Electroacupuncture protects the intestinal mucosal barrier in diarrhea-predominant Irritable Bowel Syndrome rats by regulating the MCs/Tryptase/PAR-2/MLCK pathway.

OBJECTIVE: The pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D) is related to damage to the intestinal mucosal barrier function. Based on the Mast cell (MC)/Tryptase/Protease-activated receptor-2 (PAR-2)/Myosin light chain kinase (MLCK) pathway, this study explored the effect of electroacupuncture (EA) on IBS-D rats and its possible mechanism of protecting the intestinal mucosal barrier. METHODS: The IBS-D rat model was established by mother-offspring separation, acetic acid enema, and chronic restraint stress. The efficacy of EA on IBS-D rats was evaluated by observing the rate of loose stool (LSP) and the minimum volume threshold of abdominal withdrawal reflex (AWR) in rats. Mast cells and the ultrastructure of intestinal mucosa were observed by H&E staining, toluidine blue staining, and transmission electron microscopy. The expression levels of Tryptase, PAR-2, MLCK, zonula occludens-1 (ZO-1), and Occludin in rats were detected by ELISA, qRT-PCR, and western blot. RESULTS: After 7 days of intervention, compared to the IBS-D group, the loose stool rates of rats in IBS-D + EA group and IBS-D + ketotifen group were decreased (P < 0.01), the minimum volume thresholds of AWR were improved (P < 0.01), the inflammation of colon tissue decreased, the number of MCs were decreased (P < 0.01), the expression of Tryptase, PAR-2, and MLCK were lowered (P < 0.01, P < 0.05), and the expression of ZO-1 and Occludin were enhanced (P < 0.01, P < 0.05). Compared to the EA group, there was no significant difference in each index between the ketotifen groups (P > 0.05). CONCLUSION: EA has a good therapeutic effect on IBS-D rats. Regulating the MCs/Tryptase/PAR-2/MLCK pathway may be a mechanism to protect the intestinal mucosal barrier.

Nitrogen-doped mesoporous carbon supported CuSb for electroreduction of CO2.

The construction of an efficient catalyst for electrocatalytic reduction of CO2 to high value-added fuels has received extensive attention. Herein, nitrogen-doped mesoporous carbon (NMC) was used to support CuSb to prepare a series of materials for electrocatalytic reduction of CO2 to CH4. The catalytic activity of the composites was significantly improved compared with that of Cu/NMC. In addition, the Cu content also influenced the activity of electrocatalytic CO2 reduction reaction. Among the materials used, the CuSb/NMC-2 (Cu: 5.9 wt%, Sb: 0.49 wt%) catalyst exhibited the best performance for electrocatalytic CO2 reduction, and the faradaic efficiency of CH4 reached 35%, and the total faradaic efficiency of C1-C2 products reached 67%.

Half-Sandwich Ruthenium Complexes for One-Pot Synthesis of Quinolines and Tetrahydroquinolines: Diverse Catalytic Activity in the Coupled Cyclization and Hydrogenation Process.

Four types of half-sandwich ruthenium complexes with an N,O-coordinate mode based on hydroxyindanone-imine ligands have been prepared in good yields. These stable ruthenium complexes exhibited high activity in the catalytic synthesis of quinolines from the reactions of amino alcohols with different types of ketones or secondary alcohols under very mild conditions. Moreover, the methodology for the direct one-pot synthesis of tetrahydroquinoline derivatives from amino alcohols and ketones has been also developed on the basis of the continuous catalytic activity of this ruthenium catalyst in the selective hydrogenation of the obtained quinoline derivatives with a low catalyst loading. The corresponding products, quinolines and tetrahydroquinoline derivatives, were afforded in good to excellent yields. The efficient and diverse catalytic activity of these ruthenium complexes suggested their potential large-scale application. All of the ruthenium complexes were characterized by various spectroscopies to confirm their structures.

An Antisense Oligonucleotide Drug Targeting miR-21 Induces H1650 Apoptosis and Caspase Activation.

Non-small cell lung cancer is the most common malignant tumor in the world. Currently, chemotherapy is still the major method for non-small cell lung cancer treatment, but the problem of cancer drug resistance still exists, so we designed 5 different phosphorothioate oligonucleotides to silence key genes in tumor cell development, which could help avoid inducing cancer cell drug resistance. MicroRNAs have been shown to play a crucial role in the pathogenesis and progression of many malignancies, such as breast, colon, lung, and pancreatic cancer. According to the data from the Gene Expression Omnibus database, miR-21 has been reported to be one of the top 20 differentially expressed microRNAs screened using the Morpheus online tool, and miR-21 has been revealed to regulate a series of biological behaviors in cancer cells, including cell proliferation, migration, invasion, metastasis, and apoptosis. In recent years, gene therapy has emerged as a new therapeutic strategy for cancer treatment. Antisense oligonucleotides have recently been suggested as a novel approach for targeting microRNAs by antisense-based gene silencing. Five phosphorothioate oligonucleotides were designed, synthesized, and screened for anticancer activity. Reverse transcription-polymerase chain reaction was used to detect the relative expression of miR21. Among these 5 sequences, only phosphorothioate oligonucleotide 4 inhibited the proliferation of H1650 cells, and this effect was due to the induction of cancer cell apoptosis by activating the caspase-8 apoptotic pathway. In conclusion, this research confirmed the anticancer activity of phosphorothioate oligonucleotide 4 and revealed the underlying mechanism, which has the potential to be a novel anticancer strategy.

