Effect of Prepregnancy Obesity on Litter Size in Primiparous Minipigs.

Obesity is a public health problem in both developed and developing countries, and the negative effects of obesity on reproductive physiology have been highlighted recently. We evaluated the effects of porcine obesity index, sex hormones, and peptide hormones on litter size in various breeds of minipigs. Blood samples were collected from sedated 8-,10-, and 12-mo-old minipigs to measure preovulatory levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin) and peptide hormones (insulin-like growth factor, glucagon, cortisol, growth hormone, free thyroxine, free triiodothyronine, insulin, and leptin). We also measured weight, abdominal circumference, neck circumference, and body length and then calculated the porcine obesity index. Data were analyzed by one-way ANOVA, and means were compared by least significance difference testing. Pearson correlation between parameters and litter size was analyzed. Prepregnancy porcine obesity index and litter size were negatively correlated in primiparous minipigs. Litter size was influenced by luteinizing hormone, estradiol, progesterone, testosterone, prolactin, follicle-stimulating hormone, cortisol, insulin-like growth factor 1, growth hormone, free thyroxine, insulin, and leptin. In conclusion, prepregnancy obesity reduces litter size in primiparous minipigs.

Huge retroperitoneal liposarcoma with renal involvement requires nephrectomy: A case report and literature review.

A 60-year-old female visited Guihang Guiyang Hospital (Guiyang, China). She presented with abdominal pain in the right side for the previous 2-months, with a touchable mass identified for the previous 1-month. Computed tomography with magnetic resonance imaging revealed a huge mass in the right abdomen. The diagnosis of well-differentiated retroperitoneal liposarcoma with renal involvement was made. During surgery, the tumor was removed, including the fatty renal capsule; however, the kidney was preserved. It is currently debatable whether resection of adjacent organs is required to obtain the negative margins. Conventional viewpoints advise that multi-organ resection is required in order to obtain the negative-margin. However, even if an R0 resection is achieved, the local recurrence rate remains markedly high. Additionally, the complications of organ resection have more impact on patients. Radiotherapy and chemotherapy are an important adjuvant method for these patients. In conclusion, retroperitoneal liposarcoma is a rare disease with a high rate of recurrence. Complete resection is the predominant treatment; however, combined resection of adjacent organs must be considered.

SiRNA-mediated serotonin transporter knockdown in the dorsal raphe nucleus rescues single prolonged stress-induced hippocampal autophagy in rats.

The neurobiological mechanisms underlying the development of post-traumatic stress disorder (PTSD) remain elusive. One of the hypotheses is the dysfunction of serotonin (5-HT) neurotransmission, which is critically regulated by serotonin transporter (SERT). Therefore, we hypothesized that attenuation of SERT gene expression in the hippocampus could prevent hippocampal autophagy and the development of PTSD-like behavior. To this end, we infused SLC6A4 siRNAs into the dorsal raphe nucleus (DRN) to knockdown SERT gene expression after a single prolonged stress (SPS) treatment in rats. Then, we evaluated the effects of SERT gene knockdown on anxiety-related behaviors and extinction of contextual fear memory. We also examined the histological changes and the expression of Beclin-1, LC3-I, and LC3-II in the hippocampus. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT level, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the hippocampus. Furthermore, intra-DRN infusion of SLC6A4 siRNAs promoted the extinction of contextual fear memory, prevented hippocampal autophagy, increased 5-HT level, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio. These results indicated that SERT may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the development of PTSD.

Expression of transcription factor FOXC2 in cervical cancer and effects of silencing on cervical cancer cell proliferation.

