Search Results (7)

Schistosomiasis is a neglected tropical disease and the second most common parasitic disease after malaria. While praziquantel remains the primary treatment, concerns about drug resistance highlight the urgent need for new drugs and effective vaccines to achieve sustainable control. Previous proteomic studies from our group revealed that the expression of Schistosoma japonicum glycosyltransferase and nicastrin as proteins was higher in single-sex males than mated males, suggesting their critical roles in parasite reproduction and their potential as vaccine candidates. In this study, bioinformatic tools were employed to analyze the structural and functional properties of these proteins, including their signal peptide regions, transmembrane domains, tertiary structures, and protein interaction networks. Recombinant forms of glycosyltransferase and nicastrin were expressed and purified, followed by immunization experiments in BALB/c mice. Immunized mice exhibited significantly elevated specific IgG antibody levels after three immunizations compared to adjuvant and PBS controls. Furthermore, immunization with recombinant glycosyltransferase and nicastrin significantly reduced the reproductive capacity of female worms and liver egg burden, though egg hatchability and adult worm survival were unaffected. These findings demonstrate that recombinant glycosyltransferase and nicastrin are immunogenic and reduce female worm fecundity, supporting their potential as vaccine candidates against schistosomiasis. Full article

The NOTCH-signaling pathway is responsible for intercellular interactions and cell fate commitment. Recently, NOTCH pathway genes were demonstrated to play an important role in aortic valve development, leading to an increased calcified aortic valve disease (CAVD) later in life. Here, we further investigate the association between genetic variants in the NOTCH pathway genes and aortic stenosis in a case–control study of 90 CAVD cases and 4723 controls using target panel sequencing of full-length 20 genes from a NOTCH-related pathway (DVL2, DTX2, MFNG, NUMBL, LFNG, DVL1, DTX4, APH1A, DTX1, APH1B, NOTCH1, ADAM17, DVL3, NCSTN, DTX3L, ILK, RFNG, DTX3, NOTCH4, PSENEN). We identified a common intronic variant in NOTCH1, protecting against CAVD development (rs3812603), as well as several rare and unique new variants in NOTCH-pathway genes (DTX4, NOTCH1, DTX1, DVL2, NOTCH1, DTX3L, DVL3), with a prominent effect of the protein structure and function. Full article

Hidradenitis suppurativa (HS), recognized as a chronic and debilitating skin disease, presents significant challenges in both diagnosis and treatment. This review explores the clinical manifestations, genetic landscape, and molecular mechanisms underlying HS. The disease’s association with a predisposing genetic background, obesity, smoking, and skin occlusion underscores the complexity of its etiology. Genetic heterogeneity manifests in sporadic, familial, and syndromic forms, with a focus on mutations in the γ-secretase complex genes, particularly NCSTN. The dysregulation of immune mediators, including TNF-α, IL-17, IL-1β, and IL-12/23, plays a crucial role in the chronic inflammatory nature of HS. Recent advancements in genetic research have identified potential therapeutic targets, leading to the development of anti-TNF-α, anti-IL-17, anti-IL-1α, and anti-IL-12/23 therapies and JAK inhibitors. These interventions offer promise in alleviating symptoms and improving the quality of life for HS patients. Full article

Canine lymphoma (CL) is one of the most common malignant tumors in dogs. The cause of CL remains unclear. Genetic mutations that have been suggested as possible causes of CL are not fully understood. Whole-exome sequencing (WES) is a time- and cost-effective method for detecting genetic variants targeting only the protein-coding regions (exons) that are part of the entire genome region. A total of eight patients with B-cell lymphomas were recruited, and WES analysis was performed on whole blood and lymph node aspirate samples from each patient. A total of 17 somatic variants (GOLIM4, ITM2B, STN1, UNC79, PLEKHG4, BRF1, ENSCAFG00845007156, SEMA6B, DSC1, TNFAIP1, MYLK3, WAPL, ADORA2B, LOXHD1, GP6, AZIN1, and NCSTN) with moderate to high impact were identified by WES analysis. Through a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 17 genes with somatic mutations, a total of 16 pathways were identified. Overall, the somatic mutations identified in this study suggest novel candidate mutations for CL, and further studies are needed to confirm the role of these mutations. Full article

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A–C (1–3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan–ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1–3 all reduce Aβ42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer’s disease [AD] associated with BACE1-, NCSTN-, GSK3β-, and CDK5-mediated pathways, suggesting these alkaloids’ potential against AD. Full article

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on miRNA–target interactions (MTI) associated with AD are scattered across databases and publications, thus making the identification of promising miRNA biomarkers for AD difficult. In response to this, a list of experimentally validated AD-associated MTIs was obtained from miRTarBase. Cytoscape was used to create a visual MTI network. STRING software was used for protein–protein interaction analysis and mirPath was used for pathway enrichment analysis. Several targets regulated by multiple miRNAs were identified, including: BACE1, APP, NCSTN, SP1, SIRT1, and PTEN. The miRNA with the highest numbers of interactions in the network were: miR-9, miR-16, miR-34a, miR-106a, miR-107, miR-125b, miR-146, and miR-181c. The analysis revealed seven subnetworks, representing disease modules which have a potential for further biomarker development. The obtained MTI network is not yet complete, and additional studies are needed for the comprehensive understanding of the AD-associated miRNA targetome. Full article

Derivative chromosome der(1;16), isochromosome 1q, and deleted 16q—producing arm-level 1q-gain and/or 16q-loss—are recurrent cytogenetic abnormalities in breast cancer, but their exact role in determining the malignant phenotype is still largely unknown. We exploited The Cancer Genome Atlas (TCGA) data to generate and analyze groups of breast invasive carcinomas, called 1,16-chromogroups, that are characterized by a pattern of arm-level somatic copy number aberrations congruent with known cytogenetic aberrations of chromosome 1 and 16. Substantial differences were found among 1,16-chromogroups in terms of other chromosomal aberrations, aneuploidy scores, transcriptomic data, single-point mutations, histotypes, and molecular subtypes. Breast cancers with a co-occurrence of 1q-gain and 16q-loss can be distinguished in a “low aneuploidy score” group, congruent to der(1;16), and a “high aneuploidy score” group, congruent to the co-occurrence of isochromosome 1q and deleted 16q. Another three groups are formed by cancers showing separately 1q-gain or 16q-loss or no aberrations of 1q and 16q. Transcriptome comparisons among the 1,16-chromogroups, integrated with functional pathway analysis, suggested the cooperation of overexpressed 1q genes and underexpressed 16q genes in the genesis of both ductal and lobular carcinomas, thus highlighting the putative role of genes encoding gamma-secretase subunits (APH1A, PSEN2, and NCSTN) and Wnt enhanceosome components (BCL9 and PYGO2) in 1q, and the glycoprotein E-cadherin (CDH1), the E3 ubiquitin-protein ligase WWP2, the deubiquitinating enzyme CYLD, and the transcription factor CBFB in 16q. The analysis of 1,16-chromogroups is a strategy with far-reaching implications for the selection of cancer cell models and novel experimental therapies. Full article