MRGPRX2 facilitates IgE-mediated systemic anaphylaxis in a newly established knock-in mouse model.

Background: In addition to FcεRI, a subtype of human mast cells (MCs) expresses Mas-related G protein-coupled receptor X2 (MRGPRX2; mouse counterpart MrgprB2). Although MrgprB2 contributes to IgE-mediated passive systemic anaphylaxis (PSA) in vivo, an MRGPRX2 inhibitor, compound 9 (C9), does not block MrgprB2- or IgE-mediated MC degranulation in vitro.

Objective: Our aim was to generate mice expressing human MRGPRX2 to study receptor function in vitro and PSA in vivo.

Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8 T cell activity and biomarker during the evolution of type 1 diabetes.

Aims/hypothesis: Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death protein 1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesised that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.

Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of Type 1 Diabetes.

Aims/hypothesis: Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death-1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesized that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.

Large-Scale Screening of Per- and Polyfluoroalkyl Substance Binding Interactions and Their Mixtures with Nuclear Receptors.

Despite their significant impact, comprehensive screenings and detailed analyses of per- and polyfluoroalkyl substance (PFAS) binding strengths at the orthosteric and allosteric sites of NRs are currently lacking. This study addresses this gap by focusing on the binding interaction analysis of both common and uncommon PFAS with the nuclear receptors (NRs) vitamin D receptor (VDR), peroxisome proliferator-activated receptor gamma (PPARγ), pregnane X receptor (PXR), and estrogen receptor alpha (ERα). Advanced docking simulations were used to screen 9507 PFAS chemicals at the orthosteric and allosteric sites of PPARγ, PXR, VDR, and ERα.

Decoding the immune dance: Unraveling the interplay between beta cells and type 1 diabetes.

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the specific destruction of insulin-producing beta cells in the pancreas by the immune system, including CD4 cells which orchestrate the attack and CD8 cells which directly destroy the beta cells, resulting in the loss of glucose homeostasis.

Scope Of Review: This comprehensive document delves into the complex interplay between the immune system and beta cells, aiming to shed light on the mechanisms driving their destruction in T1D. Insights into the genetic predisposition, environmental triggers, and autoimmune responses provide a foundation for understanding the autoimmune attack on beta cells.

Ultrasmall copper-metal organic framework (Cu-MOF) quantum dots decorated on waste derived biochar for enhanced removal of emerging contaminants: Synergistic effect and mechanistic insight.

This study proposes a novel one-pot hydrothermal impregnation strategy for surface decoration of waste derived pisum sativum biochar with zero‒dimensional Cu‒MOF Quantum dots (PBC‒HK), with an average particle size of 5.67 nm, for synergistic removal of an emerging sulfur containing drug pantoprazole (PTZ) and Basic Blue 26 (VB) dye within 80 min and 50 min of visible-light exposure, respectively. The designed Integrated Photocatalytic Adsorbent (IPA) presented an enhanced PTZ removal efficiency of 95.

ZnO-based Cu metal-organic framework (MOF) nanocomposite for boosting and tuning the photocatalytic degradation performance.

Although metal-organic frameworks (MOFs) are a viable choice for photocatalysts with large surface area and tunable pore structure, the rapid recombination of excited photogenerated charges results in low activity towards photodegradation. Aiming at improving the photocatalytic activities of MOFs, different strategies to incorporate MOF with light-harvesting semiconductors have been developed. In this research, we report an effective photocatalyst designed by incorporating Cu-MOF with ZnO for the photocatalytic degradation of Rose Bengal exhibiting excellent degradation efficiency of 97.

Sustainable degradation of pollutants, generation of electricity and hydrogen evolution via photocatalytic fuel cells: An Inclusive Review.

Environmental pollution and energy crisis have recently become one of the major global concerns. Insincere discharge of massive amount of organic and inorganic wastes into the aqueous bodies causes serious impact on our environment. However, these organic substances are significant sources of carbon and energy that could be sustainably utilized rather than being discarded.

Role of MrgprB2 in Rosacea-Like Inflammation in Mice: Modulation by β-Arrestin 2.

