Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several dru...Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.展开更多
Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty...Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.展开更多
Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of...Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of reduced villus height and crypt depth,increased permeability,as well as altered sugar and peptide absorption in the small intestine after induction of inflammation in experimental models,which is supported by some clinical data.Identification of inflammatory factors which may promote the process of gastrointestinal dysfunction as well as clinical research to verify experimental observations of inflammatory modulation of gastrointestinal function are required.Moreover,nutritional strategies to support functional restitution are needed.展开更多
目的:由年龄增长造成的慢性低度炎症在中老年人群中易发生,并引发多种慢性疾病,从事抗阻运动能否有效降低中老年人炎症因子水平尚无定论。定量评价抗阻训练对中老年人白细胞介素6与C-反应蛋白水平的影响,并分析不同干预对象、干预时间...目的:由年龄增长造成的慢性低度炎症在中老年人群中易发生,并引发多种慢性疾病,从事抗阻运动能否有效降低中老年人炎症因子水平尚无定论。定量评价抗阻训练对中老年人白细胞介素6与C-反应蛋白水平的影响,并分析不同干预对象、干预时间和干预方式对效果的影响,旨在为从事抗阻训练在中老年人健身中应用提供理论依据。方法:检索中国知网、万方数据、PubMed、Web of Science与EBSCO数据库,检索抗阻训练对中老年人白细胞介素6与C-反应蛋白水平影响的随机对照试验或自身对照试验研究,检索截止日期为2020年5月,根据制定的文献纳入与排除标准筛选文献、提取数据资料并采用Cochrane手册5.1.0标准与ROBINS-I 2.0标准评价文献质量,采用Rev Man 5.3软件进行Meta分析,对纳入文献中不同干预性别、干预时间与干预方式进行分组亚组分析。结果:(1)最终纳入13篇文献,受试对象共计246例,总体评估为低风险偏倚文献;(2)Meta分析结果显示,抗阻训练能显著降低中老年人白细胞介素6水平(MD=-0.30,95%CI:-0.48至-0.11,P=0.002),不能显著降低C-反应蛋白水平(MD=-0.26,95%CI:-0.54至-0.02,P=0.07);(3)亚组分析结果显示,中老年群体中抗阻训练有效降低白细胞介素6水平,受干预对象与干预时间影响小(P <0.05),≤12周的抗阻训练能有效降低C-反应蛋白水平(P <0.05),抗阻训练(MD=-0.25,95%CI:-0.54-0.04,P=0.05)较弹力带抗阻训练(MD=-0.34,95%CI:-1.39-0.71,P=0.87)对降低C-反应蛋白水平效果较为明显。结论:(1)抗阻训练能有效降低中老年人白细胞介素6水平,且不排除抗阻训练显著降低中老年人C-反应蛋白水平的可能;(2)中老年人短期从事抗阻运动训练(≤12周)对降低白细胞介素6与C-反应蛋白炎症因子水平效果明显,且进行机械抗阻训练相较于弹力带抗阻训练可能获得更大效益;(3)明确抗阻训练对C-反应蛋白水平干预效果或不同研究对象间干预效果是否存在显著性差异,还需要未来更多的研究进一步验证。展开更多
Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some ...Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some recent reports have found an interesting correlation between obesity and IBS.A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD,leading to an increased cardiovascular risk,and IBS,leading to microbial dysbiosis,impaired intestinal barrier and altered intestinal motility.It is not known when considering local and systemic inflammation/immune system activation,which one has greater importance in NAFLD and IBS pathogenesis.Also,the nervous system is implicated.In fact,inflammation participates in the development of mood disorders,such as anxiety and depression,characteristics of obesity and consequently of NAFLD and,on the other hand,in intestinal hypersensitivity and dysmotility.展开更多
In the past 10 years the prevalence of type 2 diabetes mel itus(T2DM) has increased hugely worldwide,driven by a rise in the numbers of overweight and obese individuals.A number of diets have been shown to be effectiv...In the past 10 years the prevalence of type 2 diabetes mel itus(T2DM) has increased hugely worldwide,driven by a rise in the numbers of overweight and obese individuals.A number of diets have been shown to be effective for the management of T2DM:the Mediterranean diet,the vegetarian diet and the low-calorie diet.Results of studies clearly indicate,however,that the efficacy of these diets is not solely related to the biochemical structure of the individual nutrients they contain.This review discusses this point with reference to the potential role of the intestinal microbiota in diabetes.The macrobiotic Ma-Pi 2 diet is rich in carbohydrates,whole grains and vegetables,with no animal fat or protein or added sugar.In shortand medium-term trials conducted in patients with T2 DM,the Ma-Pi 2 diet has been found to significantly improve indicators of metabolic control,including fasting blood glucose,glycosylated hemoglobin,the serum lipid profile,body mass index,body weight and blood pressure.The diet may also alter the gut microbiota composition,which could additionally affect glycemic control.As a result,the Ma-Pi 2 diet could be considered a valid additional shortto medium-term treatment for T2 DM.展开更多
Whether obesity is a disease or a risk factor of metabolic diseases including type 2 diabetes and fatty liver remains debating, we report here that a high-fat diet (HFD) alone or HFD-combined intramuscular injection w...Whether obesity is a disease or a risk factor of metabolic diseases including type 2 diabetes and fatty liver remains debating, we report here that a high-fat diet (HFD) alone or HFD-combined intramuscular injection with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces mouse peripheral noninflammatory obesity. In contrast, HFD-combined intraperitoneal injection with a low dose (0.25 mg/kg) of LPS induces mouse visceral low-grade inflammatory obesity. While the noninsulin-dependent diabetes mellitus (NIDDM) and nonalcoholic fatty liver disease (NAFLD)- related genes are globally upregulated in HFD + low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD + high-dose LPS mice. The mitochondrial uncoupler 2,4-dini- trophenol (DNP) in the dosage of 16 mg/kg was found to exert a weight-reducing effect in obese mice by compromising NF-κB-primed inflammatory responses, thereby down regulating NIDDM and NAFLD genes. Conclusively, mouse visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.展开更多
