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Topic Review
Human Drug-Drug Interactions
Patients suffering from complex diseases (infectious diseases, oncology) or several conditions (co-morbidities) require combination therapies of different drugs. Combining different drugs will potentially lead to drug-drug interactions, influencing the efficacy and safety of the treatment. Development of novel drugs that are intended to be used in combination should consider drug-drug interactions as early as possible. Even with limited data, drug-drug interactions in humans can be predicted using model-informed drug discovery and development (MID3). The concept to utilize and integrate data from in vitro combination experiments combined with preclinical in vivo data on the exposure-response relationships of the drugs in combination through a computational model-informed approach, is introduced here with tuberculosis as case study.
  • 1.1K
  • 29 May 2021
Topic Review
Royleanones
Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities.The abietane diterpenes 6,7-dehydroroyleanone (DeRoy), 7alfa-acetoxy-6 -hydroxyroyleanone (Roy), and Parvifloron D (ParvD) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity on several cancer cell lines, including cancer stem cell inducing sphere cells. In silico studies comparied the possible binding modes of active compounds and derivatives against different PKC isoforms alpha/beta/delta/iota/lambda/theta/zeta.
  • 1.1K
  • 27 Oct 2020
Topic Review
The Subcutaneous Route of Administration for Therapeutic Antibodies
Therapeutic antibodies (Abs) are used in the treatment of numerous diseases, including infection, cancer, and autoimmune disorders, in which they have already demonstrated their efficacy. The success of Abs is due to (I) a high level of specificity and affinity to their target antigen, (II) a favorable safety profile, and (III) a unique pharmacokinetic profile, supporting a longer half-life as compared to other drugs. While the majority of Abs are delivered through IV injection, evidence in the literature showed that beyond the reduction of invasiveness, a better efficacy could be achieved with a local delivery of Abs. Among those routes, one has been in full development these last few years, with already good clinical results and still promising developments: The Subcutaneous route.
  • 1.1K
  • 13 Sep 2022
Topic Review
Advantages of Intranasal Administration in Treatment of Depression
As a mental disease in modern society, depression shows an increasing occurrence, with low cure rate and high recurrence rate. It has become the most disabling disease in the world. At present, the treatment of depression is mainly based on drug therapy combined with psychological therapy, physical therapy, and other adjuvant therapy methods. Antidepressants are primarily administered peripherally (oral and intravenous) and have a slow onset of action. Antidepressant active ingredients, such as neuropeptides, natural active ingredients, and some chemical agents, are limited by factors such as the blood–brain barrier (BBB), first-pass metabolism, and extensive adverse effects caused by systemic administration. The potential anatomical link between the non-invasive nose–brain pathway and the lesion site of depression may provide a more attractive option for the delivery of antidepressant active ingredients.
  • 1.1K
  • 21 Oct 2022
Topic Review
Extracellular Vesicle-based Therapeutics
This is a entry of recent developments of bio-inspired drug delivery systems based on extracellular vesicles (EVs). The main hurdles and limitations for therapeutic and clinical applications of EV-based formulations and various attempts to solve these problems are described. 
  • 1.1K
  • 09 Dec 2020
Topic Review
Sinomenine-Type Drugs to Treat Rheumatoid Arthritis
Sinomenine is the main component of the vine Sinomenium acutum. It was first isolated in the early 1920s and has since attracted special interest as a potential anti-rheumatoid arthritis (RA) agent, owing to its successful application in traditional Chinese medicine for the treatment of neuralgia and rheumatoid diseases.
  • 1.1K
  • 23 Dec 2022
Topic Review
Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts
Fritillaria bulbs are used in Traditional Chinese Medicine to treat several illnesses. Peimine (Pm), an anti-inflammatory compound from Fritillaria, is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion channels remains unexplored.
