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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/28428633/inhibition-of-glutathione-metabolism-attenuates-esophageal-cancer-progression
#1
Liang Peng, Ruixia Linghu, Demeng Chen, Jing Yang, Xiaoxue Kou, Xiang-Zhen Wang, Yi Hu, Yi-Zhou Jiang, Junlan Yang
Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to mortality and prognosis, and the 5-year survival rate for all patients diagnosed with ESCC remains poor. A better understanding of the biological mechanisms of ESCC tumorigenesis and progression is of great importance to improve treatment of this disease. In this study, we demonstrated that the glutathione metabolism pathway is highly enriched in ESCC cells compared with normal esophageal epithelial cells in an in vivo mouse model...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28428632/cyclophosphamide-induced-hcn1-channel-upregulation-in-interstitial-cajal-like-cells-leads-to-bladder-hyperactivity-in-mice
#2
Qian Liu, Zhou Long, Xingyou Dong, Teng Zhang, Jiang Zhao, Bishao Sun, Jingzhen Zhu, Jia Li, Qingqing Wang, Zhenxing Yang, Xiaoyan Hu, Longkun Li
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28428631/an-overview-of-the-synergy-and-crosstalk-between-pentraxins-and-collectins-ficolins-their-functional-relevance-in-complement-activation
#3
REVIEW
Ying Jie Ma, Bok Luel Lee, Peter Garred
The complement system is an innate immune defense machinery comprising components that deploy rapid immune responses and provide efficient protection against foreign invaders and unwanted host elements. The complement system is activated upon recognition of pathogenic microorganisms or altered self-cells by exclusive pattern recognition molecules (PRMs), such as collectins, ficolins and pentraxins. Recent accumulating evidence shows that the different classes of effector PRMs build up a co-operative network and exert synergistic effects on complement activation...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28408750/transcriptional-regulatory-networks-underlying-the-reprogramming-of-spermatogonial-stem-cells-to-multipotent-stem-cells
#4
Hoe-Su Jeong, Jinhyuk Bhin, Hyung Joon Kim, Daehee Hwang, Dong Ryul Lee, Kye-Seong Kim
Spermatogonial stem cells (SSCs) are germline stem cells located along the basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and biological networks underlying this reprogramming remain elusive. Here, we present transcriptional regulatory networks (TRNs) that control cellular processes related to the SSC-to-mSSC reprogramming. Previously, we established intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene expression profiles of SSCs, iSSCs and mSSCs...
April 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28408749/high-prevalence-of-tp53-mutations-is-associated-with-poor-survival-and-an-emt-signature-in-gliosarcoma-patients
#5
Sung-Yup Cho, Changho Park, Deukchae Na, Jee Yun Han, Jieun Lee, Ok-Kyoung Park, Chengsheng Zhang, Chang Ohk Sung, Hyo Eun Moon, Yona Kim, Jeong Hoon Kim, Jong Jae Kim, Shin Kwang Khang, Do-Hyun Nam, Jung Won Choi, Yeon-Lim Suh, Dong Gyu Kim, Sung Hye Park, Hyewon Youn, Kyuson Yun, Jong-Il Kim, Charles Lee, Sun Ha Paek, Hansoo Park
Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues...
April 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28408748/the-microbiome-of-the-lung-and-its-extracellular-vesicles-in-nonsmokers-healthy-smokers-and-copd-patients
#6
Hyun Jung Kim, You-Sun Kim, Kang-Hyun Kim, Jun-Pyo Choi, Yoon-Keun Kim, Sunmi Yun, Lokesh Sharma, Charles S Dela Cruz, Jae Seung Lee, Yeon-Mok Oh, Sang-Do Lee, Sei Won Lee
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, and bacterial infection plays a role in its pathogenesis. Bacteria secrete nanometer-sized extracellular vesicles (EVs), which may induce more immune dysfunction and inflammation than the bacteria themselves. We hypothesized that the microbiome of lung EVs might have distinct characteristics depending on the presence of COPD and smoking status. We analyzed and compared the microbiomes of 13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of surgical lung tissue and lung EVs...
April 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28386127/amplification-of-distinct-%C3%AE-synuclein-fibril-conformers-through-protein-misfolding-cyclic-amplification
#7
Byung Chul Jung, Yoon-Ju Lim, Eun-Jin Bae, Jun Sung Lee, Min Sun Choi, Michael K Lee, He-Jin Lee, Yoon Suk Kim, Seung-Jae Lee
Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, the conformers may possess specific biological properties, thus providing a biochemical framework for strains of prions. However, the precise relationship between various fibril conformers and their pathogenic functions has not been determined because of limited accessibility to adequate amounts of fibrils from tissue samples. α-Synuclein is one such protein, and it has been implicated in Parkinson disease...
April 7, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28386126/mir-24-mediated-knockdown-of-h2ax-damages-mitochondria-and-the-insulin-signaling-pathway
#8
Jae Hoon Jeong, Young Cheol Kang, Ying Piao, Sora Kang, Youngmi Kim Pak
Mitochondrial deficits or altered expressions of microRNAs are associated with the pathogenesis of various diseases, and microRNA-operated control of mitochondrial activity has been reported. Using a retrovirus-mediated short-hairpin RNA (shRNA) system, we observed that miR-24-mediated H2AX knockdown (H2AX-KD) impaired both mitochondria and the insulin signaling pathway. The overexpression of miR-24 decreased mitochondrial H2AX and disrupted mitochondrial function, as indicated by the ATP content, membrane potential and oxygen consumption...
