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https://www.readbyqxmd.com/read/29332143/conjunction-of-g-quadruplex-and-stem-loop-in-the-5-untranslated-region-of-mouse-hepatocyte-nuclear-factor-4-alpha1-mediates-strong-inhibition-of-protein-expression
#1
Shangdong Guo, Hong Lu
Hepatocyte nuclear factor 4-alpha (HNF4α) is a well-established master regulator of liver development and function. Restoration of HNF4α can treat multiple liver disorders and liver cancers. To date, HNF4α is still "undruggable" due to lack of known activating ligands. Thus, understanding the regulatory mechanism of HNF4α expression may help develop an alternative approach to modulate HNF4α protein levels. G-quadruplexes (G4) are non-canonical stable secondary structures discovered mostly in the promoters of oncogenes...
January 13, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29331071/hepatic-ppar%C3%AE-function-is-controlled-by-polyubiquitination-and-proteasome-mediated-degradation-via-the-coordinated-actions-of-paqr3-and-huwe1
#2
Zilong Zhao, Daqian Xu, Zheng Wang, Lin Wang, Ruomei Han, Zhenzhen Wang, Lujian Liao, Yan Chen
Peroxisome proliferator-activated receptor α (PPARα) is a key transcriptional factor that regulates hepatic lipid catabolism by stimulating fatty acid oxidation and ketogenesis in an adaptive response to nutrient starvation. However, how PPARα is regulated by post-translational modification is poorly understood. Here, we identified that PAQR3 promotes PPARα ubiquitination through the E3 ubiquitin ligase HUWE1, thereby negatively modulating PPARα functions both in vitro and in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid oxidation and ketogenesis upon fasting...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29329052/efficient-and-cost-effective-generation-of-hepatocyte-like-cells-through-microparticle-mediated-delivery-of-growth-factors-in-a-3d-culture-of-human-pluripotent-stem-cells
#3
Zeinab Heidariyan, Mohammad Hossein Ghanian, Mohsen Ashjari, Zahra Farzaneh, Mostafa Najarasl, Mehran Rezaei Larijani, Abbas Piryaei, Massoud Vosough, Hossein Baharvand
Biomedical application of human pluripotent stem cell-derived hepatocyte-like cells (hPSC-HLCs) relies on efficient large-scale differentiation, which is commonly performed by a suspension culture of three-dimensional (3D) multicellular spheroids in bioreactors. However, this approach requires large amounts of growth factors (GFs) and the need to overcome limited diffusional transport posed by the inherent 3D structure of hPSC spheroids. Here, we have hypothesized that localized delivery of GFs by incorporation of GF-laden degradable polymeric microparticles (MPs) within the hPSC spheroids would circumvent such limitations...
January 2, 2018: Biomaterials
https://www.readbyqxmd.com/read/29327584/gama-aminobutyric-acid-enriched-rice-bran-diet-attenuates-insulin-resistance-and-balances-energy-expenditure-via-modification-of-gut-microbiota-and-scfas
#4
Xu Si, Wenting Shang, Zhongkai Zhou, Guanghou Shui, Sin Man Lam, Christopher L Blanchard, Padraig Strappe
In this study, gama-aminobutyric acid (GABA) enriched rice bran (ERB) was supplemented to obese rats to investigate the attenuation of metabolic syndromes induced by high-fat diet. ERB-containing diet stimulated butyrate and propionate production by promoting Anaerostipes, Anaerostipes sp. and associated synthesizing enzymes. This altered SCFA distribution further enhanced circulatory levels of leptin and glucagon-like peptide-1, controlling food intake by down-regulating orexigenic factors. Together with the enhanced fatty acid β-oxidation highlighted by Prkaa2, Ppara, Scd1 expression via AMPK signaling pathway and Non-alcoholic fatty liver disease pathway, energy expenditure was positively modulated...
January 12, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29327118/effect-of-cpap-therapy-on-liver-disease-in-patients-with-osa-a-review
#5
REVIEW
Xin Liu, Yuyang Miao, Fan Wu, Tingting Du, Qiang Zhang
Obstructive sleep apnea (OSA) may play an important role in the progression of nonalcoholic fatty liver disease (NAFLD).The effect of continuous positive airway pressure (CPAP) treatment, the first-line therapy for OSA, on liver disease in OSA patients is still debated. We provide this review of previous studies to summarize the effects of CPAP treatment on liver disease in OSA patients in aspects of liver function, liver steatosis, fibrosis, and incidence of liver disease. CPAP treatment may be beneficial to liver disease in subjects with OSA independent of metabolic risk factors, but a sufficiently long therapeutic duration (perhaps greater than 3 months) may be needed to achieve these positive effects...
