1,450 results match your criteria disrupting secondary

A proline-rich motif in the large intracellular loop of the glycine receptor α1 subunit interacts with the Pleckstrin homology domain of collybistin.

J Adv Res 2021 Mar 8;29:95-106. Epub 2020 Oct 8.

Department of Biochemistry, German University in Cairo, Egypt.

Introduction: The inhibitory glycine receptor (GlyR), a mediator of fast synaptic inhibition, is located and held at neuronal synapses through the anchoring proteins gephyrin and collybistin. Stable localization of neurotransmitter receptors is essential for synaptic function. In case of GlyRs, only beta subunits were known until now to mediate synaptic anchoring. Read More

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Urinary phthalate exposures and risk of breast cancer: the Multiethnic Cohort study.

Breast Cancer Res 2021 Apr 6;23(1):44. Epub 2021 Apr 6.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

Background: The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women.

Methods: We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. Read More

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Investigating blunt force trauma to the larynx: The role of inferior-superior vocal fold displacement on phonation.

J Biomech 2021 Mar 16;121:110377. Epub 2021 Mar 16.

Department of Mechanical and Aeronautical Engineering, Clarkson University, 8 Clarkson Ave, Potsdam, NY 13699, United States. Electronic address:

Blunt force trauma to the larynx, which may result from motor vehicle collisions, sports activities, etc., can cause significant damage, often leading to displaced fractures of the laryngeal cartilages, thereby disrupting vocal function. Current surgical interventions primarily focus on airway restoration to stabilize the patient, with restoration of vocal function usually being a secondary consideration. Read More

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All-Atom MD Simulations of the HBV Capsid Complexed with AT130 Reveal Secondary and Tertiary Structural Changes and Mechanisms of Allostery.

Viruses 2021 03 26;13(4). Epub 2021 Mar 26.

Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA.

The hepatitis B virus (HBV) capsid is an attractive drug target, relevant to combating viral hepatitis as a major public health concern. Among small molecules known to interfere with capsid assembly, the phenylpropenamides, including AT130, represent an important antiviral paradigm based on disrupting the timing of genome packaging. Here, all-atom molecular dynamics simulations of an intact AT130-bound HBV capsid reveal that the compound increases spike flexibility and improves recovery of helical secondary structure in the spike tips. Read More

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Cell Cytoskeleton and Stiffness Are Mechanical Indicators of Organotropism in Breast Cancer.

Biology (Basel) 2021 Mar 25;10(4). Epub 2021 Mar 25.

Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518000, China.

Tumor metastasis involves the dissemination of tumor cells from the primary lesion to other organs and the subsequent formation of secondary tumors, which leads to the majority of cancer-related deaths. Clinical findings show that cancer cell dissemination is not random but exhibits organ preference or organotropism. While intrinsic biochemical factors of cancer cells have been extensively studied in organotropism, much less is known about the role of cell cytoskeleton and mechanics. Read More

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Modeling of Urinary Microbiota Associated With Cystitis.

Front Cell Infect Microbiol 2021 16;11:643638. Epub 2021 Mar 16.

Laboratory for Bioinformatics, Faculty of Food Technology and Biotechnology, Zagreb University, Zagreb, Croatia.

A decade ago, when the Human Microbiome Project was starting, urinary tract (UT) was not included because the bladder and urine were considered to be sterile. Today, we are presented with evidence that healthy UT possesses native microbiota and any major event disrupting its "equilibrium" can impact the host also. This dysbiosis often leads to cystitis symptoms, which is the most frequent lower UT complaint, especially among women. Read More

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The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants.

Caren Weinhouse

Free Radic Biol Med 2021 Mar 28. Epub 2021 Mar 28.

Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon, 97214. Electronic address:

People are exposed to wide range of redox-active environmental pollutants. Air pollution, heavy metals, pesticides, and endocrine disrupting chemicals can disrupt cellular redox status. Redox-active pollutants in our environment all trigger their own sets of specific cellular responses, but they also activate a common set of general stress responses that buffer the cell against homeostatic insults. Read More

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The transcription regulator ACTR controls ACT-toxin biosynthesis and pathogenicity in the tangerine pathotype of Alternaria alternata.

Microbiol Res 2021 Mar 16;248:126747. Epub 2021 Mar 16.

