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Galangin mitigates iron overload-triggered liver injury: Up-regulation of PPARγ and Nrf2 signaling, and abrogation of the inflammatory responses.

Life Sci 2021 Jul 27:119856. Epub 2021 Jul 27.

Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751, Egypt.

Aim: Hepatotoxicity is a critical consequence of the iron overload conditions such as hemochromatosis and blood transfusion-requiring anemia. Iron induces hepatotoxicity largely through disruption of cellular redox homeostasis and induction of inflammatory responses. The present work explored the hepatoprotective activity of the bio-active flavone galangin against iron-evoked hepatotoxicity. Read More

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In-situ monitoring of chlorophyll a fluorescence in Nannochloropsis oceanica cultures to assess photochemical changes and the onset of lipid accumulation during nitrogen deprivation.

Biotechnol Bioeng 2021 Jul 28. Epub 2021 Jul 28.

CNR-IBE - Consiglio Nazionale delle Ricerche - Istituto per la BioEconomia, Via Madonna del Piano 10, Sesto Fiorentino, 50019, Florence, Italy.

In-situ chlorophyll a fluorescence measurements were applied to monitor changes in the photochemical variables of Nannochloropsis oceanica cultures under nitrogen-deplete and nitrogen-replete (control) conditions. In addition, growth, lipid, fatty acid, and pigment contents were also followed. In the control culture, growth was promoted along with pigment content, electron transport rate, and polyunsaturated fatty acids, while total lipid content and fatty acid saturation level diminished. Read More

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Effects of an articular cartilage lubrication with a viscosupplement in vitro and in vivo following osteochondral fractures in horses.

Am J Vet Res 2021 Aug;82(8):611-618

Objective: To assess whether the combination of hyaluronan, sodium chondroitin sulfate, and -acetyl-d-glucosamine (HCSG) lubricates articular cartilage in vitro and modulates joint lubrication in vivo.

Animals: 16 healthy adult horses.

Procedures: The effects of HCSG injections on SF lubricant properties and joint health, immediately after injury and 2 weeks later, were analyzed by use an equine osteochondral fracture model of post-traumatic osteoarthritis (OA). Read More

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Downregulation of Stemness Genes and Induction of Necrosis in Rat LA7 Cancer Stem Cells Induced Tumors Treated with Starved Fibroblasts Culture Supernatant.

Rep Biochem Mol Biol 2021 Apr;10(1):105-118

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

Background: Stem cell differentiation therapy is a promising strategy in cancer treatment. we show that protein cocktail prepared from serum starved fibroblasts has therapeutic potential based on this strategy.

Methods: The condition medium was prepared from foreskin isolated fibroblasts and analyzed by Liquid chromatography electrospray ionization mass spectrometry-mass spectrometry (LC-ESI-MS/MS). Read More

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Dopamine D1 receptor-expressing neurons activity is essential for locomotor and sensitizing effects of a single injection of cocaine.

Eur J Neurosci 2021 Jul 17. Epub 2021 Jul 17.

INSERM UMR-S 1270, Paris, France.

Dopamine D1 receptors play an important role in the effects of cocaine. Here, we investigated the role of neurons which express these receptors (D1-neurons) in the acute locomotor effects of cocaine and the locomotor sensitization observed after a second injection of this drug, using the previously established two-injection protocol of sensitization. We inhibited D1-neurons using double transgenic mice conditionally expressing the inhibitory Gi-coupled designer receptor exclusively activated by designer drugs (Gi-DREADD) in D1-neurons. Read More

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Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells.

Clin Breast Cancer 2021 Jun 23. Epub 2021 Jun 23.

Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201100, China. Electronic address:

Background: The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor aggressiveness. However, limited study has investigated the effect of silencing PDGF-D on the biological function of breast cancer. The purpose of this study is to clarify the potential value of PDGF-D as a target for breast cancer treatment. Read More

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Complete Peripheral Blast Clearance is Superior to the Conventional Cut-Off of 1000/µL in Predicting Relapse in Pediatric Pre-B Acute Lymphoblastic Leukemia.