OBJECTIVE: Forkhead box C2 (FOXC2) is a member of the winged helix/forkhead box (Fox) family of transcription factors. It has been suggested to regulate tumor vasculature, growth, invasion and metastasis, although it has not been studied in cervical cancer. Here, we analyzed FOXC2 expression in cervical tissues corresponding to different stages of cervical cancer development and examined its correlation with clinicopathological characteristics. In addition, we examined the effects of targeting FOXC2 on the biological behavior of human cervical cancer cells. METHODS: The expression of FOXC2 in normal human cervix, CIN I-III and cervical cancer was examined by immunohistochemistry and compared among the three groups and between cervical cancers with different pathological subtypes. Endogenous expression of FOXC2 was transiently knocked down in human Hela and SiHa cervical cells by siRNA, and cell viability and migration were examined by scratch and CCK8 assays, respectively. RESULTS: In normal cervical tissue the frequency of positive staining was 25% (10/40 cases), with a staining intensity (PI) of 0.297 ± 0.520, in CIN was 65% (26/40 cases), with a PI of 3.00 ± 3.29, and in cancer was 91.8% (68/74 cases), with a PI of 5.568 ± 3.449. The frequency was 100% in adenocarcinoma (5/5 cases) and 91.3% in SCCs (63/69 cases). The FOXC2 positive expression rate was 88.5% in patients with cervical SCC stage I and 100% in stage II, showing significant differences compared with normal cervix and CIN. With age, pathologic differentiation degree and tumor size, FOXC2 expression showed no significant variation. On transient transfection of Hela and SiHa cells, FOXC2-siRNA inhibition rates were 76.2% and 75.7%; CCK8 results showed reduced proliferation and relative migration (in Hela cells from 64.5 ± 3.16 to 49.5 ± 9.24 and in SiHa cells from 60.1 ± 3.05 to 44.3 ± 3.98) (P < 0.05). CONCLUSION: FOXC2 gene expression increases with malignancy, especially with blood vessel hyperplasia and invasion degree. Targeted silencing was associated with reduced cell proliferation as well as invasion potential.

Selective beta-1 blockers deteriorate glucose metabolism. A meta-analysis.

OBJECTIVE: To provide an up-to-date synthesis of available data, and to quantify the effect of highly selective beta-1 blockers on glucose metabolism in patients with essential hypertension and type diabetes mellitus (T2DM) by using pooled analysis techniques. METHODS: Cochrane Library, PubMed, MEDLINE, and EMBASE databases were searched from inception to July 2013 in the Third Affiliated Hospital of Nanchang University, Nanchang, China. We collected randomized controlled trails reporting on the effect of highly selective beta-1 blockers on glucose metabolism in patients with hypertension and type 2 diabetes. Data was screened, evaluated, and extracted by 2 independent researchers according to the inclusion and exclusion criteria. Meta-analysis was conducted using RevMan5.0 software. RESULTS: Seven trials were enrolled in the meta-analysis including a total of 1354 patients. Meta-analysis results revealed that when compared with the control group, selective beta-1 blockers were associated with a higher fasting blood glucose (weighed mean difference: 0.21, 95% confidence interval [CI]: 0.16-0.27; p<0.00001). But results revealed no significant difference in glycosylated hemoglobin (weighed mean difference: 0.13, 95% CI: -0.11 to 0.37; p=0.28), fasting insulin (weighed mean difference: -1.13, 95% CI: -4.27 to 2.01; p=0.48), and gain in body weight (weighed mean difference: 1, 95% CI: -1.08 to 3.08; p=0.35). CONCLUSION: Selective beta-1 blockers were associated with elevated fasting blood glucose. Thus, it should not be used for patients with essential hypertension and diabetes.

Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels.

Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) for articular cartilage and fibrocartilage tissue engineering, with each material offering distinct advantages and disadvantages. Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. Results show that when the fibrin/alginate ratio decreased, the fibrin architecture transitioned from uniform to interconnected fibrous and finally to disconnected islands against an alginate background, with opposing trends in the alginate architecture. Fibrin maintained gel extensibility and promoted cell proliferation, while alginate improved the gel biostability and better supported glycosaminoglycan and collagen II production and chondrogenic gene expression. Blended gels had physical and biological characteristics intermediate between fibrin and alginate. Of the blends examined, FA 40:8 (40 mg ml(-1) fibrinogen blended with 8 mg ml(-1) alginate) was found to be the most appropriate group for future studies on tension-driven BM-MSC fibrochondrogenesis. As BM-MSC differentiation appeared to vary between fibrin and alginate regions of blended scaffolds, this study also highlighted the potential to develop spatially heterogeneous tissues through manipulating the heterogeneity of scaffold composition.

