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FGF21 as Modulator of Metabolism in Health and Disease
In conclusion, FGF21 belongs to a promising class of cytokines that are induced in response to stress and that can be used as a drug, drug target, or through a biomarker, depending on the physio-pathological context. All these findings will become clear when FGF21 will be used as a therapeutic molecule, exploiting the beneficial effects of FGF21 for treating metabolic disease or when it will be blocked to ameliorate disease progression and the onset of disease. Author Contributions CT and MS wrote the manuscript. VR contributed to the discussion. Funding This work was supported from the AFM-Telethon (19524), Italian Mi...
Source: Frontiers in Physiology - April 16, 2019 Category: Physiology Source Type: research

An Ensemble Strategy to Predict Prognosis in Ovarian Cancer Based on Gene Modules
Conclusion Considering the heterogeneity and complexity of ovarian cancer, we demonstrated a new method to predict the prognosis of ovarian cancer based on the clustering information and gene co-expression network in each subtype of cancer patients. We divided the ovarian cancer data into three subtypes by clustering analysis and we found that the survival risks in these three subtypes were significantly different. We mined the important communities based on the co-expression networks in each subtype. There are 50, 73, and 92 communities in the first, second and third subtype, respectively. Next, we constructed a new ense...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells 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

The NCATS BioPlanet – An Integrated Platform for Exploring the Universe of Cellular Signaling Pathways for Toxicology, Systems Biology, and Chemical Genomics
We report here the construction, features, and utilization of a comprehensive integrated and non-redundant pathway resource, the NCATS BioPlanet (Figure 1). The resource hosts information only from public sources that have been herein further manually curated to ensure the quality of the data. Along with our pathway warehouse, the NCATS BioPlanet software platform allows easy browsing and visualization of the universe of pathways, and exploration of associations among them. Additionally, we curated the set of annotated pathways in terms of the biological space covered and the current availability of assays, either commerci...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration
Conclusion In conclusion our results evidenced that 3D-COL/hPDLSCs/PEI-EVs may be an efficacious strategy to induce bone regeneration and vascularization of bone defects, thanks to its capacity to increase the levels of VEGF. Ethics Statement The study was performed in accordance with the guidelines of the Helsinki Declaration (2013). The written approval for the human periodontal ligament collection performed in this study has been obtained from the Medical Ethics Committee at the Medical School, “G. d’Annunzio” University of Chieti–Pescara, Chieti, Italy (n°266/17.04.14, Principal in...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/ β-Catenin Pathway in a Murine Model of Lupus Nephritis
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Gr...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir
Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant wit...
Source: Frontiers in Pharmacology - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

Porcine deltacoronavirus enters cells via two pathways: A protease-mediated one at the cell surface and another facilitated by cathepsins in the endosome Microbiology
Porcine deltacoronavirus (PDCoV) is a pathogen belonging to the genus Deltacoronavirus that in 2014 caused outbreaks of piglet diarrhea in the United States. To identify suitable therapeutic targets, a more comprehensive understanding of the viral entry pathway is required, particularly of the role of proteases. Here, we identified the proteases that activate the viral spike (S) glycoprotein to initiate cell entry and also pinpointed the host-cellular pathways that PDCoV uses for entry. Our results revealed that cathepsin L (CTSL) and cathepsin B (CTSB) in lysosomes and extracellular trypsin in cell cultures independently ...
Source: Journal of Biological Chemistry - June 20, 2019 Category: Chemistry Authors: Jialin Zhang, Jianfei Chen, Da Shi, Hongyan Shi, Xin Zhang, Jianbo Liu, Liyan Cao, Xiangdong Zhu, Ye Liu, Xiaobo Wang, Zhaoyang Ji, Li Feng Tags: Microbiology Source Type: research

Study identifies therapeutic target for high blood pressure in the lungs
This study was supported by grants from the National Institutes of Health and the American Heart Association; and by the Foundation for Anesthesia Education and Research.
Source: UCLA Newsroom: Health Sciences - October 1, 2019 Category: Universities & Medical Training Source Type: news

Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells.
The objective of this study was to determine whether NOTCH signaling regulates goblet cell differentiation in response to cigarette smoke. Primary human bronchial epithelial cells (HBECs) from nonsmokers and COPD smokers were differentiated in vitro on air-liquid interface and exposed to cigarette smoke extract (CSE) for 7 days. NOTCH signaling activity was modulated using (1) the NOTCH/γ-secretase inhibitor Dibenzazepine (DBZ), (2) lentiviral over-expression of the NOTCH3-intracellular domain (NICD3) or (3) NOTCH3-specific siRNA. Cell differentiation and response to CSE were evaluated by qPCR, Western blotting, immunosta...
Source: Am J Respir Cell Mol... - January 14, 2021 Category: Respiratory Medicine Authors: Bodas M, Moore AR, Subramaniyan B, Georgescu C, Wren JD, Freeman WM, Brown BR, Metcalf JP, Walters MS Tags: Am J Respir Cell Mol Biol Source Type: research

Delivery of Thrombospondin-2 Small Interfering RNA for Suppression of Intimal Hyperplasia
Treatments of peripheral arterial disease, which affects>8.5 million individuals in the United States, include angioplasty and stenting and graft bypass. However, these have been limited by the pervasive development of intimal hyperplasia, which leads to in-stent restenosis and reduced graft patency. We propose a novel technique to suppress the progression of intimal hyperplasia using bioengineered hydrogels (ClickGels) for localized small interfering RNA (siRNA) delivery and suppression of thrombospondin-2 (TSP2), an upregulated gene of intimal hyperplasia, in an in vivo rat carotid angioplasty model.
Source: Journal of Vascular Surgery - August 24, 2021 Category: Surgery Authors: Jennifer R. Li, Kimberly Piper, Patric Liang, Max Zhu, Mauricio Contreras, Alexander Stafford, David Mooney, Leena Pradhan-Nabzdyk, Frank Logerfo Tags: PC: Poster Competition Source Type: research

Drug repurposing of dextromethorphan as a cellular target for the management of influenza
ConclusionInfluenza viruses continue to emerge and cause infection (including pandemics) in humans, so there remains a critical need to advance the understanding of influenza treatment. Our results demonstrated reduced hospitalization rates for influenza patients treated with DM. Further research on cellular targets and / or DM are warranted for the treatment of influenza.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - August 24, 2021 Category: Drugs & Pharmacology Authors: Tammy H. Cummings, Joseph Magagnoli, James W. Hardin, S. Scott Sutton Tags: ORIGINAL RESEARCH ARTICLE Source Type: research