2,126 results match your criteria signalling aberrant

Notch Signalling in Breast Development and Cancer.

Front Cell Dev Biol 2021 6;9:692173. Epub 2021 Jul 6.

Division of Cancer Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.

The Notch signalling pathway is a highly conserved developmental signalling pathway, with vital roles in determining cell fate during embryonic development and tissue homeostasis. Aberrant Notch signalling has been implicated in many disease pathologies, including cancer. In this review, we will outline the mechanism and regulation of the Notch signalling pathway. 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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Long non-coding RNAs and microorganism-associated cancers.

Cell Biochem Funct 2021 Jul 5. Epub 2021 Jul 5.

Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

Cancerous cells are abnormal cells characterized by aberrant growth and proliferation, which can involve various types of cells and tissues. Through numerous signalling pathways, many mechanisms are involved in cells that keep them normal. These signalling pathways are tightly set by different proteins whose expression is regulated by a large number of factors. Read More

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Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Nat Commun 2021 07 5;12(1):4117. Epub 2021 Jul 5.

KU Leuven Flow & Mass Cytometry Facility, KU Leuven, Leuven, Belgium.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Read More

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Maternal Contributes to the Extra-Large G Protein α-Subunit (XLαs) Expression in a Cell Type-Specific Manner.

Front Genet 2021 17;12:680537. Epub 2021 Jun 17.

Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

encodes the stimulatory G protein alpha-subunit (Gsα) and its large variant XLαs. Studies have suggested that XLαs is expressed exclusively paternally. Thus, XLαs deficiency is considered to be responsible for certain findings in patients with paternal mutations, such as pseudo-pseudohypoparathyroidism, and the phenotypes associated with maternal uniparental disomy of chromosome 20, which comprises . Read More

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Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts.

Cell Death Dis 2021 Jul 2;12(7):662. Epub 2021 Jul 2.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Bone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Read More

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Regulation of mRNA Translation by Hormone Receptors in Breast and Prostate Cancer.

Cancers (Basel) 2021 Jun 29;13(13). Epub 2021 Jun 29.

Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA 5042, Australia.

Breast and prostate cancer are the second and third leading causes of death amongst all cancer types, respectively. Pathogenesis of these malignancies is characterised by dysregulation of sex hormone signalling pathways, mediated by the estrogen receptor-α (ER) in breast cancer and androgen receptor (AR) in prostate cancer. ER and AR are transcription factors whose aberrant function drives oncogenic transcriptional programs to promote cancer growth and progression. Read More

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3,4-Difluorobenzocurcumin Inhibits Vegfc-Vegfr3-Erk Signalling to Block Developmental Lymphangiogenesis in Zebrafish.

Pharmaceuticals (Basel) 2021 Jun 26;14(7). Epub 2021 Jun 26.

Cancer Research Malaysia, Subang Jaya 47500, Selangor, Malaysia.

Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing vasculature, plays critical roles in disease, including in cancer metastasis and chronic inflammation. Preclinical and recent clinical studies have now demonstrated therapeutic utility for several anti-lymphangiogenic agents, but optimal agents and efficacy in different settings remain to be determined. We tested the anti-lymphangiogenic property of 3,4-Difluorobenzocurcumin (CDF), which has previously been implicated as an anti-cancer agent, using zebrafish embryos and cultured vascular endothelial cells. Read More

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Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing.

Biomolecules 2021 Jun 28;11(7). Epub 2021 Jun 28.

Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark.

Cutaneous wound healing is a vital biological process that aids skin regeneration upon injury. Wound healing failure results from persistent inflammatory conditions observed in diabetes, or autoimmune diseases like psoriasis. Chronic wounds are incurable due to factors like poor oxygenation, aberrant function of peripheral sensory nervature, inadequate nutrients and blood tissue supply. Read More

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Targeting interleukin-1 for reversing fat browning and muscle wasting in infantile nephropathic cystinosis.

J Cachexia Sarcopenia Muscle 2021 Jun 30. Epub 2021 Jun 30.

Division of Pediatric Nephrology, Department of Pediatrics, Rady Children's Hospital San Diego, University of California, San Diego, La Jolla, CA, USA.

