Hyaluronic acid-coated liposomes for enhanced in vivo efficacy of neogambogic acid via active tumor cell targeting and prolonged systemic exposure.

Neogambogic acid (NGA), which possesses a variety of anticancer activities, is visualized as an anticancer bioactive ingredient. However, the huge vascular stimulation, poor aqueous solubility, and short half-life restricted its clinical use. In this work, an effective nanocarrier was explored to reduce toxicity and enhance the tumor-targeted delivery. Two liposomal formulations, neogambogic acid liposomes (NGA-L), and hyaluronic acid-coated neogambogic acid liposomes (HA-NGA-L) were prepared and characterized with high encapsulation efficiency, slow pattern of drug release, narrow size distribution and higher stability. The cytotoxicity and cellular uptake of HA-NGA-L were higher than those of NGA-L in MDA-MB-231 cells (high CD44 expression), while no obvious differences in MCF-7 cells with (low CD44 expression), suggesting the CD44-mediated cellular internalization of hyaluronic acid-modified liposomes enhanced the cytotoxicity. Mechanistically, elevation of Bax and caspase-3 as well as downregulation of Bcl-2 led to cell apoptosis. Besides, the vascular stimulation and the hemolysis test indicated good safety of HA-NGA-L. In addition, HA-NGA-L was the effective nanocarrier to repress tumor proliferation in MDA-MB-231 tumor xenograft mouse through CD44 mediated active targeting without any obvious histopathological abnormities on major organs. Immunohistochemistry analysis revealed the enhanced elevation of Bax and caspase-3, and reduced expression of Bcl-2 contribute to apoptosis in tumors. Meanwhile, HA-NGA-L increased the AUC and t1/2 by 5.34-fold and 3.94-fold, respectively. In summary, the present study shows that HA-NGA-L may be safe and effective for the tumor-targeted delivery of neogambogic acid.

Could patients with chronic obstructive pulmonary disease benefit from renin angiotensin system inhibitors? A meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered related to chronic systemic inflammation. Renin angiotensin system (RAS) inhibitor, exerting an anti-inflammatory action in many systems, has been demonstrated relevant to the pathogenesis of COPD. However, the association between RAS inhibitor use and prognosis of patients with COPD remains controversial. Therefore, we conducted a meta-analysis and systematic review to summarise current evidence. MATERIAL AND METHODS: Databases, including Medline, Embase, Web of Science and Cochran Library, were searched for eligible studies by the end of 30 September 2022. Observational studies or randomised controlled trials (RCTs) that investigated the association of RAS inhibitor use with prognosis of COPD (mortality or risk of acute exacerbation) were selected. The Newcastle-Ottawa Scale was used for quality assessment of observational studies, while the Cochrane risk-of-bias tool was used to assess the quality of RCTs. Statistical analyses were performed using Stata V.15. We selected relative risk (RR) with 95% CI as the effect measure. Heterogeneity was assessed by I-squared (I2) statistics. The funnel plot was used for visual assessment of publication bias. RESULTS: A total of 20 studies with 5 51 649 subjects were included in the meta-analysis. The overall analysis indicated that RAS inhibitor use decreased the risk of death in patients with COPD (RR: 0.69, 95% CI: 0.61 to 0.78). Subgroup analyses were conducted according to comorbidities, race and type of RAS inhibitors, and the results kept consistent. However, in the pooled analysis of prospective studies, RAS inhibitor use did not significantly decrease the mortality (RR: 0.89, 95% CI: 0.78 to 1.02). Additionally, the risk of exacerbations of COPD did not decrease in patients who were prescribed RAS inhibitors (RR: 0.99, 95% CI: 0.80 to 1.23). The funnel plot indicated significant publication bias. CONCLUSION: RAS inhibitor use seemed to be associated with a reduction of mortality in patients with COPD. However, the available evidence is weak due to potential biases from retrospective studies and the heterogeneity across included studies.

Upregulation of H19 promotes invasion and induces epithelial-to-mesenchymal transition in esophageal cancer.

Long non-coding RNAs (lncRNAs) have previously been reported to be involved in cancer invasion, proliferation and apoptosis. However, the association between the lncRNA, H19, and esophageal cancer (EC) has remained elusive. In the present study, reverse transcription quantitative-polymerase chain reaction revealed that the expression of H19 was significantly increased and associated with tumor depth and metastasis in 133 EC samples. Furthermore, MTT and Transwell assays revealed that overexpression of H19 in vitro promoted the proliferation and invasion of EC cell lines, whereas knockdown of H19 inhibited the proliferation and invasion of EC cell lines. In addition, it was identified that an upregulation of H19 induced epithelial-to-mesenchymal transition, while the opposite effect was observed following the downregulation of H19. In conclusion, H19 has a significant role in the development of EC and may serve as a potential prognostic marker and therapeutic target for EC.