José-Noel Ibrahim

Full Papers; Authors: A. Chaaban, Z. Skaineh, R. Hammoud, A. Chebly, L. Karam, E. Eldawra, J.-N. Ibrahim

Short-chain fatty acids (SCFAs) are microbial metabolites produced by the gut microbiome through the fermentation of dietary fibers and non-digestible carbohydrates. SCFAs have received considerable interest as potential regulators of various cancers, including colorectal cancer and breast cancer. However, their roles and underlying mechanisms in ovarian cancer remain elusive. This study aimed to investigate and compare the anti-cancer effects of sodium butyrate (NaB) and sodium propionate (NaP) in two distinct ovarian cancer cell lines, SKOV-3 and PA-1. Both NaB and NaP significantly reduced proliferation and colony formation, and impaired spheroid formation of SKOV-3 and PA-1 cells in a dose- and time-dependent manner. Notably, NaB exhibited greater anti-cancer potency than NaP, as evidenced by its lower IC₅₀ values—being 4.8-fold and 3.2-fold lower at 72 h and 96 h, respectively, in SKOV-3 cells, and 4.4-fold and 1.7-fold lower at 72 h and 96 h, respectively, in PA-1 cells. Additionally, treatment with NaB for 24 h and with NaP for 24–48 h induced cell cycle arrest at the G2/M phase in both cell lines, accompanied by an upregulation of p21 and a decrease in the expression of cyclins A2, B1, and B2. Moreover, 48 h post-treatment, both compounds induced apoptosis, with NaB demonstrating more pronounced effects. NaB increased the percentage of late apoptotic cells to 21.85% at 10 mM in SKOV-3 cells and to 69.9% at 5 mM in PA-1 cells, while 15 mM NaP resulted in 4.3% and 16.8% late apoptotic cells in SKOV-3 and PA-1, respectively. This was accompanied by modulation of apoptosis-regulatory proteins, including PARP-1 cleavage and an increased BAX/BCL2 ratio in the treated cells, suggesting the involvement of the intrinsic apoptotic pathway. Our study demonstrated that NaB and NaP inhibited the growth and survival of two different ovarian cancer subtypes through cell cycle arrest and apoptosis. While NaB exhibited greater potency, our findings highlight the promising therapeutic potential of both compounds in ovarian cancer and lay the groundwork for further mechanistic and clinical studies. The online version contains supplementary material available at 10.1186/s12935-026-04284-5.

Afin de mieux comprendre le mécanisme physiopathologique et inflammatoire impliqué dans la fièvre Méditerranéenne familiale (FMF), nous avons étudié le profil cytokinique ex vivo monocytaire et lymphocytaire des patients FMF. Nous avons ensuite étudié l’implication potentielle dans la FMF de la protéine RAC1, qui semble jouer un rôle dans la production de l’IL-1β, d’une part, et dans la production du stress oxydant, d’autre part. Enfin, nous avons recherché une association potentielle entre les gènes IL-1β et IL-1RA et la susceptibilité et/ou la sévérité de la maladie.La première partie de l’étude a porté sur 34 patients FMF génétiquement confirmés, dont 9 ont été prélevés à deux reprises, en crise et hors crise, et 24 sujets sains. Les marqueurs inflammatoires MBL et CRP ont été dosés dans le sérum par ELISA, et les cytokines ont été quantifiées par Luminex dans le sérum et les surnageants de culture de PBMC de patients et des contrôles avec ou sans stimulation des monocytes par LPS et des lymphocytes par anti-CD3/CD28.Dans la deuxième partie de ce travail, une étude comparative des niveaux d’expression du gène RAC1 chez les patients FMF, en crise ou non, et les contrôles a été effectuée par PCR quantitative en temps réel. L’IL-1β et l’IL-6 ont été dosées par ELISA en présence ou en absence de l’inhibiteur de RAC1 dans les surnageants de culture de PBMC, avec ou sans stimulation par LPS. La quantification des marqueurs du stress oxydant a été effectuée dans le plasma ainsi que dans les surnageants de culture de PMN stimulés ou non par LPS, en présence ou en absence de l’inhibiteur de RAC1.Les génotypes au niveau des 3 polymorphismes à la position -511, -31 et +3954 d

