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Erastin synergizes with cisplatin via ferroptosis to inhibit ovarian cancer growth in vitro and in vivo.

J Obstet Gynaecol Res 2021 Apr 21. Epub 2021 Apr 21.

Department of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, China.

Aim: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment or serious side effects often occurs in ovarian cancer, and thus, there is an urgent need for effective and combined therapies to overcome such obstacles. In the present study, we aimed to uncover synergistic effects between erastin and cisplatin (CDDP) in inhibiting ovarian cancer cell growth by inducing ferroptosis in vitro and in vivo. Read More

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An in vitro air-liquid interface inhalation platform for petroleum substances and constituents.

ALTEX 2021 Apr 20. Epub 2021 Apr 20.

VITO NV (Flemish Institute for Technological Research), Unit HEALTH, Mol, Belgium.

The goal is to optimize and show the validity of an in vitro method for inhalation testing of petroleum substances and its constituents at the air-liquid interface (ALI). The approach is demonstrated in a pilot study with ethylbenzene (EB), a mono-constituent petroleum substance using a human alveolar epithelial cell line model. This included the development and validation of a generation facility to obtain EB vapors and the optimization of an exposure system for a negative control (clean air, CA), positive control (nitrogen dioxide), and EB vapors. Read More

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Anal squamous cell carcinoma: standards of care, new data and ongoing clinical trials.

Curr Opin Oncol 2021 Apr 20. Epub 2021 Apr 20.

Medical Oncology Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy Department of Medical Oncology, Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium.

Purpose Of Review: To summarize current standards of care, discuss results of recent studies and present ongoing clinical trials for anal squamous cell carcinoma (ASCC).

Recent Findings: Over the last year, no practice changing studies have been reported in the setting of localised ASCC. A number of retrospective analyses, however, have provided practice-informing data, such as those confirming the negative impact of low compliance to chemoradiotherapy (CRT) on patient outcomes. Read More

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Methylation of microRNA-338-5p by EED promotes METTL3-mediated translation of oncogene CDCP1 in gastric cancer.

Aging (Albany NY) 2021 Apr 21;13. Epub 2021 Apr 21.

Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.

Unmasking the complex regulatory pathways that mediate the malignant phenotypes of cancer cells can provide novel targets for therapies that could limit the recurrence and metastasis of gastric cancer (GC). Herein, we intended to clarify the role of embryonic ectoderm development protein (EED), microRNA-228-5p (miR-338-5p), methyltransferase like 3 (METTL3) and CUB domain containing protein 1 (CDCP1) in GC. Differentially expressed miRNAs and their target genes were extracted by analysis. Read More

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circUBAP2 exacerbates malignant capabilities of NSCLC by targeting KLF4 through miR-3182 modulation.

Aging (Albany NY) 2021 Mar 19;13. Epub 2021 Mar 19.

Department of Thoracic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China.

Chemo-resistance and refractoriness remain challenges for Non-small cell lung cancer (NSCLC) patients and the underlying molecular mechanisms haven't been fully explained. In this study, we investigated the influence of circUBAP2 on the NSCLC tumor cells. This study might provide novel therapeutic targets for NSCLC treatment. Read More

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Evaluation of disease staging and chemotherapeutic response in non-small cell lung cancer from patient tumor-derived metabolomic data.

Lung Cancer 2021 Apr 15;156:20-30. Epub 2021 Apr 15.

Department of Pharmacology and Toxicology, University of Louisville, United States; James Graham Brown Cancer Center, University of Louisville, United States; Department of Bioengineering, University of Louisville, United States; Center for Predictive Medicine, University of Louisville, United States. Electronic address:

Objectives: Despite extensive effort, the search for clinically-relevant metabolite biomarkers for early detection, disease monitoring, and outcome prediction in lung cancer remains unfulfilled. Although biofluid evaluation has been explored, the complexity inherent in metabolite data and the dynamic discrepancy between metabolites in biofluids vs. tumor tissue have prevented conclusive results. Read More

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Generation of an induced pluripotent stem cell line SDQLCHi026-A from a hereditary tyrosinemia type I patient carrying compound heterozygote mutations in FAH gene.

