32,246 results match your criteria downstream target

Shotgun proteomics coupled to transient-inducible gene silencing reveal rice susceptibility genes as new sources for blast disease resistance.

J Proteomics 2021 Apr 9:104223. Epub 2021 Apr 9.

Embrapa Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil. Electronic address:

A comparative proteomic analysis between two near-isogenic rice lines, displaying a resistant and susceptible phenotype upon infection with Magnaporthe oryzae was performed. We identified and validated factors associated with rice disease susceptibility, representing a flourishing source toward a more resolute rice-blast resistance. Proteome profiles were remarkably different during early infection (12 h post-inoculation), revealing several proteins with increased abundance in the compatible interaction. Read More

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TWIST1-mediated transcriptional activation of PDGFRβ in breast cancer stem cells promotes tumorigenesis and metastasis.

Biochim Biophys Acta Mol Basis Dis 2021 Apr 9:166141. Epub 2021 Apr 9.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad -500 007, TS 500 007, India; Academy of Science and Innovative Research (AcSIR), Ghaziabad, UP - 201 002, India. Electronic address:

Triple-negative breast cancer (TNBC) patients often exhibit poor prognosis and breast cancer relapse due to metastasis. This results in secondary tumor generation at distant-unrelated organs that account for the majority of breast cancer-related deaths. Although breast cancer stem cells (CSCs) have been attributed to metastasis, a mechanistic understanding is essential for developing therapeutic interventions to combat breast cancer relapse. Read More

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SETD2 alterations and histone H3K36 trimethylation in phyllodes tumor of breast.

Breast Cancer Res Treat 2021 Apr 12. Epub 2021 Apr 12.

Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong SAR.

Purpose: SETD2 is one of the key epigenetic regulatory genes involved in histone modifications. Its alterations were potentially oncogenic and commonly found in cancers. Interestingly, SETD2 is one of the most frequent mutated genes found exclusively in phyllodes tumor of the breast (PT). Read More

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Automated Dissection Protocol for Tumor Enrichment in Low Tumor Content Tissues.

J Vis Exp 2021 Mar 29(169). Epub 2021 Mar 29.

Departments of Research Pathology, Genentech;

Tumor enrichment in low tumor content tissues, those below 20% tumor content depending on the method, is required to generate quality data reproducibly with many downstream assays such as next generation sequencing. Automated tissue dissection is a new methodology that automates and improves tumor enrichment in these common, low tumor content tissues by decreasing the user-dependent imprecision of traditional macro-dissection and time, cost, and expertise limitations of laser capture microdissection by using digital image annotation overlay onto unstained slides. Here, digital hematoxylin and eosin (H&E) annotations are used to target small tumor areas using a blade that is 250 µm in diameter in unstained formalin fixed paraffin embedded (FFPE) or fresh frozen sections up to 20 µm in thickness for automated tumor enrichment prior to nucleic acid extraction and whole exome sequencing (WES). Read More

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Stem cell concepts in myelodysplastic syndromes: lessons and challenges.

J Intern Med 2021 Apr 12. Epub 2021 Apr 12.

From the, Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.

According to the cancer stem cell (CSC) hypothesis, CSCs are the only cancer cells that can give rise to and sustain all cells that constitute a cancer as they possess inherent or acquired self-renewal potential, and their elimination is required and potentially sufficient to achieve a cure. Whilst establishing CSC identity remains challenging in most cancers, studies of low-intermediate risk myelodysplastic syndromes (MDS), other chronic myeloid malignancies and clonal haematopoiesis of indeterminant potential (CHIP) strongly support that the primary target cell usually resides in the rare haematopoietic stem cell (HSC) compartment. This probably reflects the unique self-renewal potential of HSCs in normal human haematopoiesis, combined with the somatic initiating genomic driver lesion not conferring extensive self-renewal potential to downstream progenitor cells. Read More

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O-GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity.

