Soluble fms-like tyrosine kinase receptor (sFlt-1) is a soluble form of extramembrane part of vascular endothelial growth factor receptor-1 (VEGFR-1) that has antitumor effects. Bifidobacterium Infantis is a kind of non-pathogenic and anaerobic bacteria that may have specific targeting property of hypoxic environment inside of solid tumors. The aim of this study was to construct Bifidobacterium Infantis-mediated sFlt-1 gene transferring system and investigate its antitumor effect on Lewis lung cancer (LLC) in mice. Our results demonstrated that the Bifidobacterium Infantis-mediated sFlt-1 gene transferring system was constructed successfully and the system could express sFlt-1 at the levels of gene and protein. This system could not only significantly inhibit growth of human umbilical vein endothelial cells induced by VEGF in vitro, but also inhibit the tumor growth and prolong survival time of LLC C57BL/6 mice safely. These data suggest that Bifidobacterium Infantis-mediated sFlt-1 gene transferring system presents a promising therapeutic approach for the treatment of cancer.
Background: Psychological stress was an important mental health problem among the general population and warrant research to inform strategies for effective prevention. iMBIs provide a possibility to offer easily accessible, efficacious, convenient, and low-cost interventions on a wide scale. However, the efficacy of iMBIs in the general population remains unclear. The aim of this meta-analysis is to evaluate the effects of iMBIs for stress reduction in the general population. Methods: A systematic search in PubMed, Embase, Web of Science, Medline, Cochrane Library, CNKI, and Wanfang Data databases was performed up to April 10, 2019. The overall effect sizes of the iMBIs on stress, depression, anxiety, and mindfulness were recorded by the metric of Hedges’ g with 95% confidence interval (CI), Z-value, and P value. Results: Sixteen eligible studies were included in the meta-analysis. The overall results indicated that iMBIs had small to moderate effects on stress (Hedges’ g = −0.393) and mindfulness (Hedges’ g = −0.316) compared with the control group. Results from subgroup analyses revealed that the type of sample and delivery mode had a greater impact on heterogeneity across the studies. Meta-regression found that the overall effect might be moderated by guidance for iMBIs. Conclusion: The present meta-analysis suggested that iMBIs had small to moderate effects in reducing stress and improving mindfulness of the general population in comparison with the control group. Future research is needed to explore how iMBIs are remolded to improve adherence and suit specific individuals.
Background: Mindfulness-based interventions (MBIs) have been reported to be efficacious in treating attention deficit hyperactivity disorder (ADHD). However, the value of the control effect of MBIs on ADHD core symptoms remains controversial. To clarify the literature on the control effect of MBIs on the symptoms of ADHD and guide future researches, an effect-size analysis was conducted. Methods: A systematic search in PubMed, Embase, Web of Science, Medline, Cochrane Library, China National Knowledge Infrastructure, and Wangfang Data databases was performed up to January 11, 2019. The overall effect size of MBIs on ADHD core symptoms (ie, inattention and hyperactivity/impulsivity) was recorded by the metric of Hedges’ g with 95% confidence interval, Z-value, and P-value. Results: Eleven eligible studies featuring 682 participants were included in the meta-analysis. The overall results indicated that MBIs had large effects on inattention (Hedges’ g = −0.825) and hyperactivity/impulsivity (Hedges’ g = −0.676) relative to the control group. Results from subgroup analyses between self- and observer rating on ADHD symptoms revealed that the effect of MBIs both remained in a large range and self-rated ADHD core symptom had a greater impact on heterogeneity across the studies. Meta-regression found that the overall effect might be moderated by participant age group and control condition. Conclusion: The present meta-analysis suggested that MBIs had large effects in reducing ADHD core symptoms in comparison with the control group. Future researches are needed to assess follow-up effects of MBIs on ADHD core symptoms and explore the correlation between the individual level of mindfulness and reduction of ADHD symptoms.
Cytokine storm (CS) emerges as an exacerbated inflammatory response triggered by various factors such as pathogens and excessive immunotherapy, posing a significant threat to life if left unchecked. Quercetin, a monomer found in traditional Chinese medicine, exhibits notable anti-inflammatory and antiviral properties. This study endeavors to explore whether quercetin intervention could mitigate CS through a combination of network pharmacology analysis and experimental validation. First, common target genes and potential mechanisms affected by quercetin and CS were identified through network pharmacology, and molecular docking experiments confirmed quercetin and core targets. Subsequently, in vitro experiments of Raw264.7 cells stimulated by lipopolysaccharide (LPS) showed that quercetin could effectively inhibit the overexpression of pro-inflammatory mediators and regulate the AKT1-FoxO1 signaling pathway. At the same time, quercetin can reduce ROS through the Keap1-Nrf2 signaling pathway. In addition, in vivo studies of C57BL/6 mice injected with LPS further confirmed quercetin's inhibitory effect on CS. In conclusion, this investigation elucidated novel target genes and signaling pathways implicated in the therapeutic effects of quercetin on CS. Moreover, it provided compelling evidence supporting the efficacy of quercetin in reversing LPS-induced CS, primarily through the regulation of the AKT1-FoxO1 and Keap1-Nrf2 signaling pathways.
Background: To construct the Bifidobacterium infantis-mediated soluble kinase insert domain receptor (sKDR) prokaryotic expression system and to observe its inhibitory effect on growth of human umbilicus vessel endothelial cells (HUVECs) in vitro and Lewis lung cancer (LLC) on mice in vivo. Methods: The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed through electroporation and subsequently identified through PCR and Western blot analysis. HUVECs were added to the products of this system to evaluate the anti-angiogenesis effect through MTT assay in vitro. The LLC mice models were divided into three groups: one group treated with saline (group a); one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT plasmid group (group b); and one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid group (group c). The quality of life and survival of mice were recorded. Tumor volume, tumor weight, inhibitive rate, and necrosis rate of tumor were also evaluated. Necrosis of tumor and signals of blood flow in tumors were detected through color Doppler ultrasound. In addition, microvessel density (MVD) of the tumor tissues was assessed through CD31 immunohistochemical analysis. Results: The positively transformed Bifidobacterium infantis with recombinant pTRKH2-PsT/sKDR plasmid was established, and was able to express sKDR at gene and protein levels. The proliferation of HUVECs cultivated with the extract of positively transformed bacteria was inhibited significantly compared with other groups (P < 0. 05). The quality of life of mice in group c was better than in group a and b. The recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid enhanced the efficacy of tumor growth suppression and prolongation of survival, increased the necrosis rate of tumor significantly, and could obviously decrease MVD and the signals of blood flow in tumors. Conclusion: The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed successfully. This system could express sKDR at gene and protein levels and significantly inhibit the growth of HUVECs induced by VEGF in vitro. Moreover, it could inhibit tumor growth and safely prolong the survival time of LLC C57BL/6 mice.