@Article{info:doi/10.2196/67052, author="Sardar, Sakshi and Coon, D. Cheryl and Kern, Scottie and Huynh, Huong and Stephenson, Diane and Abrams, Rubin Joshua and Lee, V. Grace and Ollivier, Cecile and Hedrick, A. Joseph and M{\"u}ller, LTM Martijn and Evers, W. Luc J. and Leyens, Lada and Hovinga, Collin and Ma, Chin Shu and Romero, Klaus", title="Advancing the Integration of Digital Health Technologies in the Drug Development Ecosystem", journal="J Med Internet Res", year="2025", month="Jul", day="31", volume="27", pages="e67052", keywords="digital health technologies", keywords="drug development", keywords="DHT", keywords="digital health", keywords="drugs", keywords="disease management", keywords="clinical research", keywords="technologies", keywords="frameworks", keywords="viewpoints", doi="10.2196/67052", url="https://www.jmir.org/2025/1/e67052" } @Article{info:doi/10.2196/69800, author="Braga, Melvin David and Rawal, Bharat", title="Harnessing AI and Quantum Computing for Revolutionizing Drug Discovery and Approval Processes: Case Example for Collagen Toxicity", journal="JMIR Bioinform Biotech", year="2025", month="Jul", day="22", volume="6", pages="e69800", keywords="generative AI", keywords="quantum computing", keywords="computational data", keywords="new drug discovery", keywords="computer-aided drug discovery", keywords="artificial intelligence", doi="10.2196/69800", url="https://bioinform.jmir.org/2025/1/e69800" } @Article{info:doi/10.2196/71675, author="Olatoye, Isaac Toba", title="Discovery of Novel Inhibitors of HMG-CoA Reductase Using Bioactive Compounds Isolated From Cochlospermum Species Through Computational Methods: Virtual Screening and Algorithm Validation Study", journal="JMIRx Bio", year="2025", month="Jul", day="10", volume="3", pages="e71675", keywords="HMGR", keywords="statins", keywords="hypercholesterolemia", keywords="cochlospermum", keywords="phytochemicals", keywords="molecular docking", keywords="3-hydroxy-3-methylglutaryl coenzyme-A reductase", abstract="Background: Cholesterol biosynthesis is a critical pathway in cellular metabolism, with 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) catalyzing its committed step. HMGR inhibition has been widely explored as a therapeutic target for managing hypercholesterolemia, and statins are the most commonly used competitive inhibitors. However, the search for novel, natural HMGR inhibitors remains a vital area of research, due to the adverse effects associated with long-term statin use. Cochlospermum planchonii and Cochlospermum tinctorium are West African medicinal plants traditionally used to treat metabolic disorders, including dyslipidemia. Despite their usefulness, the specific bioactive compounds responsible for these effects are currently poorly characterized, justifying further investigations. Objective: This study investigates the potential of phytochemicals from Cochlospermum planchonii and Cochlospermum tinctorium as natural inhibitors of human HMGR using molecular docking techniques. Methods: A total of 84 phytochemicals from 2 species of Cochlospermum as reported in literature, were evaluated as potential inhibitors of HMGR. Using DataWarrior software, their drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties were screened in accordance with Lipinski's Rule of Five. The 32 compounds that met the criteria were docked on PyRx against the HMG-binding site of HMGR, alongside atorvastatin (native ligand) and 6 known statins, which served as control ligands. Results: Docking analysis of their two best binding modes showed that 10 (31.3\%) out of the 32 screened phytochemicals demonstrated strong binding affinities and interactions with the HMG-binding pocket (residues 682?694) of HMGR, with binding energy ($\Delta$G) scores ranging from ?4.6 to ?6.0 kcal/mol, comparable to or exceeding those of statins (?4.6 to ?5.7 kcal/mol). Their docking scores (?13.272 to ?32.103) also compared favorably with those of statins (?25.939 to ?36.584). Interestingly, 3-O-methylellagic acid (ID\_13915428) demonstrated the strongest interaction, forming 26 binding interactions with the HMG-binding pocket residues, more than any compound, including statins. One-way ANOVA of the mean and SEM of the binding affinity scores for the phytochemicals and statins (9 replicates each) indicated a statistically significant difference at P<.05 (total sample size n=153; actual P=.0001). Conclusions: This study is the first to virtually screen and identify specific bioactive compounds isolated from Cochlospermum planchonii and Cochlospermum tinctorium with potential cholesterol-lowering effects in humans. The findings not only support the traditional use of these plants in West Africa to manage dyslipidemia and other ailments, but also present the phytochemicals as promising drug candidates for further optimization as natural inhibitors of HMGR. However, while this study provides valuable computational insights into the molecular interactions of the compounds with HMGR, further advanced computational, in vitro, and in vivo studies are still necessary to validate their inhibitory potential and therapeutic applications. ", doi="10.2196/71675", url="https://bio.jmirx.org/2025/1/e71675" } @Article{info:doi/10.2196/66197, author="Beleva, Elina and Diukendjieva, Antonia and Pajeva, Ilza and Tsakovska, Ivanka", title="Identification of Compounds With Potential Dual Inhibitory Activity Against Drug Efflux Pumps in Resistant Cancer Cells and Bacteria: Protocol for a Systematic Review", journal="JMIR Res Protoc", year="2025", month="Jun", day="5", volume="14", pages="e66197", keywords="drug resistance", keywords="bacterial", keywords="neoplasm", keywords="reversing agents", keywords="efflux pump inhibitors", keywords="cancer cells", keywords="bacteria", keywords="protocols", keywords="systematic reviews", keywords="antimicrobial", keywords="PRISMA-P", abstract="Background: Drug efflux mediated by transporter proteins is one of the major mechanisms conferring multidrug resistance (MDR) to antimicrobial agents in bacteria and to chemotherapeutics in cancer cells. Therefore, the development or identification of efflux modulators represents a promising strategy to overcome the resistant phenotype. Various chemical compounds have been tested in experimental studies as reversal agents either in combination with antimicrobial or anticancer drugs and