We have studied the presence of novel inflammatory markers as soluble urokinase plasminogen activator receptor (suPAR) and natural IgM antibodies directed against phosphorylcholine (αPC-IgM) in Swedish diabetic patie...We have studied the presence of novel inflammatory markers as soluble urokinase plasminogen activator receptor (suPAR) and natural IgM antibodies directed against phosphorylcholine (αPC-IgM) in Swedish diabetic patients (n = 164) and in healthy control subjects (n = 41). SuPAR is expressed by several types of immune cells and has been shown to be a marker of disease severity and predict mortality during infections. It has also been associated with low-grade inflammation. High levels of αPC-IgM have been shown to negatively associate with the risk of cardiovascular disease and vascular inflammation. This has been suggested to be more common among diabetic patients than in the background population. The patients were 15-34 years of age and were included in the diabetes incidence study in Sweden (DISS). They were all clinically diagnosed to have either T1D (n = 82) or T2D (n = 82). All subjects were matched in gender and age. Commercially available ELISA was used to detect suPAR and αPC-IgM. We found that suPAR levels were higher in diabetic patients (n = 164, Q2 = 4.5 mg/L) compared to in healthy control subjects (n = 41, Q2 = 2.7 mg/L;p 2 = 4.9) compared to in patients classified with T1D (n = 82;p=0.0002). The difference between T2D and T1D was even more obvious when LADA (n = 17) was extracted from the T2D group. SuPAR levels did also correlate with BMI (rs = 0.50;p s = 0.23;p s = 0.58;p < 0.0001). Titers of αPC-IgM did not significantly differ between patients and controls. This is the first study to show the difference in suPAR levels between T1D and T2D patients. The high levels of suPAR in T2D patients indicate a strong activation of the immune system and its relation to disease progression needs to be further investigated. However, our data do not support a role for αPC-IgM in the development of diabetes.展开更多
文摘Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.
文摘Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.
文摘Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of reduced villus height and crypt depth,increased permeability,as well as altered sugar and peptide absorption in the small intestine after induction of inflammation in experimental models,which is supported by some clinical data.Identification of inflammatory factors which may promote the process of gastrointestinal dysfunction as well as clinical research to verify experimental observations of inflammatory modulation of gastrointestinal function are required.Moreover,nutritional strategies to support functional restitution are needed.
文摘目的:由年龄增长造成的慢性低度炎症在中老年人群中易发生,并引发多种慢性疾病,从事抗阻运动能否有效降低中老年人炎症因子水平尚无定论。定量评价抗阻训练对中老年人白细胞介素6与C-反应蛋白水平的影响,并分析不同干预对象、干预时间和干预方式对效果的影响,旨在为从事抗阻训练在中老年人健身中应用提供理论依据。方法:检索中国知网、万方数据、PubMed、Web of Science与EBSCO数据库,检索抗阻训练对中老年人白细胞介素6与C-反应蛋白水平影响的随机对照试验或自身对照试验研究,检索截止日期为2020年5月,根据制定的文献纳入与排除标准筛选文献、提取数据资料并采用Cochrane手册5.1.0标准与ROBINS-I 2.0标准评价文献质量,采用Rev Man 5.3软件进行Meta分析,对纳入文献中不同干预性别、干预时间与干预方式进行分组亚组分析。结果:(1)最终纳入13篇文献,受试对象共计246例,总体评估为低风险偏倚文献;(2)Meta分析结果显示,抗阻训练能显著降低中老年人白细胞介素6水平(MD=-0.30,95%CI:-0.48至-0.11,P=0.002),不能显著降低C-反应蛋白水平(MD=-0.26,95%CI:-0.54至-0.02,P=0.07);(3)亚组分析结果显示,中老年群体中抗阻训练有效降低白细胞介素6水平,受干预对象与干预时间影响小(P <0.05),≤12周的抗阻训练能有效降低C-反应蛋白水平(P <0.05),抗阻训练(MD=-0.25,95%CI:-0.54-0.04,P=0.05)较弹力带抗阻训练(MD=-0.34,95%CI:-1.39-0.71,P=0.87)对降低C-反应蛋白水平效果较为明显。结论:(1)抗阻训练能有效降低中老年人白细胞介素6水平,且不排除抗阻训练显著降低中老年人C-反应蛋白水平的可能;(2)中老年人短期从事抗阻运动训练(≤12周)对降低白细胞介素6与C-反应蛋白炎症因子水平效果明显,且进行机械抗阻训练相较于弹力带抗阻训练可能获得更大效益;(3)明确抗阻训练对C-反应蛋白水平干预效果或不同研究对象间干预效果是否存在显著性差异,还需要未来更多的研究进一步验证。
文摘Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some recent reports have found an interesting correlation between obesity and IBS.A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD,leading to an increased cardiovascular risk,and IBS,leading to microbial dysbiosis,impaired intestinal barrier and altered intestinal motility.It is not known when considering local and systemic inflammation/immune system activation,which one has greater importance in NAFLD and IBS pathogenesis.Also,the nervous system is implicated.In fact,inflammation participates in the development of mood disorders,such as anxiety and depression,characteristics of obesity and consequently of NAFLD and,on the other hand,in intestinal hypersensitivity and dysmotility.
