Detection of cardiac abnormalities from 12-lead ecg using complex wavelet sub-band features.

AIM OF THE STUDY: This research endeavours to optimize cardiac anomaly detection by introducing a method focused on selecting the most effective Daubechis wavelet families. The principal aim is to differentiate between cardiac states that are normal and abnormal by utilizing longer electrocardiogram (ECG) signal events based on the Apnea ECG dataset. Apnea ECG is often used to detect sleep apnea, a sleep disorder characterized by repeated interruptions in breathing during sleep. By using machine learning methods, such as Principal Component Analysis (PCA) and different classifiers, the goal is to improve the precision of cardiac irregularity identification. Used method. To extract important statistical and sub-band information from lengthy ECG signal episodes, the study uses a novel method that combines discrete wavelet transform with Principal Component Analysis (PCA) for dimension reduction. The methodology focuses on successfully categorizing ECG signals by utilizing several classifiers, including multilayer perceptron (MLP) neural network, Ensemble Subspace K-Nearest Neighbour(KNN), and Ensemble Bagged Trees, together with varied Daubechis wavelet families (db2, db3, db4, db5, db6). Brief Description of Results. The results emphasize the importance of the chosen Daubechis wavelet family, db5, and its superiority in ECG representation. The method distinguishes normal and abnormal ECG signals well on the Physionet Apnea ECG database. The Neural Network-based method accurately recognizes 100% of healthy signals and 97.8% of problematic ones with 98.6% accuracy. FINDINGS: The Ensemble Subspace K-Nearest Neighbour (KNN) and Ensemble Bagged Trees methods got 87.1% accuracy and 0.89 and 0.87 AOC curve values on this dataset, showing that the method works. Precision values of 0.96, 0.86, and 0.86 for MLP Neural Network, KNN Subspace, and Ensemble Bagged Trees confirm their robustness. These findings suggest wavelet families and machine learning can improve cardiac abnormality detection and categorization.

In Silico and In vitro Analysis of Phenolic Acids for Identification of Potential DHFR Inhibitors as Antimicrobial and Anticancer Agents.

BACKGROUND: DHFR is an indispensable enzyme required for the survival of almost all prokaryotic and eukaryotic cells, making it an attractive molecular target for drug design. OBJECTIVE: In this study, a combined in silico and in vitro approach was utilized to screen out potential anticancer and antimicrobial agents by using DHFR PDB ID 2W9S (for antimicrobial) and 1U72 (for anticancer). METHODS: Computational work was performed using Maestro Schrodinger Glide software. The DHFR inhibitory activity of the selected compounds was assessed using the DHFR test kit (CS0340-Sigma- Aldrich). RESULTS: Exhaustive analysis of in silico results revealed that some natural phenolic acids have a good docking score when compared to standards, i.e., trimethoprim and methotrexate, and have astonishing interactions with crucial amino acid residues available in the binding pocket of DHFR, such as Phe 92, Asp 27, Ser 49, Asn 18, and Tyr 98. In particular, digallic acid and chlorogenic acid have amazing interactions with docking scores of -9.9 kcal/mol and -9.6 kcal/mol, respectively, for the targeted protein 2W9S. Docking scores of -10.3 kcal/mol and -10.2 kcal/mol, respectively, for targeted protein 1U72. The best hits were then tested in vitro to evaluate the DHFR inhibitory activity of the compounds. DHFR inhibition activity results are in correlation with molecular docking results. CONCLUSION: In silico and in vitro results confirmed the good binding and inhibitory activity of some phenolic acids to the modeled target proteins. Among all the studied natural phenolic acids, chlorogenic acid, digallic acid, and rosmarinic acid appeared to be the most potential leads for future chemical alteration. This study can provide significant speculative guidance for the design and development of potent DHFR inhibitors in the future by using these compounds as leads.

In silico design of novel bioactive molecules to treat breast cancer with chlorogenic acid derivatives: a computational and SAR approach.

Introduction: Cancer is a vast group of diseases comprising abnormal cells that multiply and grow uncontrollably, and it is one of the top causes of death globally. Several types of cancers are diagnosed, but the incidence of breast cancer, especially in postmenopausal women, is increasing daily. Chemotherapeutic agents used to treat cancer are generally associated with severe side effects on host cells, which has led to a search for safe and potential alternatives. Therefore, the present research has been conducted to find novel bioactive molecules to treat breast cancer with chlorogenic acid and its derivatives. Chlorogenic acid was selected because of its known activity in the field. Methods: Several chlorogenic acid derivatives were subjected to computational studies such as molecular docking, determination of absorption, distribution, metabolism, and excretion (ADME), druglikeness, toxicity, and prediction of activity spectra for substances (PASS) to develop a potential inhibitor of breast cancer. The Protein Data Bank (PDB) IDs used for docking purposes were 7KCD, 3ERT, 6CHZ, 3HB5, and 1U72. Result: Exhaustive analysis of results has been conducted by considering various parameters, like docking score, binding energy, types of interaction with important amino acid residues in the binding pocket, ADME, and toxicity data of compounds. Among all the selected derivatives, CgE18, CgE11, CgAm13, CgE16, and CgE9 have astonishing interactions, excellent binding energy, and better stability in the active site of targeted proteins. The docking scores of compound CgE18 were -11.63 kcal/mol, -14.15 kcal/mol, and -12.90 kcal/mol against breast cancer PDB IDs 7KCD, 3HB5, and 1U72, respectively. The docking scores of compound CgE11 were -10.77 kcal/mol and -9.11 kcal/mol against breast cancer PDB IDs 3ERT and 6CHZ, respectively, whereas the docking scores of epirubicin hydrochloride were -3.85 kcal/mol, -6.4 kcal/mol, -8.76 kcal/mol, and -10.5 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5. The docking scores of 5-fluorouracil were found to be -5.25 kcal/mol, -3.43 kcal/mol, -3.73 kcal/mol, and -5.29 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5, which indicates the designed compounds have a better docking score than some standard drugs. Conclusion: Taking into account the results of molecular docking, drug likeness analysis, absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation, and PASS, it can be concluded that chlorogenic acid derivatives hold promise as potent inhibitors for the treatment of breast cancer.

