Biochemical Genetics最新文献

Pain following endodontic treatment is a common complication potentially linked with genetic polymorphisms that modulate pain biomarkers. Hence, this study aimed to explore the association between pain experienced after endodontic treatment and genetic polymorphisms in the genes encoding inducible nitric oxide synthase (NOS2), and suppressor of cytokine signaling (SOCS1). The study involved 108 participants with single-rooted teeth, single canals, and necrotic pulp related to asymptomatic apical periodontitis. All endodontic treatments were executed in a single session. Pain and tenderness levels were measured using a visual analog scale (VAS) on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th, and 30th day post-treatment. Genomic deoxyribonucleic acid (DNA) was extracted from saliva cells and the genetic polymorphisms rs2779249, rs2297518, rs243327 and rs33977706 were genotyped using real-time polymerase chain reaction. Genotype distribution was assessed using univariate and multivariate Poisson regressions through generalized estimating equations (GEE) and categorized based on the presence or absence of pain and tenderness, and the significance threshold was set at p < 0.05. The genetic polymorphism rs2297518 in the NOS2 gene was associated with pain in the recessive model (p = 0.019) and to tenderness in both the codominant (p = 0.008) and recessive (p < 0.001) models. The genetic polymorphisms rs2779249 in NOS2 and rs243327 and rs33977706 in SOCS1 showed no association with pain or tenderness (p > 0.05). In conclusion, the genetic polymorphism rs2297518 in the NOS2 gene was associated with pain after root canal treatment. These findings contribute to a better understanding of the genetic factors influencing postoperative pain in endodontics, which may help in developing personalized pain management strategies and improving patient care.

Plants exhibit sophisticated defense mechanisms orchestrated by intricate molecular responses to biotic stresses. Here, we investigate the transcriptional dynamics of the CABMV-resistant cowpea line IT85F-2687 following mechanical injury and Cowpea aphid-borne mosaic virus (CABMV) inoculation. Transcriptome analysis revealed rapid up-regulation of genes associated with the shikimate pathway, notably DAHPS, ADT-PDT, and ADH, within one hour post-inoculation. Subsequent activation of phenylpropanoid and isoflavonoid pathways underscored the cowpea's adaptive responses, probably enhancing the synthesis of secondary metabolites crucial for defense. Transcripts encoding enzymes such as PAL, 4CL, and CHS were prominently upregulated, potentially directing metabolic flux towards lignin, flavonoid, and phytoalexin biosynthesis. The study also identified enrichment of transcription factor families (WRKY, MYB, bHLH) implicated in stress responses and secondary metabolism regulation. Comparative genomics highlighted conservation of orthologs among legume species, suggesting evolutionary significance and potential utility for breeding resilient cultivars. These findings advance our understanding of plant-pathogen interactions and propose strategies for developing cowpea varieties with enhanced resistance to biotic stresses, contributing to sustainable agriculture.

Acute lung injury (ALI) is a severe respiratory syndrome for which there is still a lack of effective treatment. Salvianolic acid A (Sal A) is a bioactive polyphenol extracted from Salvia miltiorrhiza Bunge, which has anti-inflammatory and antioxidant effects, but its role in ALI is unclear. We injected 50 µL LPS into the trachea of mice, and treated MLE-12 cells with 1 µg/mL LPS to construct ALI mouse and cell model. The levels of genes and proteins was identified using RT‒qPCR, western blot and immunofluorescence. The damage of MLE-12 cells and mouse lung tissue was evaluated by CCK-8, ELISA, TUNEL and HE staining. Sal A treatment can significantly inhibit LPS-induced inflammation and apoptosis, and then inhibit MLE-12 cell damage and ALI progression. From a mechanistic standpoint, Sal A promotes the expression of LC3 II/I and Beclin1, suppresses p62 expression, increases cell autophagy, and suppresses LPS-induced inflammatory cytokines IL-6, IL-1β, and TNF-α expression, ultimately reducing LPS-induced inflammation in lung epithelial cells and alleviating ALI progression. The main function of Sal A is to achieve this by inhibiting the expression of miR-217-5p and thereby promoting the expression of FOXO1. Our research results may provide a new target for the treatment of ALI with Sal A.

