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Background: Folic acid (FA) supplementation before and during the first trimester can reduce the risk of occurrence of preterm delivery (PTD). Preconception body mass index (BMI) is also associated with PTD. This study aimed to investigate the combined effect of FA supplements and preconception BMI on the risk of PTD.Methods: The data of a cohort from 2010-2011 that was obtained through a preconception care service in China was used (including 172,206 women). A multivariable regression model was used to investigate the association between maternal preconception conditions and the risk of PTD. The interaction of preconception BMI and FA supplementation was measured by a logistic regression model.Results: Taking FA supplements in the preconception period or in the first trimester reduced the risk of PTD (odds ratio [OR] = 0.58 and OR = 0.61, respectively). Women with an abnormal BMI had an increased risk of PTD (OR = 1.09, OR = 1.10, and OR = 1.17 for underweight, overweight, and obese, respectively). Preconception BMI showed an interaction with the protective effect of FA supplementation for PTD. With regard to the interaction of FA supplementation, the adjusted odds ratio (aOR) was 0.57 (95% CI: 0.51, 0.64) in underweight women, 0.85 (95% CI: 0.73, 0.98) in overweight women, and 0.77 (95% CI, 0.65, 0.91) in obese women. Preconception BMI also showed an interaction with the time of FA supplementation. Women with a normal BMI who began to take FA supplements in the preconception period had the lowest risk of PTD (aORs: 0.58 vs. 0.65 beginning in the first trimester). The aORs at preconception and the first trimester in the underweight group were 0.56 vs. 0.60. The aORs at preconception and the first trimester were 0.94 vs. 0.65 and 1.15 vs. 0.60 in the overweight and obesity groups, respectively.Conclusions: In our study, FA supplements reduced the risk of PTD, while abnormal BMI raised the risk of PTD, although higher BMI categories did not have this higher risk once adjusted analysis was conducted. The protective effect of FA supplementation for PTD was reduced in women with overweight or obesity. To get better protection of FA supplementation, women with normal BMI or underweight should begin to use in preconception, while women with overweight or obesity should begin to use after conception. [ABSTRACT FROM AUTHOR]

Background: Alcohol abuse has dramatic effects on the health of the elderly. Recent studies indicate that ethanol increases immune activity in younger animals and that some of these proinflammatory molecules alter alcohol consumption and addiction. However, the effects of alcohol on immune activation in aged animals have not been thoroughly investigated. Findings: We compared the effects of ethanol on chemokine and cytokine expression in the hippocampus, cerebellum, and cerebral cortex of aged C57BL/6 mice. Mice were treated via gavage with 6 g/kg ethanol for 10 days and tissue was harvested 1 day post-treatment. Ethanol selectively increased mRNA levels of the chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 in the hippocampus and cerebellum, but not in the cortex of aged mice relative to control animals. In this paradigm, ethanol did not affect mRNA levels of the cytokines IL-6 or TNF-α in any of these brain regions in aged animals. Conclusions: Collectively, these data indicate a region-specific susceptibility to ethanol regulation of neuroinflammatory and addiction-related molecules in aged mice. These studies could have important implications concerning alcohol-induced neuropathology and alcohol addiction in the elderly. [ABSTRACT FROM AUTHOR]

T-helper cells that produce interleukin-17 (TH17 cells) are a recently identified CD4+ T-cell subset with characterized pathological roles in autoimmune diseases. The nuclear receptors retinoic-acid-receptor-related orphan receptors α and γt (RORα and RORγt, respectively) have indispensible roles in the development of this cell type. Here we present SR1001, a high-affinity synthetic ligand-the first in a new class of compound-that is specific to both RORα and RORγt and which inhibits TH17 cell differentiation and function. SR1001 binds specifically to the ligand-binding domains of RORα and RORγt, inducing a conformational change within the ligand-binding domain that encompasses the repositioning of helix 12 and leads to diminished affinity for co-activators and increased affinity for co-repressors, resulting in suppression of the receptors' transcriptional activity. SR1001 inhibited the development of murine TH17 cells, as demonstrated by inhibition of interleukin-17A gene expression and protein production. Furthermore, SR1001 inhibited the expression of cytokines when added to differentiated murine or human TH17 cells. Finally, SR1001 effectively suppressed the clinical severity of autoimmune disease in mice. Our data demonstrate the feasibility of targeting the orphan receptors RORα and RORγt to inhibit specifically TH17 cell differentiation and function, and indicate that this novel class of compound has potential utility in the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

