[The association between Cathepsin S and pulmonary function and CT phenotypes in patients with chronic obstructive pulmonary disease].

Objective: To explore the value of cathepsin S in the bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD) in the evaluation of pulmonary function and CT phenotypes. Method: From April 2014 to April 2017, 46 patients with stable COPD were enrolled, and 29 healthy volunteers served as the control group. The patients were divided into 4 subgroups: GOLD Ⅰ(n=12), GOLD Ⅱ(n=6), GOLD Ⅲ(n=14), GOLD Ⅳ(n=14). The levels of cathepsin S and IFN-γ in BALF were determined by enzyme-linked immunosorbent assay (ELISA). The percentage ratio of low attenuation area to total lung area (LAA%), two times the ratio of airway wall thickness to outer diameter(2T/D), and the ratio of wall area to total cross-sectional area (WA) were measured by HRCT. Results: There were significant differences in the levels of cathepsin S in BALF between the groups (F=6.639, P=0.000). BALF cathepsin S levels were as follows: GOLD Ⅳ grou P>GOLD Ⅲ grou P>GOLD Ⅱ grou P>GOLD group Ⅰ >healthy control group (P value were all<0.05); LAA grade 3>LAA grade 2>LAA grade 1>LAA grade 0 (P value were all<0.05). Correlation analysis showed that BALF cathepsin S levels were correlated negatively with FEV(1)/FVC, FEV(1)% predicted, and DLCO% (r value was -0.065、-0.576、-0.392, respectively, P value were all<0.05), and but positively with RV/TLC%, LAA%, 2T/D, WA and IFN-γ(r value was 0.695, 0.497, 0.142, 0.309, 0.148, respectively, P value were all<0.05). Conclusion: The levels of cathepsin S were associated with the degree of airflow limitation and emphysema phenotype in COPD.

[Correlation analysis of serum secreted frizzled-related protein 5 levels with airway inflammation and insulin resistance in chronic obstructive pulmonary disease patients].

Objective: To investigate the relationship between serum secreted frizzled-related protein 5(sfrp5) levels, insulin resistance, and airway inflammation in patients with chronic obstructive pulmonary disease(COPD). Method: A total of 178 COPD patients visiting our respiratory outpatient clinic from February 2015 to January 2017 were enrolled, and 99 healthy control subjects from the same time period were selected. Serum sfrp5 levels were compared between the 2 groups. Serum sfrp5 and inflammatory cytokines in induced sputum were observed in the 4 subgroups: insulin resistant COPD group [homeostasis model assessment of insulin resistance (HOMA-IR)≥2.29], non-insulin resistant COPD group, non-COPD insulin resistant group, and healthy control group. Results: Serum sfrp5 levels were found to be significantly higher in the COPD group as compared to the healthy control group (t=-14.29, P<0.001). Serum sfrp5 levels in the insulin resistant COPD group [(8±3)ng/ml] were significantly lower than that of the non-insulin resistant COPD group [(10±5)ng/ml], non-COPD insulin resistant group [(13±3)ng/ml], and normal control group [(14±4)ng/ml, F=35.85, P<0.01]. The insulin resistant COPD group had higher levels of In(Homa-IR), as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in induced sputum as compared to the non-insulin resistant COPD group, non-COPD insulin resistant group, and healthy control group (F values were 64.968, 41.40, 64.15, respectively, P value <0.01 for all items). The non-insulin resistant COPD group had higher levels of In(HOMA-IR) as well as TNF-α and IL-6 in induced sputum as compared to the non-COPD insulin resistant group and healthy control group. FEV(1)/FVC and FEV(1)% predicted were significantly lower in the insulin resistant COPD group as compared to those of non-insulin resistant COPD group and non-COPD insulin resistant group, and healthy control group (F values were 2.481 and 8.37, respectively, P value<0.05 for all items). FEV(1)/FVC and FEV(1)% predicted were significantly lower in the non-insulin resistant COPD group as compared to those of the healthy control group and non-COPD insulin-resistant group. Serum sfrp5 levels were positively correlated to FEV(1)/FVC and FEV(1) predicted (r values were 0.466 and 0.412, respectively; P values were <0.001 and 0.007, respectively) and inversely correlated to In(HOMA-IR) and TNF-α and IL-6 in induced sputum (r values were -0.304, -0.459, -0.517, respectively; P values were <0.001, 0.002, <0.001, respectively). BMI, ln(HOMA-IR), and IL-6 in induced sputum were independent related factors (r(2) values were 0.286, 0.176, 14.69, respectively; P values were <0.01 for all items) Conclusion: Sfrp5 may be concurrently associated with COPD and insulin resistance; insulin resistance may be associated with airway inflammation and airflow limitation. Sfrp5 may be involved in the development of COPD and may be the key link by which insulin resistance exerts its effects on airway inflammation.

