Search Results (6,494)

The risk of Helicobacter pylori (H. pylori)-related gastric tumorigenesis is closely associated with the degree of chronic gastritis, although other gastric mucosa microbes may be relevant in this process. The morphological identification of the gastric mucosa associated with the cancer-promoting microbiome may have important implications for gastric cancer prevention. This study characterized gastric mucosa microbiome communities in relation to their mucosal morphologies. A total of 94 biopsies from non-neoplastic gastric bodies underwent 16S rRNA sequencing. Microbiome structures were characterized in relation to their mucosal morphologies, which were obtained using narrow-band imaging with magnifying endoscopy. H. pylori infection- and inflammatory mucosa-associated gastric mucosal morphologies exhibited decreased bacterial alpha diversity measures and an increase in the abundance of the Helicobacter genus, while the mucosal morphology associated with severely atrophic mucosa exhibited increased bacterial alpha diversity measures and a decrease in the abundance of the Helicobacter genus. This type of mucosal morphology was also associated with increased levels of well-known gastric cancer-related bacteria, e.g., Streptococcus. The microbial dysbiosis associated with gastric mucosa morphology also correlated well with the occurrence of gastric cancer and the DNA methylation status. Our results suggest that gastric microbiome communities correlate well with their premalignant condition-associated mucosal morphologies. Full article

G-quadruplexes (G4s) are four-stranded DNA or RNA structures formed by guanine-rich sequences. They occur in functional regions of the genomic material, including the promoter part of genes, regulatory region, and telomeric threads. G4s play a key role in various biological processes, including transcription, replication, and telomere maintenance. Guanidine-containing derivatives can bind to G-quadruplexes, either by intercalating into the structure or by interacting with the grooves or loops. The binding can stabilize the G-quadruplex, potentially affecting its biological function. In this paper, the ability of guanidinium-containing hordatines to interact with G4 was evaluated. Analogues lacking the guanidinium group or showing the benzofuran system instead of the dihydrobenzofuran core were prepared and tested as well. NMR titration and docking calculations were used to probe the binding of the compounds to G4 of c-MYC oncogene. Spectroscopic analyses were consistent with a significant interaction of benzofurans 3 and 4 at the 5′-end and 3′-end tetrads and with the formation of ligand/G-quadruplex complexes with a 2:1 stoichiometry. The resulting data were supported by docking simulations. Cytotoxic activity was evaluated on a model of U2OS osteosarcoma (ATCC HTB-96) and breast cancer (MDA-MB-231) cell lines, further highlighting the key role of the guanidinium fragment and the benzofuran core in the G-quadruplex stabilization. Full article

(1) Background: This study investigated the presence of human papillomavirus (HPV), HPV genotypes, Epstein–Barr virus (EBV), cytomegalovirus (CMV) and herpes simplex virus (HSV) in patients with Head and Neck Cancer (HNC) at both molecular and serological levels. (2) Methods Fifty patients with histopathologically confirmed HNC who were admitted to the Department of Otorhinolaryngology, Istanbul Faculty of Medicine. Viral DNA was detected using quantitative real-time PCR, and serological IgM and IgG antibodies were analyzed using the CMIA method; (3) Results: In blood samples, CMV and HSV DNA were not detected, whereas EBV DNA was identified in 2% and HPV DNA in 4% of patients. In tumor tissues, CMV DNA was detected in 8%, EBV DNA in 10%, and HPV DNA in 6%; HSV DNA is 6%. HPV genotypes 18, 45, and 69 were found in tissue samples. Serologically, IgG positivity for CMV, EBV, and HSV-1 exceeded 90%, whereas IgM positivity was low and not statistically significant; (4) Conclusions: HPV, EBV, and CMV DNA were detected at low frequencies in patients with HNC, while HSV DNA was absent. These findings underline the need for larger multi-center studies and support the consideration of routine viral screening, particularly for HPV, in specific tumor subtypes. Full article

