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Pim-1 kinase, a serine/threonine kinase, is often overexpressed in various cancers, contributing to disease progression and poor prognosis. In this study, we explored the potential of flavonoids as inhibitors of Pim-1 kinase using a combination of molecular docking and steered molecular dynamics (SMD) simulations. Our docking studies revealed two main binding orientations for the flavonoid molecules. The SMD simulations showed that the binding mode with higher pulling forces was linked to stronger inhibitory activity, with a strong positive correlation (R2 = 0.92) between pulling forces and IC50 values. Quercetin stood out as the most potent inhibitor, showing a pulling force of about 820 pN and an IC_(5) 0 of less than 6 µM. Further dynamic simulations indicated that quercetin's hydroxyl groups at the C3, C-5 and C-7 positions formed stable hydrogen bonds with key residues GLU-121, Leu-44 and Val-126, respectively enhancing its binding stability and effectiveness. Our results emphasized the critical role of the hydroxyl group at the C-3 position, which plays a pivotal function in effectively anchoring these molecules in the active site of Pim-1 kinase. Principal component analysis (PCA) of Pim-1 kinase's conformational changes revealed that potent inhibitors like quercetin, galangin, and kaempferol significantly restricted the enzyme's flexibility, suggesting potential inhibitory effect. These findings provide insights into the structural interactions between flavonoids and Pim-1 kinase, offering a foundation for future experimental investigations. However, further studies, including in vitro and in vivo validation, are necessary to assess the pharmacological relevance and specificity of flavonoids in cancer therapy. [ABSTRACT FROM AUTHOR]

This document is an editorial for a special issue of the journal "Symmetry" focused on qualitative studies of fractional differential equations, fractional integro-differential equations, and related topics. The editorial provides an overview of the published articles in the special issue, summarizing their contents and contributions. The articles cover a range of topics, including numerical simulations of fractional differential equations, analysis of cancer models using stem cells and chemotherapy, analysis of image segmentation algorithms, and control of bioreactors using fractional order models. The editorial concludes by listing the authors and titles of the contributions. [Extracted from the article]

In this work, we study the existence of one and exactly one solution x∈C[0,1]x\in C\left[0,1], for a delay quadratic integral equation of Volterra-Stieltjes type. As special cases we study a delay quadratic integral equation of fractional order and a Chandrasekhar cubic integral equation.

Background: One of the biggest global health issues and the main cause of intensive care unit (ICU) admissions is sepsis. Biomarkers can have a very vital role in sepsis diagnosis. The 16 kDa, 167-amino acid peptide leptin is mainly produced by adipocytes and has a role in controlling energy balance by telling the brain adipose tissue volume in the body, which in turn controls how much food is consumed and how much energy is used. Leptin is also a cytokine that is involved in cytokine crosstalk and cell-mediated immunity. According to earlier researches, sepsis patients' leptin level is elevated when compared to controls. Objective: Our study aimed to test the validity of serum leptin as a biomarker for sepsis diagnosis and to correlate between the level of leptin and sepsis prognosis and mortality. Methods: Twenty five critically ill patients diagnosed with sepsis were included in our study, ten healthy volunteers as a control group. The patients were admitted to the critical care department in Beni-Suef university hospital in the period from October 2023 to February 2024.Serum samples were collected from the studied patients on admission day (day 0), 2nd day of admission (day 2) and 5th day of admission (day 5), and only once in control group to correlate between leptin levels in patients and control group and to find the correlation between leptin and mortality. Results: Our study showed that leptin levels showed strong positive correlation with body mass index (BMI). No significant correlation was found between leptin in the studied group and control group on admission (day 0) while there was a highly significant correlation on day 2 and day 5. There was no significant difference in leptin levels between sepsis and septic shock patient on day 0, day 2 and day 5. There was a weak linear relation between leptin level with APACHE II & SOFA scores. There was non-significant difference in leptin level between survivors and non-survivors on day 0, 2 and 5. Conclusion: From our study we could suggest that leptin level in serum can be used as a good diagnostic marker in sepsis but not a good prognostic one. [ABSTRACT FROM AUTHOR]

Here, a coupled system of nonlinear weighted Cauchy-type problem of a diffre-integral equations of fractional order will be considered. We study the existence of at least one integrable solution of this system by using Schauder fixed point Theorem. The continuous dependence of the uniqueness of the solution is proved.

Coleus forskohlii (Willd.) Briq. is a medicinal herb of the Lamiaceae family. It is native to India and widely present in the tropical and sub-tropical regions of Egypt, China, Ethiopia, and Pakistan. The roots of C. forskohlii are edible, rich with pharmaceutically bioactive compounds, and traditionally reported to treat a variety of diseases, including inflammation, respiratory disorders, obesity, and viral ailments. Notably, the emergence of viral diseases is expected to quickly spread; consequently, these data impose a need for various approaches to develop broad active therapeutics for utilization in the management of future viral infectious outbreaks. In this study, the naturally occurring labdane diterpenoid derivative, Forskolin, was obtained from Coleus forskohlii. Additionally, we evaluated the antiviral potential of Forskolin towards three viruses, namely the herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), hepatitis A virus (HAV), and coxsackievirus B4 (COX-B4). We observed that Forskolin displayed antiviral activity against HAV, COX-B4, HSV-1, and HSV-2 with IC50 values of 62.9, 73.1, 99.0, and 106.0 μg/mL, respectively. Furthermore, we explored the Forskolin's potential antiviral target using PharmMapper, a pharmacophore-based virtual screening platform. Forskolin's modeled structure was analyzed to identify potential protein targets linked to its antiviral activity, with results ranked based on Fit scores. Cathepsin L (PDB ID: 3BC3) emerged as a top-scoring hit, prompting further exploration through molecular docking and MD simulations. Our analysis revealed that Forskolin's binding mode within Cathepsin L's active site, characterized by stable hydrogen bonding and hydrophobic interactions, mirrors that of a co-crystallized inhibitor. These findings, supported by consistent RMSD profiles and similar binding free energies, suggest Forskolin's potential in inhibiting Cathepsin L, highlighting its promise as an antiviral agent. [ABSTRACT FROM AUTHOR]

Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90 μg/mL within 72 h. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves. [ABSTRACT FROM AUTHOR]

This research paper focuses on investigating the solvability of a constrained problem involving a nonlinear delay functional equation subject to a quadratic functional integral constraint, in two significant cases: firstly, the existence of nondecreasing solutions in a bounded interval L 1 [ 0 , T ] and, secondly, the existence of nonincreasing solutions in unbounded interval L 1 (R +) . Moreover, the paper explores various qualitative properties associated with these solutions for the given problem. To establish the validity of our claims, we employ the De Blasi measure of noncompactness (MNC) technique as a basic tool for our proofs. In the first case, we provide sufficient conditions for the uniqueness of the solution ψ ∈ L 1 [ 0 , T ] and rigorously demonstrate its continuous dependence on some parameters. Additionally, we establish the equivalence between the constrained problem and an implicit hybrid functional integral equation (IHFIE). Furthermore, we delve into the study of Hyers–Ulam stability. In the second case, we examine both the asymptotic stability and continuous dependence of the solution ψ ∈ L 1 (R +) on some parameters. Finally, some examples are provided to verify our investigation. [ABSTRACT FROM AUTHOR]