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Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells
CONCLUSIONS/INTERPRETATION: We provide the first account of epigenetic changes in diabetic corneas including dual inhibition of WNT5A by DNA methylation and miRNA action. Overall, Wnt-5a is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea.DATA AVAILABILITY: The DNA methylation dataset is available from the public GEO repository under accession no. GSE229328 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229328 ).PMID:37460827 | DOI:10.1007/s00125-023-05960-1
Source: Cancer Control - July 17, 2023 Category: Cancer & Oncology Authors: Ruchi Shah Tanya M Spektor Daniel J Weisenberger Hui Ding Rameshwar Patil Cynthia Amador Xue-Ying Song Steven T Chun Jake Inzalaco Sue Turjman Sean Ghiam Jiho Jeong-Kim Sasha Tolstoff Sabina V Yampolsky Onkar B Sawant Yaron S Rabinowitz Ezra Maguen Pedram Source Type: research

Urinary Proteomics Identifies Cathepsin D as a Biomarker of Rapid eGFR Decline in Type 1 Diabetes
CONCLUSIONS: Urine cathepsin D is associated with rapid eGFR decline in T1D and reflects kidney tubulointerstitial injury.PMID:35377940 | DOI:10.2337/dc21-2204
Source: Cancer Control - April 4, 2022 Category: Cancer & Oncology Authors: Christine P Limonte Erkka Valo Viktor Drel Loki Natarajan Manjula Darshi Carol Forsblom Clark M Henderson Andrew N Hoofnagle Wenjun Ju Matthias Kretzler Daniel Montemayor Viji Nair Robert G Nelson John F O'Toole Robert D Toto Sylvia E Rosas John Ruzinski Source Type: research

The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Increasing Upstream Chromatin Long –Range Interactions May Favor Induction of Circular RNAs in LysoPC-Activated Human Aortic Endothelial Cells
We examined the sponging potential of all significantly changed circRNAs using the CircInteractome database (Montefiori et al., 2018), recording two miRNAs with four or more predicted binding sites in a single circRNA transcript, a threshold above which meaningful sponging activity is likely to occur Memczak et al. (2013). Another four significantly changed circRNAs are experimentally shown to sponge miRNAs (Dudekula et al., 2016; Chen et al., 2017; Yan et al., 2017; Wang et al., 2018), for six total circRNAs with miRNA sponging activity including miR125, miR143, miR1272, miR153, miR515-5p, and miR196a-5p (Table 4). In Fig...
Source: Frontiers in Physiology - April 17, 2019 Category: Physiology Source Type: research

PGC1 β Regulates Breast Tumor Growth and Metastasis by SREBP1-Mediated HKDC1 Expression
Conclusions: PGC1β regulates breast cancer tumor growth and metastasis by SREBP1-mediated HKDC1 expression. This provides a novel therapeutic strategy through targeting the PGC1β/HKDC1 signaling pathway for breast cancer treatment. Introduction Breast cancer is a very common cancer with significant premature mortality in women. Around 12% of women in USA will have chance to be diagnosed with breast cancer during their lifetimes (1, 2). The development of breast cancer is regulated by many factors, and even as average survival rates have increased significantly as a result of many advanced treatments...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

NF κB and Kidney Injury
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective
Conclusion Most head and neck pathologies show a broad cellular heterogeneity making it difficult to achieve an accurate diagnosis and efficient treatment (Graf and Zavodszky, 2017; Lo Nigro et al., 2017). Single cell analysis of circadian omics (Lande-Diner et al., 2015; Abraham et al., 2018), may be a crucial tool needed in the future to fully understand the circadian control of head and neck diseases. It becomes more obvious that there is only a small genetic component but a largely unknown epigenetics and/or environmental component for most of the head and neck pathologies (Moosavi and Motevalizadeh Ardekani, 2016; He...
Source: Frontiers in Physiology - April 15, 2019 Category: Physiology Source Type: research

lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2
Conclusion We report the discovery that ZEB1-AS1 functionally participates in ox-LDL-induced ECs injury via LRPPRC-mediated stabilization of NOD2. Uncovering the precise role of ZEB1-AS1/LRPPRC/NOD2 pathway in the progression of ox-LDL-induced ECs death and AS will not only increase our knowledge of ox-LDL-induced AS, but also enable the development of novel therapeutic strategies to overcome oxidation product-induced diseases. Author Contributions XX and CL designed and mainly did the study. CM, ZD, and YD helped and did the study. Conflict of Interest Statement The authors declare that the research was conducted in ...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Hyperglycemia aggravates microenvironment hypoxia and promotes the metastatic ability of pancreatic cancer
ConclusionOur results demonstrate that the association between hyperglycemia and poor prognosis can be attributed to microenvironment hypoxia in pancreatic cancer.Graphical Abstract
Source: Computational and Structural Biotechnology Journal - October 30, 2018 Category: Biotechnology Source Type: research

The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.
Authors: Shimada H, Satohisa S, Kohno T, Takahashi S, Hatakeyama T, Konno T, Tsujiwaki M, Saito T, Kojima T Abstract Lipolysis-stimulated lipoprotein receptor (LSR) has been identified as a novel molecular constituent of tricellular contacts that have a barrier function for the cellular sheet. LSR recruits tricellulin (TRIC), which is the first molecular component of tricellular tight junctions. Knockdown of LSR increases cell motility and invasion of certain cancer cells. However, the behavior and the roles of LSR in endometrial cancer remain unknown. In the present study, we investigated the behavior and roles of...
Source: Oncotarget - April 3, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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