👤 Abdullah Al Noman

Alzheimer's disease (AD) is a neurodegenerative disorder and the predominant cause of dementia, characterized by amyloid β (Aβ) plaques and tau tangles that disrupt neurons in memory-related brain regions. This study explores the therapeutic potential of santonin using integrated Show less

Lung cancer is the second most common malignancy globally and the leading cause of cancer-related deaths. Interleukin-39 (IL-39), a member of the IL-12 family secreted by B cells, acts as a pro-inflammatory cytokine and induces IL-23p19 expression in endothelial cells. Recent findings suggest reduced IL-39 expression in autoimmune thyroid disorders and breast cancer, indicating its possible role in disease progression. To evaluate the role of IL-39 as an early prognostic biomarker in lung cancer. A case-control study was conducted between February and September 2024, involving 180 individuals aged 45-77. The cohort included 90 lung cancer patients (45 with small-cell carcinoma and 45 with non-small cell carcinoma) and 90 healthy controls. Blood samples were analyzed using ELISA to quantify IL-39 and additional tests, including CBC, liver enzymes (ALT, AST, ALP), and lipid profile (cholesterol, triglycerides). Statistical analysis was performed to assess correlations and diagnostic performance. IL-39 levels were significantly lower in stage IV compared to stage III in both cancer types, with a greater reduction observed in small-cell carcinoma. Significant negative correlations were found between IL-39 and total cholesterol, NLR, ALT, AST, and ALP, while positive correlations were noted with hemoglobin and triglycerides. IL-39 demonstrated excellent diagnostic accuracy in small-cell carcinoma with a cut-off value of 3.26950 pg/mL (sensitivity 100%, specificity 100%, AUC 1.000). In non-small cell carcinoma, the cut-off value was 4.88700 pg/mL (sensitivity 63.5%, specificity 92.6%, AUC 0.689). IL-39 shows promise as a predictive and diagnostic biomarker in lung cancer, particularly in small-cell carcinoma, and may play a protective role in disease modulation through immune-related pathways. Show less

Cardiovascular diseases remain a significant reason for illness and death globally. Although certain interleukins have been extensively researched about cardiovascular disease (CVD), new findings have identified unique members of the interleukin family that could potentially play a role in cardiovascular well-being and ailments. This review discusses the current understanding of the role of these recently identified interleukins, such as IL-27, IL-31, IL-32, IL-33, and the IL-28 group (IL-28A, IL-28B, IL-29), in the development of cardiovascular diseases. Every interleukin has various impacts achieved through particular receptors and signaling pathways that affect inflammatory processes, differentiation of immune cells, and the functioning of blood vessels. IL-27 controls the development of inflammatory Th17 cells and might decrease inflammation in atherosclerosis. IL-31 plays a role in the interaction between the immune system and nerves, as well as in itching. IL-32 enhances the generation of inflammatory proteins and has been linked to coronary artery disease. IL-33 has beneficial effects on the cardiovascular system, whereas its imitation receptor sST2 could potentially be used as a biomarker. Additional studies are needed to investigate the antiviral and immune-system regulating effects of the IL-28 group in cardiovascular diseases. In general, explaining the ways in which new interleukins contribute to the progression of cardiovascular diseases can help discover fresh targets for therapy and new approaches toward enhancing the prevention and treatment of heart disorders. Additional research on the way these cytokines engage with established disease pathways is necessary. Show less

Triple-negative subtype of breast cancer (TNBC) is hallmarked by frequent disease relapse and shows highest mortality rate. Although PD-1/PD-L1 immune checkpoint blockades have recently shown promising clinical benefits, the overall response rate remains largely insufficient. Hence, alternative therapeutic approaches are warranted. Given the immunosuppressive properties of CD73-mediated adenosine release, CD73 blocking approaches are emerging as attractive strategies in cancer immunotherapy. Understanding the precise mechanism regulating the expression of CD73 is required to develop effective anti-CD73-based therapy. Our previous observations demonstrate that the transcription factors driving epithelial-to-mesenchymal transition (EMT-TF) can regulate the expression of several inhibitory immune checkpoints. Here we analyzed the role of the EMT-TF SNAI1 in the regulation of CD73 in TNBC cells. We found that doxycycline-driven SNAI1 expression in the epithelial -like TNBC cell line MDA-MB-468 results in CD73 upregulation by direct binding to the CD73 proximal promoter. SNAI1-dependent upregulation of CD73 leads to increased production and release of extracellular adenosine by TNBC cells and contributes to the enhancement of TNBC immunosuppressive properties. Our data are validated in TNBC samples by showing a positive correlation between the mRNA expression of CD73 and SNAI1. Overall, our results reveal a new CD73 regulation mechanism in TNBC that participates in TNBC-mediated immunosuppression and paves the way for developing new treatment opportunities for CD73-positive TNBC. Show less

CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells. Driving a mesenchymal phenotype in SNAI1-inducible MCF-7 cells (MCF-7 Show less

Cancer immunotherapy based on Immune checkpoint blockade (ICB) is a promising strategy to treat patients with advanced highly aggressive therapy-resistant tumors. Unfortunately, the clinical reality is that only a small number of patients benefit from the remarkable clinical remissions achieved by ICB. Experimental and clinical evidence claimed that durable clinical benefit observed using ICB depends on the immune status of tumors, notably the presence of cytotoxic effector immune cells. In our paper, we revealed that genetically targeting the autophagy-related protein PIK3C3/VPS34 in melanoma and colorectal tumor cells, or treating tumor-bearing mice with selective inhibitors of the PIK3C3/VPS34 kinase activity, reprograms cold immune desert tumors into hot, inflamed immune infiltrated tumors. Such reprograming results from the establishment of a proinflammatory signature characterized by the release of CCL5 and CXCL10 in the tumor microenvironment, and the subsequent recruitment of natural killer (NK) and CD8 Show less