Detoxification of glutathione (GSH) and insufficient cellular uptake of cisplatin (CDDP) severely compromised the therapeutic efficacy of CDDP. Here, a nano-delivery system (BT-4@PtPPNPs) for CDDP prodrug (C16-Pt(Ⅳ)-PEG) based on a novel sulfhydryl blocking reagent methyl 2-(methylsulfonyl) benzothiazole-6-carboxylate (BT-4) was developed. On the one hand, BT-4 can deplete GSH in tumor cells by directly interacting with reactive sulfhydryl group on GSH, thereby increasing the cytotoxicity of CDDP. On the other hand, the CDDP prodrug carrier C16-Pt(IV)-PEG can promote the distribution of CDDP in tumors, reduce the probability of unexpected inactivation of CDDP, and reduce the content of GSH in tumor cells during the conversion to CDDP, thereby making CDDP more effective for treatment. The results showed that the optimized BT-4@PtPPNPs with a small particle size (130 nm) exhibited notable cytotoxicity and apoptosis of 4T1 cells. BT-4@PtPPNPs not only significantly improved the uptake of drugs by tumor cells, but also rapidly targeted and accumulated in the tumors for a long time. Moreover, in vivo efficacy studies showed that BT-4@PtPPNPs could effectively inhibit tumor growth, inhibiting 60.85 % of tumors in a 4T1 breast cancer mice model, showing superior antitumor activity, which can be attributed to GSH-triggered CDDP tolerance reversal. Overall, this study provides an attractive and simple strategy to combine novel sulfhydryl blockers and CDDP prodrugs to potentiate the efficacy of CDDP in breast cancer.
2021-12-16·Biopreservation and biobanking4区 · 生物学
Effect of Milk Type Subjected to Different Heat Treatments on Cryo-Survivability and In Vivo Fertility of Buffalo (Bubalus bubalis) Spermatozoa in a Milk-Based Extender.
4区 · 生物学
作者: Haseeb Ali Tariq ; Arslan Tariq ; Nasim Ahmad ; Muhammad Nadeem ; Amjad Riaz
Oxidative stress is a major contributory factor to cellular damage during semen cryopreservation and results in a decreased fertilizing capacity of cryopreserved bull sperm. The inclusion of exogenous antioxidants sometimes exerts deleterious effects on sperm quality. Thus, enhancing the endogenous production of antioxidants is a requirement. This study aimed to investigate the effect of milk type heated at different temperatures on the antioxidant potential of extenders, and the subsequent post-thaw quality parameters and in vivo fertility of buffalo bull semen. Cow (C) and buffalo whole milk (B) were used separately for semen extender preparation, heated at five different temperatures (T1 = 90°C, T2 = 100°C, T3 = 110°C, T4 = 120°C, T5 = 130°C) for 10 minutes. Reactive sulfhydryl groups were measured in each subgroup by Ellman's reagents as CT1 = 143.2 μM, CT2 = 147.4 μM, CT3 = 151.5 μM, CT4 = 157.2 μM, CT5 = 161.8 μM, BT1 = 168.3 μM, BT2 = 172.5 μM, BT3 = 176.7 μM, BT4 = 196.3 μM, and BT5 = 205.7 μM. All semen samples were cryopreserved in milk-based extenders by using standard procedures. Post-thaw quality parameters including total and progressive motility, mitochondrial membrane potential, plasma membrane integrity, and acrosome integrity were found to be higher (p < 0.05) in the group (BT3) containing buffalo milk heated at 110°C, whereas in the same group, lipid peroxidation was found to be lower (p < 0.05) as compared with other treatment groups and control group. In vivo fertility of cryopreserved buffalo sperm was compared among BT3, CT1 (conventionally used milk extender), and a Tris egg yolk extender group. The fertility rates [47% (54/114), 30% (33/108), and 36% (37/103)] were higher (p < 0.05) in BT3 as compared with other groups. This study suggests that buffalo milk heated at 110°C has high antioxidant potential and improves post-thaw quality and in vivo fertility of cryopreserved buffalo bull semen.
2012-11-01·Chemosphere2区 · 环境科学与生态学
Mineralization and deflourization of 2,2,3,3-tetrafluoro-1-propanol (TFP) by UV/persulfate oxidation and sequential adsorption
This work demonstrates the combination of UV/persulfate and adsorption processes for treating 2,2,3,3-tetrafluoro-1-propanol (TFP) wastewater. Under the optimum conditions, 20mM persulfate (S(2)O(8)(2-)), 254 nm UV-C, and pH 3, 99.7% of TOC removal from an initial TFP solution of 1.39 mM was achieved. The photolysis of persulfate (S(2)O(8)(2-)) by UV irradiation yielded the sulfate radical (SO(4)(-)) with high activity, which mineralized most of the TFP in 2h. The released fluoride ions were then removed by using a waste iron oxide, BT-4 adsorbent. 20 g L(-1) BT-4 adsorbed 95% of the fluoride that was produced by mineralization of 1.39 mM TFP. The kinetics and isotherms of adsorption were examined to determine the fluoride removal efficiency of BT-4 which co-existed with the sulfate ions from the consumed sulfate radicals. Accordingly, the kinetics of adsorption was described by a pseudo-second-order rate model, while the adsorption isotherms were well fitted with the Langmuir model. BT-4 had a high adsorption capacity of 26.4 mg g(-1) (25°C) in removing the fluoride from TFP mineralization, suggesting that the co-existing sulfate ions never significantly affected the fluoride removal efficiency.