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A Data Mining Approach on Polypharmacy and Drug-drug Interactions of Common Diabetes Medications
Available online: 17 April 2025More LessBackgroundWhen managing diabetes, polypharmacy the use of several drugs simultaneously to obtain the best possible glucose control is typical. Drug-drug interactions (DDIs), which can result in side effects and reduced treatment efficacy, have increased.
ObjectiveThis study evaluated the data mining approach of polypharmacy-based drug-drug interactions for common diabetes medication.
MethodsTo identify publications that met the inclusion criteria, several scientific reviews and research papers were searched, including Scopus, Web of Science, Google Scholar, PubMed, Science Direct, Springer Link, and NCBI, using keywords such as diabetes, drug-drug interaction, polypharmacy, data mining, and herbal interaction.
ResultsMany important drug-drug interactions among popular anti-diabetic drugs have been identified using data mining. Using iodinated contrast media and metformin together increased the risk of lactic acidosis, and using NSAIDs and sulfonylureas simultaneously increased the risk of hypoglycemia. A higher incidence of DDIs was found in an analysis of elderly individuals and those with several comorbidities. Predictive models have demonstrated high sensitivity and accuracy in detecting possible DDIs from patient and drug data.
ConclusionFinding and evaluating DDIs in polypharmacy related to diabetes care are made possible through data mining. These results could potentially improve patient safety by influencing more individualized and cautious prescription techniques. The improvement of these methods and their application in standard clinical practice should be the main goal of future studies.
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Exploring the Gut-Brain Axis: Microbiome Contributions to Pathophysiology of Attention Deficit Hyperactivity Disorder and Potential Therapeutic Strategies
Authors: Manasi Phatak, Bhavi Nair, Urvashi Soni and Rohini PujariAvailable online: 08 April 2025More LessAttention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by symptoms of hyperactivity, inattention, and impulsivity, significantly impacting individuals' daily functioning and quality of life. This manuscript explores the intricate relationship between the gut microbiome and ADHD, emphasizing the role of the gut-brain axis, a bidirectional communication pathway linking the central nervous system (CNS) and the gastrointestinal tract (GIT). The composition of gut microbiota influences several physiological processes, including immune function, metabolism, and the production of neuroactive metabolites, which are critical for cognitive functions such as memory and decision-making. The review discusses alternative therapeutic options, including dietary modifications, synbiotics, and specific diets like the ketogenic diet, which may offer promising outcomes in managing ADHD symptoms. Further research is necessary to establish the efficacy and mechanisms of action of synbiotics and dietary interventions, despite preliminary studies suggesting their potential benefits. This review article aims to provide a comprehensive overview of the current understanding of the gut microbiome's impact on ADHD, highlighting the need for continued investigation into innovative treatment strategies that leverage the gut-brain connection.
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Effect of Wuzhi Capsule (WZC) on the Pharmacokinetics of Tacrolimus in Renal Transplantation Recipients
Authors: Weiyue Zhang, Ruidong Wang, Lin Li, Jiani Chen, Jingwen Zhai, Wei Wang, Shiyi Liu, Hong Liu, Hua Wei and Shu HanAvailable online: 19 March 2025More LessBackgroundPrevious studies have shown that WZC can increase tacrolimus blood concentration when co-administered. However, limited knowledge exists regarding the pharmacokinetics of both tacrolimus and the bioactive lignans in WZC when administered simultaneously in renal transplantation patients.
AimsThis study aimed to investigate the pharmacokinetics of tacrolimus and multiple bioactive lignans in Wuzhi capsule (WZC) when co-administered with 5 bioactive components in renal transplantation recipients.
ObjectiveThe objective of this study was to develop a method for simultaneous quantification of tacrolimus and multiple bioactive lignans in WZC using liquid-liquid extraction followed by LC-MS/MS analysis.
MethodsA liquid-liquid extraction method combined with LC-MS/MS analysis was developed for simultaneous quantification of tacrolimus and multiple bioactive lignans in WZC. Human whole blood samples were analyzed, and the accuracy and precision of the method were evaluated.
ResultsThe developed method showed good linearity and accuracy for the quantification of tacrolimus and bioactive lignans in WZC. Pharmacokinetic analysis revealed significant effects of WZC co-administration on both V/F and CL/F in renal transplantation patients.
ConclusionThis study demonstrated that simultaneous administration of WZC had notable effects on the pharmacokinetics of tacrolimus and bioactive lignans in renal transplantation patients. The developed method proved to be reliable and sensitive for determining the whole blood concentrations of tacrolimus and WZC, making it suitable for pharmacokinetic studies in transplant patients.
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Prediction of Pharmacokinetics of Valeric Acid: Alternative Tool to Minimize Animal Studies
Authors: Bindu Kumari, Dhananjay Kumar Singh, Ravi Bhushan Singh and Gireesh Kumar SinghAvailable online: 19 March 2025More LessBackgroundThe use of computer-aided toxicity and Pharmacokinetic (PK) prediction studies are of significant interest to pharmaceutical industries as a complementary approach to traditional experimental methods in predicting potential drug candidates.
MethodsIn the present study, in-silico pharmacokinetic properties (ADME), drug-likeness, and toxicity profiles of valeric acid were examined using SwissADME and ADMETlab web tools.
