Hsa_circ_0008833 promotes COPD progression via inducing pyroptosis in bronchial epithelial cells.

Purpose: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder. Pyroptosis represents a distinctive form of inflammatory cell death that is mediated through the activation of Caspase-1 and inflammasomes. CircRNAs have emerged as a novel class of biomolecules with implications in various human diseases. This study aims to investigate the circRNAs profile of in COPD progression and identify pivotal circRNAs associated with the development of this disease. Methods: he expression profiles of circRNAs in peripheral blood mononuclear cells of COPD patients were assessed by circRNA microarray. Furthermore, flag-labeled vectors were constructed to assess the potential protein-coding capacity of has-circ-0008833. 16HBE cells were stably transfected with lentivirus approach, and cell proliferation and death were assessed to clarify the functional roles of has-circ-0008833 and its encoded protein circ-0008833aa. Additionally, western blot analysis was furthered performed to determine the level of Caspase-1, IL-18, IL-1ß, NLRP3, ASC, and cleaved GSDMD regulated by has-circ-0008833 and circ-0008833-57aa. Results: Initially, we screened the expression profiles of human circRNAs in peripheral blood mononuclear cells of COPD patients, and found that has-circ-0008833 exhibited a significant increase in COPD mononuclear cells. Subsequently, we demonstrated that has-circ-0008833 carried an open reading frame (ORF), which encoded a functional protein, referred to as circ-0008833-57aa. By employing gain-of-function approaches, our results suggested that both circ-0008833 and circ-0008833-57aa inhibited proliferation, but accelerated the rate of 16HBE cell death. Finally, we discovered that circ-0008833 and circ-0008833-57aa promoted the expression of Caspase-1, IL-18, IL-1ß, NLRP3, ASC, and cleaved GSDMD in 16HBE cells. Conclusions: Upregulation of circ-0008833 might promote COPD progression by inducing pyroptosis of bronchial epithelial cells through the encoding of a 57-amino acid peptide.

Association of CYP4A22 gene polymorphisms with cerebral stroke risk in the Chinese Han population.

BACKGROUND: Cerebral stroke (stroke) is an acute cerebrovascular disease with high incidence and mortality. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of CYP4A22 and stroke risk in the Chinese Han population. METHODS: A total of 550 stroke patients and 545 healthy people were recruited. Four candidate SNPs (rs76011927 T/C, rs12564525 C/T, rs2056900 A/G and rs4926581 T/G) of CYP4A22 were screened. The association between CYP4A22 SNPs and stroke risk was assessed using genetic models and the relationship between SNPs and clinical biochemical indicators was analyzed by one-way analysis of variance (one-way ANOVA). RESULTS: The overall analysis showed that rs12564525 could significantly reduce stroke risk only under the recessive model (OR = 0.72, 95% CI 0.53-0.99), but rs2056900 and rs4926581 were significantly associated with increased stroke risk under the homozygote (OR = 1.49, 95% CI 1.06-2.09; OR = 1.49, 95% CI 1.06-2.10), heterozygote (OR = 1.49, 95% CI 1.11-2.00; OR = 1.48, 95% CI 1.11-1.99), additive (OR = 1.22, 95% CI 1.03-1.45; OR = 1.22, 95% CI 1.03-1.45) and dominant (OR = 1.49, 95% CI 1.13-1.97; OR = 1.49, 95% CI 1.13-1.96) models (all p < 0.05). Subgroup analyses further indicated that rs2056900 and rs4926581 could significantly increase stroke risk in participants aged >63 years and females. In addition, high-density lipoprotein cholesterol (HDL-C) levels differed considerably among different genotypes of rs12564525, rs2056900 and rs4926581. CONCLUSIONS: This study revealed that CYP4A22 SNPs are associated with stroke risk in the Chinese Han population, and in particular, rs2056900 and rs4126581 have a significant correlation with increased stroke risk.

