Increased Expression Levels of Soluble Fms-Like Tyrosine Kinase-1 Inhibit the Development of the Nervous System.

INTRODUCTION: Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity. At present, only limited options are available for the treatment of PE. Consequently, many patients need to terminate their pregnancies to relieve the disease. Soluble fms-like tyrosine kinase-1 (sFlt-1) is a decoy receptor of placental growth factor and vascular endothelial growth factor which can promote angiogenesis. Throughout pregnancy, the expression level of sFlt-1 continues to increase in both the mother with PE and her offspring. MATERIAL AND METHODS: In this experiment, we generated a zebrafish line expressing high levels of sFlt-1 and investigated changes in behavior and development of the nervous system. RESULTS: At 96 h post-fertilization (hpf), the brain volume area of zebrafish in the experimental group (zFLT1+CasRx) was significantly smaller after injection than in the WT group (p < 0.05) and the negative control group (CasRx) (p < 0.05). At 96 hpf, compared with the WT group, the cerebral blood vessels in the CasRx control group and experimental group (zFLT1-sgRNA+CasRx) were significantly lower after injection (p < 0.05). Compared with the CasRx control group, the track movement distance and the mean track speed of zebrafish in the experimental group (zFLT1-sgRNA+CasRx) after the 6th injection were significantly decreased (p < 0.05). CONCLUSIONS: The increased expression levels of sFlt-1 in zebrafish inhibited the development of the cerebral blood vessels, influenced brain volumes, and inhibited behavioral activities. Our data suggest that the elevation of sFlt-1 in the pathological state of PE can inhibit the development of the nervous system in offspring.

Effects of the probiotic Bacillus coagulans BC69 on the metabolic and histological alterations induced by a high-sugar and high-fat diet in C57BL/6J mice.

Western-style diets are associated with metabolic syndrome, characterized by obesity and hyperglycemia, which is a major public health problem in the 21st century. Recent studies have proven that probiotics have promising effects in the management of metabolic syndrome. This study aimed to investigate the effects of Bacillus coagulans BC69 on the metabolic and histological alterations associated with metabolic syndrome in C57BL/6J mice fed with a high-sugar and high-fat (HSHF) diet. The body weight, biochemistry, histology, and gut microbiome were assessed. The results showed that administration of BC69 from the first week reduced body weight gain, liver weight, and production of pro-inflammatory cytokines (TNF-α), and restored faecal acetate and butyrate concentrations in mice. Histological sections showed that BC-69 also reduced HSHF-induced liver pathological damage in mice by improving hepatocyte disorganization and reducing inflammatory cell infiltration. In addition, 16S rRNA gene sequencing showed that BC69 improved the gut microbiome of HSHF diet-fed mice. This study revealed that BC69 has the potential to be a safe and effective tool in the treatment of metabolic syndrome.

Mannose inhibits Plasmodium parasite growth and cerebral malaria development via regulation of host immune responses.

D-mannose can be transported into a variety of cells via glucose transporter (GLUT), and supraphysiological levels of D-mannose impairs tumor growth and modulates immune cell function through mechanisms such as interference with glycolysis and induction of oxidative stress. Blood-stage Plasmodium mainly depends on glycolysis for energy supply and pathological immune response plays a vital role in cerebral malaria. However, it is not clear whether mannose affects malaria blood-stage infection. Here, we fed D-mannose to Plasmodium berghei-infected mice and found weight loss and reduced parasitemia without apparent side effects. Compromised parasitemia in C57BL/6 mice was accompanied by an increase in splenic macrophages compared to an untreated group. When mannose was applied to a rodent experimental cerebral malaria (ECM) model, the incidence of ECM decreased. Expression of activation marker CD69 on T cells in peripheral blood and the brain were reduced, and cerebral migration of activated T cells was prevented by decreased expression of CXCR3. These findings suggest that mannose inhibits Plasmodium infection by regulating multiple host immune responses and could serve as a potential strategy for facilitating malaria treatment.