Indian J Hematol Blood Transfus 2021 Jul 13;37(3):366-371. Epub 2020 Sep 13.

Paediatric Haematology-Oncology Unit, Department of Paediatrics, Christian Medical College and Hospital, Vellore, India.

Risk-stratification has contributed to a dramatic improvement in survival in pediatric acute lymphoblastic leukemia (ALL). This study evaluated the utility of prephase response and day 15 bone marrow when a minimal residual disease (MRD) assessment was available. A file review of children aged ≤ 15 years diagnosed with precursor-B ALL from 2014 to 2019 was performed. Read More

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Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation Without Proteasome Inhibition.

Am J Respir Cell Mol Biol 2021 Jul 8. Epub 2021 Jul 8.

University of Michigan Health System, 21707, Ann Arbor, Michigan, United States;

The FDA-approved proteasomal inhibitor bortezomib (BTZ) has attracted interest for its potential anti-fibrotic actions. However, neither its in vivo efficacy in lung fibrosis nor its dependence on proteasome inhibition has been conclusively defined. In this study, we assessed the therapeutic efficacy of BTZ in a mouse model of pulmonary fibrosis, developed an in vitro protocol to define its actions on diverse fibroblast activation parameters, determined its reliance on proteasome inhibition for these actions in vivo and in vitro and explored alternative mechanisms of action. Read More

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Induction of IL-25 Expression in Human Nasal Polyp Epithelium by Influenza Virus Infection is Abated by Interferon-Alpha Pretreatment.

J Inflamm Res 2021 28;14:2769-2780. Epub 2021 Jun 28.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.

Background: Epithelial cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TLSP) are recently established as drivers of type 2 chronic inflammatory diseases such as chronic rhinosinusitis with nasal polyps (CRSwNP). Here, we further confirmed the increased expression of IL-25 in CRSwNP and investigated potential contributors of IL-25 in CRSwNP epithelium.

Methods: Sixty CRSwNP, 25 CRSsNP and 15 healthy control tissues were examined for IL-25 expression and for the accompanying type 2 inflammatory cytokines. Read More

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Coenzyme Q, a novel quinone derivative of Antrodia camphorata, induces ROS-mediated cytotoxic autophagy and apoptosis against human glioblastoma cells in vitro and in vivo.

Food Chem Toxicol 2021 Jul 3;155:112384. Epub 2021 Jul 3.

Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan; Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan. Electronic address:

Coenzyme Q (CoQ, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) derived from Antrodia camphorata exerts anticancer activities against breast, melanoma, and ovarian carcinoma. Glioblastoma multiforme is a common tumor affecting the central nervous system. This study explored anticancer properties of CoQ on human glioblastoma both in vitro and in vivo, and explained the molecular mechanism behind it. Read More

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ErbB4 promotes inhibitory synapse formation by cell adhesion, independent of its kinase activity.

Transl Psychiatry 2021 06 29;11(1):361. Epub 2021 Jun 29.

School of Life Sciences, Nanchang University, Nanchang, China.

The precise control of the nervous system function under the vitality of synapses is extremely critical. Efforts have been taken to explore the underlying cellular and molecular mechanisms for synapse formation. Cell adhesion molecules have been found important for synapse assembly in the brain. Read More

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Voluntary exercise blocks ongoing pain and diminishes bone remodeling while sparing protective mechanical pain in a rat model of advanced osteoarthritis pain.

Pain 2021 Jun 28. Epub 2021 Jun 28.

Department of Biomedical Sciences, College of Osteopathic Medicine, Center for Excellence in the Neurosciences, University of New England, Biddeford ME 04005 Department of Psychology, College of Arts and Sciences, University of New England, Biddeford ME 04005.

