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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/28729640/radiation-induced-liver-disease-current-understanding-and-future-perspectives
#1
REVIEW
Jieun Kim, Youngmi Jung
Although radiotherapy (RT) is used for the treatment of cancers, including liver cancer, radiation-induced liver disease (RILD) has emerged as a major limitation of RT. Radiation-induced toxicities in nontumorous liver tissues are associated with the development of numerous symptoms that may limit the course of therapy or have serious chronic side effects, including late fibrosis. Although the clinical characteristics of RILD patients have been relatively well described, the understanding of RILD pathogenesis has been hampered by a lack of reliable animal models for RILD...
July 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28729639/stimulation-of-osteoclast-migration-and-bone-resorption-by-c-c-chemokine-ligands-19-and-21
#2
Jiyeon Lee, Cheolkyu Park, Hyung Joon Kim, Yong Deok Lee, Zang Hee Lee, Yeong Wook Song, Hong-Hee Kim
Osteoclasts are responsible for the bone erosion associated with rheumatoid arthritis (RA). The upregulation of the chemokines CCL19 and CCL21 and their receptor CCR7 has been linked to RA pathogenesis. The purpose of this study was to evaluate the effects of CCL19 and CCL21 on osteoclasts and to reveal their underlying mechanisms. The expression of CCL19, CCL21 and CCR7 was higher in RA patients than in osteoarthritis patients. In differentiating osteoclasts, tumor necrosis factor-α, interleukin-1β and lipopolysaccharide stimulated CCR7 expression...
July 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28729638/inhibition-of-microrna-214-promotes-epithelial-mesenchymal-transition-process-and-induces-interstitial-cystitis-in-postmenopausal-women-by-upregulating-mfn2
#3
Jian-Wei Lv, Wei Wen, Chen Jiang, Qi-Bo Fu, Yin-Jun Gu, Ting-Ting Lv, Zhen-Dong Li, Wei Xue
Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups...
July 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28706299/findings-of-a-1303-korean-whole-exome-sequencing-study
#4
Soo Heon Kwak, Jeesoo Chae, Seongmin Choi, Min Jung Kim, Murim Choi, Jong-Hee Chae, Eun-Hae Cho, Tai Ju Hwang, Se Song Jang, Jong-Il Kim, Kyong Soo Park, Yung-Jue Bang
Ethnically specific data on genetic variation are crucial for understanding human biology and for clinical interpretation of variant pathogenicity. We analyzed data obtained by deep sequencing 1303 Korean whole exomes; the data were generated by three independent whole exome sequencing projects (named the KOEX study). The primary focus of this study was to comprehensively analyze the variant statistics, investigate secondary findings that may have clinical actionability, and identify loci that should be cautiously interpreted for pathogenicity...
July 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28706298/ckap2-phosphorylation-by-cdk1-cyclinb1-is-crucial-for-maintaining-centrosome-integrity
#5
Bum Ho Yoo, Du-Seock Kang, Chi-Hu Park, Kyeongjin Kang, Chang-Dae Bae
Previously, we have reported that CKAP2 is involved in the maintenance of centrosome integrity, thus allowing for proper mitosis in primary hepatocytes. To understand this biological process, we identified the mitosis-specific phosphorylation sites in mouse CKAP2 and investigated CKAP's possible role in cell cycle progression. Because we observed mouse CKAP2 depletion in amplified centrosomes and aberrant chromosomal segregation, which was rescued by ectopic expression of wild-type CKAP2, we focused on the centrosome duplication process among the various aspects of the cell cycle...
July 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28706297/harmless-effects-of-argon-plasma-on-caudal-fin-regeneration-and-embryogenesis-of-zebrafish-novel-biological-approaches-for-safe-medical-applications-of-bioplasma
#6
Min-Kyung Nam, Goo-Young Kim, Si-Eun Yun, Ja-Young Jang, Yong-Hee Kim, Eun Ha Choi, Seongman Kang, Hyangshuk Rhim
The argon plasma jet (Ar-PJ) is widely used in medical fields such as dermatology and dentistry, and it is considered a promising tool for cancer therapy. However, the in vivo effects of Ar-PJ for medical uses have not yet been investigated, and there are no biological tools to determine the appropriate clinical dosages of Ar-PJ. In this study, we used the caudal fin and embryo of zebrafish as novel in vivo tools to evaluate the biosafety of Ar-PJ. Typically, Ar-PJ is known to induce cell death in two-dimensional (2D) cell culture systems...
