Objective:Finding an effective therapy against Alzheimer’s disease(AD)has been associate increasingly pressing issue and traditional Chinese medicine(TCM)is widespread in the prevention and treatment of AD in China.T...Objective:Finding an effective therapy against Alzheimer’s disease(AD)has been associate increasingly pressing issue and traditional Chinese medicine(TCM)is widespread in the prevention and treatment of AD in China.The aim of this study was to judge the efficaciousness and safety of TCM kidney-nourishing(the changes of pathological state of kidney deficiency by means of TCM treatment and so on)formula(TKNF)for AD in comparison with donepezil.Methods:The retrieval period of seven databases was from the establishment of each database to April 2019.Two authors independently identified randomized controlled trials(RCTs),fetched data and assessed bias risk.Comprehensive analysis process was conducted with review manager for eligible and appropriate RCTs.Results:A complete of 981 AD patients from 13 studies were enclosed.Meta-analysis of RCTs showed that there was no significant difference in the improvement of Alzheimer's disease assessment scale-cognitive subscale score between 2 groups in short term,but the effect of long-term treatment may exceed donepezil;there was a significant difference in the improvement of activities of daily living score between 2 groups;there was a significant difference in TCM curative efficacy between 2 groups with long-term treatment.There was no significant difference in the incidence of adverse events between 2 groups.The quality of the evidence was high or moderate.Conclusion:Compared with donepezil,TKNF was an effective drug for AD patients and the clinical application of TKNF was safe.TKNF's long-term benefits need more evidence to verify.展开更多
BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Rand...BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(P<0.00001),left ventricular ejection fraction by 6.69%[mean difference(MD)=6.69,95%CI:4.42-8.95,P<0.00001]and 6-min walk test by 49.82 m(MD=49.82,95%C:38.84-60.80,P<0.00001),and reduced N-terminal pro-Btype natriuretic peptide by 1.03 ng/L[standardized MD(SMD)=-1.03,95%CI:-1.32 to-0.74,P<0.00001],brain natriuretic peptide by 80.95 ng/L(MD=-80.95,95%CI:-143.31 to-18.59,P=0.01),left ventricular end-diastolic diameter by 3.92 mm(MD=-3.92,95%CI:-5.06 to-2.78,P<0.00001),and left ventricular endsystolic diameter by 4.34 mm(MD=-4.34,95%CI:-6.22 to-2.47,P<0.00001).Regarding safety,neither group reported any serious adverse events during treatment(RR=0.54,95%CI:0.15-1.90,P=0.33).In addition,Egger's test results indicated no significant publication bias(P=0.557).CONCLUSION YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.展开更多
BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attract...BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.展开更多
Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like...Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.展开更多
High mortality rates from cardiovascular diseases(CVDs)persist worldwide.Older people are at a higher risk of developing these diseases.Given the current high treatment cost for CVDs,there is a need to prevent CVDs an...High mortality rates from cardiovascular diseases(CVDs)persist worldwide.Older people are at a higher risk of developing these diseases.Given the current high treatment cost for CVDs,there is a need to prevent CVDs and or develop treatment alternatives.Western and Chinese medicines have been used to treat CVDs.However,several factors,such as inaccurate diagnoses,non-standard prescriptions,and poor adherence behavior,lower the benefits of the treatments by Chinese medicine(CM).Artificial intelligence(AI)is increasingly used in clinical diagnosis and treatment,especially in assessing efficacy of CM in clinical decision support systems,health management,new drug research and development,and drug efficacy evaluation.In this study,we explored the role of AI in CM in the diagnosis and treatment of CVDs,and discussed application of AI in assessing the effect of CM on CVDs.展开更多
Background:Knee osteoarthritis is a chronic degenerative disease responsible for a substantial disease burden worldwide.Multiple protocols of systematic reviews of interventions for knee osteoarthritis have been publi...Background:Knee osteoarthritis is a chronic degenerative disease responsible for a substantial disease burden worldwide.Multiple protocols of systematic reviews of interventions for knee osteoarthritis have been published,but their reporting quality remains unknown,with potential influencing factors failing to be explored.Therefore,the present systematic review was designed to fill those gaps in our knowledge.Methods:The protocols of systematic reviews of interventions for knee osteoarthritis will be searched systematically through the PubMed and Embase online databases from inception to May 2021.Two reviewers will independently screen the literature and abstract data,and cross-check the results.The reporting quality of protocols included in the review will be evaluated using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols checklist,and potential influencing factors(e.g.,methodologist involvement and number of authors)for reporting quality will be explored using univariable and multivariable linear regression methods.The general information of the protocols included in the review will be reported qualitatively.Excel 2019 and Stata 13.0 software will be used to manage and analyze the data.P-values<0.05 will be considered statistically significant.Results:The results of this methodological systematic review will be submitted to a peer-reviewed journal for publication.Conclusion:The systematic review will provide evidence of the reporting quality of protocols of systematic reviews of interventions for knee osteoarthritis.The evidence from the present review will be available to inform the reporting of future protocols.展开更多
Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This co...Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.展开更多
