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

Abstract of a poster presentation

Regulation of Exosomes in the Pathogenesis of Breast Cancer

Extracellular vesicles (EVs) are a heterogeneous group of endogenous nanoscale vesicles that are secreted by various cell types. Based on their biogenesis and size distribution, EVs can be broadly classified as exosomes and microvesicles. Exosomes are enveloped by lipid bilayers with a size of 30–150 nm in diameter, which contain diverse biomolecules, including lipids, proteins and nucleic acids. Exosomes transport their bioactive cargoes from original cells to recipient cells, thus play crucial roles in mediating intercellular communication. Breast cancer is the most common malignancy among women and remains a major health problem worldwide, diagnostic strategies and therapies aimed at breast cancer are still limited. Growing evidence shows that exosomes are involved in the pathogenesis of breast cancer, including tumorigenesis, invasion and metastasis. Here, we provide a straightforward overview of exosomes and highlight the role of exosomes in the pathogenesis of breast cancer, moreover, we discuss the potential application of exosomes as biomarkers and therapeutic tools in breast cancer diagnostics and therapeutics

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

Identification and Functional Evaluation of miR-4633-5p as a Biomarker and Tumor Suppressor in Metastatic Melanoma

Background/Aims: Sinonasal mucosal melanoma (SMM) is a rare but extremely aggressive disease. Interestingly, however, as lethal as SMM, a few patients could survive for over 5 years without metastasis. However, biomarkers for metastatic SMM are lacking. Methods: Laser-capture microdissection combined with microRNA microarray and RT-qPCR was performed in formalin-fixed paraffin-embedded tissue samples from SMM patients whose follow-up studies were carried out in parallel. In vitro cell proliferation and invasion assays, gelatin zymography, western blot analysis and RT-qPCR were performed in melanoma cell lines. Results: In the discovery stage, miR-4633-5p expressed differentially in sinonasal mucosal melanoma patients with short and long disease-specific survival. Subsequent large-sample validation revealed that expression of miR-4633-5p was lower in metastatic SMM than in non-metastatic patients (P< 0.001). Moreover, miR-4633-5plow was able to identify metastatic SMM with specificity of 100% (5/5) and sensitivity of 87.5% (21/24). Multivariate analysis further pinpointed miR-4633-5p as an independent marker for metastasis (relative risk: 54.22, P< 0.001). In vitro, overexpression of miR-4633-5p suppressed the growth and invasiveness of melanoma cells through inhibiting activation of Akt pathway and secretion of MMP2, while knockdown of miR-4633-5p reversed the inhibitory effects. Conclusion: Our findings underpin miR-4633-5p as a predictive biomarker in metastatic SMM and a pivotal tumor suppressor that negatively regulates the invasive growth of melanoma cells. Quantitative detection of miR-4633-5p can diagnostically predict the risk of metastasis in SMM patients, which, in turn, may lead to more personalized treatment with better prognosis

Microbial-environmental interactions reveal the evaluation of fermentation time on the nutrient properties of soybean meal

Microbial fermentation techniques are often used to improve their quality, where the keys are fermentation strains and fermentation time. This study studied the interaction between microbiota and environmental (or nutritional) factors and microbiota at different fermentation times to determine the most appropriate time, using lactic acid bacteria as fermentation strains. It can be concluded that fermentation improved the nutritional value of soybean meals. In the early stages of fermentation, debris in soybean meal highly proliferated and destabilized the microbial community, while pH and nutritional conditions played an important role in helping its stabilization. In addition, we must pay attention to the interspecific interactions of microorganisms, which makes it easy to understand how the microbial community maintains community stability. A 4-day fermentation of soybean meal with Lactobacillus is recommended

Stress CMR T1-mapping technique for assessment of coronary microvascular dysfunction in a rabbit model of type II diabetes mellitus: Validation against histopathologic changes

BackgroundCoronary microvascular dysfunction (CMD) is an early character of type 2 diabetes mellitus (T2DM), and is indicative of adverse events. The present study aimed to validate the performance of the stress T1 mapping technique on cardiac magnetic resonance (CMR) for identifying CMD from a histopathologic perspective and to establish the time course of CMD-related parameters in a rabbit model of T2DM.MethodsNew Zealand white rabbits (n = 30) were randomly divided into a control (n = 8), T2DM 5-week (n = 6), T2DM 10-week (n = 9), and T2DM 15-week (n = 7) groups. The CMR protocol included rest and adenosine triphosphate (ATP) stress T1-mapping imaging using the 5b(20b)3b-modified look-locker inversion-recovery (MOLLI) schema to quantify stress T1 response (stress ΔT1), and first-pass perfusion CMR to quantify myocardial perfusion reserve index (MPRI). After the CMR imaging, myocardial tissue was subjected to hematoxylin-eosin staining to evaluate pathological changes, Masson trichrome staining to measure collagen volume fraction (CVF), and CD31 staining to measure microvascular density (MVD). The associations between CMR parameters and pathological findings were determined using Pearson correlation analysis.ResultsThe stress ΔT1 values were 6.21 ± 0.59%, 4.88 ± 0.49%, 3.80 ± 0.40%, and 3.06 ± 0.54% in the control, T2DM 5-week, 10-week, and 15-week groups, respectively (p < 0.001) and were progressively weakened with longer duration of T2DM. Furthermore, a significant correlation was demonstrated between the stress ΔT1 vs. CVF and MVD (r = −0.562 and 0.886, respectively; p < 0.001).ConclusionThe stress T1 response correlated well with the histopathologic measures in T2DM rabbits, indicating that it may serve as a sensitive CMD-related indicator in early T2DM

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

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke

BackgroundDual antiplatelet treatment has been shown to reduce recurrence of stroke compared to aspirin alone when initiated early after an acute stroke. The effect of clopidogrel and aspirin versus aspirin alone within 72 hours of acute cerebral ischemia from atherosclerosis has not been well studied.MethodsWe conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause, not receiving thrombolysis or thrombectomy in 222 hospitals in China. Patients were randomly assigned within 72 hours after symptom onset in a 1:1 ratio, to receive clopidogrel (300mg on day 1, 75mg daily on days 2-90) and aspirin (100-300mg on day1, 100mg daily on days 2-21), or clopidogrel placebo and aspirin (100-300mg on day1, 100mg daily on days 2-90). There was no interaction between this component of the factorial trial design trial and a second part that tested immediate vs delayed stain treatment and is reported separately. The primary efficacy outcome was a new stroke, and the primary safety outcome was moderate-to-severe bleeding, both within 90 days.ResultsA total of 6100 patients were enrolled, 3050 assigned to each trial group. The qualifying event for enrollment was TIA in 13%. Approximately 13% of patients were assigned to a treatment group within 24 hours and 87% were assigned between 24 and 72 hours of onset of stroke. A new stroke occurred in 222 (7.3%) in the clopidogrel-aspirin group, and 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.008). Moderate-to-severe bleeding occurred in 27 (0.9%) and 13 patients (0.4%), respectively (hazard ratio, 2.08; 95% CI, 1.07-4.04, P=0.03).ConclusionsAmong patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin initiated within 72 hours of onset was superior to aspirin alone in reducing the risk of new stroke at 90 days but was associated with a low but increased risk of moderate-to-severe bleeding