BACKGROUND Gait is influenced by race,age,and diseases type.Reference values for gait are closely related to numerous health outcomes.To gain a comprehensive understanding of gait patterns,particularly in relation to ...BACKGROUND Gait is influenced by race,age,and diseases type.Reference values for gait are closely related to numerous health outcomes.To gain a comprehensive understanding of gait patterns,particularly in relation to race-related pathologies and disorders,it is crucial to establish reference values for gait in daily life considering sex and age.Therefore,our objective was to present sex and age-based reference values for gait in daily life,providing a valuable foundation for further research and clinical applications.AIM To establish reference values for lower extremity joint kinematics and kinetics during gait in asymptomatic adult women and men.METHODS Spatiotemporal,kinematics and kinetics parameters were measured in 171 healthy adults(70 males and 101 females)using the computer-aided soft tissue foot model.Full curve statistical parametric mapping was performed using independent and paired-samples t-tests.RESULTS Compared with females,males required more time(cycle time,double-limb support time,stance time,swing time,and stride time),and the differences were statistically significant.In addition,the step and stride lengths of males were longer.Compared to males,female cadence was faster,and statures-per-second and stride-per-minute were higher.There were no statistical differences in speed and stride width between the two groups.After adjusting for height,it was observed that women walked significantly faster than men,and they also had a higher cadence.However,in terms of step length,stride length,and stride width,both genders exhibited similarities.CONCLUSION We established reference values for gait speed and spatiotemporal gait parameters in Chinese university students.This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.展开更多
Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets ...Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.展开更多
Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the R...Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].展开更多
Current treatment strategies for diabetic retinopathy(DR),an eye condition that can lead to blindness,have mainly focused on proliferative DR,including vitreous injection,retinal photocoagulation,and vitrectomy.Vitreo...Current treatment strategies for diabetic retinopathy(DR),an eye condition that can lead to blindness,have mainly focused on proliferative DR,including vitreous injection,retinal photocoagulation,and vitrectomy.Vitreous injections mainly depend on anti-vascular endothelial growth factor therapy.In this editorial,we comment on the article by Sun et al.We focus specifically on the mechanisms of the protective effect of genipin on the retina.Genipin is a gardenia extract used in traditional Chinese medicine(TCM).In their study,the authors suggest that controlling advanced glycosylation by the intraocular injection of genipin may be a strategy for preventing retinopathy.The innovative use of a Chinese medicine extract injected into the eye to achieve a curative effect has attracted our attention.Although TCM is effective in treating DR,the topical application of DR,especially intraocular injections,is not yet feasible.Herein,we present a brief analysis of effective Chinese medicines for the treatment of DR.The effectiveness of local injections of TCM applied directly into the eyes holds promise as an effective treatment approach for DR.展开更多
The article focuses on the dissemination and development of Chinese medicine in Pakistan.Religious records show that Chinese medicine was introduced to Pakistan as early as 1,400 years ago,while Hijama(Chinese cupping...The article focuses on the dissemination and development of Chinese medicine in Pakistan.Religious records show that Chinese medicine was introduced to Pakistan as early as 1,400 years ago,while Hijama(Chinese cupping)was used by Prophet Hazrat Muhammad to cure different types of diseases.Exchanges and cooperations between China and Pakistan continue to the present day.Acupuncture and moxibustion therapy,cupping therapy and herbal medicine are practiced with significant merits in today’s Pakistan.In the future,with the proposal of the Belt and Road Initiative and the landmark project of China-Pakistan Economic Corridor,Chinese medicine can be strengthened through cooperations at the herbal medicine trade level,the research and development level,the educational level,and the social association level.展开更多
Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focus...Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.展开更多
In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands ...In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.展开更多
