A comprehensive whole genome database of ethnic minority populations.

China, is characterized by its remarkable ethnical diversity, which necessitates whole genome variation data from multiple populations as crucial tools for advancing population genetics and precision medical research. However, there has been a scarcity of research concentrating on the whole genome of ethnic minority groups. To fill this gap, we developed the Guizhou Multi-ethnic Genome Database (GMGD). It comprises whole genome sequencing data from 476 healthy unrelated individuals spanning 11 ethnic minorities groups in Guizhou Province, Southwest China, including Bouyei, Dong, Miao, Yi, Bai, Gelo, Zhuang, Tujia, Yao, Hui, and Sui. The GMGD database comprises more than 16.33 million variants in GRCh38 and 16.20 million variants in GRCh37. Among these, approximately 11.9% (1,956,322) of the variants in GRCh38 and 18.5% (3,009,431) of the variants in GRCh37 are entirely new and do not exist in the dbSNP database. These novel variants shed light on the genetic diversity landscape across these populations, providing valuable insights with an average coverage of 5.5 ×. This makes GMGD the largest genome-wide database encompassing the most diverse ethnic groups to date. The GMGD interactive interface facilitates researchers with multi-dimensional mutation search methods and displays population frequency differences among global populations. Furthermore, GMGD is equipped with a genotype-imputation function, enabling enhanced capabilities for low-depth genomic research or targeted region capture studies. GMGD offers unique insights into the genomic variation landscape of different ethnic groups, which are freely accessible at https://db.cngb.org/pop/gmgd/ .

Correlations between polymorphisms in the uridine diphosphate-glucuronosyltransferase 1A and C-C motif chemokine receptor 5 genes and infection with the hepatitis B virus in three ethnic groups in China.

Objective To determine whether genetic polymorphisms in the uridine diphosphate-glucuronosyltransferase 1A ( UGT1A) and the C-C motif chemokine receptor 5 ( CCR5) genes are associated with hepatitis B virus (HBV) infection in Yi, Yao and Han ethnic groups in the Guizhou Province of China. Methods The study enrolled subjects with and without HBV infection. Whole blood was used for DNA genotyping using standard techniques. The study determined the frequencies of several polymorphic alleles ( UGT1A6 [rs2070959], UGT1A1 [rs8175347], CCR5-59029 [rs1799987] and CCR5Δ32 [rs333]) and then characterized their relationship with HBV infection. Results A total of 404 subjects were enrolled in the study: 138 from the Yao group, 101 from the Yi group and 165 from the Han group. There was a significant difference in the frequency of UGT1A1 rs8175347 polymorphisms among the three groups. The rates of 7TA carriers of UGT1A1 rs8175347 in all three groups were significantly higher than the other genotypes. Individuals with genotype AA of UGT1A6 rs2070959 in the Yi group had a higher risk for HBV infection than in the Yao and Han groups. The frequency of genotype GG in CCR5-59029 in the Yao group was significantly higher than in the Yi group. The genotypes of CCR5Δ32 were not associated with HBV infection. Conclusion These findings provide genetic and epidemiological evidence for an association of UGT1A and CCR5-59029 polymorphisms with HBV infection in Chinese Yi and Yao populations.

Characterization of polymorphisms in the mitochondrial DNA of twelve ethnic groups in the Guizhou province of China.

To characterize the genetic profiles and relationships between ancient ethnic populations, we analyzed polymorphisms in mitochondrial DNA (mtDNA) isolated from the blood of 753 members of 12 ethnic groups (Buyi, Dong, Gelao, Hui, Man, Miao, Menggu, Mulao, Maonan, Qiang, She and Zhuang) living in the Guizhou Province of China. The 9-bp deletion of mtDNA was detected by the polymerase chain reaction (PCR) and PCR-PAGE, and 11 SNPs by restriction fragment length polymorphism and mini-sequencing. Thereafter, these genotyping results were verified by PCR-DNA sequencing. The mtDNA of these populations exhibited considerable diversity, both with respect to the haplogroups M and N, and subgroups thereof. The differences between the major ethnic groups reflected the maternal inheritance. These ethnic groups in Guizhou demonstrated a genetic profile that differed considerably from that of other Asian populations. Our findings indicate that the matrilineal genetic profiles of Guizhou groups are relatively complex and distinct, showing relationships that reflect national history and geography.

