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https://www.readbyqxmd.com/read/28330992/localized-hepatic-lobular-regeneration-by-central-vein-associated-lineage-restricted-progenitors
#1
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...
March 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325574/decoy-receptor-3-analogous-supplement-protects-steatotic-rat-liver-from-ischemia-reperfusion-injury
#2
Tzu-Hao Li, Chih-Wei Liu, Pei-Chang Lee, Chia-Chang Huang, Kuei-Chuan Lee, Yun-Cheng Hsieh, Ying-Ying Yang, Shie-Liang Hsieh, Han-Chieh Lin, Chang-Youh Tsai
BACKGROUND: For steatotic livers, pharmacological approaches to minimize the hepatic neutrophil and macrophage infiltration, and cytokine and chemokine release in ischemia-reperfusion (IR) injury are still limited. Tumor necrosis factor (TNF)-α superfamily-stimulated pathogenic cascades and M1 macrophage/Kupffer cells (KC) polarization from Th1 cytokines are important in the pathogenesis of IR liver injury with hepatic steatosis (HS). Conversely, anti-inflammatory M2 macrophages produce Th2 cytokine (interleukin-4), which reciprocally enhances M2 polarization...
March 16, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28318408/bone-marrow-derived-mesenchymal-stem-cells-attenuate-immune-mediated-liver-injury-and-compromise-virus-control-during-acute-hepatitis-b-virus-infection-in-mice
#3
Mengmeng Qu, Xu Yuan, Dan Liu, Yuhong Ma, Jun Zhu, Jun Cui, Mengxue Yu, Changyong Li, Deyin Guo
Mesenchymal stem cells (MSCs) have been used as therapeutic tools not only for their ability to differentiate toward different cells, but also for their unique immunomodulatory properties. However, it is still unknown how MSCs may affect immunity during hepatitis B virus (HBV) infection. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in a mouse model of acute HBV infection. Mice were injected with 1 × 10(6) BM-MSCs, which stained with chloromethyl derivatives of fluorescein diacetate fluorescent probe, 24 h before hydrodynamic injection of viral DNA (pHBV1...
February 2, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28317925/liver-macrophages-in-tissue-homeostasis-and-disease
#4
REVIEW
Oliver Krenkel, Frank Tacke
Macrophages represent a key cellular component of the liver, and are essential for maintaining tissue homeostasis and ensuring rapid responses to hepatic injury. Our understanding of liver macrophages has been revolutionized by the delineation of heterogeneous subsets of these cells. Kupffer cells are a self-sustaining, liver-resident population of macrophages and can be distinguished from the monocyte-derived macrophages that rapidly accumulate in the injured liver. Specific environmental signals further determine the polarization and function of hepatic macrophages...
March 20, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28299189/molecular-signature-of-anastasis-for-reversal-of-apoptosis
#5
Ho Man Tang, C Conover Talbot, Ming Chiu Fung, Ho Lam Tang
Apoptosis is a type of programmed cell death that is essential for normal organismal development and homeostasis of multicellular organisms by eliminating unwanted, injured, or dangerous cells. This cell suicide process is generally assumed to be irreversible. However, accumulating studies suggest that dying cells can recover from the brink of cell death. We recently discovered an unexpected reversibility of the execution-stage of apoptosis in vitro and in vivo, and proposed the term anastasis (Greek for "rising to life") to describe this cell recovery phenomenon...
2017: F1000Research
https://www.readbyqxmd.com/read/28288070/novel-synthetic-host-defense-peptide-protects-against-organ-injury-dysfunction-in-a-rat-model-of-severe-hemorrhagic-shock
#6
Noriaki Yamada, Lukas B Martin, Elisabeth Zechendorf, Gareth S D Purvis, Fausto Chiazza, Barbara Varrone, Massimo Collino, Joanna Shepherd, Lena Heinbockel, Thomas Gutsmann, Wilmar Correa, Klaus Brandenburg, Gernot Marx, Tobias Schuerholz, Karim Brohi, Christoph Thiemermann
OBJECTIVE: To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. BACKGROUND: HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. METHODS: (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center...
March 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28287406/mesothelin-mucin-16-signaling-in-activated-portal-fibroblasts-regulates-cholestatic-liver-fibrosis
#7
Yukinori Koyama, Ping Wang, Shuang Liang, Keiko Iwaisako, Xiao Liu, Jun Xu, Mingjun Zhang, Mengxi Sun, Min Cong, Daniel Karin, Kojiro Taura, Chris Benner, Sven Heinz, Tapan Bera, David A Brenner, Tatiana Kisseleva
Cholestatic liver fibrosis is caused by obstruction of the biliary tract and is associated with early activation of portal fibroblasts (PFs) that express Thy-1, fibulin 2, and the recently identified marker mesothelin (MSLN). Here, we have demonstrated that activated PFs (aPFs) and myofibroblasts play a critical role in the pathogenesis of liver fibrosis induced by bile duct ligation (BDL). Conditional ablation of MSLN+ aPFs in BDL-injured mice attenuated liver fibrosis by approximately 50%. Similar results were observed in MSLN-deficient mice (Msln-/- mice) or mice deficient in the MSLN ligand mucin 16 (Muc16-/- mice)...
