ß-cell neogenesis: A rising star to rescue diabetes mellitus.

BACKGROUND: Diabetes Mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose, is caused by various degrees of insulin resistance and dysfunctional insulin secretion, resulting in hyperglycemia. The loss and failure of functional ß-cells are key mechanisms resulting in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). AIM OF REVIEW: Elucidating the underlying mechanisms of ß-cell failure, and exploring approaches for ß-cell neogenesis to reverse ß-cell dysfunction may provide novel strategies for DM therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: Emerging studies reveal that genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modification linked to multiple signaling pathways contribute to DM pathogenesis. Over the past few years, replenishing functional ß-cell by ß-cell neogenesis to restore the number and function of pancreatic ß-cells has remarkably exhibited a promising therapeutic approach for DM therapy. In this review, we provide a comprehensive overview of the underlying mechanisms of ß-cell failure in DM, highlight the effective approaches for ß-cell neogenesis, as well as discuss the current clinical and preclinical agents research advances of ß-cell neogenesis. Insights into the challenges of translating ß-cell neogenesis into clinical application for DM treatment are also offered.

HEATR3 involved in the cell proliferation, metastasis and cell cycle development of bladder cancer acts as a tumor suppressor.

The study was designed to detect the expression and clinical significance of the HEATR3 gene in bladder cancer (BCa) and to preliminarily explore whether this gene can affect the occurrence and development of BCa through the AKT/ERK signaling pathway. The expression and prognostic value of HEATR3 were explored based on The Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression (GTEx) databases. Microarray immunohistochemical analysis was performed in 30 BCa cases to investigate the level of HEATR3 protein and to explore the relationship between HEATR3 and the clinicopathological features of BCa. Western Blot and qRT-PCR were used to detect HEATR3 protein and mRNA in BCa cell lines (5637, TCCSUP, SW780) and fallopian tube epithelial cell (SV-HUC-1). CCK8 method was employed to study the proliferation of BCa cells after heat treatment. Transwell assay was conducted to analyze the effect of HEATR3 on cell migration and invasion. And cell cycle and apoptosis were detected by flow cytometry. Furthermore, Western Blot assay was used to probe the effects of down-regulation of HEATR3 expression on the expression and phosphorylation levels of AKT and ERK proteins in BCa cells. Bioinformatics analysis showed that HEATR3 was significantly up-regulated in BCa, and high HEATR3 expression was associated with poor prognosis of BCa patients. In vitro experiments demonstrated that HEATR3 expression was up-regulated in BCa tissues compared with that in adjacent tissues. HEATR3 protein was also up-regulated in malignant cell lines. HEATR3 knockdown in BCa cells could inhibit cell proliferation, invasion and migration, block cell cycle and promote cell apoptosis. At the same time, HEATR3 knockdowns reduced the expression levels of p-AKT and p-ERK proteins. HEATR3 knockdown inhibits the development of BCa cells through the AKT/ERK signaling pathway. and it may become one of the most promising molecular targets for BCa treatment.

Aberrant hyper-expression of the RNA binding protein GIGYF2 in endothelial cells modulates vascular aging and function.

Vascular endothelial cells (ECs) senescence plays a crucial role in vascular aging that promotes the initiation and progression of cardiovascular disease. The mutation of Grb10-interacting GYF protein 2 (GIGYF2) is strongly associated with the pathogenesis of aging-related diseases, whereas its role in regulating ECs senescence and dysfunction still remains elusive. In this study, we found aberrant hyperexpression of GIGYF2 in senescent human ECs and aortas of old mice. Silencing GIGYF2 in senescent ECs suppressed eNOS-uncoupling, senescence, and endothelial dysfunction. Conversely, in nonsenescent cells, overexpressing GIGYF2 promoted eNOS-uncoupling, cellular senescence, endothelial dysfunction, and activation of the mTORC1-SK61 pathway, which were ablated by rapamycin or antioxidant N-Acetyl-l-cysteine (NAC). Transcriptome analysis revealed that staufen double-stranded RNA binding protein 1 (STAU1) is remarkably downregulated in the GIGYF2-depleted ECs. STAU1 depletion significantly attenuated GIGYF2-induced cellular senescence, dysfunction, and inflammation in young ECs. Furthermore, we disclosed that GIGYF2 acting as an RNA binding protein (RBP) enhances STAU1 mRNA stability, and that the intron region of the late endosomal/lysosomal adaptor MAPK and mTOR activator 4 (LAMTOR4) could bind to STAU1 protein to upregulate LAMTOR4 expression. Immunofluorescence staining showed that GIGYF2 overexpression promoted the translocation of mTORC1 to lysosome. In the mice model, GIGYF2flox/flox Cdh-Cre+ mice protected aged mice from aging-associated vascular endothelium-dependent relaxation and arterial stiffness. Our work discloses that GIGYF2 serving as an RBP enhances the mRNA stability of STAU1 that upregulates LAMTOR4 expression through binding with its intron region, which activates the mTORC1-S6K1 signaling via recruitment of mTORC1 to the lysosomal membrane, ultimately leading to ECs senescence, dysfunction, and vascular aging. Disrupting the GIGYF2-STAU1-mTORC1 signaling cascade may represent a promising therapeutic approach against vascular aging and aging-related cardiovascular diseases.

