Current Issue : January-March Volume : 2026 Issue Number : 1 Articles : 6 Articles
Background Autosomal Dominant Alport Syndrome (ADAS) is a rare genetic disorder caused by mutations in the COL4A3, COL4A4, or COL4A5 genes. ADAS often presents with proteinuria and hematuria, and while progressive renal insufficiency can develop, it typically progresses more slowly compared to other forms of Alport syndrome. Due to the absence of extrarenal manifestations, such as sensorineural hearing loss or ocular abnormalities, ADAS is frequently misdiagnosed or underdiagnosed. Here, we report a novel heterozygous COL4A4 mutation in a patient with ADAS to raise awareness of this disease and emphasize the importance of genetic testing in unexplained kidney disease cases. Case presentation A 55-year-old woman presented with persistent proteinuria detected over 10 months. Her clinical history was significant for hypertension. Laboratory tests revealed proteinuria (680 mg/24 h) and hematuria. A renal biopsy showed mild mesangial proliferation and extensive glomerular basement membrane thinning. Genetic testing identified a novel heterozygous missense mutation in the COL4A4 gene (c.913G > C, p.Gly305Arg), which was also present in her son. The patient’s diagnosis was confirmed as ADAS. Conclusions This case highlights the importance of considering ADAS in patients with unexplained proteinuria and hematuria, even in the absence of family history or extrarenal symptoms. Early diagnosis through renal biopsy and genetic testing is crucial for proper management. The identification of this novel COL4A4 mutation expands the known mutational spectrum and emphasizes the need for increased clinical awareness to prevent misdiagnosis and ensure timely intervention....
Glioblastoma (GBM) is a highly aggressive and heterogeneous brain tumor. Glioma stemlike cells (GSCs) play a central role in tumor progression, therapeutic resistance, and recurrence. Although immune cells are known to shape the GBM microenvironment, the impact of antigen-presenting-cell (APC) signature genes on tumor-intrinsic phenotypes remains underexplored. We analyzed both bulk- and single-cell RNA sequencing datasets of GBM to investigate the association between APC gene expression and tumor-cell states, including stemness and metabolic reprogramming. Signature scores were computed using curated gene sets related to APC activity, KEGG metabolic pathways, and cancer hallmark pathways. Protein–protein interaction (PPI) networks were constructed to examine the links between immune regulators and metabolic programs. The high expression of APCrelated genes, such as HLA-DRA, CD74, CD80, CD86, and CIITA, was associated with lower stemness signatures and enhanced inflammatory signaling. These APC-high states (mean difference = –0.43, adjusted p < 0.001) also showed a shift in metabolic activity, with decreased oxidative phosphorylation and increased lipid and steroid metabolism. This pattern suggests coordinated changes in immune activity and metabolic status. Furthermore, TNF-α and other inflammatory markers were more highly expressed in the less stem-like tumor cells, indicating a possible role of inflammation in promoting differentiation. Our findings revealed that elevated APC gene signatures are associated with more differentiated and metabolically specialized GBM cell states. These transcriptional features may also reflect greater immunogenicity and inflammation sensitivity. The APC metabolic signature may serve as a useful biomarker to identify GBM subpopulations with reduced stemness and increased immune engagement, offering potential therapeutic implications....
Aims and background Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, and poses major treatment challenges due to its incompleteness, hazardous side effects and resistance to chemotherapy. In response, the use of molecular and targeted therapies to treat the disease is begin explored. We aimed in this study to investigate the effects of up- or down-regulation of the enhancer of zeste homolog 2 (EZH2) gene on the Wnt signaling pathway and on the invasiveness capacity of MKN-45 and AGS GC cell lines. Material and methods MKN-45 and AGS GC cell lines were transfected with EZH2-silencing and expression inducing vectors. RNA extraction and cDNA synthesis were performed to analyze the effect of EZH2 on Wnt signaling by using RT-qPCR. Additionally, the transwell test was performed to assess cell invasion capacity of manipulated cells. Results The results showed that EZH2 downregulation led to a significant decrease in expression of several involved genes in Wnt signaling pathway. Conversely, EZH2 upregulation resulted in a meaningful increase in expression of Wnt genes, including DVL1, CTNNB1 (β-catenin), VNT16, AXIN, and RNF43. The expression of LGR5 and LEF1 genes showed an inverse relationship with EZH2 up- and down-regulation. Additionally, the transwell assay demonstrated that upand down-regulation of the EZH2 gene had a direct effect on cell invasion in MKN-45 and AGS cell lines. Conclusion Our findings demonstrate the regulatory role of EZH2 on the Wnt signaling pathway in the GC and its contribution in tumor invasiveness. EZH2 may be suggested as a potential therapeutic target to inhibit invasion of GC cell....
