14,677 results match your criteria reduced signalling

Effects of canagliflozin on human myocardial redox signalling: clinical implications.

Eur Heart J 2021 Jul 19. Epub 2021 Jul 19.

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, L6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.

Aims: Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in heart failure patients, but the underlying mechanisms remain unknown. We explored the direct effects of canagliflozin, an SGLT2 inhibitor with mild SGLT1 inhibitory effects, on myocardial redox signalling in humans.

Methods And Results: Study 1 included 364 patients undergoing cardiac surgery. Read More

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Airway monocyte modulation relates to tumour necrosis factor dysregulation in neutrophilic asthma.

ERJ Open Res 2021 Jul 19;7(3). Epub 2021 Jul 19.

Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, NSW, Australia.

Background: Dysregulation of tumour necrosis factor-α (TNF-α) signalling is implicated in neutrophilic asthma. TNF-α signalling involves membrane-bound and soluble ligand (TNF-α) and receptors (TNFRs); however, little is known about how these proteins are altered in asthma. We hypothesised that intercompartment-, immune cell- and/or asthma inflammatory phenotype-dependent regulation could relate to TNF dysregulation in neutrophilic asthma. Read More

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Reduced neutrophil elastase inhibitor elafin and elevated transforming growth factor-β are linked to inflammatory response in sputum of cystic fibrosis patients with .

ERJ Open Res 2021 Jul 19;7(3). Epub 2021 Jul 19.

CF Center, Children's Hospital, Faculty of Medicine, University of Cologne, Cologne, Germany.

Research Question: Pulmonary disease progression in patients with cystic fibrosis (CF) is characterised by inflammation and fibrosis and aggravated by (Pa). We investigated the impact of Pa specifically on: 1) protease/antiprotease balance; 2) inflammation; and 3) the link of both parameters to clinical parameters of CF patients.

Methods: Transforming growth factor-β (TGF-β), interleukin (IL)-1β, IL-8, neutrophil elastase (NE) and elastase inhibitor elafin were measured (ELISA assays), and gene expression of the NF-κB pathway was assessed (reverse transcriptase PCR) in the sputum of 60 CF patients with a minimum age of 5 years. Read More

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Minocycline Treatment Reduces Mass and Force Output From Fast-Twitch Mouse Muscles and Inhibits Myosin Production in C2C12 Myotubes.

Front Physiol 2021 5;12:696039. Epub 2021 Jul 5.

School of Medicine, Western Sydney University, Sydney, NSW, Australia.

Minocycline, a tetracycline-class of antibiotic, has been tested with mixed effectiveness on neuromuscular disorders such as amyotrophic lateral sclerosis, autoimmune neuritis and muscular dystrophy. The independent effect of minocycline on skeletal muscle force production and signalling remain poorly understood. Our aim here is to investigate the effects of minocycline on muscle mass, force production, myosin heavy chain abundance and protein synthesis. Read More

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Tonic prime-boost of STING signalling mediates Niemann-Pick disease type C.

Nature 2021 Jul 21. Epub 2021 Jul 21.

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

The classic mode of STING activation is through binding the cyclic dinucleotide 2'3'-cyclic GMP-AMP (cGAMP), produced by the DNA sensor cyclic GMP-AMP synthase (cGAS), which is important for the innate immune response to microbial infection and autoimmune disease. Modes of STING activation that are independent of cGAS are much less well understood. Here, through a spatiotemporally resolved proximity labelling screen followed by quantitative proteomics, we identify the lysosomal membrane protein Niemann-Pick type C1 (NPC1) as a cofactor in the trafficking of STING. Read More

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Trophoblast derived extracellular vesicles specifically alter the transcriptome of endometrial cells and may constitute a critical component of embryo-maternal communication.

Reprod Biol Endocrinol 2021 Jul 21;19(1):115. Epub 2021 Jul 21.

Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, Faculty of Medicine, Tartu University, Tartu, Estonia.

Background: The period of time when the embryo and the endometrium undergo significant morphological alterations to facilitate a successful implantation-known as "window of implantation"-is a critical moment in human reproduction. Embryo and the endometrium communicate extensively during this period, and lipid bilayer bound nanoscale extracellular vesicles (EVs) are purported to be integral to this communication.