Stem Cell Res 2021 Apr 9;53:102331. Epub 2021 Apr 9.

Pediatric Research Institute, Qilu Children's Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250022, China. Electronic address:

Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as hereditary tyrosinemia type I (HT1) caused by FAH gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and MYC. The established iPSC line (SDQLCHi026-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original FAH gene mutation. Read More

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Proteomic signatures of radioresistance: Alteration of inflammation, angiogenesis and metabolism-related factors in radioresistant oesophageal adenocarcinoma.

Cancer Treat Res Commun 2021 Apr 18;27:100376. Epub 2021 Apr 18.

Department of Surgery, Trinity Translational Medicine Institute, Trinity St. James's Cancer Institute, St. James's Hospital, Trinity College Dublin, Dublin, Ireland.

The clinical management of locally advanced oesophageal adenocarcinoma (OAC) involves neoadjuvant chemoradiotherapy (CRT), but as radioresistance remains a major clinical challenge, complete pathological response to CRT only occurs in 20-30% of patients. In this study we used an established isogenic cell line model of radioresistant OAC to detect proteomic signatures of radioresistance to identify novel molecular and cellular targets of radioresistance in OAC. A total of 5785 proteins were identified of which 251 were significantly modulated in OE33R cells, when compared to OE33P. Read More

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Survival predictors and outcomes of patients with recurrent and/or metastatic head and neck cancer treated with chemotherapy plus cetuximab as first-line therapy: A real-world retrospective study.

Cancer Treat Res Commun 2021 Apr 14;27:100375. Epub 2021 Apr 14.

Instituto Português de Oncologia de Coimbra Francisco Gentil Av. Prof. Dr. Bissaya Barreto n.º 98, 3000-075 Coimbra Portugal.

Background: In patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) the estimated prognosis is usually poor. Patient-specific factors that affect prognosis should be considered when choosing therapy. We conducted a retrospective, single-center analysis in patients treated with first line platinum and antiEGFR antibody-containing regimen. Read More

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Clinical outcomes of non-small cell lung cancer patients with leptomeningeal metastases after immune checkpoint inhibitor treatments.

Eur J Cancer 2021 Apr 18;150:23-30. Epub 2021 Apr 18.

Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China. Electronic address:

Objective: Leptomeningeal metastases (LM) occur in up to 5% of non-small cell lung cancer (NSCLC) patients and often develop after previous systemic treatments. In this article, we explored whether immune checkpoint inhibitors (ICIs) enhanced the dismal survival of patients with LM.

Materials And Methods: Data on NSCLC patients with LM prescribed ICIs were collected at the Guangdong Lung Cancer Institute. Read More

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LncRNA CRNDE promotes the progression and angiogenesis of pancreatic cancer via miR-451a/CDKN2D axis.

Transl Oncol 2021 Apr 18;14(7):101088. Epub 2021 Apr 18.

Department of General Surgery, Suqian First Hospital, Suqian 223800, Jiangsu Province, China. Electronic address:

Background: The lncRNA colorectal neoplasia differentially expressed (lncRNA CRNDE) has been reported to play a pivotal role in various cancers. However, the expression and function of CRNDE in pancreatic cancer remain unclear. The objective of this study was to investigate the effects of CRNDE on pancreatic cancer and the underlying mechanisms. Read More

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Subiculum as a generator of sharp wave-ripples in the rodent hippocampus.

Cell Rep 2021 Apr;35(3):109021

German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; NeuroCure Cluster of Excellence, Charitéplatz 1, 10117 Berlin, Germany; Bernstein Center for Computational Neuroscience (BCCN) Berlin, 10115 Berlin, Germany; Einstein Center for Neurosciences (ECN) Berlin, 10117 Berlin, Germany; Max-Delbrück-Centrum (MDC) for Molecular Medicine, 13125 Berlin, Germany. Electronic address:

Sharp wave-ripples (SWRs) represent synchronous discharges of hippocampal neurons and are believed to play a major role in memory consolidation. A large body of evidence suggests that SWRs are exclusively generated in the CA3-CA2 network. In contrast, here, we provide several lines of evidence showing that the subiculum can function as a secondary SWRs generator. Read More

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Cytoplasmic polyadenylation by TENT5A is required for proper bone formation.