January 11, 2018: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/29326488/resveratrol-prevents-liver-fibrosis-via-two-possible-pathways-modulation-of-alpha-fetoprotein-transcriptional-levels-and-normalization-of-protein-kinase-c-responses
#6
Alyaa Farouk Hessin, Rehab Rehab Hegazy, Azza Ahmed Hassan, Nemat Zakaria Yassin, Sanaa Abdel-Baky Kenawy
OBJECTIVE: Liver fibrosis is a global health problem that causes approximately 1.4 million deaths per year. It is associated with inflammation, oxidative stress, necrosis and ends with cirrhosis, liver cancer, or liver failure. Therefore, the present study was constructed to investigate the protective effect of resveratrol (RVT) on liver fibrosis, focusing on the possible involvement of alpha 1-fetoprotein and protein kinase C signaling. MATERIALS AND METHODS: Rats received thioacetamide (TAA) (200 mg/kg, intraperitoneal) twice weekly, for 4 successive weeks to induce liver fibrosis...
July 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29325711/effects-of-cortisol-and-lipopolysaccharide-on-expression-of-select-growth-stress-and-immune-related-genes-in-rainbow-trout-liver
#7
Brian S Shepherd, Allyn R Spear, Anju M Philip, Douglas W Leaman, Carol A Stepien, Osvaldo J Sepulveda-Villet, Debra E Palmquist, Mathilakath M Vijayan
Many studies have shown that stress-induced cortisol levels negatively influence growth and immunity in finfish. Despite this knowledge, few studies have assessed the direct effects of cortisol on liver immune function in finfish. Using real-time PCR, the expression of three cortisol-responsive genes (GR: glucocorticoid receptor, IGF-1: insulin-like growth factor-I and SOCS-1: suppressor of cytokine signaling-I), genes involved with innate and adaptive immunity (IL-1β: interleukin-1 beta, IgM: immunoglobin-M and Lyz: lysozyme), and liver-specific antimicrobial peptides (hepcidin and LEAP-2A: liver-expressed antimicrobial peptide-2A) were studied in vitro using rainbow trout liver slices...
January 8, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29324627/effects-of-the-humanized-anti-adrenomedullin-antibody-adrecizumab-ham8101-on-vascular-barrier-function-and-survival-in-rodent-models-of-systemic-inflammation-and-sepsis
#8
Christopher Geven, Esther Peters, Mathias Schroedter, Joachim Struck, Andreas Bergmann, Oscar McCook, Peter Radermacher, Matthijs Kox, Peter Pickkers
PURPOSE: Adrenomedullin (ADM) is an important regulator of endothelial barrier function during sepsis. Administration of a murine antibody targeted against the N-terminus of ADM (HAM1101) resulted in improved outcome in models of murine sepsis. We studied the effects of a humanized form of this antibody (HAM8101, also known as Adrecizumab) on vascular barrier dysfunction and survival in rodent models of systemic inflammation and sepsis. METHODS: Rats (n=48) received different dosages of HAM8101 or placebo (n = 8 per group), directly followed by administration of lipopolysaccharide (5 mg/kg)...
