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https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#1
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29141998/vanillic-acid-attenuates-obesity-via-activation-of-the-ampk-pathway-and-thermogenic-factors-in-vivo-and-in-vitro
#2
Yunu Jung, Jinbong Park, Hye-Lin Kim, Jung-Eun Sim, Dong-Hyun Youn, JongWook Kang, Seona Lim, Mi-Young Jeong, Woong Mo Yang, Seok-Geun Lee, Kwang Seok Ahn, Jae-Young Um
Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice...
November 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29141455/methionine-adenosyltransferases-in-cancers-mechanisms-of-dysregulation-and-implications-for-therapy
#3
Lauren Y Maldonado, Diana Arsene, José M Mato, Shelly C Lu
Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29140985/notch-signaling-and-progenitor-ductular-reaction-in-steatohepatitis
#4
Carola M Morell, Romina Fiorotto, Marica Meroni, Aileen Raizner, Barbara Torsello, Massimiliano Cadamuro, Gaia Spagnuolo, Eleanna Kaffe, Salvatore Sutti, Emanuele Albano, Mario Strazzabosco
BACKGROUND AND OBJECTIVE: Persistent hepatic progenitor cells (HPC) activation resulting in ductular reaction (DR) is responsible for pathologic liver repair in cholangiopathies. Also, HPC/DR expansion correlates with fibrosis in several chronic liver diseases, including steatohepatitis. Increasing evidence indicates Notch signaling as a key regulator of HPC/DR response in biliary and more in general liver injuries. Therefore, we aimed to investigate the role of Notch during HPC/DR activation in a mouse model of steatohepatitis...
2017: PloS One
https://www.readbyqxmd.com/read/29140570/rapid-screening-of-the-endodermal-differentiation-potential-of-human-pluripotent-stem-cells
#5
Richard Siller, Gareth J Sullivan
Human pluripotent stem cells (hPSCs) hold tremendous promise for regenerative medicine, disease modeling, toxicology screening, and developmental biology. These applications are hindered due to inherent differences in differentiation potential observed among different hPSC lines. This is particularly true for the differentiation of hPSCs toward the endodermal lineage. Several groups have developed methods to screen hPSCs for their endodermal differentiation potential (EP). Particularly notable studies include (i) the use of WNT3A expression as a predictive biomarker, (ii) an embryoid body-based screen, and (iii) a transcriptomics-based approach...
November 15, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/29132537/nfil3-is-a-negative-regulator-of-hepatic-gluconeogenesis
#6
Geon Kang, Hye-Sook Han, Seung-Hoi Koo
OBJECTIVE: Nuclear factor interleukin-3 regulated (NFIL3) has been known as an important transcriptional regulator of the development and the differentiation of immune cells. Although expression of NFIL3 is regulated by nutritional cues in the liver, the role of NFIL3 in the glucose metabolism has not been extensively studied. Thus, we wanted to explore the potential role of NFIL3 in the control of hepatic glucose metabolism. MATERIALS/METHODS: Mouse primary hepatocytes were cultured to perform western blot analysis, Q-PCR and chromatin immunoprecipitation assay...
December 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29130076/crispr-correction-of-a-homozygous-low-density-lipoprotein-receptor-mutation-in-familial-hypercholesterolemia-induced-pluripotent-stem-cells
#7
Linda Omer, Elizabeth A Hudson, Shirong Zheng, James B Hoying, Yuan Shan, Nolan L Boyd
Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans...
November 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29128830/metabolism-of-the-synthetic-cannabinoid-5f-py-pica-by-human-and-rat-hepatocytes-and-identification-of-biliary-analytical-targets-by-directional-efflux-in-sandwich-cultured-rat-hepatocytes-using-uhplc-hr-ms-ms
#8
Marie Mardal, Pieter Annaert, Carolina Noble, Marlies Oorts, Kristian Linnet
Analytical strategies for detecting drugs in biological samples rely on information on metabolism and elimination. 5F-PY-PICA belongs to the group of synthetic cannabinoids that are known to undergo excretion into the bile. The aims of this study were the in vitro identification of metabolites of 5F-PY-PICA and to determine which analytical targets are excreted into the bile and urine. Metabolites identified after incubation of 5F-PY-PICA with pooled human liver microsomes (pHLM), pooled human hepatocytes (pHH), or suspended and sandwich-cultured rat hepatocytes (SCRH)...