  • 1.1K
  • 29 Mar 2022
Topic Review
PDE2A for Mouse Liver Development
cAMP and cGMP are intracellular signaling molecules produced in response to a plethora of extracellular signals in order to coordinate cellular metabolism, proliferation, differentiation and apoptosis. Phosphodiesterases (PDEs) are the enzymes that hydrolyze cAMP and cGMP in order to end or to limit the responses to these signals. To date 11 PDE families (named PDE1 to PDE11) have been identified across each cell type expressed in a peculiar pattern. They enclose 21 genes that codify approximately 100 enzymes that form a redundant network ensuring the compensation of activity in case of alteration of activity or lack of expression of one of the members. PDE2A, a cAMP-hydrolyzing enzyme, represents the exception to this picture, as PDE2A knockout is embryonic lethal. Knockout embryos show that the lack of the enzyme has the greatest impact on the development of the heart and of the liver, which is no longer able to assume its hematopoietic role. The increase of the intracellular cAMP level and the downregulation of the anti-apoptotic gene Bcl2 might explain the loss of integrity in the PDE2A knockout liver niche that compromises the hematopoietic function and maturation.
  • 1.1K
  • 29 Oct 2020
Topic Review
Pathophysiology of Drug-Induced Hyponatremia
Drug-induced hyponatremia caused by renal water retention is mainly due to syndrome of inappropriate antidiuresis (SIAD). SIAD can be grouped into syndrome of inappropriate antidiuretic hormone secretion (SIADH) and nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The former is characterized by uncontrolled hypersecretion of arginine vasopressin (AVP), and the latter is produced by intrarenal activation for water reabsorption and characterized by suppressed plasma AVP levels. Desmopressin is useful for the treatment of diabetes insipidus because of its selective binding to vasopressin V2 receptor (V2R), but it can induce hyponatremia when prescribed for nocturnal polyuria in older patients. Oxytocin also acts as a V2R agonist and can produce hyponatremia when used to induce labor or abortion. 
  • 1.1K
  • 25 Oct 2022
Topic Review
Clozapine, Pharmacogenetic Biomarkers, Particularities COVID-19
Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed andWeb of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor then the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.
  • 1.1K
  • 20 Nov 2020
Topic Review
CAR-T Therapy
Chimeric antigen receptor-T (CAR-T) therapy targeting CD19 has revolutionised the treatment of advanced acute lymphoblastic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The success of CAR-T therapy in the first two indications led to the initiation of a large number of studies testing CAR-T therapy in different haematologic tumours such as acute myelogenous leukaemia (AML), Hodgkin’s disease (HD), chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), as well as different solid tumours. Notwithstanding, this did not prohibit further development of this new therapy to treat other malignancies.
  • 1.1K
  • 31 May 2021
Topic Review
Uses of Traditional Plants for Diabetes Nephropathy
Diabetic nephropathy (DN) is a serious kidney illness characterized by proteinuria, glomerular enlargement, reduced glomerular filtration, and renal fibrosis. DN is the most common cause of end-stage kidney disease, accounting for nearly one-third of all cases of diabetes worldwide.
  • 1.1K
  • 08 Jul 2022
Topic Review
Bacteriophage-Delivering Hydrogels
Hydrogels are non-toxic polymeric materials exhibiting three-dimensional networks along with their hydrophilic characteristics playing an essential role in containing large water content, which serves as a biocompatible environment suited for formulation and delivery of bacteriophages.
  • 1.1K
  • 25 Feb 2021
Topic Review
Dinoflagellate Phycotoxins
Dinoflagellates are single-celled eukaryotes constitute an important group of phytoplanktons, characterized by two dissimilar flagella and distinctive features of both plants and animals.
  • 1.1K
  • 30 Dec 2020
Topic Review
Therapeutic Sequencing in ALK+ NSCLC
Anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC) is a model disease for the use of targeted pharmaceuticals in thoracic oncology. This entry summarizes the state-of-the-art treatment for these tumors as of January 2021, with a special emphasis in the sequential use of various compounds as well as the growing importance of molecular profiling and monitoring for patient management.
