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https://www.readbyqxmd.com/read/28435131/repression-of-acetaminophen-induced-hepatotoxicity-by-a-combination-of-celastrol-and-brilliant-blue-g
#1
Heba A Abdelaziz, Mohamed E Shaker, Mohamed F Hamed, Nariman M Gameil
The sterile inflammatory response is an eminent contributor to acetaminophen (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of signaling events preceded the NLRP3-inflammasome activation, like the transcription factor NF-κB and the purinergic receptor P2×7, is still unclear and needs further elucidation. Here, we investigated the pharmacological inhibition of these upstream signaling molecules by celastrol and brilliant blue G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice...
April 20, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28432428/tranexamic-acid-for-treatment-and-prophylaxis-of-bleeding-and-hyperfibrinolysis
#2
Ingrid Pabinger, Dietmar Fries, Herbert Schöchl, Werner Streif, Wolfgang Toller
Uncontrolled massive bleeding with subsequent derangement of the coagulation system is a major challenge in the management of both surgical and seriously injured patients. Under physiological conditions activators and inhibitors of coagulation regulate the sensitive balance between clot formation and fibrinolysis. In some cases, excessive and diffuse bleeding is caused by systemic activation of fibrinolysis, i. e. hyperfibrinolysis (HF). Uncontrolled HF is associated with a high mortality. Polytrauma patients and those undergoing surgical procedures involving organs rich in plasminogen proactivators (e...
April 21, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28431976/the-impact-of-exposure-to-environmental-contaminant-on-hepatocellular-lipid-metabolism
#3
Zongguang Hui, Rujiang Li, Li Chen
Increasing evidences show that ubiquitous perfluorooctanoic acid (PFOA), a representative environmental pollutant, is found to be linked to lipid dysmetabolism. However, the biological mechanism behind this outcome remains uninvestigated. In the present study, we established the PFOA-injured liver in mice to explore the underlying mechanism associated with PFOA-induced lipid disturbance in the liver via a group of biochemical and molecular assays. As results, PFOA-exposed mice showed increased transaminase (ALT), reduced triglyceride and free fatty acid contents in serum, as well as elevated level of hepatic triglyceride...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28420460/-bone-marrow-mesenchymal-stem-cells-modulated-the-inflammatory-response-by-regulating-the-expression-of-il-4-and-rage-products-in-the-rats-with-mods
#4
Xia Zhou, Guanghui Xiu, Yichao Zhu, Xiaolei Chen, Wei Xiong, Xinghua Pan, Jie Sun, Bin Ling
OBJECTIVE: To investigate the underlying mechanism of bone marrow mesenchymal stem cells (BMSC) modulating the inflammatory response during the multiple organ dysfunction syndrome (MODS), especially the expression of inflammatory cytokines, which will provide new theoretical and experimental basis of MODS in clinic. METHODS: BMSC of Sprague-Dawley (SD) rat (female, 4 weeks) was extracted and cultivated, and the 4th passage were used in experimental study. According to the random number table, 60 female SD rats were divided into three groups (n = 20 per group): sham group, MODS group, BMSC group...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28415724/pharmacological-inhibition-of-src-kinase-protects-against-acute-kidney-injury-in-a-murine-model-of-renal-ischemia-reperfusion
#5
Chongxiang Xiong, Xiujuan Zang, Xiaoxu Zhou, Lirong Liu, Monica V Masucci, Jinhua Tang, Xuezhu Li, Na Liu, George Bayliss, Ting C Zhao, Shougang Zhuang
Activation of Src kinase has been implicated in the pathogenesis of acute brain, liver, and lung injury. However, the role of Src in acute kidney injury (AKI) remains unestablished. To address this, we evaluated the effects of Src inhibition on renal dysfunction and pathological changes in a murine model of AKI induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in increased Src phosphorylation at tyrosine 416 (activation). Administration of PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved renal function and ameliorated renal pathological damage...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413861/preconditioning-with-melatonin-improves-therapeutic-outcomes-of-bone-marrow-derived-mesenchymal-stem-cells-in-targeting-liver-fibrosis-induced-by-ccl4
#6
Keywan Mortezaee, Neda Khanlarkhani, Fatemeh Sabbaghziarani, Saeid Nekoonam, Jamal Majidpoor, Amir Hosseini, Parichehr Pasbakhsh, Iraj Ragerdi Kashani, Adib Zendedel
Preconditioning of mesenchymal stem cells (MSCs) with melatonin (MT) has shown promising results in animal models of myocardial infarction, renal ischemia and cerebral ischemia. Here, we use this strategy in the liver fibrosis induced by CCl4. There were five groups: normal, CCl4, CCl4 + vehicle, CCl4 + BMMSCs and CCl4 + MT-bone marrow (BM)-derived MSCs (MT-BMMSCs). CCl4 was injected twice weekly for 8 weeks and treatment either with cells or vehicle was performed at the beginning of week 5 with a single dose...