Background/Objectives: This study aims to critically appraise the role of para-aortic surgical staging in locally advanced cervical cancer (LACC) in the era of advanced imaging, and to outline how selective surgery and biomarkers could be integrated within modern, quality-assured treatment pathways. Methods: Narrative review of randomized trials, large databases, and prospective/retrospective series comparing para-aortic lymphadenectomy with imaging-based staging; focused appraisal of Uterus-11, NCDB analyses, and ongoing prospective trials (PAROLA with Senti-PAROLA as one of its sub-studies and PALDISC). Emerging technologies (PET/MRI, radiomics/AI) and molecular assays (OSNA, HPV-ctDNA) were also assessed. Results: PET/CT remains the standard for distant staging, but sensitivity for low-volume nodal disease (<5 mm) is poor; in pelvic-positive/para-aortic-negative patients, occult para-aortic metastases approach ~21%. Para-aortic surgical staging modifies radiotherapy planning in ~18% of cases and can act as a de-escalation tool by avoiding unnecessary extended-field CRT (EF-CRT) when para-aortic nodes are negative. Uterus-11 showed no overall survival difference versus CT-based staging, but suggested benefit in FIGO 2009 stage IIB; its design (CT comparator, optimistic assumptions, limited power) constrains inference. Minimally invasive extraperitoneal/transperitoneal staging is feasible with low morbidity in expert centers, yet real-world management may worsen outcomes. The role of systemic intensification in node-positive disease remains undefined: PALN-positive patients were excluded from the INTERLACE trial. In the KEYNOTE-826 study, subgroup analyses according to nodal status were not reported, although the benefit of pembrolizumab remained consistent irrespective of bevacizumab use. Sentinel para-aortic mapping and biomarkers (e.g., HPV-ctDNA) may refine selection and reduce morbidity. Conclusions: Surgical staging is the most accurate method to detect occult para-aortic disease. Its routine use is not justified, but it may benefit selected high-risk patients, particularly where decisions on EF-CRT or systemic therapy hinge on para-aortic status. Future practice should integrate advanced imaging, selective surgery, and biomarkers within accredited centers, guided by large collaborative trials conducted under international quality frameworks such as ESGO/ESTRO/ESP guidelines. Full article

Background: Asthenozoospermia is defined as a condition in which the total motility of sperm in a semen sample is less than 40%. Due to impairing sperm motility, asthenozoospermia was linked to different mitochondrial DNA (mtDNA) alterations. The current study aimed to investigate the relationship between MT-CO2 gene variants and the development of asthenozoospermia and male infertility in the Jordanian population. Materials and Methods: Semen samples were collected from 196 men, including 119 asthenozoospermic (infertile) and 77 normozoospermia (control), from the Royal Jordanian Medical Services in vitro fertilization (IVF) unit. The isolated mitochondrial DNA (mtDNA) was subjected to a polymerase chain reaction to amplify the MT-CO2 gene. Genetic variants were screened using direct Sanger sequencing. Genotypes and allele frequencies between the case and control groups were compared by the chi-square test and Fisher’s exact test. Results: Three novel variants in the MT-CO2 gene were identified in nine asthenozoospermic cases, including two missense variants (m.8222T>A and m.7997G>A) and one synonymous variant (m.7846 A>G). In addition, the current study reported twenty-three known substitutions. In particular, the rs1556423316 T>C variant showed a significant association with asthenozoospermic infertile men in the studied population (p < 0.05). Conclusion: The detected missense variants in the MT-CO2 gene in asthenozoospermic infertile men underscore the important role of these variants in the development of asthenozoospermic male infertility. Full article

Compared with capillary electrophoresis (CE), gel electrophoresis (GE) is a traditional method for the analysis of nucleic acids because of its low cost, although the operation process is complicated. The electropherogram from CE can offer more information (e.g., DNA size and its concentration) for researchers. Based on the self-built integrated biochip GE system, we proposed a computational method that converts conventional agarose GE images into CE-like fluorescence profiles for enhanced DNA analysis. The gel images were processed using an image-based algorithm involving median filtering to remove background noise and pixel-wise intensity summation along the migration axis to generate one-dimensional records of electrophoretic separations. Each DNA band in the gel was thereby transformed into a distinct fluorescence peak, reflecting its migration distance and relative intensity. To further enhance resolution and peak separation, Gaussian modeling was applied to fit the fluorescence intensity distribution, providing smoother and more distinguishable spectral peaks. To validate the method, three periodontal pathogens—Porphyromonas gingivalis (P.g), Treponema denticola (T.d), and Tannerella forsythia (T.f)—were amplified using PCR and analyzed by gel electrophoresis. The method successfully identified distinct electrophoretic patterns for the three pathogens by using a 50 bp DNA ladder as an internal calibration reference. The results demonstrate that image-based reconstruction of electrophoretic data provides a reliable, quantitative, and visually interpretable representation of DNA migration, comparable to CE output. This approach bridges a gap between traditional GE and modern capillary systems, allowing for the semi-quantitative analysis of DNA fragments without specialized CE instrument. The proposed method offers a valuable analysis method for the separation of DNA, RNA, protein and polypeptides. Full article

