.

Use of traditional Chinese medicine bezoars and bezoar-containing preparations in hepatocarcinoma

This manuscript used network pharmacology and experimental verification to analyze the anti-hepatocarcinoma mechanism of action of bezoars in traditional Chinese medicine(TCM),discovering that it can affect the immune cells within the tumor microenvironment and related pathways to produce inhibitory effects in liver cancer.In TCM,bezoars have a unique therapeutic advantage in the prevention and treatment of tumors.They play an anti-tumorigenic role by regulating the immune microenvironment through multi-component,multi-target and multi-pathway mechanisms.With the application of nanotechnology,bezoars and their compound preparations have been developed into anti-cancer drugs with unique therapeutic advantages,providing novel treatment options for tumor patients.

Research progress of data mining in the treatment of hypertension by traditional Chinese medicine

With the gradual development of data mining technology,more and more data mining software emerges as the times require,and the data mining methods are diversified,which provides a strong support in the study of the treatment of hypertension by traditional Chinese medicine.This research systematically introduces the advantages,disadvantages and application examples of data mining software such as SPSS,TCM inheritance support platform,TCM clinical research information sharing system and data mining methods such as cluster analysis,bayesian network,system evaluation.It is expected to enhance the practical application of data mining in the study of prevention,diagnosis and medication rule of TCM treatment of hypertension,and provide reference for the development of new software and new technology.

Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

The research progress of epigenetics and metabolic memory in diabetic kidney disease

Diabetic kidney disease(DKD)is a clinical syndrome that is one of the major causes of end-stage renal disease(ESRD).The pathogenesis of DKD is complex and multifaceted,with most studies indicating its association with genetics,advanced glycosylation end-product deposition,polyol pathway and protein C activation,lipid metabolism abnormalities,microcirculatory dysfunction,oxidative stress,inflammatory factors,and the kallikrein-kinin system.Epigenetics is the science studying gene expression regulation without changes in the DNA sequence.In recent years,increasing evidence has shown that epigenetic mechanisms play a crucial role in the initiation and progression of DKD.For instance,epigenetic modifications such as DNA methylation,histone modifications,and non-coding RNAs can influence the expression of DKD-related genes,thereby regulating the development and progression of DKD.On the other hand,metabolic memory is an important concept in DKD research.Metabolic memory refers to the phenomenon where cells maintain a certain metabolic state even after the disappearance of metabolic stress factors.This state can influence cell function and fate.In DKD,metabolic stress factors such as hyperglycemia can lead to metabolic memory in renal cells,affecting their function and fate,ultimately leading to the development and progression of DKD.Therefore,to further explore the pathogenesis of DKD,research on epigenetics should be strengthened,aiming to provide new ideas and methods for the prevention and treatment of DKD.

The Influence of Academic Self-Efficacy on Learning Engagement in Online Education in China:The Mediating Role of Effort

The shift towards online intelligent learning has become the norm in education and is now a fundamental part of modern educational activities.However,this new model can influence students’learning behavior and lead to changes in their approach to learning.Based on online intelligent learning,we investigated how the academic self-efficacy of nursing students affects their engagement with learning and explored the role of academic attribution as a mediator.Five hundred fifty-three nursing college students from Hebei and Hunan provinces in China participated in the online questionnaire.The results revealed that effort plays a mediating role in the relationship between academic self-efficacy and learning engagement.

Effects of NLRP3 Inflammasome Mediated Pyroptosis on Cardiovascular Diseases and Intervention Mechanism of Chinese Medicine

Activation of the NOD-like receptor protein 3(NLRP3)inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases(CVDs),such as diabetic cardiomyopathy,ischemia/reperfusion injury,myocardial infarction,heart failure and hypertension.Noncoding RNAs(nc RNAs)are important regulatory factors.Many Chinese medicine(CM)compounds,including their effective components,can regulate pyroptosis and exert myocardium-protecting effects.The mechanisms underlying this protection include inhibition of inflammasome protein expression,Toll-like receptor 4–NF-κB signal pathway activation,oxidative stress,endoplasmic reticulum stress(ERS),and mixed lineage kinase 3 expression and the regulation of silent information regulator 1.The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM.Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

Exosomes derived from human umbilical cord mesenchymal stem cells alleviate Parkinson’s disease and neuronal damage through inhibition of microglia