Rectus abdominis diastasis is a common condition in postpartum women,causing back pain,and in severe cases,it can result in abdominal wall hernias and downward migration of abdominal organs.At present,there is no clea...Rectus abdominis diastasis is a common condition in postpartum women,causing back pain,and in severe cases,it can result in abdominal wall hernias and downward migration of abdominal organs.At present,there is no clearly established optimal non-surgical treatment for rectus abdominis diastasis,but traditional Chinese medicine(TCM)nursing techniques have proven to be an effective intervention for postpartum rectus abdominis separation.This paper comprehensively analyzes the TCM nursing technology as an intervention for postpartum rectus abdominis separation,discusses the shortcomings and prospects of TCM nursing technology,and provides references for further exploring and optimizing the intervention program for postpartum rectus abdominis separation.展开更多
Traditional Chinese medicine(TCM)is actually a comprehensive medical system that encompasses not only medicine but also philosophy and art,forming a distinct contrast to modern medicine based on molecules[1].Compared ...Traditional Chinese medicine(TCM)is actually a comprehensive medical system that encompasses not only medicine but also philosophy and art,forming a distinct contrast to modern medicine based on molecules[1].Compared to modern medicine,TCM places more emphasis on a holistic approach.In clinical practice,many diseases have shown significant therapeutic efficacy with TCM treatments.Taking the example of the kidney,a study involving 29 randomized controlled trials with 1982 patients conducted by Shan et al.展开更多
Objective This study aims to evaluate the association between lower grip strength and mortality hazard.Methods We selected 10,280 adults aged 45 to 96 years old from the China Health and Retirement Longitudinal Study ...Objective This study aims to evaluate the association between lower grip strength and mortality hazard.Methods We selected 10,280 adults aged 45 to 96 years old from the China Health and Retirement Longitudinal Study and used multivariate Cox proportional hazard models to assess the association of grip strength with mortality hazard.In addition,we explored the possibility of a nonlinear relationship using a 4-knot restricted spline regression.Results We found that elevated grip strength was associated with lower mortality up to a certain threshold.The baseline quartile values of grip strength were 30,37,and 44 kg for males and 25,30,and35 kg for females.After adjusting for confounders,with category 1 as the reference group,the adjusted HRs were 0.58(0.42-0.79)in males and 0.70(0.48-0.99)in females(category 4).We also found a linear association between grip strength values and all-cause death risk(males,P=0.274;females,P=0.883)using restricted spline regression.For males with a grip strength<37 kg and females with a grip strength<30 kg,grip strength and death were negatively associated.Conclusion Grip strength below a sex-specific threshold is inversely associated with mortality hazard among middle-aged and older Chinese adults with chronic diseases.展开更多
Background:To investigate the clinical medication approach of Professor Guiqi Xuan(Prof.Xuan)in treating pediatric patients with attention-deficit hyperactivity disorder(ADHD)and the potential mechanism of the core he...Background:To investigate the clinical medication approach of Professor Guiqi Xuan(Prof.Xuan)in treating pediatric patients with attention-deficit hyperactivity disorder(ADHD)and the potential mechanism of the core herbal prescription.Methods:Following medical record information pretreatment,the Traditional Chinese Medicine(TCM)inheritance computing platform system V3.0 was utilized to analyze the standardized data.The associate rules were summarized to identify the core prescription for treating ADHD.The extracted core herbal prescription’s active compounds and potential targets were used to establish a protein-protein interaction network of active ingredient-disease targets.Cytoscape 3.9.1 software was used to analyze the network’s topological parameters to obtain the key active ingredients and their targets.The Bioconductor data package of R4.0.2 was used to analyze the gene ontology biological functions and Kyoto Encyclopedia of Genes and Genomes pathways of key targets.Results:Two hundred and twenty-seven entries derived from TCM record information were selected.Through data mining,it was found that 62.5%of pediatric patients had short-tempered behavior,nearly half had sleep problems,and 30%-40%had picky eating and polyphagia issues.The highest-frequency syndrome type was kidney deficiency and liver hyperactivity.Deficiency,fire,phlegm,and dyspeptic food were the main pathological factors for ADHD.Prof.Xuan’s treatment of ADHD mainly focused on replenishing kidney essence and subduing