Genomic DNA methylation is an epigenetic modification that primarily occurs at CpG sites and is associated with the transcriptional repression of genes. This process plays a crucial role in maintaining cellular homeostasis and is catalyzed by a family of enzymes known as DNA methyltransferases (DNMTs), which includes DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L. DNMT1 is classified as a maintenance methyltransferase, whereas DNMT3A and DNMT3B are responsible for de novo methylation. Altered expression of DNMTs has been reported in various human diseases, including cancer. Cancer remains a major global health issue, with an estimated 20 million new cases and 9.7 million deaths reported in 2022. Among women, cervical cancer (CC) ranks fourth in both incidence and mortality worldwide, with persistent infection by high-risk human papillomavirus (HR-HPV) being the primary risk factor. Several studies have demonstrated that DNMT expression and activity are upregulated in CC, suggesting their potential as diagnostic and prognostic biomarkers. HR-HPV infection appears to increase DNMT expression, thereby promoting cervical carcinogenesis through aberrant methylation and subsequent silencing of tumor-suppressor genes such as PTEN, PAX1, and TSLC1. Furthermore, DNMTs are being explored as therapeutic targets in CC. In this review, we summarize the current state of the art regarding DNMTs in cervical cancer and discuss their functional roles and potential utility as diagnostic, prognostic, and therapeutic biomarkers. Full article

Perilla frutescens, “Nga-Kee-Mon” in Thai, is a high-nutritional-value plant. This study aims to identify the phytochemicals, apoptosis induction and immunomodulating activities of the perilla seed extract (PSE) and highlight the high pharmaceutical value of perilla. The phytochemical profile of PSE was characterized using HPLC. Antioxidant capacity was studied using DPPH assay. Apoptosis was confirmed by morphological changes and DNA fragmentation of the human colon adenocarcinoma cell line (HT-29). Immunomodulating activity was studied in an LPS-stimulated murine macrophage cell line (RAW 264.7). PSE had high levels of TPC (375.04 ± 11.45 mg GAE/g) and TFC (223.45 ± 16.02 mg QE/g) with strong radical scavenging capacity (312.87 ± 12.98 mg TE/100 g). Rosmarinic acid (0.116 g%) and luteolin (0.010 g%) were the major phytochemicals. PSE at 50 µg/mL, equivalent to 0.85 and 0.08 µg/mL of rosmarinic acid and luteolin, respectively, caused morphological alterations and DNA fragmentation within 24 h. PSE at 200 µg/mL, equivalent to 3.38 and 0.30 µg/mL of rosmarinic acid and luteolin, respectively, had significant inhibitory activity on IL-1β, IL-6, and TNF-α secretion. These results demonstrate that PSE has high antioxidant capacity, with rosmarinic acid and luteolin as the major phytochemicals. It can trigger apoptosis in HT-29 cells and has immunomodulatory effects. These findings highlight the potential of perilla seed extract as a promising natural source for therapeutic applications related to oxidative stress, cancer prevention, and immune modulation. Full article

