Current Drug Research Reviews - Volume 14, Issue 1, 2022

A mega-journal is a peer-reviewed scientific open-access journal designed to be much larger than a traditional classical journal. The low selectivity review criteria largely focused on the scientific soundness of the research methodology and ethical issues regardless of the importance and application of the results, the fast peer review, and a very broad scope usually covering a whole discipline, such as biomedicine or social science, are the major hallmarks. This publishing model was pioneered by PLOS One and was soon followed by other publishers. A few years ago, it was believed that the academic journal landscape would dominate by the mega-journals model, but a decline has been registered in the last few years. This editorial aimed at presenting the current state-of-the-art of the open-access mega-journals (OAMJs) in scientific publications.

A link between inflammatory diseases, e.g., epilepsy, dementia, diabetes, and COVID-19, has been established. For instance, observational studies involving several individuals reported that people with epilepsy show an enhanced incidence of manifesting dysfunctions related to cognition, e.g., dementia, while people with dementia have a higher incidence of manifesting epilepsy, thus an evident bidirectional relationship between epilepsy and dementia might occur. In addition, epilepsy commonly cooccurs in patients with diabetes, indicating an association between these two disorders. Intriguingly, some reports have also observed a poor prognosis of people with both diabetes and COVID-19. It is recognized that a dyshomeostasis of both Ca²⁺ and cAMP signalling pathways could be a molecular connection for these disorders. Therefore, clarifying this clinical relationship among epilepsy, dementia, diabetes, and COVID-19 may outcome in novel hypotheses for identifying the etiology of these disorders.

The novel SARS-CoV-2 is a new disease that has caused severe destruction to human lives across the globe, including infection, mortality and financial crises, for which, scientific researchers have been directed towards the development of treatment and controlling measures against coronavirus. Currently, there has been no approved drug for the treatment of the disease, but several antiviral drugs have shown therapeutic effects from which, remdesivir and favipiravir are two such drugs. These drugs have shown some therapeutic potential in the treatment of COVID-19 by inhibiting viral enzyme RNA-dependent RNA polymerase. The purpose of this systematic review is to provide an overview of the effectiveness of these two drugs based on the clinical trials reported in current published data.

The incidence of carbapenem-resistant gram-negative (CRGNB) bacterial infections has increased globally. The wide diversity of strains, multiplicity of infections, and rapid development and spread of resistance are a matter of great concern both in community and hospital settings. Cefiderocol is a novel injectable siderophore containing cephalosporin with potent microbicidal activity against most carbapenem-resistant Enterobacteriaceae (CRE). It has recently been approved by USFDA for the treatment of complicated urinary tract infections (cUTI) caused by susceptible gram-negative microorganisms. This review focuses on the salient pharmacological profile of the drug and the clinical studies that were undertaken. Cefiderocol is first in class injectable siderophore cephalosporin showing potency against carbapenem- resistant Enterobacteriaceae. It has recently been approved by US FDA for the treatment of adult patients with complicated urinary tract infections (cUTI) caused by susceptible Gram-negative microorganisms, where there are limited or no alternative treatment options.

Psoriasis is an immune-mediated skin disease that leads to the initiation of abnormal production of inflammatory mediators and keratinocytes hyper-proliferation. Th-1 cell expressing cytokines such as IL-1β and TNF-α have been the important hallmarks in the management of psoriasis. However, investigations carried out in the previous few years underline the involvement of another subset of T helper cells, i.e. Th-17 in psoriasis exacerbation, and hence have become the point of focus now. The immunopathogenesis of Th-17 is the result of the IL-23/Th-17 axis. It involves the release of IL-17 and IL-22 in response to the activated NF-kβ dependent activation of IL-23. The function of human Th-17 cells, as well as the crucial role of IL-23/Th-17 axis in the exacerbation of psoriasis and treatment, have been well explored. Therefore, considering IL-23/Th17 axis as a pertinent therapeutic target in immune driven disorders, extensive investigations are now highlighting the utility of biopharmaceuticals and/or biological agents acting on these targets. Here, we review the IL-23/Th-17 axis based therapeutic targets, different types of active moieties based on their source of availability and most useful USFDA approved Mabs targeting the IL-23/Th17 axis in psoriasis for a better understanding of the future possibilities in this area.