Yang(active,external,ascending,warm,bright,functional and excited pertain to Yang).The core herbal prescription for ADHD included Yuan-zhi,Yi-zhi,Gui-jia,Bai-shao,Long-chi,Ci-shi,Shi-chang-pu,Yu-jin,Fu-shen,and Huang-jing.The protein-protein interaction network showed that MAOA,ADRB2,FOS,MAOB,and SLC6A3 were the five key targets essential in treating ADHD with core herbal prescriptions.The gene ontology biological function of crucial targets mainly involved G protein-coupled amine receptor activity,catecholamine binding,and neurotransmitter transmembrane transporter activity.Analysis of Kyoto Encyclopedia of Genes and Genomes pathways showed that the dopaminergic synapse signaling and neuroactive ligand-receptor interaction pathways were significantly enriched and may be the primary routes for the main treatment of ADHD.Conclusion:Prof.Xuan’s treatment of ADHD has achieved satisfactory clinical effects by supplementing the kidney,replenishing the essence,opening the orifices,nourishing the Yin(static,internal,descending,cold,dim,organic,depressed and pertain to Yin),and subduing the Yang.The major prescription predominantly affects catecholamine binding,neuroactive ligand-receptor interaction,G protein-coupled amine receptor function,and signaling pathways for dopaminergic synapses.Our findings showed that the methodology and software used in this research could explore and analyze the mechanism behind Prof.Xuan’s clinical medication rule for treating ADHD in children.展开更多
Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We establi...Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.展开更多
Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world...Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.展开更多
Objective:Colorectal cancer(CRC)is one of the most common malignancies in the world,and traditional Chinese medicine(TCM)is widely used in its treatment in China.However,the medication rules of TCM for CRC treatment r...Objective:Colorectal cancer(CRC)is one of the most common malignancies in the world,and traditional Chinese medicine(TCM)is widely used in its treatment in China.However,the medication rules of TCM for CRC treatment remain unclear.Therefore,data mining combined with network pharmacology was utilized to establish treatment principles and rules.Methods:The CRC cases treated at Zhejiang Provincial Hospital of Chinese Medicine from January 1,2016 to October 31,2021 were analyzed using data mining methods.UPLC-Q/TOF-MS analysis was performed to identify the chemical composition of Jiedu Sangen decoction(JSD).Network pharmacology was used to reveal the therapeutic mechanism of JSD.Results:A total of 312 cases 2,998 prescriptions that met the inclusion criteria used 343 kinds of traditional Chinese medicines.The nature of the herbs used in treatment was mainly warm and mild.The taste was mainly sweet,bitter,and pungent.The meridian tropisms were mainly the spleen meridian,followed by lung and stomach meridians.Tonifying and replenishing herbs were the most frequently used in treatment.High-frequency herbs were classified into 11 categories by cluster analysis,and 42 association rules were obtained by association rule analysis.Combined with complex network analysis,3 core prescriptions for clinical CRC treatment were obtained.Jiedu Sangen decoction contains 64 chemical ingredients,out of which 31 active ingredients were identified,including polydatin,caffeic acid,and glutamic acid,along with 130 potential targets such as AKT1,SRC,and MAPK1.Jiedu Sangen decoction may play a role in regulating inflammation,immunity,metabolism,and hormones in the development of CRC via pathways such as the relaxin signaling pathway,IL-17 signaling pathway,prolactin signaling pathway,and T cell receptor signaling pathway.Conclusions:This study summarizes the treatment and medication principles for clinical CRC treatment,promoting the inheritance and development of the traditional Chinese medical experience.展开更多
The tumor microenvironment(TME)plays a crucial role in facilitating tumorigenesis and progression.Consequently,there is significant research interest within the oncology community in developing interventions that targ...The tumor microenvironment(TME)plays a crucial role in facilitating tumorigenesis and progression.Consequently,there is significant research interest within the oncology community in developing interventions that target the TME.Extensive research has been conducted on the mechanism of traditional Chinese medicine(TCM)in tumor therapy,revealing notable similarities between its theoretical framework and that of the TME.TCM has the ability to regulate various components of the microenvironment,including the modulation of proportions of T cell subsets,enhancement of the quantity and activity of NK cells,regulation of polarization of tumor-associated macrophages,suppression of expression of myeloid-derived suppressor cells,reduction of accumulation of tumor-associated endothelial cells,downregulation of the quantity and function of tumor-associated fibroblasts,and modulation of the architecture of the extracellular matrix.These multifaceted interventions ultimately lead to the attainment of anti-tumor objectives.This comprehensive review encompasses a thorough analysis of relevant literature from both domestic and international sources,with a specific emphasis on elucidating the mechanisms through which TCM compound formulas,single drugs,and monomeric components regulate the TME.展开更多
