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Nanomedicine 2021 Apr 7:102395. Epub 2021 Apr 7.

Department of Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry (LIC), Leiden University, P.O. Box 9502, 2300, RA, Leiden, The Netherlands; Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300, RA, Leiden, The Netherlands. Electronic address:

Clearance of nanoparticles (NPs) after intravenous injection - mainly by the liver - is a critical barrier for the clinical translation of nanomaterials. Physicochemical properties of NPs are known to influence their distribution through cell-specific interactions; however, the molecular mechanisms responsible for liver cellular NP uptake are poorly understood. Liver sinusoidal endothelial cells and Kupffer cells are critical participants in this clearance process. Read More

Br J Pharmacol 2021 Apr 10. Epub 2021 Apr 10.

State Key Laboratory of Natural Medicines and Department of TCM pharmacology, School of Traditional Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China, 211198.

Background And Purpose: Cocamide monoethanolamide (CMEA) is commonly used as a surfactant-foam booster in cosmetic formulations. Upon contact with the eye or other sensitive skin areas, CMEA elicits sting and lasting irritation. We hypothesized a specific molecular interaction with TRPV1 by which CMEA caused eye irritation. Read More

J Biol Chem 2021 Jan 8;296:100255. Epub 2021 Jan 8.

Laboratory of Immunobiology, Dana Farber Cancer Institute, Boston, Massachusetts, USA; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA; Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

T lymphocytes discriminate between healthy and infected or cancerous cells via T-cell receptor-mediated recognition of peptides bound and presented by cell-surface-expressed major histocompatibility complex molecules (MHCs). Pre-T-cell receptors (preTCRs) on thymocytes foster development of αβT lymphocytes through their β chain interaction with MHC displaying self-peptides on thymic epithelia. The specific binding of a preTCR with a peptide-MHC complex (pMHC) has been identified previously as forming a weak affinity complex with a distinct interface from that of mature αβTCR. Read More

Transl Psychiatry 2021 Apr 9;11(1):212. Epub 2021 Apr 9.

Neuronal Oscillations Laboratory, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, 17164, Solna, Sweden.

Gamma and theta brain rhythms play important roles in cognition and their interaction can affect gamma oscillation features. Hippocampal theta oscillations depend on cholinergic and GABAergic input from the medial septum-diagonal band of Broca. These projecting neurons undergo degeneration during aging and maintain high levels of neurotrophin receptor p75 (p75). Read More

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

Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455;

Classical pharmacological models have incorporated an "intrinsic efficacy" parameter to capture system-independent effects of G protein-coupled receptor (GPCR) ligands. However, the nonlinear serial amplification of downstream signaling limits quantitation of ligand intrinsic efficacy. A recent biophysical study has characterized a ligand "molecular efficacy" that quantifies the influence of ligand-dependent receptor conformation on G protein activation. Read More

Psychoneuroendocrinology 2021 Apr 1;128:105214. Epub 2021 Apr 1.

Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University of Düsseldorf, Universitätsstraße 1, 140225 Düsseldorf, Germany; Mauritius Hospital Meerbusch, Strümper Straße 111, 40670 Meerbusch, Germany. Electronic address:

Recent research suggests that when we lack a sense of control, we are prone to motivational failures and early quitting in competitions. Testosterone, on the other hand, is thought to boost competitiveness. Here we investigate the interaction between these factors, testing the testosterone's potential to enhance persistence in a competition against a stronger opponent, depending on experimentally manipulated perceived control. Read More

Immunity 2021 Apr 1. Epub 2021 Apr 1.

Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK; Genotype-to-Phenotype UK National Virology Consortium. Electronic address:

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. Read More

FASEB J 2021 May;35(5):e21374

Department of Neurobiology, School of Neurobiology, Biochemistry and Biophysics School, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor. Read More

J Integr Neurosci 2021 Mar;20(1):247-254

Department of Pharmacology, College of Medicine and Health Science, Khalifa University of Science and Technology, 127788 Abu Dhabi, United Arab Emirates.

The hiccup (Latin ) is an involuntary periodic contraction of the diaphragm followed by glottic closure, which can be a rare side effect of aripiprazole. In contrast to the structurally closely related aripiprazole, brexpiprazole was not associated with this particular adverse drug reaction. Having two very similar drugs that differ in their ability to induce hiccups represents a unique opportunity to gain insight into the receptors involved in the pathophysiology of the symptom and differences in clinical effects between aripiprazole and brexpiprazole. Read More

Histol Histopathol 2021 Apr 9:18336. Epub 2021 Apr 9.

Department of Orthodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China.

Background: Peri-miniscrew implant is a temporary assistant armamentarium for the treatment of severe malocclusion and complex tooth movement, the inflammation around it is the main reason for the failure of orthodontic treatment due to the implant loosening and falling out. Inflammation around the peri-miniscrew implant is associated with the release of pro-inflammatory cytokines. These pro-inflammatory cytokines, in turn, recruit immune cells (such as macrophages, dendritic cells, T cells, and B cells), which can produce and release inflammatory biomarkers, regulate the interaction between immune cells, periodontal ligament cells, osteoblasts, and so on. Read More

Cerebellum 2021 Apr 8. Epub 2021 Apr 8.

