- How can we improve the performance of MELDNa score in patients with HBV-related decompensated liver cirrhosis commencing antiviral treatment? [Journal Article]
- JGJ Gastroenterol Hepatol 2018 Feb 20
- CONCLUSIONS: Ascites and encephalopathy should be considered together with the MELDNa score when predicting short-term mortality and planning LT in patients with decompensated HBV-related cirrhosis starting antiviral treatment.
- A Chronic Disease Management Model for Cirrhosis is Cost-Effective: Analysis of a Randomized Controlled Trial. [Journal Article]
- JGJ Gastroenterol Hepatol 2018 Feb 20
- CONCLUSIONS: The analysis of data from a RCT suggests that the CDM intervention used is likely to cost effective, relative to usual care, due to fewer patient deaths.
- MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-β1/Smad3 Signaling Pathway. [Journal Article]
- CPCell Physiol Biochem 2018 Feb 15; 45(4):1333-1349
- CONCLUSIONS: These results indicate that miR-27a may contribute to detrusor fibrosis in STZ-induced diabetic rats by targeting PRKAA2 via the TGF-β1/Smad3 signaling pathway.
- Evaluating the impact of diabetes and diabetic cardiomyopathy rat heart on the outcome of ischemia-reperfusion associated oxidative stress. [Journal Article]
- FRFree Radic Biol Med 2018 Feb 17
- Earlier literature underlines that oxidative stress plays a major role in the pathology of myocardial ischemia-reperfusion (I/R) injury, diabetic cardiomyopathy (DCM), diabetes mellitus (DM), fibrosi...
Earlier literature underlines that oxidative stress plays a major role in the pathology of myocardial ischemia-reperfusion (I/R) injury, diabetic cardiomyopathy (DCM), diabetes mellitus (DM), fibrosis and hypertrophy which could adversely affect the normal cardiac function. However, the contributory role of oxidative stress in I/R pathology of heart with pre-existing abnormalities or diseases like DM and DCM remains to be explored. I/R injury was induced in normal (normal diet), DM (normal diet + streptozotocin: multiple low dose of 30mg/kg) and DCM (high fat diet (40% fat) + streptozotocin: multiple low dose of 30mg/kg) rat hearts using Langendorff isolated heart perfusion apparatus. Cardiac physiological recovery after I/R was assessed by hemodynamic parameters like LVDP, and LVSP, whereas cardiac injury was measured by tissue infarct size, and apoptosis, LDH, and CK release in coronary effluent. The oxidative stress was evaluated in myocardial homogenate, mitochondrial subpopulation, and microsomes. Reperfusing the ischemic DCM heart significantly deteriorated cardiac physiological recovery and elevated the cardiac injury (infarct size: 60%), compared to the control. But in DM heart, physiological recovery was prominent in the initial phase of reperfusion but deteriorated towards the end of reperfusion, supported by less infarct size. In addition, elevated lipid peroxidation (70% in DCM-I/R vs Sham) and impaired antioxidant enzymes (% decline vs Sham: GSH- 56% (DM), 63% (DCM); Catalase- 58% (DM), 35% (DCM); GPx- 19% (DM), 27% (DCM) and GR- 28% (DCM)) was observed in myocardial tissue from both DM and DCM. Interestingly, upon reperfusion, only normal heart showed significant deterioration in the antioxidant defense system. Collectively these results demonstrated that I/R induced oxidative stress is minimal in DM and DCM rat heart, despite high infarct size and low cardiac performance. This may be due to the prior adaptive modification in the antioxidant system associated with disease pathology.
- A new model of diabetic nephropathy in C57BL/6 mice challenged with advanced oxidation protein products. [Journal Article]
- FRFree Radic Biol Med 2018 Feb 17
- There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired ph...
