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Expression of LINC00847 in Peripheral Blood Mononuclear Cells of Children with Asthma and Its Prediction between Asthma Exacerbation and Remission
Objective. Asthma is defined as a heterogeneous disease that is usually characterized by chronic airway inflammation. Long noncoding RNAs play important roles in various biological processes including inflammation. To know more about the relationships between lncRNAs and asthma, we sought to the role of LINC00847 in peripheral blood mononuclear cells (PBMCs) of children with asthma exacerbation or asthma remission. Methods. Microarray analysis was performed on GSE143192 and GSE165934 datasets to screen differentially expressed lncRNAs (DElncRNAs) in human PBMCs between asthma patients and normal controls. LINC00847 was selected from DElncRNAs in human PBMCs between asthma patients and normal controls for further investigation. The expression levels of LINC00847 were quantified in PBMCs collected from 54 children with asthma exacerbation, 54 children with asthma remission, and 54 healthy children by real-time qPCR. The forced expiratory volume in the first second in percent predicted values (FEV1%), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), and peak expiratory flow rate (PEF%) were tested for evaluation of lung function. The concentration of immunoglobulin E (IgE) and eosinophil count was examined. The serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17A were determined by the ELISA method. Results. The expression level of LINC00847 in PBMCs of asthma exacerbation children was remarkably higher than that in PBMCs of asthma remission children and healthy children (); the expression level of LINC00847 in PBMCs of asthma remission children was notably higher than that in PBMCs of healthy children (). Pearson correlation analysis revealed that the expression levels of LINC00847 in PBMCs of asthma children were negatively correlated with FEV1% (r = −0.489), FEV1/FVC (r = −0.436), PEF% (r = −0.626), and IFN-γ level (r = −0.614) of asthma children, but positively correlated with IgE concentration (r = 0.680), eosinophil count (r = 0.780), IL-4 (r = 0.524), and IL-17A (r = 0.622) levels. When LINC00847 expression was used to distinguish asthma exacerbation from asthma remission, a 0.871 AUC (95% CI: 0.805–0.936) was yielded with sensitivity of 79.63% and specificity of 77.78%. Conclusion. The study demonstrates that increased LINC00847 expression may be associated with the development and progression of asthma, possibly serving as a novel biomarker for predicting asthma exacerbation from asthma remission.
TPX2 Serves as a Cancer Susceptibility Gene and Is Closely Associated with the Poor Prognosis of Endometrial Cancer
Background. Endometrial cancer (EC) is a common tumor of the genital tract that affects the female reproductive system but with only limited treatment options. We aimed to discover new prognostic biomarkers for EC. Methods. We used mRNA-seq data to detect differentially expressed genes (DEGs) between EC and control tissues. Detailed clinicopathological information was collected, and changes in the mRNA and protein levels of hub DEGs were analyzed in EC. Copy number variation (CNV) was also evaluated for its association with the pathogenesis of EC. Gene set enrichment analysis (GSEA) was conducted to enrich significant pathways driven by the hub genes. Cox regression analysis was used to select variables to create a nomogram. The nomogram was calibrated by applying the concordance index (C-index), and net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). Results. Differential expression analysis identified 24 DEGs as potential risk factors for EC. Survival analysis revealed that TPX2 expression was related to worsening overall survival in patients with advanced EC. A high CNV was associated with the overexpression of TPX2; this suggested that modifications in the cell-cycle pathway might be crucial in the advancement of EC. Moreover, an individualized nomogram was developed for TPX2 incorporating clinical factors; this was also evaluated for its ability to predict EC. Calibration and DCA analyses confirmed the robustness and clinical usefulness of the nomogram. Conclusion. We offer novel insights into the pathogenesis and molecular mechanisms of EC. The overexpression of TPX2 was related to a poorer prognosis and could serve as a biomarker for predicting prognostic outcomes in EC patients.
