Methylation of the chromatin modifier KMT2D by SMYD2 contributes to therapeutic response in hormone-dependent breast cancer.

Activating mutations in PIK3CA are frequently found in estrogen-receptor-positive (ER+) breast cancer, and the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor alpelisib with anti-ER inhibitors is approved for therapy. We have previously demonstrated that the PI3K pathway regulates ER activity through phosphorylation of the chromatin modifier KMT2D. Here, we discovered a methylation site on KMT2D, at K1330 directly adjacent to S1331, catalyzed by the lysine methyltransferase SMYD2. SMYD2 loss attenuates alpelisib-induced KMT2D chromatin binding and alpelisib-mediated changes in gene expression, including ER-dependent transcription. Knockdown or pharmacological inhibition of SMYD2 sensitizes breast cancer cells, patient-derived organoids, and tumors to PI3K/AKT inhibition and endocrine therapy in part through KMT2D K1330 methylation. Together, our findings uncover a regulatory crosstalk between post-translational modifications that fine-tunes KMT2D function at the chromatin. This provides a rationale for the use of SMYD2 inhibitors in combination with PI3Kα/AKT inhibitors in the treatment of ER+/PIK3CA mutant breast cancer.

Multiple machine-learning tools identifying prognostic biomarkers for acute Myeloid Leukemia.

BACKGROUND: Acute Myeloid Leukemia (AML) generally has a relatively low survival rate after treatment. There is an urgent need to find new biomarkers that may improve the survival prognosis of patients. Machine-learning tools are more and more widely used in the screening of biomarkers. METHODS: Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), lrFuncs, IdaProfile, caretFuncs, and nbFuncs models were used to screen key genes closely associated with AML. Then, based on the Cancer Genome Atlas (TCGA), pan-cancer analysis was performed to determine the correlation between important genes and AML or other cancers. Finally, the diagnostic value of important genes for AML was verified in different data sets. RESULTS: The survival analysis results of the training set showed 26 genes with survival differences. After the intersection of the results of each machine learning method, DNM1, MEIS1, and SUSD3 were selected as key genes for subsequent analysis. The results of the pan-cancer analysis showed that MEIS1 and DNM1 were significantly highly expressed in AML; MEIS1 and SUSD3 are potential risk factors for the prognosis of AML, and DNM1 is a potential protective factor. Three key genes were significantly associated with AML immune subtypes and multiple immune checkpoints in AML. The results of the verification analysis show that DNM1, MEIS1, and SUSD3 have potential diagnostic value for AML. CONCLUSION: Multiple machine learning methods identified DNM1, MEIS1, and SUSD3 can be regarded as prognostic biomarkers for AML.

The BAF chromatin complex component SMARCC1 does not mediate GLI transcriptional repression of Hedgehog target genes in limb buds.

Transcriptional responses to the Hedgehog (HH) signaling pathway are primarily modulated by GLI repression in the mouse limb. Previous studies suggested a role for the BAF chromatin remodeling complex in mediating GLI repression. Consistent with this possibility, the core BAF complex protein SMARCC1 is present at most active limb enhancers including the majority of GLI enhancers. However, in contrast to GLI repression which reduces chromatin accessibility, SMARCC1 maintains chromatin accessibility at most enhancers, including those bound by GLI. Moreover, SMARCC1 binding at GLI-regulated enhancers occurs independently of GLI3. Consistent with previous studies, some individual GLI target genes are mis-regulated in Smarcc1 conditional knockouts, though most GLI target genes are unaffected. Moreover, SMARCC1 is not necessary for mediating constitutive GLI repression in HH mutant limb buds. We conclude that SMARCC1 does not mediate GLI3 repression, which we propose utilizes alternative chromatin remodeling complexes.

Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia.