[Analysis of polymorphisms of mitochondrial DNA in 3 ethnic groups of Guizhou].

OBJECTIVE: To analyze the population genetics characteristics of mitochondrial DNA (mtDNA) in Gelao, Mulao, Maonan ethnic groups from Guizhou. METHODS: Minisequenceing and restriction fragment length polymorphism (RFLP) were used to analyze 12 single nucleotide polymorphism (SNPs) of mitochondrial DNA in the 3 ethnic groups. RESULTS: A total of 30 haplotypes were detected in 156 samples. The distribution of H1, H23 had differed between Mulao, Maonan and Gelao, respectively, and so did M7 among the three groups. The difference was statistically significant (P < 0.05). Mulao, Maonan had respectively differed from Gelao and the difference was also statistically significant (P < 0.05). CONCLUSION: There was a great similarity in the distribution of haplotypes of the mtDNA among the three ethnic groups, except for some difference in the distribution of certain haplotypes.

[Frequencies of 9 bp deletion of mitochondrial DNA in ethnic Miao, Buyi and Dong from Guizhou].

OBJECTIVE: To study the frequency of a 9 bp deletion polymorphism of mitochondrial DNA (mtDNA) in ethnic Miao, Buyi and Dong populations from Guizhou province. METHODS: Polymerase chain reaction-polyacrylamide gel electrophoresis (PCR-PAGE) was used to detect the 9 bp deletion. The result was verified with DNA sequencing. RESULTS: Two polymorphisms, including a standard pattern and a short pattern (the 9 bp deletion), were found among the three ethnic groups. The frequency of short pattern in 304 males was 23.0%. Respectively, those of Miao, Buyi and Dong ethnics were 28.6%, 26.8% and 13.7%. A statistically significant difference was detected among the three groups (P<0.05). CONCLUSION: The frequencies of the 9 bp polymorphism were relatively high among ethnic Miao, Buyi and Dong populations from Guizhou, and there was a significant difference between the three.

[A study of interleukin-10 gene polymorphisms in Miao, Dong and Buyi ethnics of Guizhou].

OBJECTIVE: To investigate allelic frequencies of interluekin-10 (IL-10) gene promoter in Miao, Dong and Buyi ethnics of Guizhou. METHODS: TaqMan MGB-based real-time PCR was used to determine the genotypes of IL-10 -819 and IL-10 -592 in 589 Miao, Dong and Buyi ethnics of Guizhou. RESULTS: The allelic frequency of IL-10 -819 in Miao ethnics was significantly different from those in Dong or Buyi ethnics. Allelic frequencies of IL-10 -592 in Miao ethnics was significantly different from those in Dong or Buyi ethnics. In Miao, Dong and Buyi ethnics, the distributions of genotype frequencies of IL-10 -819 and IL-10 -592 were statistically different from Han ethnics from Guizhou and Taiwan of China as well as South Koreans. CONCLUSION: There is a heterogeneity in the frequencies of polymorphisms of IL-10 promoter among different ethnic groups.

Myeloperoxidase activity and its corresponding mRNA expression as well as gene polymorphism in the population living in the coal-burning endemic fluorosis area in Guizhou of China.

