Background Male infertility is a worldwide problem but few treatments, especially irradiation-induced testicular injury. The aim of this research was to investigate novel drugs for the treatment of irradiation-induced testicular injury. Methods We administered dibucaine (0.8 mg/kg) intraperitoneally to male mice (6 mice per group) after five consecutive daily 0.5 Gy whole-body irradiation, and evaluated its ameliorating efficacy by testicular HE staining and morphological measurements. Drug affinity responsive target stability assay (Darts) were used to find target protein and pathway; mouse primary Leydig cells were isolated and to explore the mechanism (Flow cytometry, Western blot, and Seahorse palmitate oxidative stress assays); finally rescue experiments were completed by combining dibucaine with fatty acid oxidative pathway inhibitors and activators. Results The testicular HE staining and morphological measurements in dibucaine treatment group was significantly better than that in irradiation group (P < 0.05); sperm motility and mRNA levels of spermatogenic cell markers were also higher than those in the latter (P < 0.05). Darts and Western blot results showed that dibucaine targets CPT1A and downregulate fatty acid oxidation. Flow cytometry, Western blot, and Palmitate oxidative stress assays of primary Leydig cells demonstrated that dibucaine inhibits fatty acid oxidation in Leydig cells. Dibucaine combined with etomoxir/baicalin confirmed that its inhibition of fatty acid oxidation was beneficial in ameliorating irradiation-induced testicular injury. Conclusions In conclusion, our data suggest that dibucaine ameliorates irradiation-induced testicular injury in mice by inhibiting fatty acid oxidation in Leydig cells. This will provide novel ideas for the treatment of irradiation-induced testicular injury.
In this report, N, S-codoped fluorescent carbon nanodots (NSCDs) were prepared by a facile, simple, low-cost, and green thermal treatment of ammonium persulfate , glucose, and ethylenediamine . The as-prepared NSCDs displayed bright blue emission with a relatively high fluorescent quantum yield of 21.6%, good water solubility, uniform morphology, and excellent chemical stability, compared to pure CDs. The fluorescence of NSCDs can be significantly quenched by methotrexate (MTX) via fluorescence resonance energy transfer (FRET) between NSCDs and MTX, which was used for highly selective and sensitive detection of MTX with a wide linear range up to 50.0 μM and a low detection limit of 0.33 nM ( S / N =3). Moreover, this method was explored for practical detection of MTX in human serum with satisfied results.
The zirconia-coated silica (ZrO 2 /SiO 2 ) material was obtained by coupling layer-by-layer (LbL) self-assembly method and sol–gel technology, to take dual advantages of the suitable porous structure of SiO 2 and basic resistance of ZrO 2 . Adenosine 5′-monophosphate (5′-AMP) was then self-assembled onto ZrO 2 /SiO 2 via Lewis acid–base interaction, generating 5′-AMP-ZrO 2 /SiO 2 . The chromatographic properties of 5′-AMP-ZrO 2 /SiO 2 were systemically studied by evaluating the effect of acetonitrile content, pH and buffer concentration in the mobile phase. The results demonstrated that the 5′-AMP-ZrO 2 /SiO 2 possessed hydrophilic interaction chromatographic (HILIC) property comprising hydrophilic, hydrogen-bonding, electrostatic and ion-exchange interactions. For basic analytes, the column efficiency of ZrO 2 /SiO 2 and 5′-AMP-ZrO 2 /SiO 2 was superior to the bare ZrO 2 , and different selectivity was obtained after the introduction of 5′-AMP. For acidic analytes, good resolution was obtained on 5′-AMP-ZrO 2 /SiO 2 while the analysis failed on the bare ZrO 2 column owing to strong adsorption. Hence, the proposed 5′-AMP-ZrO 2 /SiO 2 had great potential in analyzing acidic compounds in HILIC mode. It was an extended application of ZrO 2 based SP.
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