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Hepatic regeneration

Bilon Khambu, Nazmul Huda, Xiaoyun Chen, Daniel J Antoine, Yong Li, Guoli Dai, Ulrike A Köhler, Wei-Xing Zong, Satoshi Waguri, Sabine Werner, Tim D Oury, Zheng Dong, Xiao-Ming Yin
Autophagy is important for liver homeostasis and the deficiency leads to injury, inflammation, ductular reaction (DR), fibrosis, and tumorigenesis. It is not clear how these events are mechanistically linked to autophagy deficiency. Here we reveal the role of highmobility group box 1 (HMGB1) in two of these processes. First, HMGB1 was required for DR, which represents the expansion of hepatic progenitor cells (HPC) implicated in liver repair and regeneration. DR caused by hepatic toxic diets (DDC or CDE) also depended on HMGB1, indicating that HMGB1 may be generally required for DR in various injury scenarios...
March 20, 2018: Journal of Clinical Investigation
Ling Ling Liau, Suzana Makpol, Abdul Ghani Nur Azurah, Kien Hui Chua
Currently, orthotopic liver transplantation is the gold standard therapy for liver failure. However, it is limited by the insufficient organ donor and risk of immune rejection. Stem cell therapy is a promising alternative treatment for liver failure. One of the most ideal sources of stem cells for regenerative medicine is adipose-derived stem cells (ADSCs). In this study, primary ADSCs seeded on cell culture insert were indirectly co-cultured with injured HepG2 to elucidate the role of ADSCs in promoting the recovery of injured HepG2 in non-contact manner...
March 16, 2018: Cytotechnology
Yoshihiro Inoue, Kensuke Fujii, Keitaro Tashiro, Masatsugu Ishii, Shinsuke Masubuchi, Masashi Yamamoto, Tetsunosuke Shimizu, Mitsuhiro Asakuma, Fumitoshi Hirokawa, Michihiro Hayashi, Yoshihumi Narumi, Kazuhisa Uchiyama
BACKGROUND: Various chemotherapy regimens have been shown to improve outcomes when administered before tumor excision surgery. However, there is no consensus on the utility of multidisciplinary treatment with preoperative chemotherapy for treating colorectal liver metastasis (CLM). MATERIALS AND METHODS: Two hundred-fifty patients who underwent hepatectomy were retrospectively analyzed using propensity score matching. Postoperative outcomes were evaluated with a focus on the effect of pre-hepatectomy chemotherapy on regeneration of the remnant liver in patients with CLM...
March 16, 2018: World Journal of Surgery
Jian Zhang, Junhong Li, Junwei Ma, Hongxin Wang, Yin Yi
Hepatitis B cirrhosis is caused by liver cell necrosis, residual liver cell nodular regeneration, connective tissue hyperplasia and fiber formation, which frequently leads to adrenal insufficiency. Previous reports have demonstrated that human fibroblast growth factor (hFGF)-21 is a multifunctional protein that exhibits potential therapeutic value for metabolic diseases. The present study investigated the diagnostic value of hFGF-21 and analyzed the potential molecular mechanism in the progression of hepatitis B cirrhosis combined with adrenal insufficiency...
April 2018: Experimental and Therapeutic Medicine
Salvatore Sutti, Frank Tacke
Drug-induced liver injury (DILI) remains a clinical challenge due to the poorly predictable outcomes. Accordingly, considerable efforts have been devoted to unravel the risk factors responsible for DILI worsening toward acute liver failure (ALF), liver transplantation (LT), and/or death. From a pathogenic point of view, exhaustion of drug metabolizing pathways, cell death mechanisms, activation of local immune cells, such as Kupffer cells, and recruitment of inflammatory leukocytes including monocytes and lymphocytes are key drivers of DILI progression...
