Cardiovascular disease (CVD) remains the leading cause of death worldwide, with underlying mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about their effects on the platelet-activating factor (PAF) pathway—a key mediator of inflammation and thrombosis. This study evaluates the antiplatelet and anti-inflammatory profiles of several commonly used cardiovascular and anti-inflammatory drugs through dual-pathway assessment of ADP- and PAF-induced platelet aggregation. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet responses in the presence of clopidogrel and a range of non-steroidal anti-inflammatory drugs (NSAIDs), including lornoxicam, diclofenac, ketoprofen, naproxen, etoricoxib, niflumic acid, allopurinol, and nimesulide. Clopidogrel confirmed its well-established ADP antagonism and also demonstrated inhibitory activity against the PAF pathway, suggesting a broader and underrecognized pharmacodynamic profile. Notably, several NSAIDs—particularly lornoxicam and diclofenac—exhibited strong inhibitory effects on both platelet activation pathways, whereas naproxen showed comparatively weak activity. These results emphasize the potential for pathway-specific pharmacological action among NSAIDs. Our findings highlight the value of evaluating drug effects beyond their conventional targets. By considering both PAF- and ADP-mediated mechanisms, this dual-pathway analysis contributes to a more nuanced understanding of drug function. Such insights may support the development of more comprehensive and personalized therapeutic strategies for cardiovascular, hypertensive, and inflammation-driven diseases.

Introduction: Wilson's disease (WD) is an autosomal recessive hereditary disorder caused by mutations in the ATP7B gene, which impair copper homeostasis. The clinical heterogeneity observed in patients suggests the involvement of modifier genes influencing phenotypic expression. Objective: We aimed to characterize the structural and functional properties of genes associated with WD through a bioinformatic approach, aiming to identify relevant molecular patterns and potential modifier genes. Methods: Genes related to WD were retrieved from the MalaCards database. Structural annotation was performed using the UCSC Genome Browser (GRCh38/hg38), including for the gene architecture, regulatory elements, repeat content, and evolutionary conservation. The data were statistically processed using Python scripts, and functional enrichment analyses (ToppGene) and protein–protein interaction analyses (STRING) were conducted. The genes were grouped based on patterns of functional convergence and structural divergence. Results: A total of 21 genes were identified with significant structural divergence in terms of their exon number, transcript variants, and conservation, yet they exhibited convergent biological functions related to key processes such as the homeostasis of metals, particularly copper. Subgroups were observed with compact gene architectures and high conservation, as well as others with greater structural complexity and lower conservation. Notable genes included COMMD1, ABCC2, HFE, ATP7A, SLC11A2, SLC31A2, and MT1E, some of which have previously been described as potential modifiers in WD. Conclusions: These findings support the existence of structurally divergent yet functionally convergent genes in the pathophysiology of WD. Their identification highlights their potential as candidates for use in functional studies aimed at understanding clinical variability and developing predictive models of this disease.

Introduction
PC-Cu (1,10-phenanthroline)(cyclobutane-1,1-dicarboxylate) is a copper-based coordination complex proposed as a novel anticancer candidate. Identifying its potential molecular targets and evaluating their expression in cancer may offer valuable insights into its therapeutic potential within the context of precision oncology.

Methods
We used the SuperPred and TargetNet platforms to predict potential molecular targets of PC-Cu, applying a cutoff of probability and accuracy ≥ 0.8. Subsequently, we analyzed gene expression profiles using GEPIA3, which integrates TCGA and GTEx transcriptomic data. Genes were considered significantly deregulated if they exhibited a log2FC > 1 or < –1 and a p-value or q-value < 0.05.

Results
A total of 34 high-confidence targets were identified. Of these, 21 showed significant differential expression across various cancer types. Strong overexpression was observed for BCL2A1 in melanoma (log2FC = 6.37), CTSD in diffuse large B-cell lymphoma (log2FC = 5.25), PRKCG in cholangiocarcinoma (log2FC = 4.37), GLRA1 in paraganglioma (log2FC = 4.28), and CDC25B in sarcoma (log2FC = 2.31). Conversely, significant downregulation was found for NR3C1 in bladder cancer (log2FC = –0.86), CYP19A1 in bladder (–0.87), NR1H4 in prostate (–0.69), GLRA1 in lung (–0.73), and APEX1 in paraganglioma (–0.68). These findings suggest that PC-Cu may modulate key molecular processes including apoptosis regulation, hormonal signaling, and tumor metabolism.

