弥漫性大B细胞淋巴瘤(diffuse large Bcell lymphoma,DLBCL)是一种具有高度异质性的侵袭性恶性肿瘤,这种异质性不仅表现在临床结局、遗传特征、细胞起源等方面,而且在能量代谢方面也存在着明显的异质性。根据能量代谢差异,DLBCL可分为...弥漫性大B细胞淋巴瘤(diffuse large Bcell lymphoma,DLBCL)是一种具有高度异质性的侵袭性恶性肿瘤,这种异质性不仅表现在临床结局、遗传特征、细胞起源等方面,而且在能量代谢方面也存在着明显的异质性。根据能量代谢差异,DLBCL可分为以有氧糖酵解为主要代谢特征的B细胞受体(BCR)-DLBCL亚型和以氧化磷酸化(OxPhos)为主要代谢特征的OxPhos-DLBCL亚型。对于这两种不同代谢方式的DLBCL,有着差异显著的细胞调控通路。目前研究表明,BCR信号通路、bcl-6和自噬等调节BCR-DLBCL亚型细胞的有氧糖酵解过程;高度活化的线粒体功能基因和高表达的脂肪酸代谢关键基因等调节OxPhos-DLBCL亚型细胞的氧化磷酸化过程。靶向DLBCL的能量代谢差异及相关调控通路,可能为DLBCL患者的治疗和预后评估提供新的思路。展开更多
With its long-term empirical clinical practice and increasing number of health benefits reported,Chinese Materia Medica(CMM)is gaining increasing global acceptance.Importantly,the identification of chemical constituen...With its long-term empirical clinical practice and increasing number of health benefits reported,Chinese Materia Medica(CMM)is gaining increasing global acceptance.Importantly,the identification of chemical constituents in vitro and exposed forms in vivo is a prerequisite for understanding how CMM formulae prevent and treat diseases.This review systematically summarizes the exciting and magical journey of CMM components from compound formulae to where they fight,the possible structural transformation of CMM components in vitro and in vivo,and their pharmacological contribution.When a decoction is prepared,significant chemical reactions are observed,including degradation and production of polymers and self-assembling supramolecules,leading to the construction of a component library with diverse decoction structures.After ingestion,compounds pass through the intestinal and blood-brain barriers and undergo a more wonderful journey involving the gut microbiota,microbial enzymes,and endogenous drug-metabolizing enzymes(mainly liver enzymes).At this stage,they are modified and assembled into novel and complex compounds,such as newly generated metabolites,conjugates,and self-assembling superamolecules.This review might provide a strategic orientation to explore the active compounds of CMM formulae in vivo.展开更多
The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy.The consumption of sugarsweetened beverages is the main source of added sugars.Fructose,to...The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy.The consumption of sugarsweetened beverages is the main source of added sugars.Fructose,together with glucose,as a component of high fructose corn syrups or as a component of the sucrose molecule,is one of the main sweeteners present in this kind of beverages.Data from prospective and intervention studies clearly point to high fructose consumption,mainly in the form of sweetened beverages,as a risk factor for several metabolic diseases in humans.The incidence of hypertension,nonalcoholic fatty liver disease(NAFLD),dyslipidemia(mainly hypertriglyceridemia),insulin resistance,type 2 diabetes mellitus,obesity,and the cluster of many of these pathologies in the form of metabolic syndrome is higher in human population segments that show high intake of fructose.Adolescent and young adults from lowincome families are especially at risk.We recently reviewed evidence from experimental animals and human data that confirms the deleterious effect of fructose on lipid and glucose metabolism.In this present review we update the information generated in the past 2 years about high consumption of fructose-enriched beverages and the occurrence of metabolic disturbances,especially NAFLD,type 2 diabetes mellitus,and metabolic syndrome.We have explored recent data from observational and experimental human studies,as well as experimental data from animal and cell models.Finally,using information generated in our laboratory and others,we provide a view of the molecular mechanisms that may be specifically involved in the development of liver lipid and glucose metabolic alterations after fructose consumption in liquid form.展开更多