March 15, 2018: Clinical Science (1979-)
Jacquelyn O Russell, Sungjin Ko, Harvinder S Saggi, Sucha Singh, Minakshi Poddar, Donghun Shin, Satdarshan P Monga
Bromodomain and extraterminal (BET) proteins recruit key components of basic transcriptional machinery to promote gene expression. Aberrant expression and mutations in BET genes have been identified in many malignancies. Small molecule inhibitors of BET proteins like JQ1 have shown efficacy in preclinical cancer models including affecting growth of hepatocellular carcinoma. BET proteins also regulate cell proliferation in nontumor settings. We recently showed that BET proteins regulate cholangiocyte-driven liver regeneration...
March 12, 2018: American Journal of Pathology
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
M Garrido, C Escobar, C Zamora, C Rejas, J Varas, C Córdova, C Papuzinski, M Párraga, S San Martín, S Montedonico
Purpose: Biliary atresia precedes liver cirrhosis and liver transplantation. Amniotic membrane (AM) promotes tissue regeneration, inhibits fibrosis, and reduces inflammation. Here, we test amniotic membrane potential as a therapeutic tool against cholestatic liver fibrosis. Methods: Three groups of rats were used: sham surgery (SS), bile duct ligature (BDL), and bile duct ligature plus human amniotic membrane (BDL + AM). After surgery, animals were sacrificed at different weeks...
2018: Stem Cells International
Meysam Nasiri, Mohammad-Hossein Karimi, Negar Azarpira, Iraj Saadat
OBJECTIVES: Toll-like receptors and downstream signal transduction pathways play pivotal roles in induction of inflammation, which is crucial for liver injury and regeneration. MATERIALS AND METHODS: Using a mouse model of partial hepatic ischemia-reperfusion injury followed by a 28-day time course for liver repair and regeneration, we assessed gene expression levels for Toll-like receptors, myeloid differentiation primary response 88, TIR-domain-containing adapter-inducing interferon-β, nuclear factor κB, interferon regulatory factors, tumor necrosis factor-α, and interleukins 1β and 6 at days 1, 4, 7, 14, and 28 after reperfusion in liver and blood cells by quantitative polymerase chain reaction...
March 9, 2018: Experimental and Clinical Transplantation
V Krishnan, N J Patel, J G Mackrell, S A Sweetana, H Bullock, Y L Ma, T H Waterhouse, B C Yaden, J Henck, Q Q Zeng, K Gavardinas, P Jadhav, A Saeed, P Garcia-Losada, D A Robins, C T Benson
We have identified a non-steroidal selective androgen receptor modulator (SARM), termed LY305, that is bioavailable through a transdermal route of administration while highly cleared via hepatic metabolism to limit parent compound exposure in the liver. Selection of this compound and its transdermal formulation was based on the optimization of skin absorption properties using both in vitro and in vivo skin models that supported PBPK modeling for human PK predictions. This molecule is an agonist in perineal muscle while being a weak partial agonist in the androgenic tissues such as prostate...
March 12, 2018: Andrology
Amber W Wang, Kirk J Wangensteen, Yue J Wang, Adam M Zahm, Nicholas G Moss, Noam Erez, Klaus H Kaestner
Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatments of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We utilize the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We employ translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes...
March 8, 2018: Journal of Clinical Investigation
Carlos Edmundo Rodrigues Fontes, Marino Jose Mardegam, Orlando Ribeiro Prado-Filho, Marcos Victor Ferreira
BACKGROUND: Obtaining effective hemostasis either in the traumatic or surgical lesions of parenchymal viscera, especially the liver, has always been a challenge. AIM: Comparative study between the use of different hemostatic sponges in hepatic wound and their capacity of integration to cells in a short period. METHODS: Fifteen Wistar rats were divided into three groups. Through laparotomy a standardized wound in hepatic right lobe was made...