文摘In the past 10 years the prevalence of type 2 diabetes mel itus(T2DM) has increased hugely worldwide,driven by a rise in the numbers of overweight and obese individuals.A number of diets have been shown to be effective for the management of T2DM:the Mediterranean diet,the vegetarian diet and the low-calorie diet.Results of studies clearly indicate,however,that the efficacy of these diets is not solely related to the biochemical structure of the individual nutrients they contain.This review discusses this point with reference to the potential role of the intestinal microbiota in diabetes.The macrobiotic Ma-Pi 2 diet is rich in carbohydrates,whole grains and vegetables,with no animal fat or protein or added sugar.In shortand medium-term trials conducted in patients with T2 DM,the Ma-Pi 2 diet has been found to significantly improve indicators of metabolic control,including fasting blood glucose,glycosylated hemoglobin,the serum lipid profile,body mass index,body weight and blood pressure.The diet may also alter the gut microbiota composition,which could additionally affect glycemic control.As a result,the Ma-Pi 2 diet could be considered a valid additional shortto medium-term treatment for T2 DM.
文摘Whether obesity is a disease or a risk factor of metabolic diseases including type 2 diabetes and fatty liver remains debating, we report here that a high-fat diet (HFD) alone or HFD-combined intramuscular injection with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces mouse peripheral noninflammatory obesity. In contrast, HFD-combined intraperitoneal injection with a low dose (0.25 mg/kg) of LPS induces mouse visceral low-grade inflammatory obesity. While the noninsulin-dependent diabetes mellitus (NIDDM) and nonalcoholic fatty liver disease (NAFLD)- related genes are globally upregulated in HFD + low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD + high-dose LPS mice. The mitochondrial uncoupler 2,4-dini- trophenol (DNP) in the dosage of 16 mg/kg was found to exert a weight-reducing effect in obese mice by compromising NF-κB-primed inflammatory responses, thereby down regulating NIDDM and NAFLD genes. Conclusively, mouse visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.
文摘We have studied the presence of novel inflammatory markers as soluble urokinase plasminogen activator receptor (suPAR) and natural IgM antibodies directed against phosphorylcholine (αPC-IgM) in Swedish diabetic patients (n = 164) and in healthy control subjects (n = 41). SuPAR is expressed by several types of immune cells and has been shown to be a marker of disease severity and predict mortality during infections. It has also been associated with low-grade inflammation. High levels of αPC-IgM have been shown to negatively associate with the risk of cardiovascular disease and vascular inflammation. This has been suggested to be more common among diabetic patients than in the background population. The patients were 15-34 years of age and were included in the diabetes incidence study in Sweden (DISS). They were all clinically diagnosed to have either T1D (n = 82) or T2D (n = 82). All subjects were matched in gender and age. Commercially available ELISA was used to detect suPAR and αPC-IgM. We found that suPAR levels were higher in diabetic patients (n = 164, Q2 = 4.5 mg/L) compared to in healthy control subjects (n = 41, Q2 = 2.7 mg/L;p 2 = 4.9) compared to in patients classified with T1D (n = 82;p=0.0002). The difference between T2D and T1D was even more obvious when LADA (n = 17) was extracted from the T2D group. SuPAR levels did also correlate with BMI (rs = 0.50;p s = 0.23;p s = 0.58;p < 0.0001). Titers of αPC-IgM did not significantly differ between patients and controls. This is the first study to show the difference in suPAR levels between T1D and T2D patients. The high levels of suPAR in T2D patients indicate a strong activation of the immune system and its relation to disease progression needs to be further investigated. However, our data do not support a role for αPC-IgM in the development of diabetes.