  • 1.1K
  • 20 Apr 2021
Topic Review
Molecular Mechanism of Drug Resistance in Pseudomonas aeruginosa
Antibiotic resistance in Pseudomonas aeruginosa remains one of the most challenging phenomena of everyday medical science. The universal spread of high-risk clones of multidrug-resistant/extensively drug-resistant (MDR/XDR) clinical P. aeruginosa has become a public health threat. The P. aeruginosa bacteria exhibits remarkable genome plasticity that utilizes highly acquired and intrinsic resistance mechanisms to counter most antibiotic challenges. In addition, the adaptive antibiotic resistance of P. aeruginosa, including biofilm-mediated resistance and the formation of multidrug-tolerant persisted cells, are accountable for recalcitrance and relapse of infections.
  • 1.1K
  • 06 Sep 2023
Topic Review
Novel Psychoactive Substances
Novel psychoactive substances (NPS) represent a severe health risk for drug users. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems.
  • 1.1K
  • 21 May 2021
Topic Review
Medicinal-Plant Extracts against Chikungunya Virus
The lack of specific treatment for chikungunya fever makes the need for anti-chikungunya virus agents more crucial. This study was conducted to evaluate 132 extracts obtained by sequential solvent extraction from 21 medicinal plants for cytopathic effect inhibitory activity using virus-infected Vero cells in two different sample introduction modes. Among the extracts, 42 extracts (31.8%) from 12 plants in the concurrent mode and three extracts (2.3%) from a plant in the non-concurrent mode displayed strong cytopathic effect inhibitory activity (cell viability ≥70%). Viral load quantification analysis unveiled that the extracts of Clinacanthus nutans (chloroform, ethyl acetate, and ethanol), Hydrocotyle sibthorpioides (ethanol), and Ocimum americanum (ethanol and methanol) hindered the release of viral progeny from the infected cells while the extracts of Ficus deltoidea (ethanol), Gynura bicolor (water), H. sibthorpioides (water), and O. americanum (chloroform and ethyl acetate) blocked the entry of virus into the cells. The extracts of Diodella sarmentosa (ethyl acetate), Diplazium esculentum (chloroform, ethyl acetate, and ethanol), and G. bicolor (ethanol) possessed virucidal effect and caused 5.41-log to 6.63-log reductions of viral load compared to the virus control. The results indicate that these medicinal plants are potential sources of anti-chikungunya virus agents that have varied modes of action. 
  • 1.1K
  • 16 Aug 2021
Topic Review
Grimelysin and Protealysin
The entry reviews the discovery, properties, and functional activities of new bacterial enzymes, proteases grimelysin (ECP 32) of Serratia grimesii and protealysin of Serratia proteamaculans, characterized by both a highly specific “actinase” activity and their ability to stimulate bacterial invasion. Grimelysin cleaves the only one polypeptide bond Gly42-Val43 in actin. This bond is not cleaved by any other proteases and leads to a reversible loss of actin polymerization. Similar properties were characteristic for another bacterial protease, protealysin. These properties made grimelysin and protealysin a unique tool to study the functional properties of actin. Furthermore, bacteria Serratia spp. producing grimelysin/protealysin invade eukaryotic cells, and the recombinant Escherichia coli expressing the grimelysin or protealysins gene become invasive. Being an intracellular enzyme, grimelysin/protealysin can be delivered by bacteria to eukaryotic cells. These data indicate that the protease is a virulence factor, and actin can be a target for the protease upon its translocation into the host cell.
  • 1.1K
  • 27 Oct 2020
Topic Review
Polymer-Based Nanovaccines
Polymer-based particles have found application as vaccine platforms and vaccine adjuvants due to their ability to prevent antigen degradation and clearance, coupled with enhanced uptake by professional antigen-presenting cells (APCs). Polymeric nanoparticles have been applied in vaccine delivery, showing significant adjuvant effects as they can easily be taken up by APCs. In other words, polymer-based systems offer a lot of advantages, including versatility and flexibility in the design process, the ability to incorporate a range of immunomodulators/antigens, mimicking infection in different ways, and acting as a depot, thereby persisting long enough to generate adaptive immune responses. 
  • 1.1K
  • 03 Jun 2021
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