January 10, 2018: Shock
https://www.readbyqxmd.com/read/29323721/brain-derived-neurotrophic-factor-modulates-cholesterol-homeostasis-and-apolipoprotein-e-synthesis-in-human-cell-models-of-astrocytes-and-neurons
#9
Maria Stefania Spagnuolo, Aldo Donizetti, Lucia Iannotta, Vincenza Aliperti, Chiara Cupidi, Amalia Cecilia Bruni, Luisa Cigliano
In the central nervous system, cholesterol is critical to maintain membrane plasticity, cellular function, and synaptic integrity. In recent years, much attention was focused on the role of cholesterol in brain since a breakdown of cholesterol metabolism has been associated with different diseases. Brain-derived neurotrophic factor (BDNF) was previously reported to elicit cholesterol biosynthesis and promote the accumulation of presynaptic proteins in cholesterol-rich lipid rafts, but no data are available on its ability to modulate physiological mechanisms involved in cholesterol homeostasis...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29312539/regulatory-t-cells-with-a-defect-in-inhibition-on-co-stimulation-deteriorated-primary-biliary-cholangitis
#10
Jianing Chen, Xianliang Hou, Hongyu Jia, Guangying Cui, Zhongwen Wu, Lin Wang, Chong Lu, Wei Wu, Yingfeng Wei, Toshimitsu Uede, Lanjuan Li, Zhexiong Lian, Hongyan Diao
Regulatory T cells (Tregs) play an indispensable role in the progression of primary biliary cholangitis (PBC). Although Tregs could normalize costimulation in in vivo and in vitro models, it is obscure whether and how Tregs mediate these effects in PBC. Herein we focused on the quantitative and functional characteristics of Tregs in PBC. The number and proportion of Tregs, and the production of interleukin (IL)-10 were all significantly less in the PBC patients than in the healthy controls (HCs). In addition, compared to the HCs, the costimulatory CD86 of the circulation and liver were significantly higher in the patients with PBC...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29301090/evaluation-of-therapeutic-effect-of-rice-husk-silica-combined-with-platelets-derived-growth-factor-in-hepatic-veno-occlusive-disease
#11
Eithar K Al Adham, Amal I Hassan, M M Hazem, Ahmed Shebl
Veno- occlusive disease is an important pattern of hepatotoxicity associated with antineoplastic drugs. The study aimed to investigate the possible therapeutic impact of rice husk silica (RHS) nanoparticles combined with a platelet-derived growth factor (PDGF) on the Veno-occlusive disease in liver (VOD) elicited by dactinomycin (DAC) in rats. Forty-eight male Sprague-Dawely rats were classified into six groups, 8 rats each. The first group served as control, the second, animals were infused by intraperitoneal injection with DAC (0...
January 4, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29299369/pretreatment-albumin-may-aid-in-patient-selection-for-intrahepatic-y-90-microsphere-transarterial-radioembolization-tare-for-malignancies-of-the-liver
#12
Kelly P Orwat, Thomas H Beckham, Samuel Lewis Cooper, Michael S Ashenafi, Michael Bret Anderson, Marcelo Guimaraes, Ricardo Yamada, David T Marshall
Background: Hepatic malignancies are common including primary malignancies and metastases. Transarterial radioembolization (TARE) is an important treatment option. We reviewed safety and efficacy of (TARE) in our patients to identify factors that may impact treatment outcomes in a heterogeneous population. Methods: All patients that received TARE at the Medical University of South Carolina from March 2006 through May of 2014 were included. Kaplan-Meier estimates on overall survival (OS) from date of first procedure are reported...
December 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29298619/developing-a-cost-effective-and-scalable-production-of-human-hepatic-competent-endoderm-from-size-controlled-pluripotent-stem-cell-aggregates
#13
Zahra Farzaneh, Mostafa Najarasl, Saeed Abbasalizadeh, Massoud Vosough, Hossein Baharvand
Dynamic suspension culture of human pluripotent stem cells (hPSCs) in stirred bioreactors provides a valuable scalable culture platform for integrated differentiation toward different lineages for potential research and therapeutic applications. However, current protocols for scalable and integrated differentiation of hPSCs limited due to high cost of growth factors and technical challenges. Here, hPSCs aggregates primed with 6 and 12 µM of CHIR99021 (CHIR), a Wnt agonist, in combination with different concentrations of high cost Activin A (10, 25, 50, 100 ng/ml)...
January 3, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29298513/andrographolide-inhibits-oxidized-ldl-induced-cholesterol-accumulation-and-foam-cell-formation-in-macrophages
#14
Hung-Chih Lin, Chong-Kuei Lii, Hui-Chun Chen, Ai-Hsuan Lin, Ya-Chen Yang, Haw-Wen Chen
oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells...
January 3, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29296191/3-methyladenine-ameliorates-liver-fibrosis-through-autophagy-regulated-by-the-nf-%C3%AE%C2%BAb-signaling-pathways-on-hepatic-stellate-cell
#15
Bingying Wang, Huan Yang, Yinyin Fan, Yong Yang, Wei Cao, Yanwei Jia, Ying Cao, Kangyun Sun, Zhi Pang, Hong Du
3-Methyladenine (3-MA) is a selective type III phosphatidylinositol 3-kinase (PI3K) inhibitor and also blocks autophagosome formation. However, the effect of 3-MA in liver fibrosis has yet to be determined. Recent studies have demonstrated that autophagy is closely related to activation of hepatic stellate cells (HSC), a process critical in the pathogenesis of liver fibrosis. And the transcription factor nuclear factor-kappaB (NF-κB) is proved to play an important role in autophagy-induced signaling pathways...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295498/bmp-signalling-at-the-crossroad-of-liver-fibrosis-and-regeneration
#16
REVIEW
Blanca Herrera, Annalisa Addante, Aránzazu Sánchez
Bone Morphogenetic Proteins (BMPs) belong to the Transforming Growth Factor-β (TGF-β) family. Initially identified due to their ability to induce bone formation, they are now known to have multiple functions in a variety of tissues, being critical not only during development for tissue morphogenesis and organogenesis but also during adult tissue homeostasis. This review focus on the liver as a target tissue for BMPs actions, devoting most efforts to summarize our knowledge on their recently recognized and/or emerging roles on regulation of the liver regenerative response to various insults, either acute or chronic and their effects on development and progression of liver fibrosis in different pathological conditions...