Abstract: Exercise is the most common treatment recommended by health care providers for treatment of musculoskeletal pain. We examined whether voluntary running wheel exercise improves pain and bone remodeling in rats with monosodium iodoacetate (MIA)-induced unilateral knee joint pain. During acquisition of wheel running prior to OA treatment, rats separated into two groups characterized by either high or low levels of voluntary wheel running as indicated by distance and peak speed. Read More

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Induction of Glutathione Synthesis Provides Cardioprotection Regulating NO, AMPK and PPARa Signaling in Ischemic Rat Hearts.

Life (Basel) 2021 Jun 29;11(7). Epub 2021 Jun 29.

Department of Blood Circulation, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomolets Str., 01024 Kyiv, Ukraine.

Glutathione (GSH) is essential for antioxidant defence, and its depletion is associated with tissue damage during cardiac ischemia-reperfusion (I/R). GSH is synthesized by the glutamate-cysteine ligase enzyme (GCL) from L-cysteine, which alternatively might be used for hydrogen sulfide production by cystathionine-gamma-lyase (CSE). Here, we have investigated whether in vivo treatment with L-cysteine and an inhibitor of CSE,D,L-propargylglycine (PAG), can modulate cardiac glutathione and whether this treatment can influence heart resistance to I/R in a Langendorff isolated rat hearts model. Read More

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JMJ27-mediated histone H3K9 demethylation positively regulates drought-stress responses in Arabidopsis.

New Phytol 2021 Jul 1. Epub 2021 Jul 1.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

Dimethylation of histone H3 at lysine 9 (H3K9me2) is associated with heterochromatinization and transcriptional gene silencing in plants. The activation of sets of genes by drought stress is correlated with reduced H3K9me2 levels, but the role of H3K9 methylation in the regulation of drought-stress responses remains elusive. Here, we show that the Jumonji domain-containing H3K9 demethylase JMJ27 positively regulates drought-stress responses through its histone demethylase activity. Read More

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TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.

Life Sci Alliance 2021 Aug 28;4(8). Epub 2021 Jun 28.

Department of Pharmacy, Ludwig-Maximilians-Universität München, München, Germany

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Read More

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Reproductive developmental transcriptome analysis of Tripidium ravennae (Poaceae).

BMC Genomics 2021 Jun 28;22(1):483. Epub 2021 Jun 28.

Department of Horticultural Science, North Carolina State University, Campus Box 7609, Raleigh, NC, 27695-7609, USA.

Background: Tripidium ravennae is a cold-hardy, diploid species in the sugarcane complex (Poaceae subtribe Saccharinae) with considerable potential as a genetic resource for developing improved bioenergy and ornamental grasses. An improved understanding of the genetic regulation of reproductive processes (e.g. Read More

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Bilateral Amygdala Radio-Frequency Ablation for Refractory Aggressive Behavior Alters Local Cortical Thickness to a Pattern Found in Non-refractory Patients.

Front Hum Neurosci 2021 9;15:653631. Epub 2021 Jun 9.

Division of Neuroscience, Sirio-Libanês Hospital, São Paulo, Brazil.

Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. Read More

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Praja1 ubiquitin ligase facilitates degradation of polyglutamine proteins and suppresses polyglutamine-mediated toxicity.

Mol Biol Cell 2021 Jun 23:mbcE20110747. Epub 2021 Jun 23.

Division of Molecular Medicine, Bose Institute, Kolkata, India.

A network of chaperones and ubiquitin ligases sustain intracellular proteostasis, and is integral in preventing aggregation of misfolded proteins associated with various neurodegenerative diseases. Using cell-based studies of polyglutamine (polyQ) diseases: Spinocerebellar ataxia Type 3 (SCA3) and Huntington's disease (HD), we aimed to identify crucial ubiquitin ligases that protect against polyQ aggregation. We report here that Praja1 (PJA1), a Ring-H2 ubiquitin ligase abundantly expressed in the brain is diminished when polyQ repeat proteins (Ataxin-3/Huntingtin) are expressed in cells. Read More

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Glucocorticoid-mediated induction of caveolin-1 disrupts cytoskeletal organization, inhibits cell migration and re-epithelialization of non-healing wounds.

