Bio-soft matter derived from traditional Chinese medicine:Characterizations of hierarchical structure,assembly mechanism,and beyond

Structural and functional explorations on bio-soft matter such as micelles,vesicles,nanoparticles,aggregates or polymers derived from traditional Chinese medicine(TCM)has emerged as a new topic in the field of TCM.The discovery of such cross-scaled bio-soft matter may provide a unique perspective for unraveling the new effective material basis of TCM as well as developing innovative medicine and biomaterials.Despite the rapid rise of TCM-derived bio-soft matter,their hierarchical structure and assembly mechanism must be unambiguously probed for a further in-depth understanding of their pharmacological activity.In this review,the current emerged TCM-derived bio-soft matter assembled from either small molecules or macromolecules is introduced,and particularly the unambiguous elucidation of their hierarchical structure and assembly mechanism with combined electron microscopic and spectroscopic techniques is depicted.The pros and cons of each technique are also discussed.The future challenges and perspective of TCM-derived bio-soft matter are outlined,particularly the requirement for their precise in situ structural determination is highlighted.

The new era of integrative medicine—the confluence of tradition and modernity

In the context of accelerated globalization and rapid advancements in science and technology,integrative medicine—combining traditional medicine with modern science—is emerging at the forefront of medical research.This article focuses on the current research hotspots and frontiers in integrative medicine.The field of integrative medicine has seen the emergence of numerous new research hotspots and cutting-edge technologies,which reveal the scientific foundations and application potential of traditional medicine from various perspectives.(1)Application of multi-omics technologies:multi-omics technologies,including metabolomics,transcriptomics,proteomics,and genomics,have become essential tools in integrative medicine research.Metabolomics analyzes metabolites within biological systems to elucidate the metabolic pathways and mechanisms of traditional medicines.Recent advancements in high-throughput technologies have enabled more comprehensive and accurate profiling of metabolic changes induced by traditional medicines,facilitating the identification of bioactive compounds and their pathways.Transcriptomics investigates the effects of traditional medicines on gene expression,revealing molecular mechanisms by comparing transcriptome data under different conditions.Innovations in single-cell RNA sequencing have allowed researchers to study the heterogeneity of cellular responses to traditional medicines,uncovering cell-specific therapeutic targets and pathways.

Integrated data mining and network pharmacology to discover a novel traditional Chinese medicine prescription against diabetic retinopathy and reveal its mechanism

Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.

The role of selected medicinal plants from Iranian traditional medicine for the treatment of fatigue in metabolic syndrome

Background:Fatigue is a symptom of metabolic disorders such as metabolic syndrome,which is currently increasing in the world.There is no specific medication for fatigue,but in many cases,such as in metabolic disorders,it can be relieved by treating the underlying causes.Oxidative stress and inflammation are associated with fatigue and metabolic syndrome.Other mechanisms in metabolic syndrome are also involved in causing fatigue.Objective:The aim of this study was to investigate the role of selected medicinal plants from Iranian traditional medicine(ITM)in improving fatigue in patients with metabolic syndrome.Methods:ITM is one of the most ancient systems of medicine.In this article,we first explained fatigue,its types,and treatment from the perspective of ITM and then introduced a list of medicinal plants used in ITM to treat fatigue.Next,we reviewed the biological effects of these plants effective in treating the manifestations of the metabolic syndrome based on a search of electronic databases.Results:They have antioxidant,anti-inflammatory,and anti-diabetic activities.Among them,Matricaria chamomilla L.,Laurus nobilis L.,Origanum majorana L.,Vitex agnus-castus L.,Lawsonia inermis L.,Anethum graveolens L.,and Pistacia terebinthus L.improve the lipid profile and reduce dyslipidemia.Also,the antihypertensive effects of Matricaria chamomilla,Laurus nobilis,and Origanum majorana have been proven.Conclusion:These plants prevent fatigue and disease progression by countering oxidative stress and inflammation and affecting the properties of the metabolic syndrome.