Conclusion
PC-Cu interacts with several genes involved in cancer biology and demonstrates a tissue-specific expression in cancer. These results support its potential as a precision oncology agent and justify further experimental validation.

Background/Objectives: Intraoperative neurophysiological monitoring (IONM) is used to detect, reduce, and prevent neurological injury during extramedullary spinal cord tumor (EMSCT) resection. This meta-analysis aims to systematically assess the performance of IONM modalities, somatosensory evoked potentials (SSEPs), transcranial motor evoked potentials (TcMEPs), and multimodal approaches in EMSCT surgery, with a particular focus on determining whether a single monitoring modality is sufficient to predict postoperative neurological deficits.
Methods: Following PRISMA-DTA guidelines, we searched MEDLINE, PubMed, and Ovid (inception to April 2025) for studies on IONM in EMSCT surgeries (PROSPERO: CRD420251047345). Pooled sensitivity, specificity, and reversibility metrics were calculated using bivariate models, with quality assessed via QUADAS-2. Z-test and Bayesian meta-analysis were used for comparisons.
Results: Across 20 studies (2,672 patients), multimodal IONM showed a log DOR of 4.310 (95% CI: 3.581–5.039) and an AUC of 94.2%, TcMEP monitoring showed a log DOR of 4.457 (95% CI: 3.775–5.139) and an AUC of 92%, while SSEP monitoring showed a log DOR of 3.463 (95% CI: 2.702–4.224) and an AUC of 82%. All modalities demonstrated high specificity (>95%), indicating low false-positive rates. Bayesian analysis revealed >90% probability that TcMEP-based approaches were superior to SSEPs. Reversible TcMEP changes were associated with an 11% (95% CI: 4–24%) postoperative deficit rate, compared to 35% (95% CI: 12–67%) for SSEPs.
Conclusions:
These findings caution against relying solely on SSEPs and support the use of multimodal IONM strategies, which enhance the early detection of impending neurological injury, enable timely surgical interventions, and help prevent permanent neurological damage in EMSCT resections. Although TcMEP and multimodal monitoring showed similar diagnostic accuracy, we continue to recommend multimodal approaches as the current standard of care, pending prospective studies to determine if TcMEP alone can reliably replace multimodal monitoring.

Background: While significant advancements have been made in breast cancer treatment, metastasis remains a negative outcome which drastically worsens the patient prognosis. Common metastatic sites include the bones, lungs, and liver, with secondary brain metastases seen in advanced disease. Treatments for disseminated tumor cells often carry risks of systemic toxicity without guaranteeing complete eradication. It is vital that we identify key molecular mechanisms underlying the systemic metastatic cascade so that we can disrupt this process. Our team has created a unique mouse model utilizing the 4T1 murine mammary tumor cell line, generating lung/brain metastases with a 100% success rate. This model will help identify the conditions necessary for the development of primary and secondary breast cancer metastases.

Methods: 4T1 parental cells (4T1-Ps) were genetically labeled with firefly luciferase and EGFP for imaging. A highly brain-metastatic subpopulation (4T1-BR) was then established via serial in vivo passage and isolation from the brains of BALB/C mice following iv 4T1-P administration. Brain metastasis was confirmed through bioluminescent imaging, the examination of neurological symptoms, and light sheet microscopy. Genes selectively upregulated in 4T1-BR cells were identified through RNA transcriptomic analysis. Twenty-eight potential candidates encoding for surface-expressed proteins were selected. Surface expression was evaluated using flow cytometry and immunofluorescent staining. Upregulated candidates were knocked out using CRISPR-Cas9 in 4T1-BR cells. Changes in the metastatic biodistribution and survival were assessed in vivo following iv administration.

Results: 4T1-BR cells demonstrate increased surface CD151 expression, as observed using flow cytometry and immunofluorescent staining. Mice transplanted with CD151-/- 4T1-BR cells demonstrated a decreased total bioluminescent signal but no change in their survival, the brain metastasis incidence, or the lung/brain tumor burden.

Conclusions: Surface CD151 expression is increased in brain-metastatic 4T1-BR populations compared to 4T1-Ps. While not directly related to survival or the brain metastatis potential, CD151 may play a functional role in altering systemic biodistribution.

Introduction
The KRAS gene plays a key role in oncogenic signaling. Regulatory variants within its 3' untranslated region (3'UTR) can affect microRNA (miRNA) binding, influencing post-transcriptional regulation. This study evaluated the potential association between the rs12245 variant in the 3'UTR of KRAS and breast cancer (BC) susceptibility and explored this variant's possible functional relevance through in silico analysis.