The myeloperoxidase (MPO) activity and its corresponding mRNA expression as well as gene polymorphism were investigated in the population who live in the endemic fluorosis area. In the study, 150 people were selected from the coal-burning endemic fluorosis area and 150 normal persons from the non-fluorosis area in Guizhou province of China. The blood samples were collected from these people. The activity of MPO in the plasma was determined by spectrophotometer; the expression of MPO mRNA was measured by employing real-time polymerase chain reaction; DNAs were extracted from the leucocytes in blood and five SNP genotypes of MPO promoter gene detected by a multiplex genotyping method, adapter-ligation-mediated allele-specific amplification. The results showed that the MPO activity and its corresponding mRNA in blood were significantly increased in the population living in the area of fluorosis. The different genotype frequencies of MPO, including -1228G/A, -585T/C, -463G/A, and -163C/T, and the three haplotypes with higher frequencies, including -163C-463G-585T-1228G-1276T, -163C-463G-585T-1228G-1276C, and -163C-463G-585T-1228A-1276T, were significantly associated with fluorosis. The results indicated that the elevated activity of MPO induced by endemic fluorosis may be connected in mechanism to the stimulated expression of MPO mRNA and the changed gene polymorphism.

The influence of inhibiting or stimulating the expression of the α3 subunit of the nicotinic receptor in SH-SY5Y cells on levels of amyloid-ß peptide and ß-secretase.

To examine the effects of the α3 subunit of the nicotinic acetylcholine receptor (nAChR) on the expression of ß-secretase and the concomitant level of amyloid-ß (Aß), SH-SY5Y neuroblastoma cells were either transfected with small interference RNAs (siRNAs) specifically targeting this subunit or exposed to nicotine. The levels of α3 nAChR mRNA and protein, as well as the corresponding levels of BACE1 (which cleaves the ß-site of APP) and BACE2 (cleaving in the Aß domain) were determined by real-time PCR and Western blotting, respectively. The levels of Aß(1-42) in culture media were determined by an Elisa procedure. In SH-SY5Y cells transfected with siRNA, the levels of α3 nAChR mRNA and protein were reduced by 96% and 88%, respectively; the levels of BACE1 mRNA and protein were significantly enhanced, while those of BACE2 were reduced; and the level of Aß in the culture medium was elevated. In contrast, when untransfected SH-SY5Y cells were exposed to nicotine, the levels of both α3 nAChR mRNA and protein were enhanced; while the levels of BACE1 mRNA and protein were diminished and the corresponding levels of BACE2 enhanced; and the level of Aß in the culture medium was attenuated. These results indicate that the α3 subunit of nAChR inhibits the production of Aß by reducing the expression of BACE1 and elevating the expression of BACE2, suggesting that this subunit might play an important neuroprotective role in connection with the pathogenesis of AD.

[Polymorphisms of homocysteine metabolism enzyme-related genes MS and MSR in Buyi, Dong and Miao ethnics from Guizhou].

OBJECTIVE: To investigate polymorphisms of homocysteine metabolism enzyme-related genes methionine synthase (MS) and methionine synthase reductase (MSR) in Buyi, Dong, Miao ethnics from Guizhou. METHODS: Genotypes of MS and MSR genes of healthy individuals from the three ethnic groups were determined with a TaqMan-MGB probe genotyping method and compared. RESULTS: For Buyi, Dong and Miao ethnics from Guizhou, frequencies of MS gene 2756G allele were respectively 12.0%, 8.9% and 15.4%. However, no significant difference was found by statistics. Frequencies of MS A2756G alleles for the three ethnic groups are similar to those of Han Chinese from Beijing and Henan, Hui ethnics from Ningxia as well as European populations, but differ significantly from those of Japanese, Indians, Africans and Nigerians (P < 0.05). Frequencies of MSR gene 66 G allele were respectively 32.3%, 30.4% and 21.2% for Buyi, Dong and Miao ethnics. Miao is significantly lower than Buyi and Dong (P< 0.05). Frequencies of MSR gene A66G alleles for the three ethnic groups are similar to those of Han Chinese from Beijing and Guangdong, Japanese, Africans and Nigerians populations, but differ significantly from those of Indians and European (P< 0.05). CONCLUSION: The distributions of MS gene A2756G and MSR gene A66G polymorphisms have differed significantly between the three ethnic groups and individuals from various regions.

