Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a ...Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.展开更多
Primary liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. The liver is also the second most common site for metastatic spread of cancer. To assist in the diagnosis of these liv...Primary liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. The liver is also the second most common site for metastatic spread of cancer. To assist in the diagnosis of these liver lesions non-invasive advanced imaging techniques are desirable. Magnetic resonance (MR) is commonly used to identify anatomical lesions, but it is a very versatile technique and also can provide specific information on tumor pathophysiology and metabolism, in particular with the application of MR spectroscopy (MRS). This may include data on the type, grade and stage of tumors, and thus assist in further management of the disease. The purpose of this review is to summarize and discuss the available literature on proton, phosphorus and carbon-13-MRS as performed on primary liver tumors and metastases, with human applications as the main perspective. Upcoming MRSapproaches with potential applications to liver tumors are also included. Since knowledge of some technical background is indispensable to understand the results, a basic introduction of MRS and some technical issues of MRS as applied to tumors and metastases in the liver are described as well. In vivo MR spectroscopy of tumors in a metabolically active organ such as the liver has been demonstrated to provide important information on tumor metabolism, but it also is challenging as compared to applications on some other tissues, in particular in humans, mostly because of its abdominal location where movement may be a disturbing factor.展开更多
Objective To preliminarily evaluate the efficacy of the Fu Zheng method(supporting resistance against pathogenic factors)applied by Professor Hong-Feng CHEN in improving the quality of life in patients with triple-neg...Objective To preliminarily evaluate the efficacy of the Fu Zheng method(supporting resistance against pathogenic factors)applied by Professor Hong-Feng CHEN in improving the quality of life in patients with triple-negative breast cancer(TNBC)to collect and organize the traditional Chinese medicine(TCM)formulas applied by Professor Hong-Feng CHEN in the treatment of TNBC in order to explore the patterns in prescription.Methods The Functional Assessment of Cancer Therapy-Breast scale(FACT-B V4.0)were collected before and after treatment;the database and data mining platform for prescribed TCM formulas were constructed using Microsoft SQL Server 2005,and the patterns in drug pairing and combination were summarized by correlation analysis of data mining.Results The formulas improved the mean scores of the patients’physical well-being,social/family well-being,emotional well-being,physical function well-being and additional concerns(P<0.01);the drug combinations and pairs frequently used by Professor Hong-Feng CHEN were summarized.Conclusion The TCM formulas applied by Professor Hong-Feng CHEN can alleviate adverse physiological reactions,improve psychological conditions and improve function in patients.The formulas take spleen invigoration and stomach nourishment as well as blood circulation promotion and stagnation dissipation as the therapeutic principles,with simplicity in prescription and focus on care and protection the foundation of acquired constitution.展开更多
Lutein is a dietary carotenoid of particular nutritional interest as it is preferentially taken up by neural tissues. Often linked with beneficial effects on vision, a broader role for lutein in neuronal differentiati...Lutein is a dietary carotenoid of particular nutritional interest as it is preferentially taken up by neural tissues. Often linked with beneficial effects on vision, a broader role for lutein in neuronal differentiation has emerged recently, although the underlying mechanisms for these effects are not yet dear. The purpose of this study was to investigate the effect of lutein on neuronal differentiation and explore the associated underpinning mechanisms. We found that lutein treatment enhanced the differentiation of SH-SYSY cells, specifically increasing neuronal arborization and expression of the neuronal process filament protein microtubule-associated protein 2. This effect was mediated by the intracellular phosphoinositide-3-kinase (PI3K) signaling pathway. While PI3K activity is a known trigger of neuronal differentiation, more recently it has also been shown to modulate the metabolic state of cells. Our analysis of bioenergetics found that lutein treatment increased glucose consumption, rates of glycolysis and enhanced respiratory activity of mitochondrial complexes. Concomitantly, the generation of reactive oxygen species was increased (con- sistent with previous reports that reactive oxygen species promote neuronal differentiation), as well as the production of the key metabolic intermediate acetyl-CoA, an essential determinant of epigenetic status in the cell. We suggest that lutein-stimulated neuronal differentiation is mediated by PI3K-dependent modulation of mitochondrial respiration and signaling, and that the consequential metabolic shifts initiate epigenetically dependent transcriptomic reprogramming in support of this morphogenesis. These obser- vations support the potential importance of micronutrients supplementation to neurogenesis, both during normal development and in regenerative repair.展开更多
The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of dige...The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.展开更多