Functional allele and genotype frequencies of CYP1A2, CYP2B6 and iNOS among mainland Chinese Tibetan, Mongolian, Uygur and Han populations.

WHAT IS KNOWN AND OBJECTIVE: Cytochrome P450 1A2 (CYP1A2), CYP2B6 and inducible nitric oxide synthase (iNOS) are involved in the metabolism and action of many important therapeutic drugs, and genetic variants have been associated with interethnic differences in response to treatment, including chemotherapy. METHODS: Eight hundred and forty-two unrelated Chinese healthy subjects (323 Tibetan, 134 Mongolian, 162 Uygur and 223 Han) were recruited for genotyping. Frequencies of CYP1A2 -163C>A, CYP2B6 516G>T and iNOS -954G>C were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS AND DISCUSSION: The frequency of CYP1A2-163A was higher in Chinese Mongolian (0·698) than in Chinese Tibetan (0·633), Uygur (0·633) and Han populations (0·608, P < 0·05), respectively. The frequency of CYP1A2-163A in the Chinese population (total, 0·636) was intermediate between those reported in Caucasians (0·682, P < 0·05) and Africans (0·549, P < 0·01). The frequency of CYP2B6 516T in Chinese Uygur (0·287) was significantly higher than those in Chinese Tibetan (0·147, P < 0·01) and Mongolian (0·179, P < 0·01), respectively, but was similar to the frequency in Chinese Han (0·226). The frequencies of CYP2B6 516T were in the order of Africans (0·500) > Caucasians (0·286) > Chinese (0·200). The variant iNOS-954C was rare in Chinese Tibetan (0·005), Mongolian (0·004), Uygur (0·000) and Han (0·007), respectively, but showed higher frequencies in African ethnic groups. The frequencies of iNOS-954C were in the order of Africans (0·098) > Chinese (0·004) > Caucasians (0·000). WHAT IS NEW AND CONCLUSION: This is the first report of the distribution frequencies of functional CYP1A2, CYP2B6 and iNOS genes among mainland Chinese Tibetan, Mongolian, Uygur and Han populations. These results should help inform studies of interethnic differences in disease susceptibility or drug responses.

Corrigendum PKR and HMGB1 expression and function in rheumatoid arthritis - Genet. Mol. Res. 14 (4): 17864-17870.

Published online: December 22, 2015 (DOI: 10.4238/2015.December.22.11). Corrected after publication: June 3, 2016 (DOI: 10.4238/gmr.150267861). The correction is only in the name of the last author and should be: W.J. Wang, S.J. Yin and R.Q. Guo.

Expression of B7-H3 in cancer tissue during osteosarcoma progression in nude mice.

Immune cells might participate in the ontogenesis of osteosarcoma. B7-H3 is a new discovered T cell co-stimulatory molecule that was found to be overexpressed in malignant tumors. We aimed to investigate the dynamic expression level of B7-H3 in nude mice with osteosarcoma. A nude mouse osteosarcoma model was successfully established. B7-H3 expression and distribution changes in the early, middle, and late phases of osteosarcoma formation after tumor implantation were observed. Reverse transcription-polymerase chain reaction and western blot analyses were applied to measure the B7-H3 mRNA and protein dynamic changes. Confocal microscopy and immunohistochemistry were used to determine B7-H3 localization and CD3+ T cell expression, respectively, in osteosarcoma tissue. B7-H3 mRNA and protein levels fluctuated during the process of osteosarcoma formation in the nude mouse model. Expression levels were lower in the early and middle phases, while B7-H3 mRNA and protein were overexpressed in the late stage. Accordingly, CD3+ T cell numbers in the early, middle, and late phases in osteosarcoma tissue were 93 ± 13, 92 ± 12, and 46 ± 15, respectively; they can be seen to have decreased significantly in the late stage (P < 0.05). Overall, our results indicated that the B7-H3 expression level is correlated with tumor volume and severity; therefore, it might serve as a tumor biomarker for osteosarcoma.