Commun Biol 2021 06 18;4(1):757. Epub 2021 Jun 18.

Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Although impaired keratinocyte migration is a recognized hallmark of chronic wounds, the molecular mechanisms underpinning impaired cell movement are poorly understood. Here, we demonstrate that both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) exhibit global deregulation of cytoskeletal organization in genomic comparison to normal skin and acute wounds. Interestingly, we found that DFUs and VLUs exhibited downregulation of ArhGAP35, which serves both as an inactivator of RhoA and as a glucocorticoid repressor. Read More

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Leptin-resistant Zucker rats with trinitrobenzene sulfonic acid colitis present a reduced inflammatory response but enhanced epithelial damage.

Am J Physiol Gastrointest Liver Physiol 2021 Aug 16;321(2):G157-G170. Epub 2021 Jun 16.

Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Granada, Spain.

The role of leptin in the development of intestinal inflammation remains controversial, since proinflammatory and anti-inflammatory effects have been described. This study describes the effect of the absence of leptin signaling in intestinal inflammation. Experimental colitis was induced by intrarectal administration of trinitrobenzene sulfonic acid (TNBS) to lean and obese Zucker rats ( = 10). Read More

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Attenuated Induction of the Unfolded Protein Response in Adult Human Primary Astrocytes in Response to Recurrent Low Glucose.

Front Endocrinol (Lausanne) 2021 26;12:671724. Epub 2021 May 26.

Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom.

Aims/hypothesis: Recurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure. Read More

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Dexmedetomidine protects against degeneration of dopaminergic neurons and improves motor activity in Parkinson's disease mice model.

Saudi J Biol Sci 2021 Jun 20;28(6):3198-3203. Epub 2021 Apr 20.

Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054 Shaanxi, China.

Parkinson's disease (PD) is the result of dopaminergic (DA) neuronal death in the substantianigra pars compacta (SNc). Current treatments for PD such as L-dopa are limited in effectiveness and fail to address the cause. Targeted anti-inflammatory therapies, particularly directed at nuclear factor kappa B (NF-κB) activity in alleviating degeneration of DA-neurons is of evolving interest. Read More

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AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction.

J Am Coll Cardiol 2021 Jun;77(23):2923-2935

Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University of Munich, Munich, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany. Electronic address:

Background: Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure.

Objectives: This study aimed to establish a novel porcine model of pressure-overload-induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model. Read More

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ERK activation via A1542/3 limonoids attenuates erythroleukemia through transcriptional stimulation of cholesterol biosynthesis genes.

BMC Cancer 2021 Jun 9;21(1):680. Epub 2021 Jun 9.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Province Science City, High Tech Zone, Baiyun District, Guiyang, 550014, Guizhou Province, People's Republic of China.

Background: Cholesterol plays vital roles in human physiology; abnormal levels have deleterious pathological consequences. In cancer, elevated or reduced expression of cholesterol biosynthesis is associated with good or poor prognosis, but the underlying mechanisms are largely unknown. The limonoid compounds A1542 and A1543 stimulate ERK/MAPK by direct binding, leading to leukemic cell death and suppression of leukemia in mouse models. Read More

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Adipogenic Differentiation Alters Properties of Vascularized Tissue-Engineered Skeletal Muscle.

Tissue Eng Part A 2021 Jun 9. Epub 2021 Jun 9.