Cell Rep 2021 Apr;35(3):109015

Laboratory of RNA Biology, International Institute of Molecular and Cell Biology in Warsaw, Trojdena 4, 02-109 Warsaw, Poland; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106 Warsaw, Poland. Electronic address:

Osteoblasts orchestrate bone formation through the secretion of type I collagen and other constituents of the matrix on which hydroxyapatite crystals mineralize. Here, we show that TENT5A, whose mutations were found in congenital bone disease osteogenesis imperfecta patients, is a cytoplasmic poly(A) polymerase playing a crucial role in regulating bone mineralization. Direct RNA sequencing revealed that TENT5A is induced during osteoblast differentiation and polyadenylates mRNAs encoding Col1α1, Col1α2, and other secreted proteins involved in osteogenesis, increasing their expression. Read More

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Bufadienolides from the Eggs of the Toad and Their Antimelanoma Activities.

J Nat Prod 2021 Apr 21. Epub 2021 Apr 21.

Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.

Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad , including two new compounds ( and ). Read More

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Development of a CRISPR-Cas9 based luciferase turn-on system as non-homologous end joining pathway reporter.

Chembiochem 2021 Apr 21. Epub 2021 Apr 21.

Tianjin Medical University Cancer Institute and Hospital, Department of Breast Cancer Pathology and Research Laboratory, Huanhuxi Road, Nankai, Tianjin, 300030, Tianjin, CHINA.

There is a need of a non-homologous end joining (NHEJ) pathway reporter system that facilitates screening and discovery of NHEJ chemical inhibitors. In this study, we developed a CRISPR-Cas9 based luciferase turn-on system as a NHEJ pathway reporter. By substituting nucleotide 205C with ATC, we introduced a reading-frame shift and a pre-stop codon into the luciferase coding region and thereby generated a bioluminescent signal mute HEK293T reporter cell line. Read More

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Exosomal LINC00355 derived from cancer-associated fibroblasts promotes bladder cancer cell proliferation and invasion by regulating miR-15a-5p/HMGA2 axis.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr 21. Epub 2021 Apr 21.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

We have previously demonstrated that exosomes derived from cancer-associated fibroblasts (CAFs) promote bladder cancer (BC) cell proliferation and invasion by transferring LINC00355. In this study, the molecular mechanisms underlying the pro-bladder cancer action of exosomal LINC00355 were explored. CAFs were obtained from BC tumor tissues, and normal fibroblasts (NFs) were obtained from adjacent normal tissues. Read More

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Identification, localization and expression of NHE isoforms in the alveolar epithelial cells.

PLoS One 2021 21;16(4):e0239240. Epub 2021 Apr 21.

Ruth & Bruce Rappaport Faculty of Medicine, Department of Physiology, Technion, Israel Institute of Technology, Haifa, Israel.

Na+/H+ exchangers (NHEs), encoded by Solute Carrier 9A (SLC9A) genes in human, are ubiquitous integral membrane ion transporters that mediate the electroneutral exchange of H+ with Na+ or K+. NHEs, found in the kidney and intestine, play a major role in the process of fluid reabsorption together via Na+,K+-ATPase pump and Na+ channels. Nevertheless, the expression pattern of NHE in the lung and its role in alveolar fluid homeostasis has not been addressed. Read More

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Saturated Oxo Fatty Acids (SOFAs): A Previously Unrecognized Class of Endogenous Bioactive Lipids Exhibiting a Cell Growth Inhibitory Activity.

J Med Chem 2021 Apr 21. Epub 2021 Apr 21.

Center of Excellence for Drug Design and Discovery, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece.