PKR and HMGB1 expression and function in rheumatoid arthritis.

The pathogenesis of rheumatoid arthritis (RA) is characterized by inflammation. We aimed to examine the roles of double-stranded RNA-activated protein kinase (PKR) and high-mobility group box chromosomal protein 1 (HMGB1) in a rat model of RA. Male SD rats were divided into three groups: control, RA model, and intervention (RA model plus treatment). The model of RA was made by injecting Freund's adjuvant into the posterior right limb of the rat and the intervention group received a PKR-specific inhibitor C16 after RA modeling. The degree of limb swelling was measured following RA modeling and intervention. In addition, plasma levels of HMGB1 were determined using ELISA. The mRNA and protein levels of PKR and HMGB1 were detected in rat synovium using quantitative PCR and western blot, respectively. The degree of limb swelling in the RA model was increased compared to control, while it was decreased in the intervention model compared to the RA model. Plasma HMGB1 levels in the model group were significantly higher compared to the control group but were lower in the intervention group compared to the model group. PKR and HMGB1 protein and mRNA levels in the rat synovium were elevated in the model group and markedly reduced in the intervention group. Increased levels of PKR and HMGB1 in synovium or blood appear to be involved in the occurrence and development of RA in a rat model. Selective inhibition of PKR improves the symptoms of RA, perhaps by inhibiting the release of HMGB1.

Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations.

WHAT IS KNOWN AND OBJECTIVE: Cytochrome P450 2C19 (CYP2C19) and CYP2D6 are important xenobiotic metabolic enzymes and both show considerable genetic variability between Orientals and Caucasians. There are known marked heterogeneity in susceptibility to various cancers and hypertension among Chinese Mongolian, Hui and Han ethnic groups, but the molecular mechanisms are unknown. Our objective was to investigate the patterns of distribution of CYP2C19 and CYP2D6 polymorphisms among healthy Chinese subjects to determine whether any observed inter-ethnic variability might be worth further investigation as possible contributors to the known differences in disease prevalence. METHODS: Blood samples were collected from 454 unrelated Chinese healthy subjects (214 Han, 111 Hui, 129 Mongolian) for genotyping analysis. The single nucleotide polymorphisms (SNPs) CYP2C19*2 (681G>A in exon 5), CYP2C19*3 (636G>A in exon 4) and CYP2D6*10 (188C>T in exon 1) were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS AND DISCUSSION: Significantly higher frequencies of the CYP2C19 poor metabolic genotypes were observed in Chinese Han (18·7%), Chinese Hui (25·0%) and Chinese Mongolian (10·9%) subjects than has been reported for Caucasians (1·7-3·0%, P < 0·01). The prevalent defective allele CYP2C19*2 occurred more frequently in both Chinese Hui (32·4%) and Han (29·7%) than in Chinese Mongolian (18·2%, P < 0·01) subjects. The CYP2C19*2 and CYP2C19*3 defective alleles were significantly more frequent in Chinese Han and Chinese Hui ethnic groups than have been reported for Caucasians (11·1-16·3% and 0-0·2%, P < 0·01). CYP2D6*1/*10 heterozygotes and CYP2D6*10/*10 homozygotes were observed more frequently in Chinese Han (43·1% and 27·2%), Hui (40·6% and 30·7%) and Mongolian subjects (31·3% and 9·6%, both P < 0·01) than have been reported for Caucasians (5·5% and 0·3%, P < 0·01). In Chinese Mongolians, the CYP2D6*10 allele occurred at a frequency (25·2%, P < 0·01) intermediate between those reported for Caucasians and the other two Chinese ethnic populations. WHAT IS NEW AND CONCLUSIONS: This is first report of interethnic differences in frequencies of functional CYP2C19 and CYP2D6 genes among Chinese Mongolian, Hui and Han populations. These differences may be important in explaining reported inter-ethnic differences in disease prevalence and response to drugs.

Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients.

