Search Results (12,475)

Introduction: Mucosal melanomas are rare, and vulvar melanoma is typically diagnosed at an advanced stage with aggressive behavior and poor prognosis. The clitoral region adds challenges due to its functional importance and lack of a dedicated staging system, requiring individualized management. This review evaluates current evidence on prognosis with emphasis on clitoral involvement and highlights diagnostic and therapeutic challenges, underscoring the need for personalized strategies and prospective multicentre studies. Materials and Methods: A systematic review, registered in PROSPERO (CRD420251151187), was conducted per PRISMA guidelines across PubMed, Scopus, Embase, and Web of Science, including English-language case reports and series of primary clitoral melanoma published until August 2025, with no historical limits. Results: 15 cases from 10 studies were identified. The mean patient age was 60 years, with most tumors presenting at advanced stages (median Breslow thickness of 8 mm, frequent ulceration). Immunohistochemical markers and gene mutations are rarely investigated in reported cases. All patients underwent surgery, with variable lymph node assessment; adjuvant therapy was rarely used. Recurrence occurred in nearly one-third of cases, sometimes more than 10 years after initial treatment. Conclusions: Primary clitoral melanoma is extremely rare and often diagnosed late, underscoring the need for heightened clinical awareness. Wide local excision with organ preservation is preferred, and bilateral sentinel lymph-node biopsy can improve staging. The absence of a dedicated staging system and limited systemic evidence highlight the need for standardized protocols. Emerging molecular and immunologic approaches are promising, but prospective multicentre studies are essential to guide management. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, for which predicting clinical outcomes remains challenging. Although immune-checkpoint pathways are known to influence tumor biology, the impact of their germline variants on DLBCL susceptibility and prognosis has not been fully elucidated. Methods: Variants in PD-L1 gene CD274 (rs4143815, rs822336), and miR-155 gene MIR155HG (rs767649, rs1893650), assessed by TaqMan assays in 99 DLBCL patients and 113 age- and sex-matched healthy controls, were associated with clinicopathological features, treatment response, overall survival (OS), relapse-free survival (RFS), and disease susceptibility. Results: The PD-L1 variant rs822336 was significantly associated with relapse status (p = 0.005) and RFS (p = 0.008), with the wild-type GG genotype showing the poorest RFS that remained independent in the multivariate Cox analysis (HR = 2.387, p = 0.003). Conversely, rs4143815 showed a nominal association with treatment resistance (p = 0.026), while patients carrying the GG genotype had worse OS (p = 0.006). In susceptibility analyses, miR-155 variant rs767649 showed a nominal association with DLBCL risk, with the rare AA genotype showing an increased risk of DLBCL (OR = 5.234, p = 0.045), which did not remain significant after Bonferroni correction. Conclusions: In a hypothesis-generating manner, these findings suggest that PD-L1 genetic variants may predominantly influence disease progression and outcomes, while miR-155 variation may contribute to DLBCL susceptibility. These findings highlight germline immunogenetic variants as stable, treatment-independent markers that may inform future studies on risk stratification and prognosis in DLBCL. Full article

Background: Obesity-associated inflammation arises from adipose dysfunction and intestinal disturbances, including altered microbiota and short-chain fatty acid (SCFA) metabolism. Beans (Phaseolus vulgaris) are rich in non-digestible carbohydrates and polyphenols, but whether kidney bean varieties differing in seed coat colour exert distinct effects on inflammation in obesity remains unclear. Objective: To determine whether supplementation of an obesogenic high-fat (HF) diet with white or dark red kidney beans modulates gut microbiota, SCFAs, and intestinal, systemic, and neuroinflammatory outcomes. Methods: Male C57Bl/6N mice (n = 12/group) were fed a basal diet (BD; modified AIN-93G), an HF diet (60% kcal from fat), or an HF diet supplemented with 15% cooked white (HF + WK) or dark red kidney beans (HF + DK) for nine weeks. Outcomes included cecal microbiota composition, predicted KEGG pathways with taxon contributors mapped with BURRITO (a tool for linking predicted microbial functions to contributing taxa), and SCFA-related pathways; cecal and fecal SCFA concentrations; colon histomorphometry and expression of gut barrier junction and inflammatory genes; serum cytokines and adipose hormones; and hippocampal inflammatory and barrier genes. Results: Mice consuming bean-supplemented HF diets had higher microbial diversity, enrichment of SCFA-producing taxa (Prevotella, Lactobacillus, Muribaculaceae), and lower obesity-associated genera versus HF alone (Mucispirillum, rc4-4). Bean diets elevated cecal acetate and butyrate concentrations, which aligned with increases in predicted acetate kinase in both bean groups versus HF and BD, and butyrate kinase in HF + DK versus BD. Bean supplementation attenuated HF-induced reduction of goblet cells and systemic interleukin (IL)-10. The HF + DK group had lower colonic tumour necrosis factor (TNF)-α and partially attenuated hippocampal IL-6. SCFAs were inversely associated with systemic and neuroinflammatory markers in HF + DK mice. Conclusions: Kidney bean supplementation mitigated HF diet-induced intestinal, systemic, and neuroinflammatory disturbances in male mice, with microbiota and SCFA modulation. Further, dark red beans exerted stronger anti-inflammatory effects, highlighting the role of seed coat colour in bean-mediated obesity outcomes. Full article

