A functional variant rs10409772 in FUT6 promoter regulates colorectal cancer progression through PKA/CREB signaling.

Fucosyltransferase 6 (FUT6) is overexpressed in colorectal cancer tissue according to TCGA samples and immunohistochemistry results of a tissue microarray. FUT6 effects cell migration, tumor formation and proliferation of colorectal cancer cells in different essays. FUT6 promotes cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by upregulating PKA/CREB pathway activation. Moreover, FUT6 expression is regulated by rs10409772 shown in the luciferase essays, a single nucleotide polymorphism in the promoter of FUT6. Our study suggests that elevated expression of FUT6 promotes PKA/CREB signaling, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased FUT6 expression.

APOE genotype, eicosapentaenoic acid (EPA) supplementation and n-3 highly unsaturated fatty acid (HUFA) levels in patients with multiple colorectal polyps: A secondary analysis of the seAFOod polyp prevention trial.

INTRODUCTION: We examined the relationship between Apolipoprotein E (APOE) genotype and n-3 highly unsaturated fatty acid (HUFA) levels in participants of the seAFOod trial, who were undergoing colonoscopy surveillance after removal of colorectal polyps. METHODS: Baseline and on-treatment (eicosapentaenoic acid [EPA] 2 g daily or placebo for 6 months) levels of n-3 HUFAs, and plasma 18-hydroxyeicosapentaenoic acid (HEPE), were analysed according to APOE genotype (based on polymorphisms rs429358 and rs7412) in 584 participants. RESULTS: Before treatment, APOE2/2 individuals had lower levels, and APOE4/4 participants had higher levels, of n-3 HUFAs, including EPA, than APOE3/3 counterparts (P < 0.01 for the APOE2/2 versus APOE4/4 comparison). After EPA supplementation, n-3 HUFA levels were not significantly different when stratified by APOE genotype, although APOE4 carriers displayed lower plasma 18-HEPE levels than individuals without an APOE4 allele (P = 0.002). CONCLUSIONS: APOE genotype is associated with differential n-3 HUFA and 18-HEPE levels in individuals with multiple colorectal polyps.

Unprecedented Packing Polymorphism of Oxindole: An Exploration Inspired by Crystal Structure Prediction.

Crystal polymorphism, characterized by different packing arrangements of the same compound, strongly ties to the physical properties of a molecule. Determining the polymorphic landscape is complex and time-consuming, with the number of experimentally observed polymorphs varying widely from molecule to molecule. Furthermore, disappearing polymorphs, the phenomenon whereby experimentally observed forms cannot be reproduced, pose a significant challenge for the pharmaceutical industry. Herein, we focused on oxindole (OX), a small rigid molecule with four known polymorphs, including a reported disappearing form. Using crystal structure prediction (CSP), we assessed OX solid-state landscape and thermodynamic stability by comparing predicted structures with experimentally known forms. We then performed melt and solution crystallization in bulk and nanoconfinement to validate our predictions. These experiments successfully reproduced the known forms and led to the discovery of four novel polymorphs. Our approach provided insights into reconstructing disappearing polymorphs and building more comprehensive polymorph landscapes. These results also establish a new record of packing polymorphism for rigid molecules.

Color Polymorphism and Room Temperature Phosphorescence of 4-bromo-2,7-di-tert-butyl-9-methoxypyrene.

The title compound has two polymorphic crystal structures having strikingly different absorption and luminescence spectra that result from different packing motifs in the crystal lattice. The polymorph with brick wall-like packing of molecules is white and shows very weak violet fluorescence whereas the second polymorph, where molecules are arranged in columnar stacks, is bright yellow and displays intense green fluorescence with maximum at 487 nm (20530 cm-1). In the white polymorph, where the distance between neighboring chromophores is increased, absorption and fluorescence spectra are similar to those of monomer in solution, and intersystem crossing to triplet manifold is the dominant pathway of relaxation. In the yellow polymorph, molecules within the columnar stacks are rotated which mitigates the steric hindrance and leads to closer π-stacking of the pyrene cores. That increases the ππ overlap and strengthens intermolecular interactions decreasing energy of the excited states. This affects emission spectra and photophysical processes - fluorescence yield grows whereas triplet formation yield decreases when S1 is lowered below higher triplet states and conditions for effective vibronic spin-orbit coupling are not favorable. The effect is not observed for other similar pyrene derivatives, testifying the uniqueness of the phenomenon.