There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired phenotypic characteristics. Most genetically modified mice are on the C57BL/6 background; however, they are notorious for resistance to develop DN. To overcome these conundrums, this study reports a novel DN model by challenging with advanced oxidation protein products (AOPPs) in streptozotocin-induced diabetic C57BL/6 mice. AOPPs-challenged diabetic C57BL/6 mice were more sensitive to develop progressive proteinuria, causing a 5.59-fold increase in urine albumin to creatinine ratio as compared to diabetic controls by 24 weeks. Typical lesions were present as demonstrated by significant diffuse mesangial expansion, diffuse podocyte foot process effacement, increased glomerular basement membrane thickness, focal arteriolar hyalinosis, mesangiolysis, and mild interstitial fibrosis. These changes were alleviated by losartan treatment. Collectively, these results suggest that AOPPs can accelerate the progression of DN in the resistant C57BL/6 mouse strain. Our studies offer a novel model for studying the pathogenesis of DN that resembles human diabetic kidney disease. It also makes it possible to interrogate the role of specific genetic modifications and to evaluate novel therapeutics to treat DN in preclinical setting.
- Safer approaches to therapeutic modulation of TGF-β signaling for respiratory disease. [Review]
- P&TPharmacol Ther 2018 Feb 17
- The transforming growth factor (TGF)-β cytokines play a central role in development and progression of chronic respiratory diseases. TGF-β overexpression in chronic inflammation, remodeling, fibrotic...
The transforming growth factor (TGF)-β cytokines play a central role in development and progression of chronic respiratory diseases. TGF-β overexpression in chronic inflammation, remodeling, fibrotic process and susceptibility to viral infection is established in the most prevalent chronic respiratory diseases including asthma, COPD, lung cancer and idiopathic pulmonary fibrosis. Despite the overwhelming burden of respiratory diseases in the world, new pharmacological therapies have been limited in impact. Although TGF-β inhibition as a therapeutic strategy carries great expectations, the constraints in avoiding compromising the beneficial pleiotropic effects of TGF-β, including the anti-proliferative and immune suppressive effects, have limited the development of effective pharmacological modulators. In this review, we focus on the pathways subserving deleterious and beneficial TGF-β to identify strategies for selective modulation of more distal signaling pathways that may result in agents with improved safety/efficacy profiles. Adverse effects of TGF-β inhibitors in respiratory clinical trials are comprehensively reviewed, including those of the marketed TGF-β modulators, pirfenidone and nintedanib. Precise modulation of TGF-β signaling may result in new safer therapies for chronic respiratory diseases.
- Hepatic and cardiac hemodynamics and systemic inflammation in cirrhosis: it takes three to tango. [Editorial]
- JHJ Hepatol 2018 Feb 17
- In this editorial the roles of systemic inflammation, elevated pressure in portal venous system and heart function and circulation in stable cirrhosis and decompensated cirrhosis with or without orga...
In this editorial the roles of systemic inflammation, elevated pressure in portal venous system and heart function and circulation in stable cirrhosis and decompensated cirrhosis with or without organ failures are described.
- Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. [Journal Article]
- KJKorean J Intern Med 2018 Feb 21
- The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiot...
The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.
- The TGFβ superfamily in cardiac dysfunction. [Journal Article]
- ABActa Biochim Biophys Sin (Shanghai) 2018 Feb 15
- TGFβ superfamily includes the transforming growth factor βs (TGFβs), bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and Activin/Inhibin families of ligands. Among the 3...
TGFβ superfamily includes the transforming growth factor βs (TGFβs), bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and Activin/Inhibin families of ligands. Among the 33 members of TGFβ superfamily ligands, many act on multiple types of cells within the heart, including cardiomyocytes, cardiac fibroblasts/myofibroblasts, coronary endothelial cells, smooth muscle cells, and immune cells (e.g. monocytes/macrophages and neutrophils). In this review, we highlight recent discoveries on TGFβs, BMPs, and GDFs in different cardiac residential cellular components, in association with functional impacts in heart development, injury repair, and dysfunction. Specifically, we will review the roles of TGFβs, BMPs, and GDFs in cardiac hypertrophy, fibrosis, contractility, metabolism, angiogenesis, and regeneration.
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- Carbohydrate Deficient Transferrin in Patients with Cirrhosis: A Tale of Bridges. [Journal Article]
- AAAlcohol Alcohol 2018 Feb 15