Traditional Chinese medicine for acute mountain sickness prevention: A systematic review and meta-analysis of randomized controlled trials

Objective: To evaluate the efficacy of traditional Chinese medicine(TCM) for preventing acute mountain sickness(AMS).Methods: We included randomized controlled trials(RCTs) which evalueded the effect of TCM for preventing AMS, compared with a placebo, no treatment or acetazolamide. The literature was searched in 6major databases. RevMan 5.4 software was used for the meta-analysis. The relative risk for discrete variables and the mean difference for continuous variables with 95% confidence intervals(CIs) were applied to express the effect size. The risk of bias in the included studies was evaluated using the Cochrane risk assessment tool 2.0(RoB 2.0), and the evidence certainty was assessed using the Grading of Recommendations Assessment and the Development and Evaluation(GRADE) approach.Results: Twenty RCTs involving 3015 participants and 16 TCM patent drugs were included. The overall risk of bias in the majority of studies(15/20) was of some concerns. In terms of the AMS incidence,Rhodiola rosea(R. rosea, Hong Jing Tian) and Ginkgo biloba(G. biloba, Yin Xing Ye) were equivalent to the placebo/no treatment [RR(95% CI): 0.66(0.43-1.01), 0.82(0.63-1.06), respectively]. The AMS incidence in the G. biloba group was higher than that in the acetazolamide group [RR(95% CI): 2.92(1.69-5.06)]. In terms of improving the AMS symptom score on days 1 and 3 in the plateau, R. rosea and G. biloba were superior to the placebo or no treatment [MD(95% CI):-0.98(-1.71,-0.25),-2.05(-3.14,-0.95), respectively]. The other 14 Chinese patent medicines were evaluated in a single trial, and the majority of the results were negative. The subgroup analysis showed that the effect of R. rosea was related to the intervention time, way of ascending, and altitude.Conclusion: R. rosea and G. biloba were effective in improving AMS symptoms but had no effect in reducing the AMS incidence. There was insufficient evidence to support the use of other TCM patent drugs to prevent AMS. More randomized double-blind placebo-controlled trials are warranted to evaluate and screen effective Chinese patent medicines for AMS prevention.

How modern teaching technology affects the transmission of traditional Chinese medicine knowledge: reflections from educators in clinical Chinese pharmaceutical education

Traditional Chinese medicine(TCM)education plays a crucial role in cultivating TCM talents and preserving the profound cultural heritage of the Chinese nation.This paper explores the current situation and problems of TCM education and proposes philosophical reflections on this issue.The analysis shows that the current TCM education faces various challenges,including an unbalanced curriculum,a narrow teaching approach,a lack of practical experience,and an insufficient number of qualified teachers.To enhance the teaching effectiveness and foster a new generation of high-quality Chinese medicine professionals,it is necessary to reform the teaching methods of TCM and integrate the depth of humanities into the teaching process.The paper argues that a philosophical perspective can provide a more comprehensive understanding of TCM education and its role in the development of Chinese medicine.

Research progress of traditional Chinese medicine compound in the treatment of gout based on intestinal flora

Because of the continuous improvement of the quality of life,the population of gout patients is also increasing,which seriously affects the quality of life of patients.Traditional Chinese medicine compound has a long history and remarkable clinical effect in treating gout patients,and has been widely used.Intestinal flora and its metabolites are the focus of current research,which can promote intestinal mucosal barrier,improve immunity and improve metabolism.The regulation of intestinal flora can reduce serum uric acid and inhibit inflammation to fight gouty arthritis.Moreover,the mechanism of intestinal flora is related to the spleen in Chinese medicine theory.Therefore,this study discusses the research mechanism and clinical application of traditional Chinese medicine compound in treating gout by regulating intestinal flora,and provides theoretical basis for the clinical application of traditional Chinese medicine and the expansion of new dosage forms.

Comparative efficacy of traditional Chinese herbal injection for chronic renal failure:A systematic review and network meta-analysis of randomized controlled trials

Objective: To conduct a systematic review and network meta-analysis(NMA) for the comparison of the efficacy and safety of Chinese herbal injection(CHI) combined with Western medicine(WM) and WM monotherapy for chronic renal failure(CRF).Methods: Eight databases were searched from inception to August 30, 2022. Randomized controlled trials(RCTs) regarding the comparison of CHI-WM combination therapy and WM monotherapy were included. Literature search, risk-of-bias assessment, and data extraction were conducted by 2 reviewers independently. NMA was performed by Stata 14.0, R 4.0.4 software, and the latest risk of bias assessment tool 2(RoB 2).Results: A total of 53 RCTs were finally included, involving 4445 participants and 16 CHIs. RoB 2 showed that 2 of these studies had a high risk of bias. Tianqi injection(TQ) + WM was the most effective in reducing serum creatinine(Scr) level. Xingding injection(XD) + WM was the most effective in reducing blood urea nitrogen(BUN) and cystatin C(Cys C) levels. Guhong injection(GH) + WM had the highest endogenous creatinine clearance rate(Ccr). Shuxuetong injection(SXT) + WM was the most effective in improving the clinical effective rate. Danhong injection(DH) + WM resulted in the lowest 24-h urinary protein quantity(24 h-UPQ), while Danshen injection(DS) + WM led to the lowest blood uric acid(UA)level. Shenfu injection(SF) + WM was the most effective in increasing hemoglobin(Hb) level.Conclusion: CHIs-WM combination therapy is more effective than WM monotherapy in treating CRF.Considering all of the indicators, SK + WM may be the optimal treatment option for improving renal function in patients with CRF.