December 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29289796/baccharis-trimera-protects-against-ethanol-induced-hepatotoxicity-in-vitro-and-in-vivo
#17
Ana Carolina Silveira Rabelo, Karine de Pádua Lúcio, Carolina Morais Araújo, Glaucy Rodrigues de Araújo, Pedro Henrique de Amorim Miranda, Ana Claudia Alvarenga Carneiro, Érica Milena de Castro Ribeiro, Breno de Melo Silva, Wanderson Geraldo de Lima, Daniela Caldeira Costa
ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera has been traditionally used in Brazil to treat liver diseases. AIM OF THE STUDY: To evaluate the protective effect of Baccharis trimera in an ethanol induced hepatotoxicity model. MATERIALS AND METHODS: The antioxidant capacity was evaluated in vitro by the ability to scavenged the DPPH radical, by the quantification of ROS, NO and the transcription factor Nrf2. Hepatotoxicity was induced in animals by administration of absolute ethanol for 2 days (acute) or with ethanol diluted for 28 days (chronic)...
December 28, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29288400/anti-inflammatory-and-antiresorptive-effects-of-calendula-officinalis-on-inflammatory-bone-loss-in-rats
#18
Joanna Trycia M Alexandre, Luzia Hermínia Teixeira Sousa, Mario Roberto Pontes Lisboa, Flávia A C Furlaneto, Danielle Rocha do Val, Mirna Marques, Hellíada C Vasconcelos, Iracema Matos de Melo, Renata Leitão, Gerly Anne Castro Brito, Paula Goes
OBJECTIVE: The aim of this work was to evaluate the anti-inflammatory and antiresorptive effects of Calendula officinalis (CLO) on alveolar bone loss (ABL) in rats. MATERIAL AND METHODS: Male Wistar rats were subjected to ABL by ligature with nylon thread around the second upper left molar. The contralateral hemimaxillae were used as control. Rats received saline solution (SAL) or CLO (10, 30, or 90 mg/kg) 30 min before ligature and daily until the 11th day. The maxillae were removed and prepared for macroscopic, radiographic, micro-tomographic, histopathologic, histometric analysis, and immunohistochemical localization of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG)...
December 29, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29287689/present-therapeutic-role-of-cholesteryl-ester-transfer-protein-inhibitors
#19
REVIEW
Nicola Ferri, Alberto Corsini, Cesare R Sirtori, Massimiliano Ruscica
Therapeutic interventions aimed at increasing high-density lipoprotein (HDL) levels, in order to reduce the residual cardiovascular (CV) risk of optimally drug treated patients have not provided convincing results, so far. Transfer of cholesterol from extrahepatic tissues to the liver appears to be the major atheroprotective function of HDL, and an elevation of HDL levels could represent an effective strategy. Inhibition of the cholesteryl ester transfer protein (CETP), raising HDL-cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, reduces low-density lipoprotein-cholesterol (LDL-C) and apoB levels, thus offering a promising approach...
December 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29285255/agrin-para-secreted-by-pdgf-activated-human-hepatic-stellate-cells-promotes-hepatocarcinogenesis-in-vitro-and-in-vivo
#20
Xing Lv, Cheng Fang, Ruozhe Yin, Bowei Qiao, Runze Shang, Jianlin Wang, Wenjie Song, Yong He, Yong Chen
Evaluating the process and mechanism of fibrogenesis is essential in hepatocellular carcinoma (HCC), especially in hepatocyte transformation and oncogenic signaling. We evaluated the oncogenic role of agrin secreted by platelet-derived growth factor (PDGF)-induced hepatic stellate cell (HSC) in HCC. Cells were co-cultured to investigate the effect of activated HSC on hepatocytes. Liquid chromatography and protein profiling analysis were used to search the distinct proteins secreted in HSC supernatant. Sprague Dawley rats with Diethylnitrosamine (DEN)-induced HCC were used to simulate human liver cancer and sorafenib was administered to investigate its effect on hepatocarcinogenesis...
December 1, 2017: Oncotarget
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