Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions wit...Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this reactive glycoprotein plays in the progression of injury but also for the insight further studies could provide towards the development of novel therapies for alcoholic liver disease.展开更多
The human liver is the largest organ in the body and has many important physiological functions. A global analysis of human liver proteins is essential for a better understanding of the molecular basis of the normal f...The human liver is the largest organ in the body and has many important physiological functions. A global analysis of human liver proteins is essential for a better understanding of the molecular basis of the normal functions of the liver and of its diseases. As part of the Human Liver Proteome Project (HLPP), the goal of the present study was to visualize and detect as many proteins as possible in normal human livers using two-dimensional gel electrophoresis (2-DE). We have constructed a reference map of the proteins of human normal liver that can be used for the comprehensive analysis of the human liver proteome and other related research. To improve the resolution and enhance the detection of low abundance proteins, we developed and optimized narrow pH range ultra-zoom 2-DE gels. High resolution patterns of human liver in pH gradients 4.5-5.5, 5-6, 5.5-6.7, 6-9 and 6-11 are presented. To improve the poor resolution in the alkaline pH range of 2-DE gels, we optimized the isoelectric focusing protocol by including sample application using cup loading at the anode and incorporating 1.2% hydroxyethyl disulfide, 15% 2-propanol and 5% glycerol in the rehydration buffer. Using the optimized protocol, we obtained reproducibly better resolution in both analytical and preparative 2-DE gels. Compared with the 2386 and 1878 protein spots resolved in the wide range 3-10 and 4-7 pH gradients respectively, we obtained 5481 protein spots from the multiple (overlapping) narrow pH range ultra-zoom gels in the range of pH 4.5-9. The visualized reference map of normal human liver proteins presented in this paper will be valuable for comparative proteomic research of the liver proteome.展开更多
As one of the most important concepts in traditional Chinese medicine, cutaneous regions have a close relationship with skin in modern medicine. According to the doctrine of traditional Chinese medicine, the cutaneous...As one of the most important concepts in traditional Chinese medicine, cutaneous regions have a close relationship with skin in modern medicine. According to the doctrine of traditional Chinese medicine, the cutaneous regions are the corresponding projections of twelve meridians in the superficial layer of the body and play an important role in body surface-viscera correlation. The symptoms of visceral disorders will reflect on cutaneous regions and one of the major patterns of manifestation is referred visceral pain accompanied by tenderness and hyperalgesia on the body surface. On the contrary, cutaneous regions participate in the treatment of visceral disorders. As major clinical applications of the cutaneous regions hypothesis, superficial acupuncture, subcutaneous needling, massage(tuina), moxibustion, and wrist-ankle acupuncture have achieved favorable therapeutic outcomes in clinical practice. Modern researches have gained insights into the biological background of cutaneous regions, however, further studies are needed to clarify the mechanisms.展开更多
Background:There are no published studies on the impact of visceral adipose tissue(VAT)change on outcomes of restorative proctocolectomy and ileal pouch-anal anastomosis(IPAA).The aim of this historic cohort study was...Background:There are no published studies on the impact of visceral adipose tissue(VAT)change on outcomes of restorative proctocolectomy and ileal pouch-anal anastomosis(IPAA).The aim of this historic cohort study was to evaluate the impact of excessive VAT gain on the outcomes of inflammatory bowel disease(IBD)patients with IPAA.Methods:We evaluated all eligible patients with at least two sequential CT scans after pouch construction from our prospectively maintained Pouchitis Registry between 2002 and 2014.The visceral fat area(VFA)was measured on CT images.The study group comprised patients with a significant VAT gain(>15%),and the control group was those without.The adverse outcomes of the pouch were defined as the new development of chronic pouch inflammation(chronic pouchitis,chronic cuffitis or Crohn’s disease of the pouch),anastomotic sinus and the combination of above(the composite adverse outcome)or pouch failure,after the inception CT.Results:Of 1564 patients in the Registry,59(3.8%)with at least 2 CT scans after pouch surgery were included.Twenty-nine patients(49.2%)were in the study group,and 30(50.8%)were in the control group.The median duration from the inception to the latest CT was 552(range:31–2598)days for the entire cohort.We compared the frequency of new chronic pouch inflammation(13.8%vs 3.3%,P=0.195),new pouch sinus(10.3%vs 0%,P=0.112),composite adverse pouch outcome(24.1%vs 3.3%,P=0.026)or pouch failure(10.3%vs 6.7%,P=0.671)between the two groups.Kaplan-Meier plot for time-to-pouch failure between the pouch patients with or without excessive body mass index(BMI)gain(>10%)showed statistical difference(P=0.011).Limited stepwise multivariate analysis showed that excessive VAT gain(odds ratio=12.608,95%confidence interval:1.190–133.538,P=0.035)was an independent risk factor for the adverse pouch comes.Conclusions:In this cohort of ileal pouch patients,excessive VAT gain as well as gain in BMI after pouch construction was found to be associated with poor long-term outcomes.展开更多
基金Supported by The National Institute on Alcohol Abuse and Al-coholism and the US Department of Veterans Affairs
文摘Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this reactive glycoprotein plays in the progression of injury but also for the insight further studies could provide towards the development of novel therapies for alcoholic liver disease.
