The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound impact on global health and socio-economic conditions. To date, various vaccines have been administered worldwide in an effort to curb the spread of the virus. Despite vaccination efforts, there have been complications. Existing antiviral drugs have shown limited effectiveness, prompting the use of computational methods to understand the dynamics of the virus and develop suitable treatments. The current study focuses on using biocompatible para-sulfonato-calix[4]arenes to dock against two key proteins of SARS-CoV-2, namely ribonucleic acid (RNA)-dependent RNA polymerase, and helicase. Docking results indicate a strong binding affinity of these compounds to the target proteins, with higher scores compared to commonly used medications. Molecular dynamics (MD) simulation validates the docking results, showing stable protein-ligand complexes over time. The compounds are also screened for absorption, distribution, metabolism, and excretion properties and toxicity, suggesting their potential as lead candidates for inhibiting the virus’s key proteins. However, further in vivo and in vitro studies are recommended to confirm these findings. COVID19 COVID 19 (COVID-19 pandemic SARSCoV2, SARSCoV2 SARSCoV SARS CoV , (SARS-CoV-2) socioeconomic socio economic conditions date efforts complications effectiveness treatments parasulfonatocalix4arenes parasulfonatocalixarenes para sulfonato calix 4 arenes 2, SARS-CoV-2 RNAdependent dependent polymerase helicase medications MD (MD proteinligand protein ligand time absorption distribution metabolism toxicity viruss s However findings COVID1 1 (COVID-1 (SARS-CoV-2 parasulfonatocalix SARS-CoV- (COVID- (SARS-CoV- SARS-CoV (COVID (SARS-CoV

The alpha-glucosidase enzyme of Candida albicans plays a vital role in the pathogenesis of candidiasis, a serious fatal disease in immune-compromised patients. The unavailability of the three-dimensional crystallographic structure of this enzyme creates a hindrance in developing novel and potent inhibitors. Here, an attempt has been made to design a stable three-dimensional conformer of alpha-glucosidase through in silico analysis which may be helpful for the designing of effective drugs. For this purpose, the oligo-1-6-glucosidase enzyme is used as a template for homology modeling of the alpha-glucosidase structure by Molecular Operating Environment 2011-12 software. The generated model was validated through ERRAT and Ramachandran tools, whereas its stability was studied through the molecular dynamics simulation technique. The obtained results indicate that model of alpha-glucosidase has stable secondary and tertiary arrangements. This finding may spur new directions for the rational designing and development of new antifungal inhibitors. Nevertheless, additional experimental investigations and validation are needed to confirm the in silico results of this study. alphaglucosidase alpha glucosidase candidiasis immunecompromised immune compromised patients threedimensional three dimensional inhibitors Here drugs purpose oligo16glucosidase oligoglucosidase oligo 1 6 201112 2011 12 2011-1 software tools technique arrangements Nevertheless study 20111 201 2011- 20 2

Resumen En este estudio se investigaron las propiedades fisicoquímicas del aceite de nuez (Juglans regia L.) recolectado de diferentes sitios en Khyber PakhtoonKhwa (KPK), Pakistán. Los aceites de nuez obtenidos mostraron variación en los valores de viscosidad, tensión superficial, densidad, acidez, saponificación e índice de yodo. El aceite obtenido del Madyan (Muestra E) mostró la menor densidad (0.981 g/cm3), tensión superficial (34.76 × 10-3 N/m), viscosidad (15.0595 cp), valores de saponificación 84.15 (mg KOH/g de aceite) y valor ácido 3.5 (mg KOH por gramo de aceite) entre otros. Las propiedades fisicoquímicas de todos los aceites también se compararon con el aceite de oliva (estándar); la muestra E mostró similitudes en las diferentes propiedades en comparación con el aceite de oliva. Además, se determinaron concentraciones más elevadas de ácido oleico (41 %) y ácido linoleico (9 %) en el aceite de nuez de la muestra E mediante el análisis GC/MS. Las similitudes del aceite de nuez obtenido de Madyan con el estándar (aceite de oliva) lo afirman como aceite de mejor calidad y adecuado para el procesamiento de alimentos.

