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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/28912572/follistatin-n-terminus-differentially-regulates-muscle-size-and-fat-in-vivo
#1
Hui Zheng, Chunping Qiao, Ruhang Tang, Jianbin Li, Karen Bulaklak, Zhenhua Huang, Chunxia Zhao, Yi Dai, Juan Li, Xiao Xiao
Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV)...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28912571/comparative-global-immune-related-gene-profiling-of-somatic-cells-human-pluripotent-stem-cells-and-their-derivatives-implication-for-human-lymphocyte-proliferation
#2
Chia-Eng Wu, Chen-Wei Yu, Kai-Wei Chang, Wen-Hsi Chou, Chen-Yu Lu, Elisa Ghelfi, Fang-Chun Wu, Pey-Shynan Jan, Mei-Chi Huang, Patrick Allard, Shau-Ping Lin, Hong-Nerng Ho, Hsin-Fu Chen
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28912570/a-focus-on-extracellular-ca-2-entry-into-skeletal-muscle
#3
REVIEW
Chung-Hyun Cho, Jin Seok Woo, Claudio F Perez, Eun Hui Lee
The main task of skeletal muscle is contraction and relaxation for body movement and posture maintenance. During contraction and relaxation, Ca(2+) in the cytosol has a critical role in activating and deactivating a series of contractile proteins. In skeletal muscle, the cytosolic Ca(2+) level is mainly determined by Ca(2+) movements between the cytosol and the sarcoplasmic reticulum. The importance of Ca(2+) entry from extracellular spaces to the cytosol has gained significant attention over the past decade...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28883547/casein-kinase-2-is-a-critical-determinant-of-the-balance-of-th17-and-treg-cell-differentiation
#4
Sung Woong Jang, Soo Seok Hwang, Hyeong Su Kim, Keoung Oh Lee, Min Kyung Kim, Wonyong Lee, Kiwan Kim, Gap Ryol Lee
Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro...
September 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28883546/api5-induces-cisplatin-resistance-through-fgfr-signaling-in-human-cancer-cells
#5
Han Sol Jang, Seon Rang Woo, Kwon-Ho Song, Hanbyoul Cho, Doo Byung Chay, Soon-Oh Hong, Hyo-Jung Lee, Se Jin Oh, Joon-Yong Chung, Jae-Hoon Kim, Tae Woo Kim
Most tumors frequently undergo initial treatment with a chemotherapeutic agent but ultimately develop resistance, which limits the success of chemotherapies. As cisplatin exerts a high therapeutic effect in a variety of cancer types, it is often used in diverse strategies, such as neoadjuvant, adjuvant and combination chemotherapies. However, cisplatin resistance has often manifested regardless of cancer type, and it represents an unmet clinical need. Since we found that API5 expression was positively correlated with chemotherapy resistance in several specimens from patients with cervical cancer, we decided to investigate whether API5 is involved in the development of resistance after chemotherapy and to explore whether targeting API5 or its downstream effectors can reverse chemo-resistance...
September 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28860664/cadmium-induced-er-stress-and-inflammation-are-mediated-through-c-ebp-ddit3-signaling-in-human-bronchial-epithelial-cells
#6
Jeeyoung Kim, Haengseok Song, Hye-Ryeon Heo, Jung Woon Kim, Hye-Ryun Kim, Yoonki Hong, Se-Ran Yang, Seon-Sook Han, Seung-Joon Lee, Woo Jin Kim, Seok-Ho Hong
Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions of airway cells and can lead to the development of various pulmonary diseases such as chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms involved in Cd-induced pulmonary diseases are poorly understood. Here, we identified a cluster of genes that are altered in response to Cd exposure in human bronchial epithelial cells (BEAS-2B) and demonstrated that Cd-induced ER stress and inflammation are mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript 3 (DDIT3) signaling in BEAS-2B cells...
