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Lung cancer remains the leading cause of cancer-related mortality worldwide. With approximately 2.2 million new cases and 1.8 million deaths annually, it contributes to 18% of all cancer fatalities. The high mortality rate, limited accessibility to affordable treatments, and the emergence of drug resistance necessitated the development of novel therapeutic strategies. In this study, we employed an HTVS, SP and XP-based molecular docking and MM/GBSA calculations to identify a potential multitargeted drug candidate from the DrugBank library against five key (Penta) lung cancer-associated proteins, including CDK2 (1AQ1), Transferase(1JWH, 1K3A), Oxidoreductase (4XZL) and Signalling (2DVJ) enzymes that led to the identification of Otamixaban, exhibiting favourable docking and MM/GBSA scores ranging from −11.841 to −6.52, and −69.96 to −45.22 kcal/mol. Molecular Interaction Fingerprints analysis was performed to gain deeper insights into its binding interactions that reveal key residues with high interaction frequencies, including 12VAL, 8LEU, 7PHE, 6LYS, 5ASP, 5GLN, and 5GLU. Pharmacokinetic evaluations confirmed drug-likeness, and its ADMET properties were consistent with standard drug approval benchmarks, QM computations using DFT further reinforced the stability and reactivity of the identified compound. The thermodynamic role of water molecules in ligand binding was assessed through 5 ns WaterMap analysis, supporting the hypothesis that Otamixaban effectively interacts with the binding pockets of multiple target proteins. Further, a 100-ns MD simulation was conducted to ensure the stability and efficacy of the drug candidate under physiological conditions in an explicit TIP3P water environment. The results demonstrated minimal structural deviations and fluctuations, with strong intermolecular interactions persisting throughout the simulation. Further evaluation of 1000 simulation frames from trajectories provided comprehensive insights into the total complex energy and binding free energy via MM/GBSA calculations, reinforcing the potential of Otamixaban as a robust multitargeted drug candidate. Despite these promising computational findings, experimental validation through in vitro and in vivo studies is crucial to confirm its therapeutic efficacy and clinical viability.

Inflammatory bowel disease (IBD) is a chronic autoimmune disorder characterized by severe inflammation and mucosal destruction of the intestine. The specific, complex molecular processes underlying IBD pathogenesis are not well understood. Therefore, this study is aimed at identifying and uncovering the role of key genetic factors in IBD. The whole exome sequences (WESs) of three consanguineous Saudi families having many siblings with IBD were analyzed to discover the causal genetic defect. Then, we used a combination of artificial intelligence approaches, such as functional enrichment analysis using immune pathways and a set of computational functional validation tools for gene expression, immune cell expression analyses, phenotype aggregation, and the system biology of innate immunity, to highlight potential IBD genes that play an important role in its pathobiology. Our findings have shown a causal group of extremely rare variants in the (Q53L, Y99N, W351G, D365A, and Q376H) and (F4L and V25I) genes in IBD-affected siblings. Findings from amino acids in conserved domains, tertiary-level structural deviations, and stability analysis have confirmed that these variants have a negative impact on structural features in the corresponding proteins. Intensive computational structural analysis shows that both genes have very high expression in the gastrointestinal tract and immune organs and are involved in a variety of innate immune system pathways. Since the innate immune system detects microbial infections, any defect in this system could lead to immune functional impairment contributing to IBD. The present study proposes a novel strategy for unraveling the complex genetic architecture of IBD by integrating WES data of familial cases, with computational analysis.

Background and aims Children with inflammatory bowel disease (IBD) generally show an alteration in their fat and soft tissue mass contents. These alterations may influence disease severity and increase the risk of post‐operative complications. Methods This is a retrospective cross‐sectional study of patients with IBD, diagnosed and followed up between 2013 and 2018, in Jeddah, Saudi Arabia, who had dual‐energy x‐ray absorptiometry (DXA) scans for bone density evaluation. Obesity was defined based on fat mass index (FMI) and myopenia based on appendicular skeletal muscle mass (SMMa). Results This study incorporated 95 child and adolescent patients (52% female) with IBD: 59 with Crohn's disease (CD) and 36 with ulcerative colitis (UC), mean age 11.8 ± 3.3 years and mean duration of illness 1.8 ± 1.9 years. The most common disease phenotype and behaviour for CD patients were ileocolonic (57.6%) and non‐stricturing and non‐penetrating (76.3%). Of UC patients, 75% had extensive disease (pancolitis). Body composition profile in the total IBD cohort was classified as normal in 49.5%, obese in 26.3%, myopenic in 23.2% and myopenic‐obese in 1.1%. The use of biological therapy was identified as a negative predictor for both obesity (OR = 7.0, 95% CI: 1.3‐37.9, P = .02) and myopenia (OR = 0.11, 95% CI:0.02‐0.47, P = .003), and female gender was shown to predict myopenia (OR = 3.5, 95% CI: 1.0‐11.8, P = .04). Conclusions Saudi Arabian children with IBD showed comparable body composition profiles to adult patients with IBD. Biological therapy was associated with a decreased incidence of both obesity and myopenia, and female gender was found to predict myopenia.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.

