Circular RNA as a Biomarker for Diagnosis, Prognosis and Therapeutic Target in Acute and Chronic Lymphoid Leukemia.

Circular RNAs (circRNAs) are single-stranded RNAs that have received much attention in recent years. CircRNAs lack a 5' head and a 3' poly-A tail. The structure of this type of RNAs make them resistant to digestion by exonucleases.

High-throughput screening and evaluation of CSB-0914; a novel small molecule NF-κB inhibitor attenuating inflammatory responses through NF-κB, Nrf2 and HO-1 cross-talk.

Unpleasant side effects of standard inflammatory drugs urges search for novel therapeutic candidates. This study aims in identifying novel anti-inflammatory NF-κB inhibitor by high-throughput computational and in-vitro pre-clinical approaches. Lead candidate selection was conducted by the use of computational docking molecular-dynamic simulations.

Identification by molecular dynamic simulation and in vitro validation of SISB-A1, N-[1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-yl]-2-[(2-oxo-4-phenyl-2H-chromen-7-yl) oxy], as an inhibitor of the Abl mutant kinase to combat imatinib resistance in chronic myeloid leukemia.

The discovery of imatinib, a specific inhibitor of Abl kinase, revolutionized the therapeutic approach to chronic myeloid leukemia (CML); however, its efficacy can be impeded by the emergence of novel mutations within the kinase domain, particularly Abl, that lead to the development of drug resistance. It therefore remains necessary to identify specific inhibitors that can effectively target imatinib-resistant CML harboring the Abl mutation. A natural product library sourced from the ZINC database was screened against the experimental structure of Abl kinase to identify compounds that selectively target the mutated kinase.

Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells.

Estrogen receptor (ER) α is expressed in a subset of patient-derived acute myeloid leukemia (AML) cells, whereas Akt is predominantly expressed in most types of AML. Targeting AML with dual inhibitors is a novel approach to combat the disease. Herein, we examined a novel small molecule, 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one (SBL-060), capable of targeting AML cells by inhibiting ERα and Akt kinase.

Insilco and Invitro approaches identify novel dual PI3K/AKT pathway inhibitors to control acute myeloid leukemia cell proliferations.

Acute myeloid leukemia (AML) is characterized by disruption of intracellular signaling due to aberration of extracellular signaling pathways, namely PI3K/AKT cascade, by dysregulating erythropoiesis and myelopoiesis. Therefore, inhibition of PI3K/AKT, either individually, or by dual inhibitors, is shown to be effective in suppression of tumorigenesis. To increase the therapeutic viability and decrease adverse effects, including cytotoxicity due to off-target kinase inhibitions, customized targeted pharmacological agents are needed that would have greater treatment potential.

Mitofusin-2 in cancer: Friend or foe?

Cancer is a category of disorders characterized by excessive cell proliferation with the ability to infiltrate or disseminate to other organs of the body. Mitochondrial dysfunction, as one of the most prominent hallmarks of cancer cells, has been related to the onset and development of various cancers. Mitofusin 2 (MFN2) is a major mediator of mitochondrial fusion, endoplasmic reticulum (ER)-mitochondria interaction, mitophagy and axonal transport of mitochondria.

Association of lncRNA LINC01173 Expression with Vitamin-D and Vitamin B12 Level Among Type 2 Diabetes Patients.

Background: Type 2 diabetes mellitus (T2DM) has risen to become the world's most serious public health problem in recent years, and the role of long noncoding RNAs (lncRNAs) in the onset and progression of T2DM, as well as special attention to vitamins, has gotten a lot of attention recently.

Methods: The aim of the study was to analyze lncRNA LINC01173 expression along with assessment of vitamin-D and B12 among the T2DM cases. Quantitative RT-PCR was used to analyze the expression of lncRNA LINC01173.

Identification of second generation benzylidene chromanone analogues as novel, potent DHODH inhibitors in acute myeloid leukemia cells.

Dihydroorotate dehydrogenase (DHODH) remains as an active target at the preclinical level against acute myeloid leukemia (AML). Herein we report potent second generation benzylidene chromanone (SBL-105) analogues to inhibit DHODH in AML cells. Virtual docking and molecular dynamic simulations were performed.

CB-RAF600E-1 exerts efficacy in vemurafenib-resistant and non-resistant-melanoma cells via dual inhibition of RAS/RAF/MEK/ERK and PI3K/Akt signaling pathways.

