39 research outputs found
Immunoinformatics and reverse vaccinology approach in designing a novel highly immunogenic multivalent peptide-based vaccine against the human monkeypox virus
Background: Monkeypox is a highly infectious zoonotic disease, often resulting in complications ranging from respiratory illnesses to vision loss. The escalating global incidence of its cases demands prompt attention, as the absence of a proven post-exposure treatment underscores the criticality of developing an effective vaccine.Methods: Interactions of the viral proteins with TLR2 and TLR4 were investigated to assess their immunogenic potentials. Highly immunogenic proteins were selected and subjected to epitope mapping for identifying B-cell and MHC class I and II epitopes. Epitopes with high antigenicity were chosen, considering global population coverage. A multi-target, multi-epitope vaccine peptide was designed, incorporating a beta-defensin 2 adjuvant, B-cell epitopes, and MHC class I and II epitopes.Results: The coordinate structure of the engineered vaccine was modeled and validated. In addition, its physicochemical properties, antigenicity, allergenicity, and virulence traits were evaluated. Molecular docking studies indicated strong interactions between the vaccine peptide and the TLR2 receptor. Furthermore, molecular dynamics simulations and immune simulation studies reflected its potent cytosolic stability and robust immune response dynamics induced by the vaccine.Conclusion: This study explored an innovative structure-guided approach in the use of immunoinformatics and reverse vaccinology in pursuit of a novel multi-epitope vaccine against the highly immunogenic monkeypox viral proteins. The simulation studies indicated the engineered vaccine candidate to be promising in providing prophylaxis to the monkeypox virus; nevertheless, further in vitro and in vivo investigations are required to prove its efficacy
Predictive Modeling for Breast Cancer Classification in the Context of Bangladeshi Patients: A Supervised Machine Learning Approach with Explainable AI
Breast cancer has rapidly increased in prevalence in recent years, making it
one of the leading causes of mortality worldwide. Among all cancers, it is by
far the most common. Diagnosing this illness manually requires significant time
and expertise. Since detecting breast cancer is a time-consuming process,
preventing its further spread can be aided by creating machine-based forecasts.
Machine learning and Explainable AI are crucial in classification as they not
only provide accurate predictions but also offer insights into how the model
arrives at its decisions, aiding in the understanding and trustworthiness of
the classification results. In this study, we evaluate and compare the
classification accuracy, precision, recall, and F-1 scores of five different
machine learning methods using a primary dataset (500 patients from Dhaka
Medical College Hospital). Five different supervised machine learning
techniques, including decision tree, random forest, logistic regression, naive
bayes, and XGBoost, have been used to achieve optimal results on our dataset.
Additionally, this study applied SHAP analysis to the XGBoost model to
interpret the model's predictions and understand the impact of each feature on
the model's output. We compared the accuracy with which several algorithms
classified the data, as well as contrasted with other literature in this field.
After final evaluation, this study found that XGBoost achieved the best model
accuracy, which is 97%.Comment: Accepted for the Scientific Reports (Nature) journal. 32 pages, 12
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The combination of multi-approach studies to explore the potential therapeutic mechanisms of imidazole derivatives as an MCF-7 inhibitor in therapeutic strategies
Breast cancer covers a large area of research because of its prevalence and high frequency all over the world. This study is based on drug discovery against breast cancer from a series of imidazole derivatives. A 3D-QSAR and activity atlas model was developed by exploring the dataset computationally, using the machine learning process of Flare. The dataset of compounds was divided into active and inactive compounds according to their biological and structural similarity with the reference drug. The obtained PLS regression model provided an acceptable r2 = 0.81 and q2 = 0.51. Protein-ligand interactions of active molecules were shown by molecular docking against six potential targets, namely, TTK, HER2, GR, NUDT5, MTHFS, and NQO2. Then, toxicity risk parameters were evaluated for hit compounds. Finally, after all these screening processes, compound C10 was recognized as the best-hit compound. This study identified a new inhibitor C10 against cancer and provided evidence-based knowledge to discover more analogs
Chemical composition and potential antioxidant, anti-inflammatory, and analgesic efficacy of Cistus albidus L.
This study aims to assess the chemical composition of the aqueous extract of Cistus albidus L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti-inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in C. albidus seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect in vivo, and albumin denaturation to evaluate the anti-inflammatory effect in vitro. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic efficacy in vivo.
Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg–1), quercitrin (1,235.8 mg kg–1) and gallic acid (628. 2 mg kg–1). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of C. albidus. The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proanthocyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL–1 for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that C. albidus extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant
Porous and highly responsive polymeric fabricated nanometrices for solubility enhancement of acyclovir; characterization and toxicological evaluation
Solubility is one of the major factors which affects several therapeutic mioeties in terms of their therapeutic efficacy. In the current study, we presented a porous and amorphous nanometrices system for the enhancement of the solubility of acyclovir. The polymeric network was fabricated by crosslinking polyethylene glycol-6000, polycaprolactone, and β-cyclodextrin with methacrylic acid by optimizing free radical polymerization technique using methylene bisacrylamide as a crosslinking agent. The formulated nanometrices were then characterized by zetasizer, FTIR, PXRD, Scanning electron microscopy, Thermogravimetric analysis, swelling, sol-gel fraction, drug loading, stability, solubility, and in-vitro dissolution analysis. Since the formulated system has to be administered orally, therefore to determine the in-vivo biocompatibility, nanometrices were administered orally to experimental animals. SEM images provided a rough and porous structure while PXRD showed an amorphous diffractogram of the unloaded and loaded nanometrices. Moreover, the particle size of the optimum loaded formulation was 25 nm higher than unloaded nanometrices due to the repulsion of the loaded drug. A significant loading of the drug with enhanced solubility and dissolution profiles was observed for the poorly soluble drug. The dissolution profile was quite satisfactory as compared to the marketed brand of drug which depicted that the solubility of the drug has been enhanced. Toxicity study conducted on rabbits confirmed the biocompatibility of the nanometrices. The systematic method of preparation, enhanced solubility and high dissolution profile of the formulated nanometrices may be proved as a promising technique to enhance the solubility of poorly aqueous soluble therapeutic agents
Isolation, identification, and characterization of resistant bacteria to antibiotics from pharmaceutical effluent and study of their antibiotic resistance
Pharmaceutical effluents primarily enter aquatic environments through the discharge of treated and untreated wastewater from various sources, including hospitals, pharmaceutical manufacturing facilities, and households. Microbes sourced from pharmaceutical effluents such as Pseudomonas spp. pose a significant public health concern because of their high levels of resistance to multiple drugs and extreme multidrug resistance. Therefore, the present study was conducted for the isolation, identification, and molecular characterization of selected isolates from pharmaceutical effluents and also determined their antibiotic sensitivity patterns. From June 2016 to March 2017, a study was conducted on four well-known pharmaceutical companies specializing in antibiotic production in Dhaka and Gazipur. Four wastewater samples were collected from various origins and then brought to the Bacteriology laboratory for microbiological examination. Twelve pure isolates were obtained and characterized through cultural and biochemical tests while molecular identification of Pseudomonas spp. was performed using the 16S rRNA gene sequence. Twelve commercially available antibiotics were used for antibiotic sensitivity tests using Kirby-Bauer disk diffusion methods. We isolated the most predominant isolates, Pseudomonas aeruginosa (41.67%), followed by Bacillus spp. (33.33%) and Staphylococcus spp. (25%) respectively. Among 12 antibiotics, ciprofloxacin is 100% sensitive against P. aeruginosa, while the remaining 11 antibiotics are 100% resistant. Bacillus spp. showed 100% resistance to all antibiotics while 50% sensitive to vancomycin and 100% to chloramphenicol, respectively. Staphylococcus spp. was 100% resistant to all antibiotics. Our research suggested that P. aeruginosa is the reservoir of antibiotic resistance genes and spreads disease to humans from the environment. The findings of this study, i.e., the isolation, identification, and characterization of antibiotic-resistant bacteria from pharmaceutical effluent have highlighted, comprehended, and mitigated the dissemination of antibiotic resistance and opportunistic bacteria
Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays
Adenanthera pavonina is a medicinal plant with numerous potential secondary metabolites showing a significant level of antidiabetic activity. The objective of the current study was to identify potential phytochemicals from the methanolic leaf extract of Adenanthera pavonina as therapeutic agents against diabetes mellitus using GC-MS and in silico methods. The GC-MS analysis of the leaf extract revealed a total of 17 phytochemicals. Molecular docking was performed using these phytochemicals, targeting the mutated insulin receptor tyrosine kinase (5hhw), which inhibits glucose uptake by cells. Diazoprogesterone (−9.2 kcal/mol), 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid (−6.9 kcal/mol), and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] (−6.6 kcal/mol) exhibited better binding with the target protein. The ADMET analysis was performed for the top three compounds with the best docking scores, which showed positive results with no observed toxicity in the AMES test. Furthermore, the molecular dynamics study confirmed the favorable binding of Diazoprogesterone, 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] with the receptor throughout the 100 ns simulation period
Anti-parasitic drug discovery against Babesia microti by natural compounds: an extensive computational drug design approach