Silicosis, an irreversible occupational lung disease resulting from prolonged exposure to respirable crystalline silica, faces challenges due to limitations in existing mammalian models. This study evaluated whether laboratory-prepared respirable α-quartz silica could induce immune cell–inflammatory–fibrotic initiation related to silicosis in zebrafish embryos as a tool for early toxicity assessment. Zebrafish embryos at 48 h post-fertilization (hpf) were microinjected into hindbrain ventricle with respirable α-quartz silica (test material 3.056 μm vs. standard material 3.217 μm) derived from natural α-quartz ore. The results indicated a significant decrease in zebrafish survival rates and an increase in malformation rates following exposure respirable α-quartz silica materials. Additionally, alterations in midbrain and hindbrain lengths were observed, while body length remained unaffected. Behavioral assessments revealed reduced touch response rates, decreased average speed, and less time spent in the central zone during open field tests in the treatment groups. In vivo imaging demonstrated sequential recruitment of neutrophils (peak at 18 h post-injection) and macrophages (peak at 24 h post-injection). qPCR analysis revealed upregulation of inflammation-related genes (tnf-α, il-6, il-1β) and fibrosis-related genes (tgf-β, acta-2, collagen). Moreover, the hydroxyproline content, a marker for fibrosis, was significantly elevated, although no mature fibrosis was observed histologically. These findings demonstrate that respirable α-quartz silica elicits pathophysiological changes associated with silicosis early initiation in zebrafish embryos. This supports the utility of the zebrafish embryo as a practical tool for early toxicity assessment and mechanistic studies of silica-induced immune–inflammatory–fibrotic initiation, with potential implications for silica exposure early risk warning. Full article

Rhizoctonia solani anastomosis group (AG)-2-2IIIB and AG-4HGI are the main pathogens causing sugar beet seedling damping-off and crown and root rot disease. In this study, 1232 loci of simple sequence repeats (SSRs) were obtained via transcriptome sequencing, with 592 from AG-2-2IIIB and 640 from AG-4HGI. Fourteen and twenty loci of SSRs were selected for studying the genetic structure of the AG-2-2IIIB and AG-4HGI populations, respectively. A population of 134 strains of AG-2-2IIIB and 145 strains of AG-4HGI, sampled from three geographic regions in China, indicated that both AG-2-2IIIB and AG-4HGI had a high level of genetic diversity, and that the selected SSR markers could reliably capture the genetic variation. Genetic analysis indicated that the individual strains of AG-2-2IIIB and AG-4HGI randomly mated within their respective population, and that a considerable degree of inbreeding was present among the populations. High to moderate gene flow and low to moderate population subdivision were detected among the populations of AG-2-2IIIB and AG-4HGI, which indicated that weak differentiation existed in these two subgroups. In addition, a founder effect (genetic drift) or a bottleneck effect was inferred to have occurred in the AG-4HGI population. This study provides the first analysis of the population genetic structure of AG-2-2IIIB and AG-4HGI associated with sugar beet seedling damping-off and crown and root rot disease, and the present results offer useful guidance for developing effective integrated disease management. Full article

