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Journal of Translational Medicine

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https://www.readbyqxmd.com/read/29052509/a-yin-yang-1-mir-30a-regulatory-circuit-modulates-autophagy-in-pancreatic-cancer-cells
#1
Chuang Yang, Jing-Jing Zhang, Yun-Peng Peng, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Wen-Tao Gao, Kui-Rong Jiang, Yi Miao
BACKGROUND: Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. METHODS: The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting...
October 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29047383/a-novel-small-molecule-inhibitor-of-p32-mitochondrial-protein-overexpressed-in-glioma
#2
Venkata Yenugonda, Natsuko Nomura, Valentina Kouznetsova, Igor Tsigelny, Valentina Fogal, Elmar Nurmemmedov, Santosh Kesari, Ivan Babic
BACKGROUND: The mitochondrial protein p32 is a validated therapeutic target of cancer overexpressed in glioma. Therapeutic targeting of p32 with monoclonal antibody or p32-binding LyP-1 tumor-homing peptide can limit tumor growth. However, these agents do not specifically target mitochondrial-localized p32 and would not readily cross the blood-brain barrier to target p32-overexpressing gliomas. Identifying small molecule inhibitors of p32 overexpressed in cancer is a more rational therapeutic strategy...
October 18, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29037244/prediction-of-microbe-disease-association-from-the-integration-of-neighbor-and-graph-with-collaborative-recommendation-model
#3
Yu-An Huang, Zhu-Hong You, Xing Chen, Zhi-An Huang, Shanwen Zhang, Gui-Ying Yan
BACKGROUND: Accumulating clinical researches have shown that specific microbes with abnormal levels are closely associated with the development of various human diseases. Knowledge of microbe-disease associations can provide valuable insights for complex disease mechanism understanding as well as the prevention, diagnosis and treatment of various diseases. However, little effort has been made to predict microbial candidates for human complex diseases on a large scale. METHODS: In this work, we developed a new computational model for predicting microbe-disease associations by combining two single recommendation methods...
October 16, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29029617/association-of-red-cell-distribution-width-with-all-cause-and-cardiovascular-specific-mortality-in-african-american-and-white-adults-a-prospective-cohort-study
#4
Salman M Tajuddin, Mike A Nalls, Alan B Zonderman, Michele K Evans
BACKGROUND: While the mortality rate is declining in the United States, the life expectancy gap among different population groups suggests a need to identify biomarkers to improve early identification of individuals at risk. Red cell distribution width (RDW), a measure of anisocytosis, is an emerging biomarker of chronic disease morbidity and mortality, particularly in the elderly. However, little is known about its association with mortality risk in younger adults. The objectives of this study were to investigate the association between RDW and overall and cause-specific mortality risk, and to identify novel determinants of RDW level...
October 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29029603/the-pathophysiological-role-of-mitochondrial-oxidative-stress-in-lung-diseases
#5
REVIEW
Xiaojing Liu, Zhihong Chen
Mitochondria are critically involved in reactive oxygen species (ROS)-dependent lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial dysfunction, including electron transport chain impairment and mitochondrial membrane potential loss. Furthermore, damaged mtDNA also acts as a damage-associated molecular pattern (DAMP) that drives inflammatory and immune responses...
October 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29025424/understanding-immune-phenotypes-in-human-gastric-disease-tissues-by-multiplexed-immunohistochemistry
#6
Le Ying, Feng Yan, Qiaohong Meng, Xiangliang Yuan, Liang Yu, Bryan R G Williams, David W Chan, Liyun Shi, Yugang Tu, Peihua Ni, Xuefeng Wang, Dakang Xu, Yiqun Hu
BACKGROUND: Understanding immune phenotypes and human gastric disease in situ requires an approach that leverages multiplexed immunohistochemistry (mIHC) with multispectral imaging to facilitate precise image analyses. METHODS: We developed a novel 4-color mIHC assay based on tyramide signal amplification that allowed us to reliably interrogate immunologic checkpoints, including programmed death-ligand 1 (PD-L1), cytotoxic T cells (CD8(+)T) and regulatory T cells (Foxp3), in formalin-fixed, paraffin-embedded tissues of various human gastric diseases...