November 7, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29128613/submicromolar-bisphenol-a-induces-proliferation-and-dna-damage-in-human-hepatocyte-cell-lines-in-vitro-and-in-juvenile-rats-in-vivo
#9
Seoyoung Kim, Gil-Im Mun, Eun Choi, Minjeong Kim, Ji Seong Jeong, Keon Wook Kang, Sunha Jee, Kyung-Min Lim, Yun-Sil Lee
An association between bisphenol A (BPA) exposure and hepatic tumors was suggested, but the employment of high-dose levels raises questions about its relevance to human health. Here, we demonstrate that submicromolar concentrations of BPA induce the proliferation and DNA damage in human hepatocyte cell lines. In HepG2 and NKNT-3, undifferentiated and differentiated hepatocyte cell lines, respectively, submicromolar BPA concentrations promoted the cell proliferation, as indicated by enhanced DNA synthesis and elevated expression of cell-cycle proteins...
November 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29128360/golga2-loss-causes-fibrosis-with-autophagy-in-the-mouse-lung-and-liver
#10
Sungjin Park, Sanghwa Kim, Minjung Kim, Youngeun Hong, Ah Young Lee, Hyunji Lee, Quangdon Tran, Minhee Kim, Hyeonjeong Cho, Jisoo Park, Kwang Pyo Kim, Jongsun Park, Myung-Haing Cho
Autophagy is a biological recycling process via the self-digestion of organelles, proteins, and lipids for energy-consuming differentiation and homeostasis. The Golgi serves as a donor of the double-membraned phagophore for autophagosome assembly. In addition, recent studies have demonstrated that pulmonary and hepatic fibrosis is accompanied by autophagy. However, the relationships among Golgi function, autophagy, and fibrosis are unclear. Here, we show that the deletion of GOLGA2, encoding a cis-Golgi protein, induces autophagy with Golgi disruption...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29127748/-issues-related-to-secondary-osteoporosis-associated-with-growth-hormone-deficiency-in-adulthood
#11
Martin Kužma, Peter Jackuliak, Zdenko Killinger, Peter Vaňuga, Juraj Payer
Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29127141/copper-deposition-in-focal-nodular-hyperplasia-and-inflammatory-hepatocellular-adenoma
#12
Vishal S Chandan, Sejal S Shah, Taofic Mounajjed, Michael S Torbenson, Tsung-Teh Wu
AIMS: To examine copper deposition in focal nodular hyperplasia (FNH) and inflammatory hepatocellular adenoma (IHA) and to determine if it can play a role in their differentiation. METHODS: 28 FNHs and 19 IHAs from surgical resections showing typical morphological and immunohistochemical features were stained with rhodanine to evaluate for copper deposition. Histological features such as nodularity, fibrous bands, ductular proliferation, steatosis, ballooned hepatocytes and lymphocytic inflammation were also scored...
November 10, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29118330/molecular-spectrum-of-secretome-regulates-the-relative-hepatogenic-potential-of-mesenchymal-stem-cells-from-bone-marrow-and-dental-tissue
#13
Ajay Kumar, Vinod Kumar, Vidya Rattan, Vivekananda Jha, Arnab Pal, Shalmoli Bhattacharyya
Liver regeneration is a spontaneous process that occurs after liver injury, but acute liver failure is a complex and fatal disease which is difficult to treat. Cell-based therapies are promising alternative therapeutic approach for liver failure and different cell sources have been tested in this regard. We investigated the comparative hepatogenic potential of human bone marrow stem cells (BMSC) with stem cells derived from human dental pulp (DPSC), apical papilla (SCAP) and follicle (DFSC) during this study...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116012/connexin-32-and-connexin-43-are-involved-in-lineage-restriction-of-hepatic-progenitor-cells-to-hepatocytes
#14
Haiyun Pei, Chao Zhai, Huilin Li, Fang Yan, Jinhua Qin, Hongfeng Yuan, Rui Zhang, Shuyong Wang, Wencheng Zhang, Mingyang Chang, Yunfang Wang, Xuetao Pei
BACKGROUND: Bi-potential hepatic progenitor cells can give rise to both hepatocytes and cholangiocytes, which is the last phase and critical juncture in terms of sequentially hepatic lineage restriction from any kind of stem cells. If their differentiation can be controlled, it might access to functional hepatocytes to develop pharmaceutical and biotechnology industries as well as cell therapies for end-stage liver diseases. METHODS: In this study, we investigated the influence of Cx32 and Cx43 on hepatocyte differentiation of WB-F344 cells by in vitro gain and loss of function analyses...