Background: Ctns mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Inflammatory cytokines such as interleukin (IL)-1 trigger inflammatory cascades and may be an important cause for cachexia. We employed genetic and pharmacological approaches to investigate the effects of IL-1 blockade in Ctns mice. Read More

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Inhibition of IL-17 prevents the progression of traumatic heterotopic ossification.

J Cell Mol Med 2021 Jun 29. Epub 2021 Jun 29.

Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.

Traumatic heterotopic ossification (HO) is the abnormal formation of bone in soft tissues as a consequence of injury. However, the pathological mechanisms leading to traumatic HO remain unknown. Here, we report that aberrant expression of IL-17 promotes traumatic HO formation by activating β-catenin signalling in mouse model. Read More

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Obesity accelerates hair thinning by stem cell-centric converging mechanisms.

Nature 2021 07 23;595(7866):266-271. Epub 2021 Jun 23.

Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

Obesity is a worldwide epidemic that predisposes individuals to many age-associated diseases, but its exact effects on organ dysfunction are largely unknown. Hair follicles-mini-epithelial organs that grow hair-are miniaturized by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs). Here we report that obesity-induced stress, such as that induced by a high-fat diet (HFD), targets HFSCs to accelerate hair thinning. Read More

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A rare case of persistent hyperkalaemia.

Ann Clin Biochem 2021 Jul 4:45632211028614. Epub 2021 Jul 4.

Department of Biochemistry & Immunology, University Hospital of Wales, Wales, UK.

Hyperkalaemia is a common biochemical finding that can allude to preanalytical or truly pathological causes. Here, we present a case of a 41-year-old female patient who has regularly presented with incidences of isolated hyperkalaemia since 2012, with otherwise normal renal function and no other associated symptoms. Investigations into the patient's family history revealed similar biochemical findings in her brother and eldest son. Read More

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Platelets, extracellular vesicles and coagulation in pulmonary arterial hypertension.

Pulm Circ 2021 Jul-Sep;11(3):20458940211021036. Epub 2021 Jun 4.

National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.

Pulmonary arterial hypertension is a rare disease of the pulmonary vasculature, characterised pathologically by proliferation, remodelling and thrombosis . Unfortunately, existing therapeutic interventions do not reverse these findings and the disease continues to result in significant morbidity and premature mortality. A number of haematological derangements have been described in pulmonary arterial hypertension which may provide insights into the pathobiology of the disease and opportunities to explore new therapeutic pathways. Read More

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The phosphatase PRL-3 affects intestinal homeostasis by altering the crypt cell composition.

J Mol Med (Berl) 2021 Jun 15. Epub 2021 Jun 15.

European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.

Expression of the phosphatase of regenerating liver-3 (PRL-3) is known to promote tumor growth in gastrointestinal adenocarcinomas, and the incidence of tumor formation upon inflammatory events correlates with PRL-3 levels in mouse models. These carcinomas and their onset are associated with the impairment of intestinal cell homeostasis, which is regulated by a balanced number of Paneth cells and Lgr5 expressing intestinal stem cells (Lgr5+ ISCs). Nevertheless, the consequences of PRL-3 overexpression on cellular homeostasis and ISC fitness in vivo are unexplored. Read More

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Synapomorphic features of hepatic and pulmonary vasculatures include comparable purinergic signaling responses in host defense and modulation of inflammation.

Am J Physiol Gastrointest Liver Physiol 2021 Jun 9. Epub 2021 Jun 9.

Division of Gastroenterology/Hepatology, Department of Medicine and Center for Inflammation Research, Department of Anesthesia, grid.239395.7Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

Hepato-splanchnic and pulmonary vasculatures constitute synapomorphic, highly comparable networks integrated with the external environment. Given functionality related to obligatory requirements of "feeding and breathing", these organs are subject to constant environmental challenges entailing infectious risk, antigenic and xenobiotic exposures. Host responses to these stimuli need to be both protective and tightly regulated. Read More

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Stress granules, RNA-binding proteins and polyglutamine diseases: too much aggregation?

Cell Death Dis 2021 Jun 8;12(6):592. Epub 2021 Jun 8.

Algarve Biomedical Center Research Institute (ABC-RI), Faro, Portugal.