The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that...The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.展开更多
BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,neces...BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.展开更多
Severe acute pancreatitis(SAP)is a serious systemic disease associated with strong local inflammatory reactions and serious systemic pathophysiological disorders caused by trypsin spillover.Patients with SAP are prone...Severe acute pancreatitis(SAP)is a serious systemic disease associated with strong local inflammatory reactions and serious systemic pathophysiological disorders caused by trypsin spillover.Patients with SAP are prone to exhibit gastrointestinal dysfunction.Meanwhile,gastrointestinal dysfunction further aggravates the systemic inflammatory response and metabolic abnormalities,resulting in a more critical condition of SAP.Gastrointestinal dysfunction is considered to be the“trigger”of multiple organ dysfunction syndrome[1].Thus,it is important to maintain gastrointestinal homeostasis in the treatment of SAP.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrate...Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.展开更多
基金Supported by Major Project of the Co-construction Science and Technology Program between the Science and Technology Department of the National Administration of Traditional Chinese Medicine and the Zhejiang Administration of Traditional Chinese Medicine,No.GZY-ZJ-KJ-23040Zhejiang Medical and Health Science and Technology Project,No.2022497035+2 种基金Quzhou City Science and Technology Project,No.2022K75Zhejiang Chinese Medical University Scientific Research Fund Project,No.2021FSYYZZ09,No.2021FSYYZZ14The study was reviewed and approved by the Department of Orthopedics,The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Traditional Chinese Medicine)Institutional Review Board[Approval No.2023-K-162-01].
文摘BACKGROUND Gait is influenced by race,age,and diseases type.Reference values for gait are closely related to numerous health outcomes.To gain a comprehensive understanding of gait patterns,particularly in relation to race-related pathologies and disorders,it is crucial to establish reference values for gait in daily life considering sex and age.Therefore,our objective was to present sex and age-based reference values for gait in daily life,providing a valuable foundation for further research and clinical applications.AIM To establish reference values for lower extremity joint kinematics and kinetics during gait in asymptomatic adult women and men.METHODS Spatiotemporal,kinematics and kinetics parameters were measured in 171 healthy adults(70 males and 101 females)using the computer-aided soft tissue foot model.Full curve statistical parametric mapping was performed using independent and paired-samples t-tests.RESULTS Compared with females,males required more time(cycle time,double-limb support time,stance time,swing time,and stride time),and the differences were statistically significant.In addition,the step and stride lengths of males were longer.Compared to males,female cadence was faster,and statures-per-second and stride-per-minute were higher.There were no statistical differences in speed and stride width between the two groups.After adjusting for height,it was observed that women walked significantly faster than men,and they also had a higher cadence.However,in terms of step length,stride length,and stride width,both genders exhibited similarities.CONCLUSION We established reference values for gait speed and spatiotemporal gait parameters in Chinese university students.This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.
基金supported by the National Natural Science Foundation of China(Grant No.:82174246)the National Key R&D Program of China(Grant No.:2019YFC1708701)the Postdoctoral Innovation Talent Support Program(Grant No.:BX20220329).
文摘Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.
基金This study was supported by grants from Zhejiang Health Science and Technology Project(2022ZA052)Zhejiang Provincial Natural Science Foundation of China(LY23H030001).
文摘Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].
基金Supported by National Natural Science Foundation of China,No.82104862Scientific Research Project Foundation of Zhejiang Chinese Medical University,No.2023FSYYZZ01 and No.2023RCZXZK49.