Suggestive evidence of genetic association of IL23R polymorphisms with chronic obstructive pulmonary disease risk in the Chinese population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a worldwide public health problem. Previous genetic association studies have identified several susceptibility loci in the interleukin genes that may participate in the nosogenesis of COPD. This study aimed to evaluate the relationship between IL23R loci and COPD susceptibility in the Chinese population. METHODS: Agena MassARRAY technology was applied to genotype five single nucleotide polymorphisms (SNPs) in the IL23R gene in 498 COPD patients and 498 healthy people. The association between IL23R SNPs and COPD risk was calculated by logistic regression analysis, with odds ratios and 95% confidence intervals. The false-positive report probability analysis was noteworthy for evaluating the significant results. Also, haplotype analysis was performed among IL23R variants, and multifactor dimensionality reduction analysis was performed to assess the SNP-SNP interactions to predict the risk of COPD. RESULTS: Overall analysis showed that rs7517847 had a significant association with an increased risk of COPD. Age-stratified analysis revealed that rs7517847 was significantly related to an increased risk of COPD in people aged over 68 years old. Sex-stratified analysis illustrated a significant association between rs2295359 and rs7517847 and COPD risk in the female population. The significant association of COPD risk with IL23R SNPs was assessed by false-positive report probability values. Additionally, we observed that the haplotypes AAC and GGA formed by rs2201841, rs12743974 and rs10889677 were associated with a reduced risk of COPD (p = 0.009, p = 0.026). Also, the five-loci interaction model formed by rs2295359, rs7517847, rs2201841, rs12743974 and rs10889677 became the best predictor of COPD, with 10/10 cross-validation consistency and 52.4% testing balance accuracy. CONCLUSION: The research indicated a remarkable association between IL23R variants and COPD susceptibility in the Chinese population. Larger samples and functional research are required to ascertain the relationship between IL23R variants and COPD susceptibility.

Association of the L3MBTL3 rs1125970 and rs4897367 Gene Polymorphisms With Coronary Heart Disease Susceptibility in the Chinese Population: A Case-Control Study.

ABSTRACT: Coronary heart disease (CHD) is a prevalent heart disease with high incidence and mortality rates worldwide, and its pathogenesis is related to genetic factors. L3MBTL3 has been reported to be potentially linked to CHD susceptibility. This study aims to explore the correlation between L3MBTL3 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese population. Three SNPs (rs1125970 A/T, rs4897367 T/C, and rs2068957 A/G) in L3MBTL3 from 649 patients with CHD and 649 healthy controls were genotyped using the Agena MassARRAY platform. The relationship between SNPs and CHD risk was evaluated by logistic regression analysis. Our study indicated that rs1125970 (TT: odds ratio [OR] = 0.76, P = 0.014) and rs4897367 (TT: OR = 0.74, P = 0.021) were related to a decreased susceptibility to CHD. Stratified analyses showed that rs1125970 could reduce the risk of CHD in males, subjects aged <60 years, with a body mass index <24 kg/m 2 , and nonhypertensive patients. rs4897367 exerted a risk-decreasing influence on CHD in nondiabetic patients. In the haplotype analysis, individuals with the T rs4897367 A rs2068957 haplotype were less likely to develop CHD (OR = 0.74, P = 0.024). In summary, L3MBTL3 rs1125970 and rs4897367 were significantly correlated with a decreased susceptibility to CHD in the Chinese population.

Association of FHL5 and LPA genetic polymorphisms with diabetes mellitus risk: a case-control study.