have shown sensitizing activity in resistant bacteria or cancer cell lines. Owing to the common resistance mechanisms exhibited by bacteria and cancer cells, the identification of chemical agents with dual reversal activity offers a strategy to simultaneously combat antibacterial and cancer multidrug resistance. Objective: This study aims to conduct a systematic review to identify compounds that have shown activity in reversing antibacterial as well as cancer MDR mediated by drug efflux pumps and to summarize their structural and biological parameters responsible for the interactions with drug efflux pumps. Methods: The protocol has been developed in accordance with PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guidelines. We searched PubMed and Scopus databases for abstracts of full-text peer-reviewed journal papers in English language published between January 2012 and September 2024. Only studies from in vitro experiments were considered if they used methods to detect changes in antibiotic sensitivity of resistant bacteria and chemosensitivity of resistant cancer cells upon treatment with efflux pump inhibitors. A total of 763 unique records were identified. Of them, 246 were selected for full-text review based on the eligibility criteria. Abstract screening was performed by 2 independent reviewers. As of March 1, 2025, the systematic review is at the stage of completed abstract screening. The next steps of the full-text review, study selection, data extraction, and risk of bias assessment will be performed by 2 independent reviewers as well. Main data elements will include a structural identifier of the tested inhibitor, bacterial strain, cancer cell line, methods proving reversal activity, half maximal inhibitory concentration, and other relevant quantitative estimates of reversal activity. Data synthesis will be performed as a narrative summary and the content will be curated in tabular and graphical form. Results: We anticipate that results from this study will outline the potential of various compounds to act as dual chemosensitizers and reverse both antimicrobial and cancer MDR. Conclusions: Our review will highlight the overlap between efflux pumps' inhibition as a strategy to combat MDR in both bacterial and cancer cells and it will provide structured data for rational drug design of dual efflux pump inhibitors. Trial Registration: PROSPERO CRD42024548350; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024548350 International Registered Report Identifier (IRRID): PRR1-10.2196/66197 ", doi="10.2196/66197", url="https://www.researchprotocols.org/2025/1/e66197" } @Article{info:doi/10.2196/63683, author="Cagnacci, Angelo and Grandi, Giovanni and Capobianco, Giampiero and Fulghesu, Maria Anna and Morgante, Giuseppe and Biondelli, Vincenzo and Piccolo, Elena and Casolati, Elena and Mangrella, Mario", title="Effects of a Monophasic Hormonal Contraceptive With Norgestimate+Ethinyl Estradiol on Menstrual Bleeding: Protocol and Design of a Multicenter, Prospective, Open-Label, Noncomparative Study in Italy", journal="JMIR Res Protoc", year="2025", month="Mar", day="31", volume="14", pages="e63683", keywords="combined oral contraceptive", keywords="ethinyl estradiol", keywords="menstrual cycle", keywords="monophasic", keywords="norgestimate", keywords="hormonal contraceptive", keywords="menstrual health", keywords="Italy", keywords="women's health", keywords="patient-reported outcomes", keywords="methodology", keywords="observational study", keywords="reproductive health", keywords="data analysis", keywords="assessment", abstract="Background: Norgestimate (NGM) is a progestin with negligible androgenic activity that is available in combination with ethinyl estradiol (EE) as a monophasic combined oral contraceptive (COC). It has been more than 30 years since a clinical study evaluated the effects of monophasic NGM/EE on menstrual cycle characteristics in healthy women, and in the interim, there has been growing recognition that clinical trials of contraceptives should evaluate a wide range of potential positive and negative impacts for users. Objective: The aim of this study is to investigate menstrual cycle control during the use of a monophasic COC formulation containing NGM 0.25 mg and EE 0.035 mg (Effimia; Italfarmaco SpA), using established methodologies as well as patient-reported outcomes. Methods: This is a prospective observational study being undertaken in a target population of 228 healthy Italian women aged 18-35 years who are starting oral contraception for the first time or switching from another COC. The participants are asked to complete a diary for 6 cycles recording information about their menstrual cycles (frequency, duration, regularity, estimated flow volume, and breakthrough bleeding), any unscheduled bleeding, and an evaluation of dysmenorrhea, using a 100-mm visual analog scale from 0=no pain to 100=very severe pain, and any adverse events. Compliance is assessed after 3 and 6 months via returned medication. The primary end point is the change from baseline in the rate of intermenstrual bleeding during the sixth cycle. At baseline, 3 months, and 6 months, acne will also be assessed using the Global Acne Grading Scale, and participants will complete a Profile of Mood State to assess premenstrual syndrome and the Female Sexual Function Index to evaluate the quality of their sex life. A subgroup of 28 participants at 1 site (Genoa) is also providing a blood sample for the assessment of metabolic, endocrine, and coagulation parameters. Results: Study enrollment began in July 2023 and is expected to be complete by December 2024. Data analysis is expected to be complete by October 2025. Conclusions: This study into the effects of monophasic NGM/EE 0.25/0.035 mg on menstrual characteristics in healthy Italian women will provide up-to-date data on these effects and includes assessments of a range of other parameters, such as acne severity and patient-reported outcomes, in line with recent international consensus recommendations. Trial Registration: ClinicalTrials.gov NCT06067256; https://clinicaltrials.gov/study/NCT06067256 and EudraCT 2021-003027-15; https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003027-15/IT International Registered Report Identifier (IRRID): DERR1-10.2196/63683 ", doi="10.2196/63683", url="https://www.researchprotocols.org/2025/1/e63683" }