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Myocardial dysfunction is a prevalent complication of sepsis (septic cardiomyopathy) with a high mortality rate and limited therapeutic options. Naringenin, a natural flavonoid compound with anti-inflammatory and antioxidant properties, holds promise as a potential treatment for sepsis-induced myocardial dysfunction. This study investigated the pharmacological effects of naringenin on septic cardiomyopathy. In vivo and in vitro experiments demonstrated that naringenin improved cardiomyocyte damage. Network pharmacology and database analysis revealed that HIF-1α is a key target protein of naringenin. Elevated expression of HIF-1α was observed in damaged cardiomyocytes, and the HIF-1α inhibitor effectively protected against LPS-induced cardiomyocyte damage. Molecular docking studies confirmed the direct binding between naringenin and HIF-1α protein. Importantly, our findings demonstrated that naringenin did not provide additional attenuation of cardiomyocyte injury on the biases of HIF-1α inhibitor treatment. In conclusion, this study proves that naringenin protects against septic cardiomyopathy through HIF-1α signaling. Naringenin is a promising therapeutic candidate for treating septic cardiomyopathy. • Naringenin protects against septic cardiomyopathy and improve cardiac health. • Molecular docking reveals naringenin's direct interaction with HIF-1α. • Naringenin is a promising therapeutic candidate for septic cardiomyopathy. [ABSTRACT FROM AUTHOR]

The high-throughput metagenomic sequencing offers a powerful technique to compare the microbial communities. Without requiring extra reference sequences, alignment-free models with short k- tuple ( k = 2–10 bp) yielded promising results. Short k- tuples describe the overall statistical distribution, but is hard to capture the specific characteristics inside one microbial community. Longer k- tuple contains more abundant information. However, because the frequency vector of long k- tuple( k ≥ 30 bp) is sparse, the statistical measures designed for short k- tuples are not applicable. In our study, we considered each tuple as a meaningful word and then each sequencing data as a document composed of the words. Therefore, the comparison between two sequencing data is processed as “topic analysis of documents” in text mining. We designed a pipeline with long k- tuple features to compare metagenomic samples combined using algorithms from text mining and pattern recognition. The pipeline is available at http://culotuple.codeplex.com/ . Experiments show that our pipeline with long k -tuple features: ①separates genomes with high similarity; ②outperforms short k -tuple models in all experiments. When k ≥ 12, the short k -tuple measures are not applicable anymore. When k is between 20 and 40, long k -tuple pipeline obtains much better grouping results; ③is free from the effect of sequencing platforms/protocols. ③We obtained meaningful and supported biological results on the 40-tuples selected for comparison. [ABSTRACT FROM AUTHOR]

To further enhance the antitumor efficacy of DNA vaccine, we proposed a synergistic strategy that targeted tumor cells and angiogenesis simultaneously. In this study, a Semliki Forest Virus (SFV) replicon DNA vaccine expressing 1–4 domains of murine VEGFR2 and IL12 was constructed, and was named pSVK-VEGFR2-GFc-IL12 (CAVE). The expression of VEGFR2 antigen and IL12 adjuvant molecule in 293T cells in vitro were verified by western blot and enzyme-linked immune sorbent assay (ELISA). Then CAVE was co-immunized with CAVA, a SFV replicon DNA vaccine targeting survivin and β-hCG antigens constructed previously. The antitumor efficacy of our combined replicon vaccines was evaluated in mice model and the possible mechanism was further investigated. The combined vaccines could elicit efficient humoral and cellular immune responses against survivin, β-hCG and VEGFR2 simultaneously. Compared with CAVE or CAVA vaccine alone, the combined vaccines inhibited the tumor growth and improved the survival rate in B16 melanoma mice model more effectively. Furthermore, the intratumoral microvessel density was lowest in combined vaccines group than CAVE or CAVA alone group. Therefore, this synergistic strategy of DNA vaccines for tumor treatment results in an increased antitumor efficacy, and may be more suitable for translation to future research and clinic. [ABSTRACT FROM AUTHOR]