A prominent example of seasonal phenotypic flexibility is the winter increase in thermogenic capacity (=summit metabolism, Msurn) in small birds, which is often accompanied by increases in pectoralis muscle mass and...A prominent example of seasonal phenotypic flexibility is the winter increase in thermogenic capacity (=summit metabolism, Msurn) in small birds, which is often accompanied by increases in pectoralis muscle mass and lipid catabolic capacity. Temperature or photoperiod may be drivers of the winter phenotype, but their relative impacts on muscle remodeling or lipid transport pathways are little known. We examined photoperiod and temperature effects on pectoralis muscle expres- sion of myostatin, a muscle growth inhibitor, and its tolloid-like protein activators (TLL-1 and TLL- 2), and sarcolemmal and intracellular lipid transporters in dark-eyed juncos Junco hyemalis. We acclimated winter juncos to four temperature (3~C or 24~C) and photoperiod [short-day (SD) = 8L:16D; long-day (LD) = 16L:8D] treatments. We found that myostatin, TLL-I, TLL-2, and lipid transporter mRNA expression and myostatin protein expression did not differ among treatments, but treatments interacted to influence lipid transporter proteinexpression. Fatty acid translocase (FAT/CD36) levels were higher for cold SD than for other treatments. Membrane-bound fatty acid binding protein (FABPpm) levels, however, were higher for the cold LD treatment than for cold SD and warm LD treatments. Cytosolic fatty acid binding protein (FABPc) levels were higher on LD than on SD at 3℃, but higher on SD than on LD at 24℃. Cold temperature groups showed upregulation of these lipid transporters, which could contribute to elevated Msum compared to warm groups on the same photoperiod. However, interactions of temperature or photoperiod effects on muscle remodeling and lipid transport pathways suggest that these effects are context-dependent.展开更多
Objective: To investigate the effects of mycotoxin moniliformin (MON) on the metabolism of aggrecan and type 11 collagen in human chondrocytes in vitro and the relationship between MON and Kashin-Beck disease (KBD...Objective: To investigate the effects of mycotoxin moniliformin (MON) on the metabolism of aggrecan and type 11 collagen in human chondrocytes in vitro and the relationship between MON and Kashin-Beck disease (KBD). Methods: Human chondrocytes were isolated and cultured on bone matrix gelatin to form an artificial cartilage model in vitro with or without MON toxin. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of aggrecan and type II collagen in the cartilage was determined using immunocytochemical staining. Results: MON toxin inhibited chondrocyte viability in dose-dependent and time-dependent manners. MON reduced aggrecan and type Ⅱ collagen syntheses in the tissue-engineered cartilage. MON also increased the expression of matrix metalloproteinase-1 (MMP-1), MMP-13, BC4 epitopes, and CD44 in cartilages. However, the expression of 3B3(-) epitopes in cartilages was inhibited by MON. Selenium partially alleviated the damage of aggrecan induced by MON toxin. Conclusion: MON toxin promoted the catabolism of aggrecan and type II collagen in human chondrocytes.展开更多
Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with ca...Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.展开更多
基金supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (No. RGPIN 435807-13) to JPLthe ANZ-MASON foundation (to DB)supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award (No. MSH-141980)
文摘Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.
基金Supported by A grant from the Dutch Cancer Society (KWF Kankerbestrijding), No. KUN 2008-4098
文摘Primary liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. The liver is also the second most common site for metastatic spread of cancer. To assist in the diagnosis of these liver lesions non-invasive advanced imaging techniques are desirable. Magnetic resonance (MR) is commonly used to identify anatomical lesions, but it is a very versatile technique and also can provide specific information on tumor pathophysiology and metabolism, in particular with the application of MR spectroscopy (MRS). This may include data on the type, grade and stage of tumors, and thus assist in further management of the disease. The purpose of this review is to summarize and discuss the available literature on proton, phosphorus and carbon-13-MRS as performed on primary liver tumors and metastases, with human applications as the main perspective. Upcoming MRSapproaches with potential applications to liver tumors are also included. Since knowledge of some technical background is indispensable to understand the results, a basic introduction of MRS and some technical issues of MRS as applied to tumors and metastases in the liver are described as well. In vivo MR spectroscopy of tumors in a metabolically active organ such as the liver has been demonstrated to provide important information on tumor metabolism, but it also is challenging as compared to applications on some other tissues, in particular in humans, mostly because of its abdominal location where movement may be a disturbing factor.
基金support from the Shanghai TCM Gushi Surgical School Heritage Research Base Construction Project of Shanghai Health Bureau(ZYSNXD-CC-APGC-JD-002)
文摘Objective To preliminarily evaluate the efficacy of the Fu Zheng method(supporting resistance against pathogenic factors)applied by Professor Hong-Feng CHEN in improving the quality of life in patients with triple-negative breast cancer(TNBC)to collect and organize the traditional Chinese medicine(TCM)formulas applied by Professor Hong-Feng CHEN in the treatment of TNBC in order to explore the patterns in prescription.Methods The Functional Assessment of Cancer Therapy-Breast scale(FACT-B V4.0)were collected before and after treatment;the database and data mining platform for prescribed TCM formulas were constructed using Microsoft SQL Server 2005,and the patterns in drug pairing and combination were summarized by correlation analysis of data mining.Results The formulas improved the mean scores of the patients’physical well-being,social/family well-being,emotional well-being,physical function well-being and additional concerns(P<0.01);the drug combinations and pairs frequently used by Professor Hong-Feng CHEN were summarized.Conclusion The TCM formulas applied by Professor Hong-Feng CHEN can alleviate adverse physiological reactions,improve psychological conditions and improve function in patients.The formulas take spleen invigoration and stomach nourishment as well as blood circulation promotion and stagnation dissipation as the therapeutic principles,with simplicity in prescription and focus on care and protection the foundation of acquired constitution.