Abstract In this study, the physicochemical properties of walnut (Juglans regia L.) oils collected from different sites in Khyber PakhtoonKhwa (KPK), Pakistan were investigated. The obtained walnut oils showed variation in viscosity, surface tension, density, acid, saponification, and iodine values. The oil obtained from the Madyan (Sample E) showed the lowest density (0.981 g/cm3), surface tension (34.76×10-3 N/m), viscosity (15.0595 cp) saponification values 84.15 (mg KOH/g of oil) and acid value 3.5 (mg KOH per gram oil) amongst all. The physicochemical properties of all the oils were also compared to olive oil (standard) where sample E showed similarities in such properties compared to olive oil. Moreover, higher concentrations of oleic acid (41 %) and linoleic acid (9 %) were detected in the walnut oil of sample E in GC/MS analysis. The similarities of walnut oil obtained from Madyan to that of standard (olive oil) thus affirm it as best quality oil and suitable for food processing purposes.

Resumo Objetivos As hemorroidas são caracterizadas por sangramento, secreção mucosa, prurido, dor e prolapso. Esta condição é conhecida como bawaseer namedicina Unani, e a Hirudinaria granulosa tem sido usada para seu tratamento na Irsal-e Alaq, ou hirudoterapia, há séculos. A H. granulosa, devido à sua ação antitrombótica e antiinflamatória, é utilizada no tratamento de doenças venosas crônicas e hemorroidas. O presente estudo teve como objetivo investigar a eficácia da hirudoterapia em hemorroidas de terceiro e quarto graus. Métodos Este ensaio clínico prospectivo e unicêntrico com delineamento pré e pósanálise foi conduzido no hospital do National Institute of Unani Medicine. Foram incluídos no estudo 20 pacientes de ambos os sexos, com média de idade de 38 anos, que apresentavam sintomas moderados avaliados pelo questionário colorectal evaluation of clinical therapeutics scale (CORECTS). Espécimes de H. granulosa foram aplicadas em volta da área afetada por um período de 15 minutos semanais, durante 4 semanas. A eficácia do tratamento foi medida por uma avaliação objetiva e subjetiva usando o questionário CORECTS. Resultados Quando analisada pelo clínico, a hirudoterapia reduziu o escore de gravidade dos sintomas nos seguintes domínios: dor (55% de melhora; p<0,001); prurido anorretal (melhora de 30%; p<0,10); e sangramento (melhora de 10%; p<0,7963). Melhora significativa (p<0,001) foi relatada no escore CORECTS em relação à dor (44,09% de melhora; p<0,001), prurido (38,55% de melhora; p<0,001), inchaço (44% de melhora; p<0,001), sangramento (17,28 % de melhora; p<0,007), desconforto (34,01% de melhora; p<0,001) e bem-estar (32,35% de melhora; p<0,001), o que resultou em uma opinião geral média sobre a terapia de 4/10. Conclusão Os resultados do estudo, embora com tamanho de amostra pequeno, mostram que a hirudoterapia é uma opção terapêutica eficaz e segura na redução dos sintomas de hemorroidas de terceiro e quarto graus.