Background And Aim: Predicting novel dual inhibitors to combat adverse effects such as the development of resistance to vemurafenib in melanoma treatment due to the reactivation of MAPK and PI3K/AKT signaling pathways is studied to help in reversal of cancer symptoms.Reversal of cancer symptoms in melanoma associated with vemurafenib resistance is driven by reactivation of MAPK and PI3K/Akt signaling pathways. Novel dual inhibitors targeting these proteins would be beneficial to combat resistance.

GC/MS characterization and computational kinome-wide screening of pomegranate fruit extract identifies key phytochemicals interacting to CDK kinases implicated in acute myeloid leukemia cells.

Punica granatum (Pomegranate fruit) and its constituents are proven effective against various cancer types. However, a kinome-wide screening for the active phytochemicals against kinases is not reported. This study aims in validating pomegranate fruit extract (PFE) against acute myeloid leukemia (AML) cells, and computationally identifying the phytochemicals interacting with active kinases.

Computational analysis and in vitro evaluation of TMF 104, for its antioxidant, antimicrobial, and anticancer efficacies.

Benzylidene chromanones are small molecules, structurally similar to active phytochemicals. Herein, we report one novel benzylidene chromanone, TMF 104, for its bio-efficacies. Its computational docking for Vanin-1, antioxidant, free radical scavenging capacities, antimicrobial effects, and anticancer efficacy were analyzed.

Mathematical modeling and stability analysis of the COVID-19 with quarantine and isolation.

The present paper focuses on the modeling of the COVID-19 infection with the use of hospitalization, isolation and quarantine. Initially, we construct the model by spliting the entire population into different groups. We then rigorously analyze the model by presenting the necessary basic mathematical features including the feasible region and positivity of the problem solution.

suppresses the growth of non-small cell lung cancer A549 cells and concomitantly induces apoptosis via downregulation of JAK1/STAT3 pathway.

Lung carcinoma is the leading cause of cancer-related mortalities worldwide, and present therapeutical interventions are not successful enough to treat this disease in many cases. Recent years have witnessed a surge in exploring natural compounds for their antiproliferative efficacy to expedite the characterization of novel anticancer chemotherapeutics. is a valued medicinal herb and possess intrinsic pharmaceutical potential.

High-throughput virtual screening and preclinical analysis identifies CB-1, a novel potent dual B-Raf/c-Raf inhibitor, effective against wild and mutant variants of B-Raf expression in colorectal carcinoma.

Paradoxical Raf activation via Raf dimerization is a major drawback of wild/mutant B-Raf inhibitors. Herein, we report that CB-1 a novel, potent B-Raf/c-Raf dual inhibitor, effective against colon cancer cells, irrespective of their genetic status. High-throughput virtual screening of the ChemBridge library against wild B-Raf (B-Raf), mutant B-Raf (B-Raf), and c-Raf was performed using an automated protocol with the AutoDock-VINA.

FNF-12, a novel benzylidene-chromanone derivative, attenuates inflammatory response in in vitro and in vivo asthma models mediated by M2-related Th2 cytokines via MAPK and NF-kB signaling.

Background And Aim: This study evaluates a novel benzylidene-chromanone derivative, FNF-12, for efficacy in in vitro and in vivo asthma models.

Methods: Rat basophilic leukemia (RBL-2H3) and acute monocytic leukemia (THP-1)-derived M2 macrophages were used. Human whole blood-derived neutrophils and basophils were employed.

Cassia auriculata leaf extract ameliorates diabetic nephropathy by attenuating autophagic necroptosis via RIP-1/RIP-3-p-p38MAPK signaling.

Diabetic nephropathy (DN) is the most common manifestation of high glucose induced diabetes mellitus. In this study, we report the effects of Cassia auriculata ethanol leaf extract (CALE) on DN-associated cell toxicity and complications. The effects of CALE were screened in vitro using RGE cells.

Computational and in vitro characterization of ICY-5: A potential candidate promoting mitochondrial apoptosis via the c-MET and STAT3 pathways.

Targeted chemotherapy remains the primary choice in controlling various forms of breast cancer (BC) due to its heterogenous gene expressions in various subtypes. In silico and in vitro evaluation of ICY-5, a novel arylidene analogue against c-MET, was performed. ICY-5 exhibited a docking score of -9.