364,616 results match your criteria molecular mechanisms

Cell identity specification in plants: lessons from flower development.

J Exp Bot 2021 Apr 17. Epub 2021 Apr 17.

Plant Cell and Molecular Biology, Institute of Biology, Humboldt-Universitaet zu Berlin, Germany.

Multicellular organisms display a fascinating complexity of cellular identities and patterns of diversification. The concept of ''cell type'' aims to describe and categorize this complexity. In this review, we discuss the traditional concept of cell types and highlight the impact of single-cell technologies and spatial omics on the understanding of cellular differentiation in plants. Read More

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Perspectives on natural compounds in chemoprevention and treatment of cancer: an update with new promising compounds.

Eur J Cancer 2021 Apr 14;149:165-183. Epub 2021 Apr 14.

Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, 25701, USA. Electronic address:

Cancer is the second deadliest disease worldwide. Although recent advances applying precision treatments with targeted (molecular and immune) agents are promising, the histological and molecular heterogeneity of cancer cells and huge mutational burdens (intrinsic or acquired after therapy) leading to drug resistance and treatment failure are posing continuous challenges. These recent advances do not negate the need for alternative approaches such as chemoprevention, the pharmacological approach to reverse, suppress or prevent the initial phases of carcinogenesis or the progression of premalignant cells to invasive disease by using non-toxic agents. Read More

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Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis.

Cell Immunol 2021 Apr 8;364:104359. Epub 2021 Apr 8.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address:

Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. Read More

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The toxic impacts of microplastics (MPs) and polycyclic aromatic hydrocarbons (PAHs) on haematic parameters in a marine bivalve species and their potential mechanisms of action.

Sci Total Environ 2021 Apr 9;783:147003. Epub 2021 Apr 9.

College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China. Electronic address:

Microplastics (MPs) and polycyclic aromatic hydrocarbons (PAHs) are universally detected in the marine ecosystem and may exert adverse impacts on marine species. Although under realistic pollution scenarios, PAH pollution usually occurs as a mixture of different PAH compounds, the toxic impacts of PAH mixtures on marine organisms remain largely unknown to date, including their interactions with other emergent pollutants such as MPs. In this study, the single and combined toxic impacts of polystyrene MPs and a mixture of PAHs (standard mix of 16 representative PAHs) on haematic parameters were evaluated in the blood clam Tegillarca granosa. Read More

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Ins and outs of cadmium-induced carcinogenesis: Mechanism and prevention.

Cancer Treat Res Commun 2021 Apr 8;27:100372. Epub 2021 Apr 8.

Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates. Electronic address:

Cadmium (Cd) is a heavy metal and a highly toxic pollutant that is released into the environment as a byproduct of most modern factories and industries. Cd enters our body in significant quantities from contaminated water, cigarette smoke, or food product to many detrimental health hazards. Based on causal association all the Cd-related or derived compounds have been classified as carcinogens. Read More

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Transcriptional regulator BOB.1: Molecular mechanisms and emerging role in chronic inflammation and autoimmunity.

Autoimmun Rev 2021 Apr 14:102833. Epub 2021 Apr 14.

Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.

Lymphocytes constitute an essential and potent effector compartment of the immune system. Therefore, their development and functions must be strictly regulated to avoid inappropriate immune responses, such as autoimmune reactions. Several lines of evidence from genetics (e. Read More

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Inhibition of soluble epoxide hydrolase alleviates insulin resistance and hypertension via downregulation of SGLT2 in the mouse kidney.

J Biol Chem 2021 Apr 14:100667. Epub 2021 Apr 14.

Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China. Electronic address:

The epoxyeicosatrienoic acid (EET) exerts beneficial effects on insulin resistance and/or hypertension. EETs could be readily converted to less biological active diols by soluble epoxide hydrolase (sEH). However, whether sEH inhibition can ameliorate the comorbidities of insulin resistance and hypertension, and the underlying mechanisms of this relationship, are unclear. Read More

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Cardiomyopathy Mutations Impact the Actin-Activated Power Stroke of Human Cardiac Myosin.

Biophys J 2021 Apr 14. Epub 2021 Apr 14.

Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033. Electronic address:

Cardiac muscle contraction is driven by the molecular motor myosin that uses the energy from ATP hydrolysis to generate a power stroke when interacting with actin filaments, while it is unclear how this mechanism is impaired by mutations in myosin that can lead to heart failure. We have applied a FRET strategy to investigate structural changes in the lever arm domain of human β-cardiac myosin subfragment 1 (M2β-S1). We exchanged the human ventricular regulatory light chain labeled at a single cysteine (V105C) with Alexa 488 onto M2β-S1, which served as a donor for Cy3ATP bound to the active site. Read More

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Molecular mechanisms of hearing loss in Nager syndrome.

Dev Biol 2021 Apr 14. Epub 2021 Apr 14.

Department of Molecular Pathobiology, New York University, College of Dentistry, New York, USA. Electronic address:

Nager syndrome is a rare human developmental disorder characterized by hypoplastic neural crest-derived craniofacial bones and limb defects. Mutations in SF3B4 gene, which encodes a component of the spliceosome, are a major cause for Nager. A review of the literature indicates that 45% of confirmed cases are also affected by conductive, sensorineural or mixed hearing loss. Read More

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Nitric oxide and dopamine metabolism converge via mitochondrial dysfunction in the mechanisms of neurodegeneration in Parkinson's disease.

Arch Biochem Biophys 2021 Apr 14:108877. Epub 2021 Apr 14.

Faculty of Pharmacy, University of Coimbra and Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

The molecular mechanisms underlying the degeneration and neuronal death associated with Parkinson's disease (PD) are not clearly understood. Several pathways and models have been explored in an overwhelming number of studies. Overall, from these studies, mitochondrial dysfunction and nitroxidative stress have emerged as major contributors to degeneration of dopaminergic neurons in PD. Read More

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Host PDZ-containing proteins targeted by SARS-Cov-2.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Institut Pasteur, Unité Récepteurs-Canaux, UMR CNRS 3571, 75015, Paris, France.

Small linear motif targeting protein interacting domains called PDZ have been identified at the C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins E, 3a, and N. Using a high-throughput approach of affinity-profiling against the full human PDZome, we identified sixteen human PDZ binders of SARS-CoV-2 proteins E, 3A and N showing significant interactions with dissociation constants values ranging from 3 μM to 82 μM. Six of them (TJP1, PTPN13, HTRA1, PARD3, MLLT4, LNX2) are also recognized by SARS-CoV while three (NHERF1, MAST2, RADIL) are specific to SARS-CoV-2 E protein. Read More

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Repressors of anthocyanin biosynthesis.

New Phytol 2021 Apr 17. Epub 2021 Apr 17.

Department of Ecology and Evolutionary Biology, University of Connecticut, 75 North Eagleville Road, Storrs, CT, USA, 06269-3043.

Anthocyanins play a variety of adaptive roles in both vegetative tissues and reproductive organs of plants. The broad functionality of these compounds requires sophisticated regulation of the anthocyanin biosynthesis pathway to allow proper localization, timing, and optimal intensity of pigment deposition. While it is well-established that the committed steps of anthocyanin biosynthesis are activated by a highly conserved MYB-bHLH-WDR (MBW) protein complex in virtually all flowering plants, anthocyanin repression seems to be achieved by a wide variety of protein and small RNA families that function in different tissue types and in response to different developmental, environmental, and hormonal cues. Read More

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Sex Differences in Glioblastoma Immunotherapy Response.

Neuromolecular Med 2021 Apr 17. Epub 2021 Apr 17.

Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, USA.

Glioblastoma (GBM), the most common primary malignant brain tumor, remains difficult to treat and shares phenotypes, including an aberrant immune response, with other neurological disorders. Understanding the cellular and molecular mechanisms underlying this pathological immune response remains a priority, particularly as standard of care for advanced cancers evolves to include immunotherapies, which have yet to show strong clinical efficacy in GBM. Epidemiological evidence supports a sex difference in GBM, with increased prevalence in males, and recent studies identified differences between males and females ranging from genetic aberrations to cellular programs. Read More

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Molecular mechanisms of physical exercise on depression in the elderly: a systematic review.

Mol Biol Rep 2021 Apr 17. Epub 2021 Apr 17.

Physical Education Department, Federal University of the Valleys of Jequitinhonha and Mucuri (UFVJM), Diamantina, MG, Brazil.

Depressive disorders are common among the elderly. Major depressive disorder will be one of the highest healthcare costs in middle and higher income countries by 2030. It is known that physical inactivity leads to negative effects on mental health in the elderly. Read More

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LEP (-2548G>A LEP) and LEPR (223Gln>Arg, 109Lys>Arg) polymorphisms as breast cancer risk factors in the Polish female population.