Key Lab of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China. Electronic address:

The host-selective ACT toxin is essential for the pathogenesis of the citrus fungal pathogen Alternaria alternata. However, the mechanism of ACT-toxin gene clusters ACT-toxin biosynthesis regulated by is still poorly understood. The biosynthesis of ACT toxin is mainly regulated by multiple ACT toxin genes located in the secondary metabolite gene cluster. Read More

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The sensitivity of multiple ecotoxicological assays for evaluating Microcystis aeruginosa cellular algal organic matter and contribution of cyanotoxins to the toxicity.

Toxicon 2021 May 9;195:69-77. Epub 2021 Mar 9.

Institute of Microbiology of the Czech Academy of Sciences, Vídeská 1083, CZ-142 20, Prague 4, Czech Republic; Institute for Environmental Studies, Faculty of Science, Charles University, Benátská 2, CZ-128 01, Prague 2, Czech Republic. Electronic address:

Secondary metabolites of cyanobacteria and algae released during algal blooms often exhibit toxic effects, but only a small number of the metabolites are the subject of routine analytical screenings. Alternatively, ecotoxicological assays offer a better representation of the overall negative effects. The aim of this work was to compare multiple assays in their sensitivity towards cellular algal organic matter (COM) of the toxin-producing cyanobacterium Microcystis aeruginosa. Read More

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PD-L1 Detection on Circulating Melanoma Cells.

Methods Mol Biol 2021 ;2265:223-233

Centre for Circulating Tumour Cell Diagnostics & Research at the Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia.

The advent of personalized medicines targeting cell signaling pathways has radically improved melanoma patient outcomes. More recently, immune-modulating therapies disrupting the PD-1/PD-L1 axis have become a powerful tool in the treatment of a range of melanoma, showing a profound improvement in the overall survival outcomes. However, immune checkpoint inhibitors (ICIs) are associated with considerable toxicities and appear to only be efficacious in a subset of melanoma patients. Read More

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Microbiome and PCOS: State-of-Art and Future Aspects.

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. Read More

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February 2021

Obesity, Nutrients and the Immune System in the Era of COVID-19.

Nutrients 2021 Feb 13;13(2). Epub 2021 Feb 13.

Department of Physiology, Faculty of Pharmacy, University of Paris, 75006 Paris, France.

The past year has shown that obesity is a risk factor for severe complications of SARS-CoV-2 infection. Excess fat mass during obesity is known to be a risk factor for chronic diseases but also for severe infections and infectious complications. We have focused here on the elements responsible for this particular susceptibility to infections and more specifically to COVID-19. Read More

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February 2021

Integration of Dual Targeting and Dual Therapeutic Modules Endows Self-Assembled Nanoparticles with Anti-Tumor Growth and Metastasis Functions.

Int J Nanomedicine 2021 18;16:1361-1376. Epub 2021 Feb 18.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.

Object: High targeting and efficient cytotoxicity toward tumor cells endow NPs excellent anti-tumor activity. Herein, a peptide polymer possessing dual-targeting ability and double therapeutic activity was developed and named TGMF, which can form NPs through self-assembly. It is composed of four functional modules: 1) Active targeting peptide TMTP1 (T) deliver NPs to tumors specifically; 2) Therapeutic peptide GO-203 (G), which can significantly inhibit tumor growth by disrupting the redox balance in cells; 3) A passively targeted enzyme-responsive peptide PLGLGA (M), which can be cleaved specifically by metalloproteinase-2 (MMP-2) highly expressed in the tumor microenvironment (TME); and 4) Hexadecyl (F), which has strong hydrophobicity, can promote the self-assembly of TGMF NPs. Read More

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Effect of microplastics in water and aquatic systems.

Environ Sci Pollut Res Int 2021 Mar 2. Epub 2021 Mar 2.

Nano-Surface Texturing Laboratory, Department of Metallurgical and Materials Engineering, Defence Institute of Advanced Technology (DU), Ministry of Defence, Girinagar, Pune, Maharashtra, 411025, India.

Surging dismissal of plastics into water resources results in the splintered debris generating microscopic particles called microplastics. The reduced size of microplastic makes it easier for intake by aquatic organisms resulting in amassing of noxious wastes, thereby disturbing their physiological functions. Microplastics are abundantly available and exhibit high propensity for interrelating with the ecosystem thereby disrupting the biogenic flora and fauna. Read More

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A multidimensional computational exploration of congenital myasthenic syndrome causing mutations in human choline acetyltransferase.

J Cell Biochem 2021 Mar 1. Epub 2021 Mar 1.

Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, Yokohama, Kanagawa, Japan.

