4,203 results match your criteria phenotype blocking

Transcriptome and plant hormone analyses provide new insight into the molecular regulatory networks underlying hybrid lethality in cabbage (Brassica oleracea).

Planta 2021 Apr 11;253(5):96. Epub 2021 Apr 11.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Ministry of Agriculture, 12# Zhongguancun Nandajie Street, Beijing, 100081, China.

Main Conclusion: Comparative morphological, transcriptomic and phytohormone analyses reveal a defence network leading to PCD involved in cabbage hybrid lethality. Hybrid lethality (HL) plays an essential role in the stability of a population by blocking gene exchange between species, but the molecular mechanism remains largely undetermined. In this study, we performed phenotype, transcriptome and plant hormone analyses of HL in cabbage. Read More

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Flavonols modulate lateral root emergence by scavenging reactive oxygen species in Arabidopsis thaliana.

J Biol Chem 2020 Dec 25;296:100222. Epub 2020 Dec 25.

Biology Department, Wake Forest University, Winston Salem, North Carolina, USA. Electronic address:

Flavonoids are a class of specialized metabolites with subclasses including flavonols and anthocyanins, which have unique properties as antioxidants. Flavonoids modulate plant development, but whether and how they impact lateral root development is unclear. We examined potential roles for flavonols in this process using Arabidopsis thaliana mutants with defects in genes encoding key enzymes in flavonoid biosynthesis. Read More

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December 2020

CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.

Immunology 2021 Apr 10. Epub 2021 Apr 10.

Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP, Cambridge, UK.

CD4 regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, contribute to tumour immunosuppression but are also required for immune homeostasis. There is interest in developing therapies that selectively target the immunosuppressive function of Treg cells within tumours without disrupting their systemic anti-inflammatory function. High levels of expression of Chemokine (C-C motif) receptor 8 (CCR8) discriminate Treg cells within tumours from those found in systemic lymphoid tissues. Read More

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Type I interferon activation and endothelial dysfunction in caveolin-1 insufficiency-associated pulmonary arterial hypertension.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD 20892.

Interferonopathies, interferon (IFN)-α/β therapy, and caveolin-1 (CAV1) loss-of-function have all been associated with pulmonary arterial hypertension (PAH). Here, CAV1-silenced primary human pulmonary artery endothelial cells (PAECs) were proliferative and hypermigratory, with reduced cytoskeletal stress fibers. Signal transducers and activators of transcription (STAT) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) were both constitutively activated in these cells, resulting in a type I IFN-biased inflammatory signature. Read More

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Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia.

Nat Genet 2021 Apr 8. Epub 2021 Apr 8.

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Transposable elements or transposons are major players in genetic variability and genome evolution. Aberrant activation of long interspersed element-1 (LINE-1 or L1) retrotransposons is common in human cancers, yet their tumor-type-specific functions are poorly characterized. We identified MPHOSPH8/MPP8, a component of the human silencing hub (HUSH) complex, as an acute myeloid leukemia (AML)-selective dependency by epigenetic regulator-focused CRISPR screening. Read More

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Absence of TNF Leads to Alternative Activation in Peritoneal Macrophages in Experimental Listeria Monocytogenes Infection.

Immunol Invest 2021 Apr 8:1-18. Epub 2021 Apr 8.

School of Life Sciences, Anhui Medical University, Hefei, China.

Macrophages are crucial effectors of innate immunity against the pathogenic bacterium . The pro-inflammatory cytokine tumour necrosis factor-α (TNF) has been shown to be crucial for resistance to and mice deficient in TNF signalling succumb quickly after infection. However, the mechanisms underlying TNF-mediated defence against infection have not been completely elucidated. Read More

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Deficiency of TMEM53 causes a previously unknown sclerosing bone disorder by dysregulation of BMP-SMAD signaling.

Nat Commun 2021 04 6;12(1):2046. Epub 2021 Apr 6.

Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.

Bone formation represents a heritable trait regulated by many signals and complex mechanisms. Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). Exploration of genes that cause SBD has significantly improved our understanding of the mechanisms that regulate bone formation. Read More

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Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling.

J Exp Clin Cancer Res 2021 Apr 6;40(1):120. Epub 2021 Apr 6.

Third Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Background: Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood. Read More

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Vaginal Epithelium Transiently Harbours HIV-1 Facilitating Transmission.

Front Cell Infect Microbiol 2021 17;11:634647. Epub 2021 Mar 17.

Department of Biochemistry and Virology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai, India.

