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mitochondria transplant

Justin Pollara, R Whitney Edwards, Liwen Lin, Victoria A Bendersky, Todd V Brennan
Brain death that occurs in the setting of deceased organ donation for transplantation is associated with systemic inflammation of unknown origin. It has recently been recognized that mitochondria-derived damage-associated molecular patterns (mtDAMPs) released into the circulation in the setting of trauma and tissue injury are associated with a systemic inflammatory response. We examined the blood of deceased organ donors and found elevated levels of inflammatory cytokines and chemokines that correlated with levels of mtDAMPs...
August 9, 2018: JCI Insight
Ricky H Bhogal, Christopher J Weston, Susanne Velduis, Henri G D Leuvenink, Gary M Reynolds, Scott Davies, Luu Nyguet Thin, Mohammed Alfaifi, Emma Shepard, Yuri Boteon, Lorraine Wallace, Ye Oo, David H Adams, Darius F Mirza, Hynek Mergental, Gillian Muirhead, Barnaby F Stephenson, Simon C Afford
BACKGROUND: Ischaemia-reperfusion injury (IRI) is the main cause of complications following liver transplantation. Reactive oxygen species (ROS) were thought to be the main regulators of IRI. However recent studies demonstrate that ROS activates the cytoprotective mechanism of autophagy promoting cell survival. Liver IRI initially damages the liver endothelial cells (LEC) but whether ROS-autophagy promotes cell survival in LEC during IRI is not known. METHODS: Primary human LEC were isolated from human liver tissue and exposed to an in vitro model of IRI to assess the role of autophagy in LEC...
July 24, 2018: Liver Transplantation
Hung Nguyen, Sydney Zarriello, Mira Rajani, Julian Tuazon, Eleonora Napoli, Cesar V Borlongan
Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cell transplantation, may hold promise as a stroke therapy, because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery...
July 21, 2018: International Journal of Molecular Sciences
Mohammad Javad Ahmadi Lahijani, Mohammad Kafi, Ahmad Nezami, Jafar Nabati, Mohammad Zare Mehrjerdi, Shirin Shahkoomahally, John Erwin
Rising atmospheric CO2 concentrations are expected to impact the productivity of plants. Cultivars demonstrate different responses to CO2 levels, hence, screening and recognizing the cultivars with a higher capacity for translocation of photoassimilates would certainly be beneficiary. To investigate the interactive impact of enhancing CO2 on physiology, cellular fine structure and photoassimilate translocation of micro-propagated potato plantlets, plantlets (cvs. Agria and Fontane) were grown under ambient (400 ppm) or elevated (800 ppm) CO2 concentrations in controlled environments...
July 19, 2018: Plant Physiology and Biochemistry: PPB
Junwon Lee, Sang-Hwi Choi, Young-Beom Kim, Ikhyun Jun, Jin Jea Sung, Dongjin R Lee, Yang In Kim, Myung Soo Cho, Suk Ho Byeon, Dae-Sung Kim, Dong-Wook Kim
Purpose: We aimed to establish an efficient method for retinal ganglion cell (RGC) differentiation from human pluripotent stem cells (hPSCs) using defined factors. Methods: To define the contribution of specific signal pathways to RGC development and optimize the differentiation of hPSCs toward RGCs, we examined RGC differentiation in three stages: (1) eye field progenitors expressing the eye field transcription factors (EFTFs), (2) RGC progenitors expressing MATH5, and (3) RGCs expressing BRN3B and ISLET1...
July 2, 2018: Investigative Ophthalmology & Visual Science
Maria N Sanz, Emilie Farine, Petra Niederberger, Natalia Méndez-Carmona, Rahel K Wyss, Maria Arnold, Patrik Gulac, Georg M Fiedler, Mélanie Gressette, Anne Garnier, Thierry P Carrel, Hendrik T Tevaearai Stahel, Sarah L Longnus
Donation after circulatory death (DCD) holds great promise for improving cardiac graft availability, however concerns persist regarding injury following warm ischemia, after donor circulatory arrest, and subsequent reperfusion. Application of pre-ischemic treatments is limited for ethical reasons, thus cardioprotective strategies applied at graft procurement (reperfusion) are of particular importance in optimizing graft quality. Given the key role of mitochondria in cardiac ischemia-reperfusion injury, we hypothesize that three reperfusion strategies: mild hypothermia, mechanical post-conditioning and hypoxia, when briefly applied at reperfusion onset, provoke mitochondrial changes that may underlie their cardioprotective effects...
