Current Pharmaceutical Design - Volume 27, Issue 25, 2021

Quorum sensing is defined as a cell to cell communication between micro-organisms, which enables micro-organisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing, as well as biofilm formation, encourage the development of drug resistance in micro-organisms. Biofilm formation and quorum sensing are causally linked to each other, playing a role in the pathogenesis of the micro-organisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the micro-organisms. This review encompasses the communication technique used by micro-organisms, how micro-organism resistance is linked to quorum sensing, and various chemical strategies to combat quorum sensing, thereby, drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds have several disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that antiquorum sensing compounds are effective in disrupting quorum sensing and could, therefore be effective in reducing micro-organism drug resistance.

The search for novel drugs that can prevent or control Alzheimer’s disease has attracted a lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

Chronic prostatitis/chronic pelvic pain syndrome type III is related to irritative voiding, sexual dysfunction, and pelvic pain. Chronic prostatitis/chronic pelvic pain syndrome weakens the quality of life and poses adverse psychological effects on the patients. A wide range of treatments, including botulinum neurotoxins, anti-inflammatories, alpha-blockers, phytotherapy, 5α-reductase inhibitors, phosphodiesterase type 4 inhibitor, phosphodiesterase type 5 inhibitor, monoclonal antibody, anticholinergics, gabapentin, pregabalin is used clinically. These therapies emphasize easing the symptoms in specific areas without curing the fundamental cause where the outcome of the treatment is not completely satisfactory. This review article explains the recent pharmacological treatments of chronic prostatitis/chronic pelvic pain syndrome in detail and offers a future perspective to treat this condition.

Background: Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) and cyclooxygenase-2 (COX-2) inhibitor. It is used for the treatment of rheumatoid arthritis, osteoarthritis, juvenile arthritis, and acute pain. Celecoxib has low systemic bioavailability due to its low water solubility. This study aimed to improve water solubility and dissolution profile by synthesizing a suitable celecoxib potassium salt (celecoxib–K salt). Methods: Four celecoxib salts were synthesized, and the solubility of these four salts was determined. Celecoxib– K monohydrate salt was chosen for tablet formulation. A simple and feasible reversed-phase high-performance liquid chromatography (HPLC) method was developed for the analysis of the formulated tablet and then validated according to international guidelines. The dissolution profile, shelf life, and accelerated stability studies on the formulated tablet were conducted. Results: Celecoxib–K monohydrate salt exhibited increased water solubility by more than 140-folds (0.464 mg/ml) compared with celecoxib. The in vitro dissolution profile of the formulated celecoxib–K salt tablet was totally dissolved after 10 min. The developed analytical HPLC method was a reliable and valid method with good linearity, accuracy, and precision. Moreover, it was sensitive, and the limit of detection and quantification (LOD and LOQ) were 0.001 and 0.1 mg/L, respectively. The formulated celecoxib–K monohydrate salt tablet was stable under room temperature and accelerated condition for 60 days. Conclusion: The potassium salt of celecoxib was highly increased, and the formulated tablet of celecoxib–K salt exhibited a good dissolution profile in the water. In addition, the developed HPLC method was valid and reliable for the analysis and quantification of the formulated tablet. The formulated tablet was stable both at room temperature and under stress conditions.

Objective: In this review, we discuss the emerging evidence for the effectiveness of cannabinoids in the treatment of cancer and inflammation. The remarkable effects of this study will help in supporting the traditional evidence for their successful application in the treatment of pain and cancer-related side effects. Methods: We searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), and preclinical (28 articles) studies, reports on cell culture models (30 articles), and other original and review articles (78 articles) related to inflammation, cancer, and cannabinoids. Results: Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phyto- and synthetic cannabinoids mediated by cannabinoid receptors has been demonstrated in the treatment of inflammatory diseases, including neurodegenerative diseases as well as gastrointestinal and respiratory inflammations. Another accepted property of cannabinoids is their anti-cancer effects. Cannabinoids were found to be effective in the treatment of lung, colorectal, prostate, breast, pancreas, and hepatic cancers. The anti-cancer effects of cannabinoids were characterized by their anti-proliferative property, inhibition of cancer cell migration, suppression of vascularization, and induction of apoptosis. Conclusion: The current review provides an overview of the role of the endocannabinoid system in the mediation of physiological functions and the type and expression of cannabinoids receptors under physiological and pathological conditions. In addition, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.

Introduction: While PCR has been recognized as one of the appropriate ways to diagnose infectious diseases, Loop-mediated isothermal amplification (LAMP) which is a nucleic acid amplification method, can be considered as an alternative to PCR, and it is faster, cost-effective, and easier to perform than nested PCR. Patients and Methods: Keywords were searched in PubMed/MEDLINE, Scopus and Institute for Scientific Information Web of Science, as well as the search engine of Google Scholar. Keywords included PCR, LAMP, RAA, RPA, Virus and COVID-19. Results: LAMP technology has been extensively applied for the detection of human pathogenic bacteria, crop pests, pathogenic organisms and components in meat products. A new isotheral method, Recombinase polymerase amplification (RPA), can amplify the DNA as well as RPA. RPA involves benefits of isothermal PCR as well as simplicity and rapid amplification. Recombinase aided amplification (RAA) assay has been favorably used in the detection of bacterial and viral pathogens and solved the technical difficulties posed by DNA amplification methods because it does not need thermal denaturation of the template and involves a low and constant temperature. Conclusion: Reverse transcription polymerase chain reaction, digital PCR, LAMP, nicking endonuclease amplification reaction, recombinase polymerase amplification, and clustered regularly interspaced short palindromic repeats are different nucleic acid amplification tests of COVID-19. LAMP methods can be more specific than qPCR and immunoassays. The LAMP assay can be applied for rapid detection of SARS-CoV, MERS-CoV, SARS-CoV-2, and influenza, because LAMP is a highly sensitive and specific DNA/RNA amplification technique.

Ulcerative colitis (UC) is one of the main subtypes of inflammatory bowel disease. UC has a negative effect on patients’ quality of life, and it is an important risk factor for the development of colitis-associated cancer. Patients with UC need to take medications for their entire life because no permanent cure is available. Therefore, approaches that target messenger RNA (mRNA) of proinflammatory cytokines and/or anti-inflammatory cytokines are needed to improve the safety of UC therapy and promote intestinal mucosa recovery. The major challenge facing RNA interference-based therapy is the delivery of RNA molecules to the intracellular space of target cells. Moreover, nonspecific and systemic protein expression inhibition can result in adverse effects and low therapeutic benefit. Thus, it is important to develop an efficient delivery strategy targeting the cytoplasm of target cells to avoid side effects caused by off-target protein expression inhibition. This review focuses on the most recent advances in the targeted nano delivery systems of siRNAs and mRNA that have shown in vivo efficacy.