FTO-mediated ZNF687 accelerates tumor growth, metastasis, and angiogenesis in colorectal cancer through the Wnt/ß-catenin pathway.

Colorectal cancer (CRC) is a common and lethal cancer. ZNF687 has been disclosed to take part in diversified cancers' progression by serving as a facilitator. However, the detailed regulatory functions of ZNF687 in the CRC have not been investigated. This work is planned to probe the impacts of ZNF687 on CRC progression. The IHC, RT-qPCR, and western blot assays were used to examine mRNA and protein gene expressions. The cell proliferation measurement was accompanied by a CCK-8 assay. The Transwell assay was performed to evaluate cell invasion and migration. The angiogenesis ability was evaluated by a tube formation experiment. The m6A level was evaluated through MeRIP and m6A dot blot assays. The binding ability between ZNF687 and FTO (fat mass and obesity associated protein) was tested through an RIP assay. The ß-catenin nuclear translocation was assessed through an immunofluorescence assay. The tumor growth was evaluated through an in vivo assay. ZNF687 exhibited higher expression in CRC cells and resulted in a poor prognosis. Additionally, ZNF687 inhibition suppressed CRC cell proliferation, invasion, migration, and angiogenesis. Furthermore, the suppression of ZNF687 retarded the Wnt pathway. Through rescue assays, the reduced cell migration, proliferation, invasion, and angiogenesis mediated by ZNF687 knockdown could be reversed after BML-284 (the activator of the Wnt pathway) treatment. Finally, it was explained that ZNF687 knockdown inhibited in vivo tumor growth. This study manifested that FTO-mediated ZNF687 aggravated tumor growth, metastasis, and angiogenesis of CRC through Wnt/ß-catenin pathway. This finding may provide a hopeful molecular target for CRC treatment.

Transvaginal approach for rectovaginal fistula: experience from a single institution.

Transvaginal (TV) repair, featuring its feasibility, effectiveness, safety, and technically less demandingness, is one of the surgical approaches for management of rectovaginal fistula (RVF). However, there are limited numbers of publications available on the transvaginal approach for RVF repair. To this end, the purpose of this study is to evaluate the preliminary outcomes of the transvaginal approach performed by the team, and to further assess its feasibility, safety and effectiveness in the management of RVF. A retrospective analysis was conducted at a single institution. Patients with RVF who had undergone three transvaginal surgical techniques, i.e. transvaginal fistulectomy and stratified suture, transvaginal flip and ligation fistula tract and transvaginal fistula stapled closure were included. Besides, the demographics, operative data, postoperative complications and follow-up outcomes of the patients were collected prospectively. A total of 49 female patients (mean age, 35.76 ± 13.97 years) underwent transvaginal approach, 42 of which were followed up with a median follow-up of 26 months (range 3-82 months), and 29 had closure of the fistula (successful closure rate of 59.1%). The successful closure rates were only significantly different between previous repair times (p = 0.031), and several minor complications including postoperative pain (n = 3), constipation (n = 1), and lower urinary tract infection (n = 1) were observed. Symptomatic improvement was reported in all patients with failed closure. Transvaginal approach for RVF repair is effective, safe, and feasible, and is therefore considered an alternative to transrectal advancement flap for low and mid-level traumatic RVF with normal sphincter function. With the advantage of better surgical access, transvaginal approach is recognized as the initial choice for the surgical repair of RVF.

Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries.

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100µM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3ß2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation and, possibly, normal blood flow in the brainstem.