April 17, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28409921/mesenchymal-stem-cell-seeded-regenerated-silk-fibroin-complex-matrices-for-liver-regeneration-in-an-animal-model-of-acute-liver-failure
#7
Lijuan Xu, Shufang Wang, Xiang Sui, Yu Wang, Yinan Su, Li Huang, Yunwei Zhang, Zheng Chen, Qianqian Chen, Haitao Du, Yaopeng Zhang, Li Yan
The main limitation of liver transplantation as a treatment for end-stage liver disease or acute liver failure is the scarcity of liver organ donors. To develop an alternative therapy for acute liver failure, mesenchymal stem cell (MSC)-seeded regenerated silk fibroin (RSF) matrices were evaluated in vitro and in vivo. Adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) were planted and grown on RSF scaffolds to form a scaffold complex. The RSF-MSC scaffold complex (the experimental group) and neat RSF scaffolds (the control group) were then placed onto the liver surface of mice induced by CCl4 and detected after 5, 7, 14, 28, and 60 days...
April 24, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28407355/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stem-cells-protect-against-murine-hepatic-ischemia-reperfusion-injury
#8
Hiroaki Haga, Irene K Yan, David Borelli, Akiko Matsuda, Mansi Parasramka, Neha Shukla, David D Lee, Tushar Patel
Hepatic ischemia-reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSC) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from MSCs (MSC-EV) on tissue injury. The effects of systemically administered mouse bone marrow derived MSC-EV were evaluated in an experimental murine model of hepatic IRI induced by cross clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of upto 6 hours...
April 13, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28405790/csh-guidelines-for-the-diagnosis-and-treatment-of-drug-induced-liver-injury
#9
EDITORIAL
Yue-Cheng Yu, Yi-Min Mao, Cheng-Wei Chen, Jin-Jun Chen, Jun Chen, Wen-Ming Cong, Yang Ding, Zhong-Ping Duan, Qing-Chun Fu, Xiao-Yan Guo, Peng Hu, Xi-Qi Hu, Ji-Dong Jia, Rong-Tao Lai, Dong-Liang Li, Ying-Xia Liu, Lun-Gen Lu, Shi-Wu Ma, Xiong Ma, Yue-Min Nan, Hong Ren, Tao Shen, Hao Wang, Ji-Yao Wang, Tai-Ling Wang, Xiao-Jin Wang, Lai Wei, Qing Xie, Wen Xie, Chang-Qing Yang, Dong-Liang Yang, Yan-Yan Yu, Min-de Zeng, Li Zhang, Xin-Yan Zhao, Hui Zhuang
Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells...
April 12, 2017: Hepatology International
https://www.readbyqxmd.com/read/28400340/eosin-fluorescence-a-diagnostic-tool-for-quantification-of-liver-injury
#10
Hamid Ali, Safdar Ali, Maryam Mazhar, Amjad Ali, Azra Jahan, Abid Ali
Hepatitis is one of the most common life threatening diseases. The diagnosis is mainly based on biochemical analysis such as liver function test. However, histopathological evaluation of liver serves far better for more accurate final diagnosis. The goal of our study was to evaluate the eosin fluorescence pattern in CCl4-induced liver injury model compared with normal and different treatment groups. For this purpose, liver tissues were stained with H/E and examined under bright field microscope but the fluorescence microscopy of H/E stained slides provided an interesting fluorescence pattern and was quite helpful in identifying different structures...
