Colorectal cancer (CRC) remains one of the leading causes of cancer mortality, with a poor survival rate of less than 15%. Imatinib (IM) and Zebularine (ZEB) alone have shown potential effects in CRC treatment, but their combination has not been thoroughly studied. This study investigates the potential effects of IM and ZEB in colon cancer cells to provide a novel therapeutic agent for managing CRC. Cell growth inhibition, oxidative stress markers, and cell cycle progression were assessed in HCT-116 cells treated with IM, ZEB, and their combinations. ZEB uptake levels were analyzed by LC-MS/MS, apoptosis was quantified by flow cytometry, and gene expression changes were analyzed by qPCR. The expression of metastatic markers, apoptotic regulators, and EGFR was assessed. Both IM and ZEB inhibited cell growth in a concentration-dependent manner, and their combination showed synergistic effects. The combination significantly enhanced oxidative stress. The combination therapy increased apoptosis and necrosis. Furthermore, the combination induced significant S-phase arrest in the cell cycle. The combination treatment reduced metastatic markers (MMP9, MMP2), and the apoptotic marker Caspase-9 was upregulated. Additionally, the Bcl-2 protein, a key regulator of apoptosis, was significantly downexpressed. Remarkably, the combination treatment showed significant inhibition in EGFR levels. Both IM and ZEB combination showed promise in the management of CRC by inducing oxidative stress, promoting apoptosis, and modulating critical genes involved in metastasis and apoptosis. Further investigation will be needed to verify their application in preclinical and clinical settings.

Triple Negative Breast Cancer (TNBC) is one of the most aggressive subtypes of breast cancer (BC), which is associated with a very poor prognosis. It is a broad category of tumors with a variety of biological, clinical, and morphological characteristics. FOXM1 is a pivotal transcription factor that modulates proliferation-associated genes through complex protein-DNA and protein-protein interactions, making it a highly attractive target in cancer therapy. However, existing small-molecule inhibitors often suffer from limited specificity and efficacy. In this study, we designed, synthesized, and evaluated novel series of 2-aminothiazole derivatives (C1-C15) as potential FOXM1 inhibitors. Molecular docking and molecular dynamics (MD) simulations were employed to investigate the binding interactions of these compounds with the FOXM1 DNA-binding domain (FOXM1-DBD). Structural analysis highlighted the importance of crucial residues, including Asn283, His287, and Arg286, in mediating inhibitory activity. Among the synthesized compounds, C11 exhibited remarkable structural alignment and interaction patterns with FOXM1-DBD, comparable to the reference inhibitor FDI-6. In vitro studies using TNBC cell lines (MDA-MB-231, BT-549, and BT-20) demonstrated that compound C11 significantly outperformed FDI-6 in potency. Western blot analysis revealed that C11 effectively suppressed FOXM1 transcriptional activity at concentrations of 10 µM in BT-549 cells and 20 µM in MDA-MB-231 cells. These findings underscore the potential of C11 as a potent FOXM1 inhibitor and highlight its promise for further development in TNBC therapy.

Metformin, a first-line antidiabetic drug, has demonstrated anticancer potential in various malignancies, yet its precise mechanisms in hepatocellular carcinoma (HCC) remain incompletely defined. Here, we show that metformin inhibits lipid accumulation and proliferation in HCC cells through modulation of N6-methyladenosine (m⁶A) RNA methylation. Treatment of HepG2 and Huh7 cells with metformin significantly reduced intracellular triglyceride and cholesterol levels, concomitant with decreased lipid droplet accumulation and impaired cell proliferation. Mechanistically, metformin lowered global m⁶A methylation by downregulating the m⁶A methyltransferase Methyltransferase-like 3 (METTL3), while upregulating the demethylase Fat mass and obesity-associated protein (FTO). Functional assays revealed that METTL3 overexpression restored lipid accumulation and proliferation in metformin-treated cells, whereas METTL3 knockdown phenocopied the lipid-lowering and anti-proliferative effects of metformin. Further analyses identified the METTL3/ACC1/FASN axis as a critical downstream pathway, with metformin suppressing m⁶A modification and expression of Fatty acid synthase (FASN) and Acetyl-CoA carboxylase 1 (ACC1) transcripts - effects reversed by METTL3 overexpression. These findings establish METTL3 as a central mediator of metformin's metabolic and antiproliferative activities in HCC, uncovering a previously unappreciated epitranscriptomic mechanism by which metformin impedes tumor progression.

Hydatid cyst disease is a parasitic disease induced by Echinococcus granulosus, which is still endemic in northern African countries. We report the case of a late-discovered pulmonary hydatid cyst in a four-year-old boy revealed by recent dyspnoea. The chest X-ray showed a complete white-out of the left hemithorax with mediastinal deviation, and the thoracoabdominal CT scan showed a giant pulmonary hydatid cyst encompassing the entire left lung associated with a hepatic cyst. An emergent superior pulmonary lobe resection was performed under deep general anaesthesia and selective intubation to prevent contralateral lung inundation. The evolution was favourable postoperatively.