Molecular genotyping is a key factor for plant breeding programming and plant variety protection (PVP). However, its potential still remains to be elucidated when considering ornamental plants like Petunia × hybrida. In this study, a petunia breeding clone collection, including sister line groups, was genotyped through double digest Restriction-site Associated DNA sequencing (ddRADseq), and its genetic diversity and structure were studied. In addition to estimating the high genetic similarity observed among sister lines, this approach allowed the unique discrimination of each clone too. Molecular results agreed with genealogy data, supporting the assessment of genotyping effectiveness. In addition, the minimal number of variants able to uniquely discriminate and/or correctly cluster the experimental lines was investigated. The loci number could be reduced to eight to achieve line discrimination, and a method to identify the specific variant sets is presented. Conversely, to preserve the original clustering with minor adjustments, one hundred loci were required and were obtained through minor allele frequency (MAF) filtering. Moreover, analysis of the chromosomal distribution of variants revealed a predominant accumulation in distal regions. Genetic analyses were repeated considering only variants located in coding sequences and results were in agreement with what previously observed, disclosing the potential of the expressed regions for genotyping purposes. Eventually, the applied approach enabled the investigation of SNPs within genes putatively involved in traits of interest. Our findings encourage the adoption of high-throughput and cost-effective sequencing techniques for petunia genotyping aimed at achieving PVP, supporting new variety registration, and developing marker-assisted breeding (MAB) and marker-assisted selection (MAS) strategies. Full article

Understanding the functional mechanisms of genes influencing economically important traits in the domestic pig is essential for optimizing marker-assisted selection (MAS). This study aimed to characterize the biological functions, molecular mechanisms, and metabolic pathways of genes associated with morphological, productive, reproductive, and carcass quality traits through a functional bioinformatics approach. Genes were compiled from 116 peer-reviewed studies published between 2000 and 2024, and subsequently grouped according to trait. A de novo functional bioinformatics analysis was performed on this dataset. Functional enrichment analysis was conducted using DAVID and the clusterProfiler package in R, applying FDR correction (≤0.05). Protein-protein interaction (PPI) networks were explored using STRING. No individual gene was consistently reported with high frequency. Among the most frequently reported genes were VRTN (17 studies) for teat number, HOMER1 (3 studies) for leg strength, and BMPR1B (3 studies) for litter size. Enriched GO terms included processes such as positive regulation of transcription (GO:0045944), chondrocyte differentiation (GO:0032331), and SMAD signaling (GO:0060391; an FDR = 7.34 × 10⁻⁷). The PPI networks revealed key genes involved in signaling and immune regulation. In conclusion, this bioinformatics analysis provides an integrated functional overview of the genes underlying key economic traits in pigs, identifying pleiotropic pathways such as SMAD/TGF-β signaling, which supports the development of more effective MAS strategies in pig breeding programs. Full article

YKL-40 and YKL-39 chitinase-like proteins (CLPs) are secreted glycoproteins involved in inflammation, macrophage polarization, and carcinogenesis. Their expression is significantly upregulated in various inflammatory and immunological conditions, including several cancers, suggesting a role as potential diagnostic markers. Colorectal cancer (CRC) remains a significant global health concern, with a continued need for reliable biomarkers to stratify patients and predict therapy response. In this study, we assessed tissue, plasma, and transcript levels of both CLPs in CRC. We found a strong association between their tissue expression and tumor budding. Notably, plasma YKL-39 levels were lower in CRC patients than in controls, while YKL-40 concentrations were higher in the patient group. Gene expression analysis for both CLPs in white blood cells (WBCs) did not reveal statistical significance between CRC patients and controls. These findings enhance our understanding of the clinical relevance of these molecular signatures and support their potential application as biomarkers in CRC stratification. Full article

Rye (Secale cereale L.) is a small-grain cereal traditionally cultivated under low-input conditions, where locally adapted populations have contributed substantially to the maintenance of genetic diversity. Despite this importance, Greek rye germplasm has received limited attention at the molecular level. In the present study, 33 rye accessions, including gene bank landraces, locally cultivated populations and one commercial variety, were analyzed using inter-simple sequence repeat (ISSR), start codon-targeted (SCoT), and exon-based amplified polymorphism (EBAP) markers. All three marker systems generated high proportions of polymorphic loci and comparable estimates of expected heterozygosity, indicating considerable genetic variability within the studied material. Multivariate analyses revealed moderate population structuring and consistently identified a small number of genetically divergent accessions, most notably T-492, K-163, and K-166. No clear clustering according to geographical origin was detected, as in most cases of landraces or local populations. Taken together, the results provide a detailed molecular overview of Greek rye germplasm—which has never been performed before for Greek rye genetic material—and offer a useful basis for conservation priorities and future pre-breeding efforts. Full article

