Prenatal infection promotes olanzapine-induced obesity in rats: implications for antipsychotic-induced obesity in schizophrenia

Abstract of a poster presentation

Survey and alignment of the synchrotron SIS18

Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue

Bardoxolone methyl prevents the development and progression of cardiac and renal pathophysiologies in mice fed a high-fat diet

Obesity caused by the consumption of a high-fat (HF) diet is a major risk factor for the development of associated complications, such as heart and kidney failure. A semi-synthetic triterpenoid, bardoxolone methyl (BM) was administrated to mice fed a HF diet for 21 weeks to determine if it would prevent the development of obesity-associated cardiac and renal pathophysiologies. Twelve week old male C57BL/6J mice were fed a lab chow (LC), HF (40% fat), or a HF diet supplemented with 10 mg/kg/day BM in drinking water. After 21 weeks, the left ventricles of hearts and cortex of kidneys of mice were collected for analysis. Histological analysis revealed that BM prevented HF diet-induced development of structural changes in the heart and kidneys. BM prevented HF diet-induced decreases in myocyte number in cardiac tissue, although this treatment also elevated cardiac endothelin signalling molecules. In the kidneys, BM administration prevented HF diet-induced renal corpuscle hypertrophy and attenuated endothelin signalling. Furthermore, in both the hearts and kidneys of mice fed a HF diet, BM administration prevented HF diet-induced increases in fat accumulation, macrophage infiltration and tumour necrosis factor alpha (TNFα) gene expression. These findings suggest that BM prevents HF diet-induced developments of cardiac and renal pathophysiologies in mice fed a chronic HF diet by preventing inflammation. Moreover, these results suggest that BM has the potential as a therapeutic for preventing obesity-induced cardiac and renal pathophysiologies

Laparoscopic Radical Hysterectomy Results in Higher Recurrence Rate Versus Open Abdominal Surgery for Stage IB1 Cervical Cancer Patients With Tumor Size Less Than 2 Centimeter: A Retrospective Propensity Score-Matched Study

ObjectiveTo compare the oncologic outcomes between laparoscopic and open radical hysterectomy in patients with stage IB1 cervical cancer lesion less than 2 cm.MethodsPatients diagnosed FIGO (2009) stage IB1 (tumor diameter <2 cm) and underwent radical hysterectomy in our hospital between March 2008 and November 2018 were studied. A propensity-matched comparison (1:2) was conducted to minimize selection biases. Demographic and baseline oncologic characteristics were balanced between groups. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan–Meier model, along with univariable and multivariable regression analysis.ResultsA total of 261 patients were enrolled in this study after propensity-matching, with 174 in the open group and 87 in the laparoscopic group. Disease relapsed in seven patients in laparoscopy group, and the recurrence rate was 8.0% (7/87). There were eight patients underwent abdominal radical hysterectomy experienced recurrence, and the recurrence rate was 4.6% (8/174). The multivariate analysis model revealed that laparoscopic operation was associated with higher risk of recurrence than abdominal radical hysterectomy (HR, 3.789; 95% CI, 1.143–12.559; p = 0.029). There were five patients or 2.9% (5/174) died in open surgery group and the corresponding percentage in laparoscopy group was 2.3% (2/87). No difference was found in OS between the two groups (HR, 1.823; 95% CI, 0.2673–12.44; log-rank p = 0.5398). All the recurrence occurred within two years after operation in the laparoscopy group, among which pelvic recurrence (85.7%) was dominant.ConclusionTraditional laparotomy radical hysterectomy has a lower recurrence rate when compared with laparoscopic operation in those cervical cancer patients with a foci diameter less than 2 cm. However, no detrimental effect on survival was found in minimal invasive operation group. Further multi-center prospective trials are needed to confirm our results on a large scale

Profiling analysis of long non-coding RNAs in early postnatal mouse hearts

Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition

Differential cognitive and behavioural impacts of LPS and PolyI:C prenatal infections on adult female offspring

Abstract of a poster presentation

Neuropathology of muscarinic receptor in the prenatal infection - rat model

Abstract of a poster presentation

Olanzapine differentially corrects altered NMDA receptor binding induced by prenatal polyIC and LPS

Abstract of a poster presentation