Lactobacillus crispatus strain SJ‐3C‐US induces human dendritic cells (DCs) maturation and confers an anti‐inflammatory phenotype to DCs

Lactobacillus crispatus is one of the most predominant species in the healthy vagina microbiota. Nevertheless, the interactions between this commensal bacterium and the immune system are largely unknown. Given the importance of the dendritic cells (DCs) in the regulation of the immunity, this study was performed to elucidate the influence of vaginal isolated L. crispatus SJ‐3C‐US from healthy Iranian women on DCs, either directly by exposure of DCs to ultraviolet‐inactivated (UVI) and heat‐killed (HK) L. crispatus SJ‐3C‐US or indirectly to its cell‐free supernatant (CFS), and the outcomes of immune response. In this work we showed that L. crispatus SJ‐3C‐US induced strong dose‐dependent activation of dendritic cells and production of high levels of IL‐10, whereas IL‐12p70 production was induced at low level in an inverse dose‐dependent manner. This stimulation skewed T cells polarization toward CD4⁺ CD25⁺ FOXP3⁺ Treg cells and production of IL‐10 in a dose‐dependent manner in mixed leukocyte reaction (MLR) test. The mode of bacterial inactivation did not affect the DCs activation pattern, upon encounter with L. crispatus SJ‐3C‐US. Moreover, while DCs stimulated with CFS showed moderate phenotypic maturation and IL‐10 production, it failed to skew T cells polarization toward CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells (Treg) and production of IL‐10. This study showed that L. crispatus SJ‐3C‐US confers an anti‐inflammatory phenotype to DCs through up‐regulation of anti‐inflammatory/regulatory IL‐10 cytokine production and induction of CD4⁺ CD25⁺ FOXP3⁺ T cells at optimal dosage. Our findings suggest that L. crispatus SJ‐3C‐US could be a potent candidate as protective probiotic against human immune‐mediated pathologies, such as chronic inflammation, vaginitis or pelvic inflammatory disease (PID).     

Expression analysis of mTOR-associated lncRNAs in multiple sclerosis

Metabolic Brain Disease - mTOR has been shown to be involved in the regulation of immune responses and differentiation of immune cells. This protein is a candidate molecule for unraveling the...     

Expression of BDNF-Associated lncRNAs in Parkinson’s disease

Metabolic Brain Disease - Decreased level of neurotrophic factor brain-derived neurotrophic factor (BDNF) has been supposed to participate in the pathoetiology of Parkinson’s disease (PD)....     

The effects of cadmium exposure in the induction of inflammation

Abstract

Inflammation is a physiological process essential for maintaining homeostatic mechanisms in human, but however, exaggerated inflammatory responses are closely related to many chronic diseases. Cadmium (Cd) is a heavy metal with high toxicity when present in food, water and air has the potential of eliciting inflammatory reactions, with a major health risk to human. This review aimed to elucidate on the major routes of Cd exposure, the main organs affected by the exposure, the degree of toxicity as well as the roles of the toxic effects on the immune system which results to inflammatory responses. Immune modulation by Cd may cause serious adverse health effects in humans. Various studies have highlighted the ability of Cd as an environmental pollutant involved in the modulation of the innate, adaptive and mucosal immune responses in relations to the release of chemokine, gene expression, and susceptibility to microbial infections.     

Newborn size, infant and childhood growth, and body composition and cardiovascular disease risk factors at the age of 6 years: the Pune Maternal Nutrition Study

OBJECTIVE: To study associations of size and body proportions at birth, and growth during infancy and childhood, to body composition and cardiovascular disease (CVD) risk factors at the age of 6 years. DESIGN: The Pune Maternal Nutrition Study, a prospective population-based study of maternal nutrition and CVD risk in rural Indian children. METHODS: Body composition and CVD risk factors measured in 698 children at 6 years were related to body proportions and growth from birth. MEASUREMENTS: Anthropometry was performed every 6 months from birth. At 6 years, fat and lean mass (dual X-ray absorptiometry) and CVD risk factors (insulin resistance, blood pressure, glucose tolerance, plasma lipids) were measured. RESULTS: Compared with international references (NCHS, WHO) the children were short, light and thin (mean weight <-1.0 s.d. at all ages). Larger size and faster growth in all body measurements from birth to 6 years predicted higher lean and fat mass at 6 years. Weight and height predicted lean mass more strongly than fat mass, mid-upper arm circumference (MUAC) predicted them both approximately equally and skinfolds predicted only fat mass. Neither birthweight nor the 'thin-fat' newborn phenotype, was related to CVD risk factors. Smaller MUAC at 6 months predicted higher insulin resistance (P<0.001) but larger MUAC at 1 year predicted higher systolic blood pressure (P<0.001). After infancy, higher weight, height, MUAC and skinfolds, and faster growth of all these parameters were associated with increased CVD risk factors. CONCLUSIONS: Slower muscle growth in infancy may increase insulin resistance but reduce blood pressure. After infancy larger size and faster growth of all body measurements are associated with a more adverse childhood CVD risk factor profile. These rural Indian children are growing below international 'norms' for body size and studies are required in other populations to determine the generalizability of the findings.     