Methods: To investigate the nature of the EV-mediated embryo-maternal communication, we have supplemented trophoblast analogue spheroid (JAr) derived EVs to an endometrial analogue (RL 95-2) cell layer and characterized the transcriptomic alterations using RNA sequencing. Read More

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Altered redox homeostasis in steroid-depleted follicles attenuates hCG regulation of follicular events: Cross-talk between endocrine and IGF axis in maturing oocytes.

Free Radic Biol Med 2021 Jul 18;172:675-687. Epub 2021 Jul 18.

Molecular and Cellular Endocrinology Laboratory, Department of Zoology, Visva-Bharati University, Santiniketan, 731235, India. Electronic address:

Steroids and insulin-like growth factors (Igfs) are indispensable for folliculogenesis and reproductive fitness in the vertebrate ovary. The intrafollicular redox balance is also of immense importance for ovarian follicles wherein low levels of ROS are being utilized for cell signalling and regulation of gene expression; its excess may interfere with normal physiological processes leading to ovotoxicity. However, the functional relevance of ovarian steroidogenesis in maintaining the follicular microenvironment with coordinated redox homeostasis and intra-ovarian growth factors axis is relatively less understood. Read More

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Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling.

J Cell Sci 2021 Jul 21. Epub 2021 Jul 21.

Leeds Institute for Medical Research, University of Leeds School of Medicine, St. James's University Hospital, Leeds LS8 2BH, UK.

Metastasis requires tumour cells to cross endothelial cell (EC) barriers using pathways similar to those used by leucocytes during inflammation. Cell surface CD99 is expressed by healthy leucocytes and EC and participates in inflammatory transendothelial migration (TEM). Tumour cells also express CD99 and we have analysed its role in tumour progression and cancer cell TEM. Read More

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CaMKII and Ca3.2 T-type calcium channel mediate Connexin-43-dependent inflammation by activating astrocytes in vincristine-induced neuropathic pain.

Cell Biol Toxicol 2021 Jul 20. Epub 2021 Jul 20.

School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.

Vincristine (VCR), an alkaloid isolated from vinca, is a commonly used chemotherapeutic drug. However, VCR therapy can lead to dose-dependent peripheral neurotoxicity, mainly manifesting as neuropathic pain, which is one of the dominant reasons for limiting its utility. Experimentally, we discovered that VCR-induced neuropathic pain (VINP) was accompanied by astrocyte activation; the upregulation of phospho-CaMKII (p-CaMKII), Ca3. Read More

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Study on the effect of shikonin on CD36 expression and phagocytic ability of microglia in the isolated cerebral haemorrhage model.

Folia Neuropathol 2021 ;59(2):198-204

Department of Neurosurgery, Yuyao People's Hospital, Yuyao, Zhejiang Province, China.

Aim Of The Study: To investigate the effects of shikonin on CD36 expression and phagocytic ability of microglia, and its protective effect on neurons and the possible mechanism within.

Material And Methods: The effects of shikonin on CD36 expression and phagocytic ability of microglia were detected by Western blot method, and cerebral haemorrhage was isolated by flow cytometry in the experiment. The protective effect of neurons was observed through neuron-microglia co-culture technique. Read More

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January 2021

Changes in Stem Cell Regulation and Epithelial Organisation during Carcinogenesis and Disease Progression in Gynaecological Malignancies.

Cancers (Basel) 2021 Jul 3;13(13). Epub 2021 Jul 3.

Department of Obstetrics and Gynaecology, University Hospital, LMU Munich, Marchioninistr 15, 81377 Munich, Germany.

Gynaecological malignancies represent a heterogeneous group of neoplasms with vastly different aetiology, risk factors, molecular drivers, and disease outcomes. From HPV-driven cervical cancer where early screening and molecular diagnostics efficiently reduced the number of advanced-stage diagnosis, prevalent and relatively well-treated endometrial cancers, to highly aggressive and mostly lethal high-grade serous ovarian cancer, malignancies of the female genital tract have unique presentations and distinct cell biology features. Recent discoveries of stem cell regulatory mechanisms, development of organoid cultures, and NGS analysis have provided valuable insights into the basic biology of these cancers that could help advance new-targeted therapeutic approaches. Read More

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A Reversible Low Frequency Alternating Current Nerve Conduction Block Applied to Mammalian Autonomic Nerves.