文摘Current treatment strategies for diabetic retinopathy(DR),an eye condition that can lead to blindness,have mainly focused on proliferative DR,including vitreous injection,retinal photocoagulation,and vitrectomy.Vitreous injections mainly depend on anti-vascular endothelial growth factor therapy.In this editorial,we comment on the article by Sun et al.We focus specifically on the mechanisms of the protective effect of genipin on the retina.Genipin is a gardenia extract used in traditional Chinese medicine(TCM).In their study,the authors suggest that controlling advanced glycosylation by the intraocular injection of genipin may be a strategy for preventing retinopathy.The innovative use of a Chinese medicine extract injected into the eye to achieve a curative effect has attracted our attention.Although TCM is effective in treating DR,the topical application of DR,especially intraocular injections,is not yet feasible.Herein,we present a brief analysis of effective Chinese medicines for the treatment of DR.The effectiveness of local injections of TCM applied directly into the eyes holds promise as an effective treatment approach for DR.
基金This research was financed by the grants from the Second Batch of Provincial Curriculum Ideological and Political Teaching Research Projects of Zhejiang Provincial Department of Education in 2022(No.Z.J.H.[2022]51)Zhejiang Educational Science Planning Project(No.2022SCG429)Special Project of Traditional Chinese Medical Culture of Zhejiang Chinese Medical University(No.2022JKZZW07 and 2022JKZZW13).
文摘The article focuses on the dissemination and development of Chinese medicine in Pakistan.Religious records show that Chinese medicine was introduced to Pakistan as early as 1,400 years ago,while Hijama(Chinese cupping)was used by Prophet Hazrat Muhammad to cure different types of diseases.Exchanges and cooperations between China and Pakistan continue to the present day.Acupuncture and moxibustion therapy,cupping therapy and herbal medicine are practiced with significant merits in today’s Pakistan.In the future,with the proposal of the Belt and Road Initiative and the landmark project of China-Pakistan Economic Corridor,Chinese medicine can be strengthened through cooperations at the herbal medicine trade level,the research and development level,the educational level,and the social association level.
基金supported by National Key Research and Development Program of China(contract No.2019YFA0904800)National Nature Science Foundation of China(32030065,31722033,92049304 to Y.Z.)+5 种基金Shanghai Sailing Program(contract No.21YF1410300)Science and Technology Commission of Shanghai Municipality(contract No.10DZ2220500)The Shanghai Committee of Science and Technology(grant No.11DZ2260600)Shanghai Frontiers Science Center of Optogenetic Techniques for CellMetabolism(Y.Z.)Research Unit of New Techniques for Live-cell Metabolic Imaging(Chinese Academy of Medical Sciences,2019-I2M-5-013 to Y.Z.)the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities.
文摘Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.
基金supported by the National Science Foundation of China(82160647)Hainan Clinical Medical Research Center Project(LCYX202310)+1 种基金Hainan Provincial Major Science and Technology Projects(ZDKJ202004)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-023).
文摘In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.
文摘Rectus abdominis diastasis is a common condition in postpartum women,causing back pain,and in severe cases,it can result in abdominal wall hernias and downward migration of abdominal organs.At present,there is no clearly established optimal non-surgical treatment for rectus abdominis diastasis,but traditional Chinese medicine(TCM)nursing techniques have proven to be an effective intervention for postpartum rectus abdominis separation.This paper comprehensively analyzes the TCM nursing technology as an intervention for postpartum rectus abdominis separation,discusses the shortcomings and prospects of TCM nursing technology,and provides references for further exploring and optimizing the intervention program for postpartum rectus abdominis separation.
文摘Traditional Chinese medicine(TCM)is actually a comprehensive medical system that encompasses not only medicine but also philosophy and art,forming a distinct contrast to modern medicine based on molecules[1].Compared to modern medicine,TCM places more emphasis on a holistic approach.In clinical practice,many diseases have shown significant therapeutic efficacy with TCM treatments.Taking the example of the kidney,a study involving 29 randomized controlled trials with 1982 patients conducted by Shan et al.
