25,667 results match your criteria repair pathways


Loss of ATRX confers DNA repair defects and PARP inhibitor sensitivity.

Transl Oncol 2021 Jun 9;14(9):101147. Epub 2021 Jun 9.

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06511, USA. Electronic address:

Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) is mutated frequently in gliomas and represents a potential target for cancer therapies. ATRX is known to function as a histone chaperone that helps incorporate histone variant, H3.3, into the genome. Read More

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Transcriptome response of maize (Zea mays L.) seedlings to heat stress.

Protoplasma 2021 Jun 12. Epub 2021 Jun 12.

School of Life Sciences, Yunnan Normal University, Kunming, 650092, People's Republic of China.

Among stresses, heat stress (HS) is a prime factor restricting plant growth and productivity. However, the molecular mechanisms of plants' response to HS need to be further uncovered. Here, the transcriptome response of maize seedlings to HS was dissected using transcriptome data analysis. Read More

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Electroactive Biomaterials and Systems for Cell Fate Determination and Tissue Regeneration: Design and Applications.

Adv Mater 2021 Jun 12:e2007429. Epub 2021 Jun 12.

Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 100083, P. R. China.

During natural tissue regeneration, tissue microenvironment and stem cell niche including cell-cell interaction, soluble factors, and extracellular matrix (ECM) provide a train of biochemical and biophysical cues for modulation of cell behaviors and tissue functions. Design of functional biomaterials to mimic the tissue/cell microenvironment have great potentials for tissue regeneration applications. Recently, electroactive biomaterials have drawn increasing attentions not only as scaffolds for cell adhesion and structural support, but also as modulators to regulate cell/tissue behaviors and function, especially for electrically excitable cells and tissues. Read More

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Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress.

Nat Struct Mol Biol 2021 Jun 10;28(6):487-500. Epub 2021 Jun 10.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Read More

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A Fast-track Pathway for Emergency General Surgery at an Academic Medical Center.

J Surg Res 2021 Jun 8;267:1-8. Epub 2021 Jun 8.

Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts. Electronic address:

Background: Fast Track Pathways (FTP) directed at reducing length of stay (LOS) and overall costs are being increasingly implemented for emergency surgeries. The purpose of this study is to evaluate implementation of a FTP for Emergency General Surgery (EGS) at an academic medical center (AMC).

Methods: The study included 165 patients at an AMC between 2016 and 2018 who underwent laparoscopic appendectomy (LA), laparoscopic cholecystectomy (LC), or laparoscopic inguinal hernia repair (LI). Read More

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SAA1/TLR2 axis directs chemotactic migration of hepatic stellate cells responding to injury.

iScience 2021 May 29;24(5):102483. Epub 2021 Apr 29.

Institute of Public Health, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, Guangdong 510530, China.

Hepatic stellate cells (HSCs) are crucial for liver injury repair and cirrhosis. However, the mechanism of chemotactic recruitment of HSCs into injury loci is still largely unknown. Here, we demonstrate that serum amyloid A1 (SAA1) acts as a chemokine recruiting HSCs toward injury loci signaling via TLR2, a finding proven by gene manipulation studies in cell and mice models. Read More

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The Role of Astrocytes in the Neurorepair Process.

Front Cell Dev Biol 2021 25;9:665795. Epub 2021 May 25.

Department of Pharmacology, Federal University of Goias, Goiânia, Brazil.

Astrocytes are highly specialized glial cells responsible for trophic and metabolic support of neurons. They are associated to ionic homeostasis, the regulation of cerebral blood flow and metabolism, the modulation of synaptic activity by capturing and recycle of neurotransmitters and maintenance of the blood-brain barrier. During injuries and infections, astrocytes act in cerebral defense through heterogeneous and progressive changes in their gene expression, morphology, proliferative capacity, and function, which is known as reactive astrocytes. Read More

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Role of HOXC10 in Cancer.

Front Oncol 2021 25;11:684021. Epub 2021 May 25.

Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.

The HOXC10 gene, a member of the HOX genes family, plays crucial roles in mammalian physiological processes, such as limb morphological development, limb regeneration, and lumbar motor neuron differentiation. HOXC10 is also associated with angiogenesis, fat metabolism, and sex regulation. Additional evidence suggests that HOXC10 dysregulation is closely associated with various tumors. Read More

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Mind the replication gap.

R Soc Open Sci 2021 Jun 9;8(6):201932. Epub 2021 Jun 9.

Chromosome Dynamics and Stability Group, Genome Damage and Stability Centre, University of Sussex, Brighton BN1 7BG, UK.