Tumor Necrosis Factor Receptor 1 (TNFR1) plays a crucial role in determining whether a breast cancer cell will survive, undergo natural cell death, or die through necroptosis. It influences these outcomes via pathways such as NF-kB, caspase-8, and the RIPK1-RIPK3-MLKL axis. TNFR1 activation causes epigenetic changes in DNA methylation, histone modification, and chromatin remodeling, which reprogram cellular responses to death signals. The direct and indirect epigenetic events leading to TNFR1-mediated cell death include DNMT enrolment, H3K4me3/H3K27ac changes, and microRNA-mediated controls. TNFR1 signaling regulates DNA methyltransferase activity and histone acetyltransferases while controlling epigenesis through metabolic reprogramming and non-coding RNA networks. The necroptotic execution pathway, triggered by pro-survival complex degradation and caspase-8 inhibition, forms the RIPK1-RIPK3 necrosome, phosphorylates MLKL, and releases damage-associated molecular patterns. TNF dual role of TNF signaling in tumor growth, necroptosis, and inflammatory remodeling presents therapeutic challenges. Biomarkers include TNFR1 expression, RIPK1/RIPK3 phosphorylation, MLKL localization, and epigenetic markers. Therapeutic combinations of epigenetic modulators, SMAC mimetics, RIPK1, and immune checkpoint inhibitors show promise in overcoming treatment resistance. Challenges in patient stratification, drug sequencing, and management of inflammatory toxicity require urgent solutions. This review provides a basis for clinical trials targeting the TNFR1-necroptosis pathway with biomarker-guided therapies and epigenetic strategies for breast cancer therapy. See also the graphical abstract(Fig. 1).

[Please see PDF for full article text] Objectives: To evaluate the association between Inflammatory bowel disease (IBD) and Ischemic heart disease (IHD). Methods: A retrospective cohort analysis included patients with and without IBD seen at the outpatient gastroenterology clinic of a large tertiary care hospital between January 2015 and October 2022. The primary outcome was the association between IBD and IHD, and the secondary outcome was predictors of IHD in patients with IBD. Results: The study included 400 patients; 291 were IBD patients, and 109 had other non-inflammatory GI disorders. The IBD group displayed significantly lower rates of hyperlipidemia (8.6% vs. 30.3%, p<0.001), diabetes mellitus (DM) (10% vs. 24.8%, p<0.001), and hypertension (11.7% vs. 32.1%, p<0.001) compared to the non-IBD group. Only 2.7% (n=8) of IBD patients developed IHD. Logistic regression analysis did not demonstrate a significant association between IBD and IHD (p=0.932). Among classical risk factors, only hypertension (OR: 26.2, 95% CI: 2.14-661, p=0.016) and hyperlipidemia (OR: 10.5, 95% CI: 1.32-132, p=0.0405) significantly increased the risk of developing IHD among patients with IBD. Conclusion: In this cohort, there is no increased risk of developing IHD in patients with IBD compared to non-IBD patients. Keywords: Inflammatory bowel disease, ischemic heart disease, coronary artery disease, ulcerative colitis, Crohn's disease

Background and aimApproximately 25% of inflammatory bowel disease (IBD) cases are diagnosed before the age of 18 years. Compared to adults, pediatric IBD is more aggressive and progresses rapidly. It is important to have a well-structured transition process in place when patients are transferred from pediatric to adult care. We aimed to evaluate the readiness of Saudi adolescents with IBD to be transitioned from pediatric to adult care using the Transition Readiness Assessment Questionnaire (TRAQ).Materials and methodsThis cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, between January and December 2021. Pediatric patients aged between 12-18 with confirmed IBD were recruited. The mean TRAQ component and the overall scores were calculated and analyzed.ResultsA total of 54 patients with IBD were included. The overall mean TRAQ scores were moderately high (3.60±0.78), including high mean values for individual domains of the TRAQ. In terms of components of TRAQ, no significant differences between males and females were encountered; however, there was a trend for males having higher scores than females in tracking health issues (P=0.07). Patients older than 15 years had higher overall scores than younger patients (P=0.04). The level of child education was found to be the only independent variable that correlated with higher overall scores (P=0.005).ConclusionsIn this cohort of Saudi adolescents with IBD, patients showed moderately high overall mean TRAQ scores reflecting high readiness for transitioning. While males demonstrated a trend for higher scores compared to females in tracking health issues, patients older than 15 had higher total scores relative to younger patients. More studies are needed to examine the impact of better transition readiness on the long-term outcome of IBD.

