A drug design strategy based on molecular docking and molecular dynamics simulations applied to development of inhibitor against triple-negative breast cancer by Scutellarein derivatives.

Triple-negative breast cancer (TNBC), accounting for 10-15% of all breast malignancies, is more prevalent in women under 40, particularly in those of African descent or carrying the BRCA1 mutation. TNBC is characterized by the absence of estrogen and progesterone receptors (ER, PR) and low or elevated HER2 expression. It represents a particularly aggressive form of breast cancer with limited therapeutic options and a poorer prognosis. In our study, we utilized the protein of TNBC collected from the Protein Data Bank (PDB) with the most stable configuration. We selected Scutellarein, a bioactive molecule renowned for its anti-cancer properties, and used its derivatives to design potential anti-cancer drugs employing computational tools. We applied and modified structural activity relationship methods to these derivatives and evaluated the probability of active (Pa) and inactive (Pi) outcomes using pass prediction scores. Furthermore, we employed in-silico approaches such as the assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and quantum calculations through density functional theory (DFT). Within the DFT calculations, we analyzed Frontier Molecular Orbitals, specifically the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO). We then conducted molecular docking and dynamics against TNBC to ascertain binding affinity and stability. Our findings indicated that Scutellarein derivatives, specifically DM03 with a binding energy of -10.7 kcal/mol and DM04 with -11.0 kcal/mol, exhibited the maximum binding tendency against Human CK2 alpha kinase (PDB ID 7L1X). Molecular dynamic simulations were performed for 100 ns, and stability was assessed using root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) parameters, suggesting significant stability for our chosen compounds. Furthermore, these molecules met the pharmacokinetics requirements for potential therapeutic candidates, displaying non-carcinogenicity, minimal aquatic and non-aquatic toxicity, and greater aqueous solubility. Collectively, our computational data suggest that Scutellarein derivatives may serve as potential therapeutic agents for TNBC. However, further experimental investigations are needed to validate these findings.

Analysis of Crystallographic Structures and Properties of Silver Nanoparticles Synthesized Using PKL Extract and Nanoscale Characterization Techniques.

In this cutting-edge research era, silver nanoparticles impose a substantial impact because of their wide applicability in the field of engineering, science, and industry. Regarding the vast applications of silver nanoparticles, in this study, the crystallographic characteristics and nanostructures of silver nanoparticles extracted from natural resources have been studied. First, biosynthetic silver nanoparticles were synthesized using the Pathor Kuchi leaf (PKL) extract as a mediator, and their crystal structures and characteristics were analyzed by UV-visible absorption spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), and energy-dispersive X-ray (EDX) analysis. The average crystallite size of the synthesized silver nanoparticle was determined to be 20.26 nm, and also the lattice strain, intrinsic stress, and dislocation density were measured to be 2.19 × 10-3, 0.08235 GPa, and 3.062045 × 10-3/nm2, respectively. Further, the prepared sample of silver nanoparticles shows four peaks in the X-ray diffraction pattern, which correspond to the (111), (200), (220), and (311) face-centered cubic (FCC) crystalline planes. The outstanding finding of this work was that when the lattice parameters of the precursor were increased, the volume of the material did not considerably change, but the particle size decreased. Second, it was clearly demonstrated that this straightforward method is a clean, cost-effective, environmentally sustainable, nontoxic, and efficient route for the synthesis of silver nanoparticles (Ag NPs) using PKL leaf at ambient temperature, which also satisfies the green chemistry requirements. Finally, this study demonstrates the scope for the production of silver nanoparticles using low-cost natural resources.

Synthesis, characterization, antibacterial activity of thiosemicarbazones derivatives and their computational approaches: Quantum calculation, molecular docking, molecular dynamic, ADMET, QSAR.