Unlike bacteria, mammalian cells need to complete DNA replication before segregating their chromosomes for the maintenance of genome integrity. Thus, cells have evolved efficient pathways to restore stalled and/or collapsed replication forks during S-phase, and when necessary, also to delay cell cycle progression to ensure replication completion. However, strong evidence shows that cells can proceed to mitosis with incompletely replicated DNA when under mild replication stress (RS) conditions. Read More

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Adipose-derived mesenchymal stromal cell-derived exosomes promote tendon healing by activating both SMAD1/5/9 and SMAD2/3.

Stem Cell Res Ther 2021 Jun 10;12(1):338. Epub 2021 Jun 10.

Department of Pediatric Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, 150001, China.

Background: The use of adipose-derived mesenchymal stromal cell-derived exosomes (ADSC-Exos) may become a new therapeutic method in biomedicine owing to their important role in regenerative medicine. However, the role of ADSC-Exos in tendon repair has not yet been evaluated. Therefore, we aimed to clarify the healing effects of ADSC-Exos on tendon injury. Read More

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Transcriptomic analysis of shell repair and biomineralization in the blue mussel, Mytilus edulis.

BMC Genomics 2021 Jun 10;22(1):437. Epub 2021 Jun 10.

British Antarctic Survey, Natural Environment Research Council, High Cross, Madingley Road, CB3 0ET, Cambridge, UK.

Background: Biomineralization by molluscs involves regulated deposition of calcium carbonate crystals within a protein framework to produce complex biocomposite structures. Effective biomineralization is a key trait for aquaculture, and animal resilience under future climate change. While many enzymes and structural proteins have been identified from the shell and in mantle tissue, understanding biomieralization is impeded by a lack of fundamental knowledge of the genes and pathways involved. Read More

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Protein signatures of remodeled airways in transplanted lungs with Bronchiolitis Obliterans Syndrome obtained using laser capture microdissection.

Am J Pathol 2021 Jun 7. Epub 2021 Jun 7.

Lung Biology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address:

Bronchiolitis obliterans syndrome (BOS), a common form of chronic lung allograft dysfunction, is the major limitation to long-term survival after lung transplantation. The histological correlate is progressive, fibrotic occlusion of small airways, obliterative bronchiolitis lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. Read More

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The role of lncRNA ANRIL in the progression of hepatocellular carcinoma.

J Pharm Pharmacol 2021 Jun 10. Epub 2021 Jun 10.

Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, Beijing 100000, China.

Objectives: The aim of the current study was to identify the long noncoding RNAs (lncRNAs) ANRIL function and molecular pathways underlying hepatocellular carcinoma progression.

Methods: ANRIL knockdown with specific siRNA, and transfected into HepG2 cells according to the protocol of Lipofectamine 2000. Cell proliferation, apoptosis, migration and metastasis were assessed with MTT assay, flow cytometry and wound healing assay, respectively. Read More

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Lineage-specific mechanisms and drivers of breast cancer chemoresistance revealed by 3D biomimetic culture.

Mol Oncol 2021 Jun 10. Epub 2021 Jun 10.

Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, Meldola, Italy.

To improve the success rate of current preclinical drug trials there is a growing need for more complex and relevant models that can help predict clinical resistance to anticancer agents. Here, we present a three-dimensional (3D) technology, based on biomimetic collagen scaffolds, that enables the modeling of the tumor hypoxic state and the prediction of in vivo chemotherapy responses in terms of efficacy, molecular alterations and emergence of resistance mechanisms. The human breast cancer cell lines MDA-MB-231 (triple negative) and MCF-7 (luminal A) were treated with scaling doses of doxorubicin in monolayer cultures, 3D collagen scaffolds or orthotopically transplanted murine models. Read More

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Epigenomics in Hurthle Cell Neoplasms: Filling in the Gaps Towards Clinical Application.

Front Endocrinol (Lausanne) 2021 24;12:674666. Epub 2021 May 24.

Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.

It has been widely described that cancer genomes have frequent alterations to the epigenome, including epigenetic silencing of various tumor suppressor genes with functions in almost all cancer-relevant signalling pathways, such as apoptosis, cell proliferation, cell migration and DNA repair. Epigenetic alterations comprise DNA methylation, histone modification, and microRNAs dysregulated expression and they play a significant role in the differentiation and proliferation properties of TC. In this review, our group assessed the published evidence on the tumorigenic role of epigenomics in Hurthle cell neoplasms (HCN), highlighting the yet limited, heteregeneous and non-validated data preventing its current use in clinical practice, despite the well developed assessment techniques available. Read More

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DNA-PK inhibitor peposertib enhances p53-dependent cytotoxicity of DNA double-strand break inducing therapy in acute leukemia.