Rheumatic valvular heart disease treated with traditional Chinese medicine:A case report

BACKGROUND Rheumatic heart disease(RHD)is an autoimmune disease that leads to irreversible valve damage and heart failure.Surgery is an effective treatment;however,it is invasive and carries risks,restricting its broad application.Therefore,it is essential to find alternative nonsurgical treatments for RHD.CASE SUMMARY A 57-year-old woman was assessed with cardiac color Doppler ultrasound,left heart function tests,and tissue Doppler imaging evaluation at Zhongshan Hospital of Fudan University.The results showed mild mitral valve stenosis with mild to moderate mitral and aortic regurgitation,confirming a diagnosis of rheumatic valve disease.After her symptoms became severe,with frequent ventricular tachycardia and supraventricular tachycardia>200 beats per minute,her physicians recommended surgery.During a 10-day preoperative waiting period,the patient asked to be treated with traditional Chinese medicine.After 1 week of this treatment,her symptoms improved significantly,including resolution of the ventricular tachycardia,and the surgery was postponed pending further follow-up.At 3-month follow-up,color Doppler ultrasound showed mild mitral valve stenosis with mild mitral and aortic regurgitation.Therefore,it was determined that no surgical treatment was required.CONCLUSION Traditional Chinese medicine treatment effectively relieves symptoms of RHD,particularly mitral valve stenosis and mitral and aortic regurgitation.

Association between metabolic syndrome and body constitution of traditional Chinese medicine:A systematic review and meta-analysis

Background:The constitution theory of traditional Chinese medicine(TCM)states that body constitution and disease are associated;therefore,the identification of body constitution can provide reference for disease prevention and treatment.A series of clinical studies evaluating the association between TCM constitution and metabolic syndrome(MetS)have been conducted in recent years.The aim of this systematic review is to summarize and evaluate the clinical evidence of the relationship between constitution and MetS.Methods:The PubMed,Embase,China National Knowledge Infrastructure(CNKI),Chongqing VIP,and Wanfang Data electronic databases were searched from April 2009 to July 2020.The search terms included“metabolic syndrome,”“constitution,”and“Chinese medicine.”Observational studies evaluating the relationship between body constitution of TCM and MetS were included.The primary outcome included the distribution of constitutional types in the MetS population,and odds ratio(OR)or relative risk(RR)between constitution and MetS.Effect size was expressed as proportion or OR with 95%confidence interval(CI).Methodological quality of included studies was evaluated by the NewcastleeOttawa Scale(NOS)or the American Agency for Healthcare Research and Quality(AHRQ)criteria.Results:Three caseecontrol and 26 cross-sectional studies involving 30435 cases were included.Phlegm-dampness,qi-deficiency,and damp-heat were the main constitution types in patients with MetS,accounting for 29%(22%e39%),18%(13%e24%),and 12%(9%e17%)of the population,respectively;the risk of MetS in people with phlegm-dampness and qi-deficiency constitution was 1.74[1.27,2.38]and 1.29[1.01,1.65]times higher than that in those with other constitutions.There were sex-and age-related differences in the distribution of TCM constitution in patients with MetS.Conclusion:Phlegm-dampness and qi-deficiency were associated with the occurrence of MetS.Welldesigned cohort and caseecontrol studies are needed to provide evidence for the use of TCM to prevent and treat MetS.

Quality assessment of systematic reviews assessing the effects of traditional Chinese exercises in the control of diabetes mellitus