基金supported by the Ministry of Education of Humanities and Social Science Project[Grant No.Y202145935]。
文摘Objective This study aims to evaluate the association between lower grip strength and mortality hazard.Methods We selected 10,280 adults aged 45 to 96 years old from the China Health and Retirement Longitudinal Study and used multivariate Cox proportional hazard models to assess the association of grip strength with mortality hazard.In addition,we explored the possibility of a nonlinear relationship using a 4-knot restricted spline regression.Results We found that elevated grip strength was associated with lower mortality up to a certain threshold.The baseline quartile values of grip strength were 30,37,and 44 kg for males and 25,30,and35 kg for females.After adjusting for confounders,with category 1 as the reference group,the adjusted HRs were 0.58(0.42-0.79)in males and 0.70(0.48-0.99)in females(category 4).We also found a linear association between grip strength values and all-cause death risk(males,P=0.274;females,P=0.883)using restricted spline regression.For males with a grip strength<37 kg and females with a grip strength<30 kg,grip strength and death were negatively associated.Conclusion Grip strength below a sex-specific threshold is inversely associated with mortality hazard among middle-aged and older Chinese adults with chronic diseases.
基金This work was supported by the Hangzhou XUANs’Pediatric School Inheritance Studio Construction Project(No.[2012]228).
文摘Background:To investigate the clinical medication approach of Professor Guiqi Xuan(Prof.Xuan)in treating pediatric patients with attention-deficit hyperactivity disorder(ADHD)and the potential mechanism of the core herbal prescription.Methods:Following medical record information pretreatment,the Traditional Chinese Medicine(TCM)inheritance computing platform system V3.0 was utilized to analyze the standardized data.The associate rules were summarized to identify the core prescription for treating ADHD.The extracted core herbal prescription’s active compounds and potential targets were used to establish a protein-protein interaction network of active ingredient-disease targets.Cytoscape 3.9.1 software was used to analyze the network’s topological parameters to obtain the key active ingredients and their targets.The Bioconductor data package of R4.0.2 was used to analyze the gene ontology biological functions and Kyoto Encyclopedia of Genes and Genomes pathways of key targets.Results:Two hundred and twenty-seven entries derived from TCM record information were selected.Through data mining,it was found that 62.5%of pediatric patients had short-tempered behavior,nearly half had sleep problems,and 30%-40%had picky eating and polyphagia issues.The highest-frequency syndrome type was kidney deficiency and liver hyperactivity.Deficiency,fire,phlegm,and dyspeptic food were the main pathological factors for ADHD.Prof.Xuan’s treatment of ADHD mainly focused on replenishing kidney essence and subduing Yang(active,external,ascending,warm,bright,functional and excited pertain to Yang).The core herbal prescription for ADHD included Yuan-zhi,Yi-zhi,Gui-jia,Bai-shao,Long-chi,Ci-shi,Shi-chang-pu,Yu-jin,Fu-shen,and Huang-jing.The protein-protein interaction network showed that MAOA,ADRB2,FOS,MAOB,and SLC6A3 were the five key targets essential in treating ADHD with core herbal prescriptions.The gene ontology biological function of crucial targets mainly involved G protein-coupled amine receptor activity,catecholamine binding,and neurotransmitter transmembrane transporter activity.Analysis of Kyoto Encyclopedia of Genes and Genomes pathways showed that the dopaminergic synapse signaling and neuroactive ligand-receptor interaction pathways were significantly enriched and may be the primary routes for the main treatment of ADHD.Conclusion:Prof.Xuan’s treatment of ADHD has achieved satisfactory clinical effects by supplementing the kidney,replenishing the essence,opening the orifices,nourishing the Yin(static,internal,descending,cold,dim,organic,depressed and pertain to Yin),and subduing the Yang.The major prescription predominantly affects catecholamine binding,neuroactive ligand-receptor interaction,G protein-coupled amine receptor function,and signaling pathways for dopaminergic synapses.Our findings showed that the methodology and software used in this research could explore and analyze the mechanism behind Prof.Xuan’s clinical medication rule for treating ADHD in children.
基金National Key Research and Development Program of China(No.2018YFC1705503).
文摘Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.
文摘Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.
基金supported by Zhejiang Provincial Science and Technology Program of Traditional Chinese Medicine(No.2023ZR095)China Postdoctoral Science Foundation(No.2021M702928)+1 种基金Young Elite Scientists Sponsorship Program by CACM(No.2021-QNRC2-B13)National College Students Innovation and Entrepreneurship Training Program(No.202210344008).
