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Spinal Muscular Atrophy: A Potential Target for in Utero Therapy.

Clin Obstet Gynecol 2021 Sep 21. Epub 2021 Sep 21.

Columbia University Irving Medical Center, New York, New York.

Spinal muscular atrophy (SMA) is a life-threatening autosomal recessive disease that leads to progressive muscle weakness and atrophy, respiratory insufficiency and scoliosis. SMA is currently the most common monogenic cause of infant mortality. Amazing advancements have been made in the therapeutic options available for these children since 2016. Read More

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September 2021

Advanced hybrid artificial pancreas system improves on unannounced meal response - In silico comparison to currently available system.

Comput Methods Programs Biomed 2021 Sep 13;211:106401. Epub 2021 Sep 13.

Center for Diabetes Technology, University of Virginia, Charlottesville, VA, USA. Electronic address:

Background And Objective: Glycemic control, especially meal-related disturbance rejection, has proven to be a major challenge for people with type 1 diabetes. In this manuscript, we introduce a novel, personalized, advanced hybrid insulin infusion system (a.k. Read More

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September 2021

Histone deacetylase inhibitor AR-42 and achiral analogues kill malaria parasites in vitro and in mice.

Int J Parasitol Drugs Drug Resist 2021 Aug 23;17:118-127. Epub 2021 Aug 23.

Griffith Institute for Drug Discovery, Griffith University, Queensland, 4111, Australia. Electronic address:

Malaria is caused by infection with Plasmodium parasites and results in significant health and economic impacts. Malaria eradication is hampered by parasite resistance to current drugs and the lack of a widely effective vaccine. Compounds that target epigenetic regulatory proteins, such as histone deacetylases (HDACs), may lead to new therapeutic agents with a different mechanism of action, thereby avoiding resistance mechanisms to current antimalarial drugs. Read More

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AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss.

Eur J Med Chem 2021 Sep 20;226:113849. Epub 2021 Sep 20.

Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, 68178, USA. Electronic address:

Cyclin-dependent kinase 2 (CDK2) is a potential therapeutic target for the treatment of hearing loss and cancer. Previously, we identified AZD5438 and AT7519-7 as potent inhibitors of CDK2, however, they also targeted additional kinases, leading to unwanted toxicities. Proteolysis Targeting Chimeras (PROTACs) are a new promising class of small molecules that can effectively direct specific proteins to proteasomal degradation. Read More

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September 2021

Insight into Shenqi Jiangtang Granule on the improved insulin sensitivity by integrating in silico and in vivo approaches.

J Ethnopharmacol 2021 Sep 21:114672. Epub 2021 Sep 21.

Department of Endocrinology, Jining No. 1 People's Hospital, Jining, Shandong, 272000, China; Institute for Chronic Disease Management, Jining No. 1 People's Hospital, Jining, Shandong, 272000, China. Electronic address:

Ethnopharmacological Relevance: Presently, insulin resistance has been a growing concern that urgently needs to be addressed, because it not only places patients at risk of developing type 2 diabetes mellitus but also results in metabolic syndrome and different aspects of cardiovascular diseases. Shenqi Jiangtang Granule (SJG) is a classic traditional Chinese medicine (TCM) prescription that is widely used to treat diabetes mellitus and its complications in clinical practice. While studies have revealed that SJG with multi-ingredients and multi-targets characteristics possesses potential anti-insulin resistance pharmacological properties, its mechanisms of action and molecular targets for the treatment of insulin resistance are still obscure, which prompt us to conduct an in-depth research. Read More

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September 2021

1,2-Dichloroethane induces apoptosis in the cerebral cortexes of NIH Swiss mice through microRNA-182-5p targeting phospholipase D1 via a mitochondria-dependent pathway.

Toxicol Appl Pharmacol 2021 Sep 21:115728. Epub 2021 Sep 21.

NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address:

1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water. Overexposure to it results in cortex edema, in both animals and humans. 1,2-DCE induces apoptosis in the cerebellum, liver and testes. Read More

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September 2021

Isolation of neural stem and oligodendrocyte progenitor cells from the brain of live rats.

Stem Cell Reports 2021 Sep 8. Epub 2021 Sep 8.

Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, UK; Lab of Developmental Biology, Department of Biology, University of Patras, 26504 Patras, Greece. Electronic address:

Postnatal brain neural stem and progenitor cells (NSPCs) cluster in anatomically inaccessible stem cell niches, such as the subependymal zone (SEZ). Here, we describe a method for the isolation of NSPCs from live animals, which we term "milking." The intracerebroventricular injection of a release cocktail, containing neuraminidase, integrin-β1-blocking antibody, and fibroblast growth factor 2, induces the controlled flow of NSPCs in the cerebrospinal fluid, where they are collected via liquid biopsies. Read More

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September 2021

LncRNA CDKN2B-AS1 contributes to glioma development by regulating the miR-199a-5p/DDR1 axis.