Sickle cell disease (SCD) is one of the most frequently observed monogenic diseases and is a major health problem worldwide. It is particularly prevalent in some countries such as Africa, the Middle East and the Mediterranean region. Due to a single point mutation in the β-globin gene HBB (c.20 A > T), the glutamic acid is replaced by valine amino acid at the sixth position of the β-globin chain (p.Glu6Val), which leads to changes in the properties of the hemoglobin protein and affects the conformation of red blood cells. Importantly, the distribution of the sickle hemoglobin (HbS) allele varies worldwide. Without knowing the distribution of this allele, the true significance of this gene mutation for SCD is unknown. The aim of this study is to determine the frequency of the HBB (c.20 A > T) gene mutation in the Nigerian and Zimbabwean populations in Northern Cyprus. Blood samples were collected from 208 volunteers (100 Nigerians and 108 Zimbabweans) living in Northern Cyprus. DNA was extracted from peripheral leukocytes. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). The distribution of the allele and genotype frequencies of the HBB (c.20 A > T) gene mutation were tested for Hardy-Weinberg equilibrium. Notably, the distribution of the HBB (c.20 A > T) gene mutation in the Zimbabwean population was found to be in agreement with Hardy-Weinberg equilibrium (p > 0.05), suggesting a consistent allele frequency in this group. Particularly, the frequency of the HbS allele was determined to be 25% and 12.5% in the Nigerian and Zimbabwean populations, respectively. In summary, the results of this study have contributed to the literature by determining the frequency of the HBB (c.20 A > T) gene mutation in the Nigerian and Zimbabwean populations. This is crucial for understanding the true significance of this particular gene mutation for SCD in these two populations, which may also shed light on the development of better structured and preventive strategies.

Mitochondrial genomes are powerful tools for investigating the evolutionary dynamics and genetic diversity of social insects, particularly ants. Here, we present the complete mitochondrial genome of Mycetophylax conformis, a psammophilous, fungus-farming ant endemic to the Atlantic coastal sand dunes of southeastern Brazil. The circular mitogenome is 16,455 base pairs long and includes the canonical 37 genes: 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and a control region (CR). Gene content and order are consistent with those of other Myrmicinae ants. The nucleotide composition is strongly biased toward adenine and thymine (A+T = 82.1%) and exhibits moderate strand asymmetries, with an AT-skew of - 0.111 and a GC-skew of - 0.171. No large intergenic spacers or atypical structural features were identified, suggesting a highly conserved genomic architecture. This newly assembled mitogenome enhances the representation of Neoattina in mitochondrial databases and provides a valuable reference for future evolutionary, ecological, and comparative genomic studies of fungus-farming ants.

NIN-like proteins (NLPs) are plant-specific transcription factors with a conserved RWP-RK domain that can bind to nitrate-responsive cis-elements (NREs) in target gene promoters. NLPs play essential roles in nitrogen uptake, transport, metabolism, and are also involved in nitrate signaling, root development, and secondary metabolism. Salvia miltiorrhiza is a medicinal plant valued for its roots and rhizomes. It mainly contains two types of active ingredients: tanshinones and salvianolic acids. Previous studies have shown that nitrogen availability significantly affects the growth of S. miltiorrhiza and the accumulation of its active ingredients, but the regulatory mechanism has not yet been fully elucidated. In this study, 11 SmNLPs were identified in the S. miltiorrhiza genome through bioinformatic analyses, and they were found to be distributed across eight chromosomes. Phylogenetic analysis grouped them into three subfamilies, with members in the same clade sharing similar gene structures and conserved domains. Promoter analysis revealed that SmNLPs harbor cis-acting elements involved in stress responses, hormone signaling, development, and light responses. Tissue-specific expression analysis of two-year-old S. miltiorrhiza plants showed that SmNLPs are broadly expressed in roots, stems, leaves, and flowers, exhibiting distinct tissue-specific patterns. Among them, most SmNLPs, particularly SmNLP3 and SmNLP8, were significantly upregulated in nitrogen-deprivation hairy roots. Co-expression analysis based on transcriptome data suggested that SmNLP3, SmNLP8, and SmNLP10 may be involved in the regulation of tanshinone and salvianolic acid biosynthesis. These findings provide new insights into the potential roles of NLPs in nitrogen response and secondary metabolism in S. miltiorrhiza, laying a foundation for future functional studies and metabolic engineering.

Esophageal carcinoma (ESCA) represents a highly aggressive malignancy with limited therapeutic options. Mounting evidence indicated that Nuclear Lamin B2 (LMNB2) was involved in tumor progression through modulation of multiple signaling pathways. However, the investigation of LMNB2 role in tumor cell stemness and the Warburg effect remains inconclusive. This study utilized the UALCAN database to perform pan-cancer, clinical sample and cell line analyses. Western blot validation demonstrated substantial LMNB2 overexpression in ESCA cells. Silencing LMNB2 expression significantly repressed ESCA cells stemness and Warburg effect. Integrated bioinformatics analyses using Linkedomics, Funrich, and String databases identified the p38 MAPK pathway as a downstream mediator. In vitro experiments verified the regulatory impact of LMNB2 on the p38 phosphorylation in the MAPK signaling pathway, implicated in the regulation of tumor sphere formation and the Warburg effect. LMNB2 also exhibited a regulatory role in tumor growth within the mouse xenograft model. This study proposed that LMNB2 could emerge as a novel therapeutic strategy for treating ESCA.