Background Human immunodeficiency virus (HIV) has been one of the most significant global health challenges since its discovery in the early 1980s. Classified as a lentivirus, HIV integrates into the host genome, leading to chronic immune dysfunction and the establishment of latent viral reservoirs. Despite the efficacy of antiretroviral therapy (ART) in controlling viral replication, a complete cure remains elusive due to the virus’s ability to mutate, evade immune responses, and persist in latent reservoirs. Purpose This review aims to provide a comprehensive overview of how genomic technologies have transformed our understanding of HIV pathogenesis, replication, and latency. Additionally, it explores novel therapeutic strategies that target both viral and host genomic factors, offering potential avenues for a curative approach to HIV. Main body Genomic technologies such as next-generation sequencing (NGS), CRISPR gene editing, and RNA sequencing (RNA-seq) have provided critical insights into HIV biology. These tools have elucidated the HIV genome, identifying viral and host factors critical for replication and latency. Advances in proteomics have revealed the interactions between viral proteins and host machinery, contributing to the development of targeted therapies. Therapeutic strategies, including RNA-based therapies and CRISPR-Cas9-mediated gene editing, demonstrate promising preclinical results in silencing viral gene expression or excising proviral DNA, though translation to clinical applications faces substantial challenges. However, significant obstacles in delivery mechanisms and safety concerns regarding off-target effects remain formidable hurdles. The persistence of latent reservoirs, which evade current ART, continues to be the primary barrier to achieve a cure. Conclusion The integration of genomics into HIV research has opened new therapeutic avenues, offering hope for a functional or complete cure. However, further research is needed to overcome delivery challenges, target latent reservoirs effectively, and ensure the safety of gene-editing technologies....
Background: Hereditary transthyretin amyloidosis (ATTRv) is a systemic disorder caused by homozygosity or compound heterozygosity for pathogenic mutations in the TTR gene, leading to destabilization of the transthyretin tetramer, misfolding of monomers, and subsequent amyloid fibril deposition. Among over 150 known TTR variants, p.Val142Ile is particularly associated with late-onset cardiac involvement and is the most prevalent amyloidogenic mutation in individuals of African and, to a lesser extent, European descent. This study reports the identification and familial segregation of the p.Val142Ile mutation in a large multigenerational family from Calabria (Southern Italy). Methods: Genomic DNA was extracted from peripheral blood, and Sanger sequencing of the TTR gene was performed in the proband and extended family. Results: The proband was a 75-year-old man with clinical features suggestive of cardiac amyloidosis. Genetic testing revealed homozygosity for the TTR p.Val142Ile variant. Family screening revealed multiple heterozygous carriers across three generations, most of whom were asymptomatic. Discussion: This is the first report of a native Calabrian family carrying this variant, previously unreported in this region, where p.Phe84Leu was considered the only endemic TTR mutation. Our findings expand the mutational landscape of ATTRv in Southern Italy and highlight the presence of p.Val142Ile in a previously unrecognized geographic area. These results reinforce the importance of including TTR sequencing in the work-up of unexplained cardiomyopathy, particularly in Southern Italy, where atypical variants may be emerging....
Background/Objectives: Long non-coding RNAs (lncRNAs) play a crucial role in trophoblast invasion, immune tolerance, and placental angiogenesis. To delineate their diagnostic and pathological significance, we critically evaluated the evidence for correlations between circulating or placental lncRNA profiles with pregnancy complications. Methods: Five databases were searched from inception through September 2024. We included only the studies that assessed the expression of the lncRNA-complicated pregnancies versus a control group. Results: Three single-center case–control studies fulfilled the inclusion criteria. Eight serum lncRNAs that present <20 weeks of gestation were elevated in subsequent pregnancy-induced hypertension or preeclampsia. The three lncRNAs in intrahepatic cholestasis of pregnancy were consistently decreased with a negative correlation with bile acids. Gestational diabetes was characterized by the elevation of MALAT1. Conclusions: Different lncRNAs showed a potential for use as non-invasive markers as well as for risk stratification for pregnancy-induced hypertension or preeclampsia, metabolic, and hepatobiliary pregnancy complications. There is a need for large-scale, multi-ethnic, prospective cohorts to include lncRNA as screening or therapeutic targeting in obstetric practice....
Loading....