- Proposal for new selection criteria considering pre-transplant muscularity and visceral adiposity in living donor liver transplantation. [Journal Article]
- JCJ Cachexia Sarcopenia Muscle 2018 Feb 17
- CONCLUSIONS: Using cut-off values determined from healthy donors, we have established new selection criteria for LDLT including body composition, which should improve post-transplant outcomes.
- GQ-11: A new PPAR agonist improves obesity-induced metabolic alterations in LDLr-/-mice. [Journal Article]
- IJInt J Obes (Lond) 2018 Jan 30
- CONCLUSIONS: GQ-11 is a partial/dual PPARα/γ agonist that demonstrates anti-diabetic effects. Additionally, it improves the lipid profile and ameliorates chronic inflammation associated with obesity in atherosclerosis-prone mice.
- A persistent cough as atypical clinical presentation of intrathoracic extramedullary hematopoiesis (EMH) in a female with thalassemia intermedia. [Journal Article]
- ABActa Biomed 2018 Feb 16; 89(2-S):41-46
- Extramedullary hematopoiesis (EMH) is a rare disorder, defined as the appearance of hematopoietic elements outside the bone marrow or peripheral blood. The most common sites of EMH are liver and sple...
Extramedullary hematopoiesis (EMH) is a rare disorder, defined as the appearance of hematopoietic elements outside the bone marrow or peripheral blood. The most common sites of EMH are liver and spleen, but it has been documented in other organs such as the mediastinum, lymph nodes, breast, and central nervous system. EMH occurs as a compensatory mechanism for bone marrow dysfunction in severe thalassemia. We report a case of EMH presenting as a posterior mediastinal mass in a 34-year-old woman with thalassemia intermedia with chronic cough and shortness of breath on exertion. The diagnosis of EMH was confirmed by a CT-guided fine needle biopsy. All symptoms disappeared after surgical removal of the mass.
- Final adult height and endocrine complications in young adults with β-thalassemia major (TM) who received oral iron chelation (OIC) in comparison with those who did not use OIC. [Journal Article]
- ABActa Biomed 2018 Feb 16; 89(2-S):27-32
- CONCLUSIONS: The use of OIC years before the end of puberty was associated with a significantly lower prevalence of endocrinopathies, improvement of LIC and FA-Ht. The final adult height of patients with BTM and GHD was significantly shorter compared to their pears with NGH. rhGH therapy can be recommended for the treatment of thalassemic children and adolescents with GHD in addition to proper blood transfusion and intensive chelation to improve their final height.
- Sarcopenia and risk of nonalcoholic fatty liver disease: A meta-analysis. [Review]
- SJSaudi J Gastroenterol 2018 Jan-Feb; 24(1):12-17
- CONCLUSIONS: A significantly increased risk of NAFLD among patients with sarcopenia was observed in this study.
- SIRT2 regulates oxidative stress-induced cell death through deacetylation of c-Jun NH2-terminal kinase. [Journal Article]
- CDCell Death Differ 2018 Feb 15
- c-Jun NH2-terminal kinases (JNKs) are responsive to stress stimuli and their activation regulate key cellular functions, including cell survival, growth, differentiation and aging. Previous studies d...
c-Jun NH2-terminal kinases (JNKs) are responsive to stress stimuli and their activation regulate key cellular functions, including cell survival, growth, differentiation and aging. Previous studies demonstrate that activation of JNK requires dual phosphorylation by the mitogen-activated protein kinase kinases. However, other post-translational mechanisms involved in regulating the activity of JNK have been poorly understood. In this work, we studied the functional significance of reversible lysine acetylation in regulating the kinase activity of JNK. We found that the acetyl transferase p300 binds to, acetylates and inhibits kinase activity of JNK. Using tandem mass spectrometry, molecular modelling and molecular dynamics simulations, we found that acetylation of JNK at Lys153 would hinder the stable interactions of the negatively charged phosphates and prevent the adenosine binding to JNK. Our screening for the deacetylases found SIRT2 as a deacetylase for JNK. Mechanistically, SIRT2-dependent deacetylation enhances ATP binding and enzymatic activity of JNK towards c-Jun. Furthermore, SIRT2-mediated deacetylation favours the phosphorylation of JNK by MKK4, an upstream kinase. Our results indicate that deacetylation of JNK by SIRT2 promotes oxidative stress-induced cell death. Conversely, SIRT2 inhibition attenuates H2O2-mediated cell death in HeLa cells. SIRT2-deficient (SIRT2-KO) mice exhibit increased acetylation of JNK, which is associated with markedly reduced catalytic activity of JNK in the liver. Interestingly, SIRT2-KO mice were resistant to acetaminophen-induced liver toxicity. SIRT2-KO mice show lower cell death, minimal degenerative changes, improved liver function and survival following acetaminophen treatment. Overall, our work identifies SIRT2-mediated deacetylation of JNK as a critical regulator of cell survival during oxidative stress.
- Safety evaluation of a human chimeric monoclonal antibody that recognizes the extracellular loop domain of claudin-2. [Journal Article]
- EJEur J Pharm Sci 2018 Feb 12
- Claudin-2 (CLDN-2), a pore-forming tight-junction protein with a tetra-transmembrane domain, is involved in carcinogenesis and the metastasis of some cancers. Although CLDN-2 is highly expressed in t...