Variants in several genes have been linked to congenital syndromes involving anophthalmia and microphthalmia; however, the specific genotypes and phenotypes associated with these conditions remain unclear. Calsequestrin 2 (CASQ2) is highly expressed in rodent extraocular muscles, but its role in eye development is unclear. In a previous study, we identified a novel CASQ2 (c.241G > A, p.A81T) mutation, which replaces the alanine residue at amino acid 81 with threonine, in a patient with catecholaminergic polymorphic ventricular tachycardia (CPVT). Here, we investigated its effect on eye development. The impact of the CASQ2 mutation on eye development was studied in zebrafish embryos by overexpressing the mutant gene. RNA sequencing was used to identify changes in gene expression, involving over 22,000 genes. Overexpression of the CASQ2 mutation in zebrafish embryos resulted in significant eye morphology changes, with 27.78% of embryos exhibiting anophthalmia or microphthalmia, compared to none in the control group (P < 0.0001). RNA sequencing revealed 1,240 differentially upregulated and 1158 downregulated genes in the CASQ2 mutant group. Nine genes significantly associated with eye development were identified, along with alterations in the Wnt signaling pathway and enrichment of six pathways: arginine and proline metabolism, apoptosis, lysosomes, biosynthesis of unsaturated fats, phototransduction, and p53 signaling. The novel CASQ2 mutation (c.241G > A, p.A81T) adversely affects eye development in zebrafish embryos, suggesting additional molecular pathways involved in anophthalmia and microphthalmia. This finding will enhance our understanding of the genetic basis of these eye conditions and may inform future research and therapeutic strategies.

Chlorella vulgaris, a unicellular freshwater microalga, is widely recognised as a functional food and supplement with immunomodulatory properties attributed to its bioactive components. These bioactive components include proteins, fatty acids, polysaccharides, pigments, and antioxidants. Nonetheless, a comprehensive gene-expression profile related to the innate and adaptive immune responses of C. vulgaris supplementation is lacking. This study aimed to evaluate the immunomodulatory effects of C. vulgaris in a mouse model through the oral administration of C. vulgaris biomass into BALB/c mice. Seven days after the oral administration, spleen tissues were analysed via a qPCR array to assess the expression of 84 genes related to the innate and adaptive immune response. Results show a significant upregulation (fold change > 2.0) of seven essential immune genes, such as Irf7, Mpo, Stat1, Tlr6, Tlr7, Tlr9, and Tyk2. In contrast, five immune-related genes, including Ccl5, Ccr6, Csf2, Myd88, and Rorc, were significantly downregulated (fold change <-2.0). These results show a comprehensive immune-gene expression profile elicited following seven days after the oral administration of C. vulgaris in mice. This work offers novel insights into the immunomodulatory properties of C. vulgaris through the immune gene expression profile it exhibited and underscores its known potential as an alternative therapy to boost immunity in various health conditions.

This study aims to investigate the genetic characteristics of Acute Myeloid Leukemia (AML) patients and identify which patients derive the greatest benefit from a low-intensity regimen of decitabine combined with modified Cytarabine + Aclarubicin + Granulocyte Colony-Stimulating Factor (D-CAG) or intensive chemotherapy (IA regimen). We retrospectively analyzed cytogenetic and molecular data of 331 newly diagnosed AML patients and examined the associations between genetic characteristics, risk status, treatment approaches, and clinical outcomes. The median follow-up duration was 45 months (range: 2-120 months). Patients receiving IA therapy achieved higher complete remission (CR) rates (79.3% vs. 66.4%, P < 0.05), while objective response rates (ORR) remained comparable between the two treatment arms. Both in the total cohort and among favorable-risk patients, the median overall survival (OS) was significantly reduced in the D-CAG group compared to the IA group (P < 0.05). For intermediate- and high-risk patients who had not undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), median OS outcomes were comparable between the two treatment regimens. Patients harboring TET2 (Tet methylcytosine dioxygenase 2), NRAS (Neuroblastoma RAS viral oncogene homolog), or biallelic CEBPA mutations demonstrated superior OS in the IA group compared to the D-CAG group (P < 0.05). Notably, older patients with complex or monosomal karyotypes exhibited longer median OS than their younger counterparts (P < 0.05). In conclusion, D-CAG may represent a more suitable therapeutic option for AML patients with high-risk karyotypic profiles.