Shifted LT Code Security Scheme for Partial Information Encryption.

The existing physical layer security technology based on fountain codes needs to ensure that the legal channel is superior to the eavesdropping channel; when the quality of the legal channel and the eavesdropping channel are close, the information security cannot be guaranteed. Aiming at this problem, this paper proposes a shifted Luby transform (SLT) code security scheme for partial information encryption, which is mainly divided into two stages, partial information encryption transfer and degree distribution adjustment. The main idea is that the source randomly extracts part of the information symbols, and performs XOR encryption with the random sequence containing the main channel noise sent by the legitimate receiver. Afterward, the degree distribution is adjusted using the number of transfer information symbols received by the legitimate receiver to improve the average degree of the encoded codewords. Since the eavesdropper can only obtain fewer information symbols in the initial stage, it is difficult to decode the generated coded symbols after the degree distribution adjustment, thereby ensuring the safe transmission of information. The experimental results show that, compared with other LT anti-eavesdropping schemes, even if the legitimate channel is not dominant, the proposed scheme still has better security performance and less decoding overhead.

Arginase: An emerging and promising therapeutic target for cancer treatment.

Arginase is a key hydrolase in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. Increasing number of studies in recent years demonstrate that two mammalian arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), were aberrantly upregulated in various types of cancers, and played crucial roles in the regulation of tumor growth and metastasis through various mechanisms such as regulating L-arginine metabolism, influencing tumor immune microenvironment, etc. Thus, arginase receives increasing focus as an attractive target for cancer therapy. In this review, we provide a comprehensive overview of the physiological and biological roles of arginase in a variety of cancers, and shed light on the underlying mechanisms of arginase mediating cancer cells growth and development, as well as summarize the recent clinical research advances of targeting arginase for cancer therapy.

Arginase 2 negatively regulates sorafenib-induced cell death by mediating ferroptosis in melanoma.

Ferroptosis, a newly defined and iron-dependent cell death, morphologically and biochemically differs from other cell deaths. Melanoma is a serious type of skin cancer, and the poor efficacy of current therapies causes a major increase in mortality. Sorafenib, a multiple kinase inhibitor, has been evaluated in clinical phase trials of melanoma patients, which shows modest efficacy. Emerging evidence has demonstrated that arginase 2 (Arg2), type 2 of arginase, is elevated in various types of cancers including melanoma. To investigate the role and underlying mechanism of Arg2 in sorafenib-induced ferroptosis in melanoma, reverse transcriptase-quantitative polymerase chain reaction, western blot analysis, adenovirus and lentivirus transduction, and in vivo tumor homograft model experiments were conducted. In this study, we show that sorafenib treatment leads to melanoma cell death and a decrease in Arg2 at both the mRNA and protein levels. Knockdown of Arg2 increases lipid peroxidation, which contributes to ferroptosis, and decreases the phosphorylation of Akt. In contrast, overexpression of Arg2 rescues sorafenib-induced ferroptosis, which is prevented by an Akt inhibitor. In addition, genetic and pharmacological suppression of Arg2 is able to ameliorate the anticancer activity of sorafenib in melanoma cells in vitro and in tumor homograft models. We also show that Arg2 suppresses ferroptosis by activating the Akt/GPX4 signaling pathway, negatively regulating sorafenib-induced cell death in melanoma cells. Our study not only uncovers a novel mechanism of ferroptosis in melanoma but also provides a new strategy for the clinical applications of sorafenib in melanoma treatment.

Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases.

Ferroptosis, a recently identified and iron-dependent cell death, differs from other cell death such as apoptosis, necroptosis, pyroptosis, and autophagy-dependent cell death. This form of cell death does not exhibit typical morphological and biochemical characteristics, including cell shrinkage, mitochondrial fragmentation, nuclear condensation. The dysfunction of lipid peroxide clearance, the presence of redox-active iron as well as oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids are three essential features of ferroptosis. Iron metabolism and lipid peroxidation signaling are increasingly recognized as central mediators of ferroptosis. Ferroptosis plays an important role in the regulation of oxidative stress and inflammatory responses. Accumulating evidence suggests that ferroptosis is implicated in a variety of cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure, indicating that targeting ferroptosis will present a novel therapeutic approach against cardiovascular diseases. Here, we provide an overview of the features, process, function, and mechanisms of ferroptosis, and its increasingly connected relevance to oxidative stress, inflammation, and cardiovascular diseases.

Influence of CMTM8 polymorphisms on lung cancer susceptibility in the Chinese Han population.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide and CMTM8 is a potential tumor suppressor gene, which is down-regulated in lung cancer. The objective of this research was to assess the association of CMTM8 genetic polymorphisms with lung cancer risk. METHODS: To evaluate the correlation between CMTM8 polymorphisms and lung cancer risk, Agena MassArray platform was used for genotype determination among 509 lung cancer patients and 506 controls. Multiple genetic models, stratification analysis and Haploview analysis were used by calculating odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Significant associations were detected between CMTM8 rs6771238 and an increased lung cancer risk in codominant (adjusted OR = 1.57, 95% CI: 1.01-2.42, P = 0.044) and dominant (adjusted OR = 1.54, 95% CI: 1.01-2.36, P = 0.047) models. After sex stratification analysis, we observed that rs6771238 was related to an increased risk of lung squamous cell carcinoma, while rs6771238 was associated with an increased risk of lung adenocarcinoma. Rs9835916 was linked to increased risk of lymph node metastasis in lung cancer patients. CONCLUSION: Our study first reported that CMTM8 polymorphisms were a risk factor for lung cancer, which suggested the potential roles of CMTM8 in the development of lung cancer.

Genetic variation of pharmacogenomic VIP variants in Zhuang nationality of southern China.

Drug gene polymorphisms are strongly associated with disease. Previous studies have shown that the frequency of drug genes varies in different populations. At present, there are no reports about the polymorphism of the drug genome in the Zhuang population in southern China. This study conducted a pharmacogenomics study on the Zhuang population in southern China. Therefore, we conducted genotyping on 105 Zhuang samples, and compared the genotyping results with those of other 11 ethnic groups after statistical analysis. Our results show that, compared with the 11 populations in the HapMap data set, the differences between the CYP2E1 rs2070676 and CYP2D6 rs1065852 of the Zhuang nationality are the largest. This study fills in the blank of the drug genome information of the Zhuang nationality in southern China. The two sites of Rs2070676 (CYP2E1) and rs1065852 (CYP2D6) provide a reliable basis for the prediction of the efficacy of certain drugs. Its main purpose is to provide theoretical basis for safe drug use in the Zhuang region of southern China.

Variants in multiple genes are associated with esophageal cancer risk in a Chinese Han population: A case-control study.

