Identification of potential FAK inhibitors using mol2vec molecular descriptor-based QSAR, molecular docking, ADMET study, and molecular dynamics simulation.

This study aims to identify potential focal adhesion kinase (FAK) inhibitors through an integrated computational approach, combining mol2vec descriptor-based QSAR, molecular docking, ADMET study, and molecular dynamics simulation. A dataset of 437 compounds with known FAK inhibitory activities was used to develop QSAR models using machine learning algorithms combined with mol2vec descriptors. Subsequently, the most promising compounds were subjected to molecular docking against FAK to evaluate their binding affinities and key interactions. ADMET study and molecular dynamics simulation were also employed to investigate the pharmacokinetic, drug-like properties, and the stability of the protein-ligand complexes. The results showed that the mol2vec descriptor-based QSAR model established by support vector regression demonstrated good predictive performance (R2 = 0.813, RMSE = 0.453, MAE = 0.263 in case of training set, and R2 = 0.729, RMSE = 0.635, MAE = 0.477 in case of test set), indicating their reliability in identifying potent FAK inhibitors. Using this QSAR model and molecular docking, compound 21 (ZINC000004523722) was identified as the most potential compound, with predicted logIC50 value and binding energy of 2.59 and - 9.3 kcal/mol, respectively. The results of molecular dynamics simulation and ADMET study also further suggested its potential as a promising drug candidate. However, because our research was merely theoretical, additional in vitro and in vivo studies are required for the verification of these results.

Towards safer and efficient formulations: Machine learning approaches to predict drug-excipient compatibility.

Predicting drug-excipient compatibility is a critical aspect of pharmaceutical formulation design. In this study, we introduced an innovative approach that leverages machine learning techniques to improve the accuracy of drug-excipient compatibility predictions. Mol2vec and 2D molecular descriptors combined with the stacking technique were used to improve the performance of the model. This approach achieved a significant advancement in the predictive capacity as demonstrated by the accuracy, precision, recall, AUC, and MCC of 0.98, 0.87, 0.88, 0.93 and 0.86, respectively. Using the DE-INTERACT model as the benchmark, our stacking model could remarkably detect drug-excipient incompatibility in 10/12 tested cases, while DE-INTERACT managed to recognize only 3 out of 12 incompatibility cases in the validation experiments. To ensure user accessibility, the trained model was deployed to a user-friendly web platform (URL: https://decompatibility.streamlit.app/). This interactive interface accommodated inputs through various types, including names, PubChem CID, or SMILES strings. It promptly generated compatibility predictions alongside corresponding probability scores. However, the continual refinement of model performance is crucial before applying this model in practice.

Investigation of the mechanism of action of chemical constituents of celery seed against gout disease using network pharmacology, molecular docking, and molecular dynamics simulations.

Celery (Apium graveolens L.) has long been considered as a potential herbal medicine for the prevention and treatment of gout. However, the relationship between the chemical constituents and pharmacological activities of this medicinal plant has not been fully investigated yet. Therefore, this study aims to apply network pharmacology, molecular docking and molecular dynamics to explore the relationship between the chemical constituents of celery seed and its biological effects in the treatment of gout. Network pharmacology was built and analyzed based on the data collected from GeneCards, OMIM databases and SwissTargetPrediction web server using Cytoscape 3.9.0 software. The GO and KEGG pathway analysis of the potential targets of celery seed related to gout disease was performed using the ShinyGO v0.75 app. Molecular docking and molecular dynamics were carried out using Autodock vina and NAMD 2.14 software, respectively. The network analysis identified 16 active compounds and thirteen key targets of celery seed in the treatment of gout. The GO analysis and the KEGG pathway enrichment analysis suggested that the mechanism of action of the chemical constituents of celery seed might be involved in several pathways, notably the PI3K-Akt signaling pathway, Ras signaling pathway, and HIF-1 signaling pathway, respectively. Molecular docking and molecular dynamics revealed that apiumetin might be an important chemical that plays a key role in the pharmacological effect of celery seed. These results might be useful to select the Q-markers to control the quality of the products from celery seeds.Communicated by Ramaswamy H. Sarma.

Antimicrobial, Cytotoxic, and α-Glucosidase Inhibitory Activities of Ethanol Extract and Chemical Constituents Isolated from Homotrigona apicalis Propolis-In Vitro and Molecular Docking Studies.

