High-fat diet decreases the expression of Kiss1 mRNA and kisspeptin in the ovary, and increases ovulatory dysfunction in postpubertal female rats.

BACKGROUND: Female reproductive health is noticeably compromised by obesity. The underlying mechanisms remain to be elucidated. Accumulating evidence indicates that the expression level of ovarian Kiss1 peaks in the afternoon during prooestrus, suggesting local regulatory roles for Kiss1 in the ovulatory process. We used a diet-induced model of obesity to evaluate whether the ovarian Kiss1 system is affected by obesity, and, to investigate the association of the Kiss1 system with ovulatory disorders in female rats. METHODS: Post-weaning, female, Sprague-Dawley rats were randomly fed either a high-fat diet (HFD) or a normal chow diet (NCD) until they reached postnatal day 30 (PND 30), PND 42, or PND 70. The timing of vaginal opening was recorded, and oestrous cyclicity was monitored for 2 consecutive weeks immediately post puberty and again at 8-9 weeks of age. Tissues from the left ovary were collected for determination of the levels of Kiss1 and G protein-coupled receptor 54 (GPR54) mRNA, and tissues from the right ovary were collected for assessment of the immunoreactivity (IR) of the corresponding protein products, kisspeptin and GPR54. RESULTS: The high-fat diet resulted in a significantly higher body weight and an earlier puberty onset. Oestrous cyclicity was disrupted by the HFD with significant reductions in the expression of ovulation-related genes. A marked suppression of ovarian Kiss1 mRNA levels was observed during prooestrus and oestrus at PND 42, and, during prooestrus, oestrus, and metoestrus at PND 70 in the HFD rats compared with the NCD controls. In the HFD group, the immunoreactivity of kisspeptin was significantly lower in theca cells from antral follicles during prooestrus and oestrus at PND 42, and, during prooestrus, oestrus at PND 70. At the prooestrus stage, in the HFD group the immunoreactivity of kisspeptin was also lower in the theca cells of preovulatory follicles at both PND 42 and PND 70. CONCLUSIONS: Exposure of female rats to an post-weaning, high-fat diet has long-term deleterious effects on ovulation, that may involve down-regulation of ovarian Kiss1 mRNA and kisspeptin.

[Effects on the secretion of reproductive hormones in adult female rats exposed to lipopolysaccharide in neonatal life].

OBJECTIVE: To explore whether neonatal endotoxin challenge alters reproductive hormone secretion in adult female rats. METHODS: Rats were intraperitoneally injected with lipopolysaccharide (LPS) or normal saline at postnatal days 3 and 5. At Week 12, the animals underwent bilateral oophorectomy and were exposed to LPS or saline. The secretion levels of luteinizing hormone (LH) and estradiol were measured. RESULTS: The LPS injection in adult neonatal saline rats caused the suppressed secretion of LH and estradiol. However, the decreased secretion of both LH and estradiol were much more apparent in adult neonatal LPS-treated rats. CONCLUSION: The neonatal LPS challenge alters the secretions of LH and estradiol during adulthood. And the mechanism may be mediated by epigenetic programming of hypothalamic-pituitary-gonadal axis.

Case Report: Leiomyosarcoma of the right external iliac artery: a diagnostic-based study on a rare case.

Leiomyosarcoma (LMS) is an uncommon and aggressive form of cancer that originates in the smooth muscles. It possesses the capacity for rapid growth and often manifests with general, nonspecific symptoms arising from the displacement of nearby structures rather than direct invasion. In this particular instance, an 81-year-old woman presented with right lower abdominal pain, leading to the discovery of a mass adjacent to the right external iliac artery. In this case, the patient was misdiagnosed initially because of her nonspecific and poorly distinguished clinical symptoms. The laboratory results were within normal ranges. A well-defined tumor was detected through laparoscopic operation and subsequently surgically excised. The histopathological analysis of the tumor revealed the presence of malignant spindle cells, nuclear pleomorphism, and tumor giant cells. Immunohistochemistry tests indicated positive results for CD34 and Desmin, while CD117 and DOG1 showed adverse effects. It is worth noting that LMS of the right external iliac artery is an infrequent occurrence, potentially resulting in delayed diagnosis and misidentification. To enhance our comprehension of this uncommon cancer, more cases with detailed information are essential.

Emerging role of PD-L1 modification in cancer immunotherapy.

Accumulating evidence demonstrates that the expression levels of programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are regulated at the various levels, including transcription, post-transcriptional modification and post-translational modifications (PTMs). The PTMs of PD-1/PD-L1 contain phosphorylation, ubiquitination, methylation, glycosylation and palmitoylation. Recently, PD-L1 was reported to be acetylated at Lys263 site by p300 and was deacetylated by histone deacetylase 2 (HDAC2). Acetylation of PD-L1 prevented its translocation to the nucleus and led to a reduction of the nuclear portion of PD-L1, resulting in evading immune surveillance of tumor cells. In this review article, we briefly describe the PTMs of PD-1/PD-L1 and mainly summarize the novel findings of PD-L1 acetylation in tumor cells. Moreover, we discuss the associations of PD-L1 acetylation and ubiquitination, phosphorylation and methylation. Furthermore, we highlight that targeting acetylation of PD-L1 by HDAC inhibitors might be useful for enhancing tumor immunotherapy.

CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway.

AIMS: CNOT7 plays an important role in many biological processes, providing attractive opportunities for the treatment of malignant tumors. However, the functions and mechanism of CNOT7 in ovarian cancer (OC) have not been elucidated. The purpose of this study was to assess the role of CNOT7 in OC. MATERIALS AND METHODS: SKOV3 and A2780 cells were chosen as the cell lines for the experiments of this manuscript via the analysis of the expression of CNOT7 protein and the mRNA level in ovarian surface epithelium (OSE) cells, SKOV3, HO8910 and A2780 cells. The expression of CNOT7 was detected by western blot assays and RT-PCR in A2780 and SKOV3 cells. The MTT assays, colony formation assays and EdU assays were used to measure cell proliferation when CNOT7 was knocked down or overexpressed in A2780 and SKOV3 cells. Furthermore, cell migration and invasion ability were achieved from transwell assays. Cell cycle and apoptosis rate after small interference RNA-CNOT7 (siRNA-CNOT7) were detected by flow cytometry assays. Finally, the cell proliferation, migration and invasion ability were detected when A2780 and SKOV3 cells with CNOT7 overexpression were treated with LY294002. KEY FINDINGS: The expression of CNOT7 protein in OC cells, including SKOV3, HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.05). The mRNA level of CNOT7 in HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.01). However, the mRNA level of CNOT7 in SKOV3 cells was no significant difference compared with OSE cells (P > 0.05). The results suggested that knockdown of CNOT7 could inhibit the cell proliferation, migration and invasion ability in A2780 and SKOV3 cells, and increase cell apoptosis and autophagy. The expression of apoptosis-related molecules (PARP, Caspase3 and Caspase9) and autophagy-related protein (LC3B) were up-regulated after CNOT7 knockdown, while the expression of cycle-related protein (CDK6) and the anti-apoptotic gene (Bcl2) were downregulated. Meanwhile, the opposite results were observed when CNOT7 was overexpressed in A2780 and SKOV3 cells. It is worth noting that the effect of CNOT7 overexpression in A2780 and SKOV3 cells could be partially or completely eliminated by treatment with AKT inhibitor LY294002. SIGNIFICANCE: CNOT7 has a carcinogenic effect in OC, and the carcinogenic effect may be achieved via the AKT signaling pathway.

LINC00261 functions as a competing endogenous RNA to regulate BCL2L11 expression by sponging miR-132-3p in endometriosis.

Endometriosis is a benign disease but manifests with malignant features and limited treatment options. Women with endometriosis should not be ignored or patronized by the medical profession and society. In this regard, a major cultural change and searching for the optimum therapeutic regimen from multiple perspectives is needed in China even in the whole world. Long non-coding RNAs are crucial for various human diseases while its potential functions and mechanisms are largely unknown in endometriosis. LINC00261 was significantly downregulated in endometriosis tissues and our study indicated that it suppresses proliferation and invasion of endometriosis cells functionally in vitro. Insights of the mechanism of competitive endogenous RNAs were obtained from bioinformatic analysis, RIP, RNA pull-down and luciferase assays, which further confirmed that LINC00261 functions as a molecular sponge to regulate BCL2L11 expression by binding to miR-132-3p directly. These data defined LINC00261/miR-132-3p/BCL2L11 regulatory networks may be a novel therapeutic target for endometriosis.

Villoglandular papillary adenocarcinoma of the uterine cervix: A report of 4 cases and a review of the literature.

To investigate the clinicopathological features, management and prognosis of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix, the current study presents 4 cases of VGPA of the uterine cervix. The median age of the patients was 55 years (range, 47-70 years), with all 4 patients presenting with stage Ib disease. Human papillomavirus (HPV) infection was detected in 3 patients; this was mainly HPV-16. No history of oral contraceptive use was found in these cases. While 2 of the patients underwent a radical hysterectomy with bilateral salpingo-oophorectomy plus bilateral pelvic lymphadenectomy, 1 patient underwent a radical hysterectomy with bilateral pelvic lymphadenectomy and the remaining patient received a simple total hysterectomy plus post-operative radiotherapy. Of these patients, only 1 had been correctly diagnosed pre-operatively. In 2 patients, the biopsy results had been interpreted as cervical adenocarcinoma, and in the third, the biopsy result was of cervical intraepithelial neoplasia. All 4 patients presented with cervical wall invasion, including invasion of the inner two-thirds in 1 patient. No lymphovascular space invasion or lymph node metastasis was detected. The follow-up time ranged from 49 to 83 months (median, 64 months), and the patients are currently alive and well, with no evidence of recurrent disease. Taking these results as a whole, VGPA is an uncommon type of cervical adenocarcinoma, characterized by its excellent prognosis. HPV infection is associated with the molecular pathogenesis of VGPA, while oral contraceptive use can be excluded. As the disease has a low pre-operative diagnostic accuracy, frequent cervical wall invasion and concomitant lesions, conservative treatment strategies should be carefully considered.