J Gene Med 2021 Sep 24:e3389. Epub 2021 Sep 24.

Department of Neurosurgery, The first affiliated hospital of Guangxi Medical University, Nanning City, Guangxi Zhuang Autonomous Region, PR. China.

Background: Although cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is upregulated in glioma, its function and potential mechanism in glioma remain unclear.

Methods: CDKN2B-AS1 level in glioma tissues and cell lines LN229, U251, and U87 was measured by qRT-PCR. Loss of function assays using short hairpin RNA for CDKN2B-AS1 (sh-CDKN2B-AS1) were performed to evaluate the effect of CDKN2B-AS1 on cell invasion, migration, proliferation, and apoptosis. Read More

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September 2021

Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.

PLoS Genet 2021 Sep 24;17(9):e1009039. Epub 2021 Sep 24.

Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.

Notch signaling controls many developmental processes by regulating gene expression. Notch-dependent enhancers recruit activation complexes consisting of the Notch intracellular domain, the Cbf/Su(H)/Lag1 (CSL) transcription factor (TF), and the Mastermind co-factor via two types of DNA sites: monomeric CSL sites and cooperative dimer sites called Su(H) paired sites (SPS). Intriguingly, the CSL TF can also bind co-repressors to negatively regulate transcription via these same sites. Read More

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September 2021

The actin depolymerizing factor, Destrin, serves as a negative feedback inhibitor of smooth muscle cell differentiation.

Am J Physiol Heart Circ Physiol 2021 Sep 24. Epub 2021 Sep 24.

Department of Pathology and McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

We have previously shown that several components of the RhoA signaling pathway control SMC phenotype by altering SRF-dependent gene expression. Because our genome wide analyses of chromatin structure and transcription factor binding suggested that the actin depolymerizing factor, DSTN, was regulated in a SMC-selective fashion, the goals of the current study were to identify the transcription mechanisms that control DSTN expression in SMC and to test whether it regulates SMC function. Immunohistochemical analyses revealed strong and at least partially SMC-selective expression of DSTN in many mouse tissues, a result consistent with human data from the GTEx consortium. Read More

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September 2021

Tumor necrosis factor receptor-1 is selectively sequestered into Schwann cell extracellular vesicles where it functions as a TNFα decoy.

Glia 2021 Sep 24. Epub 2021 Sep 24.

Department of Anesthesiology, University of California, San Diego, La Jolla, California, USA.

Schwann cells (SCs) are known to produce extracellular vesicles (EV) that participate in cell-cell communication by transferring cargo to target cells, including mRNAs, microRNAs, and biologically active proteins. Herein, we report a novel mechanism whereby SC EVs may regulate PNS physiology, especially in injury, by controlling the activity of TNFα. SCs actively sequester tumor necrosis factor receptor-1 (TNFR1) into EVs at high density, accounting for about 2% of the total protein in SC EVs (~1000 copies TNFR1/EV). Read More

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September 2021

Technical note: Histological validation of anatomical imaging for breast modeling using a novel cryo-microtome.

Med Phys 2021 Sep 24. Epub 2021 Sep 24.

Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: Precise correlation between 3D imaging and histology can aid biomechanical modeling of the breast. We develop a framework to register ex vivo images to histology using a novel cryo-fluorescence tomography (CFT) device.

Methods: A formalin-fixed cadaveric breast specimen, including chest wall, was subjected to high-resolution magnetic resonance (MR) imaging. Read More

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September 2021

Can only one physiological trait determinate the adverse effect of green fluorescent protein (GFP) incorporation on Vibrio virulence?

Appl Microbiol Biotechnol 2021 Sep 24. Epub 2021 Sep 24.

Laboratory of Aquaculture & Artemia Reference Center, Department of Animal Sciences and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium.

Green fluorescent protein (GFP) has been used extensively for in situ animal studies that follow up bacterial infection under epifluorescence microscopy. It is assumed that GFP is acting as a "neutral" protein with no influence on the bacterial physiology. To verify this hypothesis, the virulence of Vibrio splendidus ME9, Vibrio anguillarum NB10, and their respective GFP-tagged strains ME9-GFP and NB10-GFP (transconjugants) was compared in vitro and tested in vivo towards blue mussel (Mytilus edulis) larvae. Read More

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September 2021

miR-23a contributes to T cellular redox metabolism in juvenile idiopathic oligoarthritis.

Rheumatology (Oxford) 2021 Sep 24. Epub 2021 Sep 24.

Dept of Pediatrics, Pediatric Rheumatology, Medical Faculty, RWTH Aachen, Germany.