Background and Objectives: Thrombophilia is a prothrombotic disorder that increases the risk of blood clotting and can pose serious health problems. It is considered a condition of gene–gene or gene–environment interactions. Variation in the prevalence of thrombophilia mutations and their interaction among populations necessitates localized genetic assessments. However, population-based genetic data remains limited for developing effective preventive strategies. Materials and Methods: This cross-sectional observational study was conducted over five years (2020–2024) at a tertiary university hospital in Northern Greece. A total of 2961 individuals aged 18–85 years (mean: 50.5) were registered based on family or medical history of venous thromboembolism (VTE) or clinical symptoms of VTE. The final analysis included 2078 participants comprising 1143 males (55%) and 935 females (45%), who met all the inclusion criteria. Inclusion criteria were absence of acute illness or malignancy, informed consent, and an adequate DNA quantity for genotyping, whereas excluded criteria included incomplete laboratory data, active inflammatory or malignant disease, and cognitive or psychiatric conditions. Peripheral blood samples were collected in 2 mL K₃-EDTA tubes, and genomic DNA was analyzed using real-time polymerase chain reaction (PCR) with melting curve analysis and hybridization probes (LightMix^® in vitro diagnostics, TIB MolBiol, Berlin, Germany). Five thrombophilia-related polymorphisms, Factor V Leiden (F5 G1691A), prothrombin (F2 G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), and Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G, were examined for allele and genotype frequencies, Hardy–Weinberg equilibrium testing, pairwise linkage disequilibrium (D′ and r²), and power analysis. For subjects tested for Factor V Leiden (n = 1476), the activated protein C resistance (APC) ratio was additionally evaluated using the ACL TOP 750 analyzer. Results: Allele frequencies were 7.3% for FV Leiden and 3.7% for FII. The PAI-1 allele was distributed at 44%, while the MTHFR (C677T and A1298C) alleles were each present at 33%. Significant linkage disequilibrium was identified between MTHFR (C677T and A1298C) and between MTHFR A1298C and PAI-1. No evolutionary pressure or demographic bias was found in the Hardy–Weinberg equilibrium. The APC ratio demonstrated a high sensitivity (99.2%) and specificity (96.6%), indicating that it may serve as a reliable screening method. Conclusions: Our findings highlight informative patterns in the genetic predisposition to thrombophilia, which may help develop rule-based strategies for implementing thromboprophylaxis guidelines and personalized medical interventions. Full article

Sirtuin 1 (SIRT1), an NAD⁺-dependent histone deacetylase, exerts complex and context-dependent effects in breast and gynecological cancers. By deacetylating histone and non-histone proteins such as p53, FOXO, and NF-κB, SIRT1 regulates essential processes including DNA repair, apoptosis, metabolism, and stress response. In breast cancer, SIRT1 may act as a tumor suppressor in early stages by maintaining genomic stability but promotes epithelial–mesenchymal transition, metastasis, and chemoresistance in aggressive subtypes such as triple-negative breast cancer. Similarly, in gynecological cancers, SIRT1 displays dual roles: promoting proliferation via estrogen signaling and p53/FOXO1 inhibition in Type I endometrial cancer yet potentially supporting DNA repair in high-grade Type II tumors. Its overexpression in ovarian and cervical cancers is linked to enhanced survival and drug resistance. Preclinical studies show that pharmacological inhibition of SIRT1 (e.g., with EX-527 or cambinol) restores chemosensitivity and reduces tumor cell viability, suggesting potential for SIRT1 inhibitors as adjuncts in cancer therapy. However, clinical trials specifically targeting SIRT1 in these cancers remain limited. Further investigation is needed to define therapeutic windows, molecular contexts, and combination strategies that could optimize SIRT1-targeted therapies. This review summarizes the current understanding of SIRT1’s roles in breast and gynecologic malignancies. Full article