Consanguinity is associated with an increased risk of autosomal recessive diseases. Its prevalence varies globally, with notably high prevalence in Middle-Eastern countries. Gaining insight into both the prevalence of consanguineous marriages and societal attitudes toward them is essential for designing effective public health interventions. This study examines the current prevalence of consanguinity in Lebanon and explores its contributing risk factors. It further evaluates the knowledge of the Lebanese population regarding this practice and premarital genetic screening, as well as their attitudes toward consanguinity and genetic counseling. A cross-sectional survey was conducted among 984 Lebanese individuals, aged 18 to 65 years, using an online self-administered questionnaire. The prevalence of consanguinity in Lebanon was found to be 24.5%, with first-cousin marriages comprising 46.5% of these unions; place of residence was the only independent factors affecting consanguinity prevalence among our sample. Most participants had a good understanding of consanguinity but misconceptions about specific genetic risks persisted. Attitudes varied, with participants from consanguineous backgrounds showing greater acceptance of the practice. Logistic regression identified gender, education, occupational status, and age as independent predictors of consanguinity while insufficient income, having consanguineous parents, and having a poor knowledge were associated with a positive attitude towards consanguinity. While the prevalence of consanguinity remains high and consistent over time, societal beliefs and cultural practices continue to influence this phenomenon. Public health interventions should focus on raising awareness and disseminating accurate information about the implications of consanguinity and the importance of genetic counseling, particularly among communities with high prevalence of consanguinity.

Background and Aims: Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease caused by mutations in the MEFV gene, resulting in recurrent inflammatory episodes and a risk of developing amyloidosis. Although its pathophysiology is well described, FMF still lacks specific biomarkers and personalized treatment strategies. MicroRNAs (miRNAs), which regulate gene expression posttranscriptionally, have emerged as promising diagnostic, prognostic, and therapeutic biomarkers. Given their complex expression patterns, bioinformatics approaches are essential for their identification and interpretation. Hence, this review aims to summarize current bioinformatics tools used in FMF‐related miRNA research and highlight additional platforms employed in other inflammatory diseases that may advance FMF research. Methods: A narrative review was conducted by examining published FMF studies that applied miRNA‐focused bioinformatics analyses, including miRWalk, TargetScan, and machine learning pipelines. To identify tools with potential relevance to FMF, platforms widely used in rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, and psoriasis, such as miRDeep2, miRTarBase, DIANA‐miRPath, miEAA, and MAGPIE, were evaluated for their analytical strengths and applicability to autoinflammatory pathways. Results: Most FMF studies rely on a narrow set of tools, primarily miRWalk or TargetScan for target prediction. Emerging machine learning approaches have also been utilized to classify patients and explore candidate biomarkers. Other inflammatory diseases use more advanced platforms enabling miRNA discovery, validated interaction mapping, pathway enrichment, and multi‐omics integration. Tools such as miRDeep2, miRTarBase, DIANA‐miRPath, miEAA, and MAGPIE remain underutilized in FMF. Key limitations include small cohorts, patient heterogeneity, and limited experimental validation. Conclusion: Broadening the bioinformatics toolkit for FMF miRNA research could significantly enhance biomarker identification and mechanistic insight. Larger datasets, integrated analysis pipelines, and cross‐disciplinary collaboration are essential to advancing precision diagnostics and targeted therapies for FMF.

Background: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI) and shows promise for other dysbiosis-related conditions such as inflammatory bowel disease (IBD). Awareness and acceptance remain underexplored in the Middle East, where cultural and social factors may influence adoption. Objectives: To evaluate awareness, perceptions, willingness, and acceptance of FMT among the Lebanese population. Design: A nationwide cross-sectional survey with nonprobability sampling was conducted between April and November 2024. Methods: A total of 725 participants were recruited through mixed sampling across Lebanon’s governorates: 379 from the general population, 109 healthcare workers, 155 physicians, and 82 IBD or CDI patients. A structured bilingual questionnaire assessed awareness, perceptions, treatment preferences, and willingness to disclose or undergo FMT. Analyses included Chi-square tests, logistic regression, and false discovery rate-adjusted comparisons. Results: Overall, 31% of participants had prior awareness of FMT, while 60.1% reported positive perception. Awareness and perception were significantly associated ( p = 0.0017) and were highest among physicians (59.4% and 70.2%) and lowest among patients (17.1% and 52.4%). Sources varied by group: universities for the general population, media for patients, and professional networks for healthcare workers and physicians. Logistic regression identified physician status, younger age, and prior awareness as predictors of favorable perception. Capsules were the preferred delivery route across groups. Willingness to disclose (81.4%) and to donate stool (68.4%) were high, while 17.2% expressed stigma-related concerns. Major concerns included hygiene, infection risk, and psychological discomfort. Conclusion: FMT awareness in Lebanon remains limited, particularly among patients and the public. Although perceptions are generally positive, misconceptions, stigma, and unrealistic expectations persist. These findings stem from a nonprobability sample that overrepresents younger, female, and highly educated participants and is not nationally representative. Targeted education, stronger physician–patient communication, and culturally sensitive approaches are needed to promote FMT acceptance and integration into practice.