[Genetic association between interleukin-10 promoter microsatellite polymorphisms and hepatitis B virus infection in Yi, Yao and Han ethnic populations of Guizhou province].

OBJECTIVE: To investigate the association between interleukin-10 (IL-10) gene promoter microsatellite polymorphisms and the susceptibility to hepatitis B virus infection in Han, Yi and Yao ethnicities in GuiZhou province. METHODS: 500 volunteers were selected from Guizhou province. Allelic frequency of IL-10.G and IL-10.R loci was identified by short tandom repeat polymerase chain reaction. The relativity between allelic frequency and HBV infection was analyzed. RESULTS: Genotype data from H-W analysis on all the IL-10 polymorphisms indicated that it was a random distribution. Very high HBV infection rates were found in the native ethnic minorities of Guizhou province. The overall HBV infection rate among the total population was 67.00%, with the HBV infection rates of Yi nationality in Weining, Yi nationality in Qianxi, Yao nationality in Libo and Han nationality in Libo as 51.85%, 42.86%, 79.52% and 84.30%, respectively. The polymorphisms distribution of IL-10.G and IL-10.R were statistically different among the ethnic groups (P < 0.05). The polymorphisms distribution of IL-10.R had no significant difference between HBV infection group and non-infection group, as well as among HBV natural removal group and non-infected group in all the ethnic groups. The frequency of IL-10.G 459 bp (19CA) was significantly higher in non-infection group than in the infected group (P < 0.05). The frequency of IL-10.G 471 bp (25CA) was significantly higher in the non-infection group than in the HBV natural removal group (P < 0.05). The polymorphisms distribution of IL-10.G did not show significant difference between the HBV infection group and the HBV natural removal group in all the ethnic groups. We did not find any differences in allelic and genotypic frequencies of IL-10.G between infection group and non-infection group in Yi nationality in Weining, and Yao nationality in Libo (P > 0.05), as well as HBV natural removal group and non-infected group (P > 0.05). CONCLUSION: The polymorphisms distribution of IL-10.R and IL-10.G did not show significant difference in Yi, Yao and Han ethnics population living in Guizhou province. IL-10.G seemed to influence the susceptibility of HBV infection in Han, Yao and Yi ethnics population of Guizhou province.

[Study on the association between RANTES-403G/A as well as -28C/G gene polymorphism and their susceptibility to the hepatitis B virus infections in Dong and Han ethnicities in Guizhou, China].

OBJECTIVE: To investigate the association between both regulated upon activation normal T cell expressed and secreted (RANTES) -403G/A, -28C/G gene polymorphism and the susceptibilities to hepatitis B virus (HBV) infection, among people with Dong and Han ethnicities, in Guizhou. METHODS: A total of 229 individuals with HBV persistence infection, 161 HBV clearanced patients and another 200 controls were recruited to conduct a case-control study among residents with Dong or Han ethnicities. Allelic frequencies of both RANTES-403G/A and -28C/G were identified by TaqMan-MGB probe. RESULTS: Both RANTES-403G/A and -28C/G polymorphism in the HBV-persistent group, when compared to the HBV-clearances group, no significant difference was found (P > 0.05). RESULTS: from the univariate analysis showed that subjects carrying -403AG and -28GG genotype had higher risk on the susceptibility to HBV persistence infection. The distributions of RANTES-28C/G gene polymorphism between Dong minority and Han ethnicities regarding HBV persistence showed statistically significant difference (P < 0.05). There was no difference on the distributions of RANTES-403G/A gene polymorphism between Dong minority and Han ethnicities. CONCLUSION: Patients that carrying both RANTES-403AG and -28GG genotype had higher risk on the persistence to HBV, while RANTES-403A had contributed to the clearance of HBV infection.

[Influence of APP(SWE) transfection on nicotinic receptors in cultured neuronal cells].