July 18, 2018: American Journal of Transplantation
Kuan-Xue Sun, Hong-Wei Xia
The aim of the present study was to elucidate the anticancer effect of pachymic acid (PA) in gastric cancer SGC-7901 cells and the potential molecular mechanisms involved. Cell Count kit-8 assay was performed to examine the effect of PA on the cell proliferation of SGC-7901 cells. Cell cycle, cell apoptosis, mitochondria membrane potential (Dψm) and reactive oxygen species (ROS) analysis were assessed by flow cytometry, respectively. DNA fragmentation assay was performed by Hoechst 33258 staining. Western blotting was performed to detect the effect of various concentrations of PA on the levels of BCL2 associated X protein (Bax) expression as well as B-cell lymphoma 2 (Bcl-2), cytochrome C (cyt-c) and caspase-3 in SGC-7901 cells...
August 2018: Oncology Letters
Yuanjing Li, Shengxin Xu, Ming Cai
The partial pressure of oxygen (PO2 ) in the tumor microenvironment directly affects tumor sensitivity to chemotherapy. In the present study, a lithium phthalocyanine probe was implanted into MCF-7 human breast cancer cells, followed by transplant of the cells into nude mice. The present study used an electron paramagnetic resonance (EPR) oximetry measuring technique to dynamically monitor PO2 in the tumor microenvironment prior to and following chemotherapy, and aimed to determine the precise time window in which the microenvironmental PO2 peaked following chemotherapy...
August 2018: Oncology Letters
Atif Abdulwahab A Oyouni, Shalini Saggu, Ehab Tousson, Hasibur Rehman
Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. Ocimum basilicum L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b...
2018: Toxicology Reports
Leilei Bao, Mingjian Zhang, Shu Han, Yangyang Zhan, Wenyuan Guo, Fei Teng, Fang Liu, Meng Guo, Luding Zhang, Guoshan Ding, Quanxiang Wang
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common human malignant diseases in the world, and the mechanisms underlying HCC carcinogenesis and progression need further investigation. MicroRNAs play important roles in the development of cancer, and miR-500a is suggested to be deregulated in some types of cancer. However, the underlying molecular mechanisms of miR-500a in HCC remain unknown. METHODS: The expression of miR-500a in HCC was analyzed in The Cancer Genome Atlas (TCGA) database and examined in 33 pairs of HCC tissues and matched nontumor tissues...
2018: Cellular Physiology and Biochemistry
Diangeng Li, Delong Zhao, Weiguang Zhang, Qian Ma, Dong Liu, Qi Huang, Ying Zheng, Xueyuan Bai, Xuefeng Sun, Xiangmei Chen
We established a young (Y)-old (O) rat kidney transplantation model. With this model, we detected no age-related differences in renal structure between Y→Y and Y→O kidneys or O→O and O→Y kidneys. However, we did detect differences in levels of the senescence markers β-gal and p16 as well as the inflammatory cytokines TNF-α and IL-1β. Using proteomics analysis we detected 66 proteins associated with suppression of aging and 73 proteins associated with enhancement of aging. After construction of a protein-protein interaction network, a total of 73 nodes and 99 edges were analyzed using MCODE, and three significant modules were selected...
June 14, 2018: Aging
Carola Ledderose, Kaifeng Liu, Yutaka Kondo, Christian J Slubowski, Thomas Dertnig, Sara Denicoló, Mona Arbab, Johannes Hubner, Kirstin Konrad, Mahtab Fakhari, James A Lederer, Simon C Robson, Gary A Visner, Wolfgang G Junger
T cells must migrate in order to encounter antigen-presenting cells (APCs) and to execute their varied functions in immune defense and inflammation. ATP release and autocrine signaling through purinergic receptors contribute to T cell activation at the immune synapse that T cells form with APCs. Here, we show that T cells also require ATP release and purinergic signaling for their migration to APCs. We found that the chemokine stromal-derived factor-1α (SDF-1α) triggered mitochondrial ATP production, rapid bursts of ATP release, and increased migration of primary human CD4+ T cells...
August 1, 2018: Journal of Clinical Investigation
Anna Moles, Sandra Torres, Anna Baulies, Carmen Garcia-Ruiz, Jose C Fernandez-Checa
Acetaminophen (APAP) toxicity is the most common cause of acute liver failure and a major indication for liver transplantion in the United States and Europe. Although significant progress has been made in understanding the molecular mechanisms underlying APAP hepatotoxicity, there is still an urgent need to find novel and effective therapies against APAP-induced acute liver failure. Hepatic APAP metabolism results in the production of the reactive metabolite N -acetyl- p -benzoquinone imine (NAPQI), which under physiological conditions is cleared by its conjugation with glutathione (GSH) to prevent its targeting to mitochondria...