Objective: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease of unknown origin. The regulation of inflammatory processes involves multiple cellular steps including mRNA transcription and translation. Different miRNAs tightly control these processes. Read More

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September 2021

The lncRNA Promotes Hepatocellular Carcinoma Cell Cycle Progression by Regulating the HuR/CDK4 Axis.

DNA Cell Biol 2021 Sep 24. Epub 2021 Sep 24.

Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Long noncoding RNAs (lncRNAs) represent promising therapeutic targets associated with hepatocellular carcinoma (HCC). lncRNA VPS9D1 antisense RNA 1 () regulates colon and prostate cancer, but its relevance in HCC remains to be clarified. Using microarray data from the NCBI Gene Expression Omnibus (GEO) database (GSE65485) and The Cancer Genome Atlas (TCGA) database, expression in HCC and normal liver tissue sample HCC were compared. Read More

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September 2021

Globo H Is a Promising Theranostic Marker for Intrahepatic Cholangiocarcinoma.

Hepatol Commun 2021 Aug 24. Epub 2021 Aug 24.

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.

Recent studies support the development of cancer therapeutics to target Globo H-ceramide, the most prevalent tumor-associated carbohydrate antigen in epithelial cancers. Herein, we evaluated the expression of Globo H and its prognostic significance in intrahepatic cholangiocarcinoma (ICC) and conducted preclinical studies to assess the antitumor activity of Globo H-specific antibody in thioacetamide (TAA)-induced ICC in rats. Globo H-ceramide in tumor specimens was detected by immunohistochemistry (IHC) and mass spectrometry. Read More

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Meta-analysis and Consolidation of Farnesoid X Receptor Chromatin Immunoprecipitation Sequencing Data Across Different Species and Conditions.

Hepatol Commun 2021 Jul 1. Epub 2021 Jul 1.

Research Unit for Translational Nuclear Receptor Research, Division of Gastroenterology and Hepatology, Medical University Graz, Graz, Austria.

Farnesoid X receptor (FXR) is a nuclear receptor that controls gene regulation of different metabolic pathways and represents an upcoming drug target for various liver diseases. Several data sets on genome-wide FXR binding in different species and conditions exist. We have previously reported that these data sets are heterogeneous and do not cover the full spectrum of potential FXR binding sites. Read More

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MicroRNA‑218 inhibits the malignant phenotypes of glioma by modulating the TNC/AKT/AP‑1/TGFβ1 feedback signaling loop.

Int J Mol Med 2021 Nov 24;48(5). Epub 2021 Sep 24.

Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Gliomas are the most malignant and common tumors of the human brain, and the prognosis of glioma patients is extremely poor. MicroRNAs (miRNAs or miRs) play critical roles in different types of cancer by performing post‑transcriptional regulation of gene expression. Although miR‑218 has been demonstrated to be decreased in gliomas, its role in gliomas remains largely unknown. Read More

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November 2021

PPARγ attenuates hepatic inflammation and oxidative stress of non‑alcoholic steatohepatitis via modulating the miR‑21‑5p/SFRP5 pathway.

Mol Med Rep 2021 Nov 24;24(5). Epub 2021 Sep 24.

Department of Endocrinology, Banan People's Hospital of Chongqing, Chongqing 401320, P.R. China.

Inflammation and oxidative stress are key steps in the progression of non‑alcoholic steatohepatitis (NASH). Intervention in these two processes will therefore benefit NASH treatment. Peroxisome proliferator‑activated receptor γ (PPARγ), as a multiple functional transcription factor, has been reported to be involved in the prevention of NASH progression. Read More

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November 2021

lncRNA cytoskeleton regulator reduces non‑small cell lung cancer radiosensitivity by downregulating miRNA‑206 and activating prothymosin α.

Int J Oncol 2021 Nov 24;59(5). Epub 2021 Sep 24.

Department of Oncology Radiotherapy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.

The present study aimed to explore the role of the long noncoding RNA cytoskeleton regulator (CYTOR) in non‑small cell lung cancer (NSCLC) radiosensitivity by manipulating the microRNA (miR)‑206/prothymosin α (PTMA) axis. First, 58 pairs of NSCLC and paracancerous tissues, normal human lung epithelial cells and NSCLC cells were collected to analyze CYTOR expression and the relationship between CYTOR and NSCLC prognosis. Subsequently, CYTOR expression in radioresistant cells was assessed. Read More

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November 2021

Knockdown of miR‑205‑5p alleviates the inflammatory response in allergic rhinitis by targeting B‑cell lymphoma 6.

Mol Med Rep 2021 Nov 24;24(5). Epub 2021 Sep 24.

Department of Otorhinolaryngology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang, Liaoning 110000, P.R. China.

Allergic rhinitis (AR) is an IgE‑mediated upper airway disease with a high worldwide prevalence. MicroRNA (miR)‑205‑5p upregulation has been observed in AR; however, its role is poorly understood. The aim of the present study was to investigate the effect of miR‑205‑5p on AR‑associated inflammation. Read More

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November 2021

Molecular Probes for Autofluorescence-Free Optical Imaging.