We investigated whether antipsychotic treatment response was influenced by the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR), and A66G of methyltetrahydrofolate–homocysteine methyltransferase reductase (MTRR)—genes central to folate and homocysteine metabolism and methylation, pathways often altered in schizophrenia patients. To our knowledge, no study has examined associations of C677T and A1298C with changes in schizophrenia symptom severity after antipsychotic treatment, while studies on metabolic outcomes remain sparse and inconsistent. The MTRR A66G has been assessed only once for metabolic parameters—not symptom severity—and sex-stratified analyses are lacking for all polymorphisms. A total of 186 antipsychotic-naïve first-episode or nonadherent chronic psychosis patients and 242 controls were genotyped using PCR-RFLP. Clinical assessments—including Positive and Negative Syndrome Scale (PANSS) scores, PANSS factor scores, and metabolic parameters (fasting plasma lipids and glucose levels, and body mass index)—were conducted at baseline and after 8 weeks. Genotype and allele frequencies did not differ between patients and controls. Significant associations emerged only for symptom changes, specifically within PANSS factor domains, in a sex-dependent manner. Female MTHFR 1298-A allele carriers (AA and AC) showed greater improvement in PANSS negative factor scores, whereas male MTRR 66-G allele carriers (GG and AG) showed reduced improvement in PANSS cognitive factor scores. Effect sizes were strong to very strong, with relatively modest contributions. MTHFR A1298C and MTRR A66G have sex-dependent impacts on symptomatic improvement—but not metabolic outcomes—after antipsychotic treatment. Accordingly, folate–homocysteine genetic markers and sex-specific factors can guide the development of personalized antipsychotic treatment approaches. Full article

Background/Objectives: UVB radiation triggers oxidative stress, inflammation and extracellular matrix (ECM) remodeling in dermal fibroblasts, contributing to skin aging and fibrosis. Plant-derived extracts with antioxidant and anti-inflammatory activity may counteract these effects. This study evaluated the protective role of Damor Triticum vulgare Aqueous Extract (DTVE) in human dermal fibroblasts (HDFs) exposed to UVB. Methods: Primary HDFs were irradiated with UVB (1.50 J/m²) and treated with DTVE either after irradiation (post-ir) or before and after irradiation (pre-ir). Cell viability was assessed by Trypan Blue and MTT assays. Inflammatory cytokines, fibrosis-related genes, p21 expression, mitochondrial ROS (MitoSOX) and αSMA accumulation were quantified by qRT-PCR, ELISA and immunofluorescence. Results: DTVE was not cytotoxic and preserved HDF viability under UVB exposure. UVB significantly increased pro-inflammatory cytokines, profibrotic markers, αSMA, mitochondrial ROS and p21. DTVE reduced all these UVB-induced alterations, with the pre-ir regimen providing the strongest protection. The extract attenuated early inflammatory activation, limited fibroblast-to-myofibroblast transition and decreased mitochondrial oxidative stress while reducing p21 upregulation. Conclusions: DTVE exerts protective antioxidant, anti-inflammatory and antifibrotic effects in UVB-exposed fibroblasts, particularly when used as pretreatment. These findings support DTVE as a promising candidate to mitigate UVB-induced dermal damage and warrant further investigation for potential therapeutic and cosmetic applications. Full article

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is a highly destructive disease affecting wheat in most growing regions worldwide. The most effective strategy for combating this disease is through the exploitation of novel and durable resistance genes derived from the relatives of wheat. Rye (Secale cereale L.) has been extensively hybridized with both tetraploid and hexaploid wheats and represents a valuable genetic resource for enhancing resistance and tolerance to both biotic and abiotic stresses. In this study, two novel 1R (1D) substitution lines, R156 and R189, derived from hexaploid triticale lines Yukuri and T4915, respectively, were comprehensively characterized using non-denaturing fluorescence in situ hybridization (ND-FISH) and immunofluorescence. To physically map the 1R-derived powdery mildew resistance gene from Yukuri, 3485 M₁-M₃ plants from the cross between R156 and susceptible wheat cultivar MY11 were studied by ND-FISH using multiple probes. A cytological bin map for Yukuri chromosome 1R was constructed using 105 molecular markers. Resistance evaluation combined with molecular mapping revealed that the novel resistance locus resides in bin 1RS-4, corresponding to the 58.60–109.28 Mb genome region of Lo7 rye chromosome 1R. Thus, these newly developed wheat–rye 1R translocation and deletion lines are expected to serve as valuable genetic resources for breeding powdery mildew resistant wheat cultivars. Full article

