Rheumatoid arthritis(RA)is a common autoimmune condition with an elusive etiology.Conventional and biological disease-modifying drugs sometimes fail or produce only partial responses.Traditional Chinese medicine(TCM)h...Rheumatoid arthritis(RA)is a common autoimmune condition with an elusive etiology.Conventional and biological disease-modifying drugs sometimes fail or produce only partial responses.Traditional Chinese medicine(TCM)has long been used in China as a treatment for RA and is achieving everincreasing acceptance worldwide.TCM treatments are traditionally guided by the theory of treatment based on TCM syndrome differentiation;however,they remain a matter of empirical practice relying on TCM theories and doctors’own experience,which places severe restrictions on worldwide TCM application.Nevertheless,TCM is a treasure trove for drug discovery,particularly as a treatment for complicated human conditions.The discoveries of artemisinin as a treatment for malaria and of TCM–arsenic trioxide(As2O3)combination therapy as a treatment for acute promyelocytic leukemia(APL)are excellent examples of the great value of TCM.Regarding RA treatments,many Chinese medicinal herbs and their formulas,extracts,ingredients,and even single compounds have been used in clinical applications.Several Chinese proprietary medicines(CPMs)derived from TCM formulas or herbal bioactive components,such as the controlled-release ZhengQingFengTongNing(ZQFTN)Tablets,Tripterygium Glycoside Tablets,and Total Glucosides of Peony(TGP)Capsules,have been included in the National Health Insurance Directory of China,and show comparable therapeutic efficacies to those of western chemical drugs with fewer side effects.As TCM research has advanced,particularly in the use of multidisciplinary technologies,the scientific foundations and characteristics of the use of TCM to treat RA have been revealed,and the quality of TCM treatments have been increasingly enhanced.However,TCM generally lacks sufficient clinical and laboratory data to be consistent with international standards for quality,safety,and efficacy in order to support its application worldwide.Therefore,intensive basic and clinical studies on TCM are required.In particular,investigations that use cutting-edge technologies in analytical chemistry,biology,and biomedical sciences,and the development of randomized clinical trials(RCTs)and personalized pragmatic randomized controlled trials(PPRCTs)are necessary.Researchers should also collaborate to advance TCM from empirical practice to evidence-based therapy,thus consistently promoting TCM development and globalization in a vital,beneficial,and contributable manner.展开更多
Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in ...Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients.In this 24 week,randomized,placebo-controlled,double-blind clinical trial,people with mild to moderate RA were randomly assigned(1:1:1,stratified by hospital)to receive SIN(120 mg,twice daily),methotrexate(MTX)(10 mg per week),or SIN+MTX therapy.The primary outcome was the proportion of patients who achieved a 50%improvement in the American College of Rheumatology(ACR50)criteria at week 24 and who showed improvement according to the clinical disease activity index(CDAI).In this prospective subgroup analysis,we also assessed whether the 24-week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine.Of the 135 enrolled participants,38,39,and 36 patients were treated with SIN,MTX,and SIN+MTX,respectively.In the SIN-treated group,52.63%of patients achieved ACR50 after 24-weeks of treatment,which was comparable to the results in the MTX-treated and SIN+MTX-treated groups.Hepatic and gastrointestinal disorders were the main adverse events;however,the ratio of patients suffering from hepatic disorder in the SIN group(1/38)was much lower than that in the MTX(10/39)and SIN+MTX(8/36)groups.A total of 221 serum samples were collected at the four follow-up time points in the three treatments,and the levels of ornithine,citrulline,and arginine were obtained through ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).The serum ornithine level decreased after the 24-week treatment along with a decrease in disease activity,and may reflect therapeutic responses with a sensitivity value of 80%.In conclusion,SIN revealed a comparable efficacy to MTX for treating RA patients,but with fewer side effects.In addition,the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA,which shows the value of this measure as an assessment indicator of drugs in treating RA.展开更多
Secondary amyloid A amyloidosis,a lethal complication,is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1(SAA1)protein and deposition in key internal organs.Previously,usin...Secondary amyloid A amyloidosis,a lethal complication,is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1(SAA1)protein and deposition in key internal organs.Previously,using the whole-exome sequencing method,we identified a novel deleterious mutation SAA1.2 in rheumatoid arthritis(RA)patients.However,the role of SAA1 in RA pathogenesis and its complications remains unknown.The purpose of this study was to determine the pathogenetic roles of SAA1 protein isoforms in RA progression.We modified an experimental adenovirus infection protocol to introduce SAA1.2 gene alleles into the knee joints of mice and used SAA1.3 and SAA1.5 as controls.Microcomputed tomography analysis was applied to determine changes in bone morphology and density.Immunohistochemical(IHC)analysis,flow cytometry,enzyme-linked immunosorbent assay(ELISA),and real-time polymerase chain reaction(RT-PCR)were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction.We found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood resulted in the stimulation of immune responses,leading to CD8^(+)T cell and pro-inflammatory cytokine elevation,such as interleukin(IL)-6,IL-22,matrix metalloproteinase(MMP)-3,MMP-9,with subsequent synovial inflammation and bone destruction.These findings indicate that SAA1 protein isoforms,particularly SAA1.2,play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction of RA.展开更多
BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal...BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.展开更多
Rheumatoid arthritis(RA),the most common inflammatory arthropathy word wild,is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate.Metabolic misregulation has emerged a...Rheumatoid arthritis(RA),the most common inflammatory arthropathy word wild,is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate.Metabolic misregulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction,while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA.Recently,natural active compounds from traditional Chinese medicines(TCMs)have potential therapeutic effects on RA and regulating immunometabolism.In this review,in addition to updating the connection between cellular metabolism and cell function in immune cells of RA,we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells,and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA.展开更多