A novel high sensitive, specificity duplex enzyme-activated differentiating probes PCR method for the SNP detection and differentiation of MS-H vaccine strains from wild-type Mycoplasma synoviae strains.

Mycoplasma synoviae (MS) is a contagious pathogen that poses a significant threat to the poultry industry. Detection plays an important role in the prevention and control of MS, particularly in differentiating between wild-type MS and live attenuated vaccine strains for vaccination selection and culling of animals with wild-type only. The live attenuated ts+ vaccine strain MS-H is recognized as the most effective and widely used vaccine. In this study, we have developed a method called double enzyme-activated differentiation probes PCR (DEA-probes PCR) for the differentiation of MS-H vaccine strain from wild-type strain by targeting the single nucleotide polymorphism (SNP) of the 367th nucleotide in the Obg gene sequence. We developed 2 modified probes with the ribonucleotide insert. When the probe perfectly complements with the target, the ribonuclease H2 (RNase H2) will cleave the ribonucleotide, resulting in the generation of fluorescent signal. With a detection limit of 5.8 copies/µL, the DEA-probes PCR method demonstrates 100% specificity in distinguishing wild-type MS from MS-H strains in 1 h. The method demonstrated great performance in real application of 100 superior palate cleft swab samples from chickens in poultry farms. Twenty-eight samples were detected as MS positive, consistent with the results of the Chinese industry standard method. Additionally, our method was able to distinguish 19 wild-type MS strains from 9 MS-H vaccine strains. The DEA-probes PCR method is rapid, specific and sensitive for SNP detection, overcoming the misidentification in MS detection and differentiation. It can be also applied to the differentiation of infected from vaccinated animals (DIVA) for other pathogens.

The Association Between CYP2R1 rs10741657 Polymorphisms and Bone Variables, Vitamin D, and Calcium in Iranian Children and Adolescents: A Cross-Sectional Study.

Osteoporosis is a common disorder with a strong genetic component. Bone mineral density (BMD), vitamin D, and calcium levels declining are a main contributor of osteoporosis and fragility fractures. This cross-sectional study designed to explore the possible link between CYP2R1 rs10741657 polymorphism and BMD of the total hip, lumbar spine and femoral neck, vitamin D, and calcium in Iranian children and adolescents. 247 children and adolescents (127 girls and 120 boys) between 9 and 18 years old from Kawar (an urban area located 50 km east of Shiraz, the capital city of the Fars province in the south of Iran) were randomly selected based on age-stratified systematic sampling and recruited for genetic analysis. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping CYP2R1 rs10741657. Anthropometric, biochemical, and bone mineral density (BMD) parameters were also measured. The results specified that in the dominant [P < 0.0001, - 2.943 (- 4.357-1.529)] and over-dominant [P < 0.0001, 2.789 (1.369-4.209)] models, vitamin D concentration significantly differed between genotypes. The highest vitamin D levels were displayed for participants carrying the rs10741657 AG genotype (16.47 ng/ml). In regard to calcium, in a dominant model [P = 0.012, 0.194 (0.043-0.345)] and over-dominant model [P = 0.008, 0.206 (- 0.357-0.055), there was a significant association. AG genotype displayed the highest (9.96 mg/dl) and GG genotype the lowest (9.75 mg/dl) calcium values. This study reported the association of CYP2R1 rs10741657 polymorphisms with calcium and vitamin D levels in Iranian children and adolescents.

Association of Interleukin-6 (rs1800795) and Interleukin-10 (rs1800896) Genetic Polymorphisms with the Outcome of COVID-19 Infection: A Single Center Study.

