SmileGNN: Drug-Drug Interaction Prediction Based on SMILES and Graph Neural Network

Background: The use of multiple drugs at the same time can lead to unexpected adverse drug reactions. The interaction between drugs can be confirmed by routine in vitro and clinical trials. But it is difficult to test the drug-drug interaction widely and effectively before the drug is put into market. Therefore, the prediction of drug-drug interaction has become an important research in biomedical field.Results: In recent years, researchers have used deep learning to predict drug-drug interaction by using drug structural features and graph theory, and they have achieved a series of achievements. A drug-drug interaction prediction model SmileGNN is proposed in this paper. The structural features of drugs are constructed by using SMILES data. The topological features of drugs in knowledge graph are obtained by graph neural network. The structural and topological features of drugs are aggregated to predict the interaction of new drug pairs. Conclusions: The experimental results show that the model proposed in this paper combines a variety of data sources, and has better prediction performance compared with the existing prediction model of drug-drug interaction prediction. The most striking result is that five out of top ten predicted new interaction of drugs are verified from the latest database, which proves the credibility of SmileGNN.

Drug-Drug Interactions at Organic Cation Transporter 1

The interaction between drugs and various transporters is one of the decisive factors that affect the pharmacokinetics and pharmacodynamics of drugs. The organic cation transporter 1 (OCT1) is a member of the Solute Carrier 22A (SLC22A) family that plays a vital role in the membrane transport of organic cations including endogenous substances and xenobiotics. This article mainly discusses the drug-drug interactions (DDIs) mediated by OCT1 and their clinical significance.

The use of cannabidiol in the treatment of epilepsy in neuropediatric: a review of the new contributions

Background: Therapeutic cannabinoids are derived from marijuana, a plant of the cannabis genus. Cannabis sativa and Cannabis indica are the two main species. Cannabis plants contain more than 100 cannabinoids, but the biologically active and therapeutically researched ones are 9 tetrahydrocannabinol (THC) and cannabinol (CBD). Cannabinoids have been advocated for a number of neurological and psychiatric disorders, including multiple sclerosis, mood disorders, schizophrenia, Parkinson’s disease, dystonia, neuropathic pain, nausea, anorexia and epilepsy. Epilepsy is a chronic disease characterized by recurrent unprovoked seizures, affecting more than 50 million people worldwide, in the pediatric age group, with childhood epilepsy being one of the most serious and developing epileptic encephalopathies. Objective: In view of the above, the present study proposed to review the use of cannabidiol in the treatment of epilepsy in neuropediatric, with sources published between 2016-2020. Methods: To perform this research, PubMed (https://pubmeed.ncbi.nlm.nih. gov/) and Scielo (https://www.scielo.org/) databases were used as a search tool, using the Key words “Cannabidiol”, “Epilepsy”, “Cannabis” and “Children”. Results: So far, 11 articles related to the study have been identified, the vast majority being reviewed, with 9 articles obtained from PubMed and 2 acquired from Scielo. Selected articles show that CBD is an effective anticonvulsant in many acute animal models, but its antiepileptic mechanisms are not yet fully recognized. In studies with children in Canada and the United States, they suggest an improvement in the frequency of seizures and an improvement in quality of life, but the numbers are still small. Studies report that CBD is well tolerated, however, it causes sedation, diarrhea and decreased appetite. Conclusions: It is necessary to investigate the safety, pharmacokinetics and interaction between drugs already used by patients and CBD, also conducting more double-blind placebo-controlled trials to obtain conclusive data on their efficacy and safety in the most frequent epilepsies in children.

CORONAVIRUS AND ITS MAIN PROTEASE: AN INSIGHT FOR DRUGS DESIGN BY MOLECULAR DOCKING

Many virus need their sulphydryl groups to be reduced in order to be allowed to enter cells. SARS-CoV-2, which belongs to Coronaviridae family and is responsible for coronavirus disease 2019 or COVID-19, has cysteine-rich proteins in its capsid as the main CoV protease (MPRO), which must be intact and active maintaining the viral activity. Considering that MPRO is an important molecular target for development of antiviral drugs, this work motivation was the structural study of the possible ways of interaction between drugs and viral cysteines by molecular docking technique for design of new potential inhibitors of MPRO and its virulence.

