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Epitope spreading often occurs in patients with autoimmune bullous diseases (ABDs), resulting in exposure of more antigenic epitopes, aggravation or transformation of pre-existing diseases, or concurrence of other diseases. With the increase in the immunological evidence for epitope spreading, more and more scholars have realized that epitope spreading plays an important role in the development of ABDs. This review introduces the phenomenon of epitope spreading in ABDs from 4 aspects, including the concurrence of or transformation between different types of pemphigoid, different types of pemphigus, pemphigus and pemphigoid, as well as between ABDs and other skin diseases.
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Nonbullous pemphigoid (NBP) , which is related to bullous pemphigoid, has various clinical manifestations, and is frequently accompanied by itching. Typical clinical manifestations of bullous pemphigoid (BP) , such as tense blisters or bullae, are absent in NBP cases. It is easy to misdiagnose. Histopathological findings are not specific, and its diagnosis should be confirmed by direct immunofluo-rescence, indirect immunofluorescence or salt-split indirect immunofluorescence. NBP may develop into BP in some cases, and the prognosis of NBP is better than that of BP. However, delayed diagnosis usually leads to a relatively high dosage of drugs for disease control, and a high rate of adverse reactions.
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Objective To explore the relationship between intestinal fatty acid binding protein(FABP2) gene G54A polymorphism and obesity,the effect of mutant 54A FABP2 gene on serum lipids metabolism.Methods The total of 84 subjects with obesity and 60 subjects with normal weight were involved in this study.The G54A FABP2 gene allele and genotype frequencies were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism(RFLP) technology.The automatic biochemical Analyzer was used to detect triglyceride(TG),high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C) levels.Results The results of study on FABP2 gene polymorphism revealed as followed:in obese groups,the frequencies of GG,GA,A/A genotypes was 19.0%(16/84),73.8%(62/84) and 7.2%(6/84),respectively;in control group,the frequencies of G/G,G/A,A/A genotypes was 38.3%(23/60),58.3%(35/60),3.3%(2/60),respectively;the differences between two groups was statistically significant(χ2=6.97,P0.05).The carriers of A/A homozygous genotypes had significantly higher plasma LDL-C((3.94±0.96) mmol/L)level than thosewith G/A wild genotype((3.94±0.96) mmol/L vs.(3.29±0.55) mmol/L,t=2.476,P0.05) and HDL-C((1.23±0.34) mmol/L vs.(1.21±0.26) mmol/L;P>0.05) level had not difference.Conclusion The FABP2 gene G54A polymorphism is related to obesity and lipid metabolism abnormality.The allele encoding in FABP2 gene may be a potential factor contributing to promoting lipid metabolism abnormality.
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AIM:To study the microRNA profiling in the serum of insulin-resistant mice and the mechanism of insulin resistance induced by related microRNAs.METHODS:A high-fat diet was used to induce insulin resistance model in KM mice.The microRNA profiling in serum of insulin-resistant and normal mice was analyzed by microarray chip and were validated by real-time PCR.miRanda data base was used to forecast target genes.miRBase was used to obtain the se-quences of related microRNAs, based on which protein interactions were predicted using the online analytical tool STRING. RESULTS:In serum of insulin-resistant mice, the expression of miR-125, miR-126, miR-143, miR-30a, miR-199a, miR-127, miR-184, miR-30e, miR-134, miR-195, miR-206, miR-429, miR-212, miR-362, miR-382, miR-154 and miR-466h was significantly up-regulated.miR-211, miR-504, miR-877 and miR-1930 were significantly down-regulated. miR-143 associated with insulin resistance was able to bind to 3'-UTR of fat mass and obesity-associated protein (FTO), and FTO was found to interact with Rpgrip1l, Tmem18, Mc4r, Npy, Hhex, Tcf712, Cdkal1, Slc30a8, Igf2bp2 and Tha-da.CONCLUSION:Twenty-one microRNAs in the serum of insulin-resistant mice induced by a high-fat diet are signifi-cantly different from those of normal mice, in which 17 kinds were significantly up-regulated.miR-143 closely related to in-sulin resistance is able to regulate FTO protein expression, which interacts with other 10 proteins associated with the occur-rence and development of diabetes.The results are also useful for further study of the molecular mechanisms in insulin re-sistance.