Objective:To assess the quality of systematic reviews assessing the effects of traditional Chinese exercises on controlling blood indices,anthropometric indices,psychological indices,and quality of life in patients with diabetes.Methods:Systematic studies/meta-analyses of intervention with traditional Chinese exercises on diabetes mellitus were searched in the Pub Med,Web of Science,the China National Knowledge Infrastructure Databases(CNKI),Wan Fang Database,and Chinese Scientific Journal Database(VIP).Two researchers independently screened the studies and extracted the data.The methodology and quality of evidence of the included studies were assessed using A Measurement Tool to Assess Systematic Reviews2(AMSTAR-2)and Grading of Recommendations Assessment,Development and Evaluation(GRADE)criteria,respectively.Results:A total of 32 systematic reviews/meta-analyses were included in the present study.Of them,the methodological quality of 4 studies was graded as low,while that of the other 28 was graded as extremely low.The most common quality flaws in key items included a lack of preliminary proposals for systematic reviews,failure to explain the reasons for the inclusion criteria,failure to provide a list of excluded studies and reasons for exclusion,failure to report potential conflicts of interest,and inadequate assessment of publication bias.The quality of evidence for most of the 18 outcomes was subsequently graded as medium or low.Overall,the results of these studies indicated that Tai Chi,health qigong,and other traditional Chinese exercises lowered fasting blood glucose(FBG),2-h postprandial blood glucose(2hPBG),hemoglobin A_(1c)(HbA_(1c)),and body mass index,and relieved anxiety and depression in patients with diabetes.Conclusion:Our findings indicate that the methodological quality of systematic reviews related to traditional Chinese exercises in the diabetic population is generally low,and the quality of evidence is also relatively poor.Therefore,we suggest that the quality of systematic reviews and meta-analyses on traditional Chinese exercises for controlling diabetes mellitus needs to be improved.In the future,researchers should conduct higher-quality clinical studies with reference to the AMSTAR2 checklist and GRADE system.

Serum protein profile of yang-deficiency constitution in traditional Chinese medicine revealed by protein microarray analyses

Background:Based on the theory of traditional Chinese medicine (TCM) and preepidemiological investigation,Professor Qi Wang classified the entire human population into nine constitutions and put forward the theory of 'Nine-Constitution Medicine.' Among these constitutions,the main feature of the yang-deficiency constitution (YADC) is intolerance of the cold,which has been proven to reduce quality of life and confer susceptibility to specific diseases.Previous studies explored the genetic and transcriptional bases of YADC.In this experiment,we explored the potential mechanism of YADC using protein microarray,to deepen our understanding of its biological mechanism.Methods:Subjects identified with a YADC (n =12) or a balance constitution (BC;n =12) in accordance with the Classification and Determination Standards of Constitutions in Traditional Chinese Medicine were selected.Blood was collected to separate serum and protein microarray technology was used to analyze serum protein expression.Results:The clustering of subjects' constitutions based on protein expression profiling largely coincided with the TCM classification.Based on false discovery rate correction (P <.01) and fold change ≥ 5 or ≤ 0.2,a total of 85 proteins differentially expressed in YADC compared with their status in BC were selected,including 64 upregulated and 21 downregulated ones.Enrichment analysis suggested that subjects with YADC are susceptible to endocrine and energy metabolism disorders,as well as decline in immune function.Conclusion:This study revealed that YADC exhibits systematic differences in its protein expression profile.Moreover,we can potentially explain the characteristics of YADC partly via differentially expressed proteins.

Correlation between Tibetan and traditional Chinese medicine body constitutions: A cross-sectional study of Tibetan college students in the Tibet Autonomous Region

Objective:To evaluate the correlation between the body constitution types of Tibetan medicine and traditional Chinese medicine (TCM).Methods:The cluster sampling method was employed to recruit participants from a university in the Tibet Autonomous Region.Tibetan medicine and TCM questionnaires were respectively used to assess the participants' constitution information.Descriptive statistics were applied to analyze the baseline and constitution characteristics of the participants.Two-factor correlation analysis and the paired chi-square test were applied to analyze the correlation between Tibetan and TCM constitution types.Results:Data from 466 Tibetan students were analyzed.The mean scores of the rlung,mkhris pa,and bad kan constitution types in Tibetan medicine were 43.2 (11.1),42.1 (10.1),and 45.0 (8.0),respectively;participants with the three-factor convergence body constitution type accounted for 13.7% of the whole population.Among the TCM constitution types,qi stagnation was the most common (21.5%),followed by the balance type (16.5%);the other constitutions detected were qi deficiency,yin deficiency,and yang deficiency.The rate of consistency for the identification of the three-factor convergence constitution in Tibetan medicine and the balance constitution in TCM was 89.1%,with a Kappa coefficient of 0.57 (P >.05).The rlung constitution in Tibetan medicine was associated with the yin deficiency,yang deficiency,and blood stasis constitutions in TCM.The mkhhris pa constitution in Tibetan medicine was associated with the damp heat and yin deficiency constitutions in TCM.The bad kan constitution in Tibetan medicine was associated with the phlegm dampness,qi deficiency,and yin deficiency constitutions in TCM.Conclusion:There is a correlation between the body constitution types of Tibetan medicine and TCM.The reliability and validity of the Questionnaire for TibetanMedicine Constitution requires improvement,and more studies with larger sample sizes and more varied populations are warranted to verify the correlation between Tibetan medicine and TCM constitutions.