Microglia-mediated inflammatory responses have been shown to play a crucial role in Parkinson’s disease. In addition, exosomes derived from mesenchymal stem cells have shown anti-inflammatory effects in the treatment of a variety of diseases. However, whether they can protect neurons in Parkinson’s disease by inhibiting microglia-mediated inflammatory responses is not yet known. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells and injected into a 6-hydroxydopamine-induced rat model of Parkinson’s disease. We found that the exosomes injected through the tail vein and lateral ventricle were absorbed by dopaminergic neurons and microglia on the affected side of the brain, where they repaired nigral-striatal dopamine system damage and inhibited microglial activation. Furthermore, in an in vitro cell model, pretreating lipopolysaccharide-stimulated BV2 cells with exosomes reduced interleukin-1β and interleukin-18 secretion, prevented the adoption of pyroptosis-associated morphology by BV2 cells, and increased the survival rate of SH-SY5Y cells. Potential targets for treatment with human umbilical cord mesenchymal stem cells and exosomes were further identified by high-throughput microRNA sequencing and protein spectrum sequencing. Our findings suggest that human umbilical cord mesenchymal stem cells and exosomes are a potential treatment for Parkinson’s disease, and that their neuroprotective effects may be mediated by inhibition of excessive microglial proliferation.

Comparison of Sulfur Dioxide Residue in Chinese Me-dicinal Materials by Titration-fluorescence Spectrome-try and Pharmacopoeia Method

With sulphur-fumigated Chinese medicinal materials （Fritillaria thunbergii , Isatis #utigotica , Asparagus cochinchinensis and Poria cocos ） as the test materials, sulfur dioxide or sulfite residue was determined by the method in Chinese Pharmacopoeia （2015 edition） and titration-fluorescence spectrometry, respec- tively. The results showed that there were significant differences in measured value between titration-fluorescence spectrometry and phmmacopoeia method. The t result of titration-fluorescence spectrometry was much closer to the actual content of sulfur dioxide in Chinese medicinal materials. Thus, titration-fluo- rescence spectrometry had higher application value

Exploring the mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells by network pharmacology method and verifying it in vitro

OBJECTIVE To explore the key mechanism of Bazi Bushen capsule(BZBS)in delaying the senescence of mesenchymal stem cells(MSCs)through network pharmacology and in vitro experiments.METHODS Network pharmacology was used to predict the mechanism targets of BZBS in delaying MSCs senescence.A MSCs senescence model induced by D-galactose(D-gal)was used to investigate the effect and mechanism of BZBS on MSCs senescence in vitro.RESULTS Network pharmacology analy⁃sis showed that BZSB could delay MSCs senes⁃cence.The experiment showed that BZBS could significantly improve the survival activity of the aged MSCs.It significantly reduced the positive rate ofβ-galactosidase staining and p16,p21 expression in aged MSCs,enhanced the ability of adipogenic differentiation and osteogenic differentiation,and increased expression of Nanog,OCT4 and SOX2 in senescent MSCs.CONCLU⁃SIONS Network pharmacology and in vitro cell experiments verified that BZBS could delay MSCs senescence.

Effects of Jiawei Danggui Buxuetang on miRNA-155 and SOCS1 in renal tissue of DKD rats

Objective:To observe the effect of Jiawei Danggui Buxuetang on the expression of microRNA-155(miR-155)and cytokine signal transduction inhibitor 1(SOCS1)in renal tissue of rats with diabetic nephropathy(DKD),and to explore the mechanism of Jiawei Danggui Buxuetang in the treatment of DKD.Methods:Firty 6-week-old SPF male SD rats were randomly divided into normal group(CON)and model group.The model group was fed with high-sugar and high-fat diet for 6 weeks,and the DKD rat model was established by intraperitoneal injection of streptozotocin(STZ)(35 mg/kg).Then the rats were randomly divided into model group(MOD),low dose group(DBTL),medium dose group(DBTM),high dose group(DBTH)and irbesartan group(IRB).Each group was given intragastric administration for 20 weeks,during which CON group and MOD group were given the same amount of normal saline.Urine samples were collected after administration,and the ratio of urinary Microalbumin to urinary creatinine(UACR)was analyzed by automatic analyzer.The renal changes in each group were observed by hematoxylin-eosin(HE)staining,Masson pine(Masson)trichromatic staining and PASM staining.The expression of miR-155 and SOCS1mRNA in renal tissue of DKD rats was detected by Real-time PCR,and the expression of SOCS1 was detected by Western blotting.Results:By comparison with CON group,UACR value,MIR-155 mRNA expression and SOCS1 mRNA expression in MOD group increased significantly,while SOCS1 mRNA expression decreased significantly compared with MOD group,UACR decreased significantly in IRB group and DBT group,SOCS1 expression increased significantly in DBTM group,DBTH group and IRB group.The expression of MIR-155 decreased significantly in all treatment groups(P<0.05),and the expression of SOCS1 in DBTM group,DBTH group and IRB group increased significantly(P<0.05).Conclusion:Jiawei Danggui Buxuetang can reduce the expression of miR-155 in high glucose and increase the expression of SOCS1 in renal tissue,so as to significantly reduce renal damage and play a role in renal protection.

