Jiawei Baitouweng Decoction affects intestinal mucosal tight junction proteins in rats with ulcerative colitis through p38 MAPK-MLCK signaling pathway / 中国中药杂志

The aim of this paper was to explore the effect and mechanism of Jiawei Baitouweng Decoction(JWBTW) against ulcerative colitis(UC) from the perspective of intestinal mucosal tight junction proteins. From 60 SPF-grade male SD rats, 10 were randomly selected as the blank control, and the remaining 50 were treated with 3% dextran sodium sulfate(DSS) solution to induce UC and then randomized into the model group, mesalazine group, and low-, medium-, and high-dose JWBTW( L-JWBTW, M-JWBTW and H-JWBTW) groups, with 10 rats in each group. After successive medication for 14 days, the rat general conditions like body weight and stool were observed and the disease activity index(DAI) was calculated. The pathological changes in colon tissue was observed under a microscope for injury severity scoring and histopathological scoring. The serum endotoxin content was determined by limulus assay, followed by the measurement of protein expression levels of ZO-1, occludin, claudin-1, p38 MAPK, MLCK, MLC2 and p-MLC in colon tissue by Western blot. The results showed that compared with the blank group, the model group exhibited significantly reduced body weight, elevated DAI, injury severity and histopathological scores and serum endotoxin content, up-regulated protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and down-regulated ZO-1, occludin and claudin-1. Compared with the model group,mesalazine and JWBTW at each dose obviously increased the body weight, lowered the DAI, injury severity and histopathological scores and serum endotoxin content, down-regulated the protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and up-regulated the ZO-1, occludin and claudin-1, with the most obvious changes noticed in the H-JWBTW group. All these have indicated that JWBTW exerts the therapeutic effect against UC by inhibiting the activation of p38 MAPK/MLCK pathway, reversing the protein expression levels of occludin, claudin-1 and ZO-1, decreasing the serum endotoxin content, promoting the repair of intestinal mucosal mechanical barrier, maintaining the integrity of tight junctions, and reducing the permeability of intestinal mucosa.

A parental case control study on the association between reduced folate carrier gene polymorphism and neural tube defects / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the association between reduced folate carrier gene (RFC1 A80G) polymorphism and the risk for child with neural tube defects (NTDs), and to provide epidemiological evidence for the existence of NTDs genetic marker.</p><p><b>METHODS</b>RFC1 (A80G) genotypes were detected using RFLP-PCR for blood DNA of 104 families with NTDs-affected children and 100 control families with no history of child-affected birth defects. Case-control study and transmission/disequilibrium test(TDT) for the RFC1 genotype of NTDs pedigree were carried out.</p><p><b>RESULTS</b>The G allele frequency of children with NTDs was higher than that of controls when compared to A allele( OR = 1. 64, 95% CI :1.08-2.49). The offspring of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to the AA genotype (OR = 2.56, 95% CI: 1.04-6.36) in our study population. There was evidence of association between G allele and the risk of parent having a child with NTDs (OR = 1.56, 95% CI: 1.07-2.28) in the TDT analysis.</p><p><b>CONCLUSION</b>Our findings indicated that there was potential association between offspring RFC1 GG genotype and the risk of NTDs, and the G allele was a possible susceptible gene marker for an increased NTDs risk in the Chinese population.</p>

Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To search the interaction between reduced folate carrier gene (RFC1 A80G) polymorphism of children with neural tube defects (NTDs) and maternal periconceptional no supplementation of folic acid. The purpose is to provide the epidemiological evidence for finding genetic marker of NTDs.</p><p><b>METHODS</b>RFC1 (A80G) genotype was detected using PCR-restricted fragment length polymorphism for the blood DNA of 104 trios with NTDs-affected child, and 100 control families with non-malformed control children. The authors investigated the gene-environment interactions between the offspring RFC1 genotype and maternal periconceptional folic acid supplementation through a case-control study.</p><p><b>RESULTS</b>It was observed that the offspring with the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to those with the AA genotype (OR = 2.56; 95% CI = 1.04-6.36) in this population under investigation. The risk of mothers who did not take folic acid for having an NTDs-affected infants was 7.69 (95% CI = 2.86-21.75). Among the mothers who did not utilize folic acid supplements, the NTDs risk was 3.30 (95% CI = 1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR = 8.80, 95% CI = 2.86 - 29.82), compared to "offspring with AA or GA genotype" and "maternal folic acid use", the interactive coefficient being 1.45.</p><p><b>CONCLUSION</b>The above findings indicate that the RFC1 genotype (GG) is a possible susceptible gene marker for an increased NTDs risk in Chinese population, and there is a potential gene-nutrient interaction between offspring RFC1 GG genotype and maternal periconceptional intake of folic acid on the risk of NTDs. However,the sample size of this study was limited, a larger sample of population-based study is required to pursue the initial observation.</p>

Study on reduced folate carrier gene (RFC1) polymorphism in the southern and northern Chinese population / 中华流行病学杂志

<p><b>OBJECTIVE</b>To describe the distribution of reduced folate carrier gene (RFC1)genotype and allele frequency between southern and northern, female and male Chinese population.</p><p><b>METHOD</b>RFC1 (A80G) genotype was detected, using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) on 720 blood spot DNA from the normal subjects.</p><p><b>RESULTS</b>The frequencies of the northern population with AA, GG and GA genotypes were 22.28%, 31.09% and 46.63%, and the frequencies of the southern population were 18.56%, 22.75% and 58.68%, respectively. Findings showed that there were significant differences between southerners and northerners in RFC1 (A80G) genotype (P < 0.01). There was no significant difference between G allele frequency of the northern (52.10%) and southern population (54.40%). The frequencies of male with RFC1 (A80G) AA, GG and GA genotype were 24.88%, 25.85% and 49.27%, and among female were 18.83%, 27.77% and 53.40%, respectively. There were no significant differences between male and female in RFC1 genotype (P > 0.05), or between G allele frequency in female (50.49%) and that in male (54.47%).</p><p><b>CONCLUSIONS</b>The distribution of RFC1 genotype seemed to be consistent with neural tube defects (NTDs) while its prevalence among the northerners was higher than that of southerners, with female having a higher NTDs prevalence. This study provided genetic epidemiological data for etiological hypothesis between RFC1 and diseases relative to folate metabolism.</p>

Study on the association between reduced folate carrier gene polymorphism and congenital heart defects and cleft lip with or without cleft palate / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the association between reduced folate carrier gene (RFC1) polymorphism and congenital heart defects (CHD) as well as cleft lip with or without cleft palate (CLP) and to provide epidemiological evidence on genetic markers of CHD and CLP.</p><p><b>METHODS</b>RFC1 (A80G) genotype was detected using RFLP-PCR for blood DNA of the 67 triads with nonsyndromic CHD-affected child, the 82 triads with child-affected cleft lip with or without CLP and the 100 control families without child-affected birth defects. We performed a family-based association test and analyzed the interaction between RFC1 A80G genotype and maternal periconceptional supplementation of folic acid.</p><p><b>RESULTS</b>Offspring of mothers who did not take folic acid had an elevated risk for CHD when comparing with offspring of mothers who did (OR = 2.68, 95% CI: 1.14 - 6.41). There was a statistical association between the risk of CHD and maternal periconceptional folic acid supplementation (chi(2) = 6.213, P < 0.05). In the family-based association test, G allele was positively associated with an increased risk for children CHD (Z = 2.140, P < 0.05) while G allele of RFC1 (A80G) polymorphism might increase the risk for CHD. Elevated risks for either CLP group were not observed between RFC1 genotype using or not using folic acid.</p><p><b>CONCLUSION</b>Our findings suggested that the G allele was likely to be a genetically susceptible allele for CHD. There was possible association between offspring with GG, GA genotype and maternal periconceptional folicacid deficiency.</p>