Methodological survey of using Bayesian Network for predicting pharmacology-based bioactivities of Chinese medicines:a scoping review

Background:It seems to be numerous unclear black-box mechanisms of Chinese Medicines(CMs)with multiple bioactivities in the real-world clinical practice.Meanwhile,prior prediction is necessary before the implementation of pharmacodynamics-pharmacokinetics-based researches.With emergent ML techniques for TCM domain,Bayesian Network(BN)has shown its potentials for CM-bioactivity prediction and syndromes identification in Traditional Chinese Medicine(TCM),benefited from many advantages,such as flexibility in addressing,data-driven and probability-based inference under complex uncertainty.Although BN has been extensively used in TCM,the scarcity of researches on refining methodological features of BN-modelling for optimization poses a significant challenge.Our goal is to present methodological overview of BN-modelling for CM-bioactivities prediction towards pharmacology,which tends to acquire a sequence of intimations for boosting in-depth and optimized CM-BN collaboration based on detected gaps.Methods:We performed systematic search of 13 databases from their inception to November 10th 2022 regardless of language written,which excluded unindexed journals and clinical trial registries,using the 3 keywords(CM,Pharmacology,BN).And full-text original researches with the given subject were under consideration.Afterwards,selection of eligible studies,data refinement and inspection were totally conducted by 6 review authors.Results:A total of 7 studies involving 17 BN models were included for synthesis and refinement,based on existing literatures and databases with 2 modelling functions:regression and tagging.There were 3 prediction patterns:property-bioactivity,efficacy-bioactivity and constituent-bioactivity inference,covering 8 feature-utilized efficacies,5 feature-utilized properties and 10 feature-utilized constituents.Thereafter,without an independent validation dataset,established BNs were mostly utilized to predict the root-node probabilities of unknown data.Indeed,incomplete report on modelling samples,directed acyclic graphs,conditional probability tables and algorithms hindered us from gathering information.Conclusion:A spot of studies were found in this work.And current evidence suggested that some breakthroughs should be achieved in CM-BN integration in the future.At last,to our knowledge,we preliminarily proposed certain recommendations and elicited implications for future work.

Structural and functional characteristics of microbiota in oropharynx of sub-healthy children with gastrointestinal heat retention syndrome differentiated by traditional Chinese medicine

Objective:To explore the structural and functional characteristics of microbiota in oropharynx of subhealthy children with gastrointestinal heat retention syndrome(GHRS)differentiated by traditional Chinese medicine,and screen the biometric operational taxonomic units(OTUs)to assist the clinical diagnosis.Methods:We recruited children according to the“GHRS diagnostic scale”,collected their oropharyngeal swabs,and sequenced the 16 SrDNA V4 region.We described the bacterial structure with alpha-indexes,beta-distances,and relative abundances;moreover,we screened the differential genera/OTUs with Wilcoxon rank-sum test,Metagenome Seq analysis,and linear discriminant analysis effect size(LEf Se)analysis,in which biometric OTUs were selected to construct the receiver operating characteristic curve to verify the diagnostic value.The bacterial function was predicted with Kyoto Encyclopedia of Genes and Genomes pathways according to 16S rDNA gene by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.Results:The study population was composed of 10 children with GHRS and 10 healthy control children.GHRS children were more likely to overeat(gluttony,P=.033).Alpha-indexes,such as Sobs,abundancebased coverage estimator,Bootstrap,and Qstat,were significantly higher in the GHRS group,while betadistances did not exhibit any significant intergroup differences.There were 9 differently distributed nonpredominant genera between the groups in Wilcoxon rank-sum test,as well as 13 non-predominant genera in Metagenome Seq analysis and 3 non-predominant OTUs in LEfSe analysis.OTU44 and OTU196 were used to construct the receiver operating characteristic curve,and the area under curve was 0.92.Predicted functions showed that pathways related to oxidative phosphorylation and carbon metabolism were enriched in healthy control samples,while the pathway related to renin secretion was remarkably enriched in GHRS samples.Conclusion:Unique oropharyngeal microbial structure and function were identified in GHRS children.OTU44 and OTU196 were specific OTUs,which could be used as biomarkers of GHRS to assist clinical diagnosis.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

Salivary metabolites are promising noninvasive biomarkers of druginduced liver injury

BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.

Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology,molecular docking,and in vitro experiments

Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.

Mechanism of Wendan decoction in preventing obesity by regulating multiple signal pathway networks based on gene promoter methylation

Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.

Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis

Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological role.Nuclear factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.Its functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been elucidated.Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis.For the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.