The corona virus disease-2019 (COVID-19) pandemic has affected most of the world with varying degrees of morbidity and mortality. The presence of genetic polymorphisms may be associated with the severity and outcome of COVID-19 infection. This work aimed to evaluate the genetic polymorphisms of interleukin (IL-6) and IL-10 genes with the outcome of COVID-19 infection. This cross-sectional study was conducted on 354 patients who were classified into moderate and severe cases (including alive and deceased cases). All individuals were genotyped for one SNP for IL-6 (rs1800795) and one SNP for IL10 (rs1800896) using allelic discrimination real-time PCR technique. In this study, 198 cases were moderate, and 156 cases were severe. The risk of allele carriage of the minor allele of IL-6 rs1800795 (C) was significantly higher among the severe group when compared with that of the moderate group (p < 0.0001), while there was a mild significant difference of same allele carriage among alive cases when compared to that of deceased one (p < 0.04). Furthermore, the risk of the C allele of IL-10 rs1800896 was significantly increased in severe cases when compared with the moderate group (p < 0.0001), while there was no significant difference of the risk of the C allele in deceased cases when compared with that of alive ones (p > 0.05). In conclusion, the C allele (rs1800795) of IL-6 and the C allele (rs1800896) of IL-10 were highly significant in severe cases than in moderate cases. The C allele carriage of IL-6 showed only a significant difference between alive and deceased patients and not with the C allele of IL-10.

Relationship between human serum metabolites and angina pectoris: a Mendelian randomization study.

PURPOSE: We aimed to explore the causal relationship between human serum metabolites and angina pectoris. METHODS: This study used two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and angina pectoris. The analytical methods employed to reduce study bias included inverse variance weighted, MR-Egger, and weighted median method. A comprehensive sensitivity analysis was performed using the leave-one-out method, while instrumental variable pleiotropy was tested with MR-Pleiotropy RESidual Sum and Outlier. Metabolic pathways of angina-associated metabolites were analysed on the MetaboAnalyst metabolomics analysis tool platform. RESULTS: In this study, 42 serum metabolites were found to be strongly associated with angina pectoris. They mainly belonged to seven groups: amino acids, carbohydrates, cofactors and vitamins, lipids, nucleotides, unknown metabolites, and exogenous substances. Pipecolate posed the highest risk for the development of angina pectoris among the 42 serum metabolites. The main metabolic pathways associated with angina pectoris were glycine, serine, threonine metabolism, primary bile acid biosynthesis, and caffeine metabolism. CONCLUSION: We identified 25 high-risk and 17 protective human serum metabolites associated with angina pectoris. Their associated major metabolic pathways were also determined. The serum metabolite pipecolate was significantly and positively correlated with the risk of angina pectoris. This finding may serve as a valuable reference for testing serum markers associated with angina pectoris.

Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. METHODS: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. RESULTS: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27-5.33; P < .0087). Comparisons of ML-derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62-0.79) for PAH. CONCLUSIONS: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.

Analysis of the effect of CYP2C19 gene properties on the anti-platelet aggregation of clopidogrel after carotid artery stenting under network pharmacology.

Antiplatelet therapy is an important factor influencing the postterm patency rate of carotid artery stenting (CAS). Clopidogrel is a platelet aggregation inhibitor mediated by the adenosine diphosphate receptor and is affected by CYP2C19 gene polymorphisms in vivo. When the CYP2C19 gene has a nonfunctional mutation, the activity of the encoded enzyme will be weakened or lost, which directly affects the metabolism of clopidogrel and ultimately weakens its antiplatelet aggregation ability. Therefore, based on network pharmacology, analyzing the influence of CYP2C19 gene polymorphisms on the antiplatelet therapeutic effect of clopidogrel after CAS is highly important for the formulation of individualized clinical drug regimens. The effect of the CYP2C19 gene polymorphism on the antiplatelet aggregation of clopidogrel after CAS was analyzed based on network pharmacology. A total of 100 patients with ischemic cerebrovascular disease who were confirmed by the neurology department and required CAS treatment were studied. CYP2C19 genotyping was performed on all patients via a gene chip. All patients were classified into the wild-type (WT) group (*1/*1), heterozygous mutation (HTM) group (CYP2C19*1/*2, CYP2C19*1/*3), and homozygous mutation (HMM) group (CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3). High-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) was used to detect the blood concentration of clopidogrel and the plasma clopidogrel clearance (CL) rate in different groups of patients before and after clopidogrel treatment. The platelet aggregation rate of patients with different genotypes was measured by turbidimetry. The incidences of clopidogrel resistance (CR) and stent thrombosis in different groups after three months of treatment were analyzed. The results showed that among the different CYP2C19 genotypes, patients from the HTM group accounted for the most patients, while patients from the HTM group accounted for the least patients. Similarly, the clopidogrel CL of patients in the HMM group was lower than that of patients in the WT group and HTM group (P < 0.01). The platelet inhibition rate of patients in the HMM group was evidently inferior to that of patients in the WT group and HTM group (P < 0.01). The incidence of CR and stent thrombosis in the WT group was notably lower than that in the HTM and HMM groups (P < 0.01). These results indicate that the CYP2C19 gene can affect CR occurrence and stent thrombosis after CAS by influencing clopidogrel metabolism and platelet count.