J Cell Physiol 2021 Apr 12. Epub 2021 Apr 12.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

O-GlcNAcylation is a posttranslational modification that regulates numerous nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes, such as transcription, signal transduction, and cell motility. Although increasing evidence has shown that elevated levels of global O-GlcNAcylation are linked to the metastasis in hepatocellular carcinoma (HCC) cells, the underlying mechanism is still ambiguous. In this study, we demonstrated that forkhead box protein A2 (FOXA2), an essential transcription factor for liver homeostasis and HCC developing, was O-GlcNAcylated by O-GlcNAc transferase (OGT) and regulates HCC cells migration and invasion. Read More

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Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18.

Front Mol Biosci 2021 24;8:641585. Epub 2021 Mar 24.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Cardiac hypertrophic preconditioning (HP) signifies cardioprotection induced by transient pressure overload to resist hypertrophic effects of subsequently sustained pressure overload. Although it is recently found that inflammation triggers the development of nonischemic cardiomyopathy, whether inflammation plays a role in the antecedent protective effects of HP remains unknown. Caspase-1 is a critical proinflammatory caspase that also induces pyroptosis; thus, we investigated the role of caspase-1 using a unique model of HP in mice subjected longitudinally to 3 days of transverse aortic constriction (TAC 3d), 4 days of de-constriction (De-TAC 4d), and 4 weeks of Re-TAC (Re-TAC 4W). Read More

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3-Deoxysappanchalcone Inhibits Skin Cancer Proliferation by Regulating T-Lymphokine-Activated Killer Cell-Originated Protein Kinase and .

Front Cell Dev Biol 2021 25;9:638174. Epub 2021 Mar 25.

Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, China.

Background: Skin cancer is one of the most commonly diagnosed cancers worldwide. The 5-year survival rate of the most aggressive late-stage skin cancer ranges between 20 and 30%. Thus, the discovery and investigation of novel target therapeutic agents that can effectively treat skin cancer is of the utmost importance. Read More

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Hematopoietic Cell Kinase (HCK) Is a Player of the Crosstalk Between Hematopoietic Cells and Bone Marrow Niche Through CXCL12/CXCR4 Axis.

Front Cell Dev Biol 2021 25;9:634044. Epub 2021 Mar 25.

Hematology and Transfusion Medicine Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, Brazil.

The crosstalk between hematopoietic stem/progenitor cells (HSC), both normal and leukemic, and their neighboring bone marrow (BM) microenvironment (niche) creates a reciprocal dependency, a master regulator of biological process, and chemotherapy resistance. In acute myeloid leukemia (AML), leukemic stem/progenitor cells (LSC) anchored in the protective BM microenvironment, reprogram and transform this niche into a leukemia-supporting and chemoprotective environment. One most important player involved in this crosstalk are CXCL12, produced by the BM mesenchymal stromal cells, and its receptor CXCR4, present onto HSC. Read More

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CircRNA circ_0092314 Induces Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells Elevating the Expression of S100P by Sponging miR-671.

Front Oncol 2021 25;11:675442. Epub 2021 Mar 25.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Circular RNAs (circRNAs) is a novel class of non-coding RNAs that regulate gene expression during cancer progression. Circ_0092314 is a newly discovered circRNA that was upregulated in pancreatic cancer (PAAD) tissues. However, the detailed functions and underlying mechanisms of circ_0092314 in PAAD cells remain unclear. Read More

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LncRNA H19 secreted by umbilical cord blood mesenchymal stem cells through microRNA-29a-3p/FOS axis for central sensitization of pain in advanced osteoarthritis.

Am J Transl Res 2021 15;13(3):1245-1256. Epub 2021 Mar 15.

Department of Hepatobiliary and Pancreatic Surgery, Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Chengdu 610072, China.

Objective: To explore the molecular mechanism of umbilical cord blood mesenchymal stem cells (UCBMSCs) in the treatment of advanced osteoarthritis pain.

Methods: Normal healthy rats were selected to establish advanced osteoarthritis (OA) model, and the rats were randomly divided into control group, intravenous group, intracavitary group and intrathecal group. The intravenous group received intravenous injection of UCBMSCs, intracavitary group received intra-articular injection of UCBMSCs, and intrathecal group received subarachnoid injection of UCBMSCs. Read More

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LncRNA RUSC1-AS1 contributes to the progression of hepatocellular carcinoma cells by modulating miR-340-5p/CREB1 axis.

Am J Transl Res 2021 15;13(3):1022-1036. Epub 2021 Mar 15.

Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University Nanjing, Jiangsu, China.

Background: Recent studies have proven that there is a relationship between long non-coding RNAs (lncRNAs) and malignant tumor hepatocellular carcinoma (HCC). However, the function of RUSC1-AS1 and its relative regulators in HCC remains unknown.

Methods: studies, CCK-8 assays, colony formation assays, transwell assays, and wound healing tests were carried out to evaluate the proliferation, migration, and invasion of HCC cells. Read More

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Proteomic Characterization, Biodistribution, and Functional Studies of Immune-Therapeutic Exosomes: Implications for Inflammatory Lung Diseases.

Front Immunol 2021 25;12:636222. Epub 2021 Mar 25.

Department of Periodontics, Dental College of Georgia at Augusta University, Augusta, GA, United States.

Dendritic cell (DC)-derived exosomes (DC EXO), natural nanoparticles of endosomal origin, are under intense scrutiny in clinical trials for various inflammatory diseases. DC EXO are eobiotic, meaning they are well-tolerated by the host; moreover, they can be custom-tailored for immune-regulatory or -stimulatory functions, thus presenting attractive opportunities for immune therapy. Previously we documented the efficacy of immunoregulatory DCs EXO (regDCs EXO) as immunotherapy for inflammatory bone disease, in an model. Read More

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NET1 promotes HCC growth and metastasis and via activating the Akt signaling pathway.

Aging (Albany NY) 2021 Apr 11;13. Epub 2021 Apr 11.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.

Neuroepithelial cell transforming gene 1 (NET1), a member of the guanine nucleotide exchange factor family, is involved in various cancers, including gastric cancer, breast cancer and glioma. However, the role of NET1 in hepatocellular carcinoma (HCC) remains largely uncovered. In this study, we found that NET1 expression was upregulated in HCC, and that upregulated NET1 expression was closely associated with poor prognosis and some clinical characteristics in HCC patients. Read More

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Mechanosensitive Piezo1 channel activation promotes ventilator-induced lung injury via disruption of endothelial junctions in ARDS rats.

Biochem Biophys Res Commun 2021 Apr 8;556:79-86. Epub 2021 Apr 8.

Department of Anesthesiology, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, 225001, China. Electronic address:

Objective: This study aimed to investigate the role of endothelial Piezo1 in mediating ventilator-induced lung injury secondary to acute respiratory distress syndrome (ARDS).

Methods: Rats and lung endothelial cells (ECs) were transfected with Piezo1 shRNA (shPiezo1) and Piezo1 siRNA, respectively, to knock down Piezo1. Intratracheal instillation or incubation with lipopolysaccharide (LPS) was used to establish an ARDS model, and high tidal volume (HVT) ventilation or 20% cyclic stretch (CS) was administered to simulate a two-hit injury. Read More

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Insulin receptor substrate 1 (IRS1), but not IRS2, plays a dominant role in regulating pancreatic alpha cell function in mice.

J Biol Chem 2021 Apr 8:100646. Epub 2021 Apr 8.

Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Dysregulated glucagon secretion deteriorates glycemic control in type 1 and type 2 diabetes. Although insulin is known to regulate glucagon secretion via its cognate receptor (insulin receptor, INSR) in pancreatic alpha cells, the role of downstream proteins and signaling pathways underlying insulin's activities are not fully defined. Using in vivo (knockout) and in vitro (knockdown) studies targeting insulin receptor substrate (IRS) proteins, we compared the relative roles of IRS1 and IRS2 in regulating alpha cell function. Read More

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Sustained IKKβ phosphorylation and NF-κB activation by superoxide-induced peroxynitrite-mediated nitrotyrosine modification of B56γ3 and PP2A inactivation.

Redox Biol 2020 Dec 18;41:101834. Epub 2020 Dec 18.

