Introduction We did a systematic review and meta-analysis to assess the efficacy and safety of immune checkpoint inhibitors combined with or without chemotherapies in patients with esophageal squamous cell carcinoma. Methods Data related to the treatment of esophageal squamous cell carcinoma with immune checkpoint inhibitors therapy were retrieved from the database construction to August 2022. The risk of bias was assessed using the Cochrane Manual standard and RevMan 5.3 software for data synthesis. The outcome measures observed included overall survival, 12-month survival, disease control rate, objective response rate, treatment-related adverse events of grade 3 or higher, and progression-free survival. The adverse reactions included fatigue, diarrhea, hypothyroidism, rash, anemia, and anorexia. Results In this meta-analysis, a total of 17 randomized controlled trials were included. In first-line therapy, immune checkpoint inhibitors combined with or without chemotherapy in the treatment of esophageal squamous cell carcinoma was more effective than chemotherapy alone. Overall survival, 12-month survival rate, and objective response rate were statistically significant. Among second-line treatments, immune checkpoint inhibitors combined with or without chemotherapy in the treatment of esophageal squamous cell carcinoma had statistically significant overall survival, 12-month survival, objective response rate, treatment-related adverse events of grade 3 or higher, and progression-free survival compared with chemotherapy alone. Conclusion Both first- and second-line immune checkpoint inhibitors are effective for esophageal squamous cell carcinoma, and the adverse reactions are controllable and safe. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42021282586.
// Hao Yang 1,* , Hui Hui 1,* , Qian Wang 1 , Hui Li 1 , Kai Zhao 1 , Yuxin Zhou 1 , Yu Zhu 3 , Xiaotang Wang 2 , Qidong You 1 , Qinglong Guo 1 and Na Lu 1 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People’s Republic of China 2 Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA 3 Department of Hematology, The First Affiliated Hospital of Nanjing Medical University; Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China * These authors contributed equally to this work Correspondence: Qing-Long Guo, email: // Na Lu, email: // Keywords : wogonin; CML; GATA-1; differentiation; cell cycle Received : May 15, 2014 Accepted : August 09, 2014 Published : August 10, 2014 Abstract Wogonin, a flavonoid derived from Scutellaria baicalensis Georgi, has been demonstrated to be highly effective in treating hematologic malignancies. In this study, we investigated the anticancer effects of wogonin on K562 cells, K562 imatinib-resistant cells, and primary patient-derived CML cells. Wogonin up-regulated transcription factor GATA-1 and enhanced binding between GATA-1 and FOG-1, thereby increasing expression of erythroid-differentiation genes. Wogonin also up-regulated the expression of p21 and induced cell cycle arrest. Studies employing benzidine staining and analyses of cell surface markers glycophorin A (GPA) and CD71 indicated that wogonin promoted differentiation of K562, imatinib-resistant K562, and primary patient-derived CML cells. Wogonin also enhanced binding between GATA-1 and MEK, resulting in inhibition of the growth of CML cells. Additionally, in vivo studies showed that wogonin decreased the number of CML cells and prolonged survival of NOD/SCID mice injected with K562 and imatinib-resistant K562 cells. These data suggested that wogonin induces cycle arrest and erythroid differentiation in vitro and inhibits proliferation in vivo .
Despite its acknowledged benefits, the selection of an optimal regional block for analgesia pediatric hernia surgery remains a subject of debate. This study endeavored to conduct a network meta-analysis and systematic review of randomized clinical trials, aiming to amalgamate insights from both direct and indirect comparisons concerning the analgesic effectiveness and safety of various regional blocks post-inguinal hernia repair in children.
Paclitaxel, a natural anticancer drug, is widely recognized and extensively utilized in the treatment of breast cancer (BC). However, it may lead to certain side effects or drug resistance. Fortunately, combination therapy with another anti-tumor agent has been explored as an option to improve the efficacy of paclitaxel in the treatment of BC. Herein, we first evaluated the synergistic effects of paclitaxel and flubendazole through combination index (CI) calculations. Secondly, flubendazole was demonstrated to synergize paclitaxel-mediated BC cell killing in vitro and in vivo. Moreover, we discovered that flubendazole could reverse the drug resistance of paclitaxel-resistant BC cells. Mechanistically, flubendazole was demonstrated to enhance the inhibitory effect of paclitaxel via HIF1α/PI3K/AKT signaling pathways. Collectively, our findings demonstrate the effectiveness of flubendazole in combination with paclitaxel for treating BC, providing an insight into exploiting more novel combination therapies for BC in the future.
Flaviviruses represent a serious global health threat, infecting millions annually with high rates of cross-infection among different flaviviruses, yet no broad-spectrum antiviral therapy currently targets these pathogens. Through biological big data analysis, we observed a significant downregulation of Canopy FGF Signaling Regulator 3 (CNPY3), a positive regulator of defense responses, in flavivirus-infected patients, with the level of downregulation correlating with infection severity. This observation was validated in cellular and animal models. Mechanistically, we demonstrate that flaviviruses hijack the RNA-binding protein Human antigen R (HuR) to destabilize CNPY3 mRNA via adenine-uridine-rich elements (AREs), thus downregulating CNPY3 expression and promoting viral replication. Our findings identify CNPY3 as a novel antiviral mediator essential for the TLR-mediated type I interferon (IFN-I) pathway in defense against flaviviruses. In vitro, CNPY3 overexpression reduced DENV and ZIKV replication, confirming its antiviral role. To explore therapeutic potential, we developed lipid nanoparticles (LNPs) encapsulating CNPY3 mRNA (LNP-CNPY3), and early administration in flavivirus-infected mice improved survival, reduced viral loads, and attenuated neuroinflammation by enhancing antiviral and interferon responses. Together, these findings establish CNPY3 as a critical antiviral target and support LNP-CNPY3 as a promising therapeutic approach against flavivirus infections.
The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples. LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.
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