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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/28642577/effects-of-chronic-alcohol-exposure-on-ischemia-reperfusion-induced-acute-kidney-injury-in-mice-the-role-of-%C3%AE-arrestin-2-and-glycogen-synthase-kinase-3
#1
Lihua Wang, Yifei Zhu, Lili Wang, Jingjing Hou, Yongning Gao, Lei Shen, Jingyu Zhang
Little is known about the effects of chronic alcohol intake on the outcome of acute kidney injury (AKI). Hence, we examined the effects of chronic alcohol intake on the development of renal fibrosis following AKI in an animal model of bilateral renal ischemia-reperfusion (IR) injury. We first found that chronic alcohol exposure exacerbated bilateral IR-induced renal fibrosis and renal function impairment. This phenomenon was associated with increased bilateral IR-induced extracellular matrix deposition and an increased myofibroblast population as well as increased bilateral IR-induced expression of fibrosis-related genes in the kidneys...
June 23, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28642576/upregulation-of-mir-223-in-the-rat-liver-inhibits-proliferation-of-hepatocytes-under-simulated-microgravity
#2
Yongjie Chen, Ji Xu, Chao Yang, Hongyu Zhang, Feng Wu, Jian Chen, Kai Li, Hailong Wang, Yu Li, Yinghui Li, Zhongquan Dai
Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports...
June 23, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28620221/mesenchymal-stem-cell-derived-exosomes-as-a-new-therapeutic-strategy-for-liver-diseases
#3
REVIEW
Guohua Lou, Zhi Chen, Min Zheng, Yanning Liu
The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. However, the risks of iatrogenic tumor formation, cellular rejection and infusional toxicity in MSC transplantation remain unresolved. Accumulating evidence now suggests that a novel cell-free therapy, MSC-secreted exosomes, might constitute a compelling alternative because of their advantages over the corresponding MSCs...
June 16, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28620220/coupling-killing-to-neutralization-combined-therapy-with-ceftriaxone-pep19-2-5-counteracts-sepsis-in-rabbits
#4
Sergio Bárcena-Varela, Guillermo Martínez-de-Tejada, Lukas Martin, Tobias Schuerholz, Ana Gloria Gil-Royo, Satoshi Fukuoka, Torsten Goldmann, Daniel Droemann, Wilmar Correa, Thomas Gutsmann, Klaus Brandenburg, Lena Heinbockel
Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice. In this study, we evaluated a rabbit model of acute sepsis caused by the intravenous inoculation of Salmonella enterica...
June 16, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28604663/elevated-traf4-expression-impaired-lps-induced-autophagy-in-mesenchymal-stem-cells-from-ankylosing-spondylitis-patients
#5
Jinteng Li, Peng Wang, Zhongyu Xie, Rui Yang, Yuxi Li, Xiaohua Wu, Hongjun Su, Wen Deng, Shan Wang, Zhenhua Liu, Shuizhong Cen, Yi Ouyang, Yanfeng Wu, Huiyong Shen
Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset and progression of AS. Recently, many studies have demonstrated that mesenchymal stem cells (MSCs) dysfunction may contribute to the pathogenesis of many rheumatic diseases. We previously demonstrated that MSCs from AS patients exhibited markedly enhanced osteogenic differentiation capacity in vitro under non-inflammatory conditions...
June 9, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28604662/upregulation-of-mitochondrial-nad-levels-impairs-the-clonogenicity-of-ssea1-glioblastoma-tumor-initiating-cells
#6
Myung Jin Son, Jae-Sung Ryu, Jae Yun Kim, Youjeong Kwon, Kyung-Sook Chung, Seon Ju Mun, Yee Sook Cho
Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD(+)) metabolism. However, the functional role of NAD(+) metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD(+) levels affect the characteristics of glioma-driven SSEA1(+) TICs, including clonogenic growth potential...
June 9, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28572574/survive-or-thrive-tradeoff-strategy-for-cellular-senescence
#7
REVIEW
Sang Chul Park
Aging-dependent cellular behaviors toward extrinsic stress are characterized by the confined localization of certain molecules to either nuclear or perinuclear regions. Although most growth factors can activate downstream signaling in aging cells, they do not in fact have any impact on the cells because the signals cannot reach their genetic targets in the nucleus. For the same reason, varying apoptotic stress factors cannot stimulate the apoptotic pathway in senescent cells. Thus, the operation of a functional nuclear barrier in an aging-dependent manner has been investigated...
June 2, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28572573/protein-tyrosine-phosphatase-1b-is-a-mediator-of-cyclic-adp-ribose-induced-ca-2-signaling-in-ventricular-myocytes
#8
Seon-Ah Park, Bing-Zhe Hong, Ki-Chan Ha, Uh-Hyun Kim, Myung-Kwan Han, Yong-Geun Kwak
Cyclic ADP-ribose (cADPR) releases Ca(2+) from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca(2+) (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca(2+) ([Ca(2+)]i) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA)...
June 2, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28546564/roles-of-intestinal-epithelial-cells-in-the-maintenance-of-gut-homeostasis
#9
REVIEW
Ryu Okumura, Kiyoshi Takeda
The intestine is a unique organ inhabited by a tremendous number of microorganisms. Intestinal epithelial cells greatly contribute to the maintenance of the symbiotic relationship between gut microbiota and the host by constructing mucosal barriers, secreting various immunological mediators and delivering bacterial antigens. Mucosal barriers, including physical barriers and chemical barriers, spatially segregate gut microbiota and the host immune system to avoid unnecessary immune responses to gut microbes, leading to the intestinal inflammation...