The thiosemicarbazones and their derivatives have been recognized as antimicrobial agents against human pathogenic bacteria and fungi. Regarding these prospective, this study was designed to address the new antimicrobial agents from thiosemicarbazones and their derivatives. These derivatives were synthesized by multi-step synthesis methods, such as alkylation, acidification, esterification, and formed the 4-(4'-alkoxybenzoyloxy) thiosemicarbazones and its derivatives (THS1, THS2, THS3, THS4, and THS5). Afterward the synthesis, compounds were characterized by 1H NMR, FTIR spectra, and melting point. Later, the computational tools were applied to evaluate the drug likeness properties, bioavailability score, Lipinski rule, absorption, distribution, metabolism, excretion, and toxicity (ADMET). Secondly, the quantum calculations, for instance HOMO, LUMO and chemical descriptors, were calculated by the density functional theory (DFT). Finally, the molecular docking was performed against seven human pathogenic bacteria, black fungus (Rhizomucor mieh, Mucor lusitanicus, Mycolicibacterium smegmatis) and white fungus strains (Candida Auris, Aspergillus luchuensis, Candida albicans). To check and validate of molecular docking procedure and stability of docked complex for ligand and protein, the molecular dynamic was performed of docked complex. From the docking score with calculating the binding affinity, these derivatives could show a higher affinity than standard drug against all pathogens. From the computational details, it could be decided to do in-vitro test as antimicrobial activity against Staphylococcus aurious, Staphylococcus homonis, Salmonella typhi, and Shigella flexneria. The obtained result of antibacterial activity compared to standard drugs, and it was found that the synthesized compounds were almost same value of standard drug. Finally, it could be said from the in-vitro and in-silico study that the thiosemicarbazones derivatives are good antimicrobial agents.

Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach.

The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study's primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses.

Anti-lung cancer drug discovery approaches by polysaccharides: an in silico study, quantum calculation and molecular dynamics study.

Lung cancer (LC) is one of the major and risky health defects even the serious cause for death in concurrent era. But no potential drugs even chemotherapeutic agents have been discovered with approval of health safety although some non-toxic biological macromolecules, such as polysaccharides and polysaccharide-protein complexes, have obtained as anti-lung cancer properties. This study conveys the anti-lung cancer properties of 45 polysaccharide derivatives collected from PubChem database. Primarily, the PASS prediction was performed to depict their anti-cancer activity, and 37 compounds showed the desired results. Next, the chemical descriptors, such as HOMO, LUMO, softness, and hardness etc, were calculated through the density functional theory (DFT) for quantum properties. Secondly, the auto molecular docking was executed to delineate the protein-ligand interactions, binding ability and inhibition of active sites of proteins. Additionally, the compounds showed docking score more than -6.40 kcal/mol, and the highest binding affinity was at -10.00 kcal/mol even 15 compounds have higher binding score (-8.6 to -10.0) than approved drugs, Gemcitabine. Succeeding, the most common protein residue, VAL 647, was blocked by ligands for the main protein (1X2J). In addition, five protein's active sites were determined to make the relative study of protein-ligand interactions. As a result, the target docking against five proteins was performed, and it was found that the targeted docking score as the binding affinity is lower than auto docking. Finally, a comparative study between auto docking and targeted docking was performed for the most common five lung cancer proteins founded in three organisms.Communicated by Ramaswamy H. Sarma.

Investigation of the New Inhibitors by Sulfadiazine and Modified Derivatives of α-D-glucopyranoside for White Spot Syndrome Virus Disease of Shrimp by In Silico: Quantum Calculations, Molecular Docking, ADMET and Molecular Dynamics Study.