Methods
A total of 627 individuals were genotyped for rs12245, including 385 BC patients and 242 individuals forming a reference group. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Predictions of altered miRNA binding were obtained from miRNASNP-v3 and PolymiRTS. The expression status of the affected miRNAs was examined in dbDEMC. In addition, eQTL analysis was performed using GTEx data for breast mammary tissue.

Results
The AT genotype was associated with a reduced risk of BC (OR = 0.55; 95% CI: 0.40 to 0.77; p = 0.0003), while the TT genotype and recessive model were associated with an increased risk (OR = 1.44; 95% CI: 1.00 to 2.06; p = 0.023). No significant associations were found with clinicopathological variables. In silico analysis suggested that rs12245 may alter the binding of several miRNAs to the KRAS 3'UTR, including hsa-miR-543, hsa-miR-544a, hsa-miR-4803, hsa-miR-5580-3p, hsa-miR-4686, hsa-miR-6738-3p, and hsa-miR-5096, which are deregulated in BC. The GTEx data indicated that rs12245 shows eQTL activity in breast tissue (p = 0.00069; slope = –0.094).

Conclusion
The rs12245 variant in KRAS may contribute to determining BC susceptibility and shows potential regulatory effects based on eQTL and miRNA binding predictions. These findings warrant further investigation to clarify this variant's biological significance.

Background: Colorectal cancer (CRC) ranks as the third most common malignancy worldwide and the leading cause of cancer-related mortality in 2024. While previous studies have explored the role of intracellular genes in CRC development, there is limited evidence regarding the involvement of fibroblast growth factor receptors (FGFR), particularly FGFR3. This gene, located on chromosome 4p16.3, consists of 19 exons and plays a key role in cell cycle regulation. Three high-variability regions, or hotspots, have been identified within the gene, with exon 7 being the most significant—accounting for approximately 88% of reported mutations. Exon 7 encodes the IgIII domain, which is essential for the formation of receptor isoforms via alternative splicing, affecting ligand-binding specificity. The synonymous variant rs2234909, located in exon 7 (codon 294), involves a T>C transition (p.Asn294Asn). Although it does not change the amino acid sequence, it may promote disulfide bond formation between adjacent monomer receptors or induce structural changes in the tyrosine kinase domain, leading to ligand-independent dimerization.

Objective: To analyze the association between the FGFR3 rs2234909 variant and CRC in the Mexican population.

Materials and Methods: A cross-sectional analytical study was conducted with 472 DNA samples from CRC patients and 395 from healthy donors. The rs2234909 variant was genotyped using real-time PCR (qPCR) with TaqMan® probes on a Bio-Rad CFX96 system. Genotypic and allelic frequencies were calculated by direct counting. Associations between genotypes and CRC risk were assessed using bivariate analysis (odds ratio, 95% CI), with statistical significance set at p < 0.05. Data were analyzed using SPSS v24.

Results: The GG genotype and recessive model of rs2234909 were significantly associated with an increased risk of CRC (OR = 5.34; 95% CI: 3.36–8.47; p < 0.05).

Conclusion: rs2234909 may serve as a potential genetic susceptibility marker for CRC.

Introduction

Thymidylate synthase (TYMS) is a key enzyme in DNA synthesis and a primary target of fluoropyrimidine-based chemotherapy. The rs45445694 variant (2R/3R), located in the 5′UTR region of TYMS, may affect gene expression and influence treatment response. This study aimed to evaluate the frequency and clinical relevance of rs45445694 in Mexican breast cancer (BC) patients and its association with chemotherapy response.

Materials and Methods

A total of 785 BC patients were genotyped for the 2R/3R polymorphism and categorized according to chemotherapy response: complete response (n=136), no response (NR, n=311), no response due to recurrence (NRR, n=249), and partial response (PR, n=90). Genotypic frequencies were determined, and associations were evaluated using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The 2R/3R genotype was the most frequent across all groups, especially among responders (68%), compared to 57.7% in NR, 62% in NRR, and 58% in PR. The 3R/3R genotype was more prevalent in NR (29.5%) and PR (41%) than in responders (13%). In contrast, the 2R/2R genotype was relatively uncommon, showing similar frequencies in responders (16%) and NR (12.5%), with slightly lower proportions in NRR (11%) and PR (10%). The 3R/3R genotype was significantly associated with increased risk of NR (OR=2.94; 95% CI: 1.67–5.16; p=0.0002), NRR (OR=2.57; p=0.0014), and PR (OR=4.88; p<0.00001). Conversely, the 2R/3R genotype was protective in NR (OR=0.64; p=0.045) and PR (OR=0.45; p=0.005).