Introduction The association between inflammatory bowel disease (IBD) - particularly its two main subtypes, ulcerative colitis (UC) and Crohn's disease (CD) - and celiac disease (CeD) has been attributed to an overlap in the mechanism of immune dysregulation that characterizes these conditions. Owing to the paucity of studies that have explored this condition in pediatric patients, we examined the prevalence of CeD in children with IBD. Materials and methods This is a cross-sectional study of children aged two to 18 years with IBD that were diagnosed between 2016 and 2018. Clinical, demographic, laboratory, and endoscopic data were analysed. Serology for CeD measured the immunoglobulin A tissue transglutaminase (IgA-tTG) antibodies, and the diagnosis was confirmed histologically through small bowel biopsies. Results The study included 101 patients with IBD (83.2% with UC and 16.8% with CD). The mean age was 8.7±4.0 years. Males constituted 59.4% of the cohort, and only 3% had perianal disease. Ileocolonic involvement was reported in 64.7% and non-stricturing and non-penetrating behaviour in 76.7% of CD patients. Pancolitis constituted 45.2% of UC patients. Ten patients (9.9%) had positive serology based on IgA-tTG antibodies, three (approximately 3%) had CeD based on biopsy findings, two patients (2%) had CD, and one patient (1%) had UC. Patients with confirmed CeD had a significantly higher frequency of symptoms of gaseous sensation and bloating (P=0.003) and abdominal distension (P=0.04). Conclusions The prevalence of CeD in Egyptian children with IBD is higher than previously reported in a number of similar studies. Abdominal bloating and gaseous sensation were identified as associated symptoms.Introduction The association between inflammatory bowel disease (IBD) - particularly its two main subtypes, ulcerative colitis (UC) and Crohn's disease (CD) - and celiac disease (CeD) has been attributed to an overlap in the mechanism of immune dysregulation that characterizes these conditions. Owing to the paucity of studies that have explored this condition in pediatric patients, we examined the prevalence of CeD in children with IBD. Materials and methods This is a cross-sectional study of children aged two to 18 years with IBD that were diagnosed between 2016 and 2018. Clinical, demographic, laboratory, and endoscopic data were analysed. Serology for CeD measured the immunoglobulin A tissue transglutaminase (IgA-tTG) antibodies, and the diagnosis was confirmed histologically through small bowel biopsies. Results The study included 101 patients with IBD (83.2% with UC and 16.8% with CD). The mean age was 8.7±4.0 years. Males constituted 59.4% of the cohort, and only 3% had perianal disease. Ileocolonic involvement was reported in 64.7% and non-stricturing and non-penetrating behaviour in 76.7% of CD patients. Pancolitis constituted 45.2% of UC patients. Ten patients (9.9%) had positive serology based on IgA-tTG antibodies, three (approximately 3%) had CeD based on biopsy findings, two patients (2%) had CD, and one patient (1%) had UC. Patients with confirmed CeD had a significantly higher frequency of symptoms of gaseous sensation and bloating (P=0.003) and abdominal distension (P=0.04). Conclusions The prevalence of CeD in Egyptian children with IBD is higher than previously reported in a number of similar studies. Abdominal bloating and gaseous sensation were identified as associated symptoms.

, a gram-negative facultative intracellular bacterium, is the causative agent of melioidosis, a life-threatening infectious disease endemic to tropical and subtropical regions, particularly Southeast Asia and Northern Australia. Key risk factors such as diabetes, alcoholism, and socioeconomic challenges were identified as major contributors to disease susceptibility and treatment outcomes in melioidosis. Globally, melioidosis accounts for approximately 89,000 deaths annually and poses a significant public health concern, particularly in resource-limited settings. exhibits remarkable environmental resilience, thrives in soil and water, and is intrinsically resistant to various antibiotics. Its pathogenicity is mediated by diverse virulence factors, including type III and VI secretion systems, a protective capsule, lipopolysaccharide (LPS), and BimA-mediated actin-based motility, which facilitate intracellular survival, immune evasion, and systemic dissemination. This bacterium can cause a wide spectrum of clinical manifestations ranging from localized skin infections to severe septicemia, pneumonia, and neurological involvement. In certain cases, may persist in a latent state for years and reactivation is often triggered by immunosuppression. The treatment of melioidosis is challenging because of its intrinsic antibiotic resistance, necessitating a two-phase approach: an intensive phase with intravenous antibiotics, such as ceftazidime or meropenem, followed by a prolonged eradication phase using trimethoprim-sulfamethoxazole. However, relapse remains a concern, particularly in patients with poor adherence to the therapy. Preventive strategies, particularly in endemic regions, focus on minimizing environmental exposure through protective measures and safe water practices. Despite advancements in therapeutic approaches, there is an urgent need for novel treatment strategies, including bacteriophage therapy and vaccine development, to enhance melioidosis prevention and control. Understanding the complex pathogenic mechanisms of is essential to improve its clinical management and reduce its global burden.

Background: Diabetes Mellitus is a chronic disease that affects 200 million worldwide. Given the long-term systemic effects of the disease, it is essential to develop a management approach for diabetes to decrease its long-term complications along with the economic burden on patients. Objective: to establish a multidisciplinary approach to the management of diabetes and the comorbidities associated with it. Materials and methods: This review is a comprehensive search of PUBMED and medical literature from the year 2014 to 2024. Conclusion Diabetes is an ailment with multisystemic consequences that significantly affect the morbidity and mortality of the patient. Hence it is essential to assess and establish a comprehensive methodology to manage the disease that targets not only glycemic control, but the complications associated with it.