Sensors (Basel) 2021 Jul 1;21(13). Epub 2021 Jul 1.

Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.

Electrical stimulation can be used to modulate activity within the nervous system in one of two modes: (1) Activation, where activity is added to the neural signalling pathways, or (2) Block, where activity in the nerve is reduced or eliminated. In principle, electrical nerve conduction block has many attractive properties compared to pharmaceutical or surgical interventions. These include reversibility, localization, and tunability for nerve caliber and type. Read More

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Roles of MicroRNAs in Osteogenesis or Adipogenesis Differentiation of Bone Marrow Stromal Progenitor Cells.

Int J Mol Sci 2021 Jul 5;22(13). Epub 2021 Jul 5.

UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.

Bone marrow stromal cells (BMSCs) are multipotent cells which can differentiate into chondrocytes, osteoblasts, and fat cells. Under pathological stress, reduced bone formation in favour of fat formation in the bone marrow has been observed through a switch in the differentiation of BMSCs. The bone/fat switch causes bone growth defects and disordered bone metabolism in bone marrow, for which the mechanisms remain unclear, and treatments are lacking. Read More

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Maternal immune activation in rodent models: A systematic review of neurodevelopmental changes in gene expression and epigenetic modulation in the offspring brain.

Neurosci Biobehav Rev 2021 Jul 16. Epub 2021 Jul 16.

Division of Evolution & Genomic Sciences, School of Biological Sciences, Manchester Academic Health Science Center, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, M13 9PT, United Kingdom.

Maternal immune activation (mIA) during pregnancy is hypothesised to disrupt offspring neurodevelopment and predispose offspring to neurodevelopmental disorders such as schizophrenia. Rodent models of mIA have explored possible mechanisms underlying this paradigm and provide a vital tool for preclinical research. However, a comprehensive analysis of the molecular changes that occur in mIA-models is lacking, hindering identification of robust clinical targets. Read More

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Heparin impairs skeletal muscle glucose uptake by inhibiting insulin binding to insulin receptor.

Endocrinol Diabetes Metab 2021 Jul 5;4(3):e00253. Epub 2021 May 5.

Guangdong Laboratory of Lingnan Modern Agriculture Guangdong Province Key Laboratory of Animal Nutritional Regulation and National Engineering Research Center for Breeding Swine Industry College of Animal Science South China Agricultural University Guangzhou China.

Aim: Heparin, a widely used antithrombotic drug has many other anticoagulant-independent physiological functions. Here, we elucidate a novel role of heparin in glucose homeostasis, suggesting an approach for developing heparin-targeted therapies for diabetes.

Methods: For serum heparin levels and correlation analysis, 122 volunteer's plasma, DIO (4 weeks HFD) and db/db mice serums were collected and used for spectrophotometric determination. Read More

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YAP Promotes Cell Proliferation and Epithelium-Derived Cytokine Expression via NF-κB Pathway in Nasal Polyps.

J Asthma Allergy 2021 9;14:839-850. Epub 2021 Jul 9.

Department of Otorhinolaryngology-Head and Neck Surgery, Department of Allergy, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and inflammation development in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the underlying mechanisms remain unclear.

Objective: This study intends to investigate the role of YAP and the nuclear factor kappa-B (NF-κB) pathway in cell proliferation and the expression of epithelium-derived cytokines in nasal polyps (NP). Read More

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Effects of Androgen Receptor Overexpression on Chondrogenic Ability of Rabbit Articular Chondrocytes.

Tissue Eng Regen Med 2021 Jul 18. Epub 2021 Jul 18.

College and Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.

Background: The role of sex hormones and their receptors has drawn much attention in the process of cartilage regeneration. This study aimed to investigate the effect of androgen receptor (AR) on the chondrogenic ability of articular chondrocytes and the related mechanism.

