RESUMEN
Gastrin is a gastrointestinal peptide hormone that plays an important role in the progression of colorectal cancer (CRC). However, the molecular mechanism remains unclear. In this study, we identified gastrin-related circRNAs via high-throughput sequencing and selected circRNA_0017065 as the research focus. We further studied its specific role and molecular mechanism in the progression of CRC. Knockdown and overexpression of circRNA_0017065 were performed, and the biological function of circRNA_0017065 in CRC progression was studied via in vitro and in vivo functional experiments. The potential downstream target genes were subsequently identified via screening of databases and gene chip data. The expression of circRNA_0017065 in tumour tissues was significantly upregulated compared with that in adjacent normal tissues. In vitro and in vivo functional experiments revealed that the proliferation and migration of CRC cells were significantly suppressed after circRNA_0017065 knockdown, while apoptosis was promoted. After overexpression of circRNA_0017065, the proliferation and migration of CRC cells were significantly promoted, while apoptosis was inhibited. Mechanistic studies revealed that circRNA_0017065 can act as a sponge for miR-3174 and promote CRC progression via the miR-3174/RBFOX2 axis. In general, gastrin-related circRNA_0017065 plays a key role in the occurrence and development of CRC and is expected to be a potential molecular target for the treatment of CRC metastasis.
Asunto(s)
Proliferación Celular , Neoplasias Colorrectales , Gastrinas , MicroARNs , ARN Circular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , ARN Circular/genética , ARN Circular/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Gastrinas/metabolismo , Gastrinas/genética , Ratones , Animales , Línea Celular Tumoral , Metástasis de la Neoplasia , Apoptosis , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Ratones DesnudosRESUMEN
Objective: To explore the efficacy and safety of Iguratimod (IGU) intervention in the treatment of Ankylosing Spondylitis (AS). Methods: We used computer to search literature databases, collected randomized controlled trials (RCTs) related to IGU treatment of AS, and searched the relevant literature in each database until Sep. 2022. Two researchers independently carried out literature screening, data extraction, and evaluation and analysis of the risk of bias in the included studies, and then used Rev Man5.3 software for meta-analysis. The protocol is CRD42020220798. Results: A total of 10 RCTs involves in 622 patients were collected. The statistical analysis showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], P<0.00001. Quality of evidence: low), the BASFI score (WMD -1.30 [-1.48, -1.12], P<0.00001. Quality of evidence: low) and the VAS (WMD -2.01 [-2.83, -1.19], P<0.00001. Quality of evidence: very low). Meanwhile, the addition of IGU into the conventional therapy would not increase the adverse events (RR 0.65 [0.43, 0.98], P=0.04. Quality of evidence: moderate). Conclusion: IGU may be an effective and safe intervention for AS. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42020220798.
Asunto(s)
Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfonamidas , CromonasRESUMEN
OBJECTIVE: To explore the molecular network mechanism of modified Taohong Siwu Decoction (MTHSWD) to interfere with premature ovarian failure based on systematic pharmacological strategy. METHODS: The network pharmacology strategy was used to explore the potential mechanism of MTHSWD intervention in POF, and then it was verified through animal experiments. Mouse zona pellucida 3 was used as an antigen to subcutaneously immunize BALB/c female mice to establish an immune POF model. Mice were divided into MTHSWD low-, medium-, and high-dose groups, positive control group, model group, and normal group. After 30 days of drug intervention, ovarian tissue was taken for pathological hematoxylin-eosin (HE) staining, and immunohistochemical methods were used to detect the expression of TGF-ß1 and TGF-ßRII and Smad2/3 protein expression in follicular wall granular cells and ovarian tissue, respectively. RESULTS: Network pharmacology studies have shown that MTHSWD may interfere with the TGF-ß signaling pathway. Animal experimental research shows that, compared with the model group, the number of ovarian mature follicles in the MTHSWD groups and the positive group was significantly increased, and the number of atresia follicles decreased. Immunohistochemistry showed that, compared with the control group, the expression of TGF-ß1, TGF-ßRII, and Smad2/3 in the follicular wall granulosa cells and ovarian tissues of MTHSWD groups was significantly higher than that of the model group (P < 0.05). CONCLUSION: MTHSWD may improve the ovarian function of POF mice by upregulating the protein expression of granulosa cells TGF-ß1, TGF-ßRII, and Smad2/3.