BACKGROUND: China is one of the countries with the fastest growing prevalence of diabetes mellitus (DM) in the world. This study intended to investigate the association of single nucleotide polymorphisms (SNPs) of FHL5 and LPA with DM risk in the Chinese population. METHODS: This case-control study involved 1,420 Chinese individuals (710 DM patients and 710 controls). Four candidate loci (rs2252816/rs9373985 in FHL5 and rs3124784/rs7765781 in LPA) were successfully screened. The association of SNPs with DM risk was assessed by logistic regression analysis. Differences in clinical characteristics among subjects with different genotypes were analyzed by one-way analysis of variance. RESULTS: Overall analysis indicated that rs3124784 was associated with an increased risk of DM. Stratification analysis showed that rs3124784 significantly increased DM risk in different subgroups (male, non-smoking, non-drinking, and BMI > 24), while rs7765781 increased DM risk only in participants with BMI ≤ 24. Rs2252816 was associated with the course of DM. We also found that rs2252816 GG genotype and rs9373985 GG genotype were linked to the increased cystatin c in DM patients. CONCLUSION: The genetic polymorphisms of LPA may be associated with DM risk in the Chinese population, which will provide useful information for the prevention and diagnosis of DM.

The Study of the Influence of IL5RA Variants on Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a complex disease, and its pathogenesis is influenced by genetic factors. This study aimed to evaluate the role of IL5RA genetic variation in the risk of COPD. In this study, 498 patients with COPD and 498 normal controls were recruited. Subsequently, five SNPs (rs3804795, rs2290610, rs13097407, rs334782, and rs3856850) in the IL5RA gene were genotyped. Logistic analysis examined the association of five single nucleotide polymorphisms (SNPs) in IL5RA with the risk of COPD under various genetic models. Furthermore, the association between IL5RA and susceptibility to COPD was comprehensively analyzed with stratification based on age, sex, smoking, and alcohol consumption. Our study showed that IL5RA rs13097407 reduced susceptibility to COPD (OR = 0.43, p < 0.001, p (FDR)< 0.001). On the other hand, rs3856850 was associated with an increased risk of COPD (OR = 1.71, p = 0.002, p (FDR) = 0.002). Interestingly, the effect of IL5RA SNPs on susceptibility to COPD was found to be influenced by factors such as sex and smoking. IL5RA gene variants were significantly associated with susceptibility to COPD.

Genome-wide association study of serum tumor markers in Southern Chinese Han population.

BACKGROUND: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers. METHODS: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci. RESULTS: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037. CONCLUSION: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.

C5orf66 rs4976270/rs639933 Are Associated with Colorectal Cancer Risk in Southern Chinese Han Population: A Case-Control Study.

BACKGROUND: Colorectal cancer (CRC) is one of the common malignant tumors, with high mortality and poor prognosis. Our study aimed to determine the association between the long noncoding RNA (LncRNA) C5orf66 polymorphism and CRC risk in southern Chinese Han population. METHOD: Using the experimental design of "case-control" study (512 cases and 513 controls), we selected 4 candidate single-nucleotide polymorphisms (SNPs) of C5orf66. All candidate SNPs were genotyped by Agena MassARRAY. Logistic regression was used to analyze the association between SNPs and CRC risk. Then, we used false-positive report probability analysis to detect whether the significant result is just a chance or noteworthy observation. Multi-factor dimensionality reduction was used to analyze the interaction of "SNP-SNP" in CRC risk. RESULTS: Our results showed that C5orf66 SNPs rs4976270 (odds ratio [OR] = 1.69, p = 0.021) and rs639933 (OR = 1.67, p = 0.024) were, respectively, associated with increasing CRC risk in the southern Chinese Han population. Stratified analysis showed that rs4976270 and rs639933 were significantly associated with an increased risk of CRC in subgroups (>60 years, body mass index ≤24 and drinking) under multiple genetic models. In addition, rs254563 and rs647161 also had potential association with CRC risk in subgroups (BMI ≤24 and drinking). Finally, haplotype analysis results showed that haplotype "TA" was significantly associated with increased CRC risk (OR = 1.21, confidence interval = 1.47-2.02, p = 0.043). CONCLUSION: Our study provides a new idea for the risk assessment of CRC. LncRNA C5orf66 SNPs have a certain association with CRC risk in the southern Chinese Han population.