文摘Lutein is a dietary carotenoid of particular nutritional interest as it is preferentially taken up by neural tissues. Often linked with beneficial effects on vision, a broader role for lutein in neuronal differentiation has emerged recently, although the underlying mechanisms for these effects are not yet dear. The purpose of this study was to investigate the effect of lutein on neuronal differentiation and explore the associated underpinning mechanisms. We found that lutein treatment enhanced the differentiation of SH-SYSY cells, specifically increasing neuronal arborization and expression of the neuronal process filament protein microtubule-associated protein 2. This effect was mediated by the intracellular phosphoinositide-3-kinase (PI3K) signaling pathway. While PI3K activity is a known trigger of neuronal differentiation, more recently it has also been shown to modulate the metabolic state of cells. Our analysis of bioenergetics found that lutein treatment increased glucose consumption, rates of glycolysis and enhanced respiratory activity of mitochondrial complexes. Concomitantly, the generation of reactive oxygen species was increased (con- sistent with previous reports that reactive oxygen species promote neuronal differentiation), as well as the production of the key metabolic intermediate acetyl-CoA, an essential determinant of epigenetic status in the cell. We suggest that lutein-stimulated neuronal differentiation is mediated by PI3K-dependent modulation of mitochondrial respiration and signaling, and that the consequential metabolic shifts initiate epigenetically dependent transcriptomic reprogramming in support of this morphogenesis. These obser- vations support the potential importance of micronutrients supplementation to neurogenesis, both during normal development and in regenerative repair.
文摘The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.
文摘A prominent example of seasonal phenotypic flexibility is the winter increase in thermogenic capacity (=summit metabolism, Msurn) in small birds, which is often accompanied by increases in pectoralis muscle mass and lipid catabolic capacity. Temperature or photoperiod may be drivers of the winter phenotype, but their relative impacts on muscle remodeling or lipid transport pathways are little known. We examined photoperiod and temperature effects on pectoralis muscle expres- sion of myostatin, a muscle growth inhibitor, and its tolloid-like protein activators (TLL-1 and TLL- 2), and sarcolemmal and intracellular lipid transporters in dark-eyed juncos Junco hyemalis. We acclimated winter juncos to four temperature (3~C or 24~C) and photoperiod [short-day (SD) = 8L:16D; long-day (LD) = 16L:8D] treatments. We found that myostatin, TLL-I, TLL-2, and lipid transporter mRNA expression and myostatin protein expression did not differ among treatments, but treatments interacted to influence lipid transporter proteinexpression. Fatty acid translocase (FAT/CD36) levels were higher for cold SD than for other treatments. Membrane-bound fatty acid binding protein (FABPpm) levels, however, were higher for the cold LD treatment than for cold SD and warm LD treatments. Cytosolic fatty acid binding protein (FABPc) levels were higher on LD than on SD at 3℃, but higher on SD than on LD at 24℃. Cold temperature groups showed upregulation of these lipid transporters, which could contribute to elevated Msum compared to warm groups on the same photoperiod. However, interactions of temperature or photoperiod effects on muscle remodeling and lipid transport pathways suggest that these effects are context-dependent.
基金Project supported by the National Natural Science Foundation of China (Nos.30872187,30471499,and 30170831)the Ministry of Education of China (No.Key 03152)the Science Foundation of Shaanxi Province of China (No.2004KW-20)
文摘Objective: To investigate the effects of mycotoxin moniliformin (MON) on the metabolism of aggrecan and type 11 collagen in human chondrocytes in vitro and the relationship between MON and Kashin-Beck disease (KBD). Methods: Human chondrocytes were isolated and cultured on bone matrix gelatin to form an artificial cartilage model in vitro with or without MON toxin. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of aggrecan and type II collagen in the cartilage was determined using immunocytochemical staining. Results: MON toxin inhibited chondrocyte viability in dose-dependent and time-dependent manners. MON reduced aggrecan and type Ⅱ collagen syntheses in the tissue-engineered cartilage. MON also increased the expression of matrix metalloproteinase-1 (MMP-1), MMP-13, BC4 epitopes, and CD44 in cartilages. However, the expression of 3B3(-) epitopes in cartilages was inhibited by MON. Selenium partially alleviated the damage of aggrecan induced by MON toxin. Conclusion: MON toxin promoted the catabolism of aggrecan and type II collagen in human chondrocytes.
基金supported by the National Natural Science Foundation of China (81530009 to Youyi Zhang, 81670205 to Han Xiao)
文摘Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.