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Pancreatic cancer risk is reduced by metformin treatment in patients with diabetes. However, the effect of metformin on pancreatic cancer overall survival is unclear. The aim of the present study was to determine the association between metformin and clinical outcomes of pancreatic cancer patients with diabetes. An electronic and manual search was conducted using PubMed, Web of Science, Medline-Ovid and Cochrane Library databases between the beginning and March 31, 2017. A total of 8 studies consisting of 4,293 patients with pancreatic cancer with diabetes were included, comprising 2,033 patients who had received metformin and 2,260 patients who had not. The meta-analysis showed that metformin was associated with a relative survival benefit in pancreatic cancer patients [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.93]. These associations were also observed in subgroups of Asian countries 0.64 (95% CI, 0.52-0.80) and Western countries 0.88 (95% CI, 0.82-0.95), as well as diabetes (no indication of diabetes type). Excluding the studies considered as be prone to immortal time bias resulted in HRs (95% CIs) of 0.86 (0.69-1.07). The results of this study support the notion that the use of metformin may improve the overall survival of patients with pancreatic cancer with concurrent diabetes. However, the proposed beneficial effect of metformin on pancreatic cancer survival may be based on immortal time bias. Further carefully designed studies with high quality are warranted to confirm this efficacy. [ABSTRACT FROM AUTHOR]

This corrects the article DOI: 10.1038/ncomms13997 [ABSTRACT FROM AUTHOR]

Cardiovascular complications have been well documented as the downside to conventional cancer chemotherapy. As a notable side effect of cisplatin, cardiotoxicity represents a major obstacle to the successful treatment of cancer. It has been reported that kaempferol (KPF) possesses cardioprotective and anti-inflammatory qualities. However, the effect of KPF on cardiac damage caused by conventional cancer chemotherapy remains unclear. In this study, we clarified the protective effect of KPF on cisplatin-induced heart injury, and conducted in-depth research on the molecular mechanism underlying this effect. The results showed that KPF protected against cardiac dysfunction and injury induced by cisplatin in vivo . In H9c2 cells, KPF dramatically reduced cispaltin-induced apoptosis and inflammatory response by modulating STING/NF-κB pathway. In conclusion, these results showed that KPF had great potential in attenuating cisplatin-induced cardiac injury. Besides, greater emphasis should be placed in the future on natural active compounds containing KPF with anti-inflammatory effects for the treatment of these diseases., Competing Interests: None., (AJTR Copyright © 2020.)

Objective: To identify hub genes and key pathways associated with anaplastic thyroid carcinoma (ATC), and to explore possible intervention strategy., Methods: The differentially expressed genes (DEGs) in ATC were identified by Gene Expression Omnibus (GEO) combined with using R language; the pathway enrichment of DEGs were performed by using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The protein-protein interaction (PPI) network of DEGs was constructed by STRING database and visualized by Cytoscape. Furthermore, the hub genes and key nodes were calculated by MCODE. Finally, the drug repurposing was performed by L1000CDS 2 ., Results: A total of 2087 DEGs were identified. The DEGs were clustered based on functions and pathways with significant enrichment analysis, among which PI3K-Akt signaling pathway, p53 signaling pathway, inflammatory response, extracellular matrix organization were significantly upregulated. The PPI network was constructed and the most significant three modules and nine genes were filtered. Twenty-two potential compounds were repurposed for ATC treatment., Conclusions: Using integrated bioinformatics analysis, we have identified hub genes and key pathways in ATC, and provide novel strategy for the treatment of ATC.

Sepsis, a typically acute inflammatory disease, is the biggest cause of death in ICU (intensive care unit). Novel anti-inflammatory alternatives are still in urgent need. In this study, we designed and synthesized 30 indole-2-one and 7-aza-2-oxindole derivatives based on the skeleton of tenidap, and their anti-inflammatory activity was determined by evaluating the inhibitory potency against lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-α and interleukin (IL)-6 release in RAW264.7 macrophages. Quantitative SAR (structure-activity relationship) analysis revealed that a high molecular polarizability and low lipid/water partition coefficient (ALogP) in indole-2-one are beneficial for anti-inflammatory activity. Moreover, compounds 7i and 8e inhibited the expression of TNF-α, IL-6, COX-2, PGES, and iNOS in LPS-stimulated macrophages, and 7i exhibited a significant protection from LPS-induced septic death in mouse models. These data present a series of new indole-2-one compounds with potential therapeutic effects in acute inflammatory diseases.

Sepsis is a systemic inflammatory response syndrome and is mainly caused by lipopolysaccharides (LPS) - a component of the cell walls of gram-negative bacteria, via toll-like receptor 4-mitogen-activated protein kinases/nuclear factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized 26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti-inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis factor-α and interleukin-6 in mouse RAW264.7 macrophages. Five active compounds (3a, 3c, 3d, 3j, and 3l) exhibited dose-dependent inhibition against the release of tumor necrosis factor-α and interleukin-6, and they also showed much higher chemical stability than curcumin in vitro. The anti-inflammatory activity of analogs 3a and 3c may be associated with their inhibition of the phosphorylation of extracellular signal-regulated kinase and the activation of nuclear factor-kappa B. In addition, 3c exhibited significant protection against LPS-induced septic death in vivo. These results indicate that asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the treatment of acute inflammatory diseases.