April 8, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28386338/pigment-epithelium-derived-factor-pedf-peptide-promotes-the-expansion-of-hepatic-stem-progenitor-cells-via-erk-and-stat3-dependent-signaling
#11
Shou-Chuan Shih, Tsung-Chuan Ho, Show-Li Chen, Yeou-Ping Tsao
Hepatic stem/progenitor cells (HPC) have been considered as a potential cell source of an alternative to liver transplantation. Production of large numbers of autologous HPC from small pieces of live tissue is crucial for the application of HPC-based liver therapy. In this study, we demonstrated that a synthetic 44-amino acid peptide (44-mer) derived from pigment epithelium-derived factor (PEDF) can facilitate the production of a large number of actively dividing HPC from normal adult rat livers in a 35-day culture period...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386095/timp-1-is-upregulated-but-not-essential-in-hepatic-fibrogenesis-and-carcinogenesis-in-mice
#12
Nina D Thiele, Jan W Wirth, David Steins, Anja C Koop, Harald Ittrich, Ansgar W Lohse, Johannes Kluwe
Tissue inhibitor of metalloproteinases-1 (TIMP-1) is upregulated during hepatic fibrogenesis and considered to promote fibrosis in the injured liver by inhibition of matrix metalloproteases (MMP) and degradation of extracellular matrix. Moreover, TIMP-1 displays anti-apoptotic properties, in patients with hepatocellular carcinoma (HCC) TIMP-1 serum levels are elevated and high TIMP-1 expression levels in HCC are associated with a poor prognosis. Therefore, TIMP-1 could functionally link fibrogenesis and carcinogenesis in the liver...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28377714/steroidal-alkaloids-as-an-emerging-therapeutic-alternative-for-investigation-of-their-immunosuppressive-and-hepatoprotective-potential
#13
Naeem U Jan, Bashir Ahmad, Safdar Ali, Achyut Adhikari, Amjad Ali, Azra Jahan, Abid Ali, Hamid Ali
The compounds, sarcovagine-D, alkaloid-C, and holaphylline isolated from Sarcococca saligna were found to possess immunosuppressive activities. These compounds were characterized for in vitro inhibition on human T-cells proliferation and IL-2 production. The compounds showed significant immunosuppressive effect on IL-2 production as well as on phytohemagglutinin stimulated T-cell proliferation in a dose dependent manner. Of all the tested compounds holaphylline was found to be less toxic and safe. These compounds were then evaluated for their in vivo hepatoprotective potential against CCl4, in which alkaloid-C and holaphylline showed markedly reduced liver inflammation and biochemical parameter (ALT, AST, and ALP) of liver injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28377509/genetic-tracing-of-hepatocytes-in-liver-homeostasis-injury-and-regeneration
#14
Yue Wang, Xiuzhen Huang, Lingjuan He, Wenjuan Pu, Yan Li, Qiaozhen Liu, Yi Li, Libo Zhang, Wei Yu, Huan Zhao, Yingqun Zhou, Bin Zhou
The liver possesses a remarkable capacity to regenerate after damage. There is a heated debate on the origin of new hepatocytes following injuries in adult liver. Hepatic stem/progenitor cells have been proposed to produce functional hepatocytes after injury. Recent studies have argued against this model and suggested that pre-existing hepatocytes, rather than stem cells, contribute new hepatocytes. This hepatocyte-to-hepatocyte model is mainly based on labeling of hepatocytes with Cre-recombinase delivered by adeno-associated virus (AAV)...