July 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28684865/dynamic-relocalization-of-nherf1-mediates-chemotactic-migration-of-ovarian-cancer-cells-toward-lysophosphatidic-acid-stimulation
#7
Yong-Seok Oh, Kyun Heo, Eung-Kyun Kim, Jin-Hyeok Jang, Sun Sik Bae, Jong Bae Park, Yun Hee Kim, Minseok Song, Sang Ryong Kim, Sung Ho Ryu, In-Hoo Kim, Pann-Ghill Suh
NHERF1/EBP50 (Na(+)/H(+) exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells...
July 7, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28684864/induction-of-thermogenic-adipocytes-molecular-targets-and-thermogenic-small-molecules
#8
REVIEW
No-Joon Song, Seo-Hyuk Chang, Dean Y Li, Claudio J Villanueva, Kye Won Park
Adipose tissue is a central metabolic organ that controls energy homeostasis of the whole body. White adipose tissue (WAT) stores excess energy in the form of triglycerides, whereas brown adipose tissue (BAT) dissipates energy in the form of heat through mitochondrial uncoupling protein 1 (Ucp1). A newly identified adipose tissue called 'beige fat' (BAT-like) is produced through a process called WAT browning. This tissue mainly resides in WAT depots and displays intermediate characteristics of both WAT and BAT...
July 7, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28684863/bcl3-a-regulator-of-nf-%C3%AE%C2%BAb-inducible-by-tweak-in-acute-kidney-injury-with-anti-inflammatory-and-antiapoptotic-properties-in-tubular-cells
#9
Jonay Poveda, Ana B Sanz, Susana Carrasco, Marta Ruiz-Ortega, Pablo Cannata-Ortiz, Maria D Sanchez-Niño, Alberto Ortiz
Acute kidney injury (AKI) is characterized by tubular cell death and interstitial inflammation. TWEAK promotes experimental kidney injury and activates the transcription factor NF-κB, a key regulator of genes involved in cell survival and inflammatory response. In search of potential therapeutic targets for AKI, we compared a transcriptomics database of NF-κB-related genes from murine AKI-kidneys with a transcriptomics database of TWEAK-stimulated cultured tubular cells. Four out of twenty-four (17%) genes were significantly upregulated (false discovery rate, FDR<0...
July 7, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28665921/rhododendrin-inhibits-toll-like-receptor-7-mediated-psoriasis-like-skin-inflammation-in-mice
#10
Yoon-Jae Jeon, Shyam Kishor Sah, Hee Seung Yang, Ji Hae Lee, Jongheon Shin, Tae-Yoon Kim
Many active compounds present in Rhododendron brachycarpum have been used in traditional Oriental medicine for the treatment of various skin diseases. However, the precise mechanism of action of the compounds isolated from R. brachycarpum and their relevance as therapeutics for the treatment of psoriasis remain elusive. In this study, we report that rhododendrin isolated from R. brachycarpum strongly inhibits imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. We showed that topical treatment with rhododendrin reduces IMQ-induced skin hyperplasia, inflammatory mononuclear cell infiltration and the expression of pro-inflammatory mediators in mouse skin...
June 30, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28665920/lineage-conversion-of-mouse-fibroblasts-to-pancreatic-%C3%AE-cells
#11
Tianjin Liu, Liangliang Sun, Beige Jiang, Limei Li, Jin Cen, Xiaotao Chen, Zhaoyun Zhang, Qinghua Wang, Xin Cheng, Yongquan Shi, Lijian Hui
α-cells, which synthesize glucagon, also support β-cell survival and have the capacity to transdifferentiate into β-cells. However, the role of α-cells in pathological conditions and their putative clinical applications remain elusive due in large part to the lack of mature α-cells. Here, we present a new technique to generate functional α-like cells. α-like cells (iAlpha cells) were generated from mouse fibroblasts by transduction of transcription factors, including Hhex, Foxa3, Gata4, Pdx1 and Pax4, which induce α-cell-specific gene expression and glucagon secretion in response to KCl and Arg stimulation...
June 30, 2017: Experimental & Molecular Medicine
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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