OBJECTIVE: To investigate the influence of APP(SWE) on the expression of neuronal acetylcholine receptors (nAChRs) and its relationship with Alzheimer's disease (AD). METHODS: APP(SWE), carried the Swedish family AD double mutants, were transfected into SH-SY5Y cells and primary cultured neurons from rat brains to build a cellular model of AD. The mRNA levels of APP and nAChRs, and the protein levels of total APP, αAPPs and nAChRs in the cultured cells were measured using real-time PCR and Western blot, respectively. The numbers of α3 nAChR were determined by receptor-[³H]epibatidine binding assay. RESULTS: Increased expressions of Swedish 670/671 APP at mRNA and protein levels, and down-regulation of αAPPs were observed in both of the cultured neuronal cells transfected with APP(SWE). A significant increase of α7 nAChR expression at protein and mRNA levels was detected in the APP(SWE) transfected SH-SY5Y cells. On the other hand, after transfection with APP(SWE), the expressions of α3 nAChR at protein and mRNA levels in SH-SY5Y cells, and α4 nAChR at mRNA level in primary cultured neurons were inhibited. In addition, the numbers of receptor binding sites were deceased in SH-SY5Y cells overexpressing with APP(SWE). CONCLUSION: Overexpression of APP(SWE) can decrease αAPPs and modify nAChRs by increasing expression of α7 nAChR and decreasing α3 and α4 nAChRs, which might play an important role in the pathogenesis of AD.

Cholinesterase activity and mRNA level of nicotinic acetylcholine receptors (alpha4 and beta2 Subunits) in blood of elderly Chinese diagnosed as Alzheimer's disease.

The aim of the study is to investigate the cholinergic deficit in Alzheimer's disease (AD) and identify candidate blood biomarkers for the diagnosis of the disease. Twenty-nine elderly Chinese diagnosed with AD and 33 age-matched controls were selected. The activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in plasma were detected by a spectrophotometric method, and the mRNA levels of alpha4 and beta2 nicotinic acetylcholine receptor (nAChR) subunits in blood leukocytes were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that AChE activity in plasma was significantly lower in the AD group than in normal controls, while BuChE activity did not show any differences between AD and controls; mRNA levels of both alpha4 and beta2 nAChR subunits in blood leukocytes were significantly lower in the AD group than in controls. The AChE activity and the mRNA levels of alpha4 and beta2 nAChR subunits in the AD patients were also significantly correlated with cognitive test scores. No differences of AChE in plasma or alpha4 and beta2 nAChR subunits in blood leukocytes were detected between smoking and non-smoking subjects. The results indicated that the decreases in the activity of AChE and in the mRNA levels of nAChR alpha4 and beta2 subunits from the peripheral blood of patients with AD might serve as supplementary indicators for the clinical diagnosis of AD.

[Influence of inhibited gene expression of alpha 3 nicotinic acetylcholine receptor by RNA interference on anti-oxidation in SH-SY5Y cells].

OBJECTIVES: To investigate the neuroprotective function of alpha 3 nicotinic acetylcholine receptor (nAChR) by inhibiting the gene expression in human neuroblastoma (SH-SY5Y) cells using small interference RNA (siRNA). METHODS: The siRNA coding oligonucleotide sequences targeting alpha 3 nAChR were designed and synthesized. The annealed product was cloned into pSilencer 3.1-H1 neo vector. The recombinant alpha 3 nAChR pSilencer 3.1-H1 neo vector was transfected into the SH-SY5Y cells. The stable clones were screened by G418 medium, and the levels of alpha 3 nAChR mRNA and protein were monitored by using real-time PCR and Western blotting, respectively. After the SH-SY5Y cells with siRNA treatment were exposed to 1 micromol/L Abeta(1-42), MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide], SOD, GSH-px and the lipid peroxidation were measured by spectrophotometry. RESULTS: Compared with the controls, the expression levels of mRNA and protein in the stable SH-SY5Y clone cells transfected with the recombinant alpha 3 nAChR pSilencer 3.1-H1 neo vector were decreased with inhibitory efficiency of 98% and 66%, respectively, the MTT reduction decreased; the product of lipid peroxidation was increased and the activities of SOD and GSH-px were decreased. Biologically, the gene expression inhibition of alpha 3 nAChR enhanced the toxicity induced by Abeta in SH-SY5Y cells. CONCLUSIONS: The expression inhibition of alpha 3 nAChR as a result of recombinant alpha 3 nAChR siRNA can induce oxidative stress and improve the toxicity of Abeta on SH-SY5Y cells, indicating that alpha 3 nAChR may play a significant neuroprotective role in the pathogenesis of Alzheimer disease.

