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Sunitinib (Sun), a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, is the standard first‐line treatment against advanced clear cell renal cell carcinoma (RCC), but resistance to therapy is inevitable. Reactive oxygen species production is associated with sensitivity to chemotherapy, but the underlying mechanisms are not completely understood. Here, we investigated the mechanisms contributing to Sun resistance using the RCC cell lines ACHN and 786‐O. We report that Sun‐resistant cells exhibited reduced apoptosis, increased cell viability, increased reactive oxygen species production and disrupted mitochondrial function. Furthermore, chronic Sun treatment resulted in an up‐regulation of Sirt5/isocitrate dehydrogenase 2 (IDH2) expression levels. Knockdown of Sirt5/IDH2 impaired mitochondrial function and partially attenuated Sun resistance. Finally, up‐regulation of Sirt5 enhanced the expression of IDH2 via modulation of succinylation at K413 and promoted protein stability. In conclusion, dysregulation of Sirt5/IDH2 partially contributes to Sun resistance in RCC cells by affecting antioxidant capacity., Sunitinib‐resistant cells exhibited up‐regulation of Sirt5/isocitrate dehydrogenase 2 (IDH2) expression levels, which confer drug resistance. Up‐regulation of Sirt5 enhanced the expression of IDH2 via modulation of succinylation at K413 and promotion of protein stability. Dysregulation of Sirt5/IDH2 partially contributes to Sun resistance by disturbing mitochondrial functions and affecting antioxidant capacity of renal cell carcinoma cells.

Sterols play an essential part in physiological activities of almost all creatures. However, there is a lack of a widely applicable routine method to investigate various sterols with both saturated and unsaturated forms in diversiform food materials. In this study, a new UPLC-MS/MS method with wider extensive applicability has been developed to fill this blank, which is considered time and cost saving, and can improve labor efficiency. The Agilent Eclipse Plus C18 column and methanol-water gradient elution system were employed to improve the separation at 40 °C and the flow rate was 0.5 mL/min. The method validation parameters include precision, recovery, linearity, and limit of detection and quantification (LOD and LOQ). The recoveries of sterols in all food matrices and the inter-day and intra-day precisions represented by RSDs were all within the recommended range of chemical analysis. The LODs and LOQs in different types of samples were in range of 0.0036–0.68 μg/mL and 0.01–2.0 μg/mL, respectively. All the results demonstrated that this method was sensitive and accurate enough. Additionally, the acid hydrolysis was found closely related to the degradation of unsaturated sterols in the pretreatment.

The ultrasound-assisted aqueous two-phase extraction (UA-ATPE) was first employed to develop an effective technique for simultaneous extraction and preliminary purification of synephrine, naringin,...

Injectable dynamic hydrogels play a key role in cell transplantation to protect the cells from shear stress during injection. However, it still remains challenging to design dynamic hydrogels with fast gelation and high stability for protecting cells under flow due to the slow formation and exchange of most dynamic bonds. Here, a novel dual-crosslinked hydrogel system with fast dynamic crosslinks is developed by using methacrylate chitosan (CHMA) and aldehyde functionalized hyaluronate (oxidized HA, OHA). Based on the cooperation of electrostatic interaction between cationic amino of chitosan and anionic carboxyl of HA and Schiff-based crosslinking through amino and aldehyde groups, the dynamic CHMA-OHA hydrogel shows rapid gelation and high injectability. Further, the CHMA-OHA hydrogel is photopolymerized for achieving a high modulus and stability. Importantly, such hydrogels loaded with stem cells remains a cell viability (~ 92%) after extrusion. These results indicate that the CHMA-OHA hydrogel is a promising tissue engineering biomaterial for therapeutic cell delivery and 3D printing of encapsulated cell scaffolds.

Background To investigate the efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non‐small cell lung cancer (NSCLC) through pooling of open published data. Methods The electronic databases of Medline (1960–2021.5), Cochrane central register of controlled trials (CENTRAL), EMBASE(1980–2021.5) and Wan fang (1986–2021.5) were systematically searched by two reviewers to identify the relevant clinical trials related to the above subject. The objective response rate (ORR), disease control rate (DCR) and drug relevant adverse reactions were pooled and demonstrated by risk ratio (RR) and 95% confidence interval (95% CI). The statistical heterogeneity across studies was assessed by I‐square test. The publication bias was evaluated by Egger's line regression test and demonstrated by Begg's funnel plot. Results Eleven prospective studies were included in the meta‐analysis. The pooled results indicated that the ORR (RR = 1.62, 95% CI: 1.32–2.00, p 0.05) except for hypertension (RR = 3.60, 95% CI: 1.26–10.31, p, All the included 11 clinical trials evaluated the ORR between apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in treatment NSCLC. And there was no statistical heterogeneity across the 11 studies (I2=0.0%, P=0.931). Therefore, the ORR was pooled in fixed effect model with RR=1.62 (95%CI:1.32‐2.00, P

Xanthine oxidase (XO) plays a vital role in inducing hyperuricemia and increasing the level of superoxide free radicals in blood, and is proved as an important target for gout. Chrysoeriol (CHE) is a natural flavone with potent XO inhibitory activity (IC50 = 2.487 ± 0.213 μM), however, the mechanism of interaction is still unclear. Therefore, a comprehensive analysis of the interaction between CHE and XO was accomplished by enzyme kinetics, isothermal titration calorimetry (ITC), multi-spectroscopic methods, molecular simulation and ADMET. The results showed that CHE acted as a rapid reversible and competitive-type XO inhibitor and its binding to XO was driven by hydrogen bonding and hydrophobic interaction. Moreover, CHE exhibited a strong fluorescence quenching effect through a static quenching procedure and induced conformational changes of XO. Its binding pattern with XO was revealed by docking study and the binding affinity to XO was enhanced by the interactions with key amino acid residues in the active pocket of XO. Further, CHE showed good stability and pharmacokinetic behavior properties in molecule dynamic simulation and ADMET prediction. Overall, this study shed some light on the mechanism of interaction between CHE and XO, also provided some valuable information concerning the future therapeutic application of CHE as natural XO inhibitor.