The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.     

κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

济阳坳陷下古生界潜山油气藏特征及成藏模式

济阳坳陷下古生界潜山具有多样性、复杂性的特点，潜山差异性的形成演化、油气成藏主控因素和控藏模式不明确，严重制约了该区潜山油气勘探。在潜山分类的基础上，综合利用系统恢复、分类对比和典型解剖等方法，揭示了济阳坳陷下古生界不同类型潜山的形成演化过程和油气成藏主控因素差异性，分类建立了油气成藏模式。研究表明，济阳坳陷下古生界主要发育高位新盖侵蚀残丘潜山、中位古盖拉张断块潜山、中位新古盖拉张剪切断块潜山、中位中古盖挤压拉张断块潜山和低位古盖拉张滑脱断块潜山5种潜山类型。不同类型潜山的形成演化和油气成藏各具特色，其中，高位新盖侵蚀残丘潜山的发育受隆升、侵蚀作用控制，油气成藏主要受控于油源和盖层条件，表现为"单向供烃、砂体-不整合岩溶体联合输导、残丘控藏"的成藏模式；中位古盖拉张断块潜山的发育受掀斜、断裂作用控制，油气成藏主要受控于储集条件，表现为"单向供烃、顺向断层输导、反向断层控藏"的成藏模式；中位新古盖拉张剪切断块潜山的发育受反转、翘倾和走滑切割作用控制，油气成藏主要受控于输导条件，表现为"多源供烃、断溶体立体输导、断裂控藏"的成藏模式；中位中古盖挤压拉张断块潜山的形成受强烈挤压、拉张滑脱作用控制，油气成藏主要受控于储集条件，表现为"多源供烃、断缝体输导、断褶控藏"的成藏模式；低位古盖拉张滑脱断块潜山的形成受强烈拉张滑脱作用控制，油气成藏主要受控于输导条件，表现为"顶部供烃、断缝体输导、断裂控藏"的成藏模式。