2018: Frontiers in Pharmacology
Yiting Jia, Meili Wang, Chenfeng Mao, Fang Yu, Yingbao Wang, Rui Xiao, Changtao Jiang, Lemin Zheng, Qingbo Xu, Ming Zheng, Yi Fu, Qinghua Hu, Wei Kong
Vascular smooth muscle cells (VSMCs) are highly phenotypically plastic, and loss of the contractile phenotype in VSMCs has been recognized at the early onset of the pathology of a variety of vascular diseases. However, the endogenous regulatory mechanism to maintain contractile phenotype in VSMCs remains elusive. Moreover, little has been known about the role of the mitochondrial bioenergetics in terms of VSMC homeostasis. Herein, we asked if glycoprotein COMP (Cartilage oligomeric matrix protein) is involved in mitochondrial bioenergetics and therefore regulates VSMCs homeostasis...
June 4, 2018: Cell Death & Disease
Sitaram M Emani, James D McCully
Mitochondrial transplantation refers to transplantation of respiratory competent mitochondria from healthy tissue into tissues injured by ischemia and reperfusion. This technique has been utilized for recovery of myocardial dysfunction in pediatric patients. The preclinical experience and initial patient experience with this technique are reviewed in this article. Initial experience is with pediatric patients undergoing extracorporeal membrane oxygenation support following myocardial ischemia and reperfusion...
April 2018: Translational Pediatrics
Guangchao Zhang, Zhe Li, Chao Meng, Jiyu Kang, Mengdi Zhang, Liangjuan Ma, Huacheng Zhou
BACKGROUND: Lung ischemia-reperfusion injury (LIRI) remains an important factor for the early mortality of lung transplantations. Hydrogen (H2) can attenuate lung injury and improve lung function in animal experiments. In previous studies, pulmonary microvascular endothelial cells (PMVECs) were used to simulate LIRI. We hypothesized that H2 can alleviate inflammatory injury in a PMVECs lung transplantation model in the cold ischemia phase. METHODS: Pulmonary microvascular endothelial cells were divided into 4 groups: blank, control, oxygen (O2), and H2...
August 2018: Transplantation
Xingyue Ji, Binghe Wang
Carbon monoxide is widely acknowledged as an important gasotransmitter in the mammalian system with importance on par with that of nitric oxide. It has also been firmly established as a potential therapeutic agent with a wide range of indications including organ transplantation, cancer, bacterial infection, and inflammation-related conditions such as colitis and sepsis. One major issue in developing CO based therapeutics is its delivery in a pharmaceutically acceptable form. Currently, there are generally five forms of deliveries: inhaled CO, photosensitive CO-releasing molecules, encapsulated CO, CO dissolved in drinks, and molecules that would release CO under physiological conditions without the need for light...
June 19, 2018: Accounts of Chemical Research
Wei Li, David Kennedy, Zhili Shao, Xi Wang, Andre Klaassen Kamdar, Malory Weber, Kayla Mislick, Kathryn Kiefer, Rommel Morales, Brendan Agatisa-Boyle, Diana M Shih, Srinivasa T Reddy, Christine S Moravec, W H Wilson Tang
BACKGROUND: Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. METHODS AND RESULTS: Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression...
June 2018: Free Radical Biology & Medicine
Jing-Jun Lyu, Jawahar L Mehta, Yi Li, Lu Ye, Sheng-Nan Sun, Hong-Shuang Sun, Jia-Chang Li, Dong-Mei Zhang, Jie Wei
Background: The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury...
May 20, 2018: Chinese Medical Journal
Ru Ying, Sheng-Wei Li, Jia-Yuan Chen, Hai-Feng Zhang, Ying Yang, Zhen-Jie Gu, Yang-Xin Chen, Jing-Feng Wang
BACKGROUND: Perivascular adipose tissue (PVAT) accelerates plaque progression and increases cardiovascular risk. We tested the hypothesis that PVAT contributed to plaque vulnerability and investigated whether endoplasmic reticulum stress (ER stress) in PVAT played an important role in vulnerable plaque. METHODS: We transplanted thoracic aortic PVAT or subcutaneous adipose tissue as a control, from donor mice to carotid arteries of recipient apolipoprotein E deficient (apoE-/- ) mice after removing carotid artery collar placed for 6 weeks...
April 18, 2018: Journal of Translational Medicine
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