基金supported by the National Natural Science Foundation of China (Grant Nos. 30621063, 20635010 and 20735005)the National Key Basic Research Program of China (Grant Nos. 2006CB910801, 2004CB518707 and 2007CB914100)the National High Technology Research and Development Program of China (Grant Nos. 2006AA02A308 and 2008AA02Z309)
文摘The human liver is the largest organ in the body and has many important physiological functions. A global analysis of human liver proteins is essential for a better understanding of the molecular basis of the normal functions of the liver and of its diseases. As part of the Human Liver Proteome Project (HLPP), the goal of the present study was to visualize and detect as many proteins as possible in normal human livers using two-dimensional gel electrophoresis (2-DE). We have constructed a reference map of the proteins of human normal liver that can be used for the comprehensive analysis of the human liver proteome and other related research. To improve the resolution and enhance the detection of low abundance proteins, we developed and optimized narrow pH range ultra-zoom 2-DE gels. High resolution patterns of human liver in pH gradients 4.5-5.5, 5-6, 5.5-6.7, 6-9 and 6-11 are presented. To improve the poor resolution in the alkaline pH range of 2-DE gels, we optimized the isoelectric focusing protocol by including sample application using cup loading at the anode and incorporating 1.2% hydroxyethyl disulfide, 15% 2-propanol and 5% glycerol in the rehydration buffer. Using the optimized protocol, we obtained reproducibly better resolution in both analytical and preparative 2-DE gels. Compared with the 2386 and 1878 protein spots resolved in the wide range 3-10 and 4-7 pH gradients respectively, we obtained 5481 protein spots from the multiple (overlapping) narrow pH range ultra-zoom gels in the range of pH 4.5-9. The visualized reference map of normal human liver proteins presented in this paper will be valuable for comparative proteomic research of the liver proteome.
基金supported by National Natural Science Foundation of China(No.81001548,No.81173341,No.81173332 and No.81202753)Shanghai Rising-star Program(No.12QA1403000)+1 种基金Shanghai Key Research Program of Traditional Chinese Medicine Development(No.ZYSNXD-CC-ZDYJ039)The Scientific Research Funds for Young Scholar of the Health System in Shanghai(No.XYQ2013081)
文摘As one of the most important concepts in traditional Chinese medicine, cutaneous regions have a close relationship with skin in modern medicine. According to the doctrine of traditional Chinese medicine, the cutaneous regions are the corresponding projections of twelve meridians in the superficial layer of the body and play an important role in body surface-viscera correlation. The symptoms of visceral disorders will reflect on cutaneous regions and one of the major patterns of manifestation is referred visceral pain accompanied by tenderness and hyperalgesia on the body surface. On the contrary, cutaneous regions participate in the treatment of visceral disorders. As major clinical applications of the cutaneous regions hypothesis, superficial acupuncture, subcutaneous needling, massage(tuina), moxibustion, and wrist-ankle acupuncture have achieved favorable therapeutic outcomes in clinical practice. Modern researches have gained insights into the biological background of cutaneous regions, however, further studies are needed to clarify the mechanisms.
文摘Background:There are no published studies on the impact of visceral adipose tissue(VAT)change on outcomes of restorative proctocolectomy and ileal pouch-anal anastomosis(IPAA).The aim of this historic cohort study was to evaluate the impact of excessive VAT gain on the outcomes of inflammatory bowel disease(IBD)patients with IPAA.Methods:We evaluated all eligible patients with at least two sequential CT scans after pouch construction from our prospectively maintained Pouchitis Registry between 2002 and 2014.The visceral fat area(VFA)was measured on CT images.The study group comprised patients with a significant VAT gain(>15%),and the control group was those without.The adverse outcomes of the pouch were defined as the new development of chronic pouch inflammation(chronic pouchitis,chronic cuffitis or Crohn’s disease of the pouch),anastomotic sinus and the combination of above(the composite adverse outcome)or pouch failure,after the inception CT.Results:Of 1564 patients in the Registry,59(3.8%)with at least 2 CT scans after pouch surgery were included.Twenty-nine patients(49.2%)were in the study group,and 30(50.8%)were in the control group.The median duration from the inception to the latest CT was 552(range:31–2598)days for the entire cohort.We compared the frequency of new chronic pouch inflammation(13.8%vs 3.3%,P=0.195),new pouch sinus(10.3%vs 0%,P=0.112),composite adverse pouch outcome(24.1%vs 3.3%,P=0.026)or pouch failure(10.3%vs 6.7%,P=0.671)between the two groups.Kaplan-Meier plot for time-to-pouch failure between the pouch patients with or without excessive body mass index(BMI)gain(>10%)showed statistical difference(P=0.011).Limited stepwise multivariate analysis showed that excessive VAT gain(odds ratio=12.608,95%confidence interval:1.190–133.538,P=0.035)was an independent risk factor for the adverse pouch comes.Conclusions:In this cohort of ileal pouch patients,excessive VAT gain as well as gain in BMI after pouch construction was found to be associated with poor long-term outcomes.