Missense mutations of human choline acetyltransferase (CHAT) are mainly associated with congenital myasthenic syndrome (CMS). To date, several pathogenic mutations have been reported, but due to the rarity and genetic complexity of CMS and difficult genotype-phenotype correlations, the CHAT mutations, and their consequences are underexplored. In this study, we systematically sift through the available genetic data in search of previously unreported pathogenic mutations and use a dynamic in silico model to provide structural explanations for the pathogenicity of the reported deleterious and undetermined variants. Read More

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Effects of dynamic high-pressure microfluidization treatment on the functional and structural properties of potato protein isolate and its complex with chitosan.

Food Res Int 2021 Feb 3;140:109868. Epub 2020 Nov 3.

College of Food Science and Technology, Huazhong Agriculture University, Wuhan 430070, PR China.

In our previous work, dynamic high-pressure microfluidization (DHPM) treatment was shown to promote the interaction between chitosan (CS) and potato protein isolate (PPI), but the modification mechanism of DHPM treatment (6 k-12 k psi) on PPI and its complex with CS remains to be elucidated. Here, moderate DHPM treatment (≤9k psi) was found to decrease the particle size, increase the surface charge, and improve the solubility of PPI and its emulsifying and foaming properties. The PPI functional properties were further improved by CS addition followed by DHPM treatment. Read More

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February 2021

Characterization and Validation of Arg286 Residue of IL-1RAcP as a Potential Drug Target for Osteoarthritis.

Front Chem 2020 3;8:601477. Epub 2021 Feb 3.

Center for Applied Proteomics and Molecular Medicine, Institute for Advanced Biomedical Research, George Mason University, Manassas, VA, United States.

Osteoarthritis (OA) is the most common form of arthritis and the fastest growing cause of chronic disability in the world. Formation of the ternary IL-1β /IL-1R1/IL-1RAcP protein complex and its downstream signaling has been implicated in osteoarthritis pathology. Current OA therapeutic approaches target either the cytokine IL-1β or the primary receptor IL-1RI but do not exploit the potential of the secondary receptor IL-1RAcP. Read More

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February 2021

Laccase and horseradish peroxidase for green treatment of phenolic micropollutants in real drinking water and wastewater.

Environ Sci Pollut Res Int 2021 Feb 19. Epub 2021 Feb 19.

Institute for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Bendlova 1409/7, 461 17, Liberec, Czech Republic.

Biologically active micropollutants that contain diverse phenolic/aromatic structures are regularly present in wastewater effluents and are even found in drinking water. Advanced green technologies utilizing immobilized laccase and/or peroxidase, which target these micropollutants directly, may provide a reasonable alternative to standard treatments. Nevertheless, the use of these enzymes is associated with several issues that may prevent their application, such as the low activity of laccase at neutral and basic pH or the necessity of hydrogen peroxide addition as a co-substrate for peroxidases. Read More

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February 2021

The plant metabolome guides fitness-relevant foraging decisions of a specialist herbivore.

PLoS Biol 2021 Feb 18;19(2):e3001114. Epub 2021 Feb 18.

Institute of Plant Sciences, University of Bern, Bern, Switzerland.

Plants produce complex mixtures of primary and secondary metabolites. Herbivores use these metabolites as behavioral cues to increase their fitness. However, how herbivores combine and integrate different metabolite classes into fitness-relevant foraging decisions in planta is poorly understood. Read More

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February 2021

Helical Antimicrobial Peptide Foldamers Containing Non-proteinogenic Amino Acids.

ChemMedChem 2021 Feb 10. Epub 2021 Feb 10.

Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki, Kanagawa, 210-9501, Japan.

Antimicrobial peptides (AMPs) are potential novel therapeutic drugs against microbial infections. Most AMPs function by disrupting microbial membranes because of their amphipathic properties and ordered secondary structures. In this minireview, we describe recent efforts to develop helical AMP foldamers containing non-proteinogenic amino acids, such as α,α-disubstituted α-amino acids, β-amino acids, γ-amino acids, side-chain stapling and N-alkyl glycines. Read More

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February 2021

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review.

Int J Environ Res Public Health 2021 Feb 4;18(4). Epub 2021 Feb 4.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece.

Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. Read More

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February 2021

Fine mapping identifies NAD-ME1 as a candidate underlying a major locus controlling temporal variation in primary and specialized metabolism in Arabidopsis.

Plant J 2021 Feb 1. Epub 2021 Feb 1.

Misión Biológica de Galicia (MBG-CSIC), P.O. Box 28, Pontevedra, 36080, Spain.

