👤 Samman Munir

Current medications for Alzheimer's disease (AD) provide symptomatic relief only and fail to prevent neurodegeneration, necessitating the development of new therapeutic agents. This study aimed to evaluate benzimidazole (BIM) analogs as potential inhibitors for AD. In vitro screening identified 1-benzyl-3-(2-((3-chlorophenyl)amino)-2-oxoethyl)-1H-benzo[d]imidazole-3-ium chloride (IMS48) as a potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC Show less

Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification. Show less

Histologic transformation (HT) of indolent non-Hodgkin lymphoma (iNHL) to diffuse large B-cell lymphoma (DLBCL) carries a poor prognosis. Using the Surveillance, Epidemiology, and End Results-17 database, we conducted a population-based study of adult patients with transformed follicular lymphoma (t-FL), marginal zone lymphoma (t-MZL), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (t-LPL/WM), and de novo DLBCL. Primary outcome was relative survival (RS), and secondary outcomes included overall survival (OS) and lymphoma-specific survival (LSS). Outcomes were modeled using flexible parametric survival models, while multivariable modeling was used to compare RS, OS, and LSS. The incidence of HT was highest in splenic MZL (SMZL, 6.78%) and lowest in extranodal MZL (EMZL, 1.62%). Median follow-up times were similar for patients with de novo DLBCL and transformed indolent lymphomas. The 5-year RS and OS were longer in de novo DLBCL compared to all other transformed iNHL subtypes (68 versus 59%, respectively). For t-FL, early transformation (within 2 years of diagnosis, Hazard ratio [HR] = 1.34) and prior treatment (HR = 1.89) were associated with inferior survival. This association was not observed in other transformed lymphoma subtypes. This is the first comparative study to show that the outcomes of t-LPL/WM were inferior compared to de novo DLBCL and highlights the need to incorporate early experimental therapies in patients with t-FL with early transformation and receipt of prior chemotherapy. Show less

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging RNA virus causing COVID-19 disease, across the globe. SARS-CoV-2 infected patients may exhibit acute respiratory distress syndrome which can be compounded by endemic respiratory viruses and thus highlighting the need to understand the genetic bases of clinical outcome under multiple respiratory infections. In this study, 42 individual datasets and a multi-parametric based selected list of over 12,000 genes against five medically important respiratory viruses (SARS-CoV-2, SARS-CoV-1, influenza A, respiratory syncytial virus (RSV) and rhinovirus were collected and analysed in an attempt to understand differentially regulated gene patterns and to cast genetic markers of individual and multiple co-infections. While a certain cohort of virus-specific genes were regulated (negatively and positively), notably results revealed a greatest correlation among genes regulation by SARS-CoV-2 and RSV. Furthermore, out of analysed genes, the MAP2K5 and NFKBIL1 were specifically and highly upregulated in SARS-CoV-2 infection both in vivo or in vitro. The most conserved genetic signature was JAK2 gene as well as the constitutively downregulated ZNF219 gene. In contrast, several genes including GPBAR1 and SC5DL were specifically downregulated in SARS-CoV-2 datasets. Finally, we catalogued a set of genes that were conserved or differentially regulated across studied respiratory viruses. These finding provide foundational and genome-wide data to gauge the markers of respiratory viral infections individually and under co-infection. This work compares the virogenomic signatures among human respiratory viruses and provides valid targets for potential antiviral therapy. Show less