INVESTIGATION AND IDENTIFICATION OF SOME ACTIVE BIOCHEMICAL IN MEDICAL PLANTS AGAINST CYP51 PROTEIN IN CANDIDA BY USING MOLECULAR DOCKING

ABSTRACT: Common and medical plants were investigated for active biochemical to bind and inhibit the CYP51 protein in candida sp., 22 important plants were chosen and 263 molecular docking reactions were done between active materials and protein, 1441 different active ligands were detected for binding in protein active site, the best 225 ligands were chosen depending the power of affinity bond. Four ligands were candidates for having the best ligand affinity bond and more safety for use according to the toxicity test program; within these ligands, the Epicatechin was found to be the best biochemical for inhibition and bonding to CYP51 protein as it subjects to Lipinski's rule of five. Keywords: molecular docking; medical plants; Candida sp.   Investigação e identificação de alguns bioquímicos ativos em plantas medicinais contra a proteína CYP51 em candida usando Molecular Docking   RESUMO: Plantas comuns e medicinais foram investigadas para bioquímicos ativos para ligar e inibir a proteína CYP51 em Candida sp., 22 plantas importantes foram escolhidas e 263 reações de docking molecular foram feitas entre materiais ativos e proteínas, 1441 ligantes ativos diferentes foram detectados para ligação em proteínas sítio ativo, o melhor ligante 225 foi escolhido dependendo do poder de ligação de afinidade. Quatro ligantes foram candidatos por ter melhor ligação por afinidade e maior segurança para uso de acordo com o programa de testes de toxicidade, dentro destes ligantes a Epicatequina mostrou ser o melhor bioquímico para inibição e ligação à proteína CYP51 por estar sujeita à regra dos cinco de Lipinski. Palavras-chave: docking molecular; plantas medicinais; Candida sp.ABSTRACT: Common and medical plants were investigated for active biochemical to bind and inhibit the CYP51 protein in candida sp., 22 important plants were chosen and 263 molecular docking reactions were done between active materials and protein, 1441 different active ligands were detected for binding in protein active site, the best 225 ligands were chosen depending the power of affinity bond. Four ligands were candidates for having the best ligand affinity bond and more safety for use according to the toxicity test program; within these ligands, the Epicatechin was found to be the best biochemical for inhibition and bonding to CYP51 protein as it subjects to Lipinski's rule of five. Keywords: molecular docking; medical plants; Candida sp.   Investigação e identificação de alguns bioquímicos ativos em plantas medicinais contra a proteína CYP51 em candida usando Molecular Docking   RESUMO: Plantas comuns e medicinais foram investigadas para bioquímicos ativos para ligar e inibir a proteína CYP51 em Candida sp., 22 plantas importantes foram escolhidas e 263 reações de docking molecular foram feitas entre materiais ativos e proteínas, 1441 ligantes ativos diferentes foram detectados para ligação em proteínas sítio ativo, o melhor ligante 225 foi escolhido dependendo do poder de ligação de afinidade. Quatro ligantes foram candidatos por ter melhor ligação por afinidade e maior segurança para uso de acordo com o programa de testes de toxicidade, dentro destes ligantes a Epicatequina mostrou ser o melhor bioquímico para inibição e ligação à proteína CYP51 por estar sujeita à regra dos cinco de Lipinski. Palavras-chave: docking molecular; plantas medicinais; Candida sp

Clinician Perspectives on Factors Affecting Shared Decision Making about Lung Cancer Screening

