Uncoupling protein and nonalcoholic fatty liver disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the current advances on the role of uncoupling protein (UCP) in the pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD).</p><p><b>DATA SOURCES</b>A comprehensive search of the PubMed literature without restriction on the publication date was carried out using keywords such as UCP and NAFLD.</p><p><b>STUDY SELECTION</b>Articles containing information related to NAFLD and UCP were selected and carefully analyzed.</p><p><b>RESULTS</b>The typical concepts, up-to-date findings, and existing controversies of UCP2 in NAFLD were summarized. Besides, the effect of a novel subtype of UCP (hepatocellular down regulated mitochondrial carrier protein, HDMCP) in NAFLD was also analyzed. Finally, the concept that any mitochondrial inner membrane carrier protein may have, more or less, the uncoupling ability was reinforced.</p><p><b>CONCLUSIONS</b>Considering the importance of NAFLD in clinics and UCP in energy metabolism, we believe that this review may raise research enthusiasm on the effect of UCP in NAFLD and provide a novel mechanism and therapeutic target for NAFLD.</p>

Changes of CD8⁺ T cells in dextran sulfate sodium-induced colitis mice pretreated with oral immune regulation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that CD8(+) regulatory cells could be induced upon oral tolerance. The purpose of this study was to investigate the changes of CD8α(+) T cells in dextran sulfate sodium (DSS)-induced colitis mice pretreated by oral immune regulation.</p><p><b>METHODS</b>The effects of five low oral doses of colitis-extracted proteins (CEP) on colitis were evaluated by clinical manifestation and histological lesions. The percentages of CD8α(+) T cells gating on CD3(+) T cells were evaluated in the gut-associated lymphoid tissues (GALT) and the spleens by flow cytometry. Differences between the two groups were compared by Student's t test or Mann-Whitney U test.</p><p><b>RESULTS</b>Compared to bovine serum albumin (BSA)-fed control mice, administration of CEP resulted in marked alleviation of colitis. The proportion of CD8α(+) T cells, not only in intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) of the large intestine (LI) but also in spleen from CEP-fed colitis mice, was significantly higher than that from BSA-fed colitis mice (LI-IELs: (71.5 ± 5.4)% vs. (60.1 ± 4.3)%, P < 0.01; LI-LPLs: (60.7 ± 5.2)% vs. (51.9 ± 4.7)%, P < 0.01; spleen: (24.1 ± 3.6)% vs. (20.3 ± 4.1)%, P < 0.05; n = 8). Mucosal repair in repair-period mice five days after termination of DSS treatment was also accompanied by an increase of CD8α(+) T cells in large intestinal mucosal lymphocytes (LI-IELs: (72.1 ± 3.7)% vs. (61.5 ± 4.5)%, P < 0.01; LI-LPLs: (62.1 ± 5.7)% vs. (52.7 ± 3.6)%, P < 0.01; n = 8). The proportion of CD3(+) T cells increased in Peyer's patches (PPs) and decreased in mesenteric lymph nodes (MLNs) from colitis mice compared to untreated mice, whereas the change pattern of CD3(+) T cells in PPs and MLNs from CEP-fed colitis mice was just on the contrary.</p><p><b>CONCLUSION</b>Improvement of DSS-induced colitis resulted from oral immune regulation is associated with an increase in CD8α(+) T cells in spleen and large intestinal mucosa.</p>

Haplotypes of four single nucleotide polymorphisms in caspase-8, -10 genes in Han nationality of Zhejiang province in China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate single nucleotide polymorphisms (SNPs) and the distribution of their haplotypes in caspase-8, -10 genes in Zhejiang Han nationality in China.</p><p><b>METHODS</b>PCR, denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing were used to detect the SNPs in the 2nd-5th exons of caspase-10 gene, the 8th-10th exons of caspase-8 and their flanking sequences. Expectation Maximization (EM) algorithm was used for haplotype frequencies analysis and pairwise linkage disequilibrium (LD) test.</p><p><b>RESULTS</b>(1) Two SNPs, A2823G and A12799G, were identified in caspase-10 gene, located in exon 2 and exon 5 respectively. A12799G was newly found with low informativeness. Three SNPs were identified in caspase-8 gene; A43466G, G51484A and G52951A were located in exon 8, exon 9 and intron 9, respectively. They do not change the primary structure of the encoded protein. (2) Linkage equilibrium was observed between A2823G in caspase-10 gene and the three sites in caspase-8 gene. A43466G and G52951A, and G51484A and G52951A in caspase-8 gene were also in linkage equilibrium. Their coefficients of disequilibrium were near 0. Whereas strong linkage disequilibrium was observed between A43466G and G51484A, because its coefficient of disequilibrium was near 1. (3) A total of 11 haplotypes were estimated within A2823G in caspase-10 gene and three sites in caspase-8 gene. A-2823/A-43466/G-51484/G-52951 was the main haplotype with a frequency of 0.3811. A-2823/A-43466/G-51484/A-52951 was the second haplotype with a frequency of 0.2536. The polymorphism information content of their haplotypes was 0.7106.</p><p><b>CONCLUSION</b>The SNPs of caspase-8, -10 genes in Han Chinese of Zhejiang could be parsed into at least three different haplotype blocks. The polymorphism information content can be improved by using haplotype analysis of several SNPs.</p>