Background: Metastasis and recurrence account for the failure of nasopharyngeal carcinoma (NPC) treatment. Growing evidence indicates the dominant roles of cancer stem cells (CSCs) in tumor progression and therapy resistance. However, the heterogeneity of CSCs and potential stemness-related markers in NPC patients are still largely unknown. Methods: Consensus clustering was first applied to identify robust stemness subtypes for NPC patients based on the activities of stem cell gene sets. The differences in clinical outcomes, tumor immune microenvironment (TIME), and drug response were compared between subtypes. The stemness-related markers were prioritized via weighted gene correlation network analysis (WGCNA) and Cox regression, and verified through in vitro experiments. Results: NPC patients were classified into C1 and C2 subtypes. The C2 subtype exhibited higher activities of stem cell gene sets, worse prognosis, and aggressive tumor progression thus defined as stem cell-like tumor phenotype. The exclusionary relationships between tumor stemness and TIME infiltration were observed. The efficacy of several drugs and immunotherapy varied between NPC stemness subtypes. Through the WGCNA and survival analysis, we found that PSMC3IP, NABP2, CDC45, and HJURP were stemness-relevant genes. Sphere formation assays and analysis of the protein expression of stem cell markers by Western blotting revealed the roles of PSMC3IP, NABP2, CDC45, and HJURP in promoting CSC properties. Moreover, these genes were found to be related to the therapeutic effect of telomerase inhibitor in CCK8 experiments. Conclusions: This study systematically characterized two NPC subtypes with distinct stemness features, clinical outcomes, and TIME features. Novel stemness-related markers will provide valuable targets against metastatic or recurrent NPC. Full article

Diseases caused by Bipolaris sorokiniana, expressed as leaf spot blotch (SB) and common root rot (CRR), continue to limit spring wheat production, particularly in dry regions where yield losses may reach 35–40%. This study evaluated resistance to SB and CRR in fifty spring wheat genotypes at both seedling and adult plant stages and identified genetic sources of resistance using molecular markers linked to the Sb1 and Sb2 genes. Field trials were conducted in 2023 and 2024 in the Aktobe region under natural infection, artificial inoculation, and a fungicide-treated background. Based on leaf spot blotch severity quantified as the area under the disease progress curve (leaf AUDPC) under natural infection, nine genotypes displayed stable resistance across both years, while fungicide-treated plots revealed twenty-three resistant genotypes in 2023 and eighteen in 2024. Artificial inoculation identified five resistant lines in 2023 and one in 2024. Resistance to common root rot (CRR) was assessed independently based on subcrown internode (SCI) browning at the adult plant stage. Seedling assays confirmed consistent resistance in six genotypes, all of which carried Sb1, Sb2, or their combination. In total, Sb genes were detected in thirty-six of the fifty accessions, including genotypes from Kazakhstan, Russia, and several other countries. The presence of Sb1 or Sb2 was associated with reduced disease severity, particularly at the seedling stage. These findings identify valuable germplasm for breeding wheat with improved resistance to B. sorokiniana in Kazakhstan. Full article

Background/Objectives: The Fagopyrum dibotrys complex is a specialized high-altitude lineage in southwestern China with medicinal and breeding potential, but species delimitation remains unresolved. Methods: We sequenced 26 complete chloroplast genomes from the Hengduan Mountains to the Yunnan–Guizhou Plateau, analyzing genomic structures, variation patterns, and phylogenetic relationships. Results: All genomes exhibited typical quadripartite structures (152,213–160,302 bp), containing 133 genes (88 protein-coding, 8 rRNA, and 37 tRNA) with GC content of 37.9%. Collinearity analysis revealed highly conserved structures without structural rearrangements. Variations were concentrated in the large single-copy(LSC)/small single-copy(SSC) non-coding regions, with hotspots at ycf4–cemA and ndhF–rpl32. Codon usage showed an A/U bias, with leucine being most abundant and cysteine the least. Simple sequence repeats (SSRs) were predominantly mononucleotide repeats enriched in the LSC, while long repeats were mainly palindromic/forward. Maximum likelihood and Bayesian phylogenies consistently resolved three clades: Tibetan high-altitude specialists, limestone specialists, and a widespread Hengduan–Yunnan–Guizhou clade, with geographic clustering indicating isolation as the primary differentiation driver. Conclusions: This study refines the phylogenetic resolution of the F. dibotrys complex and identifies informative chloroplast markers, providing a genomic foundation for reliable species delimitation, evolutionary inference, and conservation management of this medicinal lineage. Full article