Department of Psychiatry, Laboratory of Molecular Neuroscience, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.

Structural and functional abnormalities in the cerebellar midline region, including the fastigial nucleus, have been reported in neuropsychiatric disorders, also comprising the cerebellar cognitive affecting syndrome. In rats, early fastigial lesions reduce social interaction during development and lead to cognitive and emotional deficits in adults, accompanied by compromised neuronal network activity. Since epigenetic mechanisms are implicated in the etiology of neuropsychiatric disorders, we investigated whether fastigial nucleus lesions in juvenile rats would impact epigenetic regulation of neural transmission. Read More

J Assist Reprod Genet 2021 Apr 9. Epub 2021 Apr 9.

The Department of Gynecology, Longyan People Hospital, Longyan, 364000, Fujian, China.

Objective: To study the correlation between SNPs at phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) rs9838117 site, erb-b2 receptor tyrosine kinase 2 (ERBB2) rs1058808 site, and their interactions with environmental factors and the epithelial ovarian cancer (EOC) risk.

Methods: Sanger sequencing was used to analyze the genotypes of PIK3CA rs9838117 and ERBB2 rs1058808 site in 587 patients with epithelial ovarian cancer (EOC). Multi-factor dimensionality reduction (MDR) was applied to analyze the interaction between PIK3CA rs9838117 and ERBB2 rs1058808 site and the clinical data. Read More

J Mol Model 2021 Apr 8;27(5):126. Epub 2021 Apr 8.

Department of Chemistry, National Institute of Technology-Durgapur, Durgapur, West Bengal, 713209, India.

Thyroid hormone receptor (THR) belongs to the nuclear receptor (NR) superfamily that is activated by binding of appropriate ligand molecules (thyroid hormones). These receptors directly bind to specific DNA sequences for gene expression, which is essential for metabolism, homeostasis, and the development of organisms, making it an important drug target. Extensive MD-simulation studies of triiodothyronine (T3) docked modeled rnTHRβ1 structures have indicated the presence of twelve conserved water molecules at the DNA-DBD (DNA binding domain) interface. Read More

Commun Biol 2021 Apr 8;4(1):445. Epub 2021 Apr 8.

Leibniz Institute of Plant Biochemistry, Dept. Cell and Metabolic Biology, Halle (Saale), Germany.

Black pepper (Piper nigrum L.) is the world's most popular spice and is also used as an ingredient in traditional medicine. Its pungent perception is due to the interaction of its major compound, piperine (1-piperoyl-piperidine) with the human TRPV-1 or vanilloid receptor. Read More

Science 2021 Apr;372(6538):171-175

School of Life Sciences, East China Normal University, Shanghai, China.

Sexual reproduction in angiosperms relies on precise communications between the pollen and pistil. The molecular mechanisms underlying these communications remain elusive. We established that in , a stigmatic gatekeeper, the ANJEA-FERONIA (ANJ-FER) receptor kinase complex, perceives the RAPID ALKALINIZATION FACTOR peptides RALF23 and RALF33 to induce reactive oxygen species (ROS) production in the stigma papillae, whereas pollination reduces stigmatic ROS, allowing pollen hydration. Read More

SAR QSAR Environ Res 2021 Apr 9:1-25. Epub 2021 Apr 9.

Computer Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India.

HIV-1 gp120 provides a multistage viral entry process through the conserved CD4 binding site. Hunting of potential blockers can diminish the interaction of gp120 with the CD4 host receptor leading to the suppression of HIV-1 infection. Structure-based pharmacophore virtual screening followed by binding free energy calculation, molecular dynamics (MD) simulation and density functional theory (DFT) calculation is applied to discriminate the potential blockers from six small molecule databases. Read More

Ann Palliat Med 2021 Apr 1. Epub 2021 Apr 1.

Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. Read More

Chem Biol Interact 2021 Apr 5:109463. Epub 2021 Apr 5.

National Poison Control Centre, Military Medical Academy, University of Defence, Belgrade, Serbia.

Memantine is the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, used in the treatment of Alzheimer's disease. It also known that memantine pretreatment assured protection of skeletal muscles from poisoning with nerve agents and an interaction between memantine and AChE was proposed. In the study presented we examined interactions of memantine and its main metabolite (1-amino-3-hydroxymethyl-5-methyl adamantine, Mrz 2/373) with AChE in vitro as well as their effect on kinetics of the soman-induced AChE inhibition and aging. Read More

J Gen Virol 2021 Apr;102(4)

Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists. Read More

Biomed Res Int 2021 19;2021:8883800. Epub 2021 Mar 19.

Department of Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou 570208, Hainan Province, China.

This study is to study the expression of CXCRs in ovarian cancer tissues and their value in prognosis. The expressions of CXCR1-CXCR7 mRNA between ovarian tumor tissues and normal tissues and in different pathological types of ovarian tumor tissues were compared by ONCOMINE online tool. The relationship between the expression of CXCRs and clinical pathological staging was studied by GEPIA. Read More

J Pharm Bioallied Sci 2020 Nov 5;12(Suppl 2):S711-S717. Epub 2020 Nov 5.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.