Phosphodiesterase 4D interacting protein (PDE4DIP) interacts with cAMP-specific phosphodiesterase 4D and its abnormal expression promotes the development of hematological malignancies, breast cancer, and pineal cell carcinoma. However, there is currently no systematic pan-cancer analysis of the association between PDE4DIP and various cancers. Thus, this study aimed to elucidate the potential functions of PDE4DIP in various cancers. Based on the multiple public databases and online websites, we conducted comprehensive analyses for PDE4DIP in various cancers, including differential expression, prognosis, genetic variation, DNA methylation, and immunity. We thoroughly analyzed the specific role of PDE4DIP in acute myeloid leukemia (LAML). The results indicated that there were differences in PDE4DIP expression in cancers, and in kidney chromophobe, LAML, pheochromocytoma and paraganglioma, thymoma, and uveal melanoma, PDE4DIP had potential prognostic value. PDE4DIP expression was also correlated with genetic variation, DNA methylation, immune cell infiltration, and immune-related genes in cancers. Functional enrichment analysis showed that PDE4DIP was mainly related to immune-related pathways in cancers, and in LAML, PDE4DIP was mainly related to immunoglobulin complexes, T-cell receptor complexes, and immune response regulatory signaling pathways. Our study systematically revealed for the first time the potential prognostic and immunotherapeutic value of PDE4DIP in various cancers, including LAML.

IL1RL1 polymorphisms rs12479210 and rs1420101 are associated with increased lung cancer risk in the Chinese Han population.

Background: Lung cancer is one of the most common human malignant diseases. In this study, we aimed to explore the association between IL1RL1 genetic polymorphisms and lung cancer risk in the Chinese Han population. Methods: We selected and genotyped six SNPs in the IL1RL1 gene using the Agena MassARRAY system in 507 lung cancer patients and 507 healthy controls. The association between IL1RL1 variants and lung cancer risk was assessed using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Multi-factor dimensionality reduction (MDR) was used to analyze the impact of SNP-SNP interactions on the risk of lung cancer. Results: The results of overall analysis indicated that rs12479210 (T vs. C: OR = 1.42, FDR-p = 0.002; TC vs. CC: OR = 1.70, FDR-p < 0.0001; TT vs. CC: OR = 1.77, FDR-p = 0.032; TT-TC vs. CC: OR = 1.71, FDR-p = 0.001; additive: OR = 1.44, FDR-p = 0.001) and rs1420101 (T vs. C: OR = 1.31, FDR-p = 0.036; TT-TC vs. CC: OR = 1.42, FDR-p = 0.031; additive: OR = 1.30, FDR-p = 0.030) were associated with an increased the risk of lung cancer among the Chinese Han population. Stratified analysis also found the association between these two SNPs and lung cancer risk. However, there were no significant association observed between the other four SNPs (rs3771180, rs3771175, rs10208293, and rs10197862) in IL1RL1 and lung cancer risk. Furthermore, MDR analysis showed that rs12479210 was the best single model with the highest testing accuracy (0.566) and perfect CVC (10/10) for predicting lung cancer risk. The expression level of the IL1RL1 gene is lower in lung cancer tissue than normal tissue, and there are significant differences in the expression levels of IL1RL1 between rs12479210 and rs1420101 genetypes in lung cancer tissue (p < 0.05). Conclusion: Our findings suggest that IL1RL1 genetic variants (rs12479210 and rs1420101) are associated with an increased lung cancer risk in the Chinese Han population. These risk variants may serve as biomarkers for the prevention and treatment of lung cancer.

The BAF chromatin complex component SMARCC1 does not mediate GLI transcriptional repression of Hedgehog target genes in limb buds.

Transcriptional responses to the Hedgehog (HH) signaling pathway are primarily modulated by GLI repression in the mouse limb. Previous studies suggested a role for the BAF chromatin remodeling complex in mediating GLI repression. Consistent with this possibility, the core BAF complex protein SMARCC1 is present at most active limb enhancers including the majority of GLI enhancers. However, in contrast to GLI repression which reduces chromatin accessibility, SMARCC1 maintains chromatin accessibility at most enhancers, including those bound by GLI. Moreover, SMARCC1 binding at GLI-regulated enhancers occurs independently of GLI3. Consistent with previous studies, some individual GLI target genes are mis-regulated in Smarcc1 conditional knockouts, though most GLI target genes are unaffected. Moreover, SMARCC1 is not necessary for mediating constitutive GLI repression in HH mutant limb buds. We conclude that SMARCC1 does not mediate GLI3 repression, which we propose utilizes alternative chromatin remodeling complexes.

