Daporinad

Preterm birth (PTB) frequently results from the syndrome of preterm labor (PTL). PTL is linked to an atypical maternal inflammatory response, as well as intrauterine inflammation and/or infection. In this study, we explored the mechanisms involved in nicotine-mediated abnormal macrophage polarization and trophoblast invasion associated with PTL.

First, THP-1-M0 macrophages were generated by treating the human monocytic leukemia cell line (THP-1) with phorbol 12-myristate 13-acetate for a duration of 24 h. Afterward, nicotine treatment was administered, followed by coculturing with the HTR-8/SVneo trophoblast cell line (HTR-8) at a ratio of 1:1. Next, we transfected sh-α7nAChR and treated THP-1-M0 macrophages and HTR-8 cells with nicotine. In addition, we transfected THP-1-M0 macrophages with sh-NC or sh-SIRT1 or subjected them to 4 nM nicotinamide adenine dinucleotide (NAD) metabolic inhibitor FK866 treatment. Moreover, HTR-8 cells were treated with nicotine, after which THP-1-M0 macrophages were cocultured with HTR-8 cells. Finally, we constructed an in vivo RU486-induced PTL rat model to verify the effect of nicotine and the mechanisms involved.

We found that nicotine affected polarization and α7nAChR expression in HTR-8 cocultured THP-1-M0 macrophages. Knocking down α7nAChR blocked the effect of nicotine on the proliferation and invasion of HTR-8 cells. Furthermore, nicotine activated the α7nAChR/SIRT1 axis to regulate THP-1-M0 macrophage polarization through the cholinergic anti-inflammatory pathway. Additionally, NAD metabolism mediated the role of the α7nAChR/SIRT1 axis in nicotine-induced polarization of HTR-8 cocultured THP-1-M0 macrophages. In vivo experiments demonstrated that nicotine alleviated inflammation in PTL rats, which involved the α7nAChR/SIRT1 axis.

Nicotine regulated abnormal macrophage polarization and trophoblast invasion associated with PTL via the α7nAChR/SIRT1 axis.

It is now well known that visfatin is expressed in the testis and ovary of various animals. Visfatin is known to regulate gonadal functions such as steroidogenesis, proliferation, and apoptosis in the ovary and testis of mice. Recently, we have shown that visfatin has an inhibitory role in the infantile mice testis. It has also been shown that visfatin stimulates testicular steroidogenesis in adult rats. However, the role of visfatin during puberty has not been investigated in relation to the above-mentioned process.

The objective of the present study was to examine the effect of visfatin inhibition by FK866 from PND25 to PND35 (pre-pubertal to early pubertal) in male Swiss albino mice on steroidogenesis, proliferation, and apoptosis.

Sixteen mice (25 days old) were divided into two groups, one group was given normal saline and the other group was administered with an inhibitor of visfatin (FK866) at the dose of 1.5 mg/kg by intraperitoneal injection for 10 days. Histopathological and immunohistochemical analysis, western blot analysis and hormonal assay were done.

Visfatin inhibition resulted in increased estrogen secretion, body weight, seminiferous tubule diameter, germinal epithelium height, and proliferation along with increased expression of BCl2, casapse3, ERs and aromatase expression in the mice testis. Visfatin inhibition down-regulated the testicular visfatin expression and also decreased abundance in the adipose tissues.

In conclusion, decreased AR expression and increased ERs expression by FK866, suggest that visfatin might have a stimulatory effect on AR signaling than ERs in the early pubertal stage of mice.