Genomic and Computational Analysis of Novel SNPs in TNP1 Gene Promoter Region of Bos indicus Breeding Bulls
Transition nuclear proteins (TNPs), the principal proteins identified in the condensing spermatids chromatin, have been found to play a key role in histone displacement and chromatin condensation during mammalian spermatogenesis. One such gene belonging to the TNP family called TNP1 gene is abundantly expressed in the regulation of spermatogenesis, and its sequence is remarkably well conserved among mammals. Genomic analysis, by sequencing and computational approach, was used to identify the novel polymorphisms and to evaluate the molecular regulation of TNP1 gene expression in Sahiwal cattle breeding bulls. DNA samples were sequenced to identify novel single nucleotide polymorphisms (SNPs) in the TNP1 gene. Modern computational tools were used to predict putative transcription factor binding in the TNP1 promoter and CpG islands in the TNP1 promoter region. In the TNP1 gene, four SNPs, three TATA boxes, and one CAAT box were identified. One CAAT box was discovered at 89 bp upstream of start site ATG. The computational analyses indicated that the polymorphisms inside the promoter sequence results in an added HNF-1 transcription factor binding site. In contrast, the other variations may remove the naturally occurring SRF transcription factor binding site. The CpG islands in the TNP1 promoter region were predicted to be absent by the MethPrimer program before and after SNP site mutations. These findings pave the way for more research into the TNP1 gene’s promoter activity and the links between these SNPs and reproductive attributes in the Sahiwal breeding bulls.
circRNA_101277 Influences Cisplatin Resistance of Colorectal Cancer Cells by Modulating the miR-370/IL-6 Axis
Background. Colorectal cancer (CRC) is among the most prevalent malignancies globally. Early detection of precancerous lesions through routine colonoscopy has led to a dramatic reduction in CRC-related incidence and mortality among those between the ages of 50 and 70. However, in those where the disease progresses to an advanced stage, chemotherapy remains the primary available treatment option, and the associated 5-year survival rate remains low. The identification of genes associated with CRC chemoresistance would thus be a beneficial approach to identifying novel treatments for this deadly disease. Methods. The expression of circRNA_101277, miR-370, and IL-6 was assessed via qRT-PCR. IL-6 levels were measured with a human IL-6 ELISA kit based on the provided protocols. CRC cellular proliferation and cisplatin IC50 values were quantified via MTT assays. Luciferase assays were used to detect circRNA_101277 and miR-370 binding sites or miR-370 and IL-6 binding sites. Results. circRNA_101277 was increased in CRC tissues compared with control samples. circRNA_101277 overexpression was evident in CRC cells, and knockdown of this circRNA suppressed cellular proliferation and cisplatin resistance in these cancer cells. At a mechanistic level, circRNA_101277 was found to function by sequestering miR-370, thereby upregulating the miR-370 target gene IL-6 and promoting cisplatin resistance via this miR-370/IL-6 axis. Conclusion. In summary, our data highlight circRNA_101277 as a novel driver of CRC cell cisplatin resistance that functions by sequestering miR-370 and thereby enhancing IL-6 expression. These findings suggest that this circRNA_101277/miR-370/IL-6 axis may represent a critical axis of chemoresistance in CRC that can be targeted to diagnose and/or treat this cancer.