University of Texas at San Antonio, 12346, Department of Biomedical Engineering and Chemical Engineering, One UTSA Circle, San Antonio, Texas, United States, 78249-1644;

Advances in the engineering of comprehensive skeletal muscle models in vitro will improve drug screening platforms and can lead to better therapeutic approaches for the treatment of skeletal muscle injuries. To this end, a vascularized tissue-engineered skeletal muscle (TE-SkM) model that includes adipocytes was developed in order to better emulate the intramuscular adipose tissue that is observed in skeletal muscles of patients with diseases like diabetes. Muscle precursor cells (MPCs) cultured with and without microvessels derived from adipose tissue (microvascular fragments; MVFs) were used to generate TE-SkM constructs, with and without a microvasculature, respectively. Read More

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Localization matters: nuclear-trapped Survivin sensitizes glioblastoma cells to temozolomide by elevating cellular senescence and impairing homologous recombination.

Cell Mol Life Sci 2021 Jul 8;78(14):5587-5604. Epub 2021 Jun 8.

Department of Toxicology, University Medical Center, Mainz, Germany.

To clarify whether differential compartmentalization of Survivin impacts temozolomide (TMZ)-triggered end points, we established a well-defined glioblastoma cell model in vitro (LN229 and A172) and in vivo, distinguishing between its nuclear and cytoplasmic localization. Expression of nuclear export sequence (NES)-mutated Survivin (SurvNESmut-GFP) led to impaired colony formation upon TMZ. This was not due to enhanced cell death but rather due to increased senescence. Read More

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Identification of Nrf2-responsive microRNA networks as putative mediators of myocardial reductive stress.

Sci Rep 2021 Jun 7;11(1):11977. Epub 2021 Jun 7.

Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.

Although recent advances in the treatment of acute coronary heart disease have reduced mortality rates, few therapeutic strategies exist to mitigate the progressive loss of cardiac function that manifests as heart failure. Nuclear factor, erythroid 2 like 2 (Nfe2l2, Nrf2) is a transcriptional regulator that is known to confer transient myocardial cytoprotection following acute ischemic insult; however, its sustained activation paradoxically causes a reductive environment characterized by excessive antioxidant activity. We previously identified a subset of 16 microRNAs (miRNA) significantly diminished in Nrf2-ablated (Nrf2) mouse hearts, leading to the hypothesis that increasing levels of Nrf2 activation augments miRNA induction and post-transcriptional dysregulation. Read More

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Mild Mitochondrial Uncoupling Decreases Experimental Atherosclerosis, A Proof of Concept.

J Atheroscler Thromb 2021 Jun 4. Epub 2021 Jun 4.

Department of Structural and Functional Biology, Biology Institute, State University of Campinas.

Aim: Atherosclerosis is responsible for high morbidity and mortality rates around the world. Local arterial oxidative stress is involved in all phases of atherosclerosis development. Mitochondria is a relevant source of the oxidants, particularly under certain risky conditions, such as hypercholesterolemia. Read More

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H3K27 demethylases are dispensable for activation of Polycomb-regulated injury response genes in peripheral nerve.

J Biol Chem 2021 Jul 4;297(1):100852. Epub 2021 Jun 4.

Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address:

The induction of nerve injury response genes in Schwann cells depends on both transcriptional and epigenomic reprogramming. The nerve injury response program is regulated by the repressive histone mark H3K27 trimethylation (H3K27me3), deposited by Polycomb repressive complex 2 (PRC2). Loss of PRC2 function leads to early and augmented induction of the injury response gene network in peripheral nerves, suggesting H3K27 demethylases are required for derepression of Polycomb-regulated nerve injury genes. Read More

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Mutations Alter the Subcellular Localization of BRCA1 .

Anticancer Res 2021 Jun;41(6):2953-2962

Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.

Background/aim: Numerous missense mutations have been determined in the BRCT domain of the BRCA1 gene, affecting localization and interaction of BRCA1 with other proteins.

Materials And Methods: We examined whether the M1775K and V1809F mutations in the BRCT domain affect BRCA1 cellular localization. Cells were transfected with pEGFP-C3-BRCA1 and detected by fluorescence microscopy. Read More

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