Methods: Articular chondrocytes were isolated, cultured, identified by toluidine blue staining and then transduced with lentivirus carrying the AR gene. Read More

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Chloroplast calcium signalling regulates thermomemory.

J Plant Physiol 2021 Jul 8;264:153470. Epub 2021 Jul 8.

Department of Biosciences, Durham University, South Road, Durham, DH1 3LE, UK. Electronic address:

After an episode of heat stress plants retain a cellular "memory" of this event, a phenomenon known as thermomemory. This mechanism allows plants to better cope against a subsequent heat event. Thermomemory occurs through the persistence of heat shock proteins (HSPs) synthesized after the first "priming" event. Read More

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Excessive endoplasmic reticulum stress drives aberrant mouse trophoblast differentiation and placental development leading to pregnancy loss.

J Physiol 2021 Jul 16. Epub 2021 Jul 16.

Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.

Endoplasmic reticulum (ER) stress promotes placental dysmorphogenesis and is associated with poor pregnancy outcomes. We show that unfolded protein response signalling pathways located in the ER drive differentiation of mouse trophoblast stem cells into trophoblast subtypes involved in development of the placental labyrinth zone and trophoblast invasion. In a mouse model of chronic ER stress (Eif2s1 ), higher ER stress in homozygous blastocysts is accompanied by reduced trophectoderm cell number, developmental delay, and is associated with an increased incidence of early pregnancy loss. Read More

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Exogenous insulin-like growth factor 1 attenuates cisplatin-induced muscle atrophy in mice.

J Cachexia Sarcopenia Muscle 2021 Jul 16. Epub 2021 Jul 16.

Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.

Background: A reduction in the skeletal muscle mass worsens the prognosis of patients with various cancers. Our previous studies indicated that cisplatin administration to mice caused muscle atrophy. This is a concern for human patients receiving cisplatin. Read More

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The effect of IL-2 stimulation and treatment of TRPM3 on channel co-localisation with PIP and NK cell function in myalgic encephalomyelitis/chronic fatigue syndrome patients.

J Transl Med 2021 Jul 15;19(1):306. Epub 2021 Jul 15.

National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious multifactorial disorder. The origin remains ambiguous, however reduced natural killer (NK) cell cytotoxicity is a consistent immunological feature of ME/CFS. Impaired transient receptor potential melastatin 3 (TRPM3), a phosphatidylinositol dependent channel, and impaired calcium mobilisation have been implicated in ME/CFS pathology. Read More

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RUNX1T1, a potential prognostic marker in breast cancer, is co-ordinately expressed with ERα, and regulated by estrogen receptor signalling in breast cancer cells.

Mol Biol Rep 2021 Jul 15. Epub 2021 Jul 15.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India.

Background: RUNX1T1 is extensively studied in the context of AML1-RUNX1T1 fusion protein in acute myeloid leukemia. Little is known about the function of RUNX1T1 itself, although data on its function and regulation have begun to emerge from clinical, and in vitro studies. It is a putative tumor suppressor, whose expression is altered in a variety of solid tumors. Read More

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Exogenous melatonin-mediated regulation of K /Na transport, H -ATPase activity and enzymatic antioxidative defence operate through endogenous hydrogen sulphide signalling in NaCl-stressed tomato seedling roots.

Plant Biol (Stuttg) 2021 Jul 15. Epub 2021 Jul 15.

Department of Biology, Faculty of Science and Humanities, Quwayiyah, Shaqra University, Shaqra, Saudi Arabia.

Melatonin (Mel) and hydrogen sulphide (H S) have emerged as potential regulators of plant metabolism during abiotic stress. Presence of excess NaCl in the soil is one of the main causes of reduced crop productivity worldwide. The present investigation examines the role of exogenous Mel and endogenous H S in tomato seedlings grown under NaCl stress. Read More

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Epigenetic reprogramming enhances the therapeutic efficacy of osteoblast-derived extracellular vesicles to promote human bone marrow stem cell osteogenic differentiation.

J Extracell Vesicles 2021 Jul 7;10(9):e12118. Epub 2021 Jul 7.

School of Chemical Engineering University of Birmingham Birmingham UK.