Association of CYP19A1 rs28757157 polymorphism with lung cancer risk in the Chinese Han population.

BACKGROUND: Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that CYP19A1 gene plays a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population. METHODS: This study randomly recruited 489 lung cancer patients and 467 healthy controls. The genotypes of four single nucleotide polymorphisms (SNPs) of the CYP19A1 gene were identified by the Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variations and lung cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the effect of four selected SNPs on lung cancer risk. RESULTS: CYP19A1 rs28757157 might contribute to an increased risk of lung cancer (p = 0.025, OR = 1.30, 95% CI 1.03-1.64). In stratified analysis, rs28757157 was associated with an increased cancer risk in the population aged under 60 years, females, smokers, and drinkers. Besides, rs3751592 and rs59429575 were also identified as risk biomarkers in the population under 60 years and drinkers. Meanwhile, a relationship between an enhanced risk of squamous cell carcinoma and rs28757157 was found, while the rs3751592 CC genotype was identified as a risk factor for lung adenocarcinoma development. CONCLUSIONS: This study has identified revealed that the three SNPs (rs28757157, rs3751592, and rs59429575) of CYP19A1 are associated with lung cancer in the Chinese Han population. These findings will provide theoretical support for further functional studies of CYP19A1 in lung cancer.

Variants in CYP2J2 and CYP2C9 Contribute to Susceptibility of Lung Cancer.

BACKGROUND: Cytochrome P450 (CYP) enzymes are involved in the metabolism of xenobiotic and carcinogen. In the study, we evaluated the association of CYP2J2 and CYP2C9 variants with lung cancer. METHOD: Five polymorphisms in CYP2J2 and four polymorphisms in CYP2C9 were genotyped in 507 lung cancer patients and 505 controls with Agena MassARRAY platform. The linkage of variants with lung cancer risk was evaluated by odds ratio (OR) and 95% confidence interval (CI) in genetic models and haplotype analyses. RESULTS: We found that CYP2C9 rs1934967 alleles were associated with lung cancer risk (P < 0.05). In stratified analysis, rs2280274 (women, non-smoker, non-drinker and lymphatic metastasis), rs11207535 (non-smoker and non-drinker), rs10889159 (non-smoker and non-drinker) of CYP2J2, whereas rs1934967 (age ≤ 60m, BMI > 24, squamous carcinoma) of CYP2C9 decreased lung cancer risk (P < 0.05). In addition, the results of linkage disequilibrium (LD) analysis showed that rs2280274|rs4388726 - TG (with adjustment: P = 0.042) of CYP2J2 and rs10509679|rs1934967|rs1934968|rs9332220 - GTGG (without adjustment: P = 0.044) of CYP2C9 were linked with a significantly decreased lung cancer risk. CONCLUSION: Our results indicated genetic variants in CYP2J2 and CYP2C9 might contribute to the susceptibility of lung cancer in Chinese population.

Therapeutic Benefits of Pomegranate Flower Extract: A Novel Effect That Reduces Oxidative Stress and Significantly Improves Diastolic Relaxation in Hyperglycemic In Vitro in Rats.

The pomegranate flower is an ancient herb in traditional Chinese medicine with multiple properties. Recent studies have shown that pomegranate flower extract is beneficial, especially for hyperglycemia. In this experiment, we investigated the diastolic effect of pomegranate flower polyphenol (PFP) extract on the isolated thoracic aorta of rats in both the absence and presence of high glucose levels. Isotonic contractile forces were recorded from aortic rings (about 3 mm in length) from rats using the BL-420F Biological Function Test System. Tissues were precontracted with 60 mM KCl to obtain maximum tension under 1.0 g load for 1 hour before the balance was achieved, and the fluid was changed every 15 minutes. PFP (700 mg/L-900 mg/L) showed a concentration-dependent relaxant effect on the aortic rings; vasodilation in the endothelium-intact was significantly higher than that in the de-endothelialized segments (P < 0.01). The endothelium-dependent vasorelaxant effect of PFP was partially attenuated by K+ channel blockers, tetraethylammonium (TEA), glibenclamide (Glib), and BaCl2, as well as L-NAME (eNOS inhibitor) on the denuded endothelium artery ring. Concentration-dependent inhibition of PFP on releasing intracellular Ca2+ in the Ca2+-free solution and vasoconstriction of CaCl2 in Ca2+-free buffer plus K+ (60 mM) was observed. In addition, PFP (0.1-10 mg/L) showed significant inhibition of acetylcholine-induced endothelial-dependent relaxation in the aorta of rats in the presence of high glucose (44 mmol/L). Nevertheless, the vasodilating effect of PFP was inhibited by atropine and L-NAME. The results indicated that PFP-induced vasodilation was most likely related to the antioxidant effects through enhanced NO synthesis, as well as the blocking of K+ channels and inhibition of extracellular Ca2+ entry. In conclusion, these observations showed that PFP ameliorates vasodilation in hyperglycemic rats. Hence, our results suggest that PFP supplementation may be beneficial for hypertensive patients with diabetes.