Mycoplasma pneumonia (MP), as a global infectious disease in sheep, seriously affects the production performance of sheep and economic benefits of sheep industry. However, current research on sheep resistance to MP remains limited. To address this gap and explore the potential epigenetic regulation of sheep MP resistant, this study employed high-throughput sequencing techniques (ATAC-Seq and CUT&Tag) to analyze epigenetic modifications in lung tissue from healthy and MP-affected sheep and reveal differential epigenetic landscapes associated with disease resistance. Integrating transcriptome analysis related to MP and genome-wide association studies (GWAS), FOXF1 was identified as a candidate gene for MP-resistance in sheep. We established a Mycoplasma ovipneumoniae (MO)-infected sheep alveolar epithelial cell model and regulated FOXF1 expression in cells through interference and overexpression techniques to study MO's adhesion and damage. The results showed that activation promoters or enhancer elements in FOXF1 introns of healthy lungs may enhance its transcription. FOXF1 overexpression reduced MO-mediated adhesion damage to cells, while knock-down increased it. Our work has enriched the gene pool for anti-pneumonia and studied the role of the FOXF1 gene in MO-infected cells, accumulating reliable genetic resources for sheep MP disease resistant breeding.

Long-distance relationships (LDRs) reduce opportunities for physical intimacy, often prompting individuals to seek alternative sexual activities such as masturbation. Although common, its influence on sexual satisfaction, sexual health, psychological well-being, and relational stability in LDRs remains understudied. Moreover, cultural and population differences shape diverse meanings and perspectives on masturbation.

We employed a systematic review approach to explore the role of masturbation within long-distance relationships. Specifically, this review aims to examine how masturbation is associated with sexual, relational, and psychological outcomes and how these perspectives vary across cultural contexts.

A systematic review was conducted following the PRISMA guidelines, compiling both quantitative and qualitative studies on masturbation as an alternative sexual activity in LDRs as well as its implications for sexual satisfaction, relationship satisfaction, and psychological well-being.

Fourteen studies were eligible for further analysis in which men reported higher frequencies of masturbation compared to women, with significant increases observed in the context of long-distance relationships and during COVID-19 quarantine periods. Men were mainly motivated by biological release, orgasm, and stress reduction, often with pornography, whereas women reported broader motives such as relaxation, better sleep, stress relief, and emotional closeness. The effects on sexual satisfaction were mixed: masturbation was reported to be associated with greater body awareness, self-esteem, and relational harmony, yet excessive frequency was linked to lower satisfaction and arousal. Mutual, technology-mediated practices helped maintain intimacy, while excessive solitary use undermined relationship quality. From a sexual health perspective, moderate masturbation may be associated with indirect benefits through improved body awareness, whereas frequent use was linked to poorer experiences. Psychologically, it served as a coping strategy for sleep and stress, but excessive engagement increased anxiety and reduced emotional well-being.

Masturbation appears to be a common and potentially adaptive alternative sexual activity in the context of LDRs and during the COVID-19 pandemic. However, in Eastern contexts, its meaning and impact are strongly shaped by sociocultural and religious norms.

The ULTRA trial evaluated the impact of ultra-early and short-term tranexamic acid (TXA) treatment in patients with subarachnoid hemorrhage (SAH) and found no clinical benefit at six months. This post-hoc analysis examines whether TXA improves quality of life (QoL) at three and six months.

The ULTRA trial was a randomized, controlled, multicenter study conducted from July 2013 to July 2019. Patients received either TXA or standard care. This analysis included patients who completed at least one QoL questionnaire. The primary endpoint was QoL, assessed using the EQ-5D-3L questionnaire at three and six months. Linear mixed models adjusted for confounders were used to analyze the association between TXA and QoL.

Of the 955 ULTRA patients, approximately 25% died, and 63% completed at least one QoL questionnaire. At three months, the TXA group had a mean EQ-5D index score of 0.75 versus 0.71 in the control group (p = 0.11) and a mean EQ-5D Visual Analogue Scale (VAS) score of 89 versus 86 (p = 0.10). At six months, the mean EQ-5D index score was 0.84 in the TXA group compared to 0.82 in the control group (p = 0.23), and the mean VAS was 92 in the TXA group compared to 89 in the control group (p = 0.13).

Ultra-early and short-term TXA did not result in a significant improvement in QoL at three or six months in patients with SAH. Given the lack of benefit on both clinical outcome and QoL, routine use of TXA is not recommended.

Netherlands Trial Register: NTR3272.

gov: NCT02684812.