Sci Rep 2021 Jun 9;11(1):12148. Epub 2021 Jun 9.

Translational Innovation Platform Oncology and Immuno-Oncology, EMD Serono Research & Development Institute, Inc, Billerica, MA, USA.

Peposertib (M3814) is a potent and selective DNA-PK inhibitor in early clinical development. It effectively blocks non-homologous end-joining repair of DNA double-strand breaks (DSB) and strongly potentiates the antitumor effect of ionizing radiation (IR) and topoisomerase II inhibitors. By suppressing DNA-PK catalytic activity in the presence of DNA DSB, M3814 potentiates ATM/p53 signaling leading to enhanced p53-dependent antitumor activity in tumor cells. Read More

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Identification of genes required for the fitness of Rhodococcus equi during the infection of mice via signature-tagged transposon mutagenesis.

J Vet Med Sci 2021 Jun 10. Epub 2021 Jun 10.

Laboratory of Animal Hygiene, School of Veterinary Medicine, Kitasato University.

Rhodococcus equi is a Gram-positive facultative intracellular bacterium that causes pyogranulomatous pneumonia in foals and immunocompromised people. In the present study, signature-tagged transposon mutagenesis was applied for the negative selection of R. equi mutants that cannot survive in vivo. Read More

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CD151 drives cancer progression depending on integrin α3β1 through EGFR signaling in non-small cell lung cancer.

J Exp Clin Cancer Res 2021 Jun 9;40(1):192. Epub 2021 Jun 9.

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Background: Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion. Read More

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Novel Mechanisms for Resolution of Liver Inflammation: Therapeutic Implications.

Semin Liver Dis 2021 May 24;41(2):150-162. Epub 2021 Mar 24.

Department of Pediatrics, University of California, San Diego (UCSD), California and Rady Children's Hospital, San Diego, California.

Traditional concepts have classically viewed resolution of inflammation as a passive process yet insight into the pathways by which inflammation is resolved has challenged this idea. Resolution has been revealed as a highly dynamic and active event that is essential to counteract the dysregulated inflammatory response that drives diverse disease states. Abrogation of the hepatic inflammatory response through the stimulation of proresolving mechanisms represents a new paradigm in the setting of chronic inflammatory-driven liver diseases. Read More

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β-Adrenoceptor regulation of metabolism in U937 derived macrophages.

Mol Omics 2021 Jun 8. Epub 2021 Jun 8.

Drug Delivery, Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Science, Monash University, Parkville, Victoria 3052, Australia.

Macrophages have important roles in the immune system including clearing pathogens and wound healing. Metabolic phenotypes in macrophages have been associated with functional phenotypes, where pro-inflammatory macrophages have an increased rate of glycolysis and anti-inflammatory macrophages primarily use oxidative phosphorylation. β-adrenoceptor (βAR) signalling in macrophages has been implicated in disease states such as cancer, atherosclerosis and rheumatoid arthritis. Read More

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The Functional Hallmarks of Cancer Predisposition Genes.

Cancer Manag Res 2021 1;13:4351-4357. Epub 2021 Jun 1.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, USA, New York, NY, 10029, USA.

The canonical model for hereditary cancer predisposition is a cancer predisposition gene (CPG) that drives either one or both of two fundamental hallmarks of cancer, defective genomic integrity and deregulated cell proliferation, ultimately resulting in the accumulation of mutations within cells. Thus, the genes most commonly associated with cancer-predisposing genetic syndromes are tumor suppressor genes that regulate DNA repair (eg, genes) and/or cell cycle (eg, ). In recent years, however, the spectrum of high-penetrance CPGs has expanded considerably to include genes in non-canonical pathways such as oncogenic signaling, metabolism, and protein translation. Read More

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Mutations Involved in Premature-Ageing Syndromes.

Authors:
Fabio Coppedè

Appl Clin Genet 2021 2;14:279-295. Epub 2021 Jun 2.

Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.

Premature-ageing syndromes are a heterogeneous group of rare genetic disorders resembling features of accelerated ageing and resulting from mutations in genes coding for proteins required for nuclear lamina architecture, DNA repair and maintenance of genome stability, mitochondrial function and other cellular processes. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best-characterized progeroid syndromes referred to as childhood- and adulthood-progeria, respectively. This article provides an updated overview of the mutations leading to HGPS, WS, and to the spectrum of premature-ageing laminopathies ranging in severity from congenital restrictive dermopathy (RD) to adult-onset atypical WS, including RD-like laminopathies, typical and atypical HGPS, more and less severe forms of mandibuloacral dysplasia (MAD), Néstor-Guillermo progeria syndrome (NGPS), atypical WS, and atypical progeroid syndromes resembling features of HGPS and/or MAD but resulting from impaired DNA repair or mitochondrial functions, including mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome and mandibuloacral dysplasia associated to (MADaM). Read More

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A review of animal models from 2015 to 2020 for preclinical chronic wounds relevant to human health.