The HER family as therapeutic targets in colorectal cancer.

The human epidermal growth factor receptor (HER, ErbB) family has four members, epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. Although distinct in ligands and functions, all of the HER family members are receptor tyrosine kinases playing important roles in the pathogenesis of cancers. In the era of precision medicine, the HER family is one of the most important and successful cancer therapeutic targets, hallmarked by the approval of anti-EGFR therapies for the treatment of colorectal cancer and non-small cell lung cancer, and anti-HER2 therapies for the treatment of breast cancer and gastric cancer. This review briefly discusses how HER family members were discovered, their functions and roles in cancer, and most importantly, the developmental history and recent updates of therapies targeting HER family members, with colorectal cancer as a focus. We also discussed the patient selection and drug resistance to anti-EGFR therapies in the treatment of colorectal cancer.

Application evaluation of virtual reality technology in dental implant training: a new dental implant training system: A CONSORT-compliant trial.

ABSTRACT: To evaluate the application of virtual reality technology in a dental implant training system.A 3-dimensional model of mandible was established by Mimics17.0 software based on the Digital Imaging and Communications in Medicine data obtained from cone beam computed tomography scanning of the patient in mandibular. Thirty physicians were divided into 2 groups. The virtual reality dental implant training system was used for group A, while conventional theoretical knowledge training and clinical demonstration were performed in group B. All young physicians have a 1-month study. After training, all the physicians in groups A and B would conduct a questionnaire survey according to the training situation, which was compared between the 2 groups. The success rate of the operation was also evaluated and compared.The median scores in the 5 dimensions of postoperative assessment of group A was 9/9/9/8/8, and of group B was 6/7/6/7/7. The scores of the 5 dimensions were significantly higher than those of group B (P < .05), indicating that group A has a better grasp of the simulator. After the training of simulated mandibular implants in group A, the deviations in the 4 dimensions of mesiodistal, buccal and tongue, depth, and angle were significantly lower than those of group B (P < .05). Group A has smaller deviations in each of the 4 dimensions than those in group B, indicating group A has a higher operation success rate.We independently develop a set of virtual surgery system for dental implant training, which can be used for teaching and training, with good operability and predictability, to achieve a breakthrough in dental implant surgery training.

Analysis of Very Important Pharmacogenomics Variants in the Chinese Lahu Population.

BACKGROUND: Genetic polymorphism, obviously, has a potential clinical role in determining differences in drug efficacy; however, there are no reports about the pharmacogenomic information of the Lahu population. Therefore, our research aimed to screen the genotypic frequencies of the very important pharmacogenomics (VIP) mutations and determined the differences between Lahu and the other 11 populations. METHODS: Agena MassARRAY (AgenaMassARRAY) single nucleotide polymorphism (SNP) genotyping technique was used to detect 81 VIP mutations of pharmacogenomics genes in Lahu, and their genotypic frequencies were compared with the other major 11 populations. Chi-square tests were used to identify different loci among these populations. Finally, the genetic structure and pairwise Fst values of Lahu and the other 11 populations were analyzed. RESULTS: We found that the distribution of allele frequencies within different pharmacogenes in Lahu showed significantly different with other populations. Additionally, the pairwise F-statistics (Fst) values and genetic structure revealed the variants in the Lahu population as well were mostly related to the Han Chinese in Beijing, China (CHB) and the Japanese population in Tokyo, Japan (JPT) genetically. CONCLUSION: This study will provide a theoretical basis for safe drug use and help to establish the appropriate individualized treatment strategies in the Lahu population.