March 1, 2018: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
Ryosuke Inoue, Kenya Kamimura, Takuro Nagoya, Norihiro Sakai, Takeshi Yokoo, Ryo Goto, Kohei Ogawa, Yoko Shinagawa-Kobayashi, Yukari Watanabe-Mori, Akira Sakamaki, Satoshi Abe, Hiroteru Kamimura, Norio Miyamura, Hiroshi Nishina, Shuji Terai
The development of therapeutic options to promote hepatic regeneration following severe liver injury is essential. While humoral factors have been reported as mechanisms of liver regeneration, the contributions of interorgan communication to liver regeneration have not been reported. In this study, we examined the effect of a neural relay on liver regeneration via activation of serotonin release from the gastrointestinal (GI) tract. Our results demonstrated that the afferent visceral nerve from the liver activates the efferent vagus nerve from the brain, leading to activation of serotonin release from the GI tract and contributing to liver regeneration...
March 2018: FEBS Open Bio
Adrien Guillot, Imène Gasmi, Arthur Brouillet, Yeni Ait-Ahmed, Julien Calderaro, Isaac Ruiz, Bin Gao, Sophie Lotersztajn, Jean-Michel Pawlotsky, Fouad Lafdil
Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)-17-positive (+) cells and cytokeratin 19 (CK19)+ LPCs, and both cell types colocalized and their numbers positively correlated with each other...
March 2018: Hepatology Communications
Zhuolun Song, Bostjan Humar, Anurag Gupta, Eleonora Maurizio, Nathalie Borgeaud, Rolf Graf, Pierre-Alain Clavien, Yinghua Tian
Defective regeneration of small-for-size (SFS) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT) has protective effects on hepatic ischemia reperfusion injury (IRI), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR+PH group: 60 min liver ischemia (IR) plus 2/3 hepatectomy (PH); (II) IR+exPH group: 60 min liver IR plus extended hepatectomy (exPH) associated with the SFS syndrome; (III) SFS-LT group: Arterialized 30% SFS liver transplant...
March 5, 2018: Journal of Pineal Research
Ferenc Jakab
Numerous outstanding summarizing publications on the milestones of the rapid development of liver surgery in the twentieth century came to light around the year 2000, therefore in this summary only the newest principles and novelties of liver surgery after the second millennium are presented. Among the new principles, the newest indications, the bloodless surgery and the vascular exclusion of the liver, the "associating liver partition and portal vein occlusion for staged hepatectomy" (ALPPS) - as presently the fastest and most successful method for liver regeneration, and the "downsizing of tumors" treatment for the interest of resection of unresectable tumours are analyzed and evaluated...
March 2018: Orvosi Hetilap
Preeti Viswanathan, Yogeshwar Sharma, Priya Gupta, Sanjeev Gupta
OBJECTIVES: Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. MATERIALS AND METHODS: Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure...
March 5, 2018: Cell Proliferation
Hiromu Miyake, Bo Li, Carol Lee, Yuhki Koike, Yong Chen, Shogo Seo, Agostino Pierro
BACKGROUND: Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. METHODS: Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control...
February 7, 2018: Journal of Pediatric Surgery
Ming-Ming Ni, Ya-Rui Wang, Wen-Wen Wu, Chong-Cai Xia, Yi-He Zhang, Jing Xu, Tao Xu, Jun Li
Liver fibrosis is characterized by an increased and altered deposition of extracellular matrix (ECM) proteins that make up excessive tissue scarring and promote chronic liver injury. Activation of hepatic stellate cells (HSCs) is a pivotal cellular event in the progression of liver fibrosis. However, the mechanisms involved in the development of liver fibrosis are only now beginning to be unveiled. The Notch pathway is a fundamental and highly conserved pathway able to control cell-fate, including cell proliferation, differentiation, apoptosis, regeneration and other cellular activities...
March 1, 2018: European Journal of Pharmacology
Tolunay B Aydemir, Robert J Cousins
The SLC39A family of metal transporters was identified through homologies with the Zrt- and Irt-like (ZIP) proteins from yeast and plants. Of all the ZIP transporters, ZIP14 is arguably the most robustly characterized in terms of function at the integrative level. Mice with a global knockout of Zip14 are viable, thus providing the opportunity to conduct physiologic experiments. In mice, Zip14 expression is highly tissue specific, with the greatest abundance in the jejunum > liver > heart > kidney > white adipose tissue > skeletal muscle > spleen > pancreas...
February 1, 2018: Journal of Nutrition
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