Background/Objective. In 2015, the Centers for Medicare and Medicaid Services (CMS) announced coverage for annual lung cancer screening (LCS) with low dose computed tomography (LDCT) for individuals who are 55 to 77 years of age, have \u3e 30 pack years of smoking history, and undergo shared decision making (SDM) prior to screening. Most referrals for LCS are initiated in primary care. Currently, little is known about how primary care physicians view SDM and barriers in practice to SDM about LCS. This study aimed to gather information to help fill these knowledge gaps. Methods. I worked with senior leadership in the Department of Medicine to identify a set of internal medicine physicians at Thomas Jefferson University (TJU) and contacted them via email requesting their participation in an interview about SDM in LCS. I developed an interview guide that included questions about the following: understanding of SDM, perceptions about SDM in LCS, and receptivity to use of an online decision support intervention (DSI). I completed in-person, audio recorded interviews, which were transcribed for analysis. I then analyzed the interview transcripts using NVivo qualitative analysis software. Results. Nine physicians were interviewed from a pool of twenty-three physicians over a period of three weeks. With regards to understanding of SDM, physicians were in agreement that SDM is a joint decision based on a discussion about the risks and benefits of an intervention that considers patient values and medical status. Physician perceptions of SDM in LCS was influenced by patient comorbidities, LCS controversies and complexity, and limited office time. Receptivity to using an online DSI was generally positive and particularly favored its patient education component and easing of physician workload. Conclusions. Observations from this study highlight a common general understanding of SDM, yet mixed approaches to SDM in LCS. Strong support also exists for a DSI that educates patients about LCS and saves physicians time. Future steps include interviewing a set of family medicine physicians to investigate potential differences in viewpoints compared to internal medicine physicians

Naringenin as a potent inhibitor molecule for targeting microtubule affinity-regulating kinase 4 (mark4): a molecular docking and in vitro study for therapeutics of Alzheimer's disease

Background: The targeted inhibition of Microtubule Affinity-Regulating Kinase 4 (MARK4) using small molecule inhibitors has emerged as a promising therapeutic approach for diverse diseases, including neurological disorders such as Alzheimer’s disease. Ongoing research endeavors aim to develop novel and more effective MARK4 inhibitors with enhanced target specificity and reduced off-target effects. In the present study, we sought to investigate the binding affinity and impact of Naringenin on the activity of MARK4. Methods: We employed a combination of molecular docking and other bioinformatics methods, a fluorescence-based inhibition assay, as well as a kinase activity assay to assess the binding affinity and inhibition potential of Naringenin against MARK4. Additionally, we utilized the MTT assay to examine the effect of Naringenin on the viability of two cell lines: the normal human cell line HEK-293 and the neuronal cell line SH-SY5Y. The IC50 dose of Naringenin, determined from the MTT assay, provided a valuable reference point for subsequent neuronal cell line experiments.Results: The results of the molecular docking demonstrated a robust binding affinity of Naringenin (-7.8 kcal/mol) to MARK4, affirming its potency as an inhibitor. Moreover, the fluorescence inhibition and kinase activity assays confirmed the inhibitory effect of Naringenin on MARK4. Interestingly, the MTT assay outcomes indicated that increasing concentrations of Naringenin did not significantly impact the viability of HEK 293 cells, while exhibiting a pronounced effect on SH-SY5Y neuronal cells. The IC50 concentration of Naringenin was determined to be 10.0 ± 1.33 μM for SH-SY5Y neuronal cells.Conclusion: In conclusion, this study reported Naringenin as a potential inhibitor molecule for MARK4, offering promising prospects for future therapeutic interventions in neuronal disorders specifically for Alzheimer’s disease.Keywords: Inhibition; Microtubule Affinity-Regulating Kinase 4 (MARK4); Molecular docking; Naringenin; Neuronal disorders  Editorial Note: You are viewing the latest version of this manuscript having correction in abstract section, which is different from the originally published copy

A Demand-Supply Matching-Based Approach for Mapping Renewable Resources towards 100% Renewable Grids in 2050

Recently, many renewable energy (RE) initiatives around the world are based on general frameworks that accommodate the regional assessment taking into account the mismatch of supply and demand with pre-set goals to reduce energy costs and harmful emissions. Hence, relying entirely on individual assessment and RE deployment scenarios may not be effective. Instead, developing a multi-faceted RE assessment framework is vital to achieving these goals. In this study, a regional RE assessment approach is presented taking into account the mismatch of supply and demand with an emphasis on Photovoltaic (PV) and wind turbine systems. The study incorporates mapping of renewable resources optimized capacities for different configurations of PV and wind systems for multiple sites via test case. This approach not only optimizes system size but also provides the appropriate size at which the maximum renewable energy fraction in the regional power generation mix is maximized while reducing energy costs using MATLAB’s ParetoSearch algorithm. The performance of the proposed approach is tested in a realistic test site, and the results demonstrate the potential for maximizing the RE share compared to the achievable previously reported fractions. The results indicate the importance of resource mapping based on energy-demand matching rather than a quantitative assessment of anchorage sites. In the examined case study, the new assessment approach led to the identification of the best location for installing a hybrid PV / wind system with a storage system capable of achieving a nearly 100% autonomous RE system with Levelized cost of electricity of 0.05 USD/kWh