Genetic polymorphisms of pharmacogenomic VIP variants in the Dai population from Yunnan province.

BACKGROUND: Pharmacogenomics plays a crucial role in individualized therapy, but the variant information of pharmacogenomics in the Dai population is limited. We therefore aimed to screen very important pharmacogenetic (VIP) in the Dai population and compared differences between Dai and other 25 populations. METHODS: In this study, we genotyped 73 VIP variants from the PharmGKB and compared genotype distribution of variants in Dai with other 25 populations by χ2 test. To assess the genetic relationship among 26 populations, we performed the structure analysis. In addition, pair-wise F-statistics (Fst) was calculated to measure the population differentiation. RESULTS: We found 12, 10, 13, 17, 11, 39, 46, 46, 45, 43, 49, 46, 46, 46, 49, 45, 41, 42, 48, 53, 45, 50, 50, 51, 47, and 50 significantly different variants in Dai compared with other 25 populations. Genetic structure analysis showed Dai had close relationships with CDX (Chinese Dai in Xishuangbanna), CHB (Han Chinese in Beijing), JPT (Japanese in Tokyo), and KHV (Kinh in Ho Chi Minh City, Vietnam). Moreover, Dai is the most similar to KHV according to Fst analysis. CONCLUSIONS: Our study complement the pharmacogenomics information of Dai population from Yunnan province and provide a theoretical basis for personalized medicine.

Constructing Machine Tool Foundations Using an LMP Alloy.

Currently, the construction of machine tool foundations is a complicated and lengthy procedure with a limited flexibility. In this paper, we present a novel system for constructing machine tool foundations that replaces the need for concrete or concrete-polymer hybrids with a low melting point (LMP) alloy. The system uses a hot bath method to maintain the LMP alloy grouting in liquid form. A fixing device is used to control the embedded depth and positional accuracy of the foundation bolt assembly. The grouting material is injected into the foundation pit by a filling device. This can be extracted from the foundation pit in a later stage with the aid of a recycling device, enabling new machine tool foundations to be manufactured by reusing the LMP alloy grouting material. A prototype was built to test the proposed design. The results show that the system can construct machine tool foundations in a single application, without the delays associated with concrete-based construction, lowering both the economic and environmental cost.

Genetic polymorphisms analysis of pharmacogenomic VIP variants in Bai ethnic group from China.

BACKGROUND: The pharmacogenomics study has been widely used for the study of very important pharmacogenetic (VIP) variants among different ethnic groups. However, there is little known about the pharmacogenomics information regarding Bai family. Our study aimed to screen the polymorphism of the VIP gene in Bai nationality. METHODS: We genotyped 81 VIP variants (selected from the PharmGKB database) in the Bai population and then compared them to the other 11 major HapMap populations by chi-square test, structure and F-statistics (Fst) analysis. RESULTS: Our results indicated that rs20417 (PTGS2), rs4148323 (UGT1A), and rs1131596 (SLC19A1) were most different in Bai compared with most of the 11 populations from the HapMap data set. Furthermore, population structure and F-statistics (Fst) analysis also demonstrated that the Bai population has the closest genetic relationship with Han Chinese in Beijing, China (CHB), followed by Japanese in Tokyo, Japan (JPT), and the farthest population from the Yoruba in Ibadan, Nigeria (YRI). CONCLUSIONS: Our study not only presented the genotype frequency difference between the selected population of the Bai population and the other 11 populations, but also showed that the Bai population is most similar to the CHB populations, followed by JPT. These findings would contribute to the development of individualized medicine for the Bai population.

Genetic polymorphisms in IL-7 and IL-7R are correlated with lung cancer risk in the Chinese Han population.

