AIM:To explore the related risk factors for diabetic retinopathy(DR)in type 2 diabetes with insulin therapy.METHODS:We studied the relationships among blood glucose,serum C-peptide,plasma insulin,beta-cell function an...AIM:To explore the related risk factors for diabetic retinopathy(DR)in type 2 diabetes with insulin therapy.METHODS:We studied the relationships among blood glucose,serum C-peptide,plasma insulin,beta-cell function and the development of DR.Beta-cell function was assessed by a modified homeostasis model assessment(modified HOMA)which was gained by using C-peptide to replace insulin in the homeostasis model assessment(HOMA)of beta-cell function.We also studied the relationships between modified HOMA index and serum C-peptide response to 100 g tasteless steamed bread to determine the accuracy of modified HOMA.RESULTS:Our study group consisted of 170 type 2diabetic inpatients with DR(age:58.35±13.87y,mean±SD)and 205 type 2 diabetic inpatients with no DR(NDR)(age:65.52±11.59y).DR patients had higher age,longer diabetic duration,higher hypertension grade,higher postprandial plasma glucose,higher fluctuation level of plasma glucose,lower body mass index(BMI),lower postprandial serum insulin and C-peptide,lower fluctuation level of serum insulin and C-peptide(P【0.05).In our logistic regression model,duration of diabetes,hypertension grade,fasting plasma insulin and glycosylated hemoglobin(HbA1C)were significantly associated with the presence of DR after adjustment for confounding factors(P【0.05).CONCLUSION:Our results suggested although modified HOMA showed significant correlation to the occurrence of DR on Spearman’s rank-correlationanalysis,logistic regression showed no significant association between these two variables after adjustment for relevant confounding factors(such as age,sex,duration of diabetes,BMI,hypertension grade,HbA1C,plasma insulin).Duration of diabetes,hypertension grade,fasting plasma insulin and HbA1C were independently associated with the development of DR in Chinese type 2 diabetics.展开更多
Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the mol...Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the molecular mechanism underlying high PPC(HPPC)is scant.Here,an animal model of primary hyperproteinemia was constructed in an invertebrate(Bombyx mori)to investigate the effects of HPPC on circulating blood cells.Results showed that HPPC affected blood cell homeostasis,leading to increased reactive oxygen species levels,and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway.HPPC induced the proliferation of blood cells,mainly granulocytes,by activating the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway.Supplementation with the endocrine hormone active substance 20 E significantly reduced the impact of HPPC on blood cell homeostasis.Thus,we identified a novel signaling pathway by which HPPC affects blood cell homeostasis,which differs from hyperglycemia,hyperlipidemia,and hypercholesterolemia.In addition,we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.展开更多
Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understandi...Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.展开更多
Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(...Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.展开更多
目的:观察外科感染病人胰岛素抵抗(IR)状况,研究其临床意义,并探讨如何应用临床常用参数评价感染病人的胰岛素敏感性(ISI)。方法:检测外科不同病情严重程度感染患者空腹血糖(FBG)、空腹胰岛素(FINS),以正常健康人为对照,利用稳态模式评...目的:观察外科感染病人胰岛素抵抗(IR)状况,研究其临床意义,并探讨如何应用临床常用参数评价感染病人的胰岛素敏感性(ISI)。方法:检测外科不同病情严重程度感染患者空腹血糖(FBG)、空腹胰岛素(FINS),以正常健康人为对照,利用稳态模式评估法(HOMA)计算胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-)β,观察外科感染病人ISI,并且分析不同病情严重程度和不同病种感染病人之间ISI是否存在显著差异。使用多元线性回归方程和多因素Logistic进行多因素分析,应用临床常用的参数评价感染ISI状况。结果:①外科感染病人中IR发生率为92.06%(58/63)。不同病种,包括急性重症胰腺炎病人、肠瘘病人和急性胆管炎病人,不论HOMA-IRl、gHOMA-IR还是HOMA-β均无显著差异(P>0.05)。②按病情严重度和最终预后对病人分组:SIRS病人IR发生率为20%(7/35),脓毒症病人IR发生率为86.20%(25/29),脓毒性休克和MODS组病人IR发生率为95.83%(23/24),死亡组病人IR发生率为100%(10/10)。各组间IR有显著差异(P<0.01),而HOMA-β无显著差异(P>0.05)。③临床各常用参数与ISI之间相关性分析显示器官功能衰竭连续评分(sequential organ failure assessment,SOFA)、FINS、FBG、转铁蛋白、脓毒症评分(sepsis scores,SS)评分、C-反应蛋白(CRP)、前白蛋白、三酰甘油(TG)和胰岛素用量/葡萄糖用量与ISI呈独立正相关,方程的R2为0.900。各临床参数对IR的多因素Logistic回归显示FINS、FBG、低密度脂蛋白(LDL)和SOFA进入模型,其中FBG和FINS与IR的回归关系更明显,而其他临床指标与IR未显示有意义的回归关系。结论:①外科感染病人中普遍存在IR,并与引起感染的病种无关;②IR与疾病严重程度最终预后密切相关,可作为判断危重病人病情转归和预后的预警指标;③临床常用参数SOFA评分、FINS、FBG、转铁蛋白、SS评分、CRP、前白蛋白和TG与感染病人ISI的关系更为密切。展开更多
文摘AIM:To explore the related risk factors for diabetic retinopathy(DR)in type 2 diabetes with insulin therapy.METHODS:We studied the relationships among blood glucose,serum C-peptide,plasma insulin,beta-cell function and the development of DR.Beta-cell function was assessed by a modified homeostasis model assessment(modified HOMA)which was gained by using C-peptide to replace insulin in the homeostasis model assessment(HOMA)of beta-cell function.We also studied the relationships between modified HOMA index and serum C-peptide response to 100 g tasteless steamed bread to determine the accuracy of modified HOMA.RESULTS:Our study group consisted of 170 type 2diabetic inpatients with DR(age:58.35±13.87y,mean±SD)and 205 type 2 diabetic inpatients with no DR(NDR)(age:65.52±11.59y).DR patients had higher age,longer diabetic duration,higher hypertension grade,higher postprandial plasma glucose,higher fluctuation level of plasma glucose,lower body mass index(BMI),lower postprandial serum insulin and C-peptide,lower fluctuation level of serum insulin and C-peptide(P【0.05).In our logistic regression model,duration of diabetes,hypertension grade,fasting plasma insulin and glycosylated hemoglobin(HbA1C)were significantly associated with the presence of DR after adjustment for confounding factors(P【0.05).CONCLUSION:Our results suggested although modified HOMA showed significant correlation to the occurrence of DR on Spearman’s rank-correlationanalysis,logistic regression showed no significant association between these two variables after adjustment for relevant confounding factors(such as age,sex,duration of diabetes,BMI,hypertension grade,HbA1C,plasma insulin).Duration of diabetes,hypertension grade,fasting plasma insulin and HbA1C were independently associated with the development of DR in Chinese type 2 diabetics.