Wound healing is an intricate process consisting of four overlapping phases, namely hemostasis, inflammation, proliferation, and remodelling. Effective treatment of wounds depends upon the interaction of appropriate cell types, cell surface receptors, and the extracellular matrix with the therapeutic agents. Several approaches currently used for treating wounds, such as advanced wound dressing, growth factor therapy, stem cell therapy, and gene therapy, are not very effective and lead to impaired healing. Further, repeated use of antibiotics to treat open wounds leads to multi- drug resistance. Today there is considerable interest in plant-based drugs as they are believed to be safe, inexpensive, and more suitable for chronic wounds. For example, a large number of plant- based extracts and their bioactive compounds have been investigated for wound healing. In recent years the structural and mechanistic diversity of natural products have become central players in the search for newer therapeutic agents. In the present review, a thorough critical survey of the traditionally used plant-based drugs used worldwide for wound healing with special reference to the natural products/bioactive compounds isolated and screened is presented. It is hoped that this review will attract the attention of the research community involved in newer drug design and development for wound healing.

Background: Breast cancer is one of the malignant tumours which mainly affect the female population. 20% of the cases of breast cancer are due to the over-expression of Human epidermal growth factor receptor-2 (HER2), which is the dominant tyrosine kinase receptor. In general, 9-anilinoacridine derivatives play an important role in antitumor activity due to their DNA-intercalating properties. Objective: Some novel 9-anilinoacridines substituted with pyrazole moiety (1a-z) were designed and their HER2enzyme (PDB id-3PP0) inhibition activity was performed by molecular docking studies using the Glide module of Schrodinger suite 2019-4. Methods: Glide module of the Schrodinger suite was used to perform docking studies; qikprop module was used for in-silico ADMET screening and the Prime-MMGBSA module was used for free binding energy calculations. Based on GLIDE scoring functions, we can determine the binding affinity of ligands (1a-z) towards HER2. Results: The inhibitory activity of ligands against HER2 was mainly due to the strong hydrophobic and hydrogen bonding interactions. Almost all the compounds 1a-z exhibited a good binding affinity with Glide scores in the range of -4.9 to -9.75, when compared with the standard drugs CK0403 (-4.105) and Tamoxifen (-3.78). From the results of in-silico ADMET properties, it was evident that most of the compounds fell within the recommended values. MM-GBSA binding calculations of the most potent inhibitors were found to be more favourable. Conclusion: The results of in-silico studies provide strong evidence for the potential of valuable ligands in pyrazole substituted 9-anilinoacridines as HER2 inhibitors, and the compounds, 1v,s,r,d,a,o with significant Glide scores may produce significant anti-breast cancer activity.

Background: Anti-cancer effects of almond nuts or oil have been approved, but there are a few pieces of research that have evaluated, in detail, almond and other seeds' effects on cancer. Therefore, in the present project, the aim was to explore the regulatory effect of the bitter almond extract (Prunus amygdalus Batsch) on the apoptotic and anti-cancer potency of MCF-7 cells. Objective: In the current experimental research, the almond effect on MCF7 cells was evaluated by investigating the expression and the balance between Bcl-2, Bax genes to unmark the potential molecular mechanism. Methods: For 24 and 48h, the MCF7 cells were treated with the bitter almond extract (187.5-3000 μg/mL). MTT assay was used to assess the viability, and Real-time-PCR was applied to determine the expression of Bax and Bcl-2, facing β-actin. Results: Our results revealed a significant difference between different extract concentrations on the viability of MCF7 cell lines in 24 and 48 h; cell viability decreased time-dependently (P < 0.05). After 24 and 48h of extract facing MCF7 cells, the evaluated IC50 value was 3000 and 1500 μg/mL, respectively. Based on Real-Time-PCR analysis, after 24 and 48 h, the mRNA levels of BCL-2 decreased by the extract, whereas Bax was in the MCF-7 cell line. Conclusion: From the results, it can be concluded that bitter almond extract has anti-cancer properties that may influence the apoptotic pathways by regulating relative gene expression.

Objective: To report a rare case of drug induced overlap of Stevens-Johnson syndrome and Toxic Epidermal Necrosis Syndrome exacerbated by cephalexin. Case Presentation: In this case report, we present a 65-year-old female who had come to the hospital with complaints of Sloughing of the skin and redness all over the body with raised body temperature. She was on therapeutic Phenytoin to prevent the post-surgical complications of Communicating Hydrocephalus. After a detailed examination, it was found that the patient had misemployed with an overdose of Phenytoin. The patient was found with nikolsky sign and diagnosed as Stevens- Johnson syndrome and Toxic Epidermal Necrosis overlap. This case report emphasizes phenytoin induced Stevens-Johnson syndrome and Toxic Epidermal Necrosis syndrome exacerbated by cephalexin. Conclusion: By witnessing this phenomenon, we could figure out the association between cephalexin and Stevens-Johnson syndrome- Toxic Epidermal Necrosis syndrome overlap. The Immediate dismissal of the offending agent and commencement of supportive care was found to be effective.