Polyphenols: Natural Preservatives with Promising Applications in Food, Cosmetics and Pharma Industries; Problems and Toxicity Associated with Synthetic Preservatives; Impact of Misleading Advertisements; Recent Trends in Preservation and Legislation.

The global market of food, cosmetics, and pharmaceutical products requires continuous tracking of harmful ingredients and microbial contamination for the sake of the safety of both products and consumers as these products greatly dominate the consumer's health, directly or indirectly. The existence, survival, and growth of microorganisms in the product may lead to physicochemical degradation or spoilage and may infect the consumer at another end. It has become a challenge for industries to produce a product that is safe, self-stable, and has high nutritional value, as many factors such as physical, chemical, enzymatic, or microbial activities are responsible for causing spoilage to the product within the due course of time. Thus, preservatives are added to retain the virtue of the product to ensure its safety for the consumer. Nowadays, the use of synthetic/artificial preservatives has become common and has not been widely accepted by consumers as they are aware of the fact that exposure to preservatives can lead to adverse effects on health, which is a major area of concern for researchers. Naturally occurring phenolic compounds appear to be extensively used as bio-preservatives to prolong the shelf life of the finished product. Based on the convincing shreds of evidence reported in the literature, it is suggested that phenolic compounds and their derivatives have massive potential to be investigated for the development of new moieties and are proven to be promising drug molecules. The objective of this article is to provide an overview of the significant role of phenolic compounds and their derivatives in the preservation of perishable products from microbial attack due to their exclusive antioxidant and free radical scavenging properties and the problems associated with the use of synthetic preservatives in pharmaceutical products. This article also analyzes the recent trends in preservation along with technical norms that regulate the food, cosmetic, and pharmaceutical products in the developing countries.

DihydrofolateReductase (DHFR) Inhibitors: A Comprehensive Review.

BACKGROUND: Dihydrofolate reductase (DHFR) is an indispensable enzyme required for the survival of most prokaryotic and eukaryotic cells as it is involved in the biosynthesis of essential cellular components. DHFR has attracted a lot of attention as a molecular target for various diseases like cancer, bacterial infection, malaria, tuberculosis, dental caries, trypanosomiasis, leishmaniasis, fungal infection, influenza, Buruli ulcer, and respiratory illness. Various teams of researchers have reported different DHFR inhibitors to explore their therapeutic efficacy. Despite all the progress made, there is a strong need to find more novel leading structures, which may be used as better and safe DHFR inhibitors, especially against the microorganisms which are resistant to the developed drug candidates. OBJECTIVE: This review aims to pay attention to recent development, particularly made in the past two decades and published in this field, and pay particular attention to promising DHFR inhibitors. Hence, an attempt has been made in this article to highlight the structure of dihydrofolate reductase, the mechanism of action of DHFR inhibitors, most recently reported DHFR inhibitors, diverse pharmacological applications of DHFR inhibitors, reported in-silico study data and recent patents based on DHFR inhibitors to comprehensively portray the current scenery for researchers interested in designing novel DHFR inhibitors. CONCLUSION: A critical review of recent studies revealed that most novel DHFR inhibitor compounds either synthetically or naturally derived are characterized by the presence of heterocyclic moieties in their structure. Non-classical antifolates like trimethoprim, pyrimethamine, and proguanil are considered excellent templates to design novel DHFR inhibitors, and most of them have substituted 2,4-diamino pyrimidine motifs. Targeting DHFR has massive potential to be investigated for newer therapeutic possibilities to treat various diseases of clinical importance.

Phenolic Acids - Versatile Natural Moiety with Numerous Biological Applications.

BACKGROUND: Medicinal uses of natural phenolic acids and their synthetic derivatives have been augmented in recent years. Phenolic acids are chemically defined secondary plant metabolites and being moieties or leads are much versatile in nature with a wide scope of biological activities which seek the attention of researchers across the world to synthesize different derivatives of phenolic acids and screen them for their various biological properties. These compounds are of meticulous interest due to the properties they possess and their occurrence. Based on the convincing evidence reported in the literature, it is suggested that phenolic acids and their derivatives are promising molecules as a drug. OBJECTIVES: The present review article aims to bring together the information on the biosynthesis, metabolism, and sources of phenolic acids and emphasize the therapeutic potential of phenolic acid and its synthetic derivatives to comprehensively portray the current scenery for researchers interested in designing drugs for furthering this study. CONCLUSION: Phenolic acids being moieties or lead, are much versatile in nature as they possess a wide range of biological activities like antimicrobial, antioxidant, antiviral, antiulcer, antiinflammatory, antidiabetic, anticancer and many more offers researchers to explore more about these or many untapped benefits in the medicinal field. The information mentioned in this article will be helpful to the forthcoming researchers working in this area. Phenolic acids have massive potential to be investigated for novel medicinal possibilities and for the development of new chemical moieties to treat different diseases of clinical importance.