The controlling nutritional status score and clinical outcomes in patients with heart failure: Pool analysis of observational studies.

Background and aims: Malnutrition is very common in patients with heart failure (HF) and is associated with a worse clinical outcome. The Controlling Nutritional Status (CONUT) score is an easily derived index for the evaluation of malnutrition. This study aimed to evaluate the association between the CONUT score and the prognosis in patients with HF. Methods and results: Electronic databases were searched for potential studies from inception up to February 15, 2022. Observational cohort studies included adult participants with HF, and reported the associations between the CONUT score and the adjusted relative risk (RR) of all-cause mortality, and patients with composite major adverse cardiac outcomes (MACEs) were included. We finally included 18 studies comprising 12,532 participants with HF for analysis. The median age of the patients was 70.5 years old, and 35.4% were women. After a median follow-up duration of 32.5 months, patients with HF with a higher CONUT score were associated with a higher risk of all-cause mortality (per 1 increment of the CONUT score: RR, 1.21, 95% CI, 1.13-1.29, I2 = 68%, P for heterogeneity = 0.002) and MACEs (per 1 increment of the CONUT score: RR, 1.14, 95% CI, 1.06-1.23, I2 = 81%, P for heterogeneity <0.0001) after adjusting for other prognostic factors. When the CONUT score was divided into the normal nutritional status and malnourished status, malnourished patients with HF were associated with increased risks of all-cause death (RR, 1.61, 95% CI, 1.40-1.85, I2 = 17%, P for heterogeneity = 0.29) and MACEs (RR, 2.12, 95% CI, 1.49-3.02, I2 = 87%, P for heterogeneity <0.0001), compared with those with normal nutritional status. Conclusions: The CONUT score is associated with the clinical outcomes in patients with HF, and can be used as a screening tool of nutritional status in HF to improve prognosis.

Ginkgetin Alleviates Inflammation, Oxidative Stress, and Apoptosis Induced by Hypoxia/Reoxygenation in H9C2 Cells via Caspase-3 Dependent Pathway.

Ginkgetin, the extract of Ginkgo biloba leaves, has been reported to exert preventive and therapeutic effects on cardiovascular disease. However, little is known about its role in myocardial ischemia-reperfusion injury (MIRI). The present study aimed to unveil the function of ginkgetin in cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Cell Counting Kit-8 (CCK-8) was employed to evaluate the impact of ginkgetin on cell viability in the absence or presence of H/R. Proinflammatory cytokines and malondialdehyde (MDA), reactive oxygen species (SOD), and lactate dehydrogenase (LDH) were determined via corresponding kits. In addition, flow cytometry was performed to detect apoptotic level. Western blot analysis was utilized to estimate caspase-3 and cytochrome C. Ginkgetin had no significant effect on cell viability; however, it could enhance viability of H9C2 cells exposed to H/R. Inflammation and oxidative stress induced by H/R injury were relieved via pretreatment with ginkgetin. Preconditioning of ginkgetin also decreased apoptotic rate and the protein levels of caspase-3, cytochrome C under H/R condition. Furthermore, 2-HBA, an inducer of caspase-3, was used for the activation of caspase-3 signaling pathway. It was found that induction of caspase-3 eliminated the protective effect of ginkgetin on H9C2 cells exposed to H/R. These results indicated that ginkgetin attenuated inflammation, oxidative stress, and apoptosis. These protective roles of ginkgetin may attribute to caspase-3 dependent pathway.

Survival analysis of genome-wide profiles coupled with Connectivity Map database mining to identify potential therapeutic targets for cholangiocarcinoma.

Cholangiocarcinoma (CCA) is one of the most common epithelial cell malignancies worldwide. However, its prognosis is poor. The aim of the present study was to examine the prognostic landscape and potential therapeutic targets for CCA. RNA sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) dataset and processed. A total of 172 genes that were significantly associated with overall survival of patients with CCA were identified using the univariate Cox regression method. Bioinformatics tools were applied using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). It was identified that 'Wnt signaling pathway', 'cytoplasm' and 'AT DNA binding' were the three most significant GO categories of CCA survival-associated genes. 'Transcriptional misregulation in cancer' was the most significant pathway identified in the KEGG analysis. Using the Drug-Gene Interaction database, a drug-gene interaction network was constructed, and 31 identified genes were involved in it. The most meaningful potential therapeutic targets were selected via protein-protein and gene-drug interactions. Among these genes, polo-like kinase 1 (PLK1) was identified to be a potential target due to its significant upregulation in CCA. To rapidly find molecules that may affect these genes, the Connectivity Map was queried. A series of molecules were selected for their potential anti-CCA functions. 0297417-0002B and tribenoside exhibited the highest connection scores with PLK1 via molecular docking. These findings may offer novel insights into treatment and perspectives on the future innovative treatment of CCA.