September 1, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28860663/bacterial-flagellin-a-potent-immunomodulatory-agent
#7
REVIEW
Irshad A Hajam, Pervaiz A Dar, Imam Shahnawaz, Juan Carlos Jaume, John Hwa Lee
Flagellin is a subunit protein of the flagellum, a whip-like appendage that enables bacterial motility. Traditionally, flagellin was viewed as a virulence factor that contributes to the adhesion and invasion of host cells, but now it has emerged as a potent immune activator, shaping both the innate and adaptive arms of immunity during microbial infections. In this review, we summarize our understanding of bacterial flagellin and host immune system interactions and the role flagellin as an adjuvant, anti-tumor and radioprotective agent, and we address important areas of future research interests...
September 1, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28857086/ccctc-binding-factor-is-essential-to-the-maintenance-and-quiescence-of-hematopoietic-stem-cells-in-mice
#8
Tae-Gyun Kim, Sueun Kim, Soyeon Jung, Mikyoung Kim, Bobae Yang, Min-Geol Lee, Hyoung-Pyo Kim
Hematopoiesis involves a series of lineage differentiation programs initiated in hematopoietic stem cells (HSCs) found in bone marrow (BM). To ensure lifelong hematopoiesis, various molecular mechanisms are needed to maintain the HSC pool. CCCTC-binding factor (CTCF) is a DNA-binding, zinc-finger protein that regulates the expression of its target gene by organizing higher order chromatin structures. Currently, the role of CTCF in controlling HSC homeostasis is unknown. Using a tamoxifen-inducible CTCF conditional knockout mouse system, we aimed to determine whether CTCF regulates the homeostatic maintenance of HSCs...
August 25, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28857085/enteric-dysbiosis-linked-gut-barrier-disruption-triggers-early-renal-injury-induced-by-chronic-high-salt-feeding-in-mice
#9
Jingjuan Hu, Haihua Luo, Jieyan Wang, Wenli Tang, Junqi Lu, Shan Wu, Zhi Xiong, Guizhi Yang, Zhenguo Chen, Tian Lan, Hongwei Zhou, Jing Nie, Yong Jiang, Peng Chen
Chronic high-salt diet-associated renal injury is a key risk factor for the development of hypertension. However, the mechanism by which salt triggers kidney damage is poorly understood. Our study investigated how high salt (HS) intake triggers early renal injury by considering the 'gut-kidney axis'. We fed mice 2% NaCl in drinking water continuously for 8 weeks to induce early renal injury. We found that the 'quantitative' and 'qualitative' levels of the intestinal microflora were significantly altered after chronic HS feeding, which indicated the occurrence of enteric dysbiosis...
August 25, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28857084/serum-amyloid-a-inhibits-dendritic-cell-differentiation-by-suppressing-gm-csf-receptor-expression-and-signaling
#10
Ji Cheol Kim, Young Su Jung, Ha Young Lee, Joon Seong Park, Yoe-Sik Bae
In this study, we report that an acute phase reactant, serum amyloid A (SAA), strongly inhibits dendritic cell differentiation induced by GM-CSF plus IL-4. SAA markedly decreased the expression of MHCII and CD11c. Moreover, SAA decreased cell surface GM-CSF receptor expression. SAA also decreased the expression of PU.1 and C/EBPα, which play roles in the expression of GM-CSF receptor. This inhibitory response by SAA is partly mediated by the well-known SAA receptors, Toll-like receptor 2 and formyl peptide receptor 2...
August 25, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28819322/nampt-enzyme-activity-regulates-catabolic-gene-expression-in-gingival-fibroblasts-during-periodontitis
#11
Ka Hyon Park, Duck-Kyu Kim, Yun Hyun Huh, Gyuseok Lee, Su-Hyeon Lee, Yunkyung Hong, Sun-Hun Kim, Min-Suk Kook, Jeong-Tae Koh, Jang-Soo Chun, Shee Eun Lee, Je-Hwang Ryu
Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues...
August 18, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28819321/sh3bp4-a-novel-pigmentation-gene-is-inversely-regulated-by-mir-125b-and-mitf
#12
Kyu-Han Kim, Tae Ryong Lee, Eun-Gyung Cho
Our previous work has identified miR-125b as a negative regulator of melanogenesis. However, the specific melanogenesis-related genes targeted by this miRNA had not been identified. In this study, we established a screening strategy involving three consecutive analytical approaches-analysis of target genes of miR-125b, expression correlation analysis between each target gene and representative pigmentary genes, and functional analysis of candidate genes related to melanogenesis-to discover melanogenesis-related genes targeted by miR-125b...