ResultsThe drug-likeness prediction results revealed that valeric acid adheres to the Lipinski rule, Pfizer rule, and GlaxoSmithKline (GSK) rule. From a pharmacokinetic perspective, valeric acid is anticipated to have the best absorption profile including cell permeability and bioavailability. Plasma Protein Binding (PPB) and Blood–Brain Barrier (BBB) permeability may have a positive effect on Central Nervous System modulating (CNS). There is a minimal chance of it being a substrate for cytochrome P2D6 (CYP). Except for a “very slight risk” for eye corrosion and eye irritation, none of the well-known toxicities in valeric acid were anticipated, which was compatible with wet-lab data. The molecule possesses no environmental hazard as analyzed with common indicators such as bio-concentration factor and LC50 for fathead minnow and daphnia magna. The toxicity parameters identified valeric acid as nontoxic to androgen receptors, antioxidant response element, mitochondrial membrane receptor, heat shock element, and tumor suppressor protein (p53), except Peroxisome Proliferator-Activated Receptor- gamma (PPAR-γ) was found to be medium toxicity. However, no toxicophores were found out of seven parameters.
ConclusionOverall, the ADMETLab evaluated that valeric acid has favorable pharmacokinetic and drug-likeness profiles, making it a promising drug candidate for new drug development.
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Comparative in Vitro Metabolic Profile Study of Five Cathinone Derivatives
Authors: Zexuan Li, Sufang Xiang, Tian Zheng, Guoping Wu and Liang WuAvailable online: 17 March 2025More LessBackgroundCathinone derivatives as new psychoactive substances have attracted worldwide attention in recent years. They have strong excitatory effects on the human central nervous system, which is extremely abusive and harmful. As they are easy to be structurally modified, and rapidly metabolized and excreted after taken, clarifying their metabolic profile is of significant importance to provide useful information for their identification or forensic purposes.
ObjectiveIn this paper, a comparative in vitro metabolic profile study of five cathinone derivatives (4/3/2-methylmethcathinone and 4/3-methoxymethcathinone) was performed, including their metabolic stability in the simulated gastrointestinal tract, mass spectrometry fragmentation behavior, possible metabolic pathways and metabolites in human liver microsomal incubation system, and revealing the key metabolic enzyme isoforms involving in their biotransformation.
MethodsIn vitro incubation was performed in simulated gastric/intestinal fluid and human liver microsomes, fragmentation behavior study and metabolite identification were investigated by LC-Q-TOF/MS, and metabolic stability study, along with metabolic enzyme screening were analyzed using LC-MS/MS.
ResultsAlmost all the cathinone derivatives tested were stable in the simulated gastric/intestinal fluid; characteristic fragmentation pathway and diagnostic fragment ions of the cathinone derivatives were analyzed; the key metabolic pathways of 4/3-methylmethcathinone and 4/3-methoxymethcathinone revealed were hydroxylation and demethylation, which were catalyzed by CYP2D6. The methyl-substituted position would significantly affect the metabolic pathway of the methylmethcathinone.
ConclusionThis study revealed the mass spectral fragmentation pattern and the in vitro metabolic behavior of the selected cathinone derivatives, providing meaningful information and scientific evidence in predicting their metabolic potential in vivo, and also promoting their analysis, detection, and clinical use.
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Transformative CRISPR-Cas9 Technologies: A Review of Molecular Mechanisms, Precision Editing Techniques, and Clinical Progress in Sickle Cell Disease
Authors: Komal, Prabhjot Kaur, Nidhi Arora, Jyotiram A. Sawale and Amandeep SinghAvailable online: 05 March 2025More LessSickle cell disease (SCD) is a hereditary blood disorder resulting from the production of distorted hemoglobin molecules that cause red blood cells to adopt a sickle or crescent-like shape. This disease affects millions of people, particularly those of African, Mediterranean, Middle Eastern, or South Asian descent. In recent years, however, advancements in the CRISPR-Cas9 gene-editing systems have surged. CRISPR stands for clustered regularly interspaced short palindromic repeats, referring to a specific organization of short, partially repeated DNA sequences in prokaryotic genomes. The CRISPR-Cas9 technique is based on the type II CRISPR system of bacteria and involves the Cas9 nuclease, which is targeted to a particular genome section with the help of single-guide RNA. Initially used for random mutations and small sequence alterations, genome editing methods have advanced to achieve large-scale DNA segment manipulation. The BE and PE-type CRISPR-Cas9 genome editing variants provide new therapeutic options for genetic disorders, improving patients' prognosis. Curative gene editing using CRISPR-Cas9 technology to correct HBB gene mutations that cause SCD represents a revolutionary therapeutic development. These advances bring new hope to patients with previously untreatable diseases, potentially offering a future where genetic disorders can be addressed at their roots. A major objective of CRISPR technology is to enhance its precision and speed, both critical for effective gene editing. This review focuses on molecular mechanisms of CRISPR-Cas9 technology, CRISPR-Cas9-based approaches for HBB gene modification, clinical trials, patients with sickle cell disease, and advances in CRISPR technology for sickle cell disease.
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A Review on Drug-Metabolizing Enzymes, Transporters, and Gut Microbiota on Pharmacokinetics in High-Altitude Environment
Authors: Fangfang Qiu, Yuemei Sun, Wenbin Li and Rong WangAvailable online: 11 February 2025More LessThe most significant feature of the high-altitude environment is hypoxia, which affects the activity and expression of drug-metabolizing enzymes and transporters, leading to changes in pharmacokinetic parameters. Notably, gut microbiota is a hidden organ in the body. High-altitude hypoxia will change the composition and quantity of gut microbiota, affect drug metabolism, and change the bioavailability of drugs. This will provide a new perspective on changes in pharmacokinetics at high-altitude. Most studies have revealed that for drugs with low bioavailability and high clearance, the dosage may be increased accordingly. Conversely, the dosage may be reduced to achieve individualized medication. Therefore, this article reviews the changes and mechanisms of drug-metabolizing enzymes, transporters, and gut microbiota in a high-altitude environment and explains the impact of their changes on pharmacokinetics, aiming to provide theories and bases for the adjustment of drug dosage and the rational use of drugs in the clinic under high-altitude environment.
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