Folate regulation of planar cell polarity pathway and F-actin through folate receptor alpha.

Folate deficiency contribute to neural tube defects (NTDs) which could be rescued by folate supplementation. However, the underlying mechanisms are still not fully understood. Besides, there is considerable controversy concerning the forms of folate used for supplementation. To address this controversy, we prepared culture medium with different forms of folate, folic acid (FA), and 5-methyltetrahydrofolate (5mTHF), at concentrations of 5 µM, 500 nM, 50 nM, and folate free, respectively. Mouse embryonic fibroblasts (MEFs) were treated with different folates continuously for three passages, and cell proliferation and F-actin were monitored. We determined that compared to 5mTHF, FA showed stronger effects on promoting cell proliferation and F-actin formation. We also found that FOLR1 protein level was positively regulated by folate concentration and the non-canonical Wnt/planar cell polarity (PCP) pathway signaling was significantly enriched among different folate conditions in RNA-sequencing analyses. We demonstrated for the first time that FOLR1 could promote the transcription of Vangl2, one of PCP core genes. The transcription of Vangl2 was down-regulated under folate-deficient condition, which resulted in a decrease in PCP activity and F-actin formation. In summary, we identified a distinct advantage of FA in cell proliferation and F-actin formation over 5mTHF, as well as demonstrating that FOLR1 could promote transcription of Vangl2 and provide a new mechanism by which folate deficiency can contribute to the etiology of NTDs.

Effect of acupuncture on women with poor ovarian response: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Poor ovarian response (POR), a manifestation of low ovarian reserve and ovarian aging, leads to a significant reduction in the pregnancy rate after in vitro fertilization-embryo transfer. Acupuncture has increasingly been used to improve the ovarian reserve. The purpose of this study will be to evaluate the effect of acupuncture on increasing the number of retrieved oocytes after controlled ovarian hyperstimulation in women with POR. METHODS: This will be a multicenter randomized controlled trial. A total of 140 women with POR will be randomly assigned to receive acupuncture or nontreatment for 12 weeks before controlled ovarian hyperstimulation. The primary outcome will be the number of retrieved oocytes. The secondary outcomes will be antral follicle counts, serum levels of anti-Müllerian hormone, basal serum levels of follicle stimulating hormone, luteinizing hormone and estradiol levels, scores from the self-rating anxiety scale, fertilization rates, cleavage rates, available embryo rates, and high-quality embryo rates. The safety of acupuncture will also be assessed. DISCUSSION: The results of this trial will help to determine the effectiveness of acupuncture in the treatment of POR. This may provide a new treatment option for patients with POR and their physicians. TRIAL REGISTRATION: AMCTR-IPR-18000198 . Registered on 10 August 2018.

Surface Engineering of Metal-Organic Framework as pH-/NIR-Responsive Nanocarrier for Imaging-Guided Chemo-Photothermal Therapy.

BACKGROUND: Metal-organic frameworks (MOFs) have attracted intensive research interest in the biomedical field because of their unique properties. However, in order to realize the high loading capacity and therapeutic efficacy, it is still urgent to develop a multifunctional MOFs-based nanoplatform. MATERIALS AND METHODS: Herein, a pH/near-infrared (NIR) dual-responsive drug delivery system based on zeolitic imidazolate framework-8 (ZIF-8) is constructed for synergistic chemo-photothermal therapy and dual-modal magnetic resonance (MR)/photoacoustic (PA) imaging. The doxorubicin hydrochloride (DOX) is embedded into ZIF-8 through one-pot method, and the resultant ZIF-8/DOX is then successively modified with polydopamine, Mn ions and poly(ethylene glycol). The obtained ZIF-8/DMPP is systematically characterized, and both its in vitro and in vivo biological effects are evaluated in detail. RESULTS: The ZIF-8/DMPP possesses a high drug-loading content of 18.9% and displays appropriate size and morphology. The pH-dependent degradation and drug release behavior of prepared ZIF-8/DMPP are confirmed. Importantly, the results demonstrate that the photothermal effect of ZIF-8/DMPP under NIR laser irradiation can significantly accelerate its drug releasing rate, further improving the intracellular drug concentrations. Thereafter, the augmented chemotherapeutic efficiency by photothermal effect against cancer cells is verified both in vitro and in vivo. Besides, the favorable MR and PA imaging capacity of ZIF-8/DMPP is also evidenced on the tumor model. CONCLUSION: Taken together, the surface engineering of ZIF-8-based nanocarrier in this work offers a promising strategy for the multifunctional MOFs-based drug delivery system.

Supplementation with low concentrations of melatonin improves nuclear maturation of human oocytes in vitro.

PURPOSE: Studies in bovine and porcine have indicated that melatonin (MT) could induce meiotic maturation of immature oocytes in vitro. The object of the current study was to investigate if MT could ameliorate human oocytes maturation during rescue in vitro maturation (IVM). METHODS: Two hundred seventy eight germinal vesicle (GV) oocytes and 451 (MI) metaphase I oocytes were vitrified, thawed and then matured in vitro. All the oocytes were randomly allocated into six groups in which the oocytes were cultured in medium supplemented with different concentrations of MT (0, 10(-2), 1, 10(2), 10(4), 10(6) nM) and nuclear maturation was evaluated at 6 h, 12 h, 18 h, 24 h and 48 h of culture. RESULTS: The optimal MT concentration for both GV and MI oocytes was 1 nM. At 24 h of culture, nuclear maturation rate of MI oocytes cultured in 1 nM MT medium was significantly higher than other groups (P < 0.05); Nuclear maturation rate of GV oocytes cultured in 1 nM MT medium was also significantly higher than the control group (P < 0.05). On the other hand, decreased nuclear maturation rate was observed in the high MT concentration group (10(6) nM). CONCLUSIONS: The current study demonstrated that low concentration of exogenous MT could ameliorate nuclear maturation of human oocyte during rescue IVM, while high concentration of MT presented negative effects.