Computational Exploration of a Diverse Flavonoid Library for Targeted Allosteric Inhibition of AKT1 in Cancer Therapy.

Background/aim: AKT serine/threonine kinase 1 (AKT1) is an established therapeutic target in cancer therapy due to its role in promoting cell survival and proliferation. This study aimed to identify potential allosteric inhibitors of AKT1 from a large flavonoid library using computational methods.

Materials And Methods: A computational screening of a comprehensive flavonoid library to identify novel allosteric inhibitors targeting the AKT1 allosteric site was performed.

Extended phase space thermodynamics of regular-AdS black hole.

After obtaining an exact regular-AdS black hole resulting from the coupling of general relativity with nonlinear electrodynamics (NED), we explore the thermodynamics of the extended phase space, treating the cosmological constant ( ) as the pressure (P) of the black holes and its conjugate as thermodynamic volume (V). Considering the NED parameter (g), we investigate the Hawking temperature, entropy, Gibb's free energy and specific heat at the horizon radius. Due to the presence of NED charge, the black hole exhibits van der Waals-like phase transition instead of Hawking-Page phase transition, which could be observed through the plots, which display a swallowtail pattern below the critical pressure, and it gives rise to second-order phase transitions when pressure attains its critical value.

Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase.

The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular growth and survival, and its dysregulation is implicated in various cancers, making it a prime target for cancer therapy. Natural compounds known as catechins have garnered attention as promising anticancer agents. These compounds exert their anticancer effects through diverse mechanisms, primarily by inhibiting receptor tyrosine kinases (RTKs), a protein family that includes the notable member EGFR.

Synergistic inhibition of glioblastoma multiforme through an in-silico analysis of luteolin and ferulic acid derived from Angelica sinensis and Cannabis sativa: Advancements in computational therapeutics.

The primary objective of this study is to uncover novel therapeutic agents for the treatment of Glioblastoma Multiforme (GBM), a highly aggressive form of brain cancer, and Alzheimer's Disease (AD). Given the complexity and resistance associated with both conditions, the study underscores the imperative need for therapeutic alternatives that can traverse the biological intricacies inherent in both neuro-oncological and neurodegenerative disorders. To achieve this, a meticulous, target-based virtual screening was employed on an ensemble of 50 flavonoids and polyphenol derivatives primarily derived from plant sources.

Analysis of some flavonoids for inhibitory mechanism against cancer target phosphatidylinositol 3-kinase (PI3K) using computational tool.

Cancer has been one of the leading causes of mortality worldwide over the past few years. Some progress has been made in the development of more effective cancer therapeutics, resulting in improved survival rates. However, the desired outcome in the form of successful treatment is yet to be achieved.

Unlocking potential inhibitors for Bruton's tyrosine kinase through in-silico drug repurposing strategies.

Bruton's tyrosine kinase (BTK) is a non-receptor protein kinase that plays a crucial role in various biological processes, including immune system function and cancer development. Therefore, inhibition of BTK has been proposed as a therapeutic strategy for various complex diseases. In this study, we aimed to identify potential inhibitors of BTK by using a drug repurposing approach.

Investigating a Library of Flavonoids as Potential Inhibitors of a Cancer Therapeutic Target MEK2 Using in Silico Methods.

The second leading cause of death in the world is cancer. Mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK) 1 and 2 (MEK1/2) stand out among the different anticancer therapeutic targets. Many MEK1/2 inhibitors are approved and widely used as anticancer drugs.

Targeting a transcription factor NF-κB by green tea catechins using and studies in pancreatic cancer.

Pancreatic cancer remains a lethal disease and a major public health problem globally. Nuclear factor-kappa B (NF-κB) has been identified as a therapeutic target in several cancers and plays an important role in inflammatory responses. Many phytochemicals, including catechins, have been reported in the scientific literature with efficient anticancer potential and minimal side effects.

Evaluation of the correlation between interleukin 1β levels in peri-implant crevicular fluid as an adjunctive diagnostic marker with clinical and radiographic parameters for assessing the peri-implant health status.

Background: Interleukin-1β (IL-1β) is one of the most important cytokines that seems to have an important role in the inflammatory process in gingival and peri-implant tissues. As peri-implant crevicular fluid (PICF) provides with a more swift and objective measure of the disease activity, the present study was conducted to evaluate IL-1β level in PICF as a biochemical marker and to investigate its correlation with clinical parameters and radiological parameters.

Materials And Methods: After evaluating all the patients following inclusion and exclusion criteria, 60 patients were selected for the study.

Organotin Antifouling Compounds and Sex-Steroid Nuclear Receptor Perturbation: Some Structural Insights.

Organotin compounds (OTCs) are a commercially important group of organometallic compounds of tin used globally as polyvinyl chloride stabilizers and marine antifouling biocides. Worldwide use of OTCs has resulted in their ubiquitous presence in ecosystems across all the continents. OTCs have metabolic and endocrine disrupting effects in marine and terrestrial organisms.

Potential Disruption of Systemic Hormone Transport by Tobacco Alkaloids Using Computational Approaches.

Tobacco/nicotine is one of the most toxic and addictive substances and continues to pose a significant threat to global public health. The harmful effects of smoking/nicotine affect every system in the human body. Nicotine has been associated with effects on endocrine homeostasis in humans such as the imbalance of gonadal steroid hormones, adrenal corticosteroid hormones, and thyroid hormones.

In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea.

Hypericum perforatum and Echinacea are reported to have antiviral activities against several viral infections. In this study, H. perforatum (St.

Diagnostic Accuracy of Various Radiological Measurements in the Evaluation and Differentiation of Flatfoot: A Cross-Sectional Study.