August 18, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28798402/nutlin-3-enhances-the-bortezomib-sensitivity-of-p53-defective-cancer-cells-by-inducing-paraptosis
#13
Dong Min Lee, In Young Kim, Min Ji Seo, Mi Ri Kwon, Kyeong Sook Choi
The proteasome inhibitor, bortezomib, is ineffective against many solid tumors. Nutlin-3 is a potent antagonist of human homolog of murine double minute 2/p53 interaction exhibiting promising therapeutic anti-cancer activity. In this study, we show that treatment of various p53-defective bortezomib-resistant solid tumor cells with bortezomib plus nutlin-3 induces paraptosis, which is a cell death mode accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Bortezomib alone did not markedly alter cellular morphology, and nutlin-3 alone induced only a transient mitochondrial dilation...
August 11, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28798401/the-tyrosine-kinase-inhibitor-nintedanib-activates-shp-1-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#14
Chun-Yu Liu, Tzu-Ting Huang, Pei-Yi Chu, Chun-Teng Huang, Chia-Han Lee, Wan-Lun Wang, Ka-Yi Lau, Wen-Chun Tsai, Tzu-I Chao, Jung-Chen Su, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein...
August 11, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28775366/microrna-143-and-145-modulate-the-phenotype-of-synovial-fibroblasts-in-rheumatoid-arthritis
#15
Bong-Ki Hong, Sungyong You, Seung-Ah Yoo, Dohyun Park, Daehee Hwang, Chul-Soo Cho, Wan-Uk Kim
Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype...
August 4, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28775365/sex-specific-regulation-of-immune-responses-by-ppars
#16
REVIEW
Hong-Jai Park, Je-Min Choi
The prevalence of autoimmune, infectious and metabolic diseases is different for men and women owing to the respective ability of their immune systems to respond to self and foreign antigens. Although several factors, including hormones and the X-chromosome, have been suggested to contribute to such sex-specific immune responses, the underlying factors remain poorly defined. Recent studies using peroxisome proliferator-activated receptor (PPAR) ligands and knockout mice have identified sex-dimorphic expression of PPARs, and have shown that the inhibitory functions of PPAR in T cells are substantially affected by the sex hormones...
August 4, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28775364/dnp2-ctctla-4-inhibits-german-cockroach-extract-induced-allergic-airway-inflammation-and-hyper-responsiveness-via-inhibition-of-th2-responses
#17
Sangho Lim, Jung Ho Sohn, Ja-Hyun Koo, Jung-Won Park, Je-Min Choi
German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model...
August 4, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28751785/ctla4-cd28-chimera-gene-modification-of-t-cells-enhances-the-therapeutic-efficacy-of-donor-lymphocyte-infusion-for-hematological-malignancy
#18
Hyung Bae Park, Ji Eun Lee, Yu Mi Oh, Sang Jin Lee, Hyeon-Seok Eom, Kyungho Choi
Donor lymphocyte infusion (DLI) followed by hematopoietic stem cell transplantation has served as an effective prevention/treatment modality against the relapse of some hematologic tumors, such as chronic myeloid leukemia (CML). However, the therapeutic efficacies of DLI for other types of leukemia, including acute lymphocytic leukemia (ALL), have been limited thus far. Therefore, we examined whether increasing the reactivity of donor T cells by gene modification could enhance the therapeutic efficacy of DLI in a murine model of ALL...
July 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28751784/rapid-generation-of-opc-like-cells-from-human-pluripotent-stem-cells-for-treating-spinal-cord-injury
#19
Dae-Sung Kim, Se Jung Jung, Jae Souk Lee, Bo Young Lim, Hyun Ah Kim, Jeong-Eun Yoo, Dong-Wook Kim, Joong Woo Leem
Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI...
July 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28729640/radiation-induced-liver-disease-current-understanding-and-future-perspectives
#20
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
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