Gut-derived metabolite 3-methylxanthine enhances cisplatin-induced apoptosis via dopamine receptor D1 in a mouse model of ovarian cancer.

Platinum-based chemotherapy failure represents a significant challenge in the management of ovarian cancer (OC) and contributes to disease recurrence and poor prognosis. Recent studies have shed light on the involvement of the gut microbiota in modulating anticancer treatments. However, the precise underlying mechanisms, by which gut microbiota regulates the response to platinum-based therapy, remain unclear. Here, we investigated the role of gut microbiota on the anticancer response of cisplatin and its underlying mechanisms. Our results demonstrate a substantial improvement in the anticancer efficacy of cisplatin following antibiotic-induced perturbation of the gut microbiota in OC-bearing mice. 16S rRNA sequencing showed a pronounced alteration in the composition of the gut microbiome in the cecum contents following exposure to cisplatin. Through metabolomic analysis, we identified distinct metabolic profiles in the antibiotic-treated group, with a notable enrichment of the gut-derived metabolite 3-methylxanthine in antibiotic-treated mice. Next, we employed a strategy combining transcriptome analysis and chemical-protein interaction network databases. We identified metabolites that shared structural similarity with 3-methylxanthine, which interacted with genes enriched in cancer-related pathways. It is identified that 3-methylxanthinesignificantly enhances the effectiveness of cisplatin by promoting apoptosis both in vivo and in vitro. Importantly, through integrative multiomics analyses, we elucidated the mechanistic basis of this enhanced apoptosis, revealing a dopamine receptor D1-dependent pathway mediated by 3-methylxanthine. This study elucidated the mechanism by which gut-derived metabolite 3-methylxanthine mediated cisplatin-induced apoptosis. Our findings highlight the potential translational significance of 3-methylxanthine as a promising adjuvant in conjunction with cisplatin, aiming to improve treatment outcomes for OC patients.IMPORTANCEThe precise correlation between the gut microbiota and the anticancer effect of cisplatin in OC remains inadequately understood. Our investigation has revealed that manipulation of the gut microbiota via the administration of antibiotics amplifies the efficacy of cisplatin through the facilitation of apoptosis in OC-bearing mice. Metabolomic analysis has demonstrated that the cecum content from antibiotic-treated mice exhibits an increase in the levels of 3-methylxanthine, which has been shown to potentially enhance the therapeutic effectiveness of cisplatin by an integrated multiomic analysis. This enhancement appears to be attributable to the promotion of cisplatin-induced apoptosis, with 3-methylxanthine potentially exerting its influence via the dopamine receptor D1-dependent pathway. These findings significantly contribute to our comprehension of the impact of the gut microbiota on the anticancer therapy in OC. Notably, the involvement of 3-methylxanthine suggests its prospective utility as a supplementary component for augmenting treatment outcomes in patients afflicted with ovarian cancer.

Early detection of a cesarean scar pregnancy with placenta increta by contrast-enhanced ultrasound in the first trimester: A case report and literature review.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy, which is a long-term complication of cesarean section. Prompt and accurate diagnosis of CSP is important to decrease maternal mobility and mortality. However, it is difficult to make an early detection for CSP complicated with morbidly adherent placenta. Contrast-enhanced ultrasound with the advantage in blood flow imaging is low-cost, time-saving, safe and more accessible in clinical practice. Here, we report a case with early detection of CSP with placenta increta by contrast-enhanced ultrasound and its successful uterine-sparing surgical management.

Anion-conductive membranes with ultralow vanadium permeability and excellent performance in vanadium flow batteries.

Anion exchange membranes prepared from quaternized poly(tetramethyl diphenyl ether sulfone) (QAPES) were first investigated in the context of vanadium flow battery (VFB) applications. The membranes showed an impressive suppression effect on vanadium ions. The recorded vanadium permeability was 0.02×10(-7)-0.09×10(-7) cm(2) min(-1), which was two orders of magnitude lower than that of Nafion 115. The self-discharge duration of a VFB single cell with a QAPES membrane is four times longer than that of Nafion 115. The morphological difference in hydrophilic domains between QAPES and Nafion was confirmed by TEM. After soaking the membranes in VO(2)(+) solution, adsorbed vanadium ions can barely be found in QAPES, whereas the hydrophilic domains of Nafion were stained. In the ex situ chemical stability test, QAPES showed a high tolerance to VO(2)(+) and remained intact after immersion in VO(2)(+) solution for over 250 h. The performance of a VFB single cell assembled with QAPES membranes is equal to or even better than that of Nafion 115 and remains stable in a long-term cycle test. These results indicate that QAPES membranes can be an ideal option in the fabrication of high-performance VFBs with low electric capacity loss.