Abstract Objectives Hemorrhoids are characterized by bleeding, mucous discharge, itching, pain, and prolapse. This condition is known as bawaseer in Unani medicine, and Hirudinaria granulosa has been used for its treatment in Irsal-e Alaq, or medicinal leech therapy (MLT), for centuries. Hirudinaria granulosa with antithrombotic and antiinflammatory action is used in the treatment of chronic venous disease and hemorrhoids. The present study was aimed to investigate the efficacy of MLT in third and fourth-degree hemorrhoids. Methods A single-centre prospective, clinical trial with a pre and postanalysis design was conducted at the hospital of the National Institute of UnaniMedicine. Twenty male and female patients, with a mean age of 38 years, presenting moderate symptoms assessed with the colorectal evaluation of clinical therapeutics scale (CORECTS) questionnaire were included in the study. Hirudinaria granulosa were applied around the pile mass for 15 minutes weekly, for 4 weeks. The efficacy of the treatment was measured by an objective and subjective assessment using the CORECTS. Results When analyzed by the clinician, MLT reduced the symptoms’ severity score in the following domains: pain (55% improvement; p<0.001); anorectal itching (30% improvement; p<0.10); and bleeding (10% improvement; p<0.7963). Significant improvement (p<0.001) was reported in the CORECTS score in relation to pain (44.09% improvement; p<0.001), itching (38.55% improvement; p<0.001), swelling (44% improvement; p<0.001), bleeding (17.28% improvement; p<0.007), discomfort (34.01% improvement; p<0.001), and wellbeing (32.35 % improvement; p<0.001), giving an average overall opinion on the therapy of 4/10. Conclusion The results of the study albeit smaller in sample size show that MLT is an effective and safe therapeutic option in reducing the symptoms of 3rd and 4th degree haemorrhoids.

Resumen En este estudio, se analizaron debido a su toxicidad, las fracciones crudas y posteriores de las partes aéreas de Aconitum violaceum, sus efectos antimicrobianos y potencial antioxidante. Fitoquímicamente, la planta está enriquecida en alcaloides junto con antraquinonas (presentes en la fracción de acetato de etilo (AV 3) y saponinas (detectadas en la fracción de cloroformo (AV2). En el ensayo de letalidad del camarón en salmuera, AV 3 fue el más potente (59%) para matar las larvas de Artemia naupili a una dosis de 1000 µg / ml. AV 3 mostró el efecto antimicrobiano más fuerte contra las bacterias E. coli (80 %) y S. flexneri (76 %), así como contra los hongos probados, A. niger (86 %) respectivamente. Sin embargo, la fracción de cloroformo (AV2) fue el antifúngico más eficaz (casi el 90%) contra A. niger y C. albicans. En general, se observó una fuerte actividad antioxidante para AV3 con valores de CI50 de 120.04 ± 0.4 µg / ml (65.4 ± 0,01 estándar) en DPPH y 125.1 ± 0.3 µg / mL (2.0 ± 0.03 estándar) en ensayos de radicales libres ABTS. AV 3 mostró una inhibición prometedora contra la acetilcolinesterasa (AChE) 70 ± 0.8 % y la butirilcolinesterasa (BChE) 57 ± 0.2 % a una dosis de 100 µg / mL confirmando así un potente efecto inhibidor de la colinesterasa in vitro. Todos los resultados indicaron un fuerte potencial biológico de la fracción de acetato de etilo obtenida de A. violaceum y se podría formular una posible nueva fuente terapéutica a partir de sus aislados puros.

Abstract In the current studies, crude and subsequent fractions of Aconitum violaceum aerial parts were screened for their toxicity, antimicrobial effects as well as antioxidant potential. Phytochemically, the plant is enriched in alkaloids alongside anthraquinones (present in ethyl acetate fraction (AV 3) and saponins (detected in chloroform fraction (AV2). In Brine shrimp lethality assay, AV 3 was the most potent (59 %) in killing Artemia naupili larvae at a dose of 1000 µg/mL. AV 3 exhibited strongest antimicrobial effect against the bacteria E. coli (80 %) and S. flexneri (76 %) as well as against the tested fungi, A. niger (86 %) respectively. However, chloroform fraction (AV2) was the most effective (almost 90 %) antifungal against A. niger and C. albicans. Overall, strong antioxidant activity was observed for AV3 with IC50 values of 120.04 ± 0.4 µg/mL (65.4 ± 0.01 standard) in DPPH and 125.1 ± 0.3 µg/mL (2.0 ± 0.03 standard) in ABTS free radical assays. AV 3 showed promising inhibition against acetylcholinesterase (AChE) 70 ± 0.8 % and butyrylcholinesterase (BChE) 57 ± 0.2 % at dose of 100 µg/mL thus confirming a potent invitro cholinesterase inhibitory effect. The overall results indicated strong biological potential of ethyl acetate fraction obtained form A. violaceum and a possible new therapeutic source could be formulated from its pure isolates.