Maternal Lipids Are as Important as Glucose for Fetal Growth: Findings from the Pune Maternal Nutrition Study

OBJECTIVE

To study the relationship between maternal circulating fuels and neonatal size and compare the relative effects of glucose and lipids.

RESEARCH DESIGN AND METHODS

The Pune Maternal Nutrition Study (1993–1996) investigated the influence of maternal nutrition on fetal growth. We measured maternal body size and glucose and lipid concentrations during pregnancy and examined their relationship with birth size in full-term babies using correlation and regression techniques.

RESULTS

The mothers (n = 631) were young (mean age 21 years), short (mean height 151.9 cm), and thin (BMI 18.0 kg/m²) but were relatively more adipose (body fat 21.1%). Their diet was mostly vegetarian. Between 18 and 28 weeks’ gestation, fasting glucose concentrations remained stable, whereas total cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations decreased. The mean birth weight of the offspring was 2666 g. Total cholesterol and triglycerides at both 18 and 28 weeks and plasma glucose only at 28 weeks were associated directly with birth size. One SD higher maternal fasting glucose, cholesterol, and triglyceride concentrations at 28 weeks were associated with 37, 54, and 36 g higher birth weights, respectively (P < 0.05 for all). HDL-cholesterol concentrations were unrelated to newborn measurements. The results were similar if preterm deliveries also were included in the analysis (total n = 700).

CONCLUSIONS

Our results suggest an influence of maternal lipids on neonatal size in addition to the well-established effect of glucose. Further research should be directed at defining the clinical relevance of these findings.In recent years there has been a resurgence of interest in studying factors influencing fetal growth because of the demonstration that fetal growth is related to the risk of developing type 2 diabetes and cardiovascular disease in later life (1–3). The mother’s nutrition and metabolism are major determinants of fetal growth (4,5). In clinical practice, glucose is considered the most important nutrient crossing the placenta (6,7) because of the well-known association between maternal diabetes and fetal overgrowth (macrosomia) and evidence of improved pregnancy and perinatal outcomes by controlling diabetes before and during pregnancy (8–10). Current recommendations are for universal screening for diabetes in pregnancy (10). Lipids and amino acids usually are not considered in the clinical management of pregnancy because there is less known about the role of these nutrients in the well-being of the pregnancy. Studies of nondiabetic animals and humans have shown a relationship between maternal triglyceride (11–13) and cholesterol concentrations and newborn weight and body composition and placental weight (14–16). A number of studies also have shown an association between maternal lipids (mostly triglycerides) and newborn weight in hyperglycemic women (8,12,17,18).Pedersen (19) proposed that the transfer of excess maternal glucose in a diabetic pregnancy stimulates fetal islets to produce fetal hyperinsulinemia, which leads to macrosomia. Freinkel (20) proposed that a “mixture” of maternal nutrients (glucose, lipids, and amino acids) not only affects fetal growth and development but also influences risk of future obesity, diabetes, and neurocognitive development (“fuel-mediated teratogenesis”). The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study supported a role for maternal glucose in influencing newborn size in a continuous manner (21); maternal lipid concentrations were not reported. In mice, maternal hypercholesterolemia has been associated with atherosclerosis in offspring by influencing arterial gene expression (22). In humans, maternal hypercholesterolemia during pregnancy has been shown to be associated with fatty streaks in the fetal aorta (23).There is little information from undernourished mothers in low- and middle-income countries on maternal glucose and lipid concentrations during pregnancy and their role in fetal growth, body composition, and future risk of disease. The Pune Maternal Nutrition Study (PMNS) was set up in six villages near Pune, India, to investigate the influence of maternal health and nutrition on fetal growth (4). This rural community depended on labor-intensive subsistence agriculture in a drought-prone region. We have reported that we found no associations of maternal dietary energy, carbohydrate, and protein intake with newborn size, whereas higher maternal fat intake was associated with greater neonatal length (4). Mothers who ate green leafy vegetables, milk, and fruit more frequently and had higher blood concentrations of folate and vitamin C gave birth to larger newborns. This highlighted the role of maternal micronutrients in fetal growth. In this article, we report the relationship between maternal circulating fuels (glucose, total and HDL-cholesterol, and triglycerides) and neonatal size and compare the relative effects of glucose and lipids.