Latexin expression is downregulated in human gastric carcinomas and exhibits tumor suppressor potential

<p>Abstract</p> <p>Background</p> <p>Latexin, also known as endogenous carboxypeptidase inhibitor (CPI), has been found to inhibit mouse stem cell populations and lymphoma cell proliferation, demonstrating its potential role as a tumor suppressor. Our previous study also suggested a correlation between latexin expression and malignant transformation of immortalized human gastric epithelial cells. Here, we examined latexin expression in human gastric carcinomas and investigated the effect of differential latexin expression on proliferation of gastric cancer cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>Monoclonal antibody against human latexin was prepared and immunohistochemical analysis was performed to detect latexin expression in 41 paired gastric carcinomas and adjacent normal control tissues. Human gastric cancer cells MGC803 (latexin negative) stably transfected with LXN gene and BGC823 cells (latexin positive) stably transfected with antisense LXN gene were established for anchorage-dependent colony formation assay and tumorigenesis assay in nude mice. Differentially expressed genes in response to exogeneous latexin expression were screened using microarray analysis and identified by RT-PCR. Bisulfite sequencing was performed to analyze the correlation of the methylation status of LXN promoter with latexin expression in cell lines.</p> <p>Results</p> <p>Immunohistochemical analysis showed significantly reduced latexin expression in gastric carcinomas (6/41, 14.6%) compared to control tissues (31/41, 75.6%) (<it>P </it>< 0.05). Overexpression of LXN gene in MGC803 cells inhibited colony formation and tumor growth in nude mice. Conversely, BGC823 cells transfected with antisense LXN gene exhibited enhanced tumor growth and colony formation. Additionally, several tumor related genes, including Maspin, WFDC1, SLPI, S100P, and PDGFRB, were shown to be differentially expressed in MGC803 cells in response to latexin expression. Differential expression of Maspin and S100P was also identified in BGC823 cells while latexin expression was downregulated. Further bisulfite sequencing of the LXN gene promoter indicated CpG hypermethylation was correlated with silencing of latexin expression in human cells.</p> <p>Conclusions</p> <p>Latexin expression was reduced in human gastric cancers compared with their normal control tissues. The cellular and molecular evidences demonstrated the inhibitory effect of latexin in human gastric cancer cell growth and tumorigenicity. These results strongly suggest the possible involvement of latexin expression in tumor suppression.</p

A retrospective analysis of 25 cases of Addison's disease caused by adrenal tuberculosis in Tibet and review of related literature

Background: To investigate the clinical characteristics of Addison’s disease caused by adrenal tuberculosis in Tibet. After the anti-tuberculosis treatment, the clinical features between continuous glucocorticoid therapy and glucocorticoid withdrawal were analyzed. Methods: Clinical data of patients with Addison's disease caused by adrenal tuberculosis diagnosed in The People's Hospital of Tibet Autonomous Region from January 2015 to October 2021 were collected and analyzed. All patients were taking anti-tuberculosis and glucocorticoids replacement therapy, and the root cause of the disease was analyzed following prognosis observations. Results: There were 25 patients (24 Tibetan and 1 Han patient) with Addison's disease caused by adrenal tuberculosis, including 18 males and 7 females. A total of 21 cases were followed up successfully, of which 13 cases discontinued anti-tuberculosis drugs successfully, 6 cases discontinued glucocorticoid therapy among the rest, 6 cases continued anti-tuberculosis + glucocorticoid replacement therapy, and 2 cases died. Conclusion: Early diagnosis and proper anti-tuberculosis treatment can improve the prognosis of patients with adrenal tuberculosis. Moreover, screening and educating Tibetan people regarding the potential risk and adversities of adrenal tuberculosis is crucial for eradicating the disease

Polymorphisms of genes in neurotransmitter systems were associated with alcohol use disorders in a Tibetan population.

Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD). However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281) with an alcohol use disorder identification test (AUDIT) score ≥10, as well as healthy controls (N = 277) with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05). After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881) in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881) showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD

Physiological responses and evaluation of effects of BMI, smoking and drinking in high altitude acclimatization: a cohort study in Chinese Han young males.

High altitude acclimatization is a series of physiological responses taking places when subjects go to altitude. Many factors could influence these processes, such as altitude, ascending speed and individual characteristics. In this study, based on a repeated measurement design of three sequential measurements at baseline, acute phase and chronic phase, we evaluated the effect of BMI, smoking and drinking on a number of physiological responses in high altitude acclimatization by using mixed model and partial least square path model on a sample of 755 Han Chinese young males. We found that subjects with higher BMI responses were reluctant to hypoxia. The effect of smoking was not significant at acute phase. But at chronic phase, red blood cell volume increased less while respiratory function increased more for smoking subjects compared with nonsmokers. For drinking subjects, red blood cell volume increased less than nondrinkers at both acute and chronic phases, while blood pressures increased more than nondrinkers at acute phase and respiratory function, red blood cell volume and oxygen saturation increased more than nondrinkers at chronic phase. The heavy and long-term effect of smoking, drinking and other factors in high altitude acclimatization needed to be further studied

Clinical characteristics of the studied groups.

<p>Abbreviations: BMI, body mass index; RBC, red blood cell count, RBC; HB, hemoglobin; HCT, hematocrit; LVEF, left ventricular ejection fraction.</p><p>^<b>a</b> Data are means ± SD.</p><p>Clinical characteristics of the studied groups.</p

Correlation of allele frequencies of <i>HIF2A</i> variants in Tibetans and level of high altitude.

<p>solid circle, rs56721780-C; solid diamond, rs6756667-A; solid square, rs7589621-G; solid triangle, rs1868092-A</p

Association analysis between <i>HIF2A</i> tSNPs and levels of high altitude among native Tibetans.

<p>Abbreviations: Additive, additive model; Dominant, dominant model.</p><p><i>P</i>-values except the noted ones are calculated from χ² test.</p><p>^<b>a</b><i>P</i>-values are calculated from Fisher exact test.</p><p>^<b>b</b> Bold type denotes <i>P</i><0.05.</p><p>Association analysis between <i>HIF2A</i> tSNPs and levels of high altitude among native Tibetans.</p