Reduced Concentrations of NSE, S100β, Aβ, and Proinflammatory Cytokines in Elderly Patients Receiving Ultrasound-Guided Combined Lumbar Plexus-Sciatic Nerve Block during Hip Replacement
Objective. The increase of hip fractures is related to the aging of the population, which has caused a huge medical burden in many countries. Hip replacement has been approved as a highly successful surgical intervention for the patients with hip fractures. Different anesthesia choices in the surgical intervention are associated with the prognosis of patients. This study focused on investigating the application of ultrasound-guided combined lumbar plexus-sciatic nerve block in elderly patients with hip fractures. Methods. In this retrospective study, 62 elderly patients received combined spinal-epidural anesthesia and 58 elderly patients underwent ultrasound-guided combined lumbar plexus-sciatic nerve block during the surgery. Hemodynamic monitoring including pulse oxygen saturation (SpO2), heart rate and blood pressure, the assessment of pain intensity using Visual Analogue Scale (VAS), cognitive function assessment through Montreal Cognitive Assessment (MoCA) and biomarkers consisting of serum levels of neuron specific-enolase (NSE), S100 beta protein (S100-β), and amyloid beta protein (Aβ), as well as immune function by interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were detected in this study. Furthermore, length of hospital stay (LOS) and adverse reactions including hematoma, hypotension, nausea, and vomit were analyzed. Results. The findings indicated that comparing with the patients receiving combined spinal-epidural anesthesia, those undergoing ultrasound-guided combined lumbar plexus-sciatic nerve block showed significantly lower level of heart rate, higher level of SpO2, and lower level of diastolic pressure and systolic pressure at 5 minutes and 30 minutes after anesthesia and after surgery (), indicated obviously lower VAS score at 12, 24, and 48 hours after surgery (), and revealed higher MoCA score at 12 days after surgery (). A significantly higher level of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP was revealed in the two groups receiving different anesthesia methods at 10 days after surgery compared with that before surgery (). However, the patients receiving ultrasound-guided combined lumbar plexus-sciatic nerve block had obviously lower expression of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP compared with the group accepting combined spinal-epidural anesthesia (). The two groups indicated no significant difference in incidence of hypotension and vomit, etc. (), but showed remarkable difference referring to total incidence of adverse reactions and LOS (). Conclusion. The application of ultrasound-guided combined lumbar plexus-sciatic nerve block in hip replacement contributes to the stability of hemodynamics and alleviation of postoperative pain intensity. It can reduce cognitive and immune impairment of the elderly patients with hip fractures.
Reduced Circulating Levels of miR-491-5p and miR-485-3p Are Associated with the Occurrence of Vertebral Fractures in Postmenopausal Women with Osteoporosis
Objective. Postmenopausal women experiences osteoporotic structural damage and bone fragility resulting from reduced bone formation and increased bone resorption. Osteoporosis frequently affects the vertebral column and causes compression fractures. This study aims to characterize roles of miRNAs in osteoporosis and subsequent incidence risk of vertebral fractures for postmenopausal women. Methods. Differentially expressed miRNAs between osteoporotic patients with vertebral fractures and osteoporotic patients without fracture were identified. This retrospective study included 78 osteoporotic patients with vertebral fractures and 82 osteoporotic patients without vertebral fractures. The plasma levels of bone metabolic markers, 25-hydroxyvitamin D (25-(OH)VitD), propeptide of type I procollagen (PINP), and β-Carboxyl terminal peptide (β-CTx), were detected using the patented electro-chemiluminescence (ECLIA) method. The expression levels of miR-491-5p and miR-485-3p were determined by qRT-PCR. Pearson correlation analysis was carried out to assess the relationship between miR-491-5p, miR-485-3p, and bone metabolic markers. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the performance of miR-491-5p and miR-485-3p in diagnosing the occurrence of vertebral fractures in osteoporotic patients.Results: The plasma levels of PINP and β-CTx were elevated but the plasma level of 25-(OH)VitD was declined in osteoporotic patients with vertebral fractures when comparable to those without (< 0.05). The plasma expression levels of miR-491-5p and miR-485-3p were declined osteoporotic patients with vertebral fractures when comparable to those without (< 0.001). Pearson correlation analysis revealed that the relative expression level of miR-491-5p was negatively correlated with the level of 25-(OH)VitD (r = -0.518, < 0.001) but positively correlated with the levels of PINP (r = 0.547, < 0.001) and β-CTx (r = 0.380, < 0.001). We also observed a negative correlation between the relative expression level of miR-485-3p and 25-(OH)VitD (r = -0.388, < 0.001), a positive correlation between miR-485-3p and PINP (r = 0.422,< 0.001). ROC curves for prediction of vertebral fracture following osteoporosis in postmenopausal women by miR-491-5p expression yielded 0.866 AUC and by miR-485-3p expression produced 0.848 AUC. Conclusion. The data suggest that downregulated expressions of miR-491-5p and miR-485-3p may be involved in the occurrence of vertebral fractures in postmenopausal women with osteoporosis.