Brain arteriovenous malformations (BAVMs) are increasingly recognized as dynamic vascular diseases driven by endothelial genetic alterations and dysregulated signaling pathways, rather than as static structural anomalies. Accumulating evidence from both hereditary and sporadic forms of BAVMs has established endothelial signaling dysfunction as a central pathogenic mechanism underlying aberrant angiogenesis, progressive lesion remodeling, and vascular instability that predisposes to hemorrhage. These insights have fundamentally shifted the conceptual framework of BAVMs toward a pathway-driven disease model. Despite this progress, direct access to biologically informative molecular material from living AVM lesions remains limited, posing a major barrier to detailed mechanistic interrogation and the translation of molecular insights into clinical decision-making. Historically, molecular characterization of AVMs has relied almost exclusively on surgically resected tissue, restricting analyses to selected patient populations and frequently reflecting late-stage disease biology. Such approaches provide limited insight into disease initiation, temporal evolution, or treatment-induced molecular changes. Recent advances in minimally invasive biopsy strategies, particularly those leveraging endovascular access, have begun to overcome these limitations by enabling molecular interrogation of AVMs in vivo. In this mini review, we summarize emerging approaches for molecular profiling of AVMs, with a primary focus on BAVMs, while also drawing on relevant studies in extracranial and other arteriovenous malformations that share common endovascular access routes, technical principles, and translational implications.

The socio-economic situation in Lebanon has been dramatically deteriorating over the years affecting food insecurity (FI), psychological distress, and health-related quality of life (HRQoL). Therefore, the objectives of the study are to estimate the prevalence and severity of FI among Lebanese residents; evaluate the association between FI and psychological distress; and examine the association between FI and HRQoL.

A cross-sectional study was conducted among residents of Lebanon aged 18 years or older in 2024. The final sample included 519 participants. The Food Insecurity Experience Scale, Beirut Distress Scale (BDS), and EQ-5D-5 L were used to assess FI, distress, and HRQoL levels, respectively. The questionnaire also included sociodemographic and general health-related questions. Regression analysis was applied to explore the association of FI with psychological distress and HRQoL after adjustment for relevant covariates.

14.3% of the participants exhibited moderate to severe FI. A moderate level of HRQoL was shown with a mean of 74.18 (SD = 19.0) for the EQ-VAS. Moreover, FI was significantly associated with HRQoL and psychological distress. FI (B = 5.183), age (B = 0.092), gender (B = 3.998), employment status (B = 0.558), and job loss (B = 6.021), were significant predictors of the BDS (p < 0.05). Whereas FI (B = - 8.490), age (B = - 0.461), job loss (B = - 4.659), and household income (B = 1.466) were significant predictors of EQ-VAS (p < 0.05).

FI was associated with poorer mental health and lower HRQoL among Lebanese residents. This highlights the impact of the socio-economic crisis and provides data that could guide efforts to improve population health, especially for NGOs that are providing support to local communities.

To examine sociodemographic, clinical, and healthcare-related factors associated with preoperative health-related quality of life (HRQoL) among patients undergoing surgery for degenerative lumbar spine conditions in a multi-ethnic Asian population.

This cross-sectional study used baseline data from the Spine PROM Surgery Registry, including 1194 patients scheduled for surgery within a Singapore healthcare cluster between 2017 and 2022. HRQoL was measured using the EQ-5D-3L, with utility scores crosswalked to the EQ-5D-5L index using the van Hout crosswalk. Hierarchical linear regression assessed factors associated with HRQoL across three blocks: sociodemographic, clinical, and healthcare/lifestyle. Multivariable logistic regression identified factors associated with reporting problems within each EQ-5D dimension.

Mean age was 58.1 years (SD 16.1); 51.5% were female. Mean EQ-5D-5L index was 0.43 (SD 0.38). Pain/discomfort (93.6%) and usual activities problems (84.3%) were most commonly reported. Lower EQ-5D scores were independently associated with non-outpatient presentation (β = -0.37), non-Chinese ethnicity (e.g., Malay: β = -0.10), secondary education (β = -0.15), and accident/trauma history (β = -0.11). Dimension-level analyses showed secondary education was associated with higher odds of problems in mobility (OR = 2.72), self-care (OR = 1.87), usual activities (OR = 1.80), and anxiety/depression (OR = 1.97). Non-outpatient presentation was associated with markedly higher odds of self-care problems (OR = 2.98).

Patients awaiting lumbar spine surgery appear to have impaired preoperative HRQoL. Although the modest explained variance limits robust risk prediction, preoperative profiles may still help inform clinical discussions and shared decision-making. Non-outpatient presentation may help identify patients who could benefit from enhanced preoperative support, although this requires prospective validation. Differences by ethnicity and education suggest opportunities for culturally tailored counselling. EQ-5D dimension profiles may indicate targets for prehabilitation and provide Singapore-based benchmark data for a lumbar spine surgery cohort for patient-centred care, service benchmarking, and health technology assessment.