Effect of You-Gui Yin on the Activities of Seven Cytochrome P450 Isozymes in Rats

You-Gui Yin (YGY) is a traditional Chinese medicine (TCM) decoction composed of eight Chinese herbs. The interaction between TCM and Western medicine has attracted much attention nowadays. It is therefore necessary to study the clinical application of YGY in combination with Western medicine from the perspective of metabolic enzymes. This study aims to investigate the effect of YGY on the activities of seven CYP450 isozymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) in rats. Twenty-four Sprague-Dawley (SD) rats were randomly divided into four groups: high, middle, and low-dose YGY-treated groups and the control group. They were given 13.78, 20.67, and 31 g/kg/d YGY decoction by oral administration and normal saline (10 mL/kg), respectively, for 14 days. Half an hour after the last administration, a mixed probe substrate (1 mg/kg) was administered by tail vein injection. Then, blood was taken from the venous plexus at different time points. The protein expression level of the CYP450 enzymes in the control and treatment groups was determined by western blot. The effect of YGY on the activity of CYP isoenzymes was studied by comparing the plasma pharmacokinetics between the control and treatment groups. Compared with the control group, YGY at a high (31 g/kg) dosage could decrease AUC(0–t), AUC(0–∞) and Cmax of diclofenac, omeprazole, and midazolam by at least 35.4%, while increase CL by at least 88.9%; this revealed that YGY could induce CYP2C9, CYP2C19, and CYP3A4. The results show that when we use You-Gui Yin decoction in combination with other drugs, especially drugs metabolized by CYP2C9, CYP2C19, and CYP3A4 enzymes, the interaction between drugs needs special attention.

Interaction between drugs and the gut microbiome

The human gut microbiome is a complex ecosystem that can mediate the interaction of the human host with their environment. The interaction between gut microbes and commonly used non-antibiotic drugs is complex and bidirectional: gut microbiome composition can be influenced by drugs, but, vice versa, the gut microbiome can also influence an individual’s response to a drug by enzymatically transforming the drug’s structure and altering its bioavailability, bioactivity or toxicity (pharmacomicrobiomics). The gut microbiome can also indirectly impact an individual’s response to immunotherapy in cancer treatment. In this review we discuss the bidirectional interactions between microbes and drugs, describe the changes in gut microbiota induced by commonly used non-antibiotic drugs, and their potential clinical consequences and summarise how the microbiome impacts drug effectiveness and its role in immunotherapy. Understanding how the microbiome metabolises drugs and reduces treatment efficacy will unlock the possibility of modulating the gut microbiome to improve treatment.

Physicochemistry in medicine: some selected examples

Research on pathological calcifications constitutes an exciting topic at the interface between physics, chemistry and medicine. The relationship between their physicochemical characteristics and the pathology responsible for their formation offers a unique opportunity to perform a significant medical diagnosis, to assess the interaction between drugs and these biological entities as well as to develop new drugs. Regarding synchrotron radiation, the emergence of microbeam allows the clinician to perform an early diagnosis. Indeed, we will start this review with a clinical case where Fourier transform infrared spectroscopy using synchrotron radiation as a probe allowed the clinician to save the kidney function of a patient. Following this example, we will see that investigations on pathological calcifications constitute an elegant way to gather major information on different public health problems such type 2 diabetes as well as on rare diseases. To attain this goal, this mini-review dedicated to structural and chemical investigations and based on selected and recent data collected through techniques using third generation synchrotron radiation as a probe is proposed to the reader.

Possible interactions between garlic and conventional drugs: a review

Herbs can affect body function; therefore, when herbs are taken concurrently with drugs, interactions are possible. The interaction between drugs and herbal medicines is a safe concern and these interactions are especially important for drugs with narrow therapeutics index. The probability of herb-drug interaction can be higher than drug interaction, if conventional drug having single chemical entities, whereas most of the herbal medicinal product contain a mixture of pharmacologically active constituents. The herb-drug interaction may involve either an increase or decrease in the amount of drug in blood, either by altering the absorption, distribution, metabolism, and elimination (ADME) of drug and by antagonizing or synergism of the effect of drug or pharmacodynamics interaction may arise. This article we focus on how garlic interacts with conventional drug or it is favourable or not.

Drug prescriptions associated with long acting. Pharmaco-economic aspects

IntroductionThe polypharmacy is a very controversial subject; it brings together problems of interaction between drugs, side effects, and rationality of co-prescriptions, pharmaco-economic aspects. The long acting is useful to solve adherence to treatment but they are often prescribed in polytherapy.MethodThe aim of this studies is to compare long-acting haloperidol, fluphenazine, risperidone and paliperidone regard to prescribing associations and pharmaco-economy. Also we want to consider for each long-acting which and how many drugs are associated and the implications in terms of pharmaco-economics. We examined all prescriptions (126 patients) over a period of 12 months in a mental health center, identifying which long acting had the best pharmaco-economic profile.ResultsDespite being the less prescribed and not being associated with other psychiatric drugs, paliperidone palmitate shows the best pharmaco-economic profile.ConclusionsThe costs of a drug are in relationship not only with unit price but also with the question of safety in order to oppose the overmedication.Disclosure of interestThe authors have not supplied their declaration of competing interest.