Vaginal transmission accounts for majority of newly acquired HIV infections worldwide. Initial events that transpire post-viral binding to vaginal epithelium leading to productive infection in the female reproductive tract are not well elucidated. Here, we examined the interaction of HIV-1 with vaginal epithelial cells (VEC) using Vk2/E6E7, an established cell line exhibiting an HIV-binding receptor phenotype (CD4-CCR5-CD206+) similar to primary cells. Read More

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Tideglusib suppresses stem-cell-like features and progression of osteosarcoma by inhibiting GSK-3β/NOTCH1 signaling.

Biochem Biophys Res Commun 2021 Apr 1;554:206-213. Epub 2021 Apr 1.

Department of Oncology, The First Affiliated Hospital of Henan University of Chinese Medicine, 19 Renmin Road, Zhengzhou, 450000, China. Electronic address:

Osteosarcoma is the most common primary bone tumor in children, teenagers and adolescents. Cancer stem cells (CSCs) have the function to self-renew and keep the phenotype of tumor, causing clinical treatment failure. Therefore, developing effective therapies to inhibit osteosarcoma progression is urgently necessary. Read More

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NGBR is required to ameliorate type 2 diabetes in mice by enhancing insulin sensitivity.

J Biol Chem 2021 Apr 1:100624. Epub 2021 Apr 1.

Key Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address:

The reduction of insulin resistance or improvement of insulin sensitivity is the most effective treatment for type 2 diabetes (T2D). We previously reported that Nogo-B receptor (NGBR), encoded by the NUS1 gene, is required for attenuating hepatic lipogenesis by blocking nuclear translocation of liver X receptor alpha, suggesting its important role in regulating hepatic lipid metabolism. Herein, we demonstrate that NGBR expression was decreased in liver of obesity-associated T2D patients and db/db mice. Read More

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Asthma and Chronic Rhinosinusitis: How Similar Are They in Pathogenesis and Treatment Responses?

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Immunoallergology Unit, University Hospital Careggi, 50134 Florence, Italy.

Severe asthma and rhinosinusitis represent frequent comorbidities, complicating the overall management of the disease. Both asthma and chronic rhinosinusitis (CRS) can be differentiated into endotypes: those with type 2 eosinophilic inflammation and those with a non-type 2 inflammation. A correct definition of phenotype/endotype for these diseases is crucial, taking into account the availability of novel biological therapies. Read More

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An SNX10-dependent mechanism down-regulates fusion between mature osteoclasts.

J Cell Sci 2021 04 1. Epub 2021 Apr 1.

Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel

Homozygosity for the R51Q mutation in sorting nexin 10 (SNX10) inactivates osteoclasts (OCLs) and induces autosomal recessive osteopetrosis in humans and in mice. We show here that fusion of wild-type murine monocytes to form OCLs is highly regulated, and that its extent is limited by blocking fusion between mature OCLs. In contrast, monocytes from homozygous R51Q SNX10 mice fuse uncontrollably, forming giant dysfunctional OCLs that can become 10-100 fold larger than their wild-type counterparts. Read More

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Gene expression profiles of diabetic kidney disease and neuropathy in eNOS knockout mice: Predictors of pathology and RAS blockade effects.

FASEB J 2021 May;35(5):e21467

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are two common diabetic complications. However, their pathogenesis remains elusive and current therapies are only modestly effective. We evaluated genome-wide expression to identify pathways involved in DKD and DPN progression in db/db eNOS-/- mice receiving renin-angiotensin-aldosterone system (RAS)-blocking drugs to mimic the current standard of care for DKD patients. Read More

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Macrophage activation status rather than repolarization is associated with enhanced checkpoint activity in combination with PI3Kg inhibition.

Mol Cancer Ther 2021 Mar 30. Epub 2021 Mar 30.

Bioscience, Oncology, IMED Biotech Unit, AstraZeneca (United Kingdom).

Suppressive myeloid cells mediate resistance to immune checkpoint blockade. PI3Kg inhibition can target suppressive macrophages, and enhance efficacy of immune checkpoint inhibitors. However how PI3Kg inhibitors function in different tumor environments (TME) to activate specific immune cells is underexplored. Read More

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Biological functions of therapy-induced senescence in cancer.

Semin Cancer Biol 2021 Mar 26. Epub 2021 Mar 26.

European Research Institute for the Biology of Ageing, University Medical Center Groningen, 9713AV, Groningen, The Netherlands. Electronic address:

Therapy-induced cellular senescence is a state of stable growth arrest induced by common cancer treatments such as chemotherapy and radiation. In an oncogenic context, therapy-induced senescence can have different consequences. By blocking cellular proliferation and by facilitating immune cell infiltration, it functions as tumor suppressive mechanism. Read More

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Chronic adrenergic stress contributes to metabolic dysfunction and an exhausted phenotype in T cells in the tumor microenvironment.