Genomic variation across distribution of Micro-Tom, a model cultivar of tomato (Solanum lycopersicum).

Micro-Tom is a cultivar of tomato (Solanum lycopersicum), which is known as a major crop and model plant in Solanaceae. Micro-Tom has phenotypic traits such as dwarfism, and substantial EMS-mutagenized lines have been reported. After Micro-Tom was generated in Florida, USA, it was distributed to research institutes worldwide and used as a genetic resource. In Japan, the Micro-Tom lines have been genetically fixed; currently three lines have been re-distributed from three institutes, but many phenotypes among the lines have been observed. We have determined the genome sequence de novo of the Micro-Tom KDRI line, one of the Micro-Tom lines distributed from Kazusa DNA Research Institute (KDRI) in Japan, and have built chromosome-scale pseudomolecules. Genotypes among six Micro-Tom lines, including three in Japan, one in the United States, one in France, and one in Brazil showed phenotypic alternation. Here, we unveiled the swift emergence of genetic diversity in both phenotypes and genotypes within the Micro-Tom genome sequence during its propagation. These findings offer valuable insights crucial for the management of bioresources.

Structural characterization and comparative analysis of polymorphic forms of psilocin (4-hy-droxy-N,N-di-methyl-tryptamine).

The title compound, C12H16N2O, is a hy-droxy-substituted mono-amine alkaloid, and the primary metabolite of the naturally occurring psychedelic compound psilocybin. Crystalline forms of psilocin are known, but their characterization by single-crystal structure analysis is limited. Herein, two anhydrous polymorphic forms (I and II) of psilocin are described. The crystal structure of polymorphic Form I, in space group P21/c, was first reported in 1974. Along with the redeterm-ination to modern standards and unambiguous location of the acidic H atom and variable-temperature single-crystal unit-cell determinations for Form I, the Form II polymorph of the title compound, which crystallizes in the monoclinic space group P21/n, is described for the first time. The psilocin mol-ecules are present in both forms in their phenol-amine tautomeric forms (not resolved in the 1974 report). The mol-ecules in Forms I and II, however, feature different conformations of their N,N-dimethyl ethyl-ene substituent, with the N-C-C-C link in Form I being trans and in Form II being gauche, allowing the latter to bend back to the hydroxyl group of the same mol-ecule, leading to the formation of a strong intra-molecular O-H⋯N hydrogen bond between the hydroxyl moiety and ethyl-amino-nitro-gen group. In the extended structure of Form II, the mol-ecules form one-dimensional strands through N-H⋯O hydrogen bonds from the indole group to the oxygen atom of the hydroxyl moiety of an adjacent mol-ecule. Form II exhibits whole-mol-ecule disorder due to a pseudo-mirror operation, with an occupancy ratio of 0.689 (5):0.311 (5) for the two components. In contrast, Form I does not feature intra-molecular hydrogen bonds but forms a layered structure through inter-molecular N-H⋯O and O-H⋯N hydrogen bonds.

Synthesis, crystal structure and thermal properties of a new polymorphic modification of diiso-thio-cyanato-tetra-kis-(4-methyl-pyridine)cobalt(II).