National University Cancer Institute, National University Health System, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, NUS, Singapore; Integrative Science and Engineering Programme, NUS Graduate School, NUS, Singapore; Faculté de Medicine, University of Paris, Paris, France. Electronic address:

Apart from its physiological role in inflammation and immunity, the nuclear factor-kappa B (NF-κB) protein complex has been implicated in tumorigenesis and its progression. Here, we provide evidence that a pro-oxidant milieu is an upstream effector of oncogenic NF-κB signaling. Through pharmacological or genetic inhibition of SOD1, we show that elevated intracellular superoxide (O) mediates sustained IKK phosphorylation, and induces downstream degradation of IκBα, leading to the nuclear localization and transcriptional activation of NF-κB. Read More

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December 2020

Exploring unknown per- and polyfluoroalkyl substances in the German environment - The total oxidizable precursor assay as helpful tool in research and regulation.

Sci Total Environ 2021 Mar 29;782:146825. Epub 2021 Mar 29.

German Environment Agency (Umweltbundesamt), 06813 Dessau-Rosslau, Germany.

Limnetic, marine and soil samples of the German environmental specimen bank (ESB) were analyzed for per- and polyfluoroalkyl substances (PFAS) using target analysis and a modified total oxidizable precursor (TOP) assay (direct TOP assay (dTOP)) that works without prior extraction. Target analysis determined ∑PFAS concentrations in bream livers of 8.7-282 μg kg wet weight (ww) in 2019, with highest contaminations in the Rhine and lower Elbe. Read More

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MiR319-targeted OsTCP21 and OsGAmyb regulate tillering and grain yield in rice.

J Integr Plant Biol 2021 Apr 10. Epub 2021 Apr 10.

Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Agricultural Sciences, Guizhou University, Guiyang, 550025, China.

Multiple genes and microRNAs (miRNAs) improve grain yield by promoting tillering. MiR319s are known to regulate several aspects of plant development; however, whether miR319s are essential for tillering regulation remains unclear. Here, we report that miR319 is highly expressed in basal part of rice plant at different development stages. Read More

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Circular RNA circ-ARFIP2 regulates proliferation, migration and invasion in human vascular smooth muscle cells via miR-338-3p-dependent modulation of KDR.

Metab Brain Dis 2021 Apr 10. Epub 2021 Apr 10.

Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.106 Zhongshan Second Road, Guangzhou, 510000, Guangdong, China.

Dysfunction of vascular smooth muscle cells (VSMCs) plays a critical role in the pathogenesis of intracranial aneurysm (IA). Circular RNAs (circRNAs) have been implicated in the pathogenesis of IA by reducing microRNA (miRNA) activity. In this paper, we investigated the precise roles of circRNA ADP ribosylation factor interacting protein 2 (circ-ARFIP2, circ_0021001) in VSMC dysfunction. Read More

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FOXD1 Promotes Dedifferentiation and Targeted Therapy Resistance in Melanoma by Regulating the Expression of CTGF.

Int J Cancer 2021 Apr 9. Epub 2021 Apr 9.

Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Metastatic melanoma is the most aggressive skin cancer and associated with a poor prognosis. In clinical terms, targeted therapy is one of the most important treatments for patients with BRAF -mutated advanced melanoma. However, the development of resistance to this treatment compromises its therapeutic success. Read More

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Neuroendocrine control of appetite and metabolism.

Exp Mol Med 2021 Apr 9. Epub 2021 Apr 9.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

Body homeostasis is predominantly controlled by hormones secreted by endocrine organs. The central nervous system contains several important endocrine structures, including the hypothalamic-pituitary axis. Conventionally, neurohormones released by the hypothalamus and the pituitary gland (hypophysis) have received much attention owing to the unique functions of the end hormones released by their target peripheral organs (e. Read More

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Mapping the regulatory landscape of auditory hair cells from single-cell multi-omics data.

Genome Res 2021 Apr 9. Epub 2021 Apr 9.

University of Michigan, Kresge Hearing Research Institute;

Auditory hair cells transduce sound to the brain and in mammals these cells reside together with supporting cells in the sensory epithelium of the cochlea, called the organ of Corti. To establish the organ's delicate function during development and differentiation, spatiotemporal gene expression is strictly controlled by chromatin accessibility and cell type-specific transcription factors, jointly representing the regulatory landscape. Bulk-sequencing technology and cellular heterogeneity obscured investigations on the interplay between transcription factors and chromatin accessibility in inner ear development. Read More

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A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling.

Mol Cancer 2021 Apr 9;20(1):66. Epub 2021 Apr 9.

Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People's Republic of China.