Cancer Immunol Res 2021 Mar 24. Epub 2021 Mar 24.

Immunology, Roswell Park Comprehensive Cancer Center

Metabolic dysfunction and exhaustion in tumor-infiltrating T cells have been linked to ineffectual anti-tumor immunity and the failure of immune checkpoint inhibitor therapy. We report here that chronic stress plays a previously unrecognized role in regulating the state of T cells in the tumor microenvironment (TME). Using two mouse tumor models, we found that blocking chronic adrenergic stress signaling using the pan β-blocker propranolol or by using mice lacking the β2-adrenergic receptor (β2-AR), results in reduced tumor growth rates with significantly fewer infiltrating T cells that express markers of exhaustion, with a concomitant increase in progenitor exhausted T cells. Read More

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CD52 regulates monocyte adhesion and interferon type I signalling in systemic sclerosis patients.

Arthritis Rheumatol 2021 Mar 24. Epub 2021 Mar 24.

Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Objectives: Systemic sclerosis (SSc) is characterised by dysregulation of type I interferon (IFN-I) signalling. CD52 is known for its immunosuppressive functions in T-cells. We aimed to investigate the role of CD52 in monocyte adhesion and IFN-I signalling in SSc. Read More

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Inhibition of the Notch signaling pathway attenuates progression of cell motility, metastasis, and epithelial-to-mesenchymal transition-like phenomena induced by low concentrations of cisplatin in osteosarcoma.

Eur J Pharmacol 2021 Mar 21;899:174058. Epub 2021 Mar 21.

Department of Trauma Surgery, Wuhan No. 1 Hospital, Wuhan, 430022, Hubei, China.

Although advances in osteosarcoma treatment have been made in recent decades, the survival rate for patients suffering from metastatic disease, especially lung metastasis, remains disappointing. Previous studies have confirmed that epithelial-to-mesenchymal transition (EMT) is associated with tumor metastasis, and several studies have suggested that osteosarcoma cells also exhibit EMT-like characteristics. In addition, Notch signaling is known to be related to the development and progression of human malignancies, including osteosarcoma. Read More

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Myocardin-related transcription factor A (MRTF-A) regulates integrin beta 2 transcription to promote macrophage infiltration and cardiac hypertrophy in mice.

Cardiovasc Res 2021 Mar 22. Epub 2021 Mar 22.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.

Aims: Macrophage-mediated inflammatory response represents a key pathophysiological process in a host of cardiovascular diseases including heart failure. Regardless of etiology, heart failure is invariably preceded by cardiac hypertrophy. In the present study we investigated the effect of macrophage-specific deletion of myocardin-related transcription factor A (MRTF-A) on cardiac hypertrophy and the underlying mechanism. Read More

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Shaping the BRCAness mutational landscape by alternative double-strand break repair, replication stress and mitotic aberrancies.

Nucleic Acids Res 2021 Mar 21. Epub 2021 Mar 21.

Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands.

Tumours with mutations in the BRCA1/BRCA2 genes have impaired double-stranded DNA break repair, compromised replication fork protection and increased sensitivity to replication blocking agents, a phenotype collectively known as 'BRCAness'. Tumours with a BRCAness phenotype become dependent on alternative repair pathways that are error-prone and introduce specific patterns of somatic mutations across the genome. The increasing availability of next-generation sequencing data of tumour samples has enabled identification of distinct mutational signatures associated with BRCAness. Read More

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Potassium (K) channels in the pulmonary vasculature: Implications in pulmonary hypertension Physiological, pathophysiological and pharmacological regulation.

Pharmacol Ther 2021 Mar 18;225:107835. Epub 2021 Mar 18.

Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Spain. Electronic address:

The large K channel functional diversity in the pulmonary vasculature results from the multitude of genes expressed encoding K channels, alternative RNA splicing, the post-transcriptional modifications, the presence of homomeric or heteromeric assemblies of the pore-forming α-subunits and the existence of accessory β-subunits modulating the functional properties of the channel. K channels can also be regulated at multiple levels by different factors controlling channel activity, trafficking, recycling and degradation. The activity of these channels is the primary determinant of membrane potential (Em) in pulmonary artery smooth muscle cells (PASMC), providing an essential regulatory mechanism to dilate or contract pulmonary arteries (PA). Read More

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The Red Blood Cell as a Novel Regulator of Human B-cell Activation.

Immunology 2021 Mar 17. Epub 2021 Mar 17.

Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.