100% Renewable Energy Grid for Rural Electrification of Remote Areas: A Case Study in Jordan

Many developing countries suffer from high energy-import dependency and inadequate electrification of rural areas, which aggravates the poverty problem. In this work, Al-Tafilah in Jordan was considered as a case study, where the technical, economic, and environmental benefits of a decentralized hybrid renewable energy system that can match 100% of the city demand were investigated. A tri-hybrid system of wind, solar, and hydropower was integrated with an energy storage system and optimized to maximize the match between the energy demand and production profiles. The optimization aimed at maximizing the renewable energy system (RES) fraction while keeping the levelized cost of electricity (LCOE) equal to the electricity purchase tariff. The techno-economic analysis showed that the optimal system in Al-Tafilah comprises a 28 MW wind system, 75.4 MW PV, and 1 MW hydropower, with a 259 MWh energy storage system, for which a RES fraction of 99% can be achieved, and 47,160 MtCO2 are avoided. This study can be easily extended to other rural cities in Jordan, as they have higher renewable energy system (RES) potential. The presented findings are essential not only for Jordan’s planning and economy-boosting but also for contributing to the ongoing force against climate change

Some new applications of the quantum-difference operator on subclasses of multivalent q-starlike and q-convex functions associated with the Cardioid domain

In this study, we consider the quantum difference operator to define new subclasses of multivalent $q$-starlike and $q$-convex functions associated with the cardioid domain. We investigate a number of interesting problems for functions that belong to these newly defined classes, such as bounds for the first two Taylor-Maclaurin coefficients, estimates for the Fekete-Szeg ö type functional, and coefficient inequalities. The important point of this article is that all the bounds that we have investigated are sharp. Many well-known corollaries are also presented to demonstrate the relationship between prior studies and the results of this article

Luteolin Causes 5′CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells

Cancer progression is linked to abnormal epigenetic alterations such as DNA methylation and histone modifications. Since epigenetic alterations, unlike genetic changes, are heritable and reversible, they have been considered as interesting targets for cancer prevention and therapy by dietary compounds such as luteolin. In this study, epigenetic modulatory behaviour of luteolin was analysed on HeLa cells. Various assays including colony forming and migration assays, followed by biochemical assays of epigenetic enzymes including DNA methyltransferase, histone methyl transferase, histone acetyl transferase, and histone deacetylases assays were performed. Furthermore, global DNA methylation and methylation‐specific PCR for examining the methylation status of CpG promoters of various tumour suppressor genes (TSGs) and the expression of these TSGs at transcript and protein level were performed. It was observed that luteolin inhibited migration and colony formation in HeLa cells. It also modulated DNA methylation at promoters of TSGs and the enzymatic activity of DNMT, HDAC, HMT, and HAT and reduced the global DNA methylation. Decrease in methylation resulted in the reactivation of silenced tumour suppressor genes including FHIT, DAPK1, PTEN, CDH1, SOCS1, TIMPS, VHL, TP53, TP73, etc. Hence, luteolin‐targeted epigenetic alterations provide a promising approach for cancer prevention and intervention

Study of quantum calculus for a new subclass of q-starlike bi-univalent functions connected with vertical strip domain

In this study, using the ideas of subordination and the quantum-difference operator, we established a new subclass $\mathcal{S} ^{\ast }\left(\delta, \sigma, q\right)$ of $q$-starlike functions and the subclass $\mathcal{S}_{\Sigma }^{\ast }\left(\delta, \sigma, q\right)$ of $q$-starlike bi-univalent functions associated with the vertical strip domain. We examined sharp bounds for the first two Taylor-Maclaurin coefficients, sharp Fekete-Szegö type problems, and coefficient inequalities for the function $h$ that belong to $\mathcal{S}^{\ast }\left(\delta, \sigma, q\right)$, as well as sharp bounds for the inverse function $h$ that belong to $\mathcal{S}^{\ast }\left(\delta, \sigma, q\right)$. We also investigated some results for the class of bi-univalent functions $\mathcal{S}_{\Sigma }^{\ast }\left(\delta, \sigma, q\right)$ and well-known corollaries were also highlighted to show connections between previous results and the findings of this paper