文摘Objective:Colorectal cancer(CRC)is one of the most common malignancies in the world,and traditional Chinese medicine(TCM)is widely used in its treatment in China.However,the medication rules of TCM for CRC treatment remain unclear.Therefore,data mining combined with network pharmacology was utilized to establish treatment principles and rules.Methods:The CRC cases treated at Zhejiang Provincial Hospital of Chinese Medicine from January 1,2016 to October 31,2021 were analyzed using data mining methods.UPLC-Q/TOF-MS analysis was performed to identify the chemical composition of Jiedu Sangen decoction(JSD).Network pharmacology was used to reveal the therapeutic mechanism of JSD.Results:A total of 312 cases 2,998 prescriptions that met the inclusion criteria used 343 kinds of traditional Chinese medicines.The nature of the herbs used in treatment was mainly warm and mild.The taste was mainly sweet,bitter,and pungent.The meridian tropisms were mainly the spleen meridian,followed by lung and stomach meridians.Tonifying and replenishing herbs were the most frequently used in treatment.High-frequency herbs were classified into 11 categories by cluster analysis,and 42 association rules were obtained by association rule analysis.Combined with complex network analysis,3 core prescriptions for clinical CRC treatment were obtained.Jiedu Sangen decoction contains 64 chemical ingredients,out of which 31 active ingredients were identified,including polydatin,caffeic acid,and glutamic acid,along with 130 potential targets such as AKT1,SRC,and MAPK1.Jiedu Sangen decoction may play a role in regulating inflammation,immunity,metabolism,and hormones in the development of CRC via pathways such as the relaxin signaling pathway,IL-17 signaling pathway,prolactin signaling pathway,and T cell receptor signaling pathway.Conclusions:This study summarizes the treatment and medication principles for clinical CRC treatment,promoting the inheritance and development of the traditional Chinese medical experience.
基金supported by the National Natural Science Foundation of China(No.81973771).
文摘The tumor microenvironment(TME)plays a crucial role in facilitating tumorigenesis and progression.Consequently,there is significant research interest within the oncology community in developing interventions that target the TME.Extensive research has been conducted on the mechanism of traditional Chinese medicine(TCM)in tumor therapy,revealing notable similarities between its theoretical framework and that of the TME.TCM has the ability to regulate various components of the microenvironment,including the modulation of proportions of T cell subsets,enhancement of the quantity and activity of NK cells,regulation of polarization of tumor-associated macrophages,suppression of expression of myeloid-derived suppressor cells,reduction of accumulation of tumor-associated endothelial cells,downregulation of the quantity and function of tumor-associated fibroblasts,and modulation of the architecture of the extracellular matrix.These multifaceted interventions ultimately lead to the attainment of anti-tumor objectives.This comprehensive review encompasses a thorough analysis of relevant literature from both domestic and international sources,with a specific emphasis on elucidating the mechanisms through which TCM compound formulas,single drugs,and monomeric components regulate the TME.
基金supported by the Natural Science Foundation of Zhejiang Province of China,Nos.LQ22H090003(to JJ),LTGY23C090001(to XZ),LY23H020008(to BH)Sci-Tech Planning Project of Jiaxing,Nos.2021AY30001(to XZ)and 2022AY30020(to JJ).
文摘The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.
文摘BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.
文摘Severe acute pancreatitis(SAP)is a serious systemic disease associated with strong local inflammatory reactions and serious systemic pathophysiological disorders caused by trypsin spillover.Patients with SAP are prone to exhibit gastrointestinal dysfunction.Meanwhile,gastrointestinal dysfunction further aggravates the systemic inflammatory response and metabolic abnormalities,resulting in a more critical condition of SAP.Gastrointestinal dysfunction is considered to be the“trigger”of multiple organ dysfunction syndrome[1].Thus,it is important to maintain gastrointestinal homeostasis in the treatment of SAP.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
基金supported by the National Natural Science Foundation of China(Grant No.:32070740)Zhejiang Provincial Natural Science Foundation(Grant No.:LZ23H160005)+1 种基金Natural Science Foundation of Jiangsu Province(Grant No.:BK20201197)Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program,Zhejiang Provincial Qianjiang Talents Program to Jianbin Zhang.
文摘Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.