Non-immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B-cells. Separation of RBC from peripheral blood mononuclear cells increased B-cell expression of HLA-DR/DP/DQ, whilst reconstitution reduced the levels of B-cell activation markers HLA-DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Read More

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Tackling Drug Resistance in EGFR Exon 20 Insertion Mutant Lung Cancer.

Pharmgenomics Pers Med 2021 9;14:301-317. Epub 2021 Mar 9.

Division of Molecular Pathology, The Institute of Cancer Research, London, UK.

Insertion mutations in exon 20 (Ex20ins) of the epidermal growth factor receptor () gene are the largest class of mutations in non-small cell lung cancer (NSCLC) for which there are currently no approved targeted therapies. NSCLC patients with these mutations do not respond to clinically approved EGFR tyrosine kinase inhibitors (TKIs) and have poor outcomes. A number of early phase clinical trials are currently underway to evaluate the efficacy of a new generation of TKIs that are capable of binding to and blocking Ex20ins. Read More

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Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma.

Front Oncol 2021 25;11:625207. Epub 2021 Feb 25.

Department of Pharmacy and Biotechnologies, University of Bologna, Bologna, Italy.

A wide range of malignancies presents amplification (MNA) or dysregulation. is associated with poor prognosis and its over-expression leads to several dysregulations including metabolic reprogramming, mitochondria alteration, and cancer stem cell phenotype. Some hints suggest that overexpression leads to cancer immune-escape. Read More

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February 2021

Survivin drives tumor-associated macrophage reprogramming: a novel mechanism with potential impact for obesity.

Cell Oncol (Dordr) 2021 Mar 12. Epub 2021 Mar 12.

Institut d'Investigació Sanitària Pere Virgili, Endocrinology and Nutrition Service, Hospital Universitari de Tarragona Joan XXIII, 43007, Tarragona, Spain.

Purpose: Recent studies point to adipose-derived stem cells (ASCs) as a link between obesity and cancer. We aimed to determine whether survivin, which is highly secreted by ASCs from subjects with obesity, might drive a pro-tumoral phenotype in macrophages.

Methods: The effect of ASC conditioned medium on the macrophage phenotype was assessed by expression studies. Read More

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Natural killer cells efficiently target multiple myeloma clonogenic tumor cells.

Cancer Immunol Immunother 2021 Mar 10. Epub 2021 Mar 10.

Hematology Department, Hospital Universitario 12 de Octubre, Complutense University, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain.

The multiple myeloma (MM) landscape has changed in the last few years, but most patients eventually relapse because current treatment modalities do not target clonogenic stem cells, which are drug-resistant and can self-renew. We hypothesized that side population (SP) cells represent myeloma clonogenic stem cells and, searching for new treatment strategies, analyzed the anti-myeloma activity of natural killer (NK) cells against clonogenic cells. Activated and expanded NK cells (NKAE) products were obtained by co-culturing NK cells from MM patients with K562-mb15-41BBL cell line and characterized by flow cytometry. Read More

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Inhibiting the MNK1/2-eIF4E axis impairs melanoma phenotype switching and potentiates anti-tumor immune responses.

J Clin Invest 2021 Mar 9. Epub 2021 Mar 9.

Lady Davis Institute, Jewish General Hospital, Montréal, Canada.

Melanomas commonly undergo a phenotype switch, from a proliferative to an invasive state. Such tumor cell plasticity contributes to immunotherapy resistance, however, the mechanisms are not completely understood and thus therapeutically unexploited. Using melanoma mouse models, we demonstrated that blocking the MNK1/2-eIF4E axis inhibited melanoma phenotype switching and sensitized melanoma to anti-PD-1 immunotherapy. Read More

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Phenotypic, Nutritional, and Antioxidant Characterization of Blanched for Preferable Cultivar.

Front Plant Sci 2021 19;12:639639. Epub 2021 Feb 19.

The State Key Laboratory of Freshwater Ecology and Biotechnology, The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Blanching is a technique used in blocking sunlight for the production of tender, sweet, and delicious stems in the field. This technique is also used in water dropwort (), an important vegetable in East Asia. In China, the steamed stems of water dropwort are prepared with boiled rice. Read More

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February 2021

Thyroid hormones regulate goblet cell differentiation and Fgf19-Fgfr4 signaling.

Endocrinology 2021 Mar 1. Epub 2021 Mar 1.

The Faculty of Life Sciences and the Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.

Hypothyroidism is a common pathological condition that is characterized by insufficient activity of the thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), in the whole body or in specific tissues. Hypothyroidism is associated with inadequate development of the intestine as well as gastrointestinal diseases. We utilized a zebrafish model of hypothyroidism in order to identify and characterize TH-modulated genes and cellular pathways controlling intestine development. Read More

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