October 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29020960/perspectives-in-immunotherapy-meeting-report-from-the-immunotherapy-bridge-napoli-november-30th-2016
#7
Paolo A Ascierto, Bruno Daniele, Hans Hammers, Vera Hirsh, Joseph Kim, Lisa Licitra, Rita Nanda, Sandro Pignata
The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies...
October 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29017562/contextual-tumor-suppressor-function-of-t-cell-death-associated-gene-8-tdag8-in-hematological-malignancies
#8
Calvin R Justus, Edward J Sanderlin, Lixue Dong, Tianai Sun, Jen-Tsan Chi, Kvin Lertpiriyapong, Li V Yang
BACKGROUND: Extracellular acidosis is a condition found within the tumor microenvironment due to inadequate blood perfusion, hypoxia, and altered tumor cell metabolism. Acidosis has pleiotropic effects on malignant progression; therefore it is essential to understand how acidosis exerts its diverse effects. TDAG8 is a proton-sensing G-protein-coupled receptor that can be activated by extracellular acidosis. METHODS: TDAG8 gene expression was analyzed by bioinformatic analyses and quantitative RT-PCR in human hematological malignancies...
October 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29017512/metastatic-pathway-and-the-microvascular-and-physicochemical-microenvironments-of-human-melanoma-xenografts
#9
Ruixia Huang, Lise Mari K Andersen, Einar K Rofstad
BACKGROUND: Malignant melanoma of the skin can metastasize through blood vessels and lymphatics. The primary tumor develops a vascular microenvironment characterized by abnormal blood vessels and lymphatics and a physicochemical microenvironment characterized by low oxygen tension, regions with hypoxic tissue, and high interstitial fluid pressure (IFP). This study aimed at identifying relationships between the metastatic route of melanomas and characteristic features of the microvascular and physicochemical microenvironments of the primary tumor...
October 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28985746/porcine-model-of-progressive-cardiac-hypertrophy-and-fibrosis-with-secondary-postcapillary-pulmonary-hypertension
#10
Mariann Gyöngyösi, Noemi Pavo, Dominika Lukovic, Katrin Zlabinger, Andreas Spannbauer, Denise Traxler, Georg Goliasch, Ljubica Mandic, Jutta Bergler-Klein, Alfred Gugerell, Andras Jakab, Zsuzsanna Szankai, Levente Toth, Rita Garamvölgyi, Gerald Maurer, Frederic Jaisser, Faiez Zannad, Thomas Thum, Sándor Bátkai, Johannes Winkler
BACKGROUND: Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. METHODS: For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28985739/a-lipidated-peptide-of-mycobacterium-tuberculosis-resuscitates-the-protective-efficacy-of-bcg-vaccine-by-evoking-memory-t-cell-immunity
#11
Pradeep K Rai, Sathi Babu Chodisetti, Weiguang Zeng, Sajid Nadeem, Sudeep K Maurya, Susanta Pahari, Ashok K Janmeja, David C Jackson, Javed N Agrewala
BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28969705/report-on-the-first-slfn11-monothematic-workshop-from-function-to-role-as-a-biomarker-in-cancer
#12
Alberto Ballestrero, Davide Bedognetti, Domenico Ferraioli, Paola Franceschelli, Sana Intidhar Labidi-Galy, Elisabetta Leo, Junko Murai, Yves Pommier, Petros Tsantoulis, Valerio Gaetano Vellone, Gabriele Zoppoli
SLFN11 is a recently discovered protein with a putative DNA/RNA helicase function. First identified in association with the maturation of thymocytes, SLFN11 was later causally associated, by two independent groups, with the resistance to DNA damaging agents such as topoisomerase I and II inhibitors, platinum compounds, and other alkylators, making it an attractive molecule for biomarker development. Later, SLFN11 was linked to antiviral response in human cells and interferon production, establishing a potential bond between immunity and chemotherapy...
October 2, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28969635/impact-of-mesenchymal-stem-cells-secretome-on-glioblastoma-pathophysiology
#13
Joana Vieira de Castro, Eduardo D Gomes, Sara Granja, Sandra I Anjo, Fátima Baltazar, Bruno Manadas, António J Salgado, Bruno M Costa
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodified or engineered to deliver anticancer therapeutic agents, as these cells present an intrinsic capacity to migrate towards malignant tumors. Nevertheless, it is still controversial whether this innate tropism of MSCs towards the tumor area is associated with cancer promotion or suppression...
