Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a pre...Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis.Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells,resulting in diverse biological consequences including decreased lipolysis,immune regulation,and anti-inflammation wound healing,and enhanced exercise performance in association with the gut microbiome.Furthermore,increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones,which accounts for its key role in immune modulation and maintenance of homeostasis.Here,we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.展开更多
Objective:The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule(LTC)on ischemic stroke rats.Methods:Twenty-six rats were randomly divided into four...Objective:The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule(LTC)on ischemic stroke rats.Methods:Twenty-six rats were randomly divided into four groups,including sham group,sham+LTC group,MCAO group,and MCAO+LTC group.Ischemic stroke rats were simulated by middle cerebral artery occlusion(MCAO),and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days.LTC therapy was validated in terms of neurobehavioral abnormality evaluation,cerebral infarct area,and histological assessments.The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis,aiming to finding the molecules in respond to the surgery or LTC treatment.Results:Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats.The interstitial edema,atrophy,and pyknosis of glial and neuronal cells occurred in the infarcted area,core area,and marginal area of cerebral cortex were improved after LTC treatment.A total of 13 potential biomarkers were observed,and Youden index of 11 biomarkers such as LysoPC,SM,and PE were more than 0.7,which were involved in neuroprotective process.The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism,together with nicotinate and nicotinamide metabolism.Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC.Conclusion:The present study could provide evidence that metabolomics,as systematic approach,revealed its capacity to evaluate the holistic efficacy of TCM,and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.展开更多
Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clin...Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.展开更多
基金supported by the National Natural Science Foundation of China(No.82060042)Guangxi Natural ScienceFoundation(China)(No.2020GXNSFBA297082)+1 种基金Guangxi Science and Technology Program Project(China)(No.AD19245005)The Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi(China)(No.2020KY12017).
文摘Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis.Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells,resulting in diverse biological consequences including decreased lipolysis,immune regulation,and anti-inflammation wound healing,and enhanced exercise performance in association with the gut microbiome.Furthermore,increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones,which accounts for its key role in immune modulation and maintenance of homeostasis.Here,we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.
基金financially supported by the National Natural Science Foundation of China(81573572,81530097,32101957)the National Key R&D Program of China(2022YFC2010104)Agricultural Science and Technology Innovation Program of Institute of Food Science and Technology,Chinese Academy of Agricultural Sciences(CAAS-ASTIP-Q2022-IFST-08)。
文摘Objective:The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule(LTC)on ischemic stroke rats.Methods:Twenty-six rats were randomly divided into four groups,including sham group,sham+LTC group,MCAO group,and MCAO+LTC group.Ischemic stroke rats were simulated by middle cerebral artery occlusion(MCAO),and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days.LTC therapy was validated in terms of neurobehavioral abnormality evaluation,cerebral infarct area,and histological assessments.The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis,aiming to finding the molecules in respond to the surgery or LTC treatment.Results:Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats.The interstitial edema,atrophy,and pyknosis of glial and neuronal cells occurred in the infarcted area,core area,and marginal area of cerebral cortex were improved after LTC treatment.A total of 13 potential biomarkers were observed,and Youden index of 11 biomarkers such as LysoPC,SM,and PE were more than 0.7,which were involved in neuroprotective process.The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism,together with nicotinate and nicotinamide metabolism.Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC.Conclusion:The present study could provide evidence that metabolomics,as systematic approach,revealed its capacity to evaluate the holistic efficacy of TCM,and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.
基金funded in part by the Beijing Natural Science Foundation(JQ20032 to N.W.and to 7191007 to Z.W.)National Natural Science Foundation of China(81822030 and 82072391 to N.W.,81772299and 81930068 to Z.W.,81772301 and 81972132 to G.Q.,81672123and 81972037 to J.Z.)+7 种基金Capital's Funds for Health Improvement and Research(2020-4-40114 to N.W.)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research ProgramNational Key Research and Development Program of China(2018YFC0910500 to N.W.and Z.W.,2016YFC0901501 to S.Z.)the PUMC Youth Fund and the Fundamental Research Funds for the Central Universities(3332019052 to Y.M.)the CAMS Initiative Fund for Medical Sciences(2016-I2M-3-003 to G.Q.and N.W.,2016-I2M-2-006 and 2017-I2M-2-001 to Z.W.)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT320025 to N.W.)sponsored by GeneScience Pharmaceuticals Co.,Ltd.(Changchun,China)funded by the United States National Institutes of Health(UM1HG006542 and K08 HG008986)。
文摘Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.