The title compound, [Co(NCS)2(C6H7N)4] or Co(NCS)2(4-methyl-pyridine)4, was prepared by the reaction of Co(NCS)2 with 4-methyl-pyridine in water and is isotypic to one of the polymorphs of Ni(NCS)2(4-methyl-pyridine)4 [Kerr & Williams (1977 ▸). Acta Cryst. B33, 3589-3592 and Soldatov et al. (2004 ▸). Cryst. Growth Des. 4, 1185-1194]. Comparison of the experimental X-ray powder pattern with that calculated from the single-crystal data proves that a pure phase has been obtained. The asymmetric unit consists of one CoII cation, two crystallographically independent thio-cyanate anions and four independent 4-meth-yl-pyridine ligands, all located in general positions. The CoII cations are sixfold coordinated to two terminally N-bonded thio-cyanate anions and four 4-methyl-pyridine coligands within slightly distorted octa-hedra. Between the complexes, a number of weak C-H⋯N and C-H⋯S contacts are found. This structure represent a polymorphic modification of Co(NCS)2(4-methyl-pyridine)4 already reported in the CCD [Harris et al. (2003 ▸). NASA Technical Reports, 211890]. In contrast to this form, the crystal structure of the new polymorph shows a denser packing, indicating that it is thermodynamically stable at least at low temperatures. Thermogravimetric and differential thermoanalysis reveal that the title compound starts to decomposes at about 100°C and that the coligands are removed in separate steps without any sign of a polymorphic transition before decomposition.

Validation of single nucleotide polymorphisms potentially related to R-CHOP resistance in diffuse large B-cell lymphoma patients.

Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma (NHL). Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis, in up to 30%-40% of patients, intrinsic or acquired drug resistance occurs. Constitutional genetics may help to predict R-CHOP resistance. This study aimed to validate previously identified single nucleotide polymorphisms (SNPs) in the literature as potential predictors of R-CHOP resistance in DLBCL patients, SNPs. Methods: Twenty SNPs, involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes, were investigated in 185 stage I-IV DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP. Results: Correlations between rs2010963 (VEGFA gene) and sex (P = 0.046), and rs1625895 (TP53 gene) and stage (P = 0.003) were shown. After multivariate analyses, a concordant effect (i.e., increased risk of disease progression and death) was observed for rs1883112 (NCF4 gene) and rs1800871 (IL10 gene). When patients were grouped according to the revised International Prognostic Index (R-IPI), both these SNPs further discriminated progression-free survival (PFS) and overall survival (OS) of the R-IPI-1-2 subgroup. Overall, patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients. Conclusions: Two out of the 20 study SNPs were validated. Thus, these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients. These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.

Meta-analysis of the effects of CYP3A5*3 gene polymorphisms on tacrolimus blood concentration and effectiveness in Chinese patients with membranous nephropathy.

Objective: The study aimed to systematically evaluate the relationship between CYP3A5*3 gene polymorphisms and the blood concentration and effectiveness of tacrolimus (TAC) in patients with membranous nephropathy (MN). Methods: PubMed, Cochrane Library, Embase, Web of Science, China Biomedical, China National Knowledge Infrastructure, Wanfang, Vipshop, ReadShow, Clinical Trials Registry, and other databases were searched. Studies on the relationship between CYP3A5*3 gene polymorphism and TAC blood concentration in MN patients were collected, and meta-analysis was performed using Stata 16 software. Results: A total of eight publications were included in the study, including 498 MN patients. CYP3A5*3 gene polymorphisms are associated with tacrolimus blood levels in patients with MN. The results of the relationship between CYP3A5*3 genotype polymorphisms and tacrolimus blood trough concentrations of the AA + AG genotype were lower than those of the GG genotype at ≤1 month [WMD = -2.08, 95% CI (-2.57, -1.59), p < 0.001] and 1-6 months [WMD = -0.63, 95% CI (-0.98, -0.27), p < 0.001]; however, they were not statistically significant at ≥6 months (p = 0.211). Furthermore, the subgroup analysis revealed that the dose-adjusted concentration of tacrolimus (C0/D) of the AA + AG genotype was lower than that of the GG genotype at ≤1 month [SMD = -1.93, 95% CI (-2.79, -1.08), p < 0.001], 1-6 months [SMD = -2.25, 95% CI (-2.71, -1.79), p < 0.001], and ≥6 months [SMD = -2.36, 95% CI (-2.86, -1.86), p < 0.001]. In addition, there was no statistically significant difference in effectiveness between the two groups at 3, 6, and 12 months of TAC administration (p > 0.05). Conclusion: Serum TAC concentrations in MN patients were correlated with CYP3A5*3 genotype polymorphisms. Detection of the CYP3A5*3 genotype before the administration of TAC may provide some clinical value for optimizing the treatment of MN patients. Systematic Review Registration: https://inplasy.com/, identifier [INPLASY202430083].