Introduction: Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties.

Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity . Read More

Nat Commun 2021 04 7;12(1):2086. Epub 2021 Apr 7.

Laboratory of Receptor Structure and Signaling, The HIT Center for Life Sciences, Harbin Institute of Technology, Harbin, China.

Histamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human HR in complex with a G protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for G engagement in a model of "squash to activate and expand to deactivate". Read More

BMC Pharmacol Toxicol 2021 Apr 7;22(1):18. Epub 2021 Apr 7.

Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Vitamin D deficiency is prevalent in patients with non-alcoholic fatty liver disease (NAFLD), but there are debates on the usefulness of vitamin D treatment. The interindividual variations in response may be due to different genetic backgrounds. The present study evaluated the efficacy of calcitriol treatment in NAFLD patients with regard to the vitamin D receptor (VDR) genotypes of FokI polymorphism. Read More

BMC Endocr Disord 2021 Apr 7;21(1):61. Epub 2021 Apr 7.

Department of Ayurveda, Rajiv Gandhi Education Society's Ayurvedic Medical College, Ron, Karanataka, 582209, India.

Background: Type 1 diabetes (T1D) is a serious threat to childhood life and has fairly complicated pathogenesis. Profound attempts have been made to enlighten the pathogenesis, but the molecular mechanisms of T1D are still not well known.

Methods: To identify the candidate genes in the progression of T1D, expression profiling by high throughput sequencing dataset GSE123658 was downloaded from Gene Expression Omnibus (GEO) database. Read More

Biochemistry (Mosc) 2021 Jan;86(Suppl 1):S50-S70

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.

Although TRPV1 ion channel has been attracting researchers' attention for many years, its functions in animal organisms, the principles of regulation, and the involvement in pathological processes have not yet been fully clarified. Mutagenesis experiments and structural studies have identified the structural features of the channel and binding sites for its numerous ligands; however, these studies are far from conclusion. This review summarizes recent achievements in the TRPV1 research with special focus on structural and functional studies of the channel and on its ligands, which are extremely diverse in their nature and interaction specificity to TRPV1. Read More

Pulm Pharmacol Ther 2021 Apr 4:102030. Epub 2021 Apr 4.

Novartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, 07936, USA.

Fevipiprant is an oral, non-steroidal, highly selective, reversible antagonist of the prostaglandin D (DP) receptor. The DP receptor is a mediator of inflammation expressed on the membrane of key inflammatory cells, including eosinophils, Th2 cells, type 2 innate lymphoid cells, CD8+ cytotoxic T cells, basophils and monocytes, as well as airway smooth muscle and epithelial cells. The DP receptor pathway regulates the allergic and non-allergic asthma inflammatory cascade and is activated by the binding of prostaglandin D. Read More

Cell Rep 2021 Apr;35(1):108949

Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO, USA. Electronic address:

The colon epithelium is a primary point of interaction with the microbiome and is regenerated by a few rapidly cycling colonic stem cells (CSCs). CSC self-renewal and proliferation are regulated by growth factors and the presence of bacteria. However, the molecular link connecting the diverse inputs that maintain CSC homeostasis remains largely unknown. Read More

J Med Chem 2021 Apr 7. Epub 2021 Apr 7.

Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts 02115, United States.

We apply the magic methyl effect to improve the potency/efficacy of GAT211, the prototypic 2-phenylindole-based cannabinoid type-1 receptor (CB1R) agonist-positive allosteric modulator (ago-PAM). Introducing a methyl group at the α-position of nitro group generated two diastereomers, the greater potency and efficacy of , (±)- vs , (±)- constitutes the first demonstration of diastereoselective CB1R-allosteric modulator interaction. Of the (±)- enantiomers, (-)-(,)- evidenced improved potency over GAT211 as a CB1R ago-PAM, whereas (+)-(,)- was a CB1R allosteric agonist biased toward G protein- vs β-arrestin1/2-dependent signaling. Read More

Eur J Neurosci 2021 Apr 7. Epub 2021 Apr 7.

Neuroscience Center - HiLife, University of Helsinki, Finland.

Cholesterol is an essential constituent of cell membranes. The discovery of cholesterol recognition amino acid consensus (CRAC) motif in proteins indicated a putative direct, non-covalent interaction between cholesterol and proteins. In the present study, we evaluated the presence of a CRAC motif and its inverted version (CARC) in the transmembrane region (TMR) of the tyrosine kinase receptor family (RTK) in several species using in silico methods. Read More

Blood 2021 Apr 6. Epub 2021 Apr 6.

Oregon Health and Science University, Portland, Oregon, United States.

Neogenin (NEO1) is a ubiquitously expressed multi-functional transmembrane protein. It interacts with hemojuvelin (HJV), a BMP co-receptor that plays a pivotal role in hepatic hepcidin expression. Earlier studies suggest that the function of HJV relies on its interaction with NEO1. Read More