Interleukin-17A Differentially Induces Inflammatory and Metabolic Gene Expression in the Adipose Tissues of Lean and Obese Mice.

The functions of interleukin-17A (IL-17A) in adipose tissues and adipocytes have not been well understood. In the present study, male mice were fed with a regular diet (n = 6, lean mice) or a high-fat diet (n = 6, obese mice) for 30 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were analyzed for IL-17A levels. SAT and VAT were treated with IL-17A and analyzed for inflammatory and metabolic gene expression. Mouse 3T3-L1 pre-adipocytes were differentiated into adipocytes, followed with IL-17A treatment and analysis for inflammatory and metabolic gene expression. We found that IL-17A levels were higher in obese SAT than lean SAT; the basal expression of inflammatory and metabolic genes was different between SAT and VAT and between lean and obese adipose tissues. IL-17A differentially induced expression of inflammatory and metabolic genes, such as tumor necrosis factor α, Il-6, Il-1ß, leptin, and glucose transporter 4, in adipose tissues of lean and obese mice. IL-17A also differentially induced expression of inflammatory and metabolic genes in pre-adipocytes and adipocytes, and IL-17A selectively activated signaling pathways in adipose tissues and adipocytes. These findings suggest that IL-17A differentially induces inflammatory and metabolic gene expression in the adipose tissues of lean and obese mice.

A randomized controlled trial reducing cesarean delivery rates in China by introducing trial of labor after cesarean and electrohysterography.

OBJECTIVE: A cesarean delivery (CD) can affect health of both mother and child and future pregnancies. Since the abandonment of the one-child policy in China, obstetricians tend to perform a repeat CD rather than a trial of labor after cesarean (TOLAC). This study aims to reduce CD rates by increasing vaginal births after cesarean (VBAC) rates and introducing electrohysterography (EHG) for accurate monitoring. METHODS: In total, 82 women received counseling regarding TOLAC at the Shijiazhuang Sixth Hospital in China. Women opting for TOLAC were randomized for either external tocodynamometry (TOCO, i.e. standard care) or EHG. The primary outcome was the VBAC rate. Secondary outcomes were indications for CD, percentage of assisted vaginal deliveries, labor duration, maternal blood loss, complications and neonatal outcomes. RESULTS: After accounting for preterm delivery and dropouts, all counseled women opted for a TOLAC (100%). After randomization, 42 women were included in the TOCO-group and 37 in the EHG-group. Women did not receive pain medication and labor was not augmented with oxytocin. The VBAC rate was 71.4% in the TOCO-group, versus 78.4% in the EHG-group (p = .48). Birth was assisted with forceps in 11.9% of TOCO-group versus 2.7% of EHG-group (p = .21). One secondary CD (i.e. a shift from intended vaginal delivery to surgical delivery within the same labor) was performed because of a suspicion of uterine rupture (TOCO-group). Other indications for CD were: fetal distress, labor dystocia, fetal position, cephalopelvic disproportion. There were no significant differences in secondary study outcomes. No complications were reported. CONCLUSION: This study showed an average VBAC rate of 75%, without any complications, in a hospital with no previous experience with TOLAC. The VBAC rate with EHG-monitoring was higher than TOCO, although this difference was not significant. To demonstrate a significant difference, larger clinical studies are necessary. TRIAL REGISTRATION: The Daily Board of the Medical Ethics Committee of The Maternal and Child Hospital of Shijiazhuang approved the study protocol (number 20171018, Dutch Trial Register NL8199).

Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer.

Endometrial cancer (EC) is the most frequent gynecological malignancy and a major cause of morbidity and mortality for women worldwide. Programmed cell death protein 1 (PD-1) and its ligands programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) have been well studied in lung cancer, melanoma and renal-cell cancer. However, few studies have been performed in EC. The purpose of the present study was to assess the expression of PD-1, PD-L1 and PD-L2 in 35 human normal endometrial tissue samples and 75 human EC tissue samples using immunohistochemical staining. It was found that 61.3% of ECs were positive for PD-1 staining, which was almost exclusively found in the tumor-infiltrating immune cells. By contrast, PD-1 was not expressed in the tumor cells or normal endometrial tissues. It was also found that 14.3% of normal endometria and 17.3% of EC tissues were positive for PD-L1 expression, while 20.0% of normal endometrium and 37.3% of EC tissues were positive for PD-L2 expression; however, there was no statistically significant difference between the normal endometrium and EC tissues. PD-1 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and non-endometrioid (type II) ECs than in the well-differentiated ECs and endometrioid (type I) ECs. Similarly, PD-L1 and PD-L2 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and type II ECs than in the type I ECs. The present findings indicate a possible better outcome for future treatment with anti-PD-1 or anti-PD-L1 antibody-based therapies against these subgroups of endometrial cancers with frequent expression of the PD-1/PD-L1/PD-L2 axis.

Expression of p-Akt in ovarian serous carcinoma and its association with proliferation and apoptosis.

The aim of the present study was to determine the expression of p-Akt in ovarian serous carcinoma (OSC) and its association with proliferation and apoptosis. Paraffin-embedded tissues of patients aged between 35 and 64 years old without history of radiotherapy, chemotherapy and hormone therapy prior to surgery were collected. In total, samples included 12 ovarian serous cystadenomas (OSAs), 18 ovarian serous borderline tumors (OS-BTs) and 46 OSCs. Of the 46 OSC samples, 16 were well-differentiated, 20 were moderately differentiated and 10 were poorly differentiated, while 22 developed lymphatic metastases and 24 were metastasis-free. An additional 10 paraffin-embedded normal ovarian tissues (NOTs) were used as controls. Streptavidin-peroxidase immunohistochemistry assays were used to investigate the expression of p-Akt and cyclin D1 in the collected samples. Compared with NOT, p-Akt expression in the OS-BT and OSC groups, as well as cyclin D1 expression in the OSA and OSC groups, was significantly elevated (P<0.05). Compared with the OSA group, p-Akt expression in the OSC group was significantly elevated (P<0.01) and reversely associated with tumor differentiation (P<0.01), whereas cyclin D1 expression showed no correlation with tumor differentiation (P>0.05). The expression of p-Akt, caspase-3 and cyclin D1 was positively associated with lymphatic metastasis (r=0.334; P=0.023). The expression of p-Akt gradually increased with carcinoma development and was associated with differentiation and metastasis of OSC, revealing that the activation of the PI3K/Akt signaling pathway is involved in the development of OSC. Furthermore, the expression of cyclin D1 gradually increased in the NOT, OSA, OS-BT and OSC groups and was associated with tumor metastasis.