The Relationship Between the hOGG1 rs1052133 Polymorphism and the Occurrence of Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Objectives: Exploring the relationship between the hOGG1 rs1052133 polymorphism and the occurrence of nasopharyngeal carcinoma (NPC). Methods: PubMed, Web of Science, Scopus, CNKI, Wanfangdata, and VIP were used to search for studies and the NOS evaluation scale was used to evaluate the quality. All studies were grouped according to different genotypes. The Cochrane's Q test and I2 test were used for heterogeneity evaluations. If heterogeneity was small, the fixed effects model was used, and conversely, the random effects model was used. Publication bias was also detected. P < .05 in all results indicated statistically significant. Results: We ultimately included 6 studies with 2021 NPC patients in the study group and 2375 healthy populations in the control group. After meta-analysis, it was found that the total OR value of the "Ser/Cys (CG) vs Ser/Ser (CC)" group was 1.00 (95% CI: 0.85-1.18) and the "Cys/Cys (GG) vs Ser/Ser (CC)" group was 1.06 (95% CI: 0.87-1.28). These results were not statistically significant (P > .05). Furthermore, the integrated total OR values of each group were not statistically significant with or without the smoking history, even in other genotype models (Allele, Dominant, Recessive, and Additive) (P > .05). Conclusion: There is no clear correlation between the hOGG1 rs1052133 polymorphism and the occurrence of NPC, even with or without the smoking history.

Microsatellite marker-assisted backcross breeding for improvement of wheat salt tolerance using Kharchia 65.

BACKGROUND: Salinity is a significant abiotic stress that affects plants from germination through all growth stages. This study was aimed to determine the morpho-physiological and genetic variations in BC1F2, BC2F1 and F3 generations resulting from the cross combination WH1105 × Kharchia 65. RESULTS: A significant reduction in germination percentage was observed under salt stress in BC1F2 and F3 seeds. Correlation, heritability in the broad sense, phenotypic coefficient of variability (PCV) and genotypic coefficient of variability (GCV) were measured for all traits. The presence of both Nax1 and Nax2 loci was confirmed in twenty-nine plants using the marker-assisted selection technique. Genetic relationships among the populations were assessed using twenty-four polymorphic SSR markers. CONCLUSION: Cluster analysis along with two and three-dimensional PCA scaling (Principal Component Analysis) revealed the distinct nature of WH 1105 and Kharchia 65. Six plants closer to the recurrent parent (WH1105) selected through this study can serve as valuable genetic material for salt-tolerant wheat improvement programs.

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population.