Expression and prognostic value of HER-2/neu, STAT3 and SOCS3 in hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations, while the viral-chemical etiology along with molecular mechanisms of HCC pathogenesis remains largely unknown. This study aimed to determine expression profile and prognostic value of HER-2/neu, STAT3 and SOCS3 in HCC. METHODS: Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to evaluate the expression of HER-2/neu, STAT3 and SOCS3 in HCC tissues and adjacent normal tissues collected from 176 HCC patients. RESULTS: HER-2/neu and STAT3 levels were higher and SOCS3 expression was lower in HCC tissues than in adjacent normal tissues. HER-2/neu, STAT3 and SOCS3 levels were associated with histological grade, tumor diameter, TNM stage, vascular invasion, lymph node metastasis and distant metastasis in HCC. SOCS3 expression was negatively associated with HER-2/neu and STAT3 expression. HCC patients with higher HER-2/neu and STAT3 levels had shorter overall, disease-free and disease-specific survival, whereas the opposite was found in patients with higher SOCS3 expression. In Cox regression analysis, tumor size, TNM stage, and STAT3 expression were identified as independent prognostic factors of HCC. CONCLUSION: Taken together, these observations suggest that HER-2/neu, STAT3 and, SOCS3 are related to the aggressive tumor behavior and STAT3 has potential value as a prognostic factor for HCC.

Catalytic hydrogenation of carbonyl and nitro compounds using an [N,O]-chelate half-sandwich ruthenium catalyst.

A series of N,O-chelate half-sandwich ruthenium complexes for both carbonyl and nitro compound hydrogenation have been synthesized based on ß-ketoamino ligands. All complexes exhibited high activity for the catalytic hydrogenation of a series of ketones and nitroarenes with molecular H2 as the reducing reagent in aqueous medium. Consequently, the catalytic system showed the catalytic TON values of 950 for 1-phenylethanol in acetophenone hydrogenation and 1960 for 1-chloro-4-nitrobenzene in p-chloroaniline hydrogenation. Good catalytic activity was displayed for various kinds of substrates with either electron-donating or electron-withdrawing groups. The neutral ruthenium complexes 1-4 were fully characterized using NMR, IR, and elemental analysis. Molecular structures of complexes 2 and 4 were further confirmed using single-crystal X-ray diffraction analysis.

Qi-Shen-Yi-Qi Dripping Pills Promote Angiogenesis of Ischemic Cardiac Microvascular Endothelial Cells by Regulating MicroRNA-223-3p Expression.

Traditional Chinese medicine (TCM) research shows that Qi-Shen-Yi-Qi Dripping Pills (QSYQ) can promote ischemic cardiac angiogenesis. Studies have shown that microRNAs (miRNAs) are the key component of gene regulation networks, which play a vital role in angiogenesis and cardiovascular disease. Mechanisms involving miRNA by which TCM promotes ischemic cardiac angiogenesis have not been reported. We found that microRNA-223-3p (mir-223-3p) was the core miRNA of angiogenesis of rats ischemic cardiac microvascular endothelial cells (CMECs) and inhibited angiogenesis by affecting RPS6KB1/HIF-1α signal pathway in previous study. Based on the results, we observed biological characteristics and optimal dosage for QSYQ intervening in rats ischemic CMECs angiogenesis and concluded that QSYQ low-dose group had the strongest ability to promote angiogenesis of ischemic myocardium. Using miRNA chip and real-time PCR techniques in this study, we identified mir-223-3p as the pivotal miRNA in QSYQ that regulated angiogenesis of ischemic CMECs. From real-time PCR and western blot analysis, research showed that gene and protein expression of factors located RPS6KB1/HIF-1α signaling pathway, including HIF-1α, VEGF, MAPK, PI3K, and AKT, were significantly upregulated by QSYQ to regulate angiogenesis of ischemic CMECs. This study showed that QSYQ promote ischemic cardiac angiogenesis by downregulating mir-223-3p expression in rats ischemic CMECs.

Mycoepoxydiene inhibits antigen-stimulated activation of mast cells and suppresses IgE-mediated anaphylaxis in mice.

Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forest. It has been shown that MED has many kinds of effects such as anti-cancer and anti-inflammatory activities. However, its effects on anaphylaxis are still unknown. Mast cells play a pivotal role in IgE-mediated allergic response. Aggregation of the high affinity IgE receptor (FcεRI) on the surface of mast cell activates a cascade of signaling events leading to the degranulation and cytokine production in mast cells. Our study showed that MED could significantly suppress antigen-stimulated degranulation and cytokine production in mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Furthermore, we found that MED suppressed antigen-induced activation of Syk, and subsequently inhibited the phosphorylation of PLCγ1, Akt, and MAPKs such as extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in mast cells. Collectively, our study demonstrates that MED can inhibit the activation of mast cells and protect mice from mast cell-mediated allergic response through inhibiting the activation of Syk. These results suggest that MED is a potential compound for developing a promising anti-anaphylaxis drug.

Well-defined lactose-containing polymer grafted onto silica particles.

Reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-O-meth-acryloyloxyethoxyl-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-beta-D-glucopyranoside (MAEL) was performed directly in CHCl3 solutions using cumyl dithiobenzoate (CDB) as the chain transfer agent to give well-defined glycopolymers. The chemical composition and structure of the glycopolymer were characterized by 1HNMR, FTIR, and SEC. The living glycopolymer chains were subsequently grafted onto gamma-methacryloxypropyl-trimethoxy (MPTMS) modified silica particles. The acetyl groups of the poly(MAEL) grafted onto the silica gel particles were converted to the hydroxyl groups with CH3ONa/CH3OH, thus obtaining silica gel particles modified with well-defined lactose-carrying polymer.