[Study on the association of IL-10-592 polymorphism with susceptibility to hepatitis B viral infection in Han, Yi and Yao ethnic groups in Guizhou province].

OBJECTIVE: To investigate the association of IL-10 gene promoter polymorphism with susceptibility to hepatitis B viral infection in Han, Yi and Yao ethnic groups from Guizhou province. METHODS: Five hundred volunteers from Guizhou province were selected to undertake PCR-RFLP for detection of IL-10 gene promoter -592 polymorphism. RESULTS: The genotypic distributions of IL-10-592 were 32.53%-51.43% (AA), 40.74%-54.82% (AC), 5.79%-18.52% (CC) whereas the allelic frequencies were 59.94%-72.38% for the A allele, and 27.62%-40.06% for the C allele in Han, Yi and Yao ethnic from Guizhou. The distributions of allele and genotype frequencies of IL-10-592 were statistically different between Yao ethnic in Libo and Yi ethnic in Qianxi, Yao ethnic in Libo and Han ethnic in Libo,Yi ethnic in Qianxi and Yi ethnic in Weining,Yi ethnic in Weining and Han ethnic in Libo (P < 0.05). IL-10-592 polymorphism was associated with HBV infection in Yi ethnic in Qianxi and the whole population. CONCLUSION: IL-10-592 gene polymorphisms influenced the susceptibility to HBV infection in Han, Yao, Yi sub-populations in Guizhou. Result of the study suggested that IL-10-592 gene polymorphisms might serve as a risk factor to HBV infection.

Inhibiting gene expression of alpha3 nicotinic receptor in SH-SY5Y cells with the effects on APP metabolism and antioxidation in Alzheimer's disease.

In order to examine the effects of alpha3 nicotinic acetylcholine receptor (nAChR) in connection with the pathogenesis of Alzheimer's disease (AD), neuroblastoma (SH-SY5Y) cells were transfected with small interference RNAs (siRNAs) that target specifically towards alpha3 nAChR. The expressions of alpha3 nAChR mRNA and protein were measured by real-time PCR and Western blotting, respectively. The levels of the alpha-form of secreted amyloid precursor protein (alphaAPPs) and total-APP were determined by Western blotting. SH-SY5Y cells transfected with siRNA were then treated with 1muM beta-amyloid peptide (Abeta)(1-42), following which the levels of lipid peroxidation, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the reduction rate of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] were characterized by utilizing spectrophotometric procedures. As compared to controls, SH-SY5Y cells transfected with siRNA expressed the decreases in the levels of alpha3 nAChR mRNA and protein by 98% and 66% lower levels, respectively; exhibited reduced level of the alphaAPPs; and demonstrated enhanced lipid peroxidation, decreased rate of MTT reduction, and declined activities of SOD and GSH-Px. Inhibited gene expression of the alpha3 nAChR enhanced the toxicity exerted by Abeta. These results indicate that alpha3 nAChR may improve cleavage of APP by alpha-secretase, enhance antioxidation and inhibit the toxicity of Abeta, suggesting that the receptor might play an important role in AD.

[Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in ethnic minority from Guizhou].