November 7, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29114949/protective-effect-of-gdnf-engineered-amniotic-fluid-derived-stem-cells-on-the-renal-ischaemia-reperfusion-injury-in-vitro
#15
Jia Wang, Fengzhen Wang, Zhuojun Wang, Shulin Li, Lu Chen, Caixia Liu, Dong Sun
OBJECTIVES: Amniotic fluid-derived stem cells (AFSCs) possessing multilineage differentiation potential are proposed as a novel and accessible source for cell-based therapy and tissue regeneration. Glial-derived neurotrophic factor (GDNF) has been hypothesized to promote the therapeutic effect of AFSCs on markedly ameliorating renal dysfunction. The aim of this study was to investigate whether AFSCs equipped with GDNF (GDNF-AFSCs) had capabilities of attenuating mouse renal tubular epithelial cells (mRTECs) apoptosis and evaluate its potential mechanisms...
November 7, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29113177/potential-role-of-indoleamine-2-3-dioxygenase-in-primary-biliary-cirrhosis
#16
Kashif Asghar, John Brain, Jeremy M Palmer, Stephen Douglass, Fatmah M A Naemi, Graeme O'Boyle, John Kirby, Simi Ali
Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111387/hyperlipidemia-induced-hepassocin-in-the-liver-contributes-to-insulin-resistance-in-skeletal-muscle
#17
Tae Woo Jung, Yoon Hee Chung, Hyoung-Chun Kim, A M Abd El-Aty, Ji Hoon Jeong
Hepassocin (HPS) has recently been identified as a novel hepatokine that causes hepatic steatosis. However, the role of HPS in the development of insulin resistance in skeletal muscle under obesity remains unclear. The effect of hyperlipidemia on hepatic HPS expression was evaluated in primary hepatocytes and liver of mice. HPS-mediated signal pathways were explored using small interfering (si) RNAs of specific genes or inhibitors. We found that treatment of primary hepatocytes with palmitate could induce HPS expression through C/EBPβ-mediated transcriptional activation...
October 27, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29110608/the-profile-of-angiogenic-factors-in-vitreous-humor-of-the-patients-with-proliferative-diabetic-retinopathy
#18
Y Yu, J Zhang, R Zhu, R Zhao, J Chen, J Jin, Y Tian, S B Su
OBJECTIVE: To explore the expression profile of angiogenic factors associated with proliferative diabetic retinopathy (PDR). METHODS: Undiluted vitreous humor samples were obtained from 10 diabetic patients with PDR (10 eyes) and 9 non-diabtic patients (9 eyes). The concentrations of 60 angiogenic factors in the vitreous humor samples were measured by RayBio Angiogenic Cytokine Antibody Array. Some differentially expressed factors were further confirmed in vitreous humor by enzyme-linked immunosorbent assay (ELISA)...
November 5, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29109103/hepatocyte-nuclear-factor-1a-deficiency-causes-hemolytic-anemia-in-mice-by-altering-erythrocyte-sphingolipid-homeostasis
#19
Karin von Wnuck Lipinski, Sarah Weske, Petra Keul, Susann Peters, Hideo A Baba, Gerd Heusch, Markus H Gräler, Bodo Levkau
The Hepatocyte Nuclear Factor (HNF) family regulates complex networks of metabolism and organ development. Human mutations in its prototypical member HNF1A cause maturity-onset of diabetes of the young (MODY) type 3. In this study, we identified an important role for HNF1A in the preservation of erythrocyte membrane integrity, calcium homeostasis and osmotic resistance through a yet unrecognized link of HNF1A to sphingolipid homeostasis. HNF1A(-/-) mice displayed microcytic hypochromic anemia with reticulocytosis that was partially compensated by avid extramedullary erythropoiesis at all erythroid stages in the spleen thereby excluding erythroid differentiation defects...
November 6, 2017: Blood
https://www.readbyqxmd.com/read/29108215/-research-advances-in-the-role-of-mesenchymal-stem-cells-and-their-exosomes-in-treatment-of-liver-diseases
#20
W H Niu, J J Zhang, Z Y Zhu
At present, liver transplantation remains the most effective treatment for acute liver failure and advanced cirrhosis, but its use and promotion are limited by insufficient organ donors, financial consideration, and requirements for lifelong immunosuppression. In recent years, stem cell transplantation has been recommended as an effective substitutive therapy for liver disease. Mesenchymal stem cells, also known as pluripotent interstitial stromal cells, are self-renewing cells that can be found in almost all postnatal organs and tissues, including the liver...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
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