Objective To compare the efficacy of treating obese patients with abnormity of lipids and serum leptin by dilatational wave or continuous wave of electroacupuncture combined with thunder-fire moxibustion in order to p...Objective To compare the efficacy of treating obese patients with abnormity of lipids and serum leptin by dilatational wave or continuous wave of electroacupuncture combined with thunder-fire moxibustion in order to provide a clinical basis for selecting wave types of electroacupuncture for different patterns of obesity. Methods Sixty obese patients with abnormal lipids and serum leptin were randomly divided into a dilatational wave group and a continuous wave group via random number table, with 30 cases in each group. They were divided by TCM differentiation into three types： stomachintestine excessive heat, weakness of the spleen-stomach and spleen-kidney yang deficiency, treated by electroacupuncture on Tianshu （天枢 ST 25）, Daheng （大横 SP 15）, Zusanli （足三里ST 36）, Shangjuxu （上巨虚 ST 37）, Fanglong （丰隆 ST 40）, Yinlingquan （阴陵泉 SP 9）, Quchi （曲池 LI 11）, Zhigou （支沟 TE 6） and Hegu （合谷 LI 4） along with thunder-fire moxibustion. The frequency of electro-acupuncture in the dilatational wave group and the continuous wave group was 2 Hz/100 Hz and 2 Hz, respectively. Patients in the two groups were treated once a day, six times a week. The treatment lasted for 4 weeks with 3-month follow-up. Body mass and body fat percentage before and after the treatment, as well as during the follow-up, were compared. The effectiveness rates in the two groups were compared, and the efficacy statistics of patients with different TCM patterns in the dilatational wave group were also analyzed. Lipid levels of the patients in two groups before and after the treatment were measured with an automatic biochemical analyzer, and serum leptin levels were detected with flow cytometry system. Results After the treatment, the patients＇ blood lipids, serum leptin levels, body mass and body fat percentage were effectively reduced in the two groups; three months＇ follow-up witnessed continuous decline of obesity indicators （P〈0.01 or P〈0.05）, and patients in the dilatat-ional wave group improved more significantly than those in continuous wave group （P〈0.05 or P〈0.01）. The efficacy in the dilatational wave group was superior to that in the continuous wave group （P〈0.01）. The best efficacy could be found among patients with weakness of the spleen and the stomach in the dilatational wave group. Conclusion Efficacy of treating obese patients with abnormity of lipids and serum leptin by electro-acupuncture combined with thunder-fire moxibustion in the dilatational wave group was significantly better than that of the continuous wave group, and efficacy for obese patients with weakness of the spleen and the stomach was superior to that of those with stomach-intestine excessive heat and spleen-kidney yang deficiency.展开更多
Polymorphisms associated with genes coding for a variety of drug-metabolizing enzymes （DMEs） and associated transport proteins can influence the drug metabolism rate of individuals, potentially affecting the efficac...Polymorphisms associated with genes coding for a variety of drug-metabolizing enzymes （DMEs） and associated transport proteins can influence the drug metabolism rate of individuals, potentially affecting the efficacy of drug and the occurrence of adverse reactions. Single nucleotide polymorphisms （SNPs） are prevalent in all types of genetic variations. Reliable SNP genotyping provides excellent markers for detecting genetic polymolphisms, genetic disorders, and resistance of pathogen to drug, which are needed for the genetic diagnosis of disease and subtle genetic factors. With a large number of SNP genotyping studies being conducted, a lot of novel SNP identifying methods have been developed. Several SNP genotyping methods and techniques have been introduced for clinical test. These include TaqMan drug metabolism genotyping assays, pH-sensing semiconductor system, high-resolution melting curve analysis （HRM） of polymerase chain reaction （PCR） amplicons, novel multiplexed electrochemical biosensor with non-fouling surface, DNA hybridization detection using less than 10-nm gap silicon nanogap structure, tetra-primer ARMS-PCR method, acoustic detection of DNA conformation in genetic assays combined with PCR, microbeads-mass spectrometry （MEMS）-based approach, and liquid chromatography-electrospray ionization mass spectrometry. Personalized medicine has changed the conventional ways of using drugs according to experiences. It focuses on making the individualized pattern for each individual based on their own characteristics. Lots of researchers are using the analysis of clinical samples to explain the relationship between the drug adverse reactions and genetic polymorphisms. But it takes a long time from collecting the blood samples for DNA extraction and genotyping to getting results on the side effect of drug through clinical study. Therefore, it is desirable to develop improved in vitro methods to study the drug metabolizing-enzymes and transport protein genetic polymorphisms.展开更多