A novel microsatellite within intron 8 in caspase10 gene in Chinese of Han nationality / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate polymorphisms in the coding exons and their splicing areas of caspase10 gene (CASP10) in Chinese of Han nationality.</p><p><b>METHODS</b>Polymerase chain reaction (PCR), denaturing high-performance liquid chromatography (DHPLC), direct sequencing and clonal sequencing were used to analyze the exon 9 and its flanking sequences.</p><p><b>RESULTS</b>In 70 blood samples of Chinese subjects researched the known single nucleotide polymorphisms (SNPs) in the exon 9 of CASP10 gene published in dbSNP of NCBI were not identified. We found a short sequence with more than ten continuous and repeated T nucleotides within the intron 8 near the exon 9 and the length of repeated sequence nucleotides T was different in samples. Clonal sequencing analysis indicated that it was a microsatellite of single nucleotide-repeated sequence. The recurrence and specificity of same result was further confirmed by PCR with high fidelity polymerase and sequencing. Furthermore all of 70 blood samples detected by DHPLC showed heterozygous profiles. We named it as IVS8-13(T)n temperately.</p><p><b>CONCLUSION</b>Our research suggested that the site be a microsatellite of single nucleotide-repeated sequence. Meanwhile, our data further showed that it was quite different from that by querying SNP database of non-Chinese population in NCBI, in the same region a SNP of type of insertion deletion existed. It could be inferred that the difference between the populations might be associated with the genetic characteristics of ethnics. The significance of the microsatellite in CASP10 gene in Chinese of Han nationality remains to be elucidated.</p>

BCL-2/IgH translocation in peripheral blood cells of healthy Chinese individuals of Han nationality located in Zhejiang area / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the frequency of BCL-2/IgH rearrangement in peripheral blood cells of healthy Chinese individuals of Han nationality located in Zhejiang area and the low incidence of follicular lymphoma (FL).</p><p><b>METHODS</b>Nested-PCR and direct DNA sequencing were used to detect the Bcl-2/IgH rearrangement in peripheral blood cells of 196 healthy individuals. DNA sequences involved were then searched and aligned in NCBI database to confine the broken points in major breakpoint region and the IgH segments involved.</p><p><b>RESULTS</b>First, in this sample the frequency of BCL-2/IgH translocation in Chinese individuals of Han nationality located in Zhejiang area is 9.66%, being much lower than that in North America and Europe countries. Second, the breakpoints tend to fall into 3 clusters: 3055, 3116 and 3165 bp. Usage of J6 segment is most common. Third, There are different subclones of BCL-2/IgH rearrangements in the same individual.</p><p><b>CONCLUSION</b>The low frequency of BCL-2/IgH translocation in healthy Chinese individuals of Han nationality located in Zhejiang area may be one of the reasons for the difference in the incidence of FL between China and Western countries.</p>

The haplotypes of three single nucleotide polymorphisms in caspase-3 gene in Han nationality of Zhejiang province in China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the single nucleotide polymorphisms (SNPs) and the distribution of their haplotypes in caspase-3 gene in Zhejiang Han nationality in China.</p><p><b>METHODS</b>Denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing were used to detect the SNPs in the regulatory region and the exons 2-7 and their flanking sequences in caspase-3 gene. Expectation maximization (EM) algorithm was used for haplotype frequencies analysis and pairwise linkage disequilibrium test.</p><p><b>RESULTS</b>(1) Three SNPs were identified in caspase-3 gene; the three sites C829A, A17532C and C20541T were located in 5' regulatory region, intron 4 and 3' regulatory region, respectively. (2) Strong linkage disequilibrium was found among these SNPs; site A17532C and C20541T were in complete linkage disequilibrium. (3) C-829/A-17532/C-20541 (54.3%) was the main haplotype of Zhejiang Han nationality.</p><p><b>CONCLUSION</b>The above findings indicated there is strong linkage disequilibrium among the three SNPs in caspase-3 gene in Han nationality of Zhejiang province and the main haplotype of Han nationality is obviously different from that of North American.</p>