Cathelicidin LL-37‒mediated activation of mast cells (MCs) has been implicated in the pathogenesis of rosacea, but the receptor involved and the mechanism of its activation and regulation remain unknown. We found that skin biopsies from patients with rosacea display higher frequencies of MCs expressing MRGPRX2 (mouse counterpart MrgprB2) than normal skin. Intradermal injection of LL-37 in wild-type mice resulted in MC recruitment, expression of inflammatory mediators, and development of rosacea-like inflammation.

Ionic liquid based composites: A versatile materials for remediation of aqueous environmental contaminants.

Water pollution is one of the most aggravated problems threatening the sustainability of human race and other life forms due to the rapid pace of civilization and industrialization. A long history exists of release of hazardous pollutants into the water bodies due to selfish human activities since the Industrial Revolution, but no effort has been completely successful in curbing the activities that result in the degradation of our environment. These pollutants are harmful, carcinogenic and have adverse health effects to all forms of life.

Inhibition of Orai Channel Function Regulates Mas-Related G Protein-Coupled Receptor-Mediated Responses in Mast Cells.

Mast cells (MCs) are tissue resident immune cells that play important roles in the pathogenesis of allergic disorders. These responses are mediated the cross-linking of cell surface high affinity IgE receptor (FcϵRI) by antigen resulting in calcium (Ca) mobilization, followed by degranulation and release of proinflammatory mediators. In addition to FcϵRI, cutaneous MCs express Mas-related G protein-coupled receptor X2 (MRGPRX2; mouse ortholog MrgprB2).

DOCK2 Promotes Pleural Fibrosis by Modulating Mesothelial to Mesenchymal Transition.

Mesothelial to mesenchymal transition (MesoMT) is one of the crucial mechanisms underlying pleural fibrosis, which results in restrictive lung disease. DOCK2 (dedicator of cytokinesis 2) plays important roles in immune functions; however, its role in pleural fibrosis, particularly MesoMT, remains unknown. We found that amounts of DOCK2 and the MesoMT marker α-SMA (α-smooth muscle actin) were significantly elevated and colocalized in the thickened pleura of patients with nonspecific pleuritis, suggesting the involvement of DOCK2 in the pathogenesis of MesoMT and pleural fibrosis.

Correction: A ferrocene functionalized Schiff base containing Cu(II) complex: synthesis, characterization and parts-per-million level catalysis for azide alkyne cycloaddition.

Correction for 'A ferrocene functionalized Schiff base containing Cu(ii) complex: synthesis, characterization and parts-per-million level catalysis for azide alkyne cycloaddition' by Firdaus Rahaman Gayen et al., Dalton Trans., 2020, 49, 6578-6586, DOI: 10.

Multifaceted MRGPRX2: New insight into the role of mast cells in health and disease.

Cutaneous mast cells (MCs) express Mas-related G protein-coupled receptor-X2 (MRGPRX2; mouse ortholog MrgprB2), which is activated by an ever-increasing number of cationic ligands. Antimicrobial host defense peptides (HDPs) generated by keratinocytes contribute to host defense likely by 2 mechanisms, one involving direct killing of microbes and the other via MC activation through MRGPRX2. However, its inappropriate activation may cause pseudoallergy and likely contribute to the pathogenesis of rosacea, atopic dermatitis, allergic contact dermatitis, urticaria, and mastocytosis.

MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants.

Perioperative hypersensitivity (POH) to the neuromuscular blocking drug (NMBD) rocuronium was previously thought to be IgE and mast cell (MC)-mediated. However, the recent seminal observation that rocuronium induces degranulation in murine peritoneal MCs (PMCs) via Mas-related G protein-coupled receptor B2 (MrgprB2) led to the idea that POH to this drug involves the activation of MRGPRX2 (human ortholog of MrgprB2). Furthermore, based on the demonstration that a patient with POH to rocuronium displayed three missense mutations (M196I, L226P and L237P) in MRGPRX2's transmembrane domains, it was proposed that this hypersensitivity reaction resulted from aberrant activation of this receptor.