文摘弥漫性大B细胞淋巴瘤(diffuse large Bcell lymphoma,DLBCL)是一种具有高度异质性的侵袭性恶性肿瘤,这种异质性不仅表现在临床结局、遗传特征、细胞起源等方面,而且在能量代谢方面也存在着明显的异质性。根据能量代谢差异,DLBCL可分为以有氧糖酵解为主要代谢特征的B细胞受体(BCR)-DLBCL亚型和以氧化磷酸化(OxPhos)为主要代谢特征的OxPhos-DLBCL亚型。对于这两种不同代谢方式的DLBCL,有着差异显著的细胞调控通路。目前研究表明,BCR信号通路、bcl-6和自噬等调节BCR-DLBCL亚型细胞的有氧糖酵解过程;高度活化的线粒体功能基因和高表达的脂肪酸代谢关键基因等调节OxPhos-DLBCL亚型细胞的氧化磷酸化过程。靶向DLBCL的能量代谢差异及相关调控通路,可能为DLBCL患者的治疗和预后评估提供新的思路。
基金supported by the National Natural Science Foundation of China(81873192 and 81202877)Postgraduate Research and Innovation Project of Tianjin(2021YJSB288 and YJSKC-20211004)the Science and Technology Program of Tianjin(Grant No.20ZYJDJC00070)
文摘With its long-term empirical clinical practice and increasing number of health benefits reported,Chinese Materia Medica(CMM)is gaining increasing global acceptance.Importantly,the identification of chemical constituents in vitro and exposed forms in vivo is a prerequisite for understanding how CMM formulae prevent and treat diseases.This review systematically summarizes the exciting and magical journey of CMM components from compound formulae to where they fight,the possible structural transformation of CMM components in vitro and in vivo,and their pharmacological contribution.When a decoction is prepared,significant chemical reactions are observed,including degradation and production of polymers and self-assembling supramolecules,leading to the construction of a component library with diverse decoction structures.After ingestion,compounds pass through the intestinal and blood-brain barriers and undergo a more wonderful journey involving the gut microbiota,microbial enzymes,and endogenous drug-metabolizing enzymes(mainly liver enzymes).At this stage,they are modified and assembled into novel and complex compounds,such as newly generated metabolites,conjugates,and self-assembling superamolecules.This review might provide a strategic orientation to explore the active compounds of CMM formulae in vivo.
基金Supported by Fundació Privada Catalana de Nutrició i Lípids and Grant SAF2010-15664 from the Spanish Ministry of Sci ence and Innovation
文摘The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy.The consumption of sugarsweetened beverages is the main source of added sugars.Fructose,together with glucose,as a component of high fructose corn syrups or as a component of the sucrose molecule,is one of the main sweeteners present in this kind of beverages.Data from prospective and intervention studies clearly point to high fructose consumption,mainly in the form of sweetened beverages,as a risk factor for several metabolic diseases in humans.The incidence of hypertension,nonalcoholic fatty liver disease(NAFLD),dyslipidemia(mainly hypertriglyceridemia),insulin resistance,type 2 diabetes mellitus,obesity,and the cluster of many of these pathologies in the form of metabolic syndrome is higher in human population segments that show high intake of fructose.Adolescent and young adults from lowincome families are especially at risk.We recently reviewed evidence from experimental animals and human data that confirms the deleterious effect of fructose on lipid and glucose metabolism.In this present review we update the information generated in the past 2 years about high consumption of fructose-enriched beverages and the occurrence of metabolic disturbances,especially NAFLD,type 2 diabetes mellitus,and metabolic syndrome.We have explored recent data from observational and experimental human studies,as well as experimental data from animal and cell models.Finally,using information generated in our laboratory and others,we provide a view of the molecular mechanisms that may be specifically involved in the development of liver lipid and glucose metabolic alterations after fructose consumption in liquid form.