LIM1863 is useful to explore collective cancer cell migration,and the group of heterogeneous cells undergoing collective migration behaves like a supracellular unit

Collective cancer cell migration(CCCM)and epithelial-to-mesenchymal transition(EMT)play key roles in metastasis.This study reports that the colorectal carcinoma cell line LIM1863 is useful for the study of CCCM and EMT.Methods:Hematoxylin and eosin staining,scanning electron microscopy,transmission electron microscopy,and western blot analysis were performed.Results:LIM1863 automatically grew as spheroids in suspension and had important typical epithelial properties,including several layers of cells arranged around a central lumen,apical-basal polarity,and types of cell-cell junctions.Treatment with a combination of both TGF beta 1 and TNF alpha induced definite and distinct EMT,a spheroid changing phenotype to form a monolayer high-confluent patch without lumen,without polarity.Spontaneous CCCM occurred in spheroids.Flat EMT cells adhered to the base of a dish,exhibited persistent movement as a cluster of cells,and then shed,resulting in a cluster.All cells from one cluster undergoing CCCM died.Otherwise,all cells undergoing EMT disappeared and almost all cells located in the cell reservoir survived and proliferated.Conclusion:LIM1863 is an excellent cell line to study CCCM and EMT.The group of heterogeneous cells undergoing CCCM behaves like a supracellular unit.

Mechanism of Baihu Renshen decoction on T2DM rats based on mitochondrial autophagy mediated by PINK1/Parkin

Background:This study will be aimed at investigating the effects of Baihu Renshen decoction(BHRS)on type 2 diabetes rats and on macromolecular enzyme 1(PINK1)/E3 ubiquitin protein ligase(Parkin)pathway.Methods:The experiment was divided into four groups:control group,model group,metformin group and BHRS low-dose group and high-dose group.Forty male rats were selected as samples and randomly assigned to at least one test group.Finally,there are 18 rats in each group.Except for the control group,the rats within the different teams got a high-fat diet associate in nursing an intraperitoneal injection of streptozotocin to make a type 2 diabetes mellitus(T2DM)rat model.The organic chemistry and inflammatory indexes of rats in every cluster were analyzed and compared once four weeks of intragastric administration of comparable reagents to review the therapeutic impact of BHRS on T2DM.In addition,we determined the pathological changes of ductal gland tissue of T2DM rats after treatment,and compared the expression of mitochondrial phagocytosis related proteins in ductal gland tissue of rats in each group.Results:FBG,LDL-C,TC,TG,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were elevated in the model group compared to the control group,while HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were decreased(P<0.05 or P<0.01).The expressions of FBG,TC,TG,LDL-C,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were lowered in the BHRS group,while the expressions of HOMA-,HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were(P<0.05 or P<0.01).After therapy with BHRS,hematoxylin-eosin staining showed that the intensity of pancreatic acinar staining increased,and islet cells became clear boundaries that were,regularly arranged,and with reduced vacuoles reduced.Conclusion:BHRS has a clear therapeutic effect on T2DM,which may be achieved by regulating mitochondrial autophagy through the PINK1/Parkin pathway.

Research Progress on Structure and Bioactivity of Longan Polysaccharide

Longan originates from southern China and has high nutritional and health value.Recent phytochemistry and pharmacology studies have shown that polysaccharides are a main bioactive component of longan.Longan polysaccharides possess antioxidant,anti-aging,anti-tumor,immunomodulatory,and other bioactivities.Hot-water extraction,ethanol precipitation,and ultrasonic extraction are generally used to extract water-soluble longan polysaccharides.However,the relationship between the structure and bioactivity of longan polysaccharides remains unclear,requiring further investigation.The aim of this review is to evaluate the current literature focusing on the extraction,purification,structural characterization,and biological activity of longan polysaccharides.We believe that this review would provide a useful bibliography for further innovation and a basis for using longan polysaccharides in functional food.