ABSTRACT Lanthanide-doped gadolinium nanomaterials have attracted considerable attention due to their promising applications in biological imaging. Sodium gadolinium fluoride (β-NaGdF4) nanomaterials act as perfect host for doping of luminescent lanthanide ions. Due to heavy nature of gadolinium, it can strongly absorb X-ray radiations. Therefore, Gd-based nanomaterials are applied as contrast agents for X-ray tomography (CT). Presence of seven unpaired electrons in Gd+3 ion, its large magnetic moment and long electronic relaxation time makes it an ideal candidate to enhance water proton relaxation rates. These characteristics make Gd-based nanomaterial useful for their potential application as MRI contrast agents. In this work, sodium gadolinium fluoride is doped with ytterbium and erbium to produce β-NaGdF4:Yb/Er as core nanocrystals. They are subsequently coated with sodium gadolinium fluoride doped with neodymium (β-NaGdF4:Nd) to produce β-NaGdF4:Yb/Er@β-NaGdF4:Nd core-shell nanocrystals. Powder X‐ray diffraction (XRD) results indicated that β-NaGdF4 (host), β-NaGdF4:Yb/Er (core) and β-NaGdF4:Yb/Er@β-NaGdF4:Nd (core-shell) nanocrystals all exist in hexagonal crystalline phase. While Dynamic Light Scattering (DLS) results indicated that the particle size of the synthesized nanocrystals was in range of 12 to 27 nm. FTIR results confirmed that the synthesized nanocrystals were stabilized by oleic acid. Nanocrystals reported in this work are expected to be useful trimodal contrast agents for photoluminescence, X-ray tomography and Magnetic Resonance Imaging (MRI).

RESUMO O presente estudo descreve o desenvolvimento de microcápsulas de teofilina pelo método sem adição de solvente e o efeito da adição de plastificante na microencapsulação. A liberação foi estudada em água destilada e os dados foram analisados por vários modelos matemáticos para determinação do mecanismo de liberação. As microcápsulas preparadas mostraram-se esféricas, livres de corrente e com mais de 80% de fármaco encapsulado. O polímero - ftalato de acetato de celulose e o plastificante - polietileno glicol - afetaram as propriedades das microcápsulas, incluindo a liberação do fármaco (tempo para liberação de 50% do fármaco, T50). A formulação com a maior proporção de polímero e sem plastificante (F3) se mostrou como a de liberação mais lenta, com T50 = 4,3 h, enquanto as formulações com menor proporção de polímero e 20% de plastificante (m/m) (F13 &14) apresentaram a liberação mais rápida do fármaco, com T50 de 1,2 h e 1,3 h, respectivamente. A liberação do fármaco para a maioria das formulações seguiu o modelo de Higuchi. Concluiu-se, dos resultados do presente estudo, que o ftalato do acetato de celulose afeta significativamente a liberação controlada do fármaco em água, enquanto que a adição de polietileno glicol aumenta ligeiramente a liberação do fármaco.

ABSTRACT The present study describes the development of theophylline microcapsules by a non-solvent addition method and the effect of plasticizer addition on microencapsulation. The release was studied in distilled water and the data were analysed by various mathematical models for determining the mechanism of release. Prepared microcapsules were found to be spherical, free flowing and having more than 80% entrapped drug. The polymer - cellulose acetate phthalate and plasticizer - polyethylene glycol was considered to be affecting the properties of microcapsules including drug release (time for 50% drug release, T50). The formulation with the highest proportion of polymer and without plasticizer (F3) showed the slowest release with T50 = 4.3 h, while the formulation with lower proportion of polymer and 20% (w/w) plasticizer (F13 &14) showed the fastest release of drug with T50 values of 1.2 h and 1.3 h, respectively. The drug release from most of the formulations was found to be following Higuchi model. It is concluded from the results of the present study that cellulose acetate phthalate significantly affects the sustained release of the drug in water, whereas the addition of polyethylene glycol slightly enhances the drug release.