High-throughput RNA sequencing reveals the anti-inflammatory mechanism of baicalin on Propionibacterium acnes-induced acne in rabbits

Objective:Propionibacterium acnes(P.acnes)plays an important role in the development of acne,an inflammatory skin disease with a high-incidence.In this study,we used high-throughput RNA sequencing(RNA-seq)to reveal the anti-inflammatory mechanism of baicalin on P.acnes-induced acne in rabbits.Methods:The Kligman method was used to induce acne in the ears of New Zealand rabbits.The effect of baicalin on the acne model was evaluated by the number of acne lesions and hematoxylin and eosin(H&E)staining of acne tissues.Enzyme-linked immunoabsorbent assay was used to measure the protein expression levels of tumor necrosis factor a(TNFA),interleukin-1 b(IL1B),IL6,and IL8 in the serum of rabbits.RNA-seq was performed to investigate the mechanism of anti-inflammatory activities of baicalin on acne.Immunohistochemical analysis and Western blot were used to validate the expression levels of related proteins in acne tissues.Results:Baicalin treatment significantly reduced the number of acne lesions and lesions of the ear as well as levels of serum inflammatory cytokines.RNA-seq data showed that baicalin treatment globally suppressed inflammation,especially the TNF signaling pathway and Staphylococcus aureus infection pathway,in the rabbit acne model.Conclusion: Baicalin effectively ameliorates P. acnes-induced acne in rabbits by suppressingthe inflammatory response in rabbits.

Fecal-associated microbiome differences between traditional Chinese medicine qi-deficiency and balanced constitutions

Objective:To explore the structural and functional characteristics of the fecal-associated microbiome(FAM)in a traditional Chinese medicine(TCM)qi-deficiency constitution(QDC)by comparing with balanced constitution(BC)and screen the related biomarkers.Methods:In this cross-sectional study,the TCM constitutions of subjects were determined based on published the Classification and Determination of constitution in TCM and further confirmed by a TCM clinician.Clinical characteristics were recorded,and fecal samples were collected for 16S rDNA sequencing using the Illumina Miseq platform.The FAM structure was described using alpha-diversity indexes,beta-diversity indexes,and the relative abundances of the dominant taxa.Differences in the FAM distribution and function were analyzed with a Wilcoxon rank-sum test,MetagenomeSeq,and LEfSe analysis,after which a receiver operating characteristic curve based on the specific operational taxonomic units(OTUs)was constructed to calculate the area under the curve.Results:Our study population was composed of 22 BCs and 9 QDCs.There were no significant differences between the two groups in the distribution of clinical characteristics or alpha-diversity indexes,except for the sweets preference and blood glucose level.In principal coordinate analysis and partial least squares discriminant analysis,the bacterial communities in the BC group samples and QDC group samples clustered separately.Notably,there were 214 OTUs significantly distributed between groups in the MetagenomeSeq analysis,200 OTUs identified by the Wilcoxon rank-sum test,and 6 OTUs found by the LEfSe analysis.Predicted function analysis revealed that six metabolic pathways were distinctly distributed between the two groups.The area under the curve for the receiver operating characteristic curve based on the four specific OTUs was 0.88.Conclusion:Unique FAM structural and related functional characteristics are displayed in individuals with a QDC,and four specific OTUs could be used as QDC biomarkers to assist in clinical diagnosis.

Serum protein profiles suggest a possible link between qi deficiency constitution and Pi-qi-deficiency syndrome of chronic superficial gastritis

Objective:To identify potential serum protein candidates involved in linking the traditional Chinese medicine(TCM)-defined qi deficiency constitution(QDC)to Pi-qi-deficiency syndrome(PQDS)of chronic superficial gastritis(CSG).Methods:Using participants with the TCM-defined balanced constitution as a control population,labelfree quantitative proteomics was adopted to identify differentially expressed proteins(DEPs)in serum samples from two case populations:case population 1(participants with QDC)and case population 2(patients with PQDS of CSG).The DEPs discovered in both case populations were analyzed to identify common DEPs as potential candidates for proteins involved in the link between QDC and PQDS.Based on Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)and Gene Ontology(GO)enrichment analysis and analysis of proteineprotein interaction networks,we evaluated the possible functions of these potential serum candidates.Results:We discovered 24 and 28 proteins that were differentially expressed in case populations 1 and 2,respectively,compared with the control population.Hierarchical clustering analysis showed that the expression profile of DEPs of individuals from the same population clustered well,while those from different populations were segregated.Furthermore,GO analysis revealed the 10 DEPs that were common to both case populations to be mainly associated with negative regulation of cellular metabolic and immune system processes while KEGG analysis indicated these proteins to be associated with complement and coagulation cascades and peroxisome proliferator-activated receptor signaling.Notably,serum levels of C4b-binding protein beta chain,glycosylphosphatidylinositol-specific phospholipase D1 and MS-F1 light chain variable region proteins were notably higher in the two case populations compared with the control,particularly in the case of CSG with PQDS.Conclusion:The results presented here provide new insights into the molecular mechanisms underlying development of PQDS of CSG from QDC,and suggest candidate serum biomarkers for future application in integrative medicine.

