Novel drug targets for monkeypox: From viral to host proteins.

Background: The ongoing threat of the monkeypox virus (MPXV) underscores the need for new antiviral treatments, yet drug targets and candidate therapies are limited.

Methods: Calculating the centrality, conservation, and immunogenicity of MPXV proteins in the network to identify viral drug targets. Constructing the MIP-human protein interaction network and identifying key human proteins as potential drug targets through network topology analysis.

Mechanistic insights into cadmium exacerbating 2-Ethylhexyl diphenyl phosphate-induced human keratinocyte toxicity: Oxidative damage, cell apoptosis, and tight junction disruption.

Organophosphate flame retardants 2-ethylhexyldiphenyl phosphate (EHDPP) and cadmium (Cd) are ubiquitous in environmental matrices, and dermal absorption is a major human exposure pathway. However, their detrimental effects on the human epidermis remain largely unknown. In this study, human keratinocytes (HaCaT cells) were employed to examine the toxicity and underlying mechanisms of co-exposure to EHDPP and Cd.

L. Extract Attenuates DSS-Induced Ulcerative Colitis in Mice by Regulating Inflammatory Factor Release and Blocking NF-B Activation.

Ulcerative colitis (UC) is a chronic gastroenteric inflammatory disease that may cause life-threatening complications. Currently available therapeutic drugs are not as effective as expected, necessitating the development of new targets and drugs. The etiology and pathogenetic mechanisms of UC are largely unclear; thus, the treatment effects are limited.

Are high-risk heavy metal(loid)s contaminated vegetables detrimental to human health? A study of incorporating bioaccessibility and toxicity into accurate health risk assessment.

Heavy metal(loid)s in the environment threaten food safety and human health. Health risk assessment of vegetables based on total or bioaccessible heavy metal(loid)s was widely used but can overestimate their risks, so exploring accurate methods is urgent for food safety evaluation and management. In this study, a total of 224 frequently consumed vegetables and their corresponding grown soils were collected from Yunnan, Southwest China.

Preparation of oral nanoparticles of oil and prevention application of cold stress in mice.

oil has an important function in relieving cold stress. However, its application in this aspect has still been restricted because of instability and low bioavailability. In this study, oil was extracted through Soxhlet extraction, analyzed through gas chromatography-mass spectrometry (GC-MS), and nanopackaged into a yeast shell for the preparation of nanoparticles for oral administration.

Organophosphorus Flame Retardant TCPP Induces Cellular Senescence in Normal Human Skin Keratinocytes: Implication for Skin Aging.

Tris (1-chloro-2-propyl) phosphate (TCPP) is one of the most frequently detected organophosphorus flames in the environment. Continuous daily exposure to TCPP may harm human skin. However, little is known about the adverse effects of TCPP on human skin.

The oral bioaccessibility and gingival cytotoxicity of metal(loid)s in wild vegetables from mining areas: Implication for human oral health.

Background: Heavy metal(loid)s are frequently detected in vegetables posing potential human health risks, especially for those grown around mining areas. However, the oral bioaccessibility and gingival cytotoxicity of heavy metals in wild vegetables remain unclear.

Methods: In this study, we assessed the total and bioaccessible Cr, As, Cd, Pb, and Ni in four wild vegetables from mining areas in Southwest China.

Mechanisms of Cd-Induced Cytotoxicity in Normal Human Skin Keratinocytes: Implication for Human Health.

Cadmium (Cd) is one of the toxic heavy metals found widely in the environment. Skin is an important target organ of Cd exposure. However, the adverse effects of Cd on human skin are still not well known.

Identification of a Novel Frameshift Variant in a Chinese Family with Neurofibromatosis Type 1.

Neurofibromatosis type 1 () is a progressive neurocutaneous disorder in humans, mainly characterized by café-au-lait macules (CALMs) and neurofibromas. is caused by variants of the neurofibromin 1 gene (), which encodes a Ras-GTPase-activating protein called neurofibromin. variants may result in loss of neurofibromin function and elevation of cell proliferation and tumor formation.

Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2X3 receptors.

P2X receptors are a family of extracellular ATP-gated trimeric cation channels that is widely distributed in human tissues. Quite some drug candidates targeting P2X receptors have entered into preclinical or main phases of clinical trials, but many of them failed due to low subtype-selectivity or species differences in pharmacological activities between human and experimental animals. Here, we identified the distinct inhibitory efficacies of NF110, a competitive inhibitor, between the rat (rP2X3) and human (hP2X3) P2X3 receptors.

A novel compound heterozygous mutation in the GJB2 gene is associated with non-syndromic hearing loss in a Chinese family.

Autosomal recessive (AR) non-syndromic hearing loss (NSHL) is the most common form of hereditary deafness. Mutations in the gap junction protein beta 2 (GJB2) gene encoding connexin 26 (Cx26) account for about 50% of cases of ARNSHL. In the current study, a combination of exome sequencing and Sanger sequencing in a Chinese Dong family with ARNSHL allowed identification of a novel compound heterozygous mutation c.

The nonproton ligand of acid-sensing ion channel 3 activates mollusk-specific FaNaC channels via a mechanism independent of the native FMRFamide peptide.

The degenerin/epithelial sodium channel (DEG/ENaC) superfamily of ion channels contains subfamilies with diverse functions that are fundamental to many physiological and pathological processes, ranging from synaptic transmission to epileptogenesis. The absence in mammals of some DEG/ENaCs subfamily orthologues such as FMRFamide peptide-activated sodium channels (FaNaCs), which have been identified only in mollusks, indicates that the various subfamilies diverged early in evolution. We recently reported that the nonproton agonist 2-guanidine-4-methylquinazoline (GMQ) activates acid-sensing ion channels (ASICs), a DEG/ENaC subfamily mainly in mammals, in the absence of acidosis.

Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel.

FMRFamide (Phe-Met-Arg-Phe-NH2)-activated sodium channel (FaNaC) is an amiloride-sensitive sodium channel activated by endogenous tetrapeptide in invertebrates, and belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. The ENaC/DEG superfamily differs markedly in its means of activation, such as spontaneously opening or gating by mechanical stimuli or tissue acidosis. Recently, it has been observed that a number of ENaC/DEG channels can be activated by small molecules or peptides, indicating that the ligand-gating may be an important feature of this superfamily.

[Study on the chemical constituents in Pouzolzia zeylanica].

Objective: To study the chemical constituents of Pouzolzia zeylanica.

Methods: Many chromatography means were used in separation and purification, and the structures of all compounds were identified by the means of spectroscopic analysis and physicochemical properties.

Results: 14 compounds were elucidated as: beta-sitosterol (1), daucosterol (2), oleanolic acid (3), epicatechin (4), alpha-amyrin (5), eugenyl-beta-rutinoside (6), 2alpha, 3alpha, 19alpha-trihydroxyurs-12-en-28-oic (7), scopolin (8), scutellarein-7-O-alpha-L-rhamnoside (9), scopoletin (10), quercetin (11), quercetin-3-O-beta-D-glucoside (12), apigenin (13), 2alpha-hydroxyursolic acid (14).