文摘Rheumatoid arthritis(RA)is a common autoimmune condition with an elusive etiology.Conventional and biological disease-modifying drugs sometimes fail or produce only partial responses.Traditional Chinese medicine(TCM)has long been used in China as a treatment for RA and is achieving everincreasing acceptance worldwide.TCM treatments are traditionally guided by the theory of treatment based on TCM syndrome differentiation;however,they remain a matter of empirical practice relying on TCM theories and doctors’own experience,which places severe restrictions on worldwide TCM application.Nevertheless,TCM is a treasure trove for drug discovery,particularly as a treatment for complicated human conditions.The discoveries of artemisinin as a treatment for malaria and of TCM–arsenic trioxide(As2O3)combination therapy as a treatment for acute promyelocytic leukemia(APL)are excellent examples of the great value of TCM.Regarding RA treatments,many Chinese medicinal herbs and their formulas,extracts,ingredients,and even single compounds have been used in clinical applications.Several Chinese proprietary medicines(CPMs)derived from TCM formulas or herbal bioactive components,such as the controlled-release ZhengQingFengTongNing(ZQFTN)Tablets,Tripterygium Glycoside Tablets,and Total Glucosides of Peony(TGP)Capsules,have been included in the National Health Insurance Directory of China,and show comparable therapeutic efficacies to those of western chemical drugs with fewer side effects.As TCM research has advanced,particularly in the use of multidisciplinary technologies,the scientific foundations and characteristics of the use of TCM to treat RA have been revealed,and the quality of TCM treatments have been increasingly enhanced.However,TCM generally lacks sufficient clinical and laboratory data to be consistent with international standards for quality,safety,and efficacy in order to support its application worldwide.Therefore,intensive basic and clinical studies on TCM are required.In particular,investigations that use cutting-edge technologies in analytical chemistry,biology,and biomedical sciences,and the development of randomized clinical trials(RCTs)and personalized pragmatic randomized controlled trials(PPRCTs)are necessary.Researchers should also collaborate to advance TCM from empirical practice to evidence-based therapy,thus consistently promoting TCM development and globalization in a vital,beneficial,and contributable manner.
基金financially supported by grants from the Macao Science and Technology Development Fund(0032/2018/AFJ,0003/2019/AKP,and 0010/2020/A1)the Key Program in Emerging Industry of the Hunan Department of Science&Technology(2014GK1058)funded by Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery(001/2020/ALC)supported by the Macao Science and Technology Development Fund。
文摘Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients.In this 24 week,randomized,placebo-controlled,double-blind clinical trial,people with mild to moderate RA were randomly assigned(1:1:1,stratified by hospital)to receive SIN(120 mg,twice daily),methotrexate(MTX)(10 mg per week),or SIN+MTX therapy.The primary outcome was the proportion of patients who achieved a 50%improvement in the American College of Rheumatology(ACR50)criteria at week 24 and who showed improvement according to the clinical disease activity index(CDAI).In this prospective subgroup analysis,we also assessed whether the 24-week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine.Of the 135 enrolled participants,38,39,and 36 patients were treated with SIN,MTX,and SIN+MTX,respectively.In the SIN-treated group,52.63%of patients achieved ACR50 after 24-weeks of treatment,which was comparable to the results in the MTX-treated and SIN+MTX-treated groups.Hepatic and gastrointestinal disorders were the main adverse events;however,the ratio of patients suffering from hepatic disorder in the SIN group(1/38)was much lower than that in the MTX(10/39)and SIN+MTX(8/36)groups.A total of 221 serum samples were collected at the four follow-up time points in the three treatments,and the levels of ornithine,citrulline,and arginine were obtained through ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).The serum ornithine level decreased after the 24-week treatment along with a decrease in disease activity,and may reflect therapeutic responses with a sensitivity value of 80%.In conclusion,SIN revealed a comparable efficacy to MTX for treating RA patients,but with fewer side effects.In addition,the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA,which shows the value of this measure as an assessment indicator of drugs in treating RA.
基金funded by The Science and Technology Development Fund,Macao SAR(FDCT-FDCT-17-002-SKL)。
文摘Secondary amyloid A amyloidosis,a lethal complication,is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1(SAA1)protein and deposition in key internal organs.Previously,using the whole-exome sequencing method,we identified a novel deleterious mutation SAA1.2 in rheumatoid arthritis(RA)patients.However,the role of SAA1 in RA pathogenesis and its complications remains unknown.The purpose of this study was to determine the pathogenetic roles of SAA1 protein isoforms in RA progression.We modified an experimental adenovirus infection protocol to introduce SAA1.2 gene alleles into the knee joints of mice and used SAA1.3 and SAA1.5 as controls.Microcomputed tomography analysis was applied to determine changes in bone morphology and density.Immunohistochemical(IHC)analysis,flow cytometry,enzyme-linked immunosorbent assay(ELISA),and real-time polymerase chain reaction(RT-PCR)were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction.We found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood resulted in the stimulation of immune responses,leading to CD8^(+)T cell and pro-inflammatory cytokine elevation,such as interleukin(IL)-6,IL-22,matrix metalloproteinase(MMP)-3,MMP-9,with subsequent synovial inflammation and bone destruction.These findings indicate that SAA1 protein isoforms,particularly SAA1.2,play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction of RA.
文摘BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.
文摘Rheumatoid arthritis(RA),the most common inflammatory arthropathy word wild,is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate.Metabolic misregulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction,while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA.Recently,natural active compounds from traditional Chinese medicines(TCMs)have potential therapeutic effects on RA and regulating immunometabolism.In this review,in addition to updating the connection between cellular metabolism and cell function in immune cells of RA,we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells,and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA.