The discovery of novel bioactive lipids that promote human health is of great importance. Combining "suspect" and targeted lipidomic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) approaches, a previously unrecognized class of oxidized fatty acids, the saturated oxo fatty acids (SOFAs), which carry the oxo functionality at various positions of the long chain, was identified in human plasma. A library of SOFAs was constructed, applying a simple green photochemical hydroacylation reaction as the key synthetic step. Read More

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Constructing 3D Macroporous Microfibrous Scaffolds with a Featured Surface by Heat Welding and Embossing.

Biomacromolecules 2021 Apr 21. Epub 2021 Apr 21.

CSIRO Manufacturing, Geelong Technology Precinct, Geelong, Victoria 3216, Australia.

Three-dimensional (3D) microfibrous scaffolds hold great promise for biomedical applications due to their good mechanical properties and biomimetic structure similar to that of the fibrous natural extracellular matrix. However, the large diameter and smooth surface of microfibers provide limited cues for regulating cell activity and behaviors. In this work, we report a facile heat-welding-and-embossing strategy to develop 3D macroporous microfibrous scaffolds with a featured surface topography. Read More

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Human cardiac fibroblasts produce pro-inflammatory cytokines upon TLRs and RLRs stimulation.

Mol Cell Biochem 2021 Apr 21. Epub 2021 Apr 21.

Department of Immunology, University Hospital Zurich, Gloriastrasse 23, CH-8091, Zurich, Switzerland.

Heart inflammation is one of the major causes of heart damage that leads to dilated cardiomyopathy and often progresses to end-stage heart failure. In the present study, we aimed to assess whether human cardiac cells could release immune mediators upon stimulation of Toll-like receptors (TLRs) and Retinoic acid-inducible gene (RIG)-I-like receptors (RLRs).Commercially available human cardiac fibroblasts and an immortalized human cardiomyocyte cell line were stimulated in vitro with TLR2, TLR3, and TLR4 agonists. Read More

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OsPG1 Encodes a Polygalacturonase that Determines Cell Wall Architecture and Affects Resistance to Bacterial Blight Pathogen in Rice.

Rice (N Y) 2021 Apr 21;14(1):36. Epub 2021 Apr 21.

State Key Laboratory of Rice Biology, China National Rice Research Institute, Zhejiang, 310006, Hangzhou, China.

Background: Plant cell walls are the main physical barrier encountered by pathogens colonizing plant tissues. Alteration of cell wall integrity (CWI) can activate specific defenses by impairing proteins involved in cell wall biosynthesis, degradation and remodeling, or cell wall damage due to biotic or abiotic stress. Polygalacturonase (PG) depolymerize pectin by hydrolysis, thereby altering pectin composition and structures and activating cell wall defense. Read More

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Functionalised molybdenum disulfide nanosheets for co-delivery of doxorubicin and siRNA for combined chemo/gene/photothermal therapy on multidrug-resistant cancer.

J Pharm Pharmacol 2021 Apr 21. Epub 2021 Apr 21.

Pharmaceutical College, Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530021, Guangxi, China.

Objective: Molybdenum disulfide (MoS2) has been developed for medical uses due to its excellent medically beneficial characteristics. This research was designed to develop a multifunctional nano-drug delivery system based on the nano-structure of MoS2 for combined chemo/gene/photothermal therapy targeting multidrug-resistant cancer.

Methods: MoS2 nanosheets were prepared by a hydrothermal reaction and modified. Read More

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N-terminal deletion of specific phosphorylation sites on PHOX2B disrupts the formation of enteric neurons in vivo.

Am J Physiol Gastrointest Liver Physiol 2021 Apr 21. Epub 2021 Apr 21.

Surgery, Children's Hospital of Los Angeles, United States.

Mutations in the paired-like homeobox 2b (PHOX2B) gene are associated with congenital central hypoventilation syndrome (CCHS), which is a rare condition in which both autonomic dysregulation with hypoventilation and an enteric neuropathy may occur. The majority of CCHS patients have a polyalanine repeat mutation (PARM) in PHOX2B, but a minority of patients have non-polyalanine repeat mutations (NPARM), some of which have been localized to exon 1. A PHOX2B-Y14X nonsense mutation previously generated in a human pluripotent stem cell (hPSC) line results in an N-terminus truncated product missing the first 17 or 20 amino acids, possibly due to translational reinitiation at an alternate ATG start site. Read More

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MOVAS Cells: A Versatile Cell Line for Studying Vascular Smooth Muscle Cell Cholesterol Metabolism.