March 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28270138/hepatocytes-express-the-antimicrobial-peptide-hbd-2-after-multiple-trauma-an-experimental-study-in-human-and-mice
#8
Stefanie Fitschen-Oestern, Matthias Weuster, Sebastian Lippross, Peter Behrendt, Sabine Fuchs, Thomas Pufe, Mersedeh Tohidnezhad, Andreas Bayer, Andreas Seekamp, Deike Varoga, Tim Klüter
BACKGROUND: Human-beta defensins (HBD) belong to the family of acute phase peptides and hold a broad antimicrobial spectrum that includes gram-positive and gram-negative bacteria. HBD are up-regulated after severe injuries but the source of posttraumatic HBD expression has not been focused on before. In the current study we analysed the role of liver tissue in expression of HBD after multiple trauma in human and mice. METHODS: HBD-2 expression has been detected in plasma samples of 32 multiple trauma patients (ISS > 16) over 14 days after trauma by ELISA...
March 7, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28261903/testing-of-microencapsulated-porcine-hepatocytes-in-a-new-model-of-fulminant-liver-failure-in-baboons
#9
Zurab Machaidze, Heidi Yeh, Lingling Wei, Christian Schuetz, Michele Carvello, Antonino Sgroi, Rex N Smith, Henk-Jan Schuurman, David H Sachs, Philippe Morel, James F Markmann, Léo H Bühler
BACKGROUND: There is no standard therapy for acute liver failure. Hepatocyte transplantation has been proposed for temporary liver function support, while the injured liver regenerates or while waiting for transplantation. We have previously shown such efficacy for microencapsulated porcine hepatocytes in mice with fulminant liver failure. We aimed to establish a large animal model for fulminant liver failure to assess the efficacy of microencapsulated porcine hepatocytes in temporary liver function support...
March 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28243716/contemporary-damage-control-surgery-outcomes-80-patients-with-severe-abdominal-injuries-in-the-right-upper-quadrant-analyzed
#10
M Hommes, S Chowdhury, D Visconti, P H Navsaria, J E J Krige, D Cadosch, A J Nicol
BACKGROUND: Damage control laparotomy (DCL) is a well-established surgical strategy in the management of the severely injured abdominal trauma patients. The selection of patients by intra-abdominal organs involvement for DCL remains controversial. The aim of this study was to assess the injury to the abdominal organs that causing severe metabolic failure, needing DCL. METHODS: Severely injured abdominal trauma patients with a complex pattern of injuries were reviewed over a 52-month period...
February 27, 2017: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/28223176/prodromal-fever-indicates-a-high-risk-of-liver-failure-in-acute-hepatitis-b
#11
Wen-Jun Du, Li Liu, Chao Sun, Jin-Hong Yu, Di Xiao, Qiang Li
OBJECTIVES: The role of prodromal fever in the clinical course of acute hepatitis B virus (HBV) infection is still largely unclear. This study was conducted to investigate the factors associated with prodromal fever and its role in the development of acute liver failure (ALF) in patients with acute hepatitis B (AHB). METHODS: Inpatients with AHB diagnosed between January 2006 and December 2010 were evaluated and followed. Clinical manifestations, results of laboratory tests, and outcomes were compared between patients with and without prodromal fever...
February 20, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28213967/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stem-cells-improve-survival-from-lethal-hepatic-failure-in-mice
#12
Hiroaki Haga, Irene K Yan, Kenji Takahashi, Akiko Matsuda, Tushar Patel
Stem cell-based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. Therapeutic effects of bone-marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d-galactosamine/tumor necrosis factor-α (TNF-α)...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205428/systemically-infused-mesenchymal-stem-cells-show-different-homing-profiles-in-healthy-and-tumor-mouse-models
#13
Chengying Xie, Zhangru Yang, Yuanzhen Suo, Qianqian Chen, Dan Wei, Xiaofu Weng, Zhengqin Gu, Xunbin Wei
Bone marrow-derived mesenchymal stem cells (MSCs) can localize in injured, inflamed, and cancerous tissues after systemic infusion. However, the dynamic homing profile of MSCs in the peripheral blood is not well characterized. Here, using in vivo flow cytometry to noninvasively monitor the dynamics of fluorescence-labeled cells, we found different clearance kinetics of systemically infused MSCs between healthy and tumor mouse models. The circulation times of MSCs in healthy mice and mice with subcutaneous tumors, orthotopically transplanted liver tumors, or metastatic lung tumors were 30, 24, 18, and 12 hours, respectively, suggesting that MSCs actively home to tumor environments...
February 16, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28196324/delivery-of-liposomal-quantum-dots-via-monocytes-for-imaging-of-inflamed-tissue
#14
Gil Aizik, Nir Waiskopf, Majd Agbaria, Yael Levi-Kalisman, Uri Banin, Gershon Golomb
Quantum dots (QDs), semiconductor nanocrystals, are fluorescent nanoparticles of growing interest as an imaging tool of a diseased tissue. However, a major concern is their biocompatibility, cytotoxicity, and fluorescence instability in biological milieu, impeding their use in biomedical applications, in general, and for inflammation imaging, in particular. In addition, for an efficient fluorescent signal at the desired tissue, and avoiding systemic biodistribution and possible toxicity, targeting is desired...