Chem Rev 2021 Sep 24. Epub 2021 Sep 24.

School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457, Singapore.

Optical imaging is an indispensable tool in clinical diagnostics and fundamental biomedical research. Autofluorescence-free optical imaging, which eliminates real-time optical excitation to minimize background noise, enables clear visualization of biological architecture and physiopathological events deep within living subjects. Molecular probes especially developed for autofluorescence-free optical imaging have been proven to remarkably improve the imaging sensitivity, penetration depth, target specificity, and multiplexing capability. Read More

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September 2021

Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier.

Front Cell Dev Biol 2021 7;9:724905. Epub 2021 Sep 7.

The Institute of Biomedical and Clinical Science, University of Exeter Medical School, St. Luke's Campus, University of Exeter, Exeter, United Kingdom.

Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (HS) are observed in diabetic patients and correlate with microvascular dysfunction. HS may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that HS could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Read More

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September 2021

MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1.

Front Pharmacol 2021 7;12:725268. Epub 2021 Sep 7.

School of Medicine, Shanghai University, Shanghai, China.

Monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide from . Our previous study found that MLIF protects against ischemic stroke in rats and mice and exerts a neuroprotection effect in human neuroblastoma SH-SY5Y cells. Microglia/macrophage polarization has been proven to be vital in the pathology of ischemic stroke. Read More

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September 2021

Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer.

Sci Rep 2021 Sep 23;11(1):18930. Epub 2021 Sep 23.

Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, BD7 1DP, West Yorkshire, UK.

Epidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. In this study, CYP1A1, CYP1B1 and CYP2W1 expression in HNC was correlated with potential as target for duocarmycin prodrug activation and selective therapy. In the HNC cell lines, elevated expression was shown at the gene level for CYP1A1 and CYP1B1 whereas CYP2W1 was hardly detected. Read More

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September 2021

Direct photoresponsive inhibition of a p53-like transcription activation domain in PIF3 by Arabidopsis phytochrome B.

Nat Commun 2021 Sep 23;12(1):5614. Epub 2021 Sep 23.

Department of Botany and Plant Sciences, Institute for Integrative Genome Biology, University of California, Riverside, CA, USA.

Photoactivated phytochrome B (PHYB) binds to antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to regulate hundreds of light responsive genes in Arabidopsis by promoting PIF degradation. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (AD) consisting of a hydrophobic activator motif flanked by acidic residues. Read More

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September 2021

Intranasal iloprost prevents tumors in a murine lung carcinogenesis model.

Cancer Prev Res (Phila) 2021 Sep 23. Epub 2021 Sep 23.

Medicine/Division of Pulmonary Sciences, Eastern Colorado Veterans Affairs Medical Center

Lung cancer chemoprevention with the prostacyclin analogue iloprost is the most promising approach to date for intercepting progression of premalignant lung lesions in former smokers. Previous pre-clinical studies of iloprost used oral delivery, but a study modeling delivery directly to the target organ was needed. In vivo and in vitro studies have identified gene expression changes following iloprost treatment, including increased E-cadherin and PPAR𝛄 and decreased COX2 and Vimentin. Read More

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September 2021

USP7 inhibition induces apoptosis in glioblastoma by enhancing ubiquitination of ARF4.

Cancer Cell Int 2021 Sep 23;21(1):508. Epub 2021 Sep 23.

Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Jiangsu, Suzhou, People's Republic of China.

Background: Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM. Read More

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September 2021

Characterization of the Nonendocrine Cell Populations in Human Embryonic Stem Cell-Derived (hESC) Islet-Like Clusters Posttransplantation.

Toxicol Pathol 2021 Sep 23:1926233211036395. Epub 2021 Sep 23.

Stem Cell Imaging and Pharmacology, Stem Cell R&D, Novo Nordisk A/S, Maaloev, Denmark.

Islet-like clusters derived from human embryonic stem cells (hESC) hold the potential to cure type 1 diabetes mellitus. Differentiation protocols of islet-like clusters lead to the generation of minor fractions of nonendocrine cells, which are mainly from endodermal and mesodermal lineages, and the risk of implanting these is unclear. In the present study, the histogenesis and the tumorigenicity of nonendocrine cells were investigated in vivo. Read More

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September 2021

Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression.

Transl Oncol 2021 Sep 21;14(12):101219. Epub 2021 Sep 21.

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China. Electronic address:

Background: It has been known for decades that circRNAs are deregulated in cancer. Here, we characterized the role and underlying mechanism of circ_0088212 in osteosarcoma.

Methods: The expression levels of circ_0088212, miR-520 h, and APOA1 were determined by RT-qPCR. Read More

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September 2021