PURPOSE: IL-7/IL-7R axis participates in the initiation and progression of lung cancer (LC). This study aimed to explore the potential influence of IL-7/IL-7R polymorphisms on LC risk. PATIENTS AND METHODS: In total, 1,010 participants (507 LC patients and 503 healthy controls) were enrolled. Five single-nucleotide polymorphisms (SNPs) in IL-7R and one SNP in IL-7 were genotyped in included samples with Agena MassARRAY system. OR and 95% CIs were computed by logistic regression analysis after adjusting for age and gender. Stratified analyses with demographic and clinical characteristics were also performed. Finally, linkage disequilibrium (LD) analysis was conducted with the PLINK version 1.07 software . RESULTS: IL-7R rs10053847 variant was related to a decreased LC risk under the allele gene (OR =0.78, P=0.043) and additive model (OR =0.77, P=0.042). The results of stratified analysis indicated that this SNP was associated with a lower LC risk among nonsmokers (AA/GG: OR =0.09, P=0.033; AA/AG+GG: OR =0.10 P=0.037) or nondrinkers (AA/GG: OR =0.07, P=0.047; AA/AG+GG: OR =0.18 P=0.049). Moreover, carriers of IL-7R rs10213865-C allele had an increased lung adenocarcinoma risk (CA/AA: OR =1.60, P=0.011; CC+CA/AA: OR =1.62, P=0.007; CA/CA/AA: OR =1.50, P=0.007). Additionally, AGAA haplotype (rs10213865, rs969129, rs118137916 and rs10053847) increased LC risk (OR =1.30, P=0.041). CONCLUSION: IL-7R rs10053847 was correlated with a decreased LC risk, while IL-7R rs10213865 was correlated with an elevated lung adenocarcinoma risk, implying these two SNPs might play essential roles in LC risk evaluation.

Genetic analysis of pharmacogenomic VIP variants in the Blang population from Yunnan Province of China.

BACKGROUND: Genetic polymorphisms in numerous pharmacogenetics studies were regarded as the essential factors involved in the response to or metabolism of drugs. These genetic variants called very important pharmacogenetic (VIP) variants played a role in drugs metabolism, which have been summarized in the PharmGKB database. In this study, we genotyped 80 VIP variants from the PharmGKB in 100 members of Blang volunteers from Yunnan province. METHODS: Based on the PharmGKB database, we genotyped 80 VIP variants loci located in 47 genes. We used χ2 tests to evaluate the significant loci between Blang and the other populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. The global variation distribution of the significant variants was observed from the ALlele FREquency Database. And then, we used F-statistics (Fst), genetic structure, and phylogenetic tree analyses to ascertain the genetic affinity among 12 populations. RESULTS: Comparing the Blang with the other 11 populations from the HapMap Project, the statistical results revealed that rs3814055 (NC_000003.12:g.119781188C>T) of nuclear receptor subfamily 1 group I member 2 (NR1I2, OMIM# 603,065) was the most significant variant, followed by rs1540339 (NC_000012.12:g.47863543C>T) of vitamin D receptor (VDR, OMIM#601,769). Furthermore, we found that genotype frequency of rs3814055 in the Blang was closer to the populations distributed in Miao. And genetic structure and F-statistics indicated that the Blangs had a relatively closer affinity with CHD, CHB, and JPT populations. In addition, the Han nationality in Shaanxi was closer to it. CONCLUSIONS: Our results will complement the pharmacogenomics information of the Blang ethnic group and provide a theoretical basis for safer drug administration for Blang.

TNIP1 Polymorphisms with the Risk of Hepatocellular Carcinoma Based on Chronic Hepatitis B Infection in Chinese Han Population.