Diagnostic value and safety of medical thoracoscopy under local anesthesia for unexplained diffuse interstitial lung disease: A retrospective study.

OBJECTIVE: We aimed to explore the safety and diagnostic value of medical thoracoscopic lung biopsy in patients with unexplained diffuse interstitial lung disease (ILD) in a single center pilot study. METHOD: We retrospectively analyzed clinical and pathological diagnostic data from 52 patients with diffuse ILD undergoing medical thoracoscopic lung biopsy. RESULTS: Forty-four cases of diffuse ILD were confirmed pathologically, giving a diagnostic rate of 84.6%. Among these 44 patients, 11 patients were diagnosed with cancer, including eight patients with lung adenocarcinoma, three patients with metastases; two from a gastrointestinal malignancy, and one from a granulosa cell tumor of the ovary. There were 17 cases of idiopathic interstitial pneumonia, including nine cases of usual interstitial pneumonia (UIP), four cases of non-specific interstitial pneumonia (NSIP), three cases of cryptogenic organizing pneumonia (COP), and one case of acute interstitial pneumonia (AIP). There were 12 cases of rare interstitial pneumonias, which included six cases of pulmonary alveolar proteinosis, one case each of pulmonary Langerhans cell histiocytosis (LCH) and pulmonary lymphangiomyomatosis, two cases of nodular sarcoidosis, and two cases of chronic eosinophilic pneumonia. We recorded various complications, including bleeding, infection, and pneumothorax. A total of 28 patients (53.8%) experienced at least one of the above complications, but there were no deaths associated with biopsy. CONCLUSIONS: Medical thoracoscopic lung biopsy appears a safe and effective method for diagnosing diffuse ILD of unknown cause but further prospective studies, with larger numbers, including comparison with other established techniques are required.

The polymorphisms of FGFR2 and MGAT5 affect the susceptibility to COPD in the Chinese people.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by incomplete reversible airflow limitation and chronic inflammatory response lesions. This study mainly explored whether FGFR2 and MGAT5 polymorphisms affected the risk of COPD in the Chinese people. METHODS: Five variants in FGFR2 and MGAT5 were chosen and genotyped using Agena MassARRAY platform from 315 COPD patients and 314 healthy controls. The correlation of FGFR2 and MGAT5 with COPD susceptibility was evaluated with odds ratio (OR) and 95% confidence interval (CI) via logistic regression. RESULTS: We found rs2420915 enhanced the risk of COPD, while rs6430491, rs2593704 reduced the susceptibility of COPD (p < 0.05). Rs2420915 could promote the incidence of COPD in the elderly and nonsmokers. Rs1907240 and rs2257129 also increased the susceptibility to COPD in nonsmokers (p < 0.05). MGAT5-rs2593704 played a protective role in COPD development in different subgroups (age ≤ 70, male, smokers, and individuals with BMI ≤ 24 kg/m2). Meanwhile, rs6430491 was linked with a lower risk of COPD in nonsmoking and BMI ≤ 24 kg/m2 subgroups. CONCLUSIONS: We concluded that FGFR2 and MGAT5 genetic polymorphisms are correlated with the risk of COPD in the Chinese people. These data underscored the important role of FGFR2 and MGAT5 gene in the occurrence of COPD and provided new biomarkers for COPD treatment. TRIAL REGISTRATION: NA.

LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. METHODS: Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. RESULTS: LINC01414 rs699467 (OR = 0.73, 95% CI 0.56-0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31-0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31-6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). CONCLUSION: Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

The effect of CYP3A4 genetic variants on the susceptibility to chronic obstructive pulmonary disease in the Hainan Han population.