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28546563/microbiota-in-t-cell-homeostasis-and-inflammatory-diseases
#10
REVIEW
Naeun Lee, Wan-Uk Kim
The etiology of disease pathogenesis can be largely explained by genetic variations and several types of environmental factors. In genetically disease-susceptible individuals, subsequent environmental triggers may induce disease development. The human body is colonized by complex commensal microbes that have co-evolved with the host immune system. With the adaptation to modern lifestyles, its composition has changed depending on host genetics, changes in diet, overuse of antibiotics against infection and elimination of natural enemies through the strengthening of sanitation...
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28546562/the-interplay-between-host-immune-cells-and-gut-microbiota-in-chronic-inflammatory-diseases
#11
REVIEW
Donghyun Kim, Melody Y Zeng, Gabriel Núñez
Many benefits provided by the gut microbiota to the host rely on its intricate interactions with host cells. Perturbations of the gut microbiota, termed gut dysbiosis, affect the interplay between the gut microbiota and host cells, resulting in dysregulation of inflammation that contributes to the pathogenesis of chronic inflammatory diseases, including inflammatory bowel disease, multiple sclerosis, allergic asthma and rheumatoid arthritis. In this review, we provide an overview of how gut bacteria modulates host metabolic and immune functions, summarize studies that examined the roles of gut dysbiosis in chronic inflammatory diseases, and finally discuss measures to correct gut dysbiosis as potential therapeutics for chronic inflammatory diseases...
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28546561/dysregulation-of-gut-microbiota-and-chronic-inflammatory-disease-from-epithelial-defense-to-host-immunity
#12
EDITORIAL
Jung Hee Koh, Wan-Uk Kim
No abstract text is available yet for this article.
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524180/aberrant-epigenetic-regulation-of-gabrp-associates-with-aggressive-phenotype-of-ovarian-cancer
#13
Hye Youn Sung, San-Duk Yang, Woong Ju, Jung-Hyuck Ahn
Metastasis is a major cause of therapeutic failure in ovarian cancer. To elucidate molecular mechanisms of ovarian cancer metastasis, we previously established a metastatic xenograft mouse model using human ovarian carcinoma SK-OV-3 cells. Using gene expression profiling, we found that γ-aminobutyric acid (GABA)A receptor π subunit (GABRP) expression was upregulated (>4-fold) in metastatic tissues from our xenograft mice compared with SK-OV-3 cells. Importantly, GABRP knockdown diminished the migration and invasion of SK-OV-3 cells, and reduced extracellular signal-regulated kinase (ERK) activation while overexpression of GABRP exhibited significantly increased cell migration, invasion and ERK activation...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524179/a-fkbp5-mutation-is-associated-with-paget-s-disease-of-bone-and-enhances-osteoclastogenesis
#14
Bingru Lu, Yulian Jiao, Yinchang Wang, Jing Dong, Muyun Wei, Bin Cui, Yafang Sun, Laicheng Wang, Bingchang Zhang, Zijiang Chen, Yueran Zhao
Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524178/transcriptome-analyses-of-chronic-traumatic-encephalopathy-show-alterations-in-protein-phosphatase-expression-associated-with-tauopathy
#15
Jeong-Sun Seo, Seungbok Lee, Jong-Yeon Shin, Yu Jin Hwang, Hyesun Cho, Seong-Keun Yoo, Yunha Kim, Sungsu Lim, Yun Kyung Kim, Eun Mi Hwang, Su Hyun Kim, Chong-Hyun Kim, Seung Jae Hyeon, Ji-Young Yun, Jihye Kim, Yona Kim, Victor E Alvarez, Thor D Stein, Junghee Lee, Dong Jin Kim, Jong-Il Kim, Neil W Kowall, Hoon Ryu, Ann C McKee
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524177/role-of-carbonic-anhydrases-in-skin-wound-healing
#16
Harlan Barker, Marleena Aaltonen, Peiwen Pan, Maria Vähätupa, Pirkka Kaipiainen, Ulrike May, Stuart Prince, Hannele Uusitalo-Järvinen, Abdul Waheed, Silvia Pastoreková, William S Sly, Seppo Parkkila, Tero Ah Järvinen
Skin wound closure occurs when keratinocytes migrate from the edge of the wound and re-epithelialize the epidermis. Their migration takes place primarily before any vascularization is established, that is, under hypoxia, but relatively little is known regarding the factors that stimulate this migration. Hypoxia and an acidic environment are well-established stimuli for cancer cell migration. The carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524176/lentivirus-mediated-microrna-124-gene-modified-bone-marrow-mesenchymal-stem-cell-transplantation-promotes-the-repair-of-spinal-cord-injury-in-rats
#17
Jia-Lin Song, Wei Zheng, Wei Chen, Yun Qian, Yuan-Ming Ouyang, Cun-Yi Fan
Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496201/engulfment-signals-and-the-phagocytic-machinery-for-apoptotic-cell-clearance
#18
REVIEW
Seung-Yoon Park, In-San Kim
The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as 'find-me' and 'eat-me' signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496200/microrna-200a-3p-increases-5-fluorouracil-resistance-by-regulating-dual-specificity-phosphatase-6-expression
#19
Heejin Lee, Chongtae Kim, Hoin Kang, Hyosun Tak, Sojin Ahn, Sungjoo Kim Yoon, Hyo-Jeong Kuh, Wook Kim, Eun Kyung Lee
Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496199/upregulation-and-biological-function-of-transmembrane-protein-119-in-osteosarcoma
#20
Zhen-Huan Jiang, Jun Peng, Hui-Lin Yang, Xing-Li Fu, Jin-Zhi Wang, Lei Liu, Jian-Nong Jiang, Yong-Fei Tan, Zhi-Jun Ge
Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time...
May 12, 2017: Experimental & Molecular Medicine
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