Chronic hepatitis B virus (HBV) infection is an important etiology for the development of hepatocellular carcinoma (HCC). Tumor necrosis factor-α-induced protein 3-interacting protein 1 (TNIP1) is linked to specific inflammatory diseases as a novel type of endogenous inflammatory regulator. However, presently, rare information is found about the association between TNIP1 polymorphisms and HBV-induced HCC risk. In this case control study, we genotyped four single nucleotide polymorphisms (SNPs) in TNIP1 gene in 248 HCC patients and 242 chronic HBV carriers using Sequenom Mass-ARRAY technology. Genetic model and haplotype analysis were performed to evaluate the association between candidate SNPs polymorphisms and HBV-induced HCC susceptibility using Pearson's χ2 test and unconditional logistic regression analysis. Overall, we found two risk alleles in TNIP1 for HBV-induced HCC in patients: the allele "G" of rs7708392 by genotype model ("G/C" vs. "C/C": OR 1.88, 95% CI 1.17-3, P = 0.009) and dominant model ("G/C-G/G" vs. "C/C": OR 1.69, 95% CI 1.08-2.65, P = 0.023), and the allele "C" of rs10036748 by genotype model ("C/T" vs. "T/T": OR 1.83, 95% CI 1.14-2.92, P = 0.012) and dominant model ("C/T-C/C" vs. "T/T": OR 1.65, 95% CI 1.05-2.59, P = 0.03). However, rs3792792 and rs4958881 polymorphisms didn't significantly correlate with the risk of HBV-induced HCC. Haplotype analysis showed no significant association between haplotypes and the HCC risk in HBV carriers. This study provides evidence for HBV-induced HCC susceptibility gene TNIP1 in the Chinese Han population.

Population genetic difference of pharmacogenomic VIP gene variants in the Lisu population from Yunnan Province.

Individual differences in drug clinical response are related to pharmacogenomics. The genetic variation of drug-metabolizing enzymes, drug receptors, and their downstream protein genes is the main factor causing individual differences in drug response. The genetic backgrounds among different ethnic groups are quite different. In this study, we aimed to detect the distribution difference of genotype frequency in very important pharmacogenetic (VIP) gene variants in the Lisu.Using the chi-squared test, we compared the genotype frequencies of the VIP variants in 105 Lisu people with those in 26 populations from the 1000 Genome project separately. Bonferroni's multiple adjustment was also conducted (P < .05/(26*49)). Moreover, Arlequin v3.5 and Structure v2.3.4 software were used to analyze the genetic distance and genetic structure.There were 9, 9, 11, 12, 11, 11, 9, 17, 13, 13, 16, 5, 3, 5, 3, 4, 17, 14, 16, 17, 16, 10, 13, 12, 10, and 9 single nucleotide polymorphisms that differed in frequency distribution, when Lisu people compared with the 26 populations separately. Only CYP2E1 rs2070676 was different in the Lisu population compared with the 26 groups from the 1000 Genome project. PTGS2 rs5275 and CYP2D6 rs1065852 were different in the Lisu population compared with most of the populations. Additionally, genetic backgrounds of Lisu and Han Chinese in Beijing were closest according to the lowest F-statistics value and resemblance in genetic structures.Our results complete the information of the Lisu population in pharmacogenomics database.

Electrochemiluminescence based competitive immunoassay for Sudan I by using gold-functionalized graphitic carbon nitride and Au/Cu alloy nanoflowers.

A flower-like Au/Cu alloy nanocomposite (Au/Cu NFs) was synthesized and used in an electrochemiluminescence (ECL) based method for sensitive determination of the dye Sudan I. The Au-g-C3N4 nanosheets as an ECL emitter were prepared by electrostatic adsorption between gold nanoparticles and g-C3N4. They form a film on a glassy carbon electrode (GCE) and then can be connected with Sudan I antigen via gold-nitrogen bond and amidation reactions. The Au/Cu NFs combined with Sudan I antibody also via the Au-N bond and was introduced into the modified GCE by specific recognition between the antibody and the antigen. The overlap between emission spectra of the Au-g-C3N4 nanosheets and absorption spectra of Au/Cu NFs enabled the appearance of ECL resonance energy transfer process. That is, when the Sudan I analyte not present, the ECL was weakened due to absorption by the gray Au/Cu NFs on applying voltages from -1.7 V to 0 V. Conversely, the Au/Cu NFs on the GCE are reduced due to the competition for the antibody between the analyte and the antigen. A strong green ECL emission was obtained. The ECL response is linear in the 0.5 pg mL-1 to 100 ng mL-1 Sudan I concentration range, and the detection limit is 0.17 pg mL-1. Graphical abstract An Au/Cu alloy flower-like nanocomposite (Au/Cu NFs) is firstly synthesized as an acceptor to constitute an electrochemiluminescence-resonance energy transfer (ECL-RET) system for sensitive measurement of Sudan I, while Au nanoparticles (Au NPs) functionalized graphitic carbon nitride (g-C3N4) acted as a donor.