Mol Biol Rep 2021 Apr 17. Epub 2021 Apr 17.

Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355, Poznan, Poland.

On a global scale, breast cancer is the most common type of cancer in women, and it is still a growing problem. Therefore, new prognostic or diagnostic markers are required that would facilitate the assessment of patients or provide more efficient therapy, respectively. In these studies, we analyzed the contribution of LEP (2548G>A) and LEPR (109 Lys>Arg and 223Gln>Arg) genes polymorphisms to the risk of breast cancer development. Read More

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Multi-conformation representation of Mpro identifies promising candidates for drug repurposing against COVID-19.

J Mol Model 2021 Apr 17;27(5):128. Epub 2021 Apr 17.

Division of Bioinformatics, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata, 700054, India.

The COVID-19 main protease (Mpro), one of the conserved proteins of the novel coronavirus is crucial for its replication and so is a very lucrative drug target. Till now, there is no drug molecule that has been convincingly identified as the inhibitor of the function of this protein. The current pandemic situation demands a shortcut to quickly reach to a lead compound or a drug, which may not be the best but might serve as an interim solution at least. Read More

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Aβ1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation.

Cell Mol Life Sci 2021 Apr 17. Epub 2021 Apr 17.

Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.

Amyloid beta (Aβ) is linked to the pathology of Alzheimer's disease (AD). At physiological concentrations, Aβ was proposed to enhance neuroplasticity and memory formation by increasing the neurotransmitter release from presynapse. However, the exact mechanisms underlying this presynaptic effect as well as specific contribution of endogenously occurring Aβ isoforms remain unclear. Read More

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Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

In the adult hippocampus, synaptic plasticity is important for information processing, learning, and memory encoding. Astrocytes, the most common glial cells, play a pivotal role in the regulation of hippocampal synaptic plasticity. While astrocytes were initially described as a homogenous cell population, emerging evidence indicates that in the adult hippocampus, astrocytes are highly heterogeneous and can differentially respond to changes in neuronal activity in a subregion-dependent manner to actively modulate synaptic plasticity. Read More

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Methamphetamine exposure induces neuronal programmed necrosis by activating the receptor-interacting protein kinase 3 -related signalling pathway.

FASEB J 2021 May;35(5):e21561

School of Forensic Medicine, Southern Medical University, Guangzhou, P.R. China.

Methamphetamine (METH) is a synthetic drug with severe neurotoxicity, however, the regulation of METH-induced neuronal programmed necrosis remains poorly understood. The aim of this study was to identify the molecular mechanisms of METH-induced neuronal programmed necrosis. We found that neuronal programmed necrosis occurred in the striatum of brain samples from human and mice that were exposed to METH. Read More

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Investigating Surface Binding Effects: Antibacterial Efficacy of Bound 8-Hydroxyquinoline against Staphylococcus aureus and Escherichia coli.

J Appl Microbiol 2021 Apr 16. Epub 2021 Apr 16.

Air Force Civil Engineer Center, AFCEC/CXAE, Tyndall Air Force Base, Panama City, Florida, 32403, USA.

Aims: Investigate the binding of the antimicrobial compound 8-hydroxyquinoline (8HQ) to a material interface and determine whether immobilization affects the antibacterial efficacy.

Methods & Results: The 8HQ derivative 5-carboxy-8-hydroxyquinoline (5C8HQ) was attached to silica beads through amide bond coupling at the carboxyl moiety of 5C8HQ. Attachment of 5C8HQ was confirmed using a combination of mass spectrometry, thermogravimetric analysis, colorimetric testing, and Soxhlet extraction. Read More

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Anticancer activity of limonene: A systematic review of target signaling pathways.

Phytother Res 2021 Apr 17. Epub 2021 Apr 17.

Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.

Limonene (LIM) is a monoterpene, which is abundant in essential oils of Citrus fruits peels (Rutaceae). More recently, LIM, as a potential natural anticancer compound, has attracted major attention and exerted a chemopreventive activity, stimulating the detoxification of carcinogenic compounds and limiting tumor growth and angiogenesis in various cancer models. Twenty-six (26) articles were selected based on previously established criteria. Read More

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Gut Microbiota in Lupus: a Butterfly Effect?

Curr Rheumatol Rep 2021 Apr 16;23(4):27. Epub 2021 Apr 16.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, The Ministry of Education Key Laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuai-Fu-Yuan, Dong-Cheng District, Beijing, 100730, China.