Aim: To identify the associations of 19 single nucleotide polymorphisms (SNPs) in genes involved in inflammation and endothelial function and carotid atherosclerosis with subsequent ischemic stroke and other vascular events in the high-risk stroke population. Methods: This was a multicenter community-based sectional survey and prospective cohort study in Sichuan, southwestern China. Eight communities were randomly selected, and the residents in each community were surveyed using a structured face-to-face questionnaire. Carotid ultrasonography and DNA information were obtained from 2,377 out of 2,893 individuals belonging to a high-risk stroke population. Genotypes of the 19 SNPs in genes involved in inflammation and endothelial function were measured. All the 2,377 subjects were followed up for 4.7 years after the face-to-face survey. The primary outcome was ischemic stroke, and the secondary outcome was a composite of vascular events. Results: Among the 2,377 subjects, 2,205 (92.8%) completed a 4.7-year follow-up, 947 (42.9%) had carotid atherosclerosis [372 (16.9%) carotid vulnerable plaque, 405 (18.4%) mean IMT > 0.9 mm, 285 (12.0%) carotid stenosis ≥15%]. Outcomes occurred in 158 (7.2%) subjects [92 (4.2%) ischemic stroke, 17 (0.8%) hemorrhagic stroke, 48 (2.2%) myocardial infarction, and 26 (1.2%) death] during follow-up. There was a significant gene-gene interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 in the 19 SNPs. The multivariate logistic regression model revealed that carotid atherosclerosis and the high-risk interactive genotypes among the three SNPs were independent with a higher risk for ischemic stroke (OR = 2.67, 95% CI: 1.52-6.78, p = 0.004; and OR = 3.11, 95% CI: 2.12-9.27, p < 0.001, respectively) and composite vascular events (OR = 3.04, 95% CI: 1.46-6.35, p < 0.001; and OR = 3.23, 95% CI: 1.97-8.52, p < 0.001, respectively). Conclusion: The prevalence of carotid atherosclerosis was shown to be very high in the high-risk stroke population. Specific SNPs, interactions among them, and carotid atherosclerosis were independently associated with a higher risk of ischemic stroke and other vascular events.

Association of single nucleotide polymorphism rs3213119 variant of IL-12B gene in diagnosed Rheumatoid Arthritis patients.

Objective: To identify the IL12B gene variant (rs3213119) and to find its association in Pakistani clinical population of Rheumatoid Arthritis. Methods: It was a population association (unrelated) case control study, performed from January - December 2022 at Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi. Blood samples were collected from all 150 study participants, followed by DNA extraction and Allele-specific polymerase chain reaction performed at Center for Research in Experimental and Applied Medicine (CREAM) Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using 'SPSS' (version-22), followed by gene analysis on 'SNPstat'. Results: About 28.0% of RA patients were smokers, 38.7% had history of RA in a first degree relative and 70.7% had positive history of consanguinity. Considering rs3213119 variant of IL12B gene, frequency of major allele C was 100%, minor allele A was 21%, genotype C/C was 79% and C/A was 21%. Applying the log additive model, the odds ratio of the genotype C/C was 1.00 (adjusted by age and gender with 95 % CI) and the odds ratio of the genotype C/A was 0.00, 52.0% of RA patients originated from four predominant ethnic groups, namely Awaans (18.7%), Rajputs (14.7%), Pathans (12.0%) and Araeens (6.7%). Conclusion: The study findings suggest the role of minor allele 'A' as risk allele in our clinical population. CA genotype confers susceptibility towards the RA development.

Association between the gut microbiota and diabetic nephropathy: a two-sample Mendelian randomization study.

Numerous studies have revealed a correlation between the risk of developing diabetic nephropathy (DN) and the gut microbiota (GM) composition. However, it remains uncertain whether the GM composition causes DN. We aimed to explore any potential causal links between the GM composition and the risk of developing DN. A meta-analysis conducted by the MiBioGen consortium of the largest genome-wide association study (GWAS) provided aggregated data on the GM. DN data were obtained from the IEU database. The inverse-variance weighting (IVW) method was employed as the primary analytical approach. The IVW analysis indicated that genus Dialister (OR = 0.51, 95% CI: 0.34-0.77, p = 0.00118) was protective against DN. In addition, class Gammaproteobacteria (OR = 0.47, 95% CI: 0.27-0.83, p = 0.0096), class Lentisphaeria (OR =0.76, 95% CI: 0.68-0.99, p = 0.04), order Victivallales (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04), and phylum Proteobacteria (OR = 0.53, 95% CI: 0.33-0.85, p = 0.00872) were negatively associated with the risk of developing DN. Genus LachnospiraceaeUCG008 (OR =1.45, 95% CI: 1.08-1.95, p = 0.01), order Bacteroidales (OR = 1.59, 95% CI: 1.02-2.49, p = 0.04), and genus Terrisporobacter (OR = 1.98, 95% CI: 1.14-3.45, p = 0.015) were positively associated with the risk of developing DN. In this study, we established a causal relationship between the genus Dialister and the risk of developing DN. Further trials are required to confirm the protective effects of probiotics on DN and to elucidate the precise protective mechanisms involving genus Dialister and DN.