Mast Cell-Specific MRGPRX2: a Key Modulator of Neuro-Immune Interaction in Allergic Diseases.

Purpose Of Review: Atopic dermatitis (AD) and allergic asthma are complex disorders with significant public health burden. This review provides an overview of the recent developments on Mas-related G protein-coupled receptor-X2 (MRGPRX2; mouse counterpart MrgprB2) as a potential candidate to target neuro-immune interaction in AD and allergic asthma.

Recent Findings: Domestic allergens directly activate sensory neurons to release substance P (SP), which induces mast cell degranulation via MrgprB2 and drives type 2 skin inflammation in AD.

MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway.

Codeine stimulates skin mast cells and is therefore used in skin tests and as an inducer of experimental itch. MRGPRX2 responds to various drugs, including opioids, to elicit pseudoallergic reactions, but whether it represents the main opiate receptor of skin mast cells remains unknown. By combining a number of approaches, including the silencing of MRGPRX2, we now report that MRGPRX2 is indeed the dominant codeine receptor of dermal mast cells.

Senna plant generates reactive oxygen species (ROS) and induces apoptosis in Hymenolepis diminuta.

Like mammalian cells, helminth parasites are equipped with an array of enzymatic anti-oxidant system which has an adaptive strategy to cope up with several conditions of stress that arise from host immune response or drug treatment. Earlier, we had reported that three species of Senna, viz. S.

A ferrocene functionalized Schiff base containing Cu(ii) complex: synthesis, characterization and parts-per-million level catalysis for azide alkyne cycloaddition.

Atom economy is one of the major factors in developing catalysis chemistry. Using the minimum amount of catalyst to obtain the maximum product yield is of the utmost priority in catalysis, which drives us to use parts-per-million (ppm) levels of catalyst loadings in syntheses. In this context, a new ferrocene functionalized Schiff base and its copper(ii) complex have been synthesized and characterized.

Corrigendum: l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of by Enhancing Arginase-Mediated Polyamine Synthesis.

[This corrects the article DOI: 10.3389/fimmu.2017.

Identification of Gain and Loss of Function Missense Variants in MRGPRX2's Transmembrane and Intracellular Domains for Mast Cell Activation by Substance P.

The neuropeptide substance P (SP) contributes to neurogenic inflammation through the activation of human mast cells via Mas-related G protein-coupled receptor-X2 (MRGPRX2). Using pertussis toxins and YM-254890, we demonstrated that SP induces Ca mobilization and degranulation via both the Gαi and Gαq family of G proteins in rat basophilic leukemia (RBL-2H3) cells stably expressing MRGPRX2. To determine the roles of MRGPRX2's transmembrane (TM) and intracellular domains on SP-induced responses, we utilized information obtained from both structural modeling and naturally occurring MRGPRX2 missense variants.

Modulation of TLR4 Sialylation Mediated by a Sialidase Neu1 and Impairment of Its Signaling in Infected Macrophages.

Altered sialylation is generally maintained by a fine balance between sialidases and sialyltransferases, which plays an essential role during disease pathogenesis. TLR4 is a membrane-bound highly sialylated glycoprotein predominantly having α2,3-linked sialic acids. It is one of the most important client molecules in the anti-leishmanial innate immune arm.

An in vitro confirmation of the ethonopharmacological use of Senna plants as anthelmintic against rumen fluke Paramphistomum gracile.

Background: Paramphistomosis is a pathogenic disease of domesticated ruminants, causing great economic loss in dairy industry and meat production. It is considered as a neglected tropical disease with highest prevalence throughout tropical and subtropical regions, particularly in Africa, Asia, Europe, and Australia. There are few trematocidal drugs available in the market.

β-Arrestin2 expressed in mast cells regulates ciprofloxacin-induced pseudoallergy and IgE-mediated anaphylaxis.

The adapter protein β-arrestin2 inhibits Mrgprb2 and FcεRI-mediated mast cell degranulation to attenuate pseudo-allergy and anaphylaxis. Thus, targeting β-arrestin2 in mast cells could provide novel therapeutic options for modulating pseudo-allergy and anaphylaxis.