Use of traditional Chinese medicine in the treatment of immune-related adverse events of cancer immunotherapy

Immune checkpoint inhibitors(ICPI)have shown considerable promise in the treatment of tumors.However,immune-related adverse events(irAEs)caused by ICPI have been reported in nearly every organ system.Whilst this represents a new challenge in the field of cancer treatment,traditional Chinese medicine(TCM)provides benefits in the treatment of irAEs.This article reviews the studies of the treatment of immune-related gastrointestinal diseases and dermatosis with TCM and introduces the collaborative efforts between China and France in the implementation of TCM for the treatment of irAEs.

Traditional medicine is the valuable resource for global health

The dramatic changes brought about by the Coronavirus Disease 2019(COVID-19)pandemic have prompted us to reassess the current global healthcare system.As we seek to identify solutions and formulate a vaccine,it is also an opportune time to consider resources that are already accessible,namely traditional medicine with a long history in dealing with contagious diseases.In this respect,Chinese medicine,with its millennia-old un-interrupted history of country-wide practice offers valuable tools.

Screening for blood leukocyte microRNA biomarkers responsible for association between qi deficiency constitution and Pi-qi-deficiency syndrome of chronic superficial gastritis

Objective:To screen for blood leukocyte microRNA(miRNA)biomarkers responsible for the association between the traditional Chinese medicine(TCM)qi deficiency constitution(QDC)and the Pi-qi-deficiency syndrome(PQDS)of chronic superficial gastritis(CSG).Methods:Peripheral blood leukocytes were separated from people of two TCM constitutions(balance and qi deficiency)and from CSG patients with PQDS.Total RNA was isolated from the leukocytes and subjected to subsequent high-throughput miRNA sequencing to identify the miRNAs that are specifically and highly expressed in persons of QDC and CSG patients with PQDS.In addition,the target genes of the associated miRNAs were predicted.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway-based enrichment analyses of these target genes were performed to further evaluate the associated miRNA candidates as potential biomarkers responsible for the association between QDC and PQDS of CSG.Results:Compared with the control group with a balance constitution(P<.05,fold change>1.5 or<0.5),31 and 38 differentially expressed miRNAs were found in persons of QDC and CSG patients with PQDS,respectively.In particular,hsa-miR-145-5p and hsa-miR-146a-3p were highly expressed in both the persons of QDC and CSG patients with PQDS.GO analysis of the target genes of the two common miRNAs showed that they were mainly associated with functions related to synthesis and metabolism,such as cellular nitrogen compound metabolic processes,biosynthetic processes,cellular protein modification processes,and cellular component assembly.KEGG analysis identified the common pathways enriched among the target genes,including the Hippo signaling pathway and the transcriptional misregulation pathway.The common target genes of the two miRNAs seemed to be associated with the spliceosome pathway and the RNA degradation pathway.Conclusion:Hsa-miR-145-5p and hsa-miR-146a-3p may serve as candidate biomarkers responsible for the association between QDC and PQDS of CSG.