February 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28175977/development-and-evaluation-of-a-novel-curved-biopsy-device-for-ct-guided-biopsy-of-lesions-unreachable-using-standard-straight-needle-trajectories
#15
Maximilian Franz Schulze-Hagen, Jochen Pfeffer, Markus Zimmermann, Martin Liebl, Saskia Freifrau von Stillfried, Christiane Kuhl, Philipp Bruners, Peter Isfort
PURPOSE: To evaluate the feasibility of a novel curved CT-guided biopsy needle prototype with shape memory to access otherwise not accessible biopsy targets. METHODS AND MATERIALS: A biopsy needle curved by 90° with specific radius was designed. It was manufactured using nitinol to acquire shape memory, encased in a straight guiding trocar to be driven out for access of otherwise inaccessible targets. Fifty CT-guided punctures were conducted in a biopsy phantom and 10 CT-guided punctures in a swine corpse...
February 7, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28168393/enhanced-colorectal-cancer-metastases-in-the-alcohol-injured-liver
#16
Ashley M Mohr, John J Gould, Jacy L Kubik, Geoffrey A Talmon, Carol A Casey, Peter Thomas, Dean J Tuma, Benita L McVicker
Metastatic liver disease is a major cause of mortality in colorectal cancer (CRC) patients. Alcohol consumption is a noted risk factor for secondary cancers yet the role of alcoholic liver disease (ALD) in colorectal liver metastases (CRLM) is not defined. This work evaluated tumor cell colonization in the alcoholic host liver using a novel preclinical model of human CRC liver metastases. Immunocompromised Rag1-deficient mice were fed either ethanol (E) or isocaloric control (C) diets for 4 weeks prior to intrasplenic injection of LS174T human CRC cells...
February 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28163111/a-compromised-liver-alters-polychlorinated-biphenyl-mediated-toxicity
#17
Banrida Wahlang, Jordan T Perkins, Michael C Petriello, Jessie B Hoffman, Arnold J Stromberg, Bernhard Hennig
Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study...
February 2, 2017: Toxicology
https://www.readbyqxmd.com/read/28162981/caveolin-1-and-g-protein-coupled-receptor-kinase-2-coregulate-endothelial-nitric-oxide-synthase-activity-in-sinusoidal-endothelial-cells
#18
Songling Liu, Richard T Premont, Shweta Singh, Don C Rockey
Liver injury leads to a vasculopathy in which post-translational modifications of endothelial nitric oxide synthase (eNOS) lead to impaired nitric oxide synthesis. We hypothesized that caveolin 1 (CAV1), a well-known eNOS interactor, regulates eNOS activity in sinusoidal endothelial cells (SECs) via its interaction with G-protein-coupled receptor kinase-2 (GRK2) that also post-translationally modifies eNOS. Liver injury with portal hypertension was established using bile duct ligation in rats. CAV1 function was modified using a CAV1 scaffolding domain construct and cDNAs encoding wild-type CAV1, and CAV1 phosphorylation was increased in injured SECs, resulting in increased GRK2-CAV1 interaction and decreased eNOS activity...
February 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28144137/plaque-hyaluronidase-responsive-high-density-lipoprotein-mimetic-nanoparticles-for-multistage-intimal-macrophage-targeted-drug-delivery-and-enhanced-anti-atherosclerotic-therapy
#19
Mengyuan Zhang, Jianhua He, Cuiping Jiang, Wenli Zhang, Yun Yang, Zhiyu Wang, Jianping Liu
Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiology of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-density lipoprotein (rHDL) for iMΦ and its limited cholesterol efflux ability, we designed a hyaluronan (HA)-anchored core-shell rHDL. This nanoparticle achieved efficient iMΦ-targeted drug delivery via a multistage-targeting approach, and excellent cellular cholesterol removal...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28137632/generation-6-hydroxyl-pamam-dendrimers-improve-cns-penetration-from-intravenous-administration-in-a-large-animal-brain-injury-model
#20
Fan Zhang, J Trent Magruder, Yi-An Lin, Todd C Crawford, Joshua C Grimm, Christopher M Sciortino, Mary Ann Wilson, Mary E Blue, Sujatha Kannan, Michael V Johnston, William A Baumgartner, Rangaramanujam M Kannan
Hypothermic circulatory arrest (HCA) provides neuroprotection during cardiac surgery but entails an ischemic period that can lead to excitotoxicity, neuroinflammation, and subsequent neurologic injury. Hydroxyl polyamidoamine (PAMAM) dendrimers target activated microglia and damaged neurons in the injured brain, and deliver therapeutics in small and large animal models. We investigated the effect of dendrimer size on brain uptake and explored the pharmacokinetics in a clinically-relevant canine model of HCA-induced brain injury...
March 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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