PURPOSE: Genetic polymorphisms act a crucial role in chronic obstructive pulmonary disease (COPD) progression. This study aimed to investigate the correlation between CYP3A4 variants and COPD risk. METHODS: We carried out a case-control study of 821 individuals (313 patients and 508 healthy subjects) to identify the correlation of CYP3A4 SNPs with COPD risk in the Hainan Han population. The association was evaluated by Odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Our study showed that rs4646437 polymorphism was related to a significantly increased susceptibility to COPD (OR 1.45, 95% CI = 1.10-1.90, p = 0.008). Stratified analyses indicated that rs4646437 polymorphism was significantly related to an increased risk of COPD in males (OR 1.95, 95% CI = 1.19-3.20, p = 0.008). However, rs4646440 played a protective role in females (OR 0.54, 95% CI = 0.31-0.93, p = 0.024). Rs4646437 was found to significantly improve the risk of COPD in smokers (OR 1.67, 95% CI = 1.12-2.48, p = 0.011). While rs4646440 had a significantly lower susceptibility to COPD in non-smokers (OR 0.64, 95% CI = 0.45-0.90, p = 0.010). Haplotype analysis revealed that Ars4646440Trs35564277 haplotype of CYP3A4 was found to increase the risk of COPD in non-smokers (OR 1.71, 95% CI = 1.04-2.82, p = 0.034). CONCLUSION: Our result gives a new understanding of the association between CYP3A4 gene and COPD in the Hainan Han population.

The correlation between CYP4F2 variants and chronic obstructive pulmonary disease risk in Hainan Han population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disease. Cytochrome P450 family 4 subfamily F member 2 (CYP4F2) belongs to cytochrome P450 superfamily of enzymes responsible for metabolism, its single nucleotide polymorphisms (SNPs) were reported to be involved in metabolism in the development of many diseases. The study aimed to assess the relation between CYP4F2 SNPs and COPD risk in the Hainan Han population. METHOD: We genotyped five SNPs in CYP4F2 in 313 cases and 508 controls by Agena MassARRAY assay. The association between CYP4F2 SNPs and COPD risk were assessed by χ2 test and genetic models. Besides, logistic regression analysis was introduced into the calculation for odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Allele model analysis indicated that rs3093203 A was significantly correlated with an increased risk of COPD. Also, rs3093193 G and rs3093110 G were associated with a reduced COPD risk. In the genetic models, we found that rs3093203 was related to an increased COPD risk, while rs3093193 and rs3093110 were related to a reduced risk of COPD. After gender stratification, rs3093203, rs3093193 and rs3093110 showed the association with COPD risk in males. With smoking stratification, rs3093144 was significantly associated with an increased risk of COPD in smokers. CYP4F2 SNPs were significantly associated with COPD risk. CONCLUSIONS: Our findings illustrated potential associations between CYP4F2 polymorphisms and COPD risk. However, large-scale and well-designed studies are needed to determine conclusively the association between the CYP4F2 SNPs and COPD risk.

Genetic Polymorphisms of CYP2C9/CYP2C19 in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a high incidence in the elderly and significantly affects the quality of life. CYP2C9 and CYP2C19 play an important role in tobacco-related diseases and inflammatory reactions. Thus, we aim to investigate the association between CYP2C9/CYP2C19 polymorphisms and the risk of COPD. In this study, a total of 821 subjects were recruited which include 313 COPD cases and 508 healthy controls. Seven SNPs of CYP2C9/CYP2C19 were selected for genotyping. The odds ratios (ORs) and 95% confidence interval (95% CI) were calculated using logistic regression analysis to evaluate the association between COPD risk and CYP2C9/CYP2C19 polymorphisms. Our study showed that A allele of rs9332220 in CYP2C9 was associated with reducing COPD risk (OR = 0.64, 95% CI = 0.43-0.94, p = 0.021). And rs111853758 G allele carrier could significantly decrease 0.35-fold COPD risk compared with T allele carrier (OR = 0.65, 95% CI = 0.45-0.96, p = 0.027). Furthermore, sex-based stratification analysis showed that rs9332220 and rs111853758 polymorphisms were associated with the risk of COPD in males. This is the first study to investigate the association between CYP2C9 and CYP2C19 genetic polymorphisms and COPD risk, which may give a new perspective on the prevention and diagnosis of COPD.

