Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.

P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.

[Compound Decoction protects diabetic rats against cardiomyopathy by inhibiting myocardial apoptosis and inflammation regulating the PI3K/Akt signaling pathway].

Objective: To explore the therapeutic mechanism of compound Decoction against diabetic cardiomyopathy (DCM).

Methods: Drugbank, Gene Cards, OMIM and PharmGKb databases were used to obtain DCM-related targets, and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis. The "Traditional Chinese Medicine-Key Component-Key Target-Key Pathway" network was constructed using Cytoscape 3.

TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception.

Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1, Trpv1, and Trpv1. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT.

Integrated 16S rRNA sequencing and nontargeted metabolomics analysis to reveal the mechanisms of Yu-Ye Tang on type 2 diabetes mellitus rats.

Introduction: Yu-Ye Tang (YYT) is a classical formula widely used in treatment of type 2 diabetes mellitus (T2DM). However, the specific mechanism of YYT in treating T2DM is not clear.

Methods: The aim of this study was to investigate the therapeutic effect of YYT on T2DM by establishing a rat model of T2DM.

[Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial].

Objective: To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation.

Methods: Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group.

Tetrahydrocurcumin Ameliorates Acute Hypobaric Hypoxia-Induced Cognitive Impairment in Mice.

Ma, Xuexinyu, Yang Pan, Yuye Xue, Yao Li, Yan Zhang, Yani Zhao, Xingzhao Xiong, Jianbo Wang, and Zhifu Yang. Tetrahydrocurcumin ameliorates acute hypobaric hypoxia-induced cognitive impairment in mice. .

The long β2,3-sheets encoded by redundant sequences play an integral role in the channel function of P2X7 receptors.

P2X receptors are a class of nonselective cation channels widely distributed in the immune and nervous systems, and their dysfunction is a significant cause of tumors, inflammation, leukemia, and immune diseases. P2X7 is a unique member of the P2X receptor family with many properties that differ from other subtypes in terms of primary sequence, the architecture of N- and C-terminals, and channel function. Here, we suggest that the observed lengthened β2- and β3-sheets and their linker (loop β2,3), encoded by redundant sequences, play an indispensable role in the activation of the P2X7 receptor.

GSK1702934A and M085 directly activate TRPC6 via a mechanism of stimulating the extracellular cavity formed by the pore helix and transmembrane helix S6.

Transient receptor potential canonical (TRPC) channels, as important membrane proteins regulating intracellular calcium (Ca) signaling, are involved in a variety of physiological and pathological processes. Activation and regulation of TRPC are more dependent on membrane or intracellular signals. However, how extracellular signals regulate TRPC6 function remains to be further investigated.

A conserved residue in the P2X4 receptor has a nonconserved function in ATP recognition.

Highly conserved amino acids are generally anticipated to have similar functions across a protein superfamily, including that of the P2X ion channels, which are gated by extracellular ATP. However, whether and how these functions are conserved becomes less clear when neighboring amino acids are not conserved. Here, we investigate one such case, focused on the highly conserved residue from P2X4, E118 (rat P2X4 numbering, rP2X4), a P2X subtype associated with human neuropathic pain.

Multifunctional bioactive Nd-Ca-Si glasses for fluorescence thermometry, photothermal therapy, and burn tissue repair.

Photothermal therapy (PTT), an emerging tumor treatment technology, has attracted tremendous interest, but excessive heat will cause damage to surrounding healthy tissues. Therefore, in situ temperature monitoring during PTT is of great importance to determine optimal treatment temperature and repair heat-damaged normal tissues. Here, we report the preparation of multifunctional Nd-Ca-Si silicate glasses and glass/alginate composite hydrogels that not only have photothermal property but also emit fluorescence under 808-nm laser irradiation, and its fluorescence intensity is linearly correlated with in situ temperature.

Intersubunit physical couplings fostered by the left flipper domain facilitate channel opening of P2X4 receptors.

P2X receptors are ATP-gated trimeric channels with important roles in diverse pathophysiological functions. A detailed understanding of the mechanism underlying the gating process of these receptors is thus fundamentally important and may open new therapeutic avenues. The left flipper (LF) domain of the P2X receptors is a flexible loop structure, and its coordinated motions together with the dorsal fin (DF) domain are crucial for the channel gating of the P2X receptors.

[Clinical observation of dysphagia after cerebral infarction treated with awn-like needle at Tiantu(CV 22)].

Objective: To observe the effect difference between awn-like needle at Tiantu(CV 22) and filiform needle for dysphagia after cerebral infarction.

Methods: One hundred patients were randomly assigned into an awn-like needle group and a filiform needle group,50 cases in each one. Based on the conventional western medicine for all the patients,awn-like needle was applied at Tiantu(CV 22) in the awn-like needle group;while acupuncture was used at Fengchi(GB 20),Shanglianquan(Extra),Shuigou(GV 26) and Tongli(HT 5) in the filiform needle group,combined with pricking at Jinjin(EX-HN 12), Yuye(EX-HN 13),posterior pharyngeal wall with three-edged needle method.

[Observation on Therapeutic Effects of Acupuncture Combined with Cutaneous Electrical Stimulation for Dysphagia in Patients with Cerebral 1nfarction].

Objective: To observe the clinical effect of acupuncture combined with neck-skin electrical stimulation (NSES) on dysphagia in patients with cerebral infarction (CI).

Methods: A total of 120 CI patients with dysphagia were randomly divided into acupuncture group, NSES group and acupuncture + NSES group (combined treatment group, n = 40 in each group). Acupuncture stimulation of Fengchi (GB20), Yifeng (TE 17), etc.