Tuberculosis Infected T Lymphocyte Spot as a Differential Diagnosis of Pulmonary Tuberculosis and Choriocarcinoma Recurrence: A Case Report and Review of the Literature

Introduction: Choriocarcinoma is an aggressive tumor, whose incidence is 0.18 per 100,000 women between the ages of 15 and 49 years [1]. Although its prognosis has improved with the development of chemotherapy regimens, the mortality rate of patients with brain metastases is reportedly 29.7% [2]. After chemotherapy, most often, the reappearance of masses in pulmonary is considered to be a sign of relapse. Case presentation: The patient was a 32-year-old Asian Chinese female who delivered a dead male infant at 33 weeks gestation. The placenta appeared to be normal. The major presentation was a haemorrhage of the vagina. The patient received combined treatment with systematic multi-agent chemotherapy and whole-brain radiation therapy at the General Hospital of Hebei Province and achieved complete remission. Two years after remission, a chest CT scan revealed a mass in the right lung that had become larger over 6 months. The patient’s serum β-human chorionic gonadotropin (β-HCG) level was normal, and the tuberculosis infected T lymphocyte spot (T-SPOT.TB) tests were positive. The patient was started on anti-tuberculosis therapy, after which the size of her right lung mass decreased. Conclusion: Lung masses after choriocarcinoma require extensive laboratory and imaging exams to exclude recurrence. This case highlights the importance of differential diagnoses of lung masses in patients with choriocarcinomas. Imaging studies, β-HCG and local lesion resection should be employed to rule out choriocarcinoma recurrence.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study

Objective To identify specific Chinese medicines(CMs)that may benefit patients with gastroesophageal reflux disease(GERD),and explore the action mechanism.Methods Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure,China Science and Technology Journal Database,Wanfang Database,and PubMed from October 1,2011 to October 1,2021.Data from all eligible articles were extracted to establish the database of CMs for GERD.Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified.A system pharmacology approach was used to explore the action mechanism of these medicines.Results A total of 278 prescriptions for GERD were analyzed,including 192 CMs.Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination.A total of 32 active ingredients and 66 targets were screened for the treatment of GERD.Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer,fluid shear stress and atherosclerosis,advanced glycation end product(AGE),the receptor for AGE signaling pathway in diabetic complications,bladder cancer,and rheumatoid arthritis.Conclusion Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Quercetin regulates depression-like behavior in CUMS rat models via TLR4/NF-κB signaling

Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.

Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus

Objective Alzheimer’s disease(AD)has become a significant global concern,but effective drugs able to slow down AD progression is still lacked.Electroacupuncture(EA)has been demonstrated to ameliorate cognitive impairment in individuals with AD.However,the underlying mechanisms remains poorly understood.This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD.Methods APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu(BL 23)and Baihui(GV 20).Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus(DRN).Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests.Golgi staining,western blot,and immunostaining were utilized to determine EA-induced neuroprotection.Results EA at Shenshu(BL 23)and Baihui(GV 20)effectively ameliorated learning and memory impairments in APP/PS1 mice.EA attenuated dendritic spine loss,increased the expression levels of PSD95,synaptophysin,and brain-derived neurotrophic factor in hippocampus.Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B.Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory.Conclusion EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN.Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

A dialogue between gut microbiota and network pharmacology

The gastrointestinal system of the human body is home for a large number and rich variety of microbes,including bacteria,viruses,fungi and protozoa,which are collectively known as the gut microbiota(the largest and most intricate“organ”within the body).Till now,the groundbreaking research has emerged elucidating the pivotal role of the gut microbiota in human health and disease.The normal gut microbiota,after long evolution with the host,has formed an interdependent and mutually limited homeostasis system,which can produce beneficial metabolites for preserving intestinal integrity and preventing the onset of leaky gut syndrome along with subsequent immune activation and inflammation.Although the number of gut microbial metabolites is not fully understood,several metabolites(e.g.,short-chain fatty acids and branched-chain amino acids)have been tested to determine positive or negative effects on the development of specific diseases,which may be a new direction for the prevention and treatment of diseases.