Tick-borne Babesiosis is a parasitic infection caused by Babesia microti that can infect both animals and humans and may spread by tick, blood transfusions, and organ transplantation. The current therapeutic options for B. microti are limited, and drug resistance is a concern. This study proposes using computational drug design approaches to find and design an effective drug against B. microti. The study investigated the potentiality of nine natural compounds against the pathogenic human B. microti parasite and identified Vasicinone and Evodiamine as the most promising drugs. The ligand structures were optimized using density functional theory, molecular docking, molecular dynamics simulations, quantum mechanics such as HOMO–LUMO, drug-likeness and theoretical absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacokinetics characteristics performed. The results showed that Vasicinone (−8.6 kcal/mol and −7.8 kcal/mol) and Evodiamine (−8.7 kcal/mol and −8.5 kcal/mol) had the highest binding energy and anti-parasitic activity against B. microti lactate dehydrogenase and B. microti lactate dehydrogenase apo form. The strongest binding energy was reported by Vasicinone and Evodiamine; the compounds were evaluated through molecular dynamics simulation at 100 ns, and their stability when they form complexes with the targeted receptors was determined. Finally, the pkCSM web server is employed to predict the ADMET qualities of specific molecules, which can help prevent negative effects that arise from taking the treatment. The SwissADME web server is used to assess the Lipinski rule of five and drug-likeness properties including topological polar surface area and bioavailability. The Lipinski rule is used to estimate significant drug-likeness. The theoretical pharmacokinetics analysis and drug-likeness of the selected compounds are confirmed to be accepted by the Lipinski rule and have better ADMET features. Thus, to confirm their experimental value, these mentioned molecules should be suggested to carry out in wet lab, pre-clinical, and clinical levels
Experimental and in silico evaluation of Carthamus tinctorius L. oil emulgel: a promising treatment for bacterial skin infections
PurposeThe current study aimed to develop a topical herbal emulgel containing Carthamus tinctorius L. (CT) oil extract, which has been scientifically proven for its antibacterial and antioxidant activities for the ailment of bacterial skin infections.MethodThe CT emulgel was formulated by response surface methodology (RSM) and was evaluated by various parameters like extrudability, spreadability, pH, viscosity, and antibacterial and antioxidant activities. Molecular docking was also performed using AutoDock.ResultsAmong all formulated CT emulgels, F9 and F8 were optimized. Optimized formulations had shown good spreadability and extrudability characteristics. Sample F8 had % inhibition of 42.131 ± 0.335, 56.720 ± 0.222, and 72.440 ± 0.335 at different concentrations. Sample F9 had % inhibition of 26.312 ± 0.280, 32.461 ± 0.328, and 42.762 ± 0.398 at concentrations of 250 µg/ml, 500 µg/ml, and 1,000 µg/ml, respectively, which shows that both samples F8 and F9 have significant antioxidant potential. Optimized CT emulgels F8 and F9 had significant antibacterial activity against Staphylococcus aureus and Escherichia coli at p-value = 0.00, the Emulgel-F8 shows zone of inhibition of 24 mm for E-coli and 19 mm for S-aureus. Emulgel-F9 shows zone of inhibition of 22 mm for E-coli and 15 mm for S-aureus while pure CT- Oil extract shows zone of inhibition of 25 mm for E-coli and 20 mm for S-aureus and ciprofloxacin used as standard shows 36mm zone of inhibition against both E-coli and S-aureus. The comparative investigation through molecular docking binding affinities and interactions of ligands with various target proteins provides insights into the molecular processes behind ligand binding and may have significance for drug discovery and design for the current study.ConclusionThe current study suggests that C. tinctorius L.-based emulgel has good antioxidant and antibacterial activities against E. coli for the treatment of bacterial skin infections
Pharmacological activities of chemically characterized essential oils from Haplophyllum tuberculatum (Forssk.)
The present work aimed at characterizing the phytochemical composition of Haplophyllum tuberculatum essential oil (HTEO), assessing its antifungal activity against various fungal strains, evaluating its insecticidal and repulsive properties against Callosobruchus maculatus, and determine its antioxidant capacity. To this end, Gas chromatography-mass spectrometry analysis detected 34 compounds in HTEO, with β-Caryophyllene being the major constituent (36.94%). HTEO demonstrated predominantly modest antifungal effects, however, it sustains notable activity, particularly against Aspergillus flavus, with an inhibition rate of 76.50% ± 0.60%. Minimum inhibitory concentrations ranged from 20.53 ± 5.08 to 76.26 ± 5.08 mg/mL, effectively inhibiting fungal growth. Furthermore, the antifungal, and antioxidant activities of HTEO were evaluated in silico against the proteins Aspergillus flavus FAD glucose dehydrogenase, and beta-1,4-endoglucanase from Aspergillus niger, NAD(P)H Oxidase. Moreover, HTEO displayed strong insecticidal activity against C. maculatus, with contact and inhalation tests yielding LC50 values of 30.66 and 40.28 μL/100g, respectively, after 24 h of exposure. A dose of 5 μL/100g significantly reduced oviposition (48.85%) and inhibited emergence (45.15%) compared to the control group. Additionally, HTEO exhibited a high total antioxidant capacity of 758.34 mg AAE/g EO, highlighting its antioxidant potential. Insilico results showed that the antifungal activity of HTEO is mostly attributed to γ-Cadinene and p-Cymen-7-ol, while antioxidant is attributed to α-Terpinyl isobutyrate displayed. Overall, HTEO offers a sustainable and environmentally friendly alternative to synthetic products used to manage diseases