The aim of the study was to investigate the prevalence of mutations of basal core promoter (BCP) and precore (PreC) region of hepatitis B virus (HBV) and their association with hepatocellular carcinoma. A total of 341 untreated older HBV patients were divided into three groups: chronic hepatitis B (CHB, 185), cirrhotic hepatocellular carcinoma (LC-HCC, 113) and non-cirrhotic hepatocellular carcinoma (non-LC-HCC, 43). HBV BCP and PreC mutations and genotypes were determined by direct sequencing. Using univariate analysis, age (≥ 45 years), single mutations including A1896 and A1899 and multiple mutations T1762/A1764 + A1896, T1762/A1764 + A1899 and T1762/A1764 + A1896 + A1899 were more frequently detected in LC-HCC and non-LC-HCC patients than in CHB patients. BCP T1762/A1764 mutations were highly detected in LC-HCC patients than in CHB patients. Multivariate logistic regression analysis (adjusted for age and gender) revealed that among HBeAg-positive patients, BCP T1762/A1764 mutations (OR, 5.975; P = 0.05), PreC A1899 mutation (OR, 4.180; P = 0.013) and multiple mutations T1762/A1764 + A1899 (OR, 6.408; P = 0.006) were independently associated with the development of LC-HCC; PreC A1899 mutation (OR, 7.347; P = 0.034) was also independently associated with the development of non-LC-HCC. On the other hand, among HBeAg-negative patients, PreC A1896 mutation (OR, 5.176; P = 0.002) and multiple mutations T1762/A1764 + A1896 (OR, 4.149; P = 0.007) were independently associated with the development of non-LC-HCC. These results indicated that older age (≥ 45 years) was associated with LC-HCC and non-LC-HCC development. BCP T1762/A1764 mutations and PreC A1899 mutation were associated with the LC-HCC development in HBeAg-positive patients. PreC A1896 mutation was associated with the non-LC-HCC development in HBeAg-negative patients.

Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians.

There is a functional polymorphism of the mitochondrial aldehyde dehydrogenase (ALDH2) gene with the variant allele (ALDH2*2) encoding a protein subunit that confers low activity to the tetrameric enzyme. Genetic epidemiologic studies have strongly suggested that homozygosity for the allele ALDH2*2 is sufficient in completely inhibiting the development of alcoholism in Asians. To study the pathophysiology of this unique pharmacogenetic effect, we recruited a total of eighteen adult Han Chinese men, matched by age, body-mass index, nutritional state and homozygosity at the alcohol dehydrogenase gene loci from a population base of 273 men. Six individuals were chosen for each of the three ALDH2 allelotypes: homozygous ALDH2*2/*2, heterozygous ALDH2*1/*2, and homozygous ALDH2*1/*1. Following a low dose of ethanol (0.2 g/kg body weight), blood ethanol/acetaldehyde concentrations, cardiac and extracranial/intracranial arterial hemodynamic parameters, as well as self-rated subjective sensations, were measured for 130 min. Homozygous ALDH2*2 individuals were found to be strikingly responsive to the small amount of alcohol, as evidenced by the pronounced cardiovascular hemodynamic effects as well as subjective perception of general discomfort for as long as 2 h following ingestion. This low-dose alcohol hypersensitivity, accompanied by a prolonged and large accumulation of acetaldehyde in blood, provides an explanation for the strong protection against heavy drinking and alcoholism in individuals homozygous for the ALDH2*2 gene allele.

Structural features of stomach aldehyde dehydrogenase distinguish dimeric aldehyde dehydrogenase as a 'variable' enzyme. 'Variable' and 'constant' enzymes within the alcohol and aldehyde dehydrogenase families.

Stomach aldehyde dehydrogenase was structurally evaluated by analysis of peptide fragments of the human enzyme and comparisons with corresponding parts from other characterized aldehyde dehydrogenases. The results establish a large part of the structure, confirming that the stomach enzyme is identical to the inducible or tumor-derived dimeric aldehyde dehydrogenase. In addition, species variations between identical sets of different aldehyde and alcohol dehydrogenases reveal that stomach aldehyde dehydrogenase exhibits a fairly rapid rate of evolutionary changes, similar to that for the likewise 'variable' classical alcohol dehydrogenase, sorbitol dehydrogenase, and cytosolic aldehyde dehydrogenase but in contrast to the 'constant' class III alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase. This establishes that rates of divergence in the aldehyde and alcohol dehydrogenases are unrelated to subunit size or quaternary structure, highlights the unique nature of class III alcohol dehydrogenase, and positions the stomach aldehyde dehydrogenase in a group with more ordinary features.

Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family.

The alcohol dehydrogenase (ADH) gene family encodes enzymes that metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Studies on 19 vertebrate animals have identified ADH orthologs across several species, and this has now led to questions of how best to name ADH proteins and genes. Seven distinct classes of vertebrate ADH encoded by non-orthologous genes have been defined based upon sequence homology as well as unique catalytic properties or gene expression patterns. Each class of vertebrate ADH shares <70% sequence identity with other classes of ADH in the same species. Classes may be further divided into multiple closely related isoenzymes sharing >80% sequence identity such as the case for class I ADH where humans have three class I ADH genes, horses have two, and mice have only one. Presented here is a nomenclature that uses the widely accepted vertebrate ADH class system as its basis. It follows the guidelines of human and mouse gene nomenclature committees, which recommend coordinating names across species boundaries and eliminating Roman numerals and Greek symbols. We recommend that enzyme subunits be referred to by the symbol "ADH" (alcohol dehydrogenase) followed by an Arabic number denoting the class; i.e. ADH1 for class I ADH. For genes we recommend the italicized root symbol "ADH" for human and "Adh" for mouse, followed by the appropriate Arabic number for the class; i.e. ADH1 or Adh1 for class I ADH genes. For organisms where multiple species-specific isoenzymes exist within a class, we recommend adding a capital letter after the Arabic number; i.e. ADH1A, ADH1B, and ADH1C for human alpha, beta, and gamma class I ADHs, respectively. This nomenclature will accommodate newly discovered members of the vertebrate ADH family, and will facilitate functional and evolutionary studies.

Expression and activities of class IV alcohol dehydrogenase and class III aldehyde dehydrogenase in human mouth.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for the oxidation of ingested ethanol in humans. To study these two enzymes in surgical specimens of attached gingiva and tongue, we have examined the isozyme patterns by agarose isoelectric focusing and determined the enzyme activities. Class IV mu-ADH, class III chi-ADH, and class III ALDH3 were detected in the oral mucosa tissues. Gingival mu-ADH exhibited a pH optimum for ethanol oxidation at 10 and the K(m) value for ethanol (pH 7.5) was estimated to be 27 mM. At pH 7.5 and 30 degrees C, the ADH activities in the gingiva and tongue samples were determined to be 90.0 +/- 5.8 (mean +/- SE; n = 24) and 50.6 +/- 5.1 (n = 3) nmol/min/g tissue (at 33 mM ethanol), and 138 +/- 11 and 55.1 +/- 4.7 nmol/min/g tissue (at 500 mM ethanol), respectively. The ALDH activities at 20 mM acetaldehyde were determined to be 169 +/- 19 and 50.3 +/- 8.1 nmol/min/g tissue for the gingiva and tongue, respectively. We conclude that ethanol can be significantly metabolized in human attached gingiva and lingual mucosa by mu-ADH. The result also suggests that, due to lacking activity of low K(m) ALDH2 and ALDH1, cytotoxic metabolite acetaldehyde may be involved in the etiology of alcohol-related oral injury.

Helicobacter pylori infection in patients with gastric adenocarcinoma.

We examined the biologic tumor behavior in Helicobacter pylori-seropositive patients with gastric adenocarcinoma. A total of 214 consecutive patients with pathologically confirmed adenocarcinoma of the stomach who underwent gastric resection were studied. The stored serum samples were tested for serum antibody to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The difference in H. pylori-seropositive and seronegative patients with gastric adenocarcinoma was evaluated in terms of various clinicopathologic parameters. A multivariate logistic regression analysis was used to adjust for potential confounding variables. Antibodies to H.pylori were detected in 65.9% of patients with gastric adenocarcinoma. H.pylori-seropositive patients were younger than seronegative patients and had infiltrative tumor according to Ming's criteria. When adjusted for age, infiltrative tumor come out stronger. These findings suggest that H.pylori infection may be related to infiltrative type gastric adenocarcinoma; further study is necessary.

Effects of acupuncture on serum cortisol level and dopamine beta-hydroxylase activity in normal Chinese.