Hepatic phosphorylase kinase(PhK)plays an important role in glycogen metabolism by activating phosphorylase.Patients with PhK deficiency may get glycogen storage disease(GSD)type-IXa,an X-linked liver glycogenosis dis...Hepatic phosphorylase kinase(PhK)plays an important role in glycogen metabolism by activating phosphorylase.Patients with PhK deficiency may get glycogen storage disease(GSD)type-IXa,an X-linked liver glycogenosis disease.To inform genetic counseling in a family with two affected GSD brothers,we performed a genetic analysis.The GSD in the older brother was confirmed by histological examination of a liver biopsy,which showed glycogen accumulation in liver cells.A liver biopsy was not available from the younger brother.The two patients and their parents were analyzed by whole exome sequencing.A pathogenic mutation in a gene encoding a regulatory subunit of PhK,PHKA2 located on chromosome Xp22,was identified as c.G3373A(p.E1125K)and confirmed by Sanger sequencing.The proband’s maternal grandparents and the brothers and sisters of the proband’s maternal grandfather were physically examined and genetically tested by Sanger sequencing.Pedigree analysis showed that the mother was a carrier and that the two patients inherited the mutation from their undiagnosed maternal grandfather.Moreover,among the maternal grandfather and four granduncles,three of them possessed the same mutation and four suffered from fatty liver.This is the first report of this mutation causing X-linked liver glycogenosis in a Chinese family and shows that GSD IXa is a mild form of glycogenosis in terms of clinical symptoms,indicating that GSD may be undiagnosed or underestimated.Nevertheless,to provide appropriate intervention and genetic counseling,early identification of the genetic cause is imperative.This study was approved by the Ethics Committee of First Affiliated Hospital,Hunan University of Chinese Medicine(approval No.HN-LL-ZFKY-2018-001-01)on January 12,2018.展开更多
In recent years,preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention.DKD has become a pervasive complication of type 2 diabetes.Given the complexity of...In recent years,preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention.DKD has become a pervasive complication of type 2 diabetes.Given the complexity of its etiology and pathological mechanisms,current interventions,including drugs,dietary modifications,exercise,hypoglycemic treatments and lipid-lowering methods,often fall short in achieving desired therapeutic outcomes.Iridoids,primarily derived from the potent components of traditional herbs,have been the subject of long-standing research.Preclinical data suggest that iridoids possess notable renal protective properties;however,there has been no summary of the research on their efficacy in the management and treatment of DKD.This article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this condition.Additionally,it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora,potentially bolstering their therapeutic effects.This review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD,offering valuable insights for future research endeavors.展开更多
基金National Natural Science Foundation of China(No.81573865).
文摘Objective:Finding an effective therapy against Alzheimer’s disease(AD)has been associate increasingly pressing issue and traditional Chinese medicine(TCM)is widespread in the prevention and treatment of AD in China.The aim of this study was to judge the efficaciousness and safety of TCM kidney-nourishing(the changes of pathological state of kidney deficiency by means of TCM treatment and so on)formula(TKNF)for AD in comparison with donepezil.Methods:The retrieval period of seven databases was from the establishment of each database to April 2019.Two authors independently identified randomized controlled trials(RCTs),fetched data and assessed bias risk.Comprehensive analysis process was conducted with review manager for eligible and appropriate RCTs.Results:A complete of 981 AD patients from 13 studies were enclosed.Meta-analysis of RCTs showed that there was no significant difference in the improvement of Alzheimer's disease assessment scale-cognitive subscale score between 2 groups in short term,but the effect of long-term treatment may exceed donepezil;there was a significant difference in the improvement of activities of daily living score between 2 groups;there was a significant difference in TCM curative efficacy between 2 groups with long-term treatment.There was no significant difference in the incidence of adverse events between 2 groups.The quality of the evidence was high or moderate.Conclusion:Compared with donepezil,TKNF was an effective drug for AD patients and the clinical application of TKNF was safe.TKNF's long-term benefits need more evidence to verify.
基金Supported by Hunan Provincial Chinese Medicine Research Program Commissioned Key Projects,No.D2023005。
文摘BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(P<0.00001),left ventricular ejection fraction by 6.69%[mean difference(MD)=6.69,95%CI:4.42-8.95,P<0.00001]and 6-min walk test by 49.82 m(MD=49.82,95%C:38.84-60.80,P<0.00001),and reduced N-terminal pro-Btype natriuretic peptide by 1.03 ng/L[standardized MD(SMD)=-1.03,95%CI:-1.32 to-0.74,P<0.00001],brain natriuretic peptide by 80.95 ng/L(MD=-80.95,95%CI:-143.31 to-18.59,P=0.01),left ventricular end-diastolic diameter by 3.92 mm(MD=-3.92,95%CI:-5.06 to-2.78,P<0.00001),and left ventricular endsystolic diameter by 4.34 mm(MD=-4.34,95%CI:-6.22 to-2.47,P<0.00001).Regarding safety,neither group reported any serious adverse events during treatment(RR=0.54,95%CI:0.15-1.90,P=0.33).In addition,Egger's test results indicated no significant publication bias(P=0.557).CONCLUSION YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+5 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005and Open Project of Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education,No.DHYX21-07,No.DHYX22-05,and No.DHYX21-01.