The chemical investigation of Homotrigona apicalis propolis collected in Binh Dinh province, Vietnam, led to the isolation of nine compounds, including four sesquiterpenes: spathulenol (1), 1αH,5ßH-aromandendrane-4ß,10α-diol (2), 1ß,6α-dihydroxy-4(15)-eudesmene (3), and 1ßH,5ßH-aromandendrane-4α,10ß-diol (4); three triterpenes: acetyl oleanolic acid (5), 3α-hydroxytirucalla-8,24-dien-21-oic acid (6), and ursolic acid (7); and two xanthones: cochinchinone A (8) and α-mangostin (9). Sesquiterpens 1-4 and triterpene 6 were isolated for the first time from stingless bee propolis. Plants in the Cratoxylum and Aglaia genus were suggested as resin sources of the propolis sample. In the antibacterial activity evaluation, the EtOH extract only showed moderate activity on S. aureus, while the isolated compounds 7-9 showed good antibacterial activity, with IC50 values of 0.56 to 17.33 µg/mL. The EtOH extract displayed selective cytotoxicity against the A-549 cancer cell line, with IC50 values of 22.82 ± 0.86 µg/mL, and the xanthones 8 and 9 exhibited good activity against the KB, HepG-2, and A-549 cancer cell lines, with IC50 values ranging from 7.55 ± 0.25 µg/mL to 29.27 ± 2.07 µg/mL. The cytotoxic effects of xanthones 8 and 9 were determined by the inhibition of the EGFR and HER2 pathways using a molecular docking study. Compounds 8 and 9 displayed strong binding affinity with EFGR and HER2, with values of -9.3 to -9.9 kcal/mol. Compounds 5, 8, and 9 showed potential α-glucosidase inhibitory activities, which were further confirmed by computational studies. The binding energies of compounds 5, 8, and 9 were lower than that of arcabose.

Patient-provider relationships: Opioid use disorder and HIV treatment in Vietnam.

Background: The provider-patient relationship has been implicated as a positive force in health outcomes. This study examined the provider-patient relationship in the setting of integrated, partially-integrated, and non-integrated opioid use disorder (OUD) and HIV care models in Vietnam. Objective: To examine the provider-patient relationship in the setting of integrated, partially integrated, and non-integrated OUD and HIV treatment in North Vietnam. Methods: Between 2013 and 2018, we conducted face-to-face qualitative interviews with 44 patients living with HIV and OUD and 43 providers in northern Vietnam. These were analyzed using a semantic, inductive approach to qualitative thematic analysis. Results: Several themes were identified. 1) Trust was important to the patient-provider relationship and sensitive to provider attitudes and competence. 2) Patients perceived greater provider competence and understanding of patient health problems in integrated treatment. 3) Patient-provider relationships were initially superficial but deepened over time, facilitated by continuity of care. Conclusions: Patient perceptions of competence and respect were important to feeling cared for. Providers felt empathy and competence came with more experience caring for patients with OUD and HIV.

Effects of Nanofillers Based on Cetyltrimethylammonium-Modified Clays in a Polypropylene Nanocomposite.

Nanocomposites of hydrophobic organo-clay/polypropylene (organo-clay/PP) were efficiently developed through a solution-blending technique. For this, we utilized various smectite clays as host agents; namely, Na-montmorillonite (Mt, ~1000 nm), Na-fluorine mica (Mica, ~1500 nm), and Na-hectorite (Ht, ~60 nm) with varied sizes, layer charges, and aspect ratios. Such clays were functionalized with cetyltrimethylammonium (CTA) bromide via an intercalation technique to obtain hydrophobic organic clays. The as-made clay particles were further mixed with a PP/xylene solution; the latter was removed to obtain the final product of the CTA-clay/PP nanocomposite. An X-ray diffraction (XRD) analysis confirmed that there were no characteristic (001) diffraction peaks for CTA-Mica in the PP nanocomposites containing CTA-Mica, assuring the fact that the Mica layers could be completely exfoliated and thereby homogenously composited within the PP. On the other hand, the CTA-Mt and CTA-Ht incorporated composites had broader (001) peaks, which might have been due to the partial exfoliation of CTA-Mt and CTA-Ht in the composites. Among the three CTA-clay/PP nanocomposites, the CTA-Mica nanohybrid showed an enhanced thermal stability by ~42 °C compared to the intact host polymer matrix. We also noted that when the CTA-Mica content was ~9 mass % in the nanocomposites, the Young's modulus was drastically maximized to 69%. Our preliminary results therefore validated that out of the three tested clay-PP nanocomposites, the CTA-Mica nanofiller served as the best one to improve both the thermal and mechanical properties of the PP nanocomposites.

An approach based on gamma backscattering technique to measuring the density of liquid using the low-intensity radioactive source.