The role of peroxisome proliferator-activated receptors (PPARs) in altering lipid and glucose metabolism is well established. More recent studies indicate that PPARs also play critical roles in controlling immune responses. We and others have previously demonstrated that PPAR-γ agonists modulate the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). This review will discuss the cellular and molecular mechanisms by which these agonists are believed to modulate disease. The therapeutic potential of PPAR-γ agonists in the treatment of multiple sclerosis will also be considered. [ABSTRACT FROM AUTHOR]

Accumulation of amyloid-β peptide (Aβ) appears to contribute to the pathogenesis of Alzheimer's disease (AD). Therapeutic hope for the prevention or removal of Aβ deposits has been placed in strategies involving immunization against the Aβ peptide. Initial Aβ immunization studies in animal models of AD showed great promise. However, when this strategy was attempted in human subjects with AD, an unacceptable degree of meningoencephalitis occurred. It is generally believed that this adverse outcome resulted from a T-cell response to Aβ. Specifically, CD4+ Th1 and Th17 cells may contribute to severe CNS inflammation and limit the utility of Aβ immunization in the treatment of AD. Interleukin (IL)-12 and IL-23 play critical roles in the development of Th1 and Th17 cells, respectively. In the present study, Aβ1-42 synergistically elevated the expression of IL-12 and IL-23 triggered by inflammatory activation of microglia, and the peroxisome proliferator-activated receptor (PPAR)-γ agonist 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) effectively blocked the elevation of these proinflammatory cytokines. Furthermore, 15d-PGJ2 suppressed the Aβ-related synergistic induction of CD14, MyD88, and Toll-like receptor 2, molecules that play critical roles in neuroinflammatory conditions. Collectively, these studies suggest that PPAR-γ agonists may be effective in modulating the development of AD. [ABSTRACT FROM AUTHOR]

Taiping Houkui green tea is mainly made from the young shoots of the sextual tea line ‘Shidacha’. In the present study, the differences in the quality and genetic evolution of green tea made from the young shoots of five ‘Shidacha’ varieties (Gaojiazao, Huangzhong, Shidacha No.2, Shidacha No.6, and Guangyangzao) and two non-‘Shidacha’ tea varieties (Fuzao No.2 and Shuchazao) were explored. The volatile and non-volatile metabolites of the seven tea samples were analyzed, and the differences in genome-wide transcriptional levels and genetic background among the seven tea varieties were analyzed using RNA sequencing (RNA-seq). No significant differences in catechin content or the total content of free amino acids were found among all tea samples except Shuchazao, whereas caffeine content differed significantly among all samples. The contents of floral aroma compounds such as linalool, linalool oxide, geraniol and jasmone were relatively high in the infusion of ‘Shidacha’ green tea. RNA sequencing results showed that the genome-wide transcriptional level of Guangyangzao was close to that of the non-‘Shidacha’ tea varieties. In principal component analysis (PCA), Guangyangzao and the other ‘Shidacha’ varieties were distributed in different quadrants. Phylogenetic analysis showed that the non-‘Shidacha’ tea varieties had a close genetic relationship with each other as well as Gaojiazao and Huangzhong, but was far away from the other ‘Shidacha’ varieties. The transcriptional levels of most of the key enzyme genes involved in the biosynthesis of linalool, indole, nerolidol and jasmone lactone were higher in the ‘Shidacha’ tea varieties than in the non-‘Shidacha’ ones. This study provides important theoretical support for the breeding of excellent ‘Shidacha’ varieties and provides a theoretical basis for follow-up research on the formation mechanism of floral aroma compounds in tea leaves.

Objectives: To provide prevalence and trends of underweight, overweight, and obesity among reproductive-age women and adolescent girls in rural China., Methods: We measured weight and height in 16 742 344 women aged 20 to 49 years and 178 556 girls aged 15 to 19 years from the National Free Preconception Health Examination Project between 2010 and 2014., Results: Among women, the prevalence of underweight was 7.8% (95% confidence interval [CI] = 7.7%, 7.9%), and overweight or obesity was 16.5% (95% CI = 16.4%, 16.6%; World Health Organization criteria). Among adolescents, prevalence of underweight was 6.0% (95% CI = 5.7%, 6.2%; Centers for Disease Control and Prevention criteria) and overweight or obesity was 8.3% (95% CI = 7.9% to 8.8%; International Obesity Task Force criteria). According to Chinese criteria, overweight and obesity prevalence was 24.8% (95% CI = 24.7%, 24.9%) for women and 17.2% (95% CI = 16.6%, 17.8%) for adolescents, and underweight prevalence was 2.9% (95% CI = 2.8%, 3.1%) for adolescents. Considerable disparities existed in prevalence and trends within subpopulations (age groups, parity, region, education levels, and socioeconomic status)., Conclusions: Our results reveal coexisting underweight and overweight or obesity among rural women and adolescents of reproductive age, which requires public health attention.