October 2, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28962576/statistically-controlled-identification-of-differentially-expressed-genes-in-one-to-one-cell-line-comparisons-of-the-cmap-database-for-drug-repositioning
#14
Jun He, Haidan Yan, Hao Cai, Xiangyu Li, Qingzhou Guan, Weicheng Zheng, Rou Chen, Huaping Liu, Kai Song, Zheng Guo, Xianlong Wang
BACKGROUND: The Connectivity Map (CMAP) database, an important public data source for drug repositioning, archives gene expression profiles from cancer cell lines treated with and without bioactive small molecules. However, there are only one or two technical replicates for each cell line under one treatment condition. For such small-scale data, current fold-changes-based methods lack statistical control in identifying differentially expressed genes (DEGs) in treated cells. Especially, one-to-one comparison may result in too many drug-irrelevant DEGs due to random experimental factors...
September 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28938915/bdnf-trkb-axis-activation-promotes-epithelial-mesenchymal-transition-in-idiopathic-pulmonary-fibrosis
#15
Emanuela Cherubini, Salvatore Mariotta, Davide Scozzi, Rita Mancini, Giorgia Osman, Michela D'Ascanio, Pierdonato Bruno, Giuseppe Cardillo, Alberto Ricci
BACKGROUND: Neurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation. Increasing evidence show that NT and their receptor are expressed in lung tissues suggesting a possible role in lung health and disease. Here we investigated the expression and functional role of the TrkB/BDNF axis in idiopathic pulmonary fibrotic lung (myo)fibroblasts. METHODS: Lung fibroblast were isolated from IPF patients and characterized for the expression of mesenchymal markers in comparison to normal lung fibroblasts isolated from non-IPF controls...
September 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28938891/treatment-of-lumbar-degenerative-disc-disease-associated-radicular-pain-with-culture-expanded-autologous-mesenchymal-stem-cells-a-pilot-study-on-safety-and-efficacy
#16
Christopher Centeno, Jason Markle, Ehren Dodson, Ian Stemper, Christopher J Williams, Matthew Hyzy, Thomas Ichim, Michael Freeman
BACKGROUND: Degenerative disc disease (DDD) is a common cause of lower back pain with radicular symptoms and has a significant socioeconomic impact given the associated disability. Limited effective conservative therapeutic options result in many turning to surgical alternatives for management, which vary in the rate of success and also carry an increased risk of morbidity and mortality associated with the procedures. Several animal based studies and a few human pilot studies have demonstrated safety and suggest efficacy in the treatment of DDD with mesenchymal stem cells (MSCs)...
September 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28927457/p53-key-conductor-of-all-anti-acne-therapies
#17
REVIEW
Bodo C Melnik
This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53...
September 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28927456/erratum-to-ockham-s-razor-for-the-met-driven-invasive-growth-linking-idiopathic-pulmonary-fibrosis-and-cancer
#18
Giulia M Stella, Alessandra Gentile, Alice Balderacchi, Federica Meloni, Melissa Milan, Silvia Benvenuti
In the original version of this article [1], published on 2 September 2016, the name of author 'Alice Balderacchi' was wrongly displayed. In this Erratum the incorrect name and correct name are shown. The original publication of this article has been corrected.
September 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28923074/expression-of-concern-to-therapeutic-potential-of-human-embryonic-stem-cell-transplantation-in-patients-with-cerebral-palsy
#19
Geeta Shroff, Anupama Gupta, Jitender Kumar Barthakur
The Editor-in-Chief of the Journal of Translational Medicine is issuing an editorial expression of concern to alert readers that concerns have been raised regarding the ethics of this study [1] and the potential association of the risk of teratoma formation with the transplantation of embryonic stem cells. Appropriate editorial action will be taken once this has been fully investigated. The authors disagree with this notice.
September 18, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28903778/jtm-advances-in-uncharted-territories-diseases-and-disorders-of-unknown-etiology
#20
EDITORIAL
Monica C Panelli
We are delighted to announce a new section in the Journal of Translational Medicine, 'Illnesses of Unknown Etiology'. This section aims to provide a translational medicine forum for the publication of research on illnesses, multisystem diseases and syndromes of unknown etiology. Examples of these include Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia Syndrome.
September 13, 2017: Journal of Translational Medicine
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