J Tissue Viability 2021 Jun 1. Epub 2021 Jun 1.

Louis Stokes Cleveland Veterans Affairs Medical Center (LSCVAMC), Cleveland, OH, USA; Dept of Orthopaedics & Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA. Electronic address:

Significance: Chronic wounds fail to heal in a timely manner and exhibit sustained inflammation with slow tissue repair and remodelling. They decrease mobility and quality of life, and remain a major clinical challenge in the long-term care of many patients, affecting 6.5 million individuals annually in the U. Read More

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Epigenetic mechanisms underlying prostate cancer radioresistance.

Clin Epigenetics 2021 Jun 8;13(1):125. Epub 2021 Jun 8.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Vico L. De Crecchio 7, 80138, Naplei, Italy.

Radiotherapy (RT) is one of the mainstay treatments for prostate cancer (PCa), a highly prevalent neoplasm among males worldwide. About 30% of newly diagnosed PCa patients receive RT with a curative intent. However, biochemical relapse occurs in 20-40% of advanced PCa treated with RT either alone or in combination with adjuvant-hormonal therapy. Read More

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Recent Advances in Therapeutic Application of DNA Damage Response Inhibitors against Cancer.

Anticancer Agents Med Chem 2021 Jun 7. Epub 2021 Jun 7.

Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be) University, Mumbai, India.

DNA integrity is continuously challenged by intrinsic cellular processes and environmental agents. To overcome this genomic damage, cells have developed multiple signaling pathways collectively named as DNA damage response (DDR) and composed of three components: (i) sensor proteins, which detect DNA damage, (ii) mediators that relay the signal downstream and recruit the repair machinery, and (iii) the repair proteins, which restore the damaged DNA. A flawed DDR and failure to repair the damage lead to the accumulation of genetic lesions and increased genomic instability, which is recognized as a hallmark of cancer. Read More

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Systematic analysis of molecular characterization and clinical relevance of m6A regulators in digestive system pan-cancers.

Exp Biol Med (Maywood) 2021 Jun 8:15353702211019681. Epub 2021 Jun 8.

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing 100032, China.

Digestive system tumors, which mainly include esophagus, stomach, colorectum, liver, pancreas, bile duct, and some other tumors, often have a poor prognosis. N6-methyladenosine (m6A) has critical functions in development and tumorigenesis and may help improve the molecular mechanisms of digestive system tumors. However, current understanding of the reconstitution of m6A in digestive system tumors is far from comprehensive. 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 Jun 8. 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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TRPM2 promotes pancreatic cancer by PKC/MAPK pathway.

Cell Death Dis 2021 Jun 7;12(6):585. Epub 2021 Jun 7.

General Surgery Department, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.

The mechanism of pancreatic cancer (PA) is not fully understanded. In our last report, TRPM2 plays a promising role in pancreatic cancer. However, the mechanism of TRPM2 is still unknown in this dismal disease. Read More

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RAD51AP1 loss attenuates colorectal cancer stem cell renewal and sensitizes to chemotherapy.

Mol Cancer Res 2021 Jun 7. Epub 2021 Jun 7.

Biochemistry and Molecular Biology, Augusta University

DNA damage, induced by either chemical carcinogens or environmental pollutants, plays an important role in the initiation of colorectal cancer (CRC). DNA repair processes, however, are involved in both protecting against cancer formation, and also contributing to cancer development, by ensuring genomic integrity and promoting the efficient DNA repair in tumor cells, respectively. Although DNA repair pathways have been well exploited in the treatment of breast and ovarian cancers, the role of DNA repair processes and their therapeutic efficacy in CRC is yet to be appreciably explored. Read More

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MicroRNAs as the critical regulators of cisplatin resistance in gastric tumor cells.

Genes Environ 2021 Jun 7;43(1):21. Epub 2021 Jun 7.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Combined chemotherapeutic treatment is the method of choice for advanced and metastatic gastric tumors. However, resistance to chemotherapeutic agents is one of the main challenges for the efficient gastric cancer (GC) treatment. Cisplatin (CDDP) is used as an important regimen of chemotherapy for GC which induces cytotoxicity by interfering with DNA replication in cancer cells and inducing their apoptosis. Read More

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