Plant metabolism is modulated by a complex interplay between internal signals and external cues. A major goal of all quantitative metabolomic studies is to clone the underlying genes to understand the mechanistic basis of this variation. Using fine-scale genetic mapping, in this work we report the identification and initial characterization of NAD-DEPENDENT MALIC ENZYME 1 (NAD-ME1) as the candidate gene underlying the pleiotropic network Met. Read More

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February 2021

Summary of reference chemicals evaluated by the fish short-term reproduction assay, OECD TG229, using Japanese Medaka, Oryzias latipes.

J Appl Toxicol 2021 Jan 24. Epub 2021 Jan 24.

Nanobioscience, Yokohama City University, Yokohama, Japan.

Under the Organisation for Economic Co-operation and Development (OECD), the Ministry of the Environment of Japan (MOE) added Japanese medaka (Oryzias latipes) to the test guideline fish short-term reproduction assay (FSTRA) developed by the United States Environmental Protection Agency (US EPA) using fathead minnow (Pimephales promelas). The FSTRA was designed to detect endocrine disrupting effects of chemicals interacting with the hypothalamic-pituitary-gonadal axis (HPG axis) such as agonists or antagonists on the estrogen receptor (Esr) and/or the androgen receptor (AR) and steroidogenesis inhibitors. We conducted the FSTRA with Japanese medaka, in accordance with OECD test guideline number 229 (TG229), for 16 chemicals including four Esr agonists, two Esr antagonists, three AR agonists, two AR antagonists, two steroidogenesis inhibitors, two progesterone receptor agonists, and a negative substance, and evaluated the usability and the validity of the FSTRA (TG229) protocol. Read More

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January 2021

Occurrence and fate of androgens, progestogens and glucocorticoids in two swine farms with integrated wastewater treatment systems.

Water Res 2021 Mar 14;192:116836. Epub 2021 Jan 14.

SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Environmental Theoretical Chemistry, South China Normal University, Guangzhou510006, China. Electronic address:

Steroid hormones are endocrine-disrupting chemicals that can cause adverse effects even at trace levels. The information about steroid hormones in animal wastes is still very limited. Here we investigated the occurrence and fate of fourteen androgens, twenty-one progestogens, and five glucocorticoids in Farm Luo Cheng (LC) and Farm Shui Tai (ST) with integrated wastewater treatment systems (WTSs) in South China. Read More

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The role of interferon-gamma and its signaling pathway in pediatric hematological disorders.

Pediatr Blood Cancer 2021 Apr 23;68(4):e28900. Epub 2021 Jan 23.

Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.

Interferon-gamma (IFN-γ) plays a key role in the pathophysiology of hemophagocytic lymphohistiocytosis (HLH), and available evidence also points to a role in other conditions, including aplastic anemia (AA) and graft failure following allogeneic hematopoietic stem cell transplantation. Recently, the therapeutic potential of IFN-γ inhibition has been documented; emapalumab, an anti-IFN-γ monoclonal antibody, has been approved in the United States for treatment of primary HLH that is refractory, recurrent or progressive, or in patients with intolerance to conventional therapy. Moreover, ruxolitinib, an inhibitor of JAK/STAT intracellular signaling, is currently being investigated for treating HLH. Read More

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Prenatal exposure to endocrine disrupting chemical mixtures and infant birth weight: A Bayesian analysis using kernel machine regression.

Environ Res 2021 Apr 17;195:110749. Epub 2021 Jan 17.

Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.

Background: Pregnant women are regularly exposed to a multitude of endocrine disrupting chemicals (EDCs). EDC exposures, both individually and as mixtures, may affect fetal growth. The relationship of EDC mixtures with infant birth weight, however, remains poorly understood. Read More

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A novel humanized Frizzled-7-targeting antibody enhances antitumor effects of Bevacizumab against triple-negative breast cancer via blocking Wnt/β-catenin signaling pathway.

J Exp Clin Cancer Res 2021 Jan 12;40(1):30. Epub 2021 Jan 12.

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, China.

Background: Anti-angiogenic therapy has been widely applied to the clinical treatment of malignant tumors. However, the efficacy of such treatments has been called into question, especially in triple-negative breast cancer (TNBC). Bevacizumab, the first anti-angiogenic agent approved by FDA, actually increases invasive and metastatic properties of TNBC cells, resulting from the activation of Wnt/β-catenin signaling in response to hypoxia. Read More

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January 2021