基金Supported by Guangxi Natural Science Foundation Project:2010 GXNSFA 013210
文摘Objective To compare the efficacy of treating obese patients with abnormity of lipids and serum leptin by dilatational wave or continuous wave of electroacupuncture combined with thunder-fire moxibustion in order to provide a clinical basis for selecting wave types of electroacupuncture for different patterns of obesity. Methods Sixty obese patients with abnormal lipids and serum leptin were randomly divided into a dilatational wave group and a continuous wave group via random number table, with 30 cases in each group. They were divided by TCM differentiation into three types： stomachintestine excessive heat, weakness of the spleen-stomach and spleen-kidney yang deficiency, treated by electroacupuncture on Tianshu （天枢 ST 25）, Daheng （大横 SP 15）, Zusanli （足三里ST 36）, Shangjuxu （上巨虚 ST 37）, Fanglong （丰隆 ST 40）, Yinlingquan （阴陵泉 SP 9）, Quchi （曲池 LI 11）, Zhigou （支沟 TE 6） and Hegu （合谷 LI 4） along with thunder-fire moxibustion. The frequency of electro-acupuncture in the dilatational wave group and the continuous wave group was 2 Hz/100 Hz and 2 Hz, respectively. Patients in the two groups were treated once a day, six times a week. The treatment lasted for 4 weeks with 3-month follow-up. Body mass and body fat percentage before and after the treatment, as well as during the follow-up, were compared. The effectiveness rates in the two groups were compared, and the efficacy statistics of patients with different TCM patterns in the dilatational wave group were also analyzed. Lipid levels of the patients in two groups before and after the treatment were measured with an automatic biochemical analyzer, and serum leptin levels were detected with flow cytometry system. Results After the treatment, the patients＇ blood lipids, serum leptin levels, body mass and body fat percentage were effectively reduced in the two groups; three months＇ follow-up witnessed continuous decline of obesity indicators （P〈0.01 or P〈0.05）, and patients in the dilatat-ional wave group improved more significantly than those in continuous wave group （P〈0.05 or P〈0.01）. The efficacy in the dilatational wave group was superior to that in the continuous wave group （P〈0.01）. The best efficacy could be found among patients with weakness of the spleen and the stomach in the dilatational wave group. Conclusion Efficacy of treating obese patients with abnormity of lipids and serum leptin by electro-acupuncture combined with thunder-fire moxibustion in the dilatational wave group was significantly better than that of the continuous wave group, and efficacy for obese patients with weakness of the spleen and the stomach was superior to that of those with stomach-intestine excessive heat and spleen-kidney yang deficiency.
基金The Influence of Artesunate on β-catenin Signaling Pathway of Hetatic Atellate Cells(Grant No.2011CDB491)
文摘Polymorphisms associated with genes coding for a variety of drug-metabolizing enzymes （DMEs） and associated transport proteins can influence the drug metabolism rate of individuals, potentially affecting the efficacy of drug and the occurrence of adverse reactions. Single nucleotide polymorphisms （SNPs） are prevalent in all types of genetic variations. Reliable SNP genotyping provides excellent markers for detecting genetic polymolphisms, genetic disorders, and resistance of pathogen to drug, which are needed for the genetic diagnosis of disease and subtle genetic factors. With a large number of SNP genotyping studies being conducted, a lot of novel SNP identifying methods have been developed. Several SNP genotyping methods and techniques have been introduced for clinical test. These include TaqMan drug metabolism genotyping assays, pH-sensing semiconductor system, high-resolution melting curve analysis （HRM） of polymerase chain reaction （PCR） amplicons, novel multiplexed electrochemical biosensor with non-fouling surface, DNA hybridization detection using less than 10-nm gap silicon nanogap structure, tetra-primer ARMS-PCR method, acoustic detection of DNA conformation in genetic assays combined with PCR, microbeads-mass spectrometry （MEMS）-based approach, and liquid chromatography-electrospray ionization mass spectrometry. Personalized medicine has changed the conventional ways of using drugs according to experiences. It focuses on making the individualized pattern for each individual based on their own characteristics. Lots of researchers are using the analysis of clinical samples to explain the relationship between the drug adverse reactions and genetic polymorphisms. But it takes a long time from collecting the blood samples for DNA extraction and genotyping to getting results on the side effect of drug through clinical study. Therefore, it is desirable to develop improved in vitro methods to study the drug metabolizing-enzymes and transport protein genetic polymorphisms.