BACKGROUND: The present study investigated whether 16 single nucleotide polymorphisms (SNPs), selected based on minor allele frequencies, Hardy-Weinberg equilibrium and reported SNPs related to the susceptibility of certain gastrointestinal cancer, were associated with esophageal cancer (EC) risk in a Chinese Han population. METHODS: We genotyped 16 SNPs among 506 cases and 507 controls using Agena MassARRAY (Agena, San Diego, CA, USA). The association between 16 SNPs and EC risk was analyzed by a chi-squared test and genetic model analysis. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: rs1050631 and the rs6214 were associated with a decreased EC risk (OR = 0.75, p = 0.038; OR = 0.74, p = 0.045, respectively). In stratification analysis, the rs9868873 was associated with an increased EC risk (age < 64 years) (OR = 5.03, p = 0.005). The rs6214 was associated with a decreased EC risk (age < 64 years) (OR = 0.59, p = 0.025). The rs861530 was significantly associated with a decreased EC risk (age ≥ 64 years) (OR = 0.67, p = 0.046). rs1050631 was associated with a decreased EC risk in males (OR = 0.71, p = 0.034). In the stratified analysis of clinical stage III/IV, the rs1800566 was associated with a decreased EC risk (OR = 0.49, p = 0.024). Finally, the rs1052133 was associated with an elevated EC risk in the stratified analysis of lymph node metastasis (OR = 1.73, p = 0.025). CONCLUSIONS: The findings of the present study demonstrate that SLC39A6, IGF1, SEMA5B, XRCC3, NQO1 and OGG1 polymorphisms were associated with EC risk under multiple models.

Impact of IL1R1 polymorphisms on the risk of head and neck cancer in Chinese Han population.

AIM: The incidence of head and neck cancer (HNC) is increasing but its pathogenic factors are complex. Changes in both internal (genetic) and external (environmental) causes HNC to some extent. The purpose of our study was to investigate the influence of IL1R1 polymorphisms on HNC risk in Chinese Han population. METHODS: Genotypes of 535 HNC patients and 538 healthy controls were analyzed by Agena MassARRAY. Odds ratio (ORs) and 95% confidence interval (CIs) were calculated by logistic regression analysis to evaluate the relationship between single nucleotide polymorphisms (SNPs) and HNC susceptibility. RESULTS: It was found that the rs956730 of IL1R1 reduced the risk of HNC in multiple models (allele: OR = 0.76, 95% CI: 0.62-0.93, p = 0.008; codominant: OR = 0.43, 95% CI: 0.25-0.75, p = 0.003; recessive: OR = 0.45, 95% CI: 0.26-0.77, p = 0.004; additive: OR = 0.77, 95% CI: 0.63-0.94, p = 0.01). IL1R1 rs956730 had a protective effect on HNC at age ≤ 46. However, the rs3917225 increased a 1.31-fold HNC risk in the codominant model (OR = 1.31, 95% CI: 1.00-1.70, p = 0.03). CONCLUSION: Our study showed that the rs956730 of IL1R1 gene in Chinese Han population was associated with a reduced risk of HNC, while the rs3917225 of IL1R1 might increase the risk of HNC.

Polymorphisms in IL-1A are associated with endometrial cancer susceptibility among Chinese Han population: A case-control study.

Endometrial cancer (EC) is one of the most common malignant tumours of the female genital tract, and it has become a serious malignant disease of the female genital tract in China. Existing researches have revealed the association between polymorphisms of IL-1A and several gynaecological diseases. In this research, we analysed the association between IL-1A gene polymorphisms and endometrial cancer susceptibility in Chinese female population. A total of 81 patients and 198 healthy people were selected. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. Genetic models and analyses showed that IL-1A rs3783550 TT and rs3783546 CC increased the risk of endometrial cancer under the recessive model, respectively (rs3783550: OR = 2.80, 95%CI: 1.32-5.92, p = .008; rs3783546: OR = 2.79, 95%CI: 1.32-5.89, p = .008). In the recessive model, we also found that both IL-1A rs1609682 and IL-1A rs3783521 increased the risk of endometrial cancer, respectively (rs1609682: OR = 2.79, 95%CI: 1.32-5.89, p = .0081; rs3783521: OR = 2.80, 95%CI: 1.32-5.92, p = .008). Haplotype analysis was performed that did not reveal any significant results. In summary, IL-1A rs3783550, rs3783546, rs1609682 and rs3783521 polymorphisms may be associated with an increased risk of endometrial cancer in Chinese female populations.

Association between ACYP2 polymorphisms and the risk of renal cell cancer.