Background: A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development of diseases through many mechanisms. The MAPK pathway is a common signal transduction pathway involved in cell proliferation, inflammation and apoptosis and plays a particularly important role in cancers. However, the role of circRNAs related to the MAPK pathway in gastric cancer has not been explored. Read More

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Cytonuclear Estrogen Receptor Alpha Regulates Proliferation and Migration of Endometrial Carcinoma Cells.

Tokai J Exp Clin Med 2021 Apr 20;46(1):7-16. Epub 2021 Apr 20.

Department of Anatomy, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.

Objective: The effects of estrogen on cells are mediated by the estrogen receptor α (ERα) which localizes at the peri-membrane, cytoplasm, and the nucleus of cells. Therefore, we intended to investigate how cytonuclear ERα plays its roles in different cellular activities.

Methods: We used amino acid substituted ERα that localized at the cytoplasm and nucleus but has no direct DNA-binding activities. Read More

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Vitamin D in follicular development and oocyte maturation.

Reproduction 2021 Apr 1. Epub 2021 Apr 1.

J Xu, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, United States.

Vitamin D (VD) is a secosteroid hormone synthesized predominantly in the skin upon ultraviolet light exposure, which can also be obtained from dietary sources. In target cells, the bioactive VD binds to specific VD receptor to regulate downstream transcription of genes that are involved in a wide range of cellular processes. There is increasing recognition that the proper physiological levels of VD are critical for optimizing reproductive potential in women. Read More

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LncRNA PWAR6 regulates proliferation and migration by epigenetically silencing YAP1 in tumorigenesis of pancreatic ductal adenocarcinoma.

J Cell Mol Med 2021 Apr 8. Epub 2021 Apr 8.

Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Long non-coding RNAs (lncRNAs) are a novel class of regulators in multiple cancer biological processes. However, the functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. In this study, we identified PWAR6 as a frequently down-regulated lncRNA in PDAC samples as well as a panel of pancreatic cancer cell lines. Read More

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Sirt-1 Regulates Physiological Process and Exerts Protective Effects against Oxidative Stress.

Biomed Res Int 2021 23;2021:5542545. Epub 2021 Mar 23.

Department of Nuclear Medicine, General Hospital of Ningxia Medical University, Ningxia, Ningxia Hui Autonomous Region, China 750004.

Background: Recent studies suggest a correlation between the reduced Sirt-1 expression with Alzheimer's diseases (AD) and depression, respectively, suggesting a possible pathogenic role of the altered Sirt-1 expression in neuronal degenerative diseases, such as AD and depression. However, the molecular mechanisms underlying how Sirt-1 reduction impairs neuronal functions remain unknown.

Methods: We used the SK-N-SH neuroblastoma cells to study the role of Sirt-1 expression on physiological roles in neuronal cells. Read More

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Repurposing cabozantinib with therapeutic potential in KIT-driven t(8;21) acute myeloid leukaemias.

Cancer Gene Ther 2021 Apr 8. Epub 2021 Apr 8.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

Cabozantinib is an orally available, multi-target tyrosine kinase inhibitor approved for the treatment of several solid tumours and known to inhibit KIT tyrosine kinase. In acute myeloid leukaemia (AML), aberrant KIT tyrosine kinase often coexists with t(8;21) to drive leukaemogenesis. Here we evaluated the potential therapeutic effect of cabozantinib on a selected AML subtype characterised by t(8;21) coupled with KIT mutation. Read More

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Temporal multiomic modeling reveals a B-cell receptor proliferative program in chronic lymphocytic leukemia.

Leukemia 2021 Apr 8. Epub 2021 Apr 8.

Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR-S1109, LabEx Transplantex, Plateforme Genomax, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.

B-cell receptor (BCR) signaling is crucial for the pathophysiology of most mature B-cell lymphomas/leukemias and has emerged as a therapeutic target whose effectiveness remains limited by the occurrence of mutations. Therefore, deciphering the cellular program activated downstream this pathway has become of paramount importance for the development of innovative therapies. Using an original ex vivo model of BCR-induced proliferation of chronic lymphocytic leukemia cells, we generated 108 temporal transcriptional and proteomic profiles from 1 h up to 4 days after BCR activation. Read More

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