LncRNAs and the Angiogenic Switch in Cancer: Clinical Significance and Therapeutic Opportunities

Angiogenesis is one of the hallmarks of cancer, and the establishment of new blood vessels is vital to allow for a tumour to grow beyond 1–2 mm in size. The angiogenic switch is the term given to the point where the number or activity of the pro-angiogenic factors exceeds that of the anti-angiogenic factors, resulting in the angiogenic process proceeding, giving rise to new blood vessels accompanied by increased tumour growth, metastasis, and potential drug resistance. Long noncoding ribonucleic acids (lncRNAs) have been found to play a role in the angiogenic switch by regulating gene expression, transcription, translation, and post translation modification. In this regard they play both anti-angiogenic and pro-angiogenic roles. The expression levels of the pro-angiogenic lncRNAs have been found to correlate with patient survival. These lncRNAs are also potential drug targets for the development of therapies that will inhibit or modify tumour angiogenesis. Here we review the roles of lncRNAs in regulating the angiogenic switch. We cover specific examples of both pro and anti-angiogenic lncRNAs and discuss their potential use as both prognostic biomarkers and targets for the development of future therapies.

The Compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01): A Potential Drug for Treatment of Inflammatory Diseases

The compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01) was structurally developed using bioisosteric modifications of a hybrid prototype as formed from fragments of indomethacin and paracetamol. Initially, in vitro assays were performed to determine cell viability (in macrophage cultures), and its ability to modulate the synthesis of nitrite and cytokines (IL-1β and TNFα) in non-cytotoxic concentrations. In vivo, anti-inflammatory activity was explored using the CFA-induced paw edema and zymosan-induced peritonitis models. To investigate possible molecular targets, molecular docking was performed with the following crystallographic structures: LT-A4-H, PDE4B, COX-2, 5-LOX, and iNOS. As results, we observed a significant reduction in the production of nitrite and IL-1β at all concentrations used, and also for TNFα with JMPR-01 at 50 and 25 μM. The anti-edematogenic activity of JMPR-01 (100 mg/kg) was significant, reducing edema at 2–6 h, similar to the dexamethasone control. In induced peritonitis, JMPR-01 reduced leukocyte migration by 61.8, 68.5, and 90.5% at respective doses of 5, 10, and 50 mg/kg. In silico, JMPR-01 presented satisfactory coupling; mainly with LT-A4-H, PDE4B, and iNOS. These preliminary results demonstrate the strong potential of JMPR-01 to become a drug for the treatment of inflammatory diseases.

Polypharmacy and the occurrence of potential drug–drug interactions among geriatric patients at the outpatient pharmacy department of a regional hospital in Durban, South Africa

Background Polypharmacy is the administration of an excessive number of medicines and a significant irrational medicine use practice. Little is known about this practice in South Africa. This study aimed to determine the level of polypharmacy and potential drug–drug interactions amongst the geriatric patient population in a facility in South Africa. Method A cross-sectional retrospective prescription chart review for 250 geriatric patients was conducted at the outpatient pharmacy department of a regional hospital. Variables extracted included demographic information, diagnosis, type of prescriber contact, and polypharmacy. Potential drug–drug interactions were determined with web-based multi-drug interaction checkers. Results The average (SD) number of diagnosed clinical problems was 3.54 ± 1.26, with hypertension, diabetes mellitus, and heart disease occurring most frequently. The level of polypharmacy was high with patients receiving an average (SD) of 12.13 ± 4.25 prescribed medicines from 3032 prescribed medicines. The level of polypharmacy was highest within the age categories, 60–64, and 70–74 years of age, respectively. The level of potential drug–drug interactions was also high with an average (SD) of 10.30 ± 7.48 from 2570 potential drug interactions. The majority of these interactions were moderate (72.5%) and pharmacodynamic (73.2%) by nature of the clinical severity of action and mechanism of action, respectively. Polypharmacy and type of prescriber contact were statistically significant contributors to the occurrence of potential drug–drug interactions, (F (2, 249) = 68.057, p < 0.05). However, in a multivariate analysis of variables to determine the strength of the association, polypharmacy was determined to be the strongest contributor to the occurrence of potential drug–drug interactions (p < 0.05) when compared with the type of prescriber contact (p value = 0.467). Therefore, irrespective of the type of prescriber contact, polypharmacy increases the potential for drug interactions among the sampled patient population. Conclusion A comprehensive consideration of disease management guidelines, patient factors, and rational medicine review could be measurable strategies towards improving medicine use. This would also limit the occurrence of significant drug interactions among the geriatric patient population. A national study is required to determine if differences occur across hospitals and regions.

Nanoemulsion Applications

Prostate cancer (PCa) is a global issue with increasing rise in morbidity and mortality. PCa treatment has been a global challenge for many years because drugs designed to combat this disease might show low efficacy as a result of low solubility. Limitations of chemo-drugs for treating PCa give birth to the use of nanomedicine which helps to improve drug delivery systems. Nanoemulsions are particles that are pharmaceutically formulated and comprised within the range of a nanometer (10-200nm). Nanoemulsions are thermodynamically stable and made up of safe gradient agents. This chapter elucidates the physiological, biological, and molecular barriers affecting drug delivery in PCa. The authors discussed the importance of nanoemulsions as potential drug delivery mechanisms in PCa therapy. This chapter focuses on reviewing different ways by which nanoemulsion can bring solution to water-solubility problems and also target specific cancer cells. Limitations of nanoemulsions in the drug delivery field were also highlighted.

Potential drug interactions analysis of COVID-19 patients at a hospital in West Java

Background: Treatment guidelines of COVID-19 are changing continuously by involving many off-label and various symptomatic or supportive drugs. The use of these various drugs might increase the patient’s risk of developing drug interactions. Objective: The study aimed to analyze potential drug-drug interactions in COVID-19 inpatients and the correlated factors. Method: A cross-sectional study was conducted in a hospital by using inpatients admitted from August-December 2020. Potential drug-drug interaction was analyzed by using Lex-Interact® software. Results: From 107 patients, the majority of them are in moderate severity-degree (98.1%), having comorbidities (93.5%), and polypharmacy (98.1%). The average of potential drug interactions was 8.47±8,04, with most of the interaction in risk rating C-monitor therapy. Major potential drug interactions found were prolongation of QT interval and disturbance of drug absorption in the gastrointestinal tract. A positive correlation occurred between drug interactions found and comorbidity (r=0.436), number of drugs per prescription (r=0.674), and length of stay (r=0.222) Conclusions: COVID-19 patient is at risk for developing potential drug interactions that can affect the patient's physiological condition and reduce drug effect. It is necessary to manage the medication schedule, therapy modification, administration route changing, dosage adjustment, and monitoring of effects that might occur because of the drug interactions. Keywords: drug interaction, COVID-19, inpatient, correlated factor