Stress granules (SGs) are membraneless cell compartments formed in response to different stress stimuli, wherein translation factors, mRNAs, RNA-binding proteins (RBPs) and other proteins coalesce together. SGs assembly is crucial for cell survival, since SGs are implicated in the regulation of translation, mRNA storage and stabilization and cell signalling, during stress. One defining feature of SGs is their dynamism, as they are quickly assembled upon stress and then rapidly dispersed after the stress source is no longer present. Read More

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Molecular mechanisms of cell death in neurological diseases.

Cell Death Differ 2021 Jul 7;28(7):2029-2044. Epub 2021 Jun 7.

Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, VIC, Australia.

Tightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture and shaping the CNS. Abnormalities in PCD signalling cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cell death associated with autophagy as well as in unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. These cell deaths can be activated in response to various forms of cellular stress (exerted by intracellular or extracellular stimuli) and inflammatory processes. Read More

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Aberrant expression of HDL-bound microRNA induced by a high-fat diet in a pig model: implications in the pathogenesis of dyslipidaemia.

BMC Cardiovasc Disord 2021 Jun 6;21(1):280. Epub 2021 Jun 6.

Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, People's Republic of China.

Background: A high-fat diet can affect lipid metabolism and trigger cardiovascular diseases. A growing body of studies has revealed the HDL-bound miRNA profiles in familial hypercholesterolaemia; in sharp contrast, relevant studies on high-fat diet-induced dyslipidaemia are lacking. In the current study, HDL-bound miRNAs altered by a high-fat diet were explored to offer some clues for elucidating their effects on the pathogenesis of dyslipidaemia. Read More

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The Microbiota and the Gut-Brain Axis in Controlling Food Intake and Energy Homeostasis.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Microbial Ecology, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), 46980 Valencia, Spain.

Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Read More

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Lack of WWC2 Protein Leads to Aberrant Angiogenesis in Postnatal Mice.

Int J Mol Sci 2021 May 18;22(10). Epub 2021 May 18.

Department of Ophthalmology, University of Münster Medical School, 48149 Münster, Germany.

The WWC protein family is an upstream regulator of the Hippo signalling pathway that is involved in many cellular processes. We examined the effect of an endothelium-specific WWC1 and/or WWC2 knock-out on ocular angiogenesis. Knock-outs were induced in C57BL/6 mice at the age of one day (P1) and evaluated at P6 (postnatal mice) or induced at the age of five weeks and evaluated at three months of age (adult mice). Read More

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Resistance to Targeted Therapy and RASSF1A Loss in Melanoma: What Are We Missing?

Int J Mol Sci 2021 May 12;22(10). Epub 2021 May 12.

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Melanoma is one of the most aggressive forms of skin cancer and is therapeutically challenging, considering its high mutation rate. Following the development of therapies to target BRAF, the most frequently found mutation in melanoma, promising therapeutic responses were observed. While mono- and combination therapies to target the MAPK cascade did induce a therapeutic response in BRAF-mutated melanomas, the development of resistance to MAPK-targeted therapies remains a challenge for a high proportion of patients. Read More

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The Emerging Role of microRNA in Periodontitis: Pathophysiology, Clinical Potential and Future Molecular Perspectives.

Int J Mol Sci 2021 May 21;22(11). Epub 2021 May 21.

Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy.

During the last few decades, it has been established that messenger ribonucleic acid (mRNA) transcription does not inevitably lead to protein translation, but there are numerous processes involved in post-transcriptional regulation, which is a continuously developing field of research. MicroRNAs (miRNAs) are a group of small non-coding RNAs, which negatively regulate protein expression and are implicated in several physiological and pathological mechanisms. Aberrant expression of miRNAs triggers dysregulation of multiple cellular processes involved in innate and adaptive immune responses. Read More

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Latest update on chemokine receptors as therapeutic targets.

Biochem Soc Trans 2021 Jun;49(3):1385-1395

School of Pharmacy, University of East Anglia, Norwich, U.K.

The chemokine system plays a fundamental role in a diverse range of physiological processes, such as homeostasis and immune responses. Dysregulation in the chemokine system has been linked to inflammatory diseases and cancer, which renders chemokine receptors to be considered as therapeutic targets. In the past two decades, around 45 drugs targeting chemokine receptors have been developed, yet only three are clinically approved. Read More

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Exercise ameliorates aberrant synaptic plasticity without enhancing adult-born cell survival in the hippocampus of serotonin transporter knockout mice.