BACKGROUND: Kidney cancer is the predominant form of malignancy of the kidney and accounts for approximately 3%-4% of all cancers. Renal cell cancer (RCC) represents more than 85% of kidney cancer. It has been reported that genetic factors may predispose individuals to RCC. This study evaluated the association between Acylphosphatase 2 (ACYP2) gene polymorphisms and RCC risk in the Han Chinese population. METHODS: Twelve single-nucleotide polymorphisms (SNPs) in ACYP2 were genotyped using the Agena MassARRAY platform from 293 RCC patients and 495 controls. The Chi-squared test, genetic models, haplotype, and stratification analyses were used to evaluate the association between SNPs and the risk of RCC. The relative risk was estimated using the odds ratio (OR) and 95% confidence interval (CI). RESULTS: We observed that the rs6713088 allele G (OR = 1.26, 95% CI: 1.03-1.53, p = .023) and rs843711 allele T (OR = 1.29, 95% CI: 1.06-1.57, p = .010) were associated with increased RCC risk. Genetic model analyses found that rs843711 was significantly associated with an increased RCC risk under the recessive model and log-additive model after adjusting for age and gender. Haplotype analysis showed that the haplotype "TTCTCGCC" (OR = 0.67, 95% CI: 0.48-0.94, p = .021) was associated with a decreased risk of RCC in the Han Chinese population. Stratification analysis also found that rs6713088 and rs843711 were significantly associated with increased RCC risk. CONCLUSION: In summary, the results suggested that ACYP2 polymorphisms could be used as a genetic marker for RCC. Additional functional and association studies are required to validate our results.

LPP and RYR2 Gene Polymorphisms Correlate with the Risk and the Prognosis of Astrocytoma.

Astrocytoma is the most common neuroepithelial tumor. Genetic factors play an important role in the development and prognosis of astrocytoma. So this study focuses on the impact of LPP and RYR2 genes on the occurrence and prognosis of astrocytoma. Rs12594 and rs16835904 in the RYR2 gene and rs1064607, rs3796283, and rs2378456 in the LPP gene were selected and genotyped using Agena MassARRAY in 365 patients and 379 healthy populations. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression to assess the influence of gene polymorphisms on occurrence of astrocytoma. The association between genotype and survival outcomes was performed by the Kaplan-Meier method, the log-rank test, and the Cox regression analysis. The survival rates of patients receiving gross total resection and postoperative chemotherapy were higher than patients receiving near total resection and subtotal resection and without chemotherapy. In recessive model, the patients with LPP rs2378456 CC genotype increased the risk of astrocytoma (OR = 1.43, 95% CI 1.01-2.02, p = 0.042). Stratified analysis shows that RYR2 rs16835904 TC-TT genotype facilitated the risk of astrocytoma in male (OR = 1.93, 95% CI 1.15-3.24, p = 0.011). Cox regression analysis shows that RYR2 rs12594 AA genotype and AG genotype were associated with OS of astrocytoma (AG genotype: HR = 1.62, 95% CI 1.04-2.53, p = 0.034; AA genotype: HR = 1.70, 95% CI 1.08-2.68, p = 0.021). RYR2 and LPP genes were found to affect the occurrence and prognosis of astrocytoma.

TIMP3 gene polymorphisms and relation to Ankylosing spondylitis susceptibility in Chinese Han population.

BACKGROUND: Ankylosing spondylitis (AS) is a type of chronic progressive inflammatory disease, which often causes significant damage to the patients on the physical function, labour ability and quality of life. The study found that the enzyme system tissue inhibitor of matrix metalloproteinases (TIMPs) was important for the development of AS. The aim of this study was to investigate the association of polymorphisms of TIMP3 gene with AS in Chinese Han population. METHODS: To evaluate the correlation of TIMP3 polymorphisms with AS risk, Agena MassARRAY was used to determine the genotypes of 268 AS patients and 654 controls. The correlation between TIMP3 variants and AS risk was examined by unconditional logistic regression analysis. Haplotype construction and analysis in TIMP3 were also applied to detect the potential association. RESULTS: We identified that rs11547635 in the TIMP3 gene (odds ratio[OR] = 0.79, 95% confidence intervals [CI]: 0.63-0.98, p = .029) was significantly associated with a decreased risk of AS in the alleles model. Rs715572 AG genotype (OR = 1.57, 95% CI: 1.05-2.34, p = .041) was potentially associated with an increased risk of AS, and also rs715572 in the dominant model (OR = 1.61, 95% CI: 1.10-2.36, p = .013) and log-additive model (OR = 1.41, 95% CI: 1.07-1.86, p = .016) adjusted by age and gender were significantly correlated with an increased AS risk. CONCLUSION: These findings suggested that polymorphisms of the TIMP3 gene may be associated with susceptibility to AS.