Conclusions

The rs45445694 variant of the TYMS gene may influence chemotherapy response in BC. The 3R/3R genotype was associated with poorer outcomes, while 2R/3R appeared more frequently in responders, suggesting a possible protective effect.

The biological heterogeneity of breast cancer complicates the choice of an effective treatment. The participation of microRNAs in the regulation of target mRNAs in biological processes and signaling cascades makes them suitable for use as diagnostic and prognostic markers or targets for therapy.

The aim of our work was to analyze the expression of microRNAs in paired samples of tumor and adjacent normal breast tissue and to assess their potential cooperative participation in biological processes and signaling pathways.

The microRNA expression was analyzed using Taq Man MicroRNA Assay Kits. The differences between the groups were assessed using the nonparametric Mann–Whitney U test. Spearman's correlation coefficient was calculated to identify co-expression. Functional annotation and enrichment analysis concerning Gene Ontology terms and KEGG signaling pathways were performed in R (clusterProfiler, org.Hs.eg.db, enrichplot) (adj. p-value<0.05 according to Benjamini–Hochberg procedure).

Positive expression correlations were found for seven pairs of microRNAs: miR-127-5p/miR-125b-5p (Rs=0.47), miR-148a-3p/miR-125b-5p (Rs=0.44), miR-148a-3p/miR-132-3p (Rs=0.46), miR-193a-5p/miR-127-5p (Rs=0.51), miR-24-2-5p/miR-127-5p (Rs=0.43), miR-34b-3p/miR-193a-5p (Rs=0.54), and miR-34b-3p/miR-24-2-5p (Rs=0.58). Enrichment analysis revealed overlapping processes for four microRNA pairs: miR-127-5p/miR-125b-5p (28), miR-148a-3p/miR-125b-5p (355), miR-148a-3p/miR-132-3p (195), and miR-34b-3p/miR-193a-5p (three common processes). We constructed a regulatory net of microRNA–mRNA interactions. MiR-125b-5p was the central node in the net; it bound to multiple oncogenic and suppressor genes, including APC, BCL2, STAT3, and LDLR. Coincident targets such as APC and CDKN1A bound by multiple microRNAs suggest coordinated post-transcriptional regulation.

The constructed net demonstrates potentially significant regulatory axes linking microRNAs and their targets, highlighting their possible common roles in breast cancer pathogenesis.

Introduction

Post-COVID-19 syndrome (PCS) is a complex multisystem condition marked by prolonged symptoms after acute SARS-CoV-2 infection. This study investigated clinical, biochemical, and gut microbiota alterations in PCS patients (n = 28) before and after a structured 14-day rehabilitation program, compared to healthy controls (n = 48).

Materials and Methods
Comprehensive evaluations included the following: hematological, coagulation, and biochemical profiling using a UniCel DxH800 hematology analyzer (Beckman Coulter, USA) and Cobas e411 system (Roche, Switzerland); serum metabolite analysis via gas chromatography–mass spectrometry (Trace GC 1310 and ISQ LT; Thermo Electron Corporation, USA); and gut microbiota assessment with real-time PCR (CFX 96, BioRad, USA) using Colonoflor-16 kits (AlphaLab, Russia) to quantify bacterial taxa.
Data were compared against reference ranges and age-matched controls.

Results
Post-rehabilitation, patients reported subjective improvements in respiratory function, mood, and overall well-being. However, persistent abnormalities included the following. Elevated metabolic markers: 4-hydroxybenzoic acid, succinic acid, and fumaric acid. Pro-inflammatory mediators: interleukin-6 levels remained 2.1× higher than controls. Microbiota dysbiosis: increased total bacterial load (4.8 log10 CFU/g), reduced Lactobacillus spp., and higher pro-inflammatory taxa. Systemic inflammation: 25% of patients showed elevated ESR (>20 mm/h), and 20% had elevated CRP (>5 mg/L).

Conclusion
While rehabilitation alleviated clinical symptoms, residual metabolic dysregulation and inflammation suggest incomplete recovery. ESR and CRP levels may serve as practical biomarkers for monitoring post-COVID-19 interventions. Acute-phase reactants and microbiota profiles could guide personalized management strategies in PCS.