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Objective:To screen the plasma microRNAs( miRNAs) of differential expression in a high fat diet-induced insulin resistance in mouse models;further investigations on the mice with insulin resistance treated by TLR4 inhibitors TAK-242,and to study the changes of plasma miRNAs expression profile and the relationship among TLR4, miRNAs and high fat diet-induced insulin resistance. Methods:The plasma samples were from 3 mouse groups of previous study,namely,the control group with general basic diet ( low fat diet,LFD) ,TLR4 inhibitors TAK-242 treatment group with a high fat diet ( HFD-T) and the high fat diet control group( HFD-C) . The differential expressed miRNAs was screened by expression profiling of plasma miRNAs, which was detected using mouse miRNA microarray. The quantitative Real-Time PCR ( qRT-PCR ) was used to verify the results of microarray. The target genes of differential expressed miRNAs were predicted in TLR4 signaling pathway using bioinformatics methods,and the GO and KEGG database molecular annotation system were used to investigate the main effects of the miRNAs targeted genes on the biological functions or signal pathway. Results:The screening results of miRNA microarray chip showed that,comparing miRNAs expression between HFD group and LFD control group,185 miRNAs were significant in the high fat diet group,including 6 up-regulated and 179 down-regulated miRANs. A significant difference of miRANs was also found between HFD-T group and LFD control group,the total number of differential expression miRNAs was 171,and all of them were down-regulated. Comparing miRNAs expression between HFD-C group and HFD-T group,13 miRNAs were significant in HFD-T group,all of them were down-regulated. Bioinformatics analysis results showed that a total of 10 in-teraction proteins with TLR4 were predicted;the difference of mmu-miR-3095-3p,mmu-miR-5113,mmu-miR-709 and mmu-miR-335-3p expression levels was more than 1 000 times between HFD-C group and HFD-T group,and their target genes can be found in TLR4-in-teraction protein or Toll like receptor signaling pathway;GO and KEGG analysis showed 74% of these target genes belonged to the biological processes genes, and the transcription factors accounted for 82%. The expression of mmu-miR-3095-3p, mmu-miR-5113, mmu-miR-709 and mmu-miR-335-3p detected by qRT-PCR exhibited the similar patterns of down regulation to those shown in microarray results. Conclusion:When insulin resistance occurs,there is a change in plasma miRNAs expression profile,this change is associated with TLR4 and its signaling pathways. The finding enrichs the possible mechanisms of insulin resistance and provides a basis for finding miRNAs diagnostic markers for early diagnosis of insulin resistance.
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BACKGROUND: Studies have shown that alanine (A) to threonine (T) substitution at codon 54 of intestinal fatty acid-binding protein (FABP2) in different populations is associated with dyslipidemia and other characteristics of metabolic syndrome.OBJECTIVE: To investigate the frequency of encoding 54Ala/Thr (A/T) single nucleotide polymorphism in the FABP2 in middle-aged and old people, and explore the association between 54T FABP2 and plasma lipids.DESIGN: A case-controlled analysis. SETTING: Department of Biochemistry, Hebei North University and Department of Clinical Laboratory, the 251 Hospital of Chinese PLA.PARTICIPANTS: 469 physical examinees were selected from the Medical Examination Center, the 251 Hospital of Chinese PLA between October 2003 and April 2005. The subjects included 217 males with mean age of (56±10) years, and 252 females with mean age of (55±13) years. Only people with normal liver and kidney function, and with no blood relation were recruited. The informed consent to this study was obtained from all subjects. The experiment was admitted by Hospital Ethics Committee. METHODS: ①After fasting for 12 hours, automatic analyzer (Olympus AU 6400) was adopted to measure plasma total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoprotein A1(Apo A1) and Apo B levels. ②1 mL venous blood was extracted and immediately mixed with anti-coagulants containing citric acid, natrium citricum and glucose. White blood cells were separated and genomic DNA was isolated using standard methods with proteinase K digestion and phenol/chloroform purification. The genotype distribution frequency in each group was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MAIN OUTCOME MEASURES: ①Plasma TC, TG, HDL-C, LDL-C, Apo A1and Apo B levels; ②Distributions of FABP2 genotypes at codon 54. RESULTS: ①The genotype frequencies of A/A, A/T, T/T were 0.48, 0.42, and 0.10 in males, and 0.44, 0.46, and 0.10 in females, respectively. The allelic frequency of point mutant 54Thr in FABP2 gene was 0.31 in males and 0.33 in females, respectively. There was no difference between males and females (χ2=0.47, P ＞ 0.05). ②The LDL-C and Apo B concentrations in fasting plasma of males with 54T allele were significantly higher than those with 54A allele (P ＜ 0.05). The TC and LDL-C concentrations in fasting plasma of females with 54T allele were significantly higher than those with 54A allele (P ＜ 0.05). CONCLUSION: In the middle-aged and old populations, the frequency of encoding 54Ala/Thr polymorphism in FABP2 gene is not correlated with gender, but with high lipoprotein profile.
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0.05). The LDL-C and apoB concentrations in fasting serum in men with 54T allele were significantly higher than those with 54A allele (2.38?0.63 vs 2.21?0.57mmol/L, P