Correlation of EYS polymorphisms with lumbar disc herniation risk among Han Chinese population.

BACKGROUND: Lumbar disc herniation (LDH) is a common spinal disease in clinical practice. Once lumbar disc herniation occurs, it seriously reduces patient's quality of life. The EYS (eyes shut homolog) was discovered in recent years and it may be related to lumbar disc herniation. So we conducted a case-control study to explore the relationship between EYS polymorphism and lumbar disc herniation risk. METHODS: We selected 5 single-nucleotide polymorphisms (SNPs) of EYS gene in a case-control study with 508 cases and 508 healthy controls to evaluate the relatedness by using genetic model, haplotype, and stratification analysis. RESULTS: We found that the minor alleles of rs62413038 (OR = 1.21, 95%CI: 1.01-1.43, p = .036) and rs9450607 (OR = 1.26, 95% CI: 1.05-1.53, p = .016) were associated with an increased risk of lumbar disc herniation in the allelic model analysis. In the genotypic model analysis, rs62413038 displayed a significantly increased risk of lumbar disc herniation in log-additive models (OR = 1.20, 95% CI: 1.01-1.43, p = .039). While the rs9450607 was also obviously associated with an increased lumbar disc herniation risk in recessive (OR = 1.98, 95% CI: 1.24-3.13, p = .004) and log-additive models (OR = 1.27, 95% CI: 1.05-1.55, p = .014). In addition, in the haplotype analyses of the SNPs, we found that the "CGGA" haplotype of rs1482456, rs9342097, rs9450607, and rs7757884 was associated with lumbar disc herniation. (OR = 0.52, 95% CI: 0.30-0.89, p = .017). CONCLUSION: These results suggest that EYS polymorphism may be associated with lumbar disc herniation among Han Chinese population. It also opens up a new exploration direction for the etiology of lumbar disc herniation.

Association between IL1B gene and cervical cancer susceptibility in Chinese Uygur Population: A Case-Control study.

BACKGROUND: Interleukin-1ß (IL-1B) has been recognized as a pro-inflammatory cytokine and associated with tumorigenesis. We aimed to evaluate the contribution of IL-1B polymorphisms to the susceptibility of cervical cancer in Chinese Uygur population. METHODS: Seven variants were genotyped by Agena MassARRAY platform in 267 cervical cancer patients and 302 healthy controls. Allelic, genotypic, and haplotypic association analyses adjusted for age were investigated using odds ratios (OR) and 95% confidence intervals (CI). GEPIA and UALCAN databases were used to evaluate expression and prognostic of IL-1B gene in cervical cancer. RESULTS: Our result revealed IL-1B rs1143627-AA (OR = 1.98, p = 0.029) and rs16944-GG (OR = 2.01, p = 0.025) was associated with an increased risk of cervical cancer. Besides, we also found two protective single nucleotide polymorphisms (SNPs) rs3136558 (OR = 0.63, p = 0.011) and rs1143630 (OR = 0.63, p = 0.019). Haplotype ″TGA″ in the block (rs1143630, rs1143627, and rs16944) significantly decreased the susceptibility of cervical cancer (OR = 0.53, p = 0.0007). IL-1B mRNA level was up-regulated in the cervical cancer patients, which was related with poor prognosis in silico. CONCLUSIONS: For the first time, our results provide evidence on polymorphism of IL-1B gene associated with cervical cancer risk in Chinese Uygur population.

Assessment of the association between ACYP2 and laryngeal squamous cell carcinoma risk in Chinese males.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant neoplasms of the upper respiratory tract. Studies have confirmed that an unstable chromosome constitution promotes the progress of laryngeal tumorigenesis, and ACYP2 has been confirmed as a telomere length-related gene. However, to date, the association between ACYP2 polymorphisms and LSCC susceptibility has not been investigated. METHODS: We performed this study to explore the effect of 11 single-nucleotide polymorphisms (SNPs) in ACYP2 on LSCC susceptibility in Chinese Han males. Unconditional logistic regression analysis adjusted for age was used to calculate the odds ratios and 95% confidence intervals. RESULTS: Based on allele and genotype models, our results showed that rs1682111 variant was significantly associated with a decreased LSCC susceptibility (p < 0.05). On the contrary, polymorphisms of rs10439478, rs11125529, rs12615793, rs843711, rs11896604, and rs17045754 were significantly associated with an increased LSCC risk (p < 0.05). The results of haplotype analysis indicated that haplotypes "TTCTCG" and "TTCTAA" in block 1 and "TG" in block 2 showed a risk factor for the development of LCSS (p = 0.009, p < 0.001, and p = 0.001, respectively). The results of Genotype-Tissue Expression analysis indicate that these significant SNPs were known to be associated with ACYP2 expression. CONCLUSION: Our data demonstrated that ACYP2 polymorphisms may exert effects on LSCC susceptibility in Chinese Han males.