文摘BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.
文摘Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.
基金Supported by the National Natural Science Foundation of China(No.82174343 and No.81673955)Key R&D Plan of Hunan Province(No.2022SK2012)。
文摘High mortality rates from cardiovascular diseases(CVDs)persist worldwide.Older people are at a higher risk of developing these diseases.Given the current high treatment cost for CVDs,there is a need to prevent CVDs and or develop treatment alternatives.Western and Chinese medicines have been used to treat CVDs.However,several factors,such as inaccurate diagnoses,non-standard prescriptions,and poor adherence behavior,lower the benefits of the treatments by Chinese medicine(CM).Artificial intelligence(AI)is increasingly used in clinical diagnosis and treatment,especially in assessing efficacy of CM in clinical decision support systems,health management,new drug research and development,and drug efficacy evaluation.In this study,we explored the role of AI in CM in the diagnosis and treatment of CVDs,and discussed application of AI in assessing the effect of CM on CVDs.
基金The authors did not receive any funding for this study.
文摘Background:Knee osteoarthritis is a chronic degenerative disease responsible for a substantial disease burden worldwide.Multiple protocols of systematic reviews of interventions for knee osteoarthritis have been published,but their reporting quality remains unknown,with potential influencing factors failing to be explored.Therefore,the present systematic review was designed to fill those gaps in our knowledge.Methods:The protocols of systematic reviews of interventions for knee osteoarthritis will be searched systematically through the PubMed and Embase online databases from inception to May 2021.Two reviewers will independently screen the literature and abstract data,and cross-check the results.The reporting quality of protocols included in the review will be evaluated using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols checklist,and potential influencing factors(e.g.,methodologist involvement and number of authors)for reporting quality will be explored using univariable and multivariable linear regression methods.The general information of the protocols included in the review will be reported qualitatively.Excel 2019 and Stata 13.0 software will be used to manage and analyze the data.P-values<0.05 will be considered statistically significant.Results:The results of this methodological systematic review will be submitted to a peer-reviewed journal for publication.Conclusion:The systematic review will provide evidence of the reporting quality of protocols of systematic reviews of interventions for knee osteoarthritis.The evidence from the present review will be available to inform the reporting of future protocols.
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+4 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005.
文摘Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.
基金This work was supported by the National Natural Science Foundation of China(No.81703917)Natural Science Foundation of Hunan Province of China(No.2017JJ3242)+1 种基金Firstclass Discipline Open Fund Project of Hunan University of Chinese Medicine(No.2018YXJS02)conducted in accordance with the Declaration of Helsinki.
文摘Hepatic phosphorylase kinase(PhK)plays an important role in glycogen metabolism by activating phosphorylase.Patients with PhK deficiency may get glycogen storage disease(GSD)type-IXa,an X-linked liver glycogenosis disease.To inform genetic counseling in a family with two affected GSD brothers,we performed a genetic analysis.The GSD in the older brother was confirmed by histological examination of a liver biopsy,which showed glycogen accumulation in liver cells.A liver biopsy was not available from the younger brother.The two patients and their parents were analyzed by whole exome sequencing.A pathogenic mutation in a gene encoding a regulatory subunit of PhK,PHKA2 located on chromosome Xp22,was identified as c.G3373A(p.E1125K)and confirmed by Sanger sequencing.The proband’s maternal grandparents and the brothers and sisters of the proband’s maternal grandfather were physically examined and genetically tested by Sanger sequencing.Pedigree analysis showed that the mother was a carrier and that the two patients inherited the mutation from their undiagnosed maternal grandfather.Moreover,among the maternal grandfather and four granduncles,three of them possessed the same mutation and four suffered from fatty liver.This is the first report of this mutation causing X-linked liver glycogenosis in a Chinese family and shows that GSD IXa is a mild form of glycogenosis in terms of clinical symptoms,indicating that GSD may be undiagnosed or underestimated.Nevertheless,to provide appropriate intervention and genetic counseling,early identification of the genetic cause is imperative.This study was approved by the Ethics Committee of First Affiliated Hospital,Hunan University of Chinese Medicine(approval No.HN-LL-ZFKY-2018-001-01)on January 12,2018.
基金supported by grants from the National Natural Science Foundation of China (No.82074400)key projects supported by the National Natural Science Foundation of China and Joint Fund for Regional Innovation and Development (No.U21A20411)。
文摘In recent years,preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention.DKD has become a pervasive complication of type 2 diabetes.Given the complexity of its etiology and pathological mechanisms,current interventions,including drugs,dietary modifications,exercise,hypoglycemic treatments and lipid-lowering methods,often fall short in achieving desired therapeutic outcomes.Iridoids,primarily derived from the potent components of traditional herbs,have been the subject of long-standing research.Preclinical data suggest that iridoids possess notable renal protective properties;however,there has been no summary of the research on their efficacy in the management and treatment of DKD.This article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this condition.Additionally,it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora,potentially bolstering their therapeutic effects.This review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD,offering valuable insights for future research endeavors.