Telomere length, ZNF208 genetic variants and risk of chronic obstructive pulmonary disease in the Hainan Li population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow limitation. It is not completely reversible and shows progressive development. ZNF208 rs8105767 affects telomere length, although the impact of telomere on COPD is still controversial. In the present study, we aimed to explore the impact of the ZNF208 gene polymorphism on telomere length and also that of telomere length on COPD in the Hainan Li population. METHODS: In total, 270 COPD patients and 288 controls were recruited. Telomere length was measured by a quantitative real-time polymerase chain reaction. Five single nucleotide polymorphisms in ZNF208 were selected and genotyping was performed using MassARRAY software (Agena Bioscience Co. Ltd, San Diego, CA, USA). Differences in telomere length among the subjects with three genotypes of related genes were assessed using analysis of variance. Unconditional logistic regression was used to calculate odds ratios (OR) as the indicator of association between telomere length and COPD risk. RESULTS: Relative telomere length in the COPD group and control group was 0.66 ± 0.47 and 1.44 ± 0.89, respectively. We grouped according to a median of 0.8284 for telomere length and observed that the risk of COPD for individuals with a telomere length less than 0.8284 is 2.92 times that for individuals with a telomere length longer than 0.8284 (OR = 2.92, 95% confidence interval = 2.01-4.25, p = 1.91 × 10-8 ). Subjects carrying the G allele of rs2188972 had a longer telomere length. Subjects carrying the carrying the CA genotype of rs8103163 and AC genotype of rs7248488 had a longer telomere length compared to wild-type individuals. CONCLUSIONS: Shorter telomeres increase COPD risk and the ZNF208 polymorphism affects telomere length in COPD patients.

CLPTM1L polymorphism as a protective factor for lung cancer: a case-control study in southern Chinese population.

Variants of the cleft lip and palate trans-membrane 1 like (CLPTM1L) gene, located on chromosome 5p15.33, were previously determined to influence lung cancer susceptibility. Here, we performed a case-control study to examine the potential association of CLPTM1L single nucleotide polymorphisms (SNPs) with lung cancer in a Chinese Han population. We selected four SNPs in the CLPTM1L gene that were previously reported to be associated with lung cancer. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to estimate the strength of the relationship between each CLPTM1L SNP and lung cancer risk. Allelic model analysis revealed that the minor alleles of all four SNPs were significantly associated with decreased lung cancer risk. Similar significant results were detected using genetic model analysis. In addition, we observed a protective effect of haplotype "TT" in the CLPTM1L gene. Our results verified that certain CLPTM1L polymorphisms are protective factors against lung cancer in a southern Chinese Han population and may be potential diagnostic and molecular markers for lung cancer patients.

The spectrum of α- and ß-thalassemia mutations of the Li people in Hainan Province of China.

This study examines the frequency and spectrum of α- and ß-thalassemia (thal) mutations of the Li people in Hainan Province of China. We have analyzed by genotyping a sample of 8600 subjects of the Li people and found that 53.45% subjects have only α-thal mutations with high frequencies of -α(4.2) and -α(3.7), but fewer --(SEA) mutation; 3.83% have ß-thal mutations all identified to be 41/42 (-TCTT); whereas 7.99% carry both α-thal and ß-thal mutations. We also examined 9800 subjects of the Han people, and the result showed 12.16% subjects have only α-thal mutations with --(SEA) and -α(3.7) the most frequent mutation types, 6.11% have only ß-thal mutations of 7 types, whereas 4.85% carry both α-thal and ß-thal mutations. Our study demonstrated that the Li people in Hainan province have a high incidence of -α(4.2) and -α(3.7) thalassemia, low frequencies of α-thal -(SEA), and a novel ß mutation, 41/42 (-TCTT). We provide the complete spectrum of α-thal and ß-thal mutations and a strategy for accurate molecular diagnostic testing in the Li people in Hainan Province of Southern China.

miR­186­5p regulates the inflammatory response of chronic obstructive pulmonary disorder by targeting HIF­1α.