Lipids 2021 Apr 21. Epub 2021 Apr 21.

Department of Food, Nutrition, and Packaging Sciences, Clemson University, Clemson, SC, USA.

Cholesterol metabolism is paramount to cells. Aberrations to cholesterol metabolism affects cholesterol homeostasis, which may impact the risk of several diseases. Recent evidence has suggested that vascular smooth muscle cell (VSMC) cholesterol metabolism may play a role in atherosclerosis. Read More

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KLaGdF:Eu hexagonal phase nanoparticles as luminescent probes for Huh-7 cancer cell imaging.

Dalton Trans 2021 Apr;50(15):5197-5207

Nanophotonics Lab, Department of Physics, Indian Institute of Technology Delhi, New Delhi, 110016 India.

A facile chemical route is reported for synthesizing red-emitting photoluminescent/MRI multi-functional KLa(0.95-x)GdxF4:Eu3+ (x = 0 to 0.4) bio-compatible nanomaterials for targeted in vitro tumor imaging. Read More

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Transdermal Delivery of Adipocyte Phospholipase A2 siRNA using Microneedles to Treat Thyroid Associated Ophthalmopathy-Related Proptosis.

Cell Transplant 2021 Jan-Dec;30:9636897211010633

Department of Obstetrics & Gynaecology, Faculty of Medicine, 26451The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.

Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease occurring in patients with thyroid disease. Patients with TAO-related proptosis is largely due to excessive orbital adipose tissue Adipocyte phospholipase A2 (AdPLA) is one of the most important regulatory factors in adipocyte lipolysis, which may be associated with TAO-related proptosis. Thus, silencing AdPLA by RNA interference may be beneficial for the treatment of TAO. Read More

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Optimized Photoactivatable Lipid Nanoparticles Enable Red Light Triggered Drug Release.

Small 2021 Apr 20:e2008198. Epub 2021 Apr 20.

Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.

Encapsulation of small molecule drugs in long-circulating lipid nanoparticles (LNPs) can reduce toxic side effects and enhance accumulation at tumor sites. A fundamental problem, however, is the slow release of encapsulated drugs from these liposomal systems at the disease site resulting in limited therapeutic benefit. Methods to trigger release at specific sites are highly warranted. Read More

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Green synthesized AgNPs from Periploca hydaspidis Falc. and its biological activities.

Microsc Res Tech 2021 Apr 21. Epub 2021 Apr 21.

Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Characterization of bio-synthesized silver nanoparticles (AgNPs) using Periploca hydaspidis (PHAgNPs) whole plant extract for the first time via UV-Visible spectroscopy, XRD, FTIR, DLS, and SEM analysis techniques was done. A rich variety of phytochemicals in P. hydaspidis aqueous extract (PHA) functioned as possible reducing and capping agents for AgNPs synthesis. Read More

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Glucagon Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Diabetes After Solid Organ Transplantation.

Transpl Int 2021 Apr 20. Epub 2021 Apr 20.

Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre-existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long-term management of PTDM or pre-existent T2DM. Read More

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Effect of prevalent polychlorinated biphenyls (PCBs) food contaminant on the MCF7, LNCap and MDA-MB-231 cell lines viability and PON1 gene expression level: proposed model of binding.

Daru 2021 Apr 21. Epub 2021 Apr 21.

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Background: Polychlorinated biphenyls (PCBs) are a group of synthetic organic chlorine compounds known as an organic pollutant in food sources, which play important roles in malignancies. The present study aimed to investigate the direct effects of prevalent PCBs in food in hormone-responsive and non-responsive cell lines.

Methods: In the current study, MCF-7, LNCap, and MDA-MB231 cell lines were treated with serial concentrations (0. Read More

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