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Liver 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
Céline Hernandez, Peter Huebener, Jean-Philippe Pradere, Daniel J Antoine, Richard A Friedman, Robert F Schwabe
Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD...
March 20, 2018: Journal of Clinical Investigation
Nan Mu, Jintao Gu, Nannan Liu, Xiaochang Xue, Zhen Shu, Kuo Zhang, Tonglie Huang, Chu Chu, Wangqian Zhang, Li Gong, Huadong Zhao, Bo Jia, Dakuan Gao, Lei Shang, Wei Zhang, Qingdong Guo
Purpose: Glioblastoma is the most common and aggressive type of primary brain malignancy and is associated with a poor prognosis. Previously, we found that phosphatase of regenerating liver-3 (PRL-3) was significantly up-regulated in glioblastoma as determined by a microarray analysis. However, the function of PRL-3 in glioblastoma remains unknown. We aimed to investigate the clinical relationship between PRL-3 and glioblastoma, and uncover the mechanisms of PRL-3 in the process of glioblastoma. Methods: PRL-3 expression was evaluated in 61 glioblastoma samples and 4 cell lines by RT-qPCR and immunohistochemistry...
2018: Theranostics
Barun Das, Jashdeep Bhattacharjee, Preeti, Alaknanda Mishra, Kshama Jain, Srikanth Iyer, Ashwani Kesarwani, Parul Sahu, Prakriti Sinha, Perumal Nagarajan, Pramod Upadhyay
Partial hepatectomy is a versatile and reproducible method to study liver regeneration and the effect of cell based therapeutics in various pathological conditions. Partial hepatectomy also facilitates the increased engraftment and proliferation of transplanted cells by accelerating neovascularization and cell migration towards the liver. Here, we describe a simple protocol for performing 30% hepatectomy and transplantation of cells in the spleen of a non-obese diabetic/severe combined immunodeficient NOD.SCID (NOD...
February 10, 2018: Journal of Visualized Experiments: JoVE
Nahide Ekici Günay, Sabahattin Muhtaroğlu, Abdulkadir Bedirli
BACKGROUND: Free radical damage is known to occur during liver regeneration. The Ginkgo biloba extract EGb761 has antioxidant properties due to its ability to scavenge free radicals. FK506 has been widely used as an immunosuppressant that stimulates hepatocyte proliferation following partial hepatectomy. AIMS: To explore whether EGb761 enhances liver regeneration after hepatectomy in rats, we investigated the effects of EGb761 alone and in combination with FK506 on the liver regenerative process...
March 15, 2018: Balkan Medical Journal
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
Sarva Mangala Praveena, Seoh Wei Teh, Ranjith Kumar Rajendran, Narayanan Kannan, Chu-Ching Lin, Rozaini Abdullah, Suresh Kumar
Phthalates have been blended in various compositions as plasticizers worldwide for a variety of purposes. Consequently, humans are exposed to a wide spectrum of phthalates that needs to be researched and understood correctly. The goal of this review is to focus on phthalate's internal exposure pathways and possible role of human digestion on liver toxicity. In addition, special focus was made on stem cell therapy in reverting liver toxicity. The known entry of higher molecular weight phthalates is through ingestion while inhalation and dermal pathways are for lower molecular weight phthalates...
March 15, 2018: Environmental Science and Pollution Research International
Li Yin, Xueqiang Guo, Chunyan Zhang, Zhihui Cai, Cunshuan Xu
The priming stage is the first step of liver regeneration (LR). This stage is characterized by the transition from G0 to cell cycle for 4 hours in rat. In this study, individual gene level and gene set level (GSEA) was performed to identify the candidate genes and significantly changed biological processes at 2 h after partial hepatectomy (PH). The leading edge analysis is performed to identify the key genes and iRegulon was employed for transcription factor (TF) analysis. A total of 53 differentially expressed genes were identified using RMA package based on R language at 2 h after PH, including the transcription factor, enzyme and cytokine...
February 20, 2018: Oncotarget
Henrik Lauridsen, Casper Bindzus Foldager, Line Hansen, Michael Pedersen
Non-invasive methods to track the progress of stem cell therapies are important in the development of future regenerative therapies. Super-paramagnetic iron oxide particles (SPIOs) have previously been applied to track cells using magnetic resonance imaging (MRI) in vivo in non-regenerative animal models. To the best of the author's knowledge, the present study investigated for the first time, the feasibility of tracking SPIO labeled cells in an intrinsic regenerative environment, the regenerating limb of the axolotl, and investigated the homing of stem cell-like blastema cells to the regenerative zone...
April 2018: Experimental and Therapeutic Medicine
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
Alexander Raven, Wei-Yu Lu, Tak Yung Man, Sofia Ferreira-Gonzalez, Eoghan O'Duibhir, Benjamin J Dwyer, John P Thomson, Richard R Meehan, Roman Bogorad, Victor Koteliansky, Yuri Kotelevtsev, Charles Ffrench-Constant, Luke Boulter, Stuart J Forbes
This corrects the article DOI: 10.1038/nature23015.
March 14, 2018: Nature
Xu-Feng Lu, Xiao-Yue Cao, Yong-Jie Zhu, Zhen-Ru Wu, Xiang Zhuang, Ming-Yang Shao, Qing Xu, Yong-Jie Zhou, Hong-Jie Ji, Qing-Richard Lu, Yu-Jun Shi, Yong Zeng, Hong Bu
Histone deacetylase 3 (HDAC3) plays pivotal roles in cell cycle regulation and is often aberrantly expressed in various cancers including hepatocellular carcinoma (HCC), but little is known about its role in liver regeneration and liver cancer cells proliferation. Using an inducible hepatocyte-selective HDAC3 knockout mouse, we find that lack of HDAC3 dramatically impaired liver regeneration and blocked hepatocyte proliferation in the G1 phase entry. HDAC3 inactivation robustly disrupted the signal transducer and activator of transcription 3 (STAT3) cascade...
March 14, 2018: Cell Death & Disease
Prachi Borude, Bharat Bhushan, Udayan Apte
Acetaminophen (APAP) overdose is the leading cause of Acute Liver Failure (ALF) with limited treatment options. It is known that liver regeneration following APAP induced ALF is a deciding factor in the final outcome. Previous studies from our laboratory using incremental dose model involving a regenerating (300 mg/kg, APAP300) and a non-regenerating (600 mg/kg, APAP600) dose of APAP in mice have revealed several pro- regenerative pathways that regulate regeneration after APAP overdose. Here we report that DNA damage and repair mechanisms regulate initiation liver regeneration following APAP overdose...
March 14, 2018: Gene Expression
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
Andrew J Lutkewitte, George G Schweitzer, Stefanie Kennon-McGill, Melissa M Clemens, Laura P James, Hartmut Jaeschke, Brian N Finck, Mitchell R McGill
No abstract text is available yet for this article.
March 10, 2018: Food and Chemical Toxicology
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
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