Celastrol alleviates arthritis by modulating the inflammatory activities of neutrophils

Objective:Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA).In this study,we used the adjuvant-induced arthritis murine model to evaluate the efficacy of celastrol on neutrophil-mediated inflammation in RA.Methods:Freund's complete adjuvant-induced arthritis was used as the murine model of RA.Celastrol was intraperitoneally administrated daily after onset of the disease.The joint diameter and inflammatory score were evaluated daily during the treatment period.Myeloperoxidase (MPO) and neutrophil elastase (NE) activities were evaluated by immunohistochemical analyses.Quantitative PCR and enzyme-linked immunoabsorbent assay were used to quantify the expression of cytokines.The expression of apoptosis-related proteins Bcl-2,Bax and caspase-3 were evaluated by western blot.Results:Celastrol suppressed inflammation in joints of arthritic mice and diminished the expression of MPO and NE in the joint tissue.Celastrol significantly inhibited the expression of TNFα and IL-6 induced by LPS in neutrophils in a dose-dependent manner in vitro.Moreover,celastrol induced apoptosis of LPS-stimulated neutrophils by increasing the expression of Bax and cleaved caspase-3 while decreasing Bcl-2 expression.Conclusion:Our findings show that celastrol significantly alleviates murine arthritis by modulating the inflammatory activities of neutrophils.These results indicate that celastrol could serve as an alternative or adjunct modality for the treatment of RA.

The development of traditional Chinese medicine

Similar to other medicines,traditional Chinese medicine(TCM)originated from the need for various practical solutions to treat diseases.It is a knowledge system summarized and condensed by the Chinese nation in the health care practice for thousands of years.TCM continues to serve the health care system.This study summarized the history,health concept,main treatment strategies and methods,current development,and future perspectives of TCM.It may provide a more comprehensive image of the overall TCM system.

Structure and function of the fecal-associated microbiome in qi stagnation constitution

Objective:To clarify the structural and functional characteristics of the gut microbiota in individuals with qi stagnation constitution(QSC)and identify the potential biomarkers related to QSC.Methods:This cross-sectional study involved individuals with QSC and balanced constitution(BC)confirmed by TCM clinicians.The clinical features were recorded,and fecal samples were collected for 16S rDNA sequencing.The structure of the fecal-associated microbiome(FAM)was described by the alpha-diversity indexes,beta-distances,and relative abundances of dominant taxa.The differences in FAM distribution were analyzed by the Wilcoxon rank-sum test,MetagenomeSeq,and LEfSe analysis.The 16S rDNA gene sequences were assigned to the KEGG dataset to predict the functional information of bacterial metabolic pathways by using PICRUSt.Differences in functional pathways between groups were assessed with the Wilcoxon rank-sum test.The ROC curve based on specific operational taxonomic units(OTUs)was constructed,and the AUC was calculated.Results:Twenty-two individuals with BC and 8 with QSC were recruited.Significant differences between the two groups were found in body mass index,health status,and low-density lipoprotein,etc.There was no significant difference in the alpha-diversity index.PCoA showed no evident clustering of bacterial communities according to constitutions.Bacteroidaceae,Lachnospiraceae,Ruminococcaceae,and Prevotellaceae were the four common bacteria with high abundances.Notably,MetagenomeSeq,LEfSe analysis,and the Wilcoxon rank-sum test identified significantly different distributions of 66,42,and 36 OTUs,respectively.Predictive function analysis showed that 13 metabolic pathways were significantly differentially distributed,including those related to fatty acid synthesis.Five specific OTUs were selected as potential biomarkers of a QSC,and the AUC was 0.94.Conclusion:Individuals with QSC have unique FAM structure and related functional characteristics.Five specific OTUs were identified to serve as potentially effective biomarkers related to QSC.

Corrigendum to“High-throughput RNA sequencing reveals the antiinflammatory mechanism of baicalin on Propionibacterium acnesinduced acne in rabbits”[J Trad Chin Med Sci 6(2019)201-210]

The authors regret<In the version of this article initially published,there was an unintended error that the first photo in the first row of Figure 5C was wrongly adopted.The corrected Fig.5C is shown here.We are sorry for the inconvenience caused by this error.

Beginning a long march

The ambition of Beijing University of Chinese Medicine(BUCM)in launching the Journal of Traditional Chinese Medical Sciences(JTCMS),an English version of BUCM’s flagship journal on traditional Chinese medicine(TCM),is to create a bridge between the TCM community and western medicine(WM)communities as well as the non-Chinese public who are unfamiliar with TCM.As the only national institute of higher learning devoted to TCM in China,BUCM must demonstrate the highest academic standards in serving the TCM community with this English language journal,as it has done clinically for more than a half century.It must responsibly carry out the mission of conveying knowledge of TCM and the scientific mechanisms underlying its clinical efficacy to the world.To achieve this goal is truly a long journey for BUCM to embark upon,given that the general public in much of the world outside China and some Asian countries has a long history of skepticism where traditional medicine is concerned.This is particularly true of the WM community,whose members may lack comprehensive information about TCM or simply be die-hard deniers of its value.Regardless of obstacles ahead,the long march to carry out the mission of JTCMS begins here.

Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression,elucidating the curative mechanism of Danzhi Xiaoyao powder

Objective:To investigate the molecular mechanism and identify potential drugs for subthreshold depression(SD),and elucidate the detalied mechanism of Danzhi Xiaoyao powder(DZXY)in SD.Methods:Using RNA-sequencing,we identified differentially expressed genes(DEGs)in leukocytes of SD compared to healthy controls,deciphered their functions and pathways,and identified the hub genes of SD.We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELis platform.The Connectivity Map database was retrieved to screen candidate drugs for SD.Based on network pharmacology,we elucidated the"multi-component,multi-target,and multi-pathway"mechanism of DZXY in the treatment of SD.Results:We identified 1080 DEGs(padj<0.05 and|log2(fold change)l≥1&protein coding)in the leukocytes of patients with SD.These DEGs,including hub genes,were primarily involved in immune and inflammatory response-related processes.Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells.Connectivity Map analysis identified 28 potential drugs for SD treatment,particularly SB-202190 and TWS-119.Constructing the"Direct Compounds-Direct Targets-Pathways"network for DZXY and SD revealed the curative mechanisms of DZXY in SD,primarily including inflammatory response,lipid metabolism,immune response,and other processes.Conclusion:These results provide new insights into the characteristics and functional changes of leukocytes in SD,partially illustrate the pathogenesis of SD,and suggest potential drugs for SD.The curative mechanisms of DZXY in SD are also partially elucidated.

Cardiomyocytes induced from hiPSCs by well-defined compounds have therapeutic potential in heart failure by secreting PDGF-BB

Recent studies have suggested that transplant of hiPS-CMs is a promising approach for treating heart failure.However,the optimally clinical benefits have been hampered by the immature nature of the hiPS-CMs,and the hiPS-CMs-secreted proteins contributing to the repair of cardiomyocytes remain largely unidentified.Here,we established a saponin+compound optimally induced system to generate hiPS-CMs with stable functional attributes in vitro and transplanted in heart failure mice.Our study showed enhanced therapeutic effects of optimally induced hiPS-CMs by attenuating cardiac remodeling and dysfunction,these beneficial effects were concomitant with reduced cardiomyocytes death and increased angiogenesis.Moreover,the optimally induced hiPS-CMs could gathering to the injured heart and secret an abundant PDGF-BB.The reparative effect of the optimally induced hiPS-CMs in the hypoxia-injured HCMs was mimicked by PDGF-BB but inhibited by PDGF-BB neutralizing antibody,which was accompanied by the changed expression of p-PI3K and p-Akt proteins.It is highly possible that the PI3K/Akt pathway is regulated by the PDGF-BB secreted from the compound induced hiPS-CMs to achieve a longer lasting myocardial repair effect compared with the standard induced hiPS-CMs.Taken together,our data strongly implicate that the compound induced hiPS-CMs promote the recovery of injured hearts via paracrine action.In this process,the paracrine factor PDGF-BB derived from the compound induced hiPS-CMs reduces isoproterenol-induced adverse cardiac remodeling,which is associated with improved cardiac function,and these effects are mediated by the PI3K/Akt pathway,suggesting that the optimally induced hiPS-CMs may serve as a new promising cell therapy for clinical applications.

U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3'end processing core factors

In eukaryotic cells,both alternative splicing and alternative polyadenylation(APA)play essential roles in the gene regulation network.U1 small ribonucleoprotein particle(U1 snRNP)is a major component of spliceosome,and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3end processing factors.However,here we show that both knockdown and overexpression of SNRPA,SNRPC,SNRNP70,and SNRPD2,the U1 snRNP proteins,promote the usage of proximal APA sites at the transcriptome level.SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate,which may reduce the repressive effects of PABPN1 on the proximal APA sites.Additionally,SNRNP70 can also promote the proximal APA sites by recruiting CPSF6,suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent.Consequently,these results reveal that,on the contrary to U1 snRNP complex,the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3end processing machinery.