Associations between polymorphisms of the ACYP2 gene and Liver cancer risk: A case-control study and meta-analysis.

BACKGROUND: ACYP2 gene may be involved in the process of telomere shortening which may be involved in the liver cancer. So, this research was to examine whether the ACYP2 gene polymorphism has impact on the risk of liver cancer in Chinese population. METHODS: Two hundred and fifty cirrhosis patients and 248 liver cancer patients were selected. Unconditional logistic regression was to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Analyze the relationship between ACYP2 gene polymorphism and tumor using meta-analysis. Analyze the expression of ACYP2 gene in liver cancer and its influence on the prognosis of liver cancer by databases (Ualcan, GTEX and Kaplan-Meier plotter). RESULTS: In the allele model, ACYP2 rs843720 was protection against the occurrence of cirrhosis developed into liver cancer (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04). Rs1682111 and rs843720 play a protective role in the additive model (rs1682111: OR = 0.69, 95% CI: 0.52-0.93, p = 0.01; rs843720: OR = 0.73, 95% CI: 0.54-0.98, p = 0.04).While rs843645 G allele increased the risk of cirrhosis developed into liver cancer under the additive model (OR = 1.42, 95% CI: 1.02-2.00, p = 0.04).The haplotype analysis detected that "ATATCGCC" decreased the risk of cirrhosis developed into liver cancer (OR = 0.69, 95% CI: 0.51-0.92, 95% CI: p = 0.013); however, "TGAGCGTC" increased the risk of cirrhosis developed into liver cancer (OR = 1.48, 95% CI: 1.04-2.10, p = 0.027). Meta-analysis shown that ACYP2 rs1682111 was associated with the risk of cancer (OR = 0.90, 95% CI: 0.78-1.05, p = 0.02). ACYP2 gene high expression was found to be associated with better OS for all liver patients. CONCLUSION: Based on this research, we surmised that ACYP2 gene may be involved in the occurrence of liver cancer in Chinese populations.

Association of glypican-6 polymorphisms with lumbar disk herniation risk in the Han Chinese population.

BACKGROUND: Lumbar disk herniation (LDH) is a degenerative disorder, which partly results from complex genetic factors. The aim of the study was to investigate the potential associations between glypican-6 (GPC6) variants and LDH risk in Han Chinese population. METHODS: A total of 508 Han Chinese LDH patients and 508 healthy controls were recruited in this study. Six single-nucleotide polymorphisms (SNPs) in GPC6 were selected and genotyped using an Agena MassARRAY platform. We used logistic regression method to evaluate the linkage between GPC6 variants and LDH risk by calculating the odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. HaploReg database was used for SNP functional annotation. RESULTS: Our result revealed GPC6 rs4773724 was associated with a decreased risk of LDH in allele model (OR = 0.82, 95% CI: 0.68-0.98, p = 0.026), whereas rs1008993 increased the LDH risk (OR = 1.34, 95% CI: 1.05-1.71, p = 0.020). Besides, we also found rs4773724 and rs9523981 were associated with susceptibility of LDH among individuals whose age are less than 45. And rs1008993 was associated with increased LDH risk in males. Furthermore, Haplotype analysis showed that the TT (rs4773724, rs1008993) haplotype and GC (rs4773724, rs1008993) haplotype had the opposite effects on the susceptibility of LDH. CONCLUSIONS: For the first time, we suggest that rs4773724 and rs1008993 in GPC6 were considered as a protective factor and a risk factor for LDH in Han Chinese population, respectively. These results provide new ideas for the treatment and prevention of LDH in Han Chinese population.