The α-D-glucopyranoside and its derivatives were as the cardinal investigation for developing an effective medication to treat the highest deadly white spot syndrome virus (WSSV) diseases in Shrimp. In our forthcoming work, both computational tools, such as molecular docking, quantum calculations, pharmaceutical kinetics, ADMET, and their molecular dynamics, as well as the experimental trial against WSSV, were executed to develop novel inhibitors. In the beginning, molecular docking was carried out to determine inhibitors of the four targeted proteins of WSSV (PDB ID: 2ED6, 2GJ2, 2GJI, and 2EDM), and to determine the binding energies and interactions of ligands and proteins after docking. The range of binding affinity was found to be between -5.40 and -7.00 kcal/mol for the protein 2DEM, from -5.10 to 6.90 kcal/mol for the protein 2GJ2, from -4.70 to -6.2 kcal/mol against 2GJI, and from -5.5 kcal/mol to -6.6 kcal/mol for the evolved protein 2ED6 whereas the L01 and L03 display the highest binding energy in the protein 2EDM. After that, the top-ranked compounds (L01, L02, L03, L04, and L05), based on their high binding energies, were tested for molecular dynamics (MD) simulations of 100 ns to verify the docking validation and stability of the docked complex by calculating the root mean square deviation (RMSD) and root mean square fluctuation (RMSF). The molecules with the highest binding energy were then picked and compared to the standard drugs that were been applied to fish experimentally to evaluate the treatment at various doses. Consequently, approximately 40-45% cure rate was obtained by applying the dose of oxytetracycline (OTC) 50% with vitamin C with the 10.0 g/kg feed for 10 days. These drugs (L09 to L12) have also been executed for molecular docking to compare with α-D-glucopyranoside and its derivatives (L01 to L08). Next, the evaluation of pharmacokinetic parameters, such as drug-likeness and Lipinski's principles; absorption; distribution; metabolism; excretion; and toxicity (ADMET) factors, were employed gradually to further evaluate their suitability as inhibitors. It was discovered that all ligands (L01 to L12) were devoid of hepatotoxicity, and the AMES toxicity excluded L05. Additionally, all of the compounds convey a significant aqueous solubility and cannot permeate the blood-brain barrier. Moreover, quantum calculations based on density functional theory (DFT) provide the most solid evidence and testimony regarding their chemical stability, chemical reactivity, biological relevance, reactive nature and specific part of reactivity. The computational and virtual screenings for in silico study reveals that these chosen compounds (L01 to L08) have conducted the inhibitory effect to convey as a possible medication against the WSSV than existing drugs (L09, L10, L11 and L12) in the market. Next the drugs (L09, L10, L11 and L12) have been used in trials.

Developing the amazing photocatalyst of ZnAg2GeSe4, ZnAg2Ge0.93Fe0.07Se4 and ZnAg2Ge0.86Fe0.14Se4 through the computational explorations by four DFT functionals.

For developing the stannite type quarterly crystal photocatalyst, the electronic structure and optical properties of ZnAg2GeSe4, ZnAg2Ge0.93Fe0.07Se4 and ZnAg2Ge0.86Fe0.14Se4 were calculated and compared with the parent stannite type quarterly crystal, ZnAg2GeS4. First of all, the four functionals, such as GGA with PBE, GGA with RPBE, GGA with WC and LDA with CA-PZ functionals were used for primary screening of electronic band structure and structural geometry for ZnAg2GeS4 while the band gap was in 0.93, 0.97, 0.77 and 0.67 eV, respectively. It must be mentioned that the experimental value of ZnAg2GeS4 was 0.94 eV so that the GGA with PBE showed the overlapping value of band gap. The main focus of this paper is to evaluate the band structure of newly predicted the stannite type quarterly crystal, ZnAg2GeSe4 using four methods replacing the Sulfur atom by Serium atom on ZnAg2GeS4. The band gap for four methods, such as GGA with PBE, GGA with RPBE, GGA with WC and LDA with CA-PZ functionals, were calculated in 0.84 eV, 0.92 eV, 0.68 eV and 0.58 eV. Afterward, Fe atom was doped by two portions, like 7% and 14%, to make the empirical formula, ZnAg2Ge0.93Fe0.07Se4 and ZnAg2Ge0.86Fe0.14Se4. The numerical values of band gaps for ZnAg2Ge0.93Fe0.07Se4 and ZnAg2Ge0.86Fe0.14Se4 were 0.43 eV, 0.53 eV, 0.35 eV and 0.18 eV and 0.24 eV, 0.31 eV, 0.18 eV and 0.08 eV, respectively, using the four respected DFT methods. For their contributed orbitals of each atom on crystal, the density of state and the partial density of state for ZnAg2GeSe4, ZnAg2Ge0.93Fe0.07Se4 and ZnAg2Ge0.86Fe0.14Se4 crystals were simulated through the GGA with PBE method as standard regarding the calculation of band gap study comparison with experimental magnitude. For giving the further information about the nature in case of optical evidence, the six optical properties, such as absorption, reflection, refractive index, conductivity, dielectric function and loss function were calculated, and make a comparative study. In case of UV light absorption in lighten to optical parameters, the ZnAg2Ge0.86Fe0.14Se4 can show the highest absorption up to convenience energy region as photocatalyst.