This work aims to develop a practical solution to measure the density of a liquid. Two purposes of this study: (1) using a low-activity source to measure the density of a liquid, and (2) simplifying the experimental arrangement to reduce the size and weight of the measuring system. The proposed solution is to develop a measurement technique without both detector and source collimators, while it considers an appropriate technique for analyzing the backscattering spectrum. To validate the proposed method, we used two groups of liquid: one group of liquids with a certified density and one group of liquids collected from the market. For the first group, the obtained results showed that the relative errors between the measured density and the reference one are below 6.8% and the uncertainties in density are below 4%, which confirms the feasibility of the proposed approach. For the second group, the liquids collected from the market include 70 percent alcohol, cooking oil, saltwater, fresh milk, diesel oil, dishwashing liquid, machine oil, and wine. The results obtained show that the relative errors between the densities determined by the proposed method and densities determined by the traditional method using density kit are less than 4.3%, the uncertainties in density when using the proposed method are below 3.2%. These results initially confirm that the proposed solution is completely applicable in measuring the density of a liquid.

Green extraction of apigenin and luteolin from celery seed using deep eutectic solvent.

In recent years, deep eutectic solvent (DES) has attracted a great deal of attention as an environmentally friendly solvent and could be used as an alternative to conventional solvents. In this study, 34 choline and betaine-based deep eutectic solvents were prepared and investigated the ability to extract apigenin and luteolin from the celery seed. The results showed that DES composed of betaine hydrochloride and propylene glycol had the best extraction efficiency. Using one factor at a time combined with response surface methodology, the optimal conditions of extraction were determined as follows: time of extraction: 19 min, extraction temperature: 75 °C, the water content in solvent: 40% (w/w). Antisolvent (water) combined with distillation was proposed as an efficient method to recover apigenin and luteolin from the DES extract. The relationship between components of DES and solubility of apigenin, luteolin was also established which was the starting point for the prediction of extractability of DES. Molecular dynamics revealed that betaine hydrochloride and propylene glycol could interact with each other by the formation of two types of hydrogen bond while water molecules might play an important role in the ability to dissolve apigenin and luteolin of DES.

Use of methamphetamine and alcohol among people with opioid use disorder and HIV in Vietnam: a qualitative study.

BACKGROUND: Heroin use continues to drive HIV transmission in Vietnam, but methamphetamine and alcohol use are growing rapidly and, as in other countries, polysubstance use is widespread. The objective of this study was to understand the interplay between heroin, methamphetamine, and alcohol use among people with opioid use disorder (OUD) and HIV in Vietnam. METHODS: We conducted 44 in-depth, face-to-face qualitative interviews with people with OUD and HIV who participated in the BRAVO trial of buprenorphine versus methadone in five Vietnam HIV clinics. Interviews probed participants' experiences of heroin, methamphetamine, and alcohol use and their interplay with HIV/OUD treatment. Interviews were professionally transcribed and analyzed using a thematic analysis approach. RESULTS: Of 44 participants interviewed 42 were male, on average 38.8 years of age, with 30 reporting a history of methamphetamine use and 33 reporting a history of alcohol use. Several themes emerged: 1) Methamphetamine and alcohol were perceived to have lower addiction potential than heroin 2) Social settings were key facilitators of alcohol and methamphetamine use 3) Some participants, but not all, used methamphetamine to help quit heroin 4) Consuming alcohol blunted the effects of heroin, while paradoxically serving as a catalyst for heroin use 5) Use of methamphetamine was perceived by many participants to be incompatible with treatment for HIV. CONCLUSIONS: Participant experiences reflected a significant impact of polysubstance use on treatment of HIV and OUD. Patterns of polysubstance use are subject to common preconceptions of alcohol and methamphetamine as having a low addictive potential, and these substances are deeply enmeshed in the social life of many people with OUD in Vietnam. Interventions to address complex social norms and potential harms of polysubstance use are urgently needed as the population of people receiving medication for OUD (MOUD) increases in Vietnam and globally. TRIAL REGISTRATION: BRAVO - NCT01936857 , September 2013.

ANN coupled with Monte Carlo simulation for predicting the concentration of acids.

The present study proposes a new approach for determining the concentration of acids. The method is based on the combination of Monte Carlo simulation and artificial neural network (ANN) technique for predicting the concentration of acids. Firstly, a Monte Carlo simulation model is validated based on the comparison of simulation data with experimental data. Then, the whole data derived from the Monte Carlo simulation using the MCNP code was used to train the ANN model. The trained ANN model was used to predict the percentage concentrations of 14 acid samples, which yields the maximum relative deviation between the predicted and the reference concentrations is less than 3.5%.