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting populations from the Mediterranean region, with a high prevalence reported among Armenians, Turks, Arabs, and Jews. The condition results from mutations in the MEFV gene, which encodes pyrin, a key regulator of inflammation. Both genetic and epigenetic factors contribute to the diverse clinical manifestations of FMF, which are characterized by recurrent episodes of fever, abdominal pain, chest pain, arthritis, and erysipelas-like erythema. In addition to these symptoms, individuals with FMF patients appear to have an increased risk of developing autoimmune and metabolic disorders, likely due to shared inflammatory pathways. In fact, FMF exemplifies a monogenic autoinflammatory disorder arising from mutations in genes related to the innate immune system, unlike autoimmune diseases that stem from defects in the adaptive immune system. Despite differences in their underlying mechanisms, both autoinflammatory and autoimmune diseases involve the production of interleukin-1β, a key cytokine that influences effector cells of the adaptive immune system, including B and T lymphocytes. Accordingly, numerous studies have investigated the increased prevalence of autoimmune and metabolic disorders among FMF patients, seeking to understand whether these comorbidities exacerbate FMF symptoms, increase the risk of complications, or affect treatment responses. This review examines the coexistence of FMF with autoimmune diseases and metabolic disorders and explores potential correlations with MEFV mutations.

Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by a wide clinical variability among individuals, indicating that both genetic and environmental factors influence disease progression. Although the Mediterranean Diet (MD) is recognized for its anti-inflammatory properties, its relationship with FMF severity remains uninvestigated. This study aims to explore the association between MD adherence and FMF severity, while considering individuals’ genetic background, lifestyle, and comorbid health conditions. A cross-sectional survey was conducted among 101 confirmed individuals with FMF in Lebanon. Data were collected using a questionnaire that included participants’ demographics, socio-economic status, disease manifestations, comorbidities, treatment, and lifestyle habits. FMF severity was determined using the International Severity Score for FMF (ISSF), dietary adherence was assessed using the Modified Mediterranean Prime Screen (MMPS), and physical activity was evaluated using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Adherence to the MD Score (MDS) was categorized as low (34%), moderate (48%), and high (19%). Most MD component intakes did not meet the recommended ranges. While no relationship was found between MD adherence and FMF severity, specific clinical manifestations, such as diarrhea, differed significantly, with a higher frequency noted in the low MD group. Obesity, high levels of physical activity, and the presence of comorbidities—particularly rheumatoid manifestations, inflammatory bowel disease, and cardiovascular diseases—were associated with a significant increase in FMF severity among participants; however, none of these factors emerged as independent predictors in multivariate models. Our findings reinforce the multifactorial aspect of FMF and underscore the need for a comprehensive approach that addresses all contributing factors collectively.

Transposable elements (TE), also called transposons, are repetitive DNA sequences making up half of the human genome. Initially, TEs were described as “junk DNA” because they lack specific function. However, they have been recognized for their ability to replicate and integrate into different genomic locations; this “jumping gene” activity results in genomic instability, variation of the chromosomal architecture, and transcriptional dysregulation, all of which represent major hallmarks of cancer. In this respect, the involvement of TE in tumorigenesis was extensively studied and their role as diagnostic and therapeutic tools in cancer is now well-established. Transposons’ products, including TE-derived cancer antigens, transcripts, and associated epigenetic modifications, mainly hypomethylation, were found to be promising biomarkers in several types of cancer ensuring early disease detection and prognosis. In addition, TE are currently used to design innovative approaches, with transposon-based systems, namely, Sleeping Beauty and PiggyBac, enabling precise genomic modifications and novel strategies for cancer therapy. Therefore, the aim of this review is to provide an overview on the dual application of TE as diagnostic and therapeutic tools in cancer, paving the way to improved clinical outcomes. Not applicable.

Objective: This study aims to investigate the roles played by NaB and NaP in breast carcinogenesis by elucidating their potential anti-metastatic effects in the context of tumor migration, invasion, and EMT regulation in two distinct breast cancer cell lines, MCF-7 and MDA-MB-231.Methods: The cytotoxic effect of both compounds on 3D spheroid formation was evaluated using a hanging drop assay. The anti-migratory and anti-invasive potentials of NaB and NaP were investigated through transwell migration and invasion assays. Moreover, their role in regulating epithelial-to-mesenchymal transition (EMT) was examined by assessing E-cadherin, vimentin, and β-catenin mRNA and protein expression levels through RT-qPCR and Western blot or flow cytometry. β-Catenin localization upon treatment was further visualized via immunofluorescence. Protein expression of MEK, p-MEK, ERK, and p-ERK was analyzed by Western blot.Results: Our results revealed a dose- and time-dependent impairment of spheroid formation in both cell lines, with NaB exerting a more potent effect than NaP. Both SCFAs were able to significantly inhibit migration and invasion of MDA-MB-231 cells following 24 h of treatment. Moreover, treatment with NaB or NaP altered the mRNA and protein profile of EMT-associated markers and abrogated the nuclear translocation of β-catenin. Finally, ERK and MEK phosphorylation was reduced in MDA-MB-231 and MCF-7 cells upon treatment with NaB, and less prominently with NaP.Conclusion: Our study highlights the promising therapeutic potential of NaB and NaP, providing insight into their inhibitory effects on 3D formation, migration, and invasion through EMT regulation and deactivation of MEK/ERK signaling in breast cancer.