April 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28373282/metformin-directly-binds-the-alarmin-hmgb1-and-inhibits-its-proinflammatory-activity
#15
Takahiro Horiuchi, Natsumi Sakata, Yoshihiro Narumi, Tomohiro Kimura, Takashi Hayashi, Keisuke Nagano, Keyue Liu, Masahiro Nishibori, Sohei Tsukita, Tetsuya Yamada, Hideki Katagiri, Ryutaro Shirakawa, Hisanori Horiuchi
Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is therefore a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin binding protein by affinity purification using a biotinylated metformin analogue...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28372277/mechanobiology-of-mesenchymal-stem-cells-which-interest-for-cell-based-treatment
#16
Céline Huselstein, R Rahouadj, N de Isla, D Bensoussan, J F Stoltz, Y P Li
Thanks to their immune properties, the mesenchymal stem cells (MSC) are a promising source for cell therapy. Current clinical trials show that MSC administrated to patients can treat different diseases (graft-versus-host disease (GVHD), liver cirrhosis, systemic lupus, erythematosus, rheumatoid arthritis, type I diabetes…). In this case, the most common mode of cell administration is the intravenous injection, and the hemodynamic environment of cells induced by blood circulation could interfere on their behavior during the migration and homing towards the injured site...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28351519/contrast-enhanced-ultrasound-for-the-evaluation-of-blunt-pediatric-abdominal-trauma
#17
Lindsey B Armstrong, David P Mooney, Harriet Paltiel, Carol Barnewolt, Beatrice Dionigi, Mary Arbuthnot, Chinwendu Onwubiko, Susan A Connolly, Delma Y Jarrett, Jill M Zalieckas
INTRODUCTION: Blunt abdominal trauma is a common problem in children. Computed tomography (CT) is the gold standard for imaging in pediatric blunt abdominal trauma, however up to 50% of CTs are normal and CT carries a risk of radiation-induced cancer. Contrast enhanced ultrasound (CEUS) may allow accurate detection of abdominal organ injuries while eliminating exposure to ionizing radiation. METHODS: Children aged 7-18years with a CT-diagnosed abdominal solid organ injury underwent grayscale/power Doppler ultrasound (conventional US) and CEUS within 48h of injury...
March 20, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28341511/open-and-endovascular-abdominal-aortic-injury-repair-outcomes-in-polytrauma-patients
#18
Anand Dayama, Aksim Rivera, Odunayo Olorunfemi, Ahmed Mahmoud, Catherine A Fontecha, John McNelis
INTRODUCTION: The management of patients with abdominal aortic injury (AAI) remains challenging. Open repair of AAI is still the standard of care although it is associated with high mortality. In past few years, endovascular surgery has evolved as a less invasive alternative to open surgery in emergency settings. The objective of this study was to compare outcomes after open repair versus endovascular repair of AAI in polytrauma patients. METHODS: The National Trauma Data Bank, from 2008 to 2012, was queried to identify trauma patients undergoing open and endovascular repair of AAI using International Classification of Diseases, ninth Edition, and Clinical Modification codes...
March 21, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28335859/making-it-new-again-insight-into-liver-development-regeneration-and-disease-from-zebrafish-research
#19
Shuang Wang, Sophie R Miller, Elke A Ober, Kirsten C Sadler
The adult liver of most vertebrates is predominantly comprised of hepatocytes. However, these cells must work in concert with biliary, stellate, vascular, and immune cells to accomplish the vast array of hepatic functions required for physiological homeostasis. Our understanding of liver development was accelerated as zebrafish emerged as an ideal vertebrate system to study embryogenesis. Through work in zebrafish and other models, it is now clear that the cells in the liver develop in a coordinated fashion during embryogenesis through a complex yet incompletely understood set of molecular guidelines...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28330992/localized-hepatic-lobular-regeneration-by-central-vein-associated-lineage-restricted-progenitors
#20
Jonathan M Tsai, Pang Wei Koh, Ania Stefanska, Liujing Xing, Graham G Walmsley, Nicolas Poux, Irving L Weissman, Yuval Rinkevich
The regeneration of organ morphology and function following tissue loss is critical to restore normal physiology, yet few cases are documented in mammalian postnatal life. Partial hepatectomy of the adult mammalian liver activates compensatory hepatocyte hypertrophy and cell division across remaining lobes, resulting in restitution of organ mass but with permanent alteration of architecture. Here, we identify a time window in early postnatal life wherein partial amputation culminates in a localized regeneration instead of global hypertrophy and proliferation...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
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