Claudin-2 (CLDN-2), a pore-forming tight-junction protein with a tetra-transmembrane domain, is involved in carcinogenesis and the metastasis of some cancers. Although CLDN-2 is highly expressed in the tight junctions of the liver and kidney, whether CLDN-2 is a safe target for cancer therapy remains unknown. We recently generated a rat monoclonal antibody (mAb, clone 1A2) that recognizes the extracellular domains of human and mouse CLDN-2. Here, we investigated the safety of CLDN-2-targeted cancer therapy by using 1A2 as a model therapeutic antibody. Because most human therapeutic mAbs are IgG1 subtype that can induce antibody-dependent cellular cytotoxicity, we generated a human-rat chimeric IgG1 form of 1A2 (xi-1A2). xi-1A2 activated Fcγ receptor IIIa in the presence of CLDN-2-expressing cells, indicating that xi-1A2 likely exerts antibody-dependent cellular cytotoxicity. At 24 h after its intravenous injection, xi-1A2 was distributed into the liver, kidney, and tumor tissues of mice bearing CLDN-2-expressing fibrosarcoma cells. Treatment of the xenografted mice with xi-1A2 attenuated tumor growth without apparent adverse effects, such as changes in body weight and biochemical markers of liver and kidney injury. These results support xi-1A2 as the lead candidate mAb for safe CLDN-2-targeted cancer therapy.
- Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is significantly correlated with liver fat accumulation in patients with type 2 diabetes mellitus. [Journal Article]
- DRDiabetes Res Clin Pract 2018 Feb 12
- CONCLUSIONS: In patients with treatment-naïve T2DM, the muscle/fat ratio and ALT are useful for estimating the presence of excess liver fat accumulation in daily clinical practice.
- Low molecular weight fucoidan attenuates liver injury via SIRT1/AMPK/PGC1α axis in db/db mice. [Journal Article]
- IJInt J Biol Macromol 2018 Feb 12
- Non-alcoholic fatty-liver disease (NAFLD), caused by elevated hepatic lipids, inflammation and oxidative stress, is the most common liver disease globally. Low molecular weight fucoidan (LMWF), a sul...
Non-alcoholic fatty-liver disease (NAFLD), caused by elevated hepatic lipids, inflammation and oxidative stress, is the most common liver disease globally. Low molecular weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweeds, has shown strong anti-inflammatory and antioxidant activities, which has not been explored in diabetes-induced NAFLD. Therefore, the present study sought to determine whether LMWF protects obese diabetic db/db mice against NAFLD. Results showed LMWF administration decreased plasma level of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and triglyceride, as well as alleviated hepatic accumulation of triglyceride and total cholesterol in db/db mice. LMWF also ameliorated hepatic oxidative stress by suppressing superoxide production and lipid peroxidation, and increasing catalase and superoxide dismutase activity in the liver of db/db mice. Furthermore, LMWF down-regulated several pro-inflammatory cytokines and transcription factor, and up-regulated the anti-inflammatory adiponectin. These changes were accompanied by the activation of hepatic SIRT1/AMPK/PGC1α signaling with LMWF treatment. In addition, blocking SIRT1 or AMPK by inhibitor notably abolished LMWF-elicited protection against palmitic acid-induced oxidative stress and inflammation in hepatocytes. These results suggest LMWF prevents NAFLD in db/db mice by activation of SIRT1/AMPK/PGC1α signaling pathway, which prevents lipotoxicity-related oxidative stress and inflammation. Therefore, LMWF provides a potential supplementary treatment for obesity/diabetes-induced NAFLD.
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- Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway. [Journal Article]
- MCMol Cell Biochem 2018 Feb 14
- This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investig...
This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2 transgenic rats were used to investigate the transcriptional level of SREBP-2 regulated by SIRT-1/FOXO1 and the molecular mechanism of rate-limiting enzyme HMGCR that affects cholesterol synthesis. Rat models of hyperlipidemia were established and administered EGCG. Cholesterol synthesis was observed. Enzyme linked immunosorbent assay was used to determine serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), superoxide dismutase (SOD), malondialdehyde (MDA), and T-AOC contents. Hematoxylin-eosin staining and oil red O staining were utilized to observe the histological changes in the liver. Biochemical method was applied to measure serum ALT and AST changes. Western blot assay and qRT-PCR were employed to detect the changes in SIRT1/FOXO1 pathway-related proteins, cholesterol synthesis-related genes, and SREBP-2. EGCG 50 mg/kg could obviously decrease the liver weight and liver coefficient, reduce serum TG, TC, LDL-C, and FFA levels (P < 0.05), and increase serum HDL-C levels in hyperlipidemic rats. EGCG could diminish hyperlipidemia-induced liver injury and reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Oil red O staining results demonstrated that the number of red lipid droplets in hepatocytes reduced to varying degrees, especially high-dose EGCG. EGCG remarkably diminished MDA content in the liver with hypercholesterolemia and increased T-AOC and SOD activity. In the model group, SIRT1 expression increased, and FOXO1 expression decreased. EGCG activated SIRT1 and increased FOXO1 expression, whose expression trend was consistent with the fenofibrate group. HMGCR, FDPS, SS, and ABCA1 expression increased, and ACAT2 expression noticeably reduced in SREBP-2+/+transgenic rats. EGCG could reverse the expression trend of each gene. Simultaneously, EGCG increased FOXO1 expression, and decrease SREBP-2 expression; however, no significant changes in these expression were found in SREBP-2-/-rats. EGCG can alleviate liver injury and oxidative stress in hyperlipidemic rats. EGCG can activate SIRT1, activate FOXO1 protein, regulate SREBP-2 protein, and inhibit hepatic cholesterol synthesis.