Chronic obstructive pulmonary disorder (COPD) is a chronic respiratory disease that is a major cause of morbidity and mortality worldwide. Previous studies have shown that miR­186­5p expression is significantly increased in COPD and is involved in multiple physiological and pathological processes. However, the role of miRNA­186­5p in the inflammatory response of COPD remains unclear. In this study, an in vitro model of COPD was established using lipopolysaccharide (LPS)­induced human bronchial epithelial cells (BEAS­2B). CCK­8 assays, flow cytometry, and a Muse cell analyzer were used to determine cell viability, cell cycle distribution, and apoptosis, respectively. The production of TNF­α and IL­6 were measured by ELISA. Reverse­transcription­quantitative PCR and western blotting were used to analyze mRNA and protein expression levels. The targeting relation between miR­186­5p and HIF­1α was discovered using dual­luciferase reporter assays. The results showed that transfection of miR­186­5p inhibitor inhibited cell proliferation and promoted cell apoptosis in the LPS­induced BEAS­2B cells. Inhibition of miR­186­5p markedly increased the levels of TNF­α and IL­6. miR­186­5p directly targeted and negatively regulated HIF­1α expression. In addition, inhibition of miR­186­5p increased the expression of the NF­κB pathway protein p­p65. In conclusion, it was found that inhibiting miR­186­5p may improve inflammation of COPD through HIF­1α in LPS­induced BEAS­2B cells, possibly by regulating NF­κB signaling. These findings provide a novel potential avenue for the clinical management of COPD. Future research is required to determine the mechanism of the interaction between miR­186­5p and HIF­1α in COPD.

Network Pharmacology and Experimental Verification Reveal the Regulatory Mechanism of Chuanbeimu in Treating Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches. Methods: Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments. Results: Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and SRC, ADRB2, MMP2, and NOS3 were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with SRC, ADRB2, MMP2, and NOS3. In vitro experiments demonstrated that peimisine significantly upregulated the expression of ADRB2 and NOS3 and downregulated the expression of SRC and MMP2. Conclusion: These findings indicate that CBM may modulate the expression of SRC, ADRB2, MMP2, and NOS3, thereby exerting a protective effect against COPD.

The polymorphisms of ANXA6 influence head and neck cancer susceptibility in the Chinese Han population.

Background: Head and neck cancer (HNC) is the sixth most common malignant tumor worldwide and imposes a serious economic burden on society and individuals. Annexin has been implicated in multiple functions which are essential in HNC development, including cell proliferation, apoptosis, metastasis, and invasion. This study focused on the linkage between ANXA6 variants and HNC susceptibility in Chinese people. Methods: Eight SNPs in ANXA6 from 139 HNC patients and 135 healthy controls were genotyped by the Agena MassARRAY platform. The correlation of SNPs with HNC susceptibility was evaluated using odds ratio and 95% confidence interval calculated by logistic regression using PLINK 1.9. Results: Overall analysis results demonstrated that rs4958897 was correlated with an increased HNC risk (allele: OR = 1.41, p = 0.049; dominant: OR = 1.69, p = 0.039), while rs11960458 was correlated with reduced HNC risk (OR = 0.54, p = 0.030). In age ≤ 53, rs4958897 was related to reduce HNC risk. In males, rs11960458 (OR = 0.50, p = 0.040) and rs13185706 (OR = 0.48, p = 0.043) were protective factors for HNC, but rs4346760 was a risk factor for HNC. Moreover, rs4346760, rs4958897, and rs3762993 were also correlated with increased nasopharyngeal carcinoma risk. Conclusions: Our findings suggest that ANXA6 polymorphisms are linked to the susceptibility to HNC in the Chinese Han population, indicating that ANXA6 may serve as a potential biomarker for HNC prognosis and diagnosis.