A mechanistic study of Anwei decoction intervention in a rat model of gastric intestinal metaplasia through the endoplasmic reticulum stress - Autophagy pathway.

OBJECTIVE: To investigate the mechanism of Anwei decoction (AWD) intervention on gastric intestinal metaplasia (GIM) using a rat model through the endoplasmic reticulum stress-autophagy pathway. METHODS: Gastric intestinal metaplasia was induced in rats using 1-methyl-3-nitro-1-nitrosoguanidine. The experiment included a normal control group, a model group, and low-, medium- and high-dose AWD groups. The specificity of intestinal epithelial cells was determined for model establishment and drug efficacy by detecting the protein expression of markers such as MUC2, VILLIN and CDX2 through western blotting (WB). The effects of AWD on endoplasmic reticulum stress and autophagy were evaluated by measuring the mRNA and protein expression levels of endoplasmic reticulum stress markers (PEPK, ATF6, CHOP and caspase-12) and autophagy markers (LC3Ⅱ and Beclin-1) using reverse transcription polymerase chain reaction and the WB method. Furthermore, the ultrastructure of gastric mucosal cells and autophagosome status were observed using transmission electron microscopy. RESULTS: Compared with the model group, the AWD-treated rats exhibited significant improvement in body weight (P < 0.01), reduced protein expression of the intestine epithelial cell-specific markers MUC2, VILLIN, CDX2 and KLF4 (P < 0.01 for all) and increased SOX2 protein expression (P < 0.01). In addition, AWD suppressed the mRNA and protein expression of endoplasmic reticulum stress markers PEPK and ATF6 (P < 0.01 for all) and promoted the mRNA and protein expression of autophagy and apoptosis markers CHOP, caspase-12, LC3Ⅱ and Beclin-1 (P < 0.01 for all). CONCLUSION: Anwei decoction effectively inhibits the further progression of GIM and prevents the occurrence of gastric mucosal carcinogenesis.

Juan-tong-yin potentially impacts endometriosis pathophysiology by enhancing autophagy of endometrial stromal cells via unfolded protein reaction-triggered endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMs) is characterized by inflammatory lesions, dysmenorrhea, infertility, and chronic pelvic pain. Single-target medications often fail to provide systemic therapeutic results owing to the complex mechanism underlying endometriosis. Although traditional Chinese medicines-such as Juan-Tong-Yin (JTY)-have shown promising results, their mechanisms of action remain largely unknown. AIM OF THE STUDY: To elucidate the therapeutic mechanism of JTY in EMs, focusing on endoplasmic reticulum (ER) stress-induced autophagy. MATERIALS AND METHODS: The major components of JTY were detected using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The potential mechanism of JTY in EMs treatment was predicted using network pharmacological analysis. Finally, the pathogenesis of EMs was validated in a clinical case-control study and the molecular mechanism of JTY was validated in vitro using endometrial stromal cells (ESCs). RESULTS: In total, 241 compounds were analyzed and identified from JTY using UPLC-MS. Network pharmacology revealed 288 targets between the JTY components and EMs. Results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that regulating autophagy, migration, apoptosis, and inflammation were the key mechanisms of JTY in treating EMs. Meanwhile, we found that protein kinase R-like endoplasmic reticulum kinase (PERK), Beclin-1, and microtubule-associated protein light chain 3 B (LC3B) expressions were lower in endometria of patients with EMs than in those with normal eutopic endometria (p < 0.05). Additionally, during in vitro experiments, treatment with 20% JTY-containing serum significantly suppressed ESC proliferation, achieving optimal effects after 48 h. Electron microscopy revealed significantly increased autophagy flux in the JTY group compared with the control group. Moreover, JTY treatment significantly reduced the migratory and invasive abilities of ESCs and upregulated protein expression of PERK, eukaryotic initiation factor 2α (eIF2α)/phospho-eukaryotic initiation factor 2α (p-eIF2α), activating Transcription Factor-4 (ATF4), Beclin-1, and LC3BII/I, while subsequently downregulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin 18 (IL-18) expression. However, administration of GSK2656157-a highly selective PERK inhibitor-reversed these changes. CONCLUSION: JTY ameliorates EMs by activating PERK associated with unfolded protein reaction, enhancing cell ER stress and autophagy, improving the inflammatory microenvironment, and decreasing the migration and invasion of ESCs.

Standing Carbon-Supported Trace Levels of Metal Derived from Covalent Organic Framework for Electrocatalysis.

Single atom catalysts (SACs) are receiving increasing interests due to their high theoretical catalytic efficiency and intriguing physiochemical properties. However, most of the synthetic methodologies involve high-temperature treatment. This usually leads to limited control over the spatial distribution of metal sites and collapse of porous network that result in limited active site exposure. A strategy to construct SAC by using a covalent organic framework as the precursor is reported in this study. The as-prepared catalyst is mainly composed of standing carbon layers with the presence of edge-site hosted metal single atoms. Such structure configuration not only allows full site exposure but also endows the metal site with high intrinsic activity. With a trace amount of cobalt loading (0.17 wt%), the nanorice-shaped catalyst displays promising electrochemical activities toward catalyzing the oxygen reduction reaction in both alkaline and acidic medium. An ultrahigh mass activity of 838 A gCo -1 at 0.9 V is achieved in the acidic electrolyte. This work suggests a new route to design SACs based on covalent organic framework for energy storage and conversion devices.

Bimetallic Covalent Organic Frameworks for Constructing Multifunctional Electrocatalyst.

Covalent organic frameworks (COFs) are a new class of crystalline porous polymers comprised mainly of carbon atoms, and are versatile for the integration of heteroatoms such as B, O, and N into the skeletons. The designable structure and abundant composition render COFs useful as precursors for heteroatom-doped porous carbons for energy storage and conversion. Herein, we describe a multifunctional electrochemical catalyst obtained through pyrolysis of a bimetallic COF. The catalyst possesses hierarchical pores and abundant iron and cobalt nanoparticles embedded with standing carbon layers. By integrating these features, the catalyst exhibits excellent electrochemical catalytic activity in the oxygen reduction reaction (ORR), with a 50 mV positive half-wave potential, a higher limited diffusion current density, and a much smaller Tafel slope than a Pt-C catalyst. Moreover, the catalyst displays superior electrochemical performance toward the hydrogen evolution reaction (HER), with overpotentials of -0.26 V and -0.33 V in acidic and alkaline aqueous solution, respectively, at a current density of 10 mA cm-2 . The overpotential in the catalysis of the oxygen evolution reaction (OER) was 1.59 V at the same current density.