WHO guideline on school health services

Schools are essential for young people to acquire knowledge, socioemotional skills including selfregulation and resilience, and critical thinking skills that provide the foundation for a healthy future. Access to education and safe and supportive school environments have been linked to better health outcomes. In turn, good health is linked to reduced drop-out rates and greater educational attainment, educational performance, employment and productivity. WHO has long recognized the link between health and education and the potential for schools to play a central role in safeguarding student health and well-being. In 1995, WHO launched the Global School Health Initiative, which aimed to strengthen approaches to health promotion in schools. Among those approaches, pairing children with health services occupies an important place. Many health conditions can be better managed or prevented if detected early. The school environment and school health services provide an opportunity for timely interventions across a range of conditions, including anxiety and depression, behavioural disorders, diabetes, overweight, obesity and undernutrition. There are many reasons why school health services are uniquely placed to contribute to the health and well-being of school-age children. First, they operate where most children are, and they have access to families. Secondly, they are free at the point of use and overcome barriers such as transport issues, limited community services, and inconvenient location or appointment systems, and therefore have the potential to better serve underprivileged populations.

WHO guideline on school health services. Web Annex F. Systematic reviews of the effectiveness and acceptability of comprehensive school health services: GRADE evidence profiles and evidence-to-decision table

WHO guideline on school health services: Web Annex F. Systematic reviews of the effectiveness and acceptability of comprehensive school health services: GRADE evidence profiles and evidence-to-decision table In partnership with WHO guideline on school health services Web Annex F. Systematic reviews of the effectiveness and acceptability of comprehensive school health services: GRADE evidence profiles and evidence-to-decision tableIn partnership with WHO guideline on school health services Web Annex F. Systematic reviews of the effectiveness and acceptability of comprehensive school health services: GRADE evidence profiles and evidence-to-decision tableWHO guideline on school health services. Web Annex F. Systematic reviews of the effectiveness and acceptability of comprehensive school health.

Línguas Indígenas - UNESCO

Site institucional da Unesco para comemoração do Ano Internacional das Línguas Indígenas.

MUSEU DO INDIO - UNESCO

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Marco de asistencia de las Naciones Unidas para el desarrollo Cuba 2014-2018

El presente Marco de Asistencia de Naciones Unidas para el Desarrollo (MANUD), acordado con el Gobierno de Cuba, define la respuesta colectiva del Sistema de Naciones Unidas a las prioridades nacionales para el período 2014-2018. Este ciclo de cooperación se enmarcará en el proceso de actualización del modelo económico, contribuyendo a las prioridades de desarrollo acordadas con las autoridades cubanas. Desde su enfoque de género, poblacional y territorial, este marco acompañará al país en sus estrategias de desarrollo centradas en el ser humano que buscan de manera sostenible mejorar la calidad de vida de la población y el desmpeño económico...

Red Latinoamericana y del Caribe de Bioética

La Red Bioética de UNESCO se constituye como un grupo colegiado que promueve el diálogo pluralista, fomentando actividades de carácter interdisciplinario para las cuestiones de bioética de América Latina y el Caribe. Su tarea se lleva a cabo en compromiso con la realidad socioeconómica, la cultural y las necesidades fundamentales de los países y pueblos de la región. Los objetivos de la Red se rigen por los principios y postulados básicos de la UNESCO.El sitio contiene información sobre congresos, foros, cursos y demás eventos en el área, noticias relacionadas con todos los ámbitos de la bioética, los miembros de la Red, el consejo directivo, estatutos.Brinda acceso a la Revista de bioética, artículos, libros, documentos, entrevistas, entre otros.