Extracellular vesicles (EVs) are emerging in tissue engineering as promising acellular tools, circumventing many of the limitations associated with cell-based therapies. Epigenetic regulation through histone deacetylase (HDAC) inhibition has been shown to increase differentiation capacity. Therefore, this study aimed to investigate the potential of augmenting osteoblast epigenetic functionality using the HDAC inhibitor Trichostatin A (TSA) to enhance the therapeutic efficacy of osteoblast-derived EVs for bone regeneration. Read More

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Dynamics of dark fermentation microbial communities in the light of lactate and butyrate production.

Microbiome 2021 07 14;9(1):158. Epub 2021 Jul 14.

Institute of Biochemistry and Biophysics - Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland.

Background: This study focuses on the processes occurring during the acidogenic step of anaerobic digestion, especially resulting from nutritional interactions between dark fermentation (DF) bacteria and lactic acid bacteria (LAB). Previously, we have confirmed that DF microbial communities (MCs) that fed on molasses are able to convert lactate and acetate to butyrate. The aims of the study were to recognize the biodiversity of DF-MCs able and unable to convert lactate and acetate to butyrate and to define the conditions for the transformation. Read More

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Fibrous Caps in Atherosclerosis Form by Notch-Dependent Mechanisms Common to Arterial Media Development.

Arterioscler Thromb Vasc Biol 2021 Jul 15:ATVBAHA120315627. Epub 2021 Jul 15.

Experimental Pathology of Atherosclerosis Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain (C.J.M.-R., D.M.-C., A.C., L.C., J.F.B.).

Objective: Atheromatous fibrous caps are produced by smooth muscle cells (SMCs) that are recruited to the subendothelial space. We tested whether the recruitment mechanisms are the same as in embryonic artery development, which relies prominently on Notch signaling to form the subendothelial medial SMC layers. Approach and Results: Notch elements were expressed in regions of fibrous cap in human and mouse plaques. Read More

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COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes.

PLoS Pathog 2021 Jul 14;17(7):e1009753. Epub 2021 Jul 14.

Sainte-Justine University Hospital Research Centre, Montréal, Québec, Canada.

To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Read More

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Resveratrol Protects SH-SY5Y Cells Against Oleic Acid-Induced Glucolipid Metabolic Dysfunction and Cell Injuries Via the Wnt/β-Catenin Signalling Pathway.

Neurochem Res 2021 Jul 14. Epub 2021 Jul 14.

School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, 230032, Anhui, China.

Resveratrol (RES) is a polyphenol with diverse beneficial biological and pharmacological activities, and our previous results have demonstrated its neuroprotective effects in several metabolic diseases, including non-alcoholic fatty liver disease. The aim of the present study is to investigate the potential effect of RES against oleic acid (OA)-induced cell injuries in SH-SY5Y cells and explore the possible mechanism. Based on the dose- and time-dependent effects of OA on cell proliferation and LDH release, SH-SY5Y cells were challenged with OA and incubated with or without RES (10-10 mM) or sitagliptin (STG, 10 mM). Read More

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Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway.

Stem Cell Res Ther 2021 Jul 13;12(1):390. Epub 2021 Jul 13.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a common, progressive, and refractory orthopaedic disease. Decreased osteogenesis and angiogenesis are considered the main factors in the pathogenesis of NONFH. We aimed to figure out whether exosomes and exosomal miRNA from necrotic bone tissues of patients with NONFH are involved in the pathogenesis of NONFH and reveal the underlying mechanisms. Read More

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Volatile oil of sensitizes colon cancer cells to TRAIL-induced cell death.

Front Biosci (Schol Ed) 2021 06;13(1):1-13

Laboratory of Biochemistry and Molecular Biology, Faculty of Sciences of Bizerte, University of Carthage, Tunisia.

TNF-related apoptosis-inducing ligand (TRAIL/Apo2L), a member of cytokine family, is known to selectively induce apoptosis in cancer cells. However, developing resistance to TRAIL is a major obstacle in cancer therapy. In this study, the effect of (TA) essential oil on inhibition of cancer cell growth and enhancing TRAIL-induced apoptosis were investigated in colon cancer cells. Read More

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