OBJECTIVE: To investigate the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in Dong, Yi and Yao ethnic groups from Guizhou. METHODS: In 321 volunteers who were population-based, GSTM1 and GSTT1 polymorphisms were analyzed by a multiplex-PCR procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP method. RESULTS: Null genotype for GSTM1 and GSTT1 was 59.6%-71.2% and 39.4%-72.5%, respectively. The genotypic distribution of GSTP1 was 63.3%-75% for AA, 23.2%-35.8% for AG, 0-1.9% for GG, whereas the allelic frequencies were 81.2%-86.6% for the A allele, and 13.4%-18.8% for the G allele. CONCLUSION: There is a significant relationship between GSTT1 frequencies and ethnic populations.

[Protection of Tianshen Yizhi Recipe against low expression of nicotinic receptor and neurotoxicity induced by beta-amyloid peptide].

OBJECTIVE: To investigate the inhibition effects of Tianshen Yizhi Recipe (TSYZR), a compound traditional Chinese herbal medicine, on decreased expression of nicotinic acetylcholine receptor (nAChR) and the neurotoxicity as well as lipid peroxidation induced by beta-amyloid peptide (Abeta) in human SH-SY5Y neuroblastoma cells. METHODS: The SH-SY5Y cells were treated by a certain concentration of TSYZR, and then exposed to Abeta(25-35). Methyl thiazolyl tetrazolium reduction assay was carried out to understand the influences of the drugs on cellular viability. Expressions of nAChR subunits (alpha3 and alpha7) at protein and mRNA levels were detected by Western-blotting and reverse transcription polymerase chain reaction, respectively. Lipid peroxidation was measured by thiobarbituric acid to observe the capacity of antioxidant of the drugs. RESULTS: TSYZR at a safe concentration could increase alpha7 protein in the cells, inhibit decreased expressions of alpha3 and alpha7 nAChR subunit proteins, prevent lower expression of alpha7 mRNA in SH-SY5Y cells induced by Abeta, reduce the neurotoxicity and lipid peroxidation resulting from Abeta, but had no significant effect on the lower expression of alpha3 mRNA. CONCLUSIONS: TSYZR can up-regulate the expression of alpha7 nAChR subunit protein and prevent decreased expressions of nAChRs and neurotoxicity as well as lipid peroxidation induced by Abeta. This drug may play an important therapeutic role in treatment of Alzheimer disease.

Blood metallothionein transcript as a biomarker for metal sensitivity: low blood metallothionein transcripts in arsenicosis patients from Guizhou, China.

BACKGROUND: Because metallothionein (MT) is a metal-binding protein that protects against metal intoxication, it could be a biomarker for individual sensitivity to metal toxicity. OBJECTIVE: We assessed the use of bloodborne MT transcript as a reflection of tissue MT levels and examined the potential role of MT in arsenic toxicity in an environmentally exposed human population. METHOD: Rodents were treated with zinc or nonmetallic MT inducers for 4 days, and the blood and tissues were collected for MT transcript analysis by real-time reverse transcriptase-polymerase chain reaction and MT protein determination by the cadmium-hemoglobin assay. Blood and buccal cell samples were collected from arsenicosis patients and healthy subjects residing in Guizhou, China, and total RNA was isolated for MT transcript analysis. RESULTS: There was a positive correlation between blood MT-1 and MT-2 transcripts and corresponding hepatic or renal MT transcript levels in rats and mice. Furthermore, there was a positive correlation between blood MT-1 and MT-2 transcript and tissue MT protein levels in these animals. A positive correlation also occurred between human blood MT and buccal cell MT transcript levels. MT-1A and MT-2A were the major isoform transcripts in human blood and buccal cells, and significantly lower MT levels were seen in arsenicosis patients compared with healthy subjects. CONCLUSIONS: Blood MT transcript appears to be a useful biomarker of tissue MT levels. Arsenicosis patients in Guizhou show significantly lower MT transcript levels in blood, which may have predisposed this population to arsenic intoxication.