April 7, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28386125/guangxi-cobra-venom-derived-ngf-promotes-the-osteogenic-and-therapeutic-effects-of-porous-bcp-ceramic
#9
Pan Jin, Fuqiang Yin, Li Huang, Li Zheng, Jinmin Zhao, Xingdong Zhang
Neuro-osteological interactions have an important role in the regulation of bone metabolism and regeneration. Neuropeptides combined with porous biphasic calcium phosphates (BCP) using protein adsorption may contribute to the acceleration of bone formation. In the present study, we investigated the effect of BCP combined with nerve growth factor (NGF) on the growth of osteoblasts in vitro and the combinational therapeutic effect on the repair of calvarial defects in vivo. NGF was separated and purified from Chinese cobra venom using a simplified three-step chromatography method...
April 7, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28360429/interleukin-20-targets-podocytes-and-is-upregulated-in-experimental-murine-diabetic-nephropathy
#10
Yu-Hsiang Hsu, Hsing-Hui Li, Junne-Ming Sung, Wei-Yu Chen, Ya-Chin Hou, Yun-Han Weng, Wei-Ting Lai, Chih-Hsing Wu, Ming-Shi Chang
Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8...
March 31, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28360428/molecular-checkpoints-controlling-natural-killer-cell-activation-and-their-modulation-for-cancer-immunotherapy
#11
REVIEW
Hyung-Joon Kwon, Nayoung Kim, Hun Sik Kim
Natural killer (NK) cells have gained considerable attention as promising therapeutic tools for cancer therapy due to their innate selectivity against cancer cells over normal healthy cells. With an array of receptors evolved to sense cellular alterations, NK cells provide early protection against cancer cells by producing cytokines and chemokines and exerting direct cytolytic activity. These effector functions are governed by signals transmitted through multiple receptor-ligand interactions but are not achieved by engaging a single activating receptor on resting NK cells...
March 31, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336959/affibody-molecules-as-engineered-protein-drugs
#12
REVIEW
Fredrik Y Frejd, Kyu-Tae Kim
Affibody molecules can be used as tools for molecular recognition in diagnostic and therapeutic applications. There are several preclinical studies reported on diagnostic and therapeutic use of this molecular class of alternative scaffolds, and early clinical evidence is now beginning to accumulate that suggests the Affibody molecules to be efficacious and safe in man. The small size and ease of engineering make Affibody molecules suitable for use in multispecific constructs where AffiMabs is one such that offers the option to potentiate antibodies for use in complex disease...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336958/from-rabbit-antibody-repertoires-to-rabbit-monoclonal-antibodies
#13
REVIEW
Justus Weber, Haiyong Peng, Christoph Rader
In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336957/next-generation-sequencing-enables-the-discovery-of-more-diverse-positive-clones-from-a-phage-displayed-antibody-library
#14
Wonjun Yang, Aerin Yoon, Sanghoon Lee, Soohyun Kim, Jungwon Han, Junho Chung
Phage display technology provides a powerful tool to screen a library for a binding molecule via an enrichment process. It has been adopted as a critical technology in the development of therapeutic antibodies. However, a major drawback of phage display technology is that because the degree of the enrichment cannot be controlled during the bio-panning process, it frequently results in a limited number of clones. In this study, we applied next-generation sequencing (NGS) to screen clones from a library and determine whether a greater number of clones can be identified using NGS than using conventional methods...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336956/preclinical-development-of-a-humanized-neutralizing-antibody-targeting-hgf
#15
Hyori Kim, Sung Hee Hong, Jung Yong Kim, In-Chull Kim, Young-Whan Park, Song-Jae Lee, Seong-Won Song, Jung Ju Kim, Gunwoo Park, Tae Min Kim, Yun-Hee Kim, Jong Bae Park, Junho Chung, In-Hoo Kim
Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336955/progress-of-antibody-based-inhibitors-of-the-hgf-cmet-axis-in-cancer-therapy
#16
REVIEW
Ki-Hyun Kim, Hyori Kim
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336954/special-issue-on-therapeutic-antibodies-and-biopharmaceuticals
#17
EDITORIAL
Junho Chung
No abstract text is available yet for this article.
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28303029/tmf-and-glycitin-act-synergistically-on-keratinocytes-and-fibroblasts-to-promote-wound-healing-and-anti-scarring-activity
#18
Ga Young Seo, Yoongho Lim, Dongsoo Koh, Jung Sik Huh, Changlim Hyun, Young Mee Kim, Moonjae Cho
Keratinocyte-fibroblast interactions are critical for skin repair after injury. During the proliferative phase of wound healing, proliferation, migration and differentiation of these cells are the major mechanisms leading to tissue remodeling. We have previously reported that glycitin, a major soy isoflavone, stimulates dermal fibroblast proliferation; and the phytochemical, 4',6,7-trimethoxyisoflavone (TMF), induces migration of HaCaT keratinocyte cells. We therefore investigated whether these compounds display synergistic effects on skin cells during wound healing in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#19
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28280265/effect-of-blood-type-on-anti-%C3%AE-gal-immunity-and-the-incidence-of-infectious-diseases
#20
Alejandro Cabezas-Cruz, Lourdes Mateos-Hernández, Pilar Alberdi, Margarita Villar, Gilles Riveau, Emmanuel Hermann, Anne-Marie Schacht, Jamal Khalife, Margarida Correia-Neves, Christian Gortazar, José de la Fuente
The identification of factors affecting the susceptibility to infectious diseases is essential toward reducing their burden on the human population. The ABO blood type correlates with susceptibility to malaria and other infectious diseases. Due to the structural similarity between blood antigen B and Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), we hypothesized that self-tolerance to antigen B affects the immune response to α-Gal, which in turn affects the susceptibility to infectious diseases caused by pathogens carrying α-Gal on their surface...
March 10, 2017: Experimental & Molecular Medicine
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