Background: Diabetes mellitus and cancer often coexist, increasing the risk of liver injury. Doxorubicin (DOXO) is a widely used antineoplastic drug with known hepatotoxic effects. Dapagliflozin (DAPA) and trimetazidine (TMZ) have been reported to exert hepatoprotective actions, but their combined effects remain unclear. Methods: Forty-eight male Sprague Dawley rats were allocated into six groups: control, streptozotocin (STZ), STZ + DOXO, STZ + DOXO + DAPA, STZ + DOXO + TMZ, and STZ + DOXO + DAPA + TMZ. Liver injury was assessed by histopathology, oxidative stress markers (MDA, GSH), and immunohistochemistry (Tumor Necrosis Factor-alpha (TNF-α), 8-Hydroxy-2′-deoxyguanosine (8-OHdG), Caspase-3, Transforming Growth Factor-beta 1 (TGF-β1), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Nuclear Factor kappa-B/p65 (NF-κB/p65)). Results: STZ and STZ + doxorubicin groups developed marked hepatic injury. Unexpectedly, the STZ + doxorubicin group showed lower alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, along with reduced Malondialdehyde (MDA) and elevated glutathione (GSH), suggesting compensatory antioxidant and apoptotic responses. Dapagliflozin more effectively normalized transaminases and reduced oxidative DNA damage, whereas trimetazidine exerted stronger effects on MDA, GSH, and inflammatory markers. The combination provided additive but not consistently superior benefits. Immunohistochemical analyses confirmed these findings, showing attenuated expression of TNF-α, 8-OHdG, caspase-3, and TGF-β1 and reduced TUNEL-positive hepatocytes and NF-κB/p65 immunoreactivity following treatment, indicating coordinated anti-apoptotic and anti-inflammatory effects. Conclusions: Dapagliflozin and trimetazidine each attenuated diabetes- and doxorubicin-related hepatic injury through partly distinct mechanisms, with the combination providing additive but not consistently superior effects. These findings suggest a potential hepatoprotective role for both agents; however, the clinical implications remain uncertain and require confirmation in further mechanistic and translational studies. Full article

Background/Objectives: Direct oral anticoagulants (DOACs) have transformed the prevention of thromboembolic events, but their efficacy and safety remain highly variable across individuals. DD217, a novel oral direct factor Xa inhibitor, has demonstrated potent anticoagulant activity in preclinical and clinical studies. No pharmacogenetic data are currently available for this compound. Based on in silico predictions of metabolic pathways and transporter involvement, and evidence from other DOACs, we hypothesized that variants in CYP2C and P-glycoprotein genes may contribute to variability in pharmacokinetics (PK) and clinical outcomes. Methods: Fifty-two patients undergoing total knee arthroplasty were enrolled, of whom 34 received the investigational drug (40 mg/day, n = 16; 60 mg/day, n = 18). DNA was extracted from peripheral blood cells, and genotyping of CYP2C9, CYP2C19, CYP2C8, CYP3A4, CYP3A5, and ABCB1 was performed by real-time PCR. Pharmacokinetics (PK) parameters (T_max, AUC_last, C_max) were assessed. In silico docking and pathway modeling predicted CYP2C and P-glycoprotein (ABCB1) involvement in drug disposition. Associations of genetic variants with PK parameters and adverse events (thrombosis, bleeding) were analyzed. Results: Carriers of reduced-function CYP2C9 alleles (intermediate [IM] or poor metabolizers [PM]) in the 60 mg group had a significantly shorter T_max compared with normal metabolizers (p = 0.005227), with trends toward higher AUC_last (p = 0.06926) and C_max (p = 0.1259). No significant associations were observed for CYP2C19, CYP3A4/5, or CYP2C8. In contrast, ABCB1 polymorphisms were associated with systemic exposure: carriers of the C allele at rs1045642 had higher AUC_last and C_max compared to TT (wild-type) homozygotes, while rs2032582 T allele carriers showed lower exposure (p < 0.05). At the haplotype level, the C–G–C–T combination of ABCB1 was more frequent in patients with thrombotic events at the 40 mg dose (p = 0.038). Overall, 5 thrombosis events and 1 bleedings were recorded on DD217, with no consistent associations to single SNPs. Conclusions: This first pharmacogenetic evaluation of DD217 shows that CYP2C9 variants are associated with differences in early-phase pharmacokinetics (T_max), while ABCB1 polymorphisms appear to modulate systemic exposure (AUC_last, C_max) and may influence thrombotic risk. These observations are consistent with in silico predictions of metabolic and transporter pathways. Despite limitations in sample size and event frequency, the study highlights the feasibility and importance of early pharmacogenetic evaluation during the drug development cycle of novel DOACs. Full article