Brain Struct Funct 2021 Jul 30;226(6):1991-1999. Epub 2021 May 30.

Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Melbourne, VIC, 3010, Australia.

Deficits in hippocampal cellular and synaptic plasticity are frequently associated with cognitive and mood disorders, and indeed common mechanisms of antidepressants are thought to involve neuroplastic processes. Here, we investigate hippocampal adult-born cell survival and synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in serotonin transporter (5-HTT) knockout (KO) mice. From 8 weeks of age, mice either continued in standard-housing conditions or were given access to voluntary running wheels for 1 month. Read More

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Abnormal ADAM17 expression causes airway fibrosis in chronic obstructive asthma.

Biomed Pharmacother 2021 Aug 27;140:111701. Epub 2021 May 27.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Patients with chronic obstructive asthma (COA) develop airflow obstruction caused by subepithelial fibrosis. Although a disintegrin and metalloproteinase 17 (ADAM17) has been implicated in lung inflammation and tissue fibrosis, its role in airway fibrosis in COA has not been explored. Here, we found marked overexpression of ADAM17, phosphorylated ADAM17, and connective tissue growth factor (CTGF) in human airway fibroblasts from COA patients, compared with those of normal subjects. Read More

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Src and Fyn regulation of NMDA receptors in health and disease.

Neuropharmacology 2021 08 26;193:108615. Epub 2021 May 26.

Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. Electronic address:

The Src family kinases (SFKs) are cytoplasmic non-receptor tyrosine kinases involved in multiple signalling pathways. In the central nervous system (CNS), SFKs are key regulators of N-methyl-d-aspartate receptor (NMDAR) function and major points of convergence for neuronal transduction pathways. Physiological upregulation of NMDAR activity by members of the SFKs, namely Src and Fyn, is crucial for induction of plasticity at Schaffer collateral-CA1 synapses of the hippocampus. Read More

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Disturbed progesterone signalling in an advanced preclinical model of endometriosis.

Reprod Biomed Online 2021 Jul 13;43(1):139-147. Epub 2021 Mar 13.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Resalat Highway, 1665659911, PO Box 16635-148 Tehran, Iran; Department of Developmental Biology, University of Science and Culture Tehran, Iran. Electronic address:

Research Question: Do human endometriosis organoids recapitulate aberrant progesterone signalling in the disease to serve as advanced experimental models for uncovering epigenetic mechanisms involved in attenuated progesterone response in endometriosis?

Design: Initially, the organoids were established from acquired biopsies (women with and without endometriosis) and characterized by morphological, histological and immunostaining analyses.

Results: A panel of endometriosis-related genes showed a pattern of expressions in cytochrome c oxidase subunit II (COX2), matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase-3 (TIMP3), transforming growth factor beta 1 (TGF-β1), and zinc finger E-box binding homeobox 1 (ZEB1), and a contradictory expression pattern for cadherin (CDH1), POU class 5 homeobox 1 (POU5F1; also known as OCT4), and Nanog homeobox (NANOG) in the endometriosis organoids that is concordant with published research. These endometriosis organoids failed to upregulate 17β-Hydroxysteroid dehydrogenase 2 (17HSDβ2), progestogen associated endometrial protein (PAEP), secreted phosphoprotein 1 (SPP1), and leukaemia inhibitory factor (LIF) in response to progesterone at the level observed in control endometrium organoids. Read More

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Phosphorylation and stabilization of PIN1 by JNK promote intrahepatic cholangiocarcinoma growth.

Hepatology 2021 May 28. Epub 2021 May 28.

Leeds Institute of Medical Research at St James', Faculty of Medicine and Health, University of Leeds, St. James' University Hospital, Leeds, UK.

Background And Aims: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive type of liver cancer in urgent need of treatment options. Aberrant activation of c-Jun N-terminal kinase (JNK) pathway is a key feature in ICC and an attractive candidate target for its treatment. However, the mechanisms by which constitutive JNK activation promotes ICC growth, and thus the key downstream effectors of this pathway remain unknown for their applicability as therapeutic targets. Read More

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Glutamate connectivity associations converge upon the salience network in schizophrenia and healthy controls.

Transl Psychiatry 2021 05 27;11(1):322. Epub 2021 May 27.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, SE5 8AF, UK.

Alterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. Read More

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