基金supported by the National Natural Science Foundation of China(31972625)China Postdoctoral Science Foundation(2020M681718)+2 种基金Priority Academic Program Development(PAPD)of Jiangsu Higher Education InstitutionsPostgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX21_2963)China Agriculture Research System(CARS)of Ministry of Finance and Ministry of Agriculture and Rural Areas。
文摘Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the molecular mechanism underlying high PPC(HPPC)is scant.Here,an animal model of primary hyperproteinemia was constructed in an invertebrate(Bombyx mori)to investigate the effects of HPPC on circulating blood cells.Results showed that HPPC affected blood cell homeostasis,leading to increased reactive oxygen species levels,and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway.HPPC induced the proliferation of blood cells,mainly granulocytes,by activating the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway.Supplementation with the endocrine hormone active substance 20 E significantly reduced the impact of HPPC on blood cell homeostasis.Thus,we identified a novel signaling pathway by which HPPC affects blood cell homeostasis,which differs from hyperglycemia,hyperlipidemia,and hypercholesterolemia.In addition,we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.
基金supported by fellowship to a grant from CRT Foundation,No.1393-2017(to LT)grants from the Fondazione Cariplo,Nos.2013-0795(to AAG),2014-1094(to DL)grants from The Universitàdel Piemonte Orientale,Nos.FAR-2016(to DL),FAR-2019(to DL)。
文摘Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.
基金Supported by the Austrian EURASIA-PACIFIC UNINET Technology Scholarship,the Austrian Federal Ministry of Science and Research and the Austrian Federal Ministry of Health(GZ 402.000/0006-II/6b/2012)the National Basic Research Program of China(No.2014CB543203)
文摘Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.
文摘目的:观察外科感染病人胰岛素抵抗(IR)状况,研究其临床意义,并探讨如何应用临床常用参数评价感染病人的胰岛素敏感性(ISI)。方法:检测外科不同病情严重程度感染患者空腹血糖(FBG)、空腹胰岛素(FINS),以正常健康人为对照,利用稳态模式评估法(HOMA)计算胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-)β,观察外科感染病人ISI,并且分析不同病情严重程度和不同病种感染病人之间ISI是否存在显著差异。使用多元线性回归方程和多因素Logistic进行多因素分析,应用临床常用的参数评价感染ISI状况。结果:①外科感染病人中IR发生率为92.06%(58/63)。不同病种,包括急性重症胰腺炎病人、肠瘘病人和急性胆管炎病人,不论HOMA-IRl、gHOMA-IR还是HOMA-β均无显著差异(P>0.05)。②按病情严重度和最终预后对病人分组:SIRS病人IR发生率为20%(7/35),脓毒症病人IR发生率为86.20%(25/29),脓毒性休克和MODS组病人IR发生率为95.83%(23/24),死亡组病人IR发生率为100%(10/10)。各组间IR有显著差异(P<0.01),而HOMA-β无显著差异(P>0.05)。③临床各常用参数与ISI之间相关性分析显示器官功能衰竭连续评分(sequential organ failure assessment,SOFA)、FINS、FBG、转铁蛋白、脓毒症评分(sepsis scores,SS)评分、C-反应蛋白(CRP)、前白蛋白、三酰甘油(TG)和胰岛素用量/葡萄糖用量与ISI呈独立正相关,方程的R2为0.900。各临床参数对IR的多因素Logistic回归显示FINS、FBG、低密度脂蛋白(LDL)和SOFA进入模型,其中FBG和FINS与IR的回归关系更明显,而其他临床指标与IR未显示有意义的回归关系。结论:①外科感染病人中普遍存在IR,并与引起感染的病种无关;②IR与疾病严重程度最终预后密切相关,可作为判断危重病人病情转归和预后的预警指标;③临床常用参数SOFA评分、FINS、FBG、转铁蛋白、SS评分、CRP、前白蛋白和TG与感染病人ISI的关系更为密切。