Purpose Of Review: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that typically displays chronic inflammatory tissue damage and miscellaneous circulatory autoantibodies, as well as distinctive type 1 interferon signatures. The etiology of SLE is unclear and currently is attributed to genetic predisposition and environmental triggers. Gut microbiota has recently been considered a critical environmental pathogenic factor in immune-related disorders, and studies are ongoing to uncover the key pathogens and the imputative mechanisms. Read More

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Neuroprotective and antioxidative effects of pioglitazone in brain tissue adjacent to the ischemic core are mediated by PI3K/Akt and Nrf2/ARE pathways.

J Mol Med (Berl) 2021 Apr 16. Epub 2021 Apr 16.

Institute of Experimental and Clinical Pharmacology, Faculty of Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Arnold Heller Strasse 3, 24105, Kiel, Germany.

The present study elucidates the neuroprotective mechanisms of the PPARγ (peroxisome proliferator-activated receptor γ) agonist pioglitazone in survival of ischemic neurons following middle cerebral artery occlusion with reperfusion (MCAO). Intracerebroventricular infusion of pioglitazone over 5 days before and 24 or 48 h after MCAO alleviated neurological impairments, inhibited apoptosis 24 h, and activated the PI3K/Akt pathway along with increased phosphorylation of Akt (ser473) and GSK-3β (ser9) in the peri-infarct cortical areas 48 h after MCAO. In primary cortical neurons, pioglitazone suppressed the glutamate-induced release of lactate dehydrogenase by a PPARγ-dependent mechanism. Read More

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Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes.

Genet Med 2021 Apr 16. Epub 2021 Apr 16.

Molecular and Clinical Sciences Institute, St George's University of London, London, UK.

Purpose: Several clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level.

Methods: Ten index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity. Read More

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Inflammatory processes in the liver: divergent roles in homeostasis and pathology.

Cell Mol Immunol 2021 Apr 16. Epub 2021 Apr 16.

School of Medicine, Trinity College Dublin, Dublin, Ireland.

The hepatic immune system is designed to tolerate diverse harmless foreign moieties to maintain homeostasis in the healthy liver. Constant priming and regulation ensure that appropriate immune activation occurs when challenged by pathogens and tissue damage. Failure to accurately discriminate, regulate, or effectively resolve inflammation offsets this balance, jeopardizing overall tissue health resulting from an either  overly tolerant or an overactive inflammatory response. Read More

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The functional roles of TCA cycle metabolites in cancer.

Oncogene 2021 Apr 16. Epub 2021 Apr 16.

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.

The tricarboxylic acid cycle (TCA cycle) has been known for decades as a hub for generating cellular energy and precursors for biosynthetic pathways. Several cancers harbor mutations that affect the integrity of this cycle, mostly at the levels of isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH). This results in dysregulation in the production of TCA cycle metabolites and is probably implicated in cancer initiation. Read More

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Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis.

Sci Rep 2021 Apr 16;11(1):8406. Epub 2021 Apr 16.

Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, 3-1-3 Hongo; Bunkyoku, Tokyo, 113-8431, Japan.

Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). Read More

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ILDR2 stabilization is regulated by its interaction with GRP78.

Sci Rep 2021 Apr 16;11(1):8414. Epub 2021 Apr 16.

Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.

Ildr2 was initially identified as a genetic modifier of diabetes susceptibility in B6.DBA Lep congenic mice, and was associated with decreased β-cell replication rates, reduced β-cell mass, and persistent mild hypoinsulinemic hyperglycemia. However, the molecular mechanisms of how the ILDR2 protein is involved in these effects are largely unknown. Read More

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The mechanism of TiaoGanYiPi formula for treating chronic hepatitis B by network pharmacology and molecular docking verification.

Sci Rep 2021 Apr 16;11(1):8402. Epub 2021 Apr 16.

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.

The Chinese herbal formula TiaoGanYiPi (TGYP) showed effective against chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection. Hence, we aimed to clarify the mechanisms and potential targets between TGYP and CHB. The active compounds and related putative targets of TGYP, and disease targets of CHB were obtained from the public databases. Read More

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Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways.

Sci Rep 2021 Apr 16;11(1):8336. Epub 2021 Apr 16.

Department of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.

Thoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but the mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of DRG responses in pain pathologies; however, its role in other sensory modalities is less understood. Read More

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