Deciphering the mysteries of crisscross heart by transthoracic echocardiography.

BACKGROUND: Accurate diagnosis of crisscross heart and its associated anomalies is important but problematic for cardiologists. This study aimed at identifying unique transthoracic echocardiographic features and common associated lesions of this complex condition. METHOD: Clinical and echocardiographic features of 10 patients with crisscross anatomy were studied. Echocardiographic findings were verified by cardiac magnetic resonance imaging or surgical inspection. RESULTS: Crisscross anatomy (10 patients, age at diagnosis ranged from 1 month to 25 years, five female) was identified in 0.076% of patients with congenital heart diseases from 1985 to 2006. All patients had cyanosis and 80% of them were underweight. Superior-inferior ventricles (SIV) and crossed ventricular inflow streams were seen in 90% and 100% of patients, respectively. All patients had abnormal ventriculo-arterial (VA) connections: five with transposition of great artery (L-type: n = 2; D-type: n = 3) and five with double outlet right ventricle. Commonly associated anomalies included ventricular septal defects (100%), right ventricular outflow tract obstruction (60%), atrioventricular valves straddling or overriding (50%), atrial septal defect (40%), and right ventricular hypoplasia (30%). Seven patients received cardiac surgery for the relief of cyanosis. CONCLUSIONS: SIV and crossed inflow streams are important diagnostic features for crisscross heart by transthoracic echocardiogram. The hemodynamic consequences of abnormal VA connections and associated defects impact surgical management.

The mechanism underlying vascular smooth muscle cell apoptosis induced by atorvastatin may be mainly associated with down-regulation of survivin expression.

PURPOSE: Studies have shown that statins may induce vascular smooth muscle cells (VSMCs) apoptosis. But its mechanisms are incompletely understood. In this study, we investigate the effects of atorvastatin and survivin antisense oligonucleotides (ASODN) on VSMCs apoptosis and the relation between survivin and VSMCs apoptosis. MATERIALS AND METHODS: Cultured VSMCs were treated with atorvastatin and vascular endothelial grow factor (VEGF). Apoptosis of VSMCs at 6-72 h after treatment with atorvastatin was detected by means of Hoechst33258 staining. Survivin and Fas factors expression were detected by means of immunohistochemistry. Survivin and Fas mRNA expression were detected by means of RT-PCR. In order to determine the relations between survivin and VSMCs apoptosis, we also performed transfection of VSMCs with survivin ASODN using GenePORTER Transfection Reagent and studied the survivin protein expression by means of western blotting. RESULTS: VSMCs apoptosis after treatment with atorvastatin was increased in a dose- and time-dependent manner. The expression of survivin and survivin mRNA in VSMCs was significantly down-regulated at 24 h and disappeared at 48-72 h after treatment with atorvastatin. Fas and Fas mRNA in VSMCs could only be detected at 72 h and not at 6-48 h after treatment with atorvastatin. We did not observe any effects of VEGF on VSMCs apoptosis, on survivin and survivin mRNA expression, and on Fas and Fas mRNA expression in VSMCs after treatment with atorvastatin. At 48 hours after the start of transfection, survivin protein expression was significantly reduced after transfection with 0.5, 1.0 and 2.0 microg/ml of survivin ASODN and there was no survivin protein expression after transfection with 3.0 and 4.0 microg/ml of survivin ASODN. In contrast, in the GenePORTER only and SODN studies, survivin protein expression was observed with western blotting. Hoechst33258 staining showed that treatment of VSMCs with survivin ASODN resulted in VSMCs apoptosis. CONCLUSIONS: Atorvastatin induces VSMCs apoptosis in a dose- and time-dependent manner. Transfection of survivin ASODN can directly induce VSMCs apoptosis. The mechanisms of VSMCs apoptosis induced by atorvastatin may be mainly associated with down-regulation of survivin expression in VSMCs. Up-regulation of Fas in VSMCs may play a role in later stages following atorvastatin treatment.