Identification of Chemical Constituents in Blumea balsamifera Using UPLC-Q-Orbitrap HRMS and Evaluation of Their Antioxidant Activities.

Blumea balsamifera (L.) DC., a perennial herb in the Asteraceae family native to China and Southeast Asia, has a notable history of medicinal use due to its pharmacological properties. Using UPLC-Q-Orbitrap HRMS techniques, we systematically investigated the chemical constituents of this plant. A total of 31 constituents were identified, of which 14 were flavonoid compounds. Significantly, 18 of these compounds were identified in B. balsamifera for the first time. Furthermore, the mass spectrometry fragmentation patterns of significant chemical constituents identified in B. balsamifera were analyzed, providing important insights into their structural characteristics. The in vitro antioxidative potential of the methanol extract of B. balsamifera was assessed using DPPH and ABTS free-radical-scavenging assays, total antioxidative capacity, and reducing power. The antioxidative activity exhibited a direct correlation with the mass concentration of the extract, with IC50 values of 105.1 ± 0.503 µg/mL and 12.49 ± 0.341 µg/mL for DPPH and ABTS, respectively. For total antioxidant capacity, the absorbance was 0.454 ± 0.009 at 400 µg/mL. In addition, the reducing power was 1.099 ± 0.03 at 2000 µg/mL. This study affirms that UPLC-Q-Orbitrap HRMS can effectively discern the chemical constituents in B. balsamifera, primarily its flavonoid compounds, and substantiates its antioxidative properties. This underscores its potential utility as a natural antioxidant in the food, pharmaceutical, and cosmetics sectors. This research provides a valuable theoretical basis and reference value for the comprehensive development and utilization of B. balsamifera and expands our understanding of this medicinally valuable plant.

Cardiovascular safety of febuxostat versus allopurinol among the Asian patients with or without gout: A systematic review and meta-analysis.

The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.

Cytoskeleton Protein BmACT1 Is Potential for the Autophagic Function and Nuclear Localization of BmAtg4b in Bombyx mori.

Homologs of Autophagy-related (Atg) protein 4 are reported to cleave LC3 protein and facilitate autophagy occurrence differently in mammals, whereas their functions have not been investigated in insects. Three homologs, including BmAtg4a and its short form BmAtg4c as well as BmAtg4b, exist in Bombyx mori. Herein, the autophagic functions of BmAtg4a and BmAtg4b were investigated. qPCR detection found that BmAtg4a and BmAtg4b both peaked during larval-pupal metamorphosis when autophagy occurs robustly. Immunofluorescent staining showed that BmAtg4a was predominantly localized at the cytoplasm, while BmAtg4b had notable nuclear localization. Overexpression of BmAtg4a and BmAtg4b both slightly promoted basal autophagy but inhibited the autophagy induced by the infection of B. mori nucleopolyhedrovirus (BmNPV) and, thereby, its proliferation. In comparison, knockout of BmAtg4a or BmAtg4b significantly upregulated BmNPV-induced autophagy and its replication in BmN cells. Results of Co-immunoprecipitation associated with mass spectrum showed that the cytoskeleton protein B. mori actin A2 (BmACT2) and B. mori actin A1 (BmACT1) bound with BmAtg4a and BmAtg4b especially. Knockout of BmACT1 and BmACT2 inhibited BmAtg4b- and BmAtg4a-induced autophagy, respectively; moreover, knockout of BmACT1 reduced the ratio of cells with nuclear BmAtg4b. Of note, BmAtg4a and BmAtg4b had physical interaction, and they had an inhibitory effect on mutual autophagic function. In this work, we provide new insights into the autophagy machinery in insects as well as its function in the proliferation of BmNPV.

Reproductive toxicity of polystyrene nanoplastics in Drosophila melanogaster under multi-generational exposure.

Micro-nanoplastics have become a new type of pollutant worldwide and have attracted widespread attention for their potential toxicity. However, the toxicity of polystyrene nanoplastics (PS-NPs) under continuous exposure of multi-generations is still unclear. In the present study, Drosophila melanogaster was selected as an in vivo biological model to investigate the reproductive toxicity and underlying mechanism induced by PS-NPs (100 nm; 1, 10, 50, and 100 mg L-1) after continuous exposure of five generations. The results showed that PS-NPs accumulated in the crop, gut and ovaries after 5 d of exposure. It was also observed that the number of egg production and eclosion rate decreased significantly (P < 0.05) accompanied by delayed development during continuous exposure PS-NPs of multi-generations. Further analysis revealed that the degree of apoptosis and necrosis of oocytes in the F5 generation increased with the increasing exposure dose. To elucidate the underlying toxicity mechanism mediated by PS-NPs, transcriptomic analysis was performed on the ovaries of the F5 generation. The results showed that there were 102 and 208 differentially expressed genes (DEGs) in the 1 mg L-1 and 100 mg L-1 PS-NPs treatment groups, respectively, compared with the control group. The transcriptome analysis further detected the KEGG pathway with significant enrichment of DEGs, revealing obvious reproductive toxicity at the molecular level. In conclusion, this research not only highlighted the negative physiological effects of multi-generational exposure to PS-NPs on Drosophila melanogaster, but also explored potential mechanisms by transcriptomic analysis to better understand reproductive toxicity induced by multi-generational exposure.

Efficacy and safety of adding bevacizumab biosimilar or original drug to platinum-based chemotherapy as first-line treatment in patients with advanced NSCLC: a systematic review and meta-analysis.

Introduction: The role of bevacizumab combined with paclitaxel and carboplatin in the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC) has been supported by a large number of data. However, whether bevacizumab biosimilars have the same efficacy and safety as the original drug is still controversial. This meta-analysis was designed to evaluate whether bevacizumab biosimilars have the same clinical efficacy and safety as the original drug in patients with advanced non-squamous NSCLC. Methods: Electronic databases (PubMed, Embase, Cochrane, CNKI, Wanfang, and VIP) and the ClinicalTrail.gov website were extensively searched using relevant search criteria. We included phase III randomized controlled trials (RCTs) to compare the efficacy and safety of marketed biosimilars and Avastin in the first-line treatment of patients with advanced NSCLC. The risk of bias of the included studies was assessed using the RoB 2 assessment scale, and the RevMan 5.4 statistical software was used for meta-analysis. Results: A total of 6360 patients were included in 11 RCTs. There was no statistical difference between the experimental group and the control group in terms of effectiveness [objective response rate (at week 18), disease control rate (at week 18), median duration of response, median progression-free survival, median overall survival (OS), and OS after 12 months]. In terms of safety [treatment-emergent adverse events (grade ⩾3) and treatment-related adverse events (grade ⩾3)], there was also no significant difference between biosimilars and Avastin. Conclusions: The efficacy and safety of bevacizumab biosimilars in the treatment of advanced non-squamous NSCLC are highly similar to those of the original drug combined with paclitaxel and carboplatin, respectively.