Arch angle is used to indicate flatfoot, but in some cases, it is not easily defined. The presence of flatfoot deformity remains difficult to diagnose due to a lack of reliable radiographic assessment tools. Although various assessment methods for flatfoot have been proposed, there is insufficient evidence to prove the diagnostic accuracy of the various tools.

Drug repurposing against galectin-3 using simulation-based studies.

The protein galectin, which binds to carbohydrates and is involved in a number of therapeutic processes including cell proliferation, inflammatory responses, apoptosis, etc., has been discovered as a potential therapeutic target. Galectin-3 is a stable biomarker that exhibits both increased and decreased expression in a variety of illnesses and infections, regardless of sex, age, or body mass index.

NAT10: An RNA cytidine transferase regulates fatty acid metabolism in cancer cells.

Background: N-4 cytidine acetylation (ac4C) is an epitranscriptomics modification catalyzed by N-acetyltransferase 10 (NAT10); important for cellular mRNA stability, rRNA biogenesis, cell proliferation and epithelial to mesenchymal transition (EMT). However, whether other crucial pathways are regulated by NAT10-dependent ac4C modification in cancer cells remains unclear. Therefore, in this study, we explored the impact of NAT10 depletion in cancer cells using unbiased RNA-seq.

Structural-Guided Identification of Small Molecule Inhibitor of UHRF1 Methyltransferase Activity.

Ubiquitin-like containing plant homeodomain Ring Finger 1 (UHRF1) protein is recognized as a cell-cycle-regulated multidomain protein. UHRF1 importantly manifests the maintenance of DNA methylation mediated by the interaction between its SRA (SET and RING associated) domain and DNA methyltransferase-1 (DNMT1)-like epigenetic modulators. However, overexpression of UHRF1 epigenetically responds to the aberrant global methylation and promotes tumorigenesis.

A novel injectable platelet-rich fibrin reinforced papilla reconstruction technique.

Formation of black triangles due to the loss of interdental papilla is one of the utmost perplexing esthetic problems of the periodontium. Many surgical and nonsurgical treatment options have been researched upon to obtain complete papillary fill, but minimally invasive procedures have always been the choice of treatment both for the operator as well as the patient. This article describes the use of injectable platelet-rich fibrin (i-PRF) as a novel nonsurgical technique for the reconstruction of deficient interdental papilla.

Venetoclax-Resistant MV4-11 Leukemic Cells Activate PI3K/AKT Pathway for Metabolic Reprogramming and Redox Adaptation for Survival.

Venetoclax (ABT199) is a selective B-cell lymphoma 2 (BCL-2) inhibitor. The US FDA recently approved it to be used in combination with low-dose cytarabine or hypomethylating agents in acute myeloid leukemia (AML) or elderly patients non-eligible for chemotherapy. However, acquiring resistance to venetoclax in AML patients is the primary cause of treatment failure.

Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods.

The Mitogen-Activated Protein Kinase (MAPK) signaling pathway plays an important role in cancer cell proliferation and survival. MAPKs' protein kinases MEK1/2 serve as important targets in drug designing against cancer. The natural compounds' flavonoids are known for their anticancer activity.

A Novel Homozygous Missense Mutation in the Zinc Finger DNA Binding Domain of GLI1 Causes Recessive Post-Axial Polydactyly.

Polydactyly is a prevalent digit abnormality characterized by having extra digits/toes. Mutations in eleven known genes have been associated to cause nonsyndromic polydactyly: . A single affected family member (IV-4) was subjected to whole-exome sequencing (WES) to identify the causal gene.

Computational Insights into the Interaction between Cytoadherence Receptor gC1qR and the DBLβ12 Domain of a PfEMP1 Ligand.

Human receptor gC1qR is a 32 kD protein that mediates the cytoadherence of -infected erythrocytes (IEs) to human brain microvascular endothelial cells (HBMEC) and platelets. The cytoadherence of IEs to gC1qR has been associated with severe malaria symptoms. The cytoadherence to gC1qR is mediated by the Duffy binding-like β12 (DBLβ12) domain of erythrocyte membrane protein 1 (PfEMP1), PFD0020c.

Endolysosome iron restricts Tat-mediated HIV-1 LTR transactivation by increasing HIV-1 Tat oligomerization and β-catenin expression.

HIV-1 transactivator of transcription (Tat) protein is required for HIV-1 replication, and it has been implicated in the pathogenesis of HIV-1-associated neurocognitive disorder (HAND). HIV-1 Tat can enter cells via receptor-mediated endocytosis where it can reside in endolysosomes; upon its escape from these acidic organelles, HIV-1 Tat can enter the cytosol and nucleus where it activates the HIV-1 LTR promoter. Although it is known that HIV-1 replication is affected by the iron status of people living with HIV-1 (PLWH), very little is known about how iron affects HIV-1 Tat activation of the HIV-1 LTR promoter.

A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm.

Background: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the coronavirus disease of 2019 (COVID-19) that killed more than 3.5 million people till now. The cytokine storm induced in severe COVID-19 patients causes hyper-inflammation, is the primary reason for respiratory and multi-organ failure and fatality.

Cytotoxicity of oleanane type triterpene from leaf extract of () and theoretical investigation of inhibitory signaling pathway.

Objective: To evaluate the cytotoxic activity of taraxerol isolated from the leaves of and its EtOH extract against human breast, colon, and lung cancer cell lines and docking studies.

Methods: The structures of the isolated compounds were elucidated by several spectroscopic methods such as H-NMR, C-NMR, DEPT-135, COSY, HSQC, and HMBC. The extract and isolated compound were analyzed for cytotoxic activity on MDA-MB-231, BT-549, A-549, and SW-480 cancer cell lines by MTT assay.