SARS-CoV-2 infection remains a global health concern, with its impact on host immune responses not fully understood. In a case–control study, we examined how COVID-19 affects DNA methylation patterns in the upper respiratory airway of hospitalized individuals. DNA methylation arrays were performed on nasopharyngeal samples at inclusion/hospitalization and 6 weeks post-inclusion. We found a distinct DNA methylation pattern in COVID-19 patients compared to healthy controls, identifying 510,099 differentially methylated CpGs. Within the transcription start sites (TSSs) and gene body, COVID-19 patients displayed a higher number of genes/CpGs with elevated methylation levels. Enrichment analysis of TSS-methylated genes revealed effects of SARS-CoV-2 on genes associated with type I interferons, anti-viral and inflammatory responses, and immune functions. Some CpG methylations were transient, and normalized at group level by 6 weeks post-inclusion. Several IFN-regulated genes, including OAS1, OAS3, IFIT3, and MX1, were identified. Among the top regulators were IL17A and ERK1/2, both involved in inflammatory processes. Networks nodes included IGF1 and EGF, associated with processes including tissue repair and activation of immune responses. Overall, our data suggests that COVID-19 can impact the upper airway by modifying gene methylation patterns. This could have implications for conditioning of the airways, how individuals respond to future airway infections, and therapeutic interventions. Full article

Background: Medulloblastoma is an aggressive pediatric brain tumor characterized by marked molecular heterogeneity, which significantly impacts prognosis. The low frequency of genomic mutations in medulloblastoma suggests that alternative mechanisms, such as epigenetic regulation, may play a critical role in its pathogenesis. Methods: Using the EpiFactors database, we investigated the expression of epigenetic regulators in two independent RNA sequencing cohorts [Pediatric Brain Tumor Atlas (PBTA) and Williamson], stratified by molecular subgroups and clinical outcomes. We further analyzed expression heterogeneity at the single-cell level in malignant medulloblastoma cells using single-cell RNA sequencing. Results: Members of the SWI/SNF superfamily were dysregulated across all four molecular subtypes of medulloblastoma. Subtype-specific alterations were also observed: the acetyltransferase complex was shared between Group 3 (with SMARCD3 as a potential marker) and Group 4 (with RBM24 as a potential marker); SWR1, β-catenin/TCF, and protein–DNA complexes were specifically enriched in SHH-MB (with EYA1 and SATB2 as SHH markers); and RSC-type, PRC1, DNA polymerase complexes, and X-chromosome-related factors were enriched in WNT-MB (with FOXA1 and PIWIL4 as WNT markers). An epigenetic score (epi-score), linked to RNA metabolism and S-adenosyl-L-methionine pathways, was developed and identified as an independent adverse prognostic factor. High epi-scores were associated with proliferative, stem-like SHH malignant cells (characterized by G2/M phase, low pseudotime, and high entropy), exhibiting alterations in RNA splicing, DNA recombination, and nuclear division. Conclusions: Expression heterogeneity of epigenetic regulators is closely associated with molecular subgroups and clinical outcomes in medulloblastoma. These findings highlight the role of epigenetic dysregulation in RNA metabolism and tumor progression, particularly in SHH-driven proliferative cells. Full article

This study focused on the multifunctional characteristics and bioremediation potential of Paracoccus spp. A novel Gram-stain-negative, aerobic, non-motile, ellipsoidal bacterium, named Paracoccus qomolangmaensis S3-43^T, was isolated from moraine samples collected from the north slope of Mount Everest at an altitude of 6109 m above sea level (a.s.l.). To clarify the phylogenetic relationship of this strain within the Paracoccus genus and systematically characterize its features, analyses were conducted using polyphasic taxonomy and comparative genomics. Results revealed two distinct functional characteristics of strain S3-43^T: First, strain S3-43^T exhibits exceptional radiation resistance, particularly tolerance to ionizing radiation. Genome annotation indicates abundant DNA repair and antioxidant-related genes (e.g., vsr, mutL, mutS, ruvC, radA, addA, recA, recN, recO). Second, strain S3-43^T contained several pyrethroids degradation related genes, including cytochrome P450, monooxygenase, and aminopeptidase. The results of the genomic comparison of strain S3-43^T with related type strains also revealed differences and distribution of key genes related to stress response, environmental variables, and bioactive metabolites. Based on the results of the polyphasic taxonomic analysis, strain S3-43^T (=KCTC 8297^T = GDMCC 1.3460^T) should be classified as a novel species of the genus Paracoccus, designated as Paracoccus qomolangmaensis sp. nov. Full article