Serum cortisol levels were determined in 40 normal Chinese and dopamine beta-hydroxylase activities were measured in 22 normal subjects before and after acupuncture treatment. All subjects were studied twice with an interval of one week or more. In the self-control study, the subjects were needled at 5 non-acupuncture loci. In the experimental study, they were needled at the following 5 traditional acupuncture loci--right side GB-20, both sides EH-6, and both sides St-36. Blood samples were withdrawn before acupuncture and 15 and 45 min. after acupuncture. No change of serum dopamine beta-hydroxylase activity was observed. Serum cortisol levels increased significantly after needling on the traditional acupuncture loci. After acupuncture for 15 and 45 min., the cortisol increase was 28 and 50%, respectively, as compared to the self-control studies. The beneficial effect of acupuncture in the treatment of functional disorders, therefore, may be mediated by cortisol or other hormones and neurohormones.

Characteristic behavioral seizures and abnormal signal asymmetry of magnetic resonance imaging in an electrogenic rat model of chronic epilepsy.

Chronic tetani (60 Hz, 2 s, 0.4~0.6 mA) were administered to the dorsal hippocampus (DHPC) or the medial temporal lobe neocortex (MTNC) of rats, to study the role of the entorhinal cortex (EC)-hippocampal loop in temporal lobe epileptogenesis. This was repeated once a day for 7 or 10 days. Magnification of hyper-intensity was induced by tetanization of the HPC or the MTNC, as detected by contralateral T(2) weighed magnetic resonance imaging (T(2)-WI). The effects were associated with an enlarged volume of the lateral ventricle (LV), which was verified histologically. T(2)-WI hper-intensities, contralateral to the tetanized hemispheres, were observed with high frequency primary wet dog shakes (WEDS) in the DHPC-stimulated rats and with low frequency WEDS in the MTNC-stimulated rats. It seems likely that the same neural mechanisms are shared by chronic tetanization of the right HPC and the righ MTNC, involving the closed EC-HPC loop. Poor correlation between contralateral T(2)-WI hper-intensities and light primary behavioral seizures in the MTNC-stimulated rats might be attributed to a controlled information flow into or out of this loop because of potential EC gating. In addition, asymmetric T(2)-WI hyper-intensities in the LV area reflected a hemispheric dependence, contralateral to the electrogenic focus in our model of rat epilepsy.

Possible role of dentate gyrus in greneration of rat temporal lobe epilepsy induced by electrical stimulation.

Possible role of the dentate gyrus (DG) and the hippocampus (HPC) in temporal lobe epileptogensis was investigated in an electrogenic model of rat epilepsy. Chronic tetani (60 Hz, 0.4-0.6 mA. 2 s) were administered once daily for 7 days to the right dorsal hippocampus (DHPC) or the right DG. Animal behavior was observed and depth electro-graphic seizures and T(2)-weighted magnetic resonance images (T(2)-WI) were measured. Results indicated that the frequency of primary wet dog shakes (WEDS) in the DG-stimulated rats was much lower than that in the DHPC-stimulated rats (P<0.05). The mean maximal wave-amplitude in DG electrographs was also much lower than that in HPC electrographs (P<0.05). The oscillations proportion of DHPC electrographs increased after DHPC-tetanization (from 2/9 up to 7/9 rats). T(2)-WI hyperintensity in the lateral ventricle area was detected only in the DHPC-tetanized rats, not in the DG-tetanized rats (P<0.05). These results suggest that the DG acts as a filtering site in the entorhinal cortex-HPC neuronal circuitry and its dysfunction causes damage to the HPC and the generation of temporal lobe epilepsy.

Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB.

Numerous studies have shown that human endogenous retrovirus W family (HERV-W) envelope gene (env) is related to various diseases but the underlying mechanism has remained poorly understood. Our previous study showed that there was abnormal expression of HERV-W env in sera of patients with schizophrenia. In this paper, we reported that overexpression of the HERV-W env elevated the levels of small conductance Ca(2+)-activated K(+) channel protein 3 (SK3) in human neuroblastoma cells. Using a luciferase reporter system and RNA interference method, we found that functional cAMP response element site was required for the expression of SK3 triggered by HERV-W env. In addition, it was also found that the SK3 channel was activated by HERV-W env. Further study indicated that cAMP response element-binding protein (CREB) was required for the activation of the SK3 channel. Thus, a novel signaling mechanism of how HERV-W env influences neuronal activity and contributes to mental illnesses such as schizophrenia was proposed.