👤 Suhail Razak

Esophageal cancer is a formidable malignancy, presenting a significant health challenge due to its widespread prevalence and associated high mortality rates. Epithelial cell adhesion molecule (EpCAM), a pro-oncogenic glycoprotein, has been identified as an upregulated protein in esophageal adenocarcinoma (ESCA) through multi-OMICS platforms. However, its functional role in ESCA remains relatively understudied. Here, we investigated the contribution of EpCAM to ESCA pathogenesis using an EpCAM-null ESCA cell line, FLO-1, as a gain-of-function model. Introduction of a recombinant EpCAM-GFP fusion construct into FLO-1 cells resulted in enhanced cell migration, adhesion, clonogenic survival, and invasive capacity, supporting a pro-tumorigenic role for EpCAM. To define EpCAM-associated regulatory networks, RNA sequencing was performed on EpCAM-overexpressing cells, revealing 797 differentially expressed genes. Functional enrichment analyses indicated significant involvement of pathways related to cell adhesion, cell motility, transmembrane activity, and neuronal-associated processes, with enrichment in plasma membrane, focal adhesion, and neuron projection terminus compartments. Protein-protein interaction network analysis identified key hub genes, including SOX2, COL1A1, LOX, COL3A1, LUM, PXDN, BDNF, NCAM1, TLR2, and CCL5, linking EpCAM signaling to PI3K-Akt, ECM-receptor interaction, and focal adhesion pathways. Importantly, quantitative polymerase chain reaction (qPCR) validation of selected hub genes confirmed significant upregulation of the extracellular matrix components COL1A1 and PXDN in EpCAM-overexpressing FLO-1 cells, supporting the transcriptomic predictions and implicating ECM remodeling as a downstream consequence of EpCAM signaling. Collectively, these findings demonstrate that EpCAM promotes aggressive cellular phenotypes in ESCA and drives transcriptional programs associated with adhesion, invasion, and extracellular matrix regulation, highlighting potential therapeutic vulnerabilities in EpCAM-driven ESCA. Show less

This study examines the influence of fish oil on brain amyloidogenesis in hyperglycaemic Alzheimer's disease animal models, emphasising the potential of omega-3 fatty acids in fish oil to prevent the development of Alzheimer's disease. Thirty males of Wistar rats were divided into five groups: 1) control rats (NS); 2) rats supplemented with 3 g/kg of fish oil (NS+FO3); 3) rats injected via intraperitoneal (i.p) with Streptozotocin-Lipopolysaccharide (STZ-LPS); 4) rats injected with STZ-LPS (i.p) and supplemented with 1 g/kg of fish oil (STZ-LPS+FO1), and 5) rats injected with STZ-LPS (i.p) and supplemented with 3 g/kg of fish oil (STZ-LPS+FO3). The cerebral brain was extracted for examination, and the αβ precursor protein (APP) level was measured using an immunoassay kit, while αβ 42 expression was evaluated using immunohistochemistry staining. Brain amyloidosis-related genes were quantified using real-time Polymerase Chain Reaction (PCR). The results revealed that fish oil supplementation significantly increased APP levels and reduced αβ 42 accumulations in STZ-LPS rats. Moreover, the Apolipoprotein E, ε4 isoform (ApoE-4) and Beta-site APP-cleaving enzyme 1 (Bace-1) genes were downregulated while the Low-density lipoprotein receptor-related protein 1 (Lrp-1) gene was upregulated in STZ-LPS rats treated with fish oil, thereby elucidating the impact of fish oil on diminishing αβ buildup in the brain. Therefore, this study contributes to a growing body of evidence supporting dietary interventions as adjunctive strategies for the prevention or delay of Alzheimer's disease progression in metabolic dysfunction. Show less

Colon cancer is reported as third most prevalent malignancy worldwide, while sericin being an antioxidant, is now used in biomedical applications due to its biochemical characteristics and has shown potential efficacy to treat colon cancer. Sericin was isolated by the degumming process followed by the characterization by using FTIR, UV, XRD, and SEM techniques to confirm the successful synthesis of SAgNPs and SChiAgNPs. The male Balb C mice were then divided into 13 groups. Group 1: Control, Group 2: DMH (20 mg/kg) (injected (IP) thrice a week for 14 weeks). Groups 3,4,5: Sericin (S) (100 mg/kg), Sericin silver nanoparticles (SAgNPs) (100 mg/kg), and Sericin Chitosan silver nanoparticles (SChiAgNPs) (100 mg/kg) were given orally for 14 weeks respectively. Groups 6,7,8,9 were considered as preventive groups and were given DMH (IP) + 5-FU (IP), DMH(IP) + S (orally), DMH (IP) + SAgNPs (orally), DMH (IP) + SChiAgNPs (orally) respectively for the period of 14 weeks Groups 10,11,12,13 were considered as treatment groups and were given 5-FU (5 mg/kg) (IP), (S) (100 mg/kg) (orally), (SAgNPs) (100 mg/kg) (orally), (SChiAgNPs) (100 mg/kg) (orally) for a period of first 7 weeks after 7 weeks of DMH administration (IP). After 14 weeks period study, blood samples and colon tissue were used for the analysis of biochemical markers i.e., CEA, CA19-9, TIMP-1, and IL-6, IL-8, IL-27, SOD, CAT, GR, GSH, GST, MDA and MMP-7 via ELISA and histopathological analysis. The UV absorption peaks obtained at 435 and 463 nm indicated the formation of SAgNPs and SChiAgNPs formation respectively. FTIR spectra peaks obtained, indicate NH stretching of primary and secondary amine group), (NH stretching of amine salt) (N=C=S stretching of thiocyanate compound), (CC stretching of alkene), (NO stretching of nitro compound), (SO stretching of sulfonyl chloride), (CN stretching of amine) and (C-O-O stretching) for sericin, SAgNPs, and SChiAgNPs, confirming, the presence of theses functional groups. The XRD pattern revealed that SAgNPs and SChiAgNPs had structure crystalline structures. EDX characterization peaks for SAgNPs indicated the presence of silver along with other elements including; calcium, oxygen carbon, while EDX characterization peaks for SChiAgNPs indicated the presence of silver along with other elements including; oxygen, carbon, sodium, phosphorus, Sulphur and chlorine. SEM analysis showed that SAgNPs are of spherical shape, while the SChiAgNPs displayed the rectangular shape. The results for biomarker analysis indicated significantly elevated levels of CEA, CA19-9, TIMP-1, IL-6, IL-8, IL-27, MDA, and MMP-7 in DMH treated group (p ≤ 0.001) which were decreased significantly in SChiAg(T) (p ≤ 0.001). In contrast, levels of SOD, GR, GSH, CAT and GST were reduced significantly in DMH treated group, which were increased significantly in SChiAg(T) (p ≤ 0.001). The histopathological analysis of proximal and distal parts of colon tissue of the DMH-treated group showed low-grade dysplasia (LGD), and high-grade dysplasia (HGD) while SChiAgNPs improved the histopathological changes induced by DMH. The findings suggest that Sericin Chitosan conjugated silver nanoparticles showed their efficacy against DMH-induced colon cancer, making a potential future in the anticancer research field. Show less

Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss- or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome. Show less