Omeprazole prevents stress induced gastric ulcer by direct inhibition of MMP-2/TIMP-3 interactions

Gao

et al. 2022

Genes

Cold stress is an important factor affecting cattle health, production performance, and reproductive efficiency. Understanding of the potential mechanism underlying genetic adaptation to local environments, particularly extreme cold environment, is limited. Here, by using FLK and hapFLK methods, we found that the Zinc finger CCCH-type containing 10 (ZC3H10) gene underwent positive selection in the Menggu, Fuzhou, Anxi, and Shigatse humped cattle breeds that are distributed in the cold areas of China. Furthermore, ZC3H10 expression significantly increased in bovine fetal fibroblast (BFF) cells at 28 °C for 4 h. ZC3H10 knockout BFFs were generated using CRISPR/Cas9. Wild and ZC3H10-deleted BFFs were treated at two temperatures and were divided into four groups (WT, wild and cultured at 38 °C; KO, ZC3H10−/− and 38 °C; WT_LT, wild, and 28 °C for 4 h; and KO_LT, ZC3H10−/− and 28 °C for 4 h. A total of 466, 598, 519, and 650 differently expressed genes (two-fold or more than two-fold changes) were identified by determining transcriptomic difference (KO_LT vs. KO, WT_LT vs. WT, KO vs. WT, and KO_LT vs. WT_LT, respectively). Loss of ZC3H10 dysregulated pathways involved in thermogenesis and immunity, and ZC3H10 participated in immunity-related pathways induced by cold stress and regulated genes involved in glucose and lipid metabolism and lipid transport (PLTP and APOA1), thereby facilitating adaptability to cold stress. Our findings provide a foundation for further studies on the function of ZC3H10 in cold stress and development of bovine breeding strategies for combatting the influences of cold climate.

Section: Resultsmentioning

confidence: 99%

Selection Signature and CRISPR/Cas9-Mediated Gene Knockout Analyses Reveal ZC3H10 Involved in Cold Adaptation in Chinese Native Cattle

Gao

et al. 2022

Genes

“…MMP9 is involved in the repair of GU tissue and can also recruit inflammatory cells and participate in the inflammatory response. MMP2 is a gelatinase involved in the remodeling of the extracellular matrix required for the healing process ( Rudra et al, 2022 ). It is well known that VEGF (including VEGFA) is a powerful stimulator of angiogenesis, and it plays a crucial role in angiogenesis and the promotion of wound healing ( Bueno et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Potential of Sarcandra glabra (Thunb.) Nakai. in Treating Ethanol-Induced Gastric Ulcer in Rats Based on Metabolomics and Network Analysis

Wen

Liu

et al. 2022

Front. Pharmacol.

Gastric ulcer (GU) is one of the most commonly diagnosed diseases worldwide, threatening human health and seriously affecting quality of life. Reports have shown that the Chinese herbal medicine Sarcandra glabra (Thunb.) Nakai (SGN) can treat GU. However, its pharmacological effects deserve further validation; in addition, its mechanism of action is unclear. An acute gastric ulcer (AGU) rat model induced by alcohol was used to evaluate the gastroprotective effect of SGN by analysis of the histopathological changes in stomach tissue and related cytokine levels; the potential mechanisms of action of SGN were investigated via serum metabolomics and network pharmacology. Differential metabolites of rat serum were identified by metabolomics and the metabolic pathways of the identified metabolites were enriched via MetaboAnalyst. Furthermore, the critical ingredients and candidate targets of SGN anti-AGU were elucidated. A compound-reaction-enzyme-gene network was established using Cytoscape version 3.8.2 based on integrated analysis of metabolomics and network pharmacology. Finally, molecular docking was applied to verify the acquired key targets. The results showed that SGN exerted a certain gastroprotective effect via multiple pathways and targets. The effects of SGN were mainly caused by the key active ingredients isofraxidin, rosmarinic, and caffeic acid, which regulate hub targets, such as PTGS2, MAPK1, and KDR, which maintain the homeostasis of related metabolites. Signal pathways involved energy metabolism as well as immune and amino acid metabolism. Overall, the multi-omics techniques were proven to be promising tools in illuminating the mechanism of action of SGN in protecting against diseases. This integrated strategy provides a basis for further research and clinical application of SGN.

“…The results are summarized in Tables 3 and 4 In both series of 1H-benzimidazole derivatives, several compounds exhibited moderate (IC 50 = 15.0-50.0 mM) or weak activity (IC 50 > 50 mM) toward HepG2, MDA-MB-231, MCF7, RMS, and C26. Compounds 2d and 2j showed good anticancer activity with IC 50 14.41 and 6.76 mM, respectively as compared to PTX (IC 50 = 6.13 mM) at the RMS cell line. Compound 2g showed moderate anticancer activity against the MDA-MB-231 cell line with an IC 50 value of 13.23 mM as compared to PTX (IC 50 = 1.38 mM).…”

Section: Anticancer Activitymentioning

confidence: 97%

“…1,2 Benzimidazole is a naturally occurring bicyclic compound consisting of fused benzene and imidazole ring and is an integral part of the structure of vitamin B 12 . Moreover, benzimidazole derivatives have showed anticancer, 1,3–5 antimicrobial, 4,6–8 anti-inflammation, 9 antiviral, 10 antihypertensive, 11 antihistamine, 12 antitubercular, 13 antiulcer, 14 analgesic, 15 anthelmintic, 16 antiprotozoal, 17 antiamoebic, 18 anticonvulsant, 19 antiparasitic. 20 In addition, benzimidazole scaffold presents in core structure of a vast list of important drugs such as antiulcer (omeprazole, lansoprazole, rabeprazole, pantoprazole), antihistamines (astemizole, clemizole, and emedastine), antihypertensives (telmisartan, candesartan, and azilsartan), anthelmintics (thiabendazole, parbendazole, mebendazole, albendazole, cambendazole, and flubendazole), antiviral (maribavir), antiparasitic (cyclobendazole, luxabendazole, and cambendazole), antidiabetic (rivoglitazone), analgesic (clonitrazene), especially antifungal (systemic fungicide, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Antimicrobial (MIC, mg mL −1 ) and anticancer (IC 50 , mM) activities of synthesized compounds 3a-3l and 4a-4k a .92 AE 3.59 73 14. AE 3.91 79.03 AE 3.30 67.39 AE 3.69 51.28 AE 3.11 .07 AE 3.43 40.81 AE 2.87 50.03 AE 2.99 44.48 AE 3.03 47.16 AE 2.94 3 3c 128 -64 128 128 512 512 53.76 AE 3.65 31.24 AE 2.46 37.02 AE 1.95 50.38 AE 3.05 31.12 AE 2.21 AE 3.98 43.29 AE 2.63 24.76 AE 1.81 33.02 AE 1.99 28.89 AE 1.60…”

mentioning

confidence: 99%

See 1 more Smart Citation

N,2,6-Trisubstituted 1H-benzimidazole derivatives as a new scaffold of antimicrobial and anticancer agents: design, synthesis, in vitro evaluation, and in silico studies

et al. 2023