Neuroinflammation, diabetes, and COVID-19: Perspectives coming from Ca2+/cAMP signalling

Background: A link between inflammatory diseases, e.g., epilepsy, dementia, diabetes, and COVID-19, has been established. For instance, observational studies with several individuals established that people with epilepsy have shown 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, so an association between these two disorders is also discussed. Intriguingly, some reports have also observed a poor prognosis for 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. Objectives: Therefore, clarifying this clinical relationship among epilepsy, dementia, diabetes, and COVID-19 may outcome in novel hypotheses for identifying the etiology of these disorders.

Cefiderocol- A New Antimicrobial for Complicated Urinary Tract Infection (CUTI) Caused by Carbapenem Resistant Enterobacteriaceae (CRE)

: 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 salientpharmacological profile of the drug and the clinical studies that were undertaken.

Investigation of the effect of Prunus Amygdalus Amara on the expression of some genes of apoptosis and immortality in breast cancer cells (MCF-7)

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. Objectives: 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.

An Insight to ncovid-19 associated coagulopathy

: Several current studies have highlighted the high occurrence of coagulopathy in nCOVID-19 infection. The corona virus often prompts hypercoagulability along with both microangiopathy and local thrombus development, and systemic coagulation limitation which causes large vessel thrombosis and key thromboembolic issues such as pulmonary embolism in seriously ill hospitalized patients. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of nCOVID-19. The clinical presentation of nCOVID-19-associated coagulopathy is organ dysfunction primarily, while hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D-dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. Overall, the patients have an increase in venous and arterial thrombotic events especially in ICU patients. Routine thromboprophylaxis with low molecular weight heparin is recommended in all hospitalized patients to reduce the incidence of thrombosis. Though, the importance of thromboembolic impediments has not been extensively spotlighted, thus the rationale of this article is to provide recent information about this severe difficulty. In this article the mechanism of coagulopathy, associated problems and possible therapeutics has been reviewed.

A Novelistic Approach for Delivering of API through a Transvermillion Route: An updated review

: Present review highlights the potential of vermillion border as an administration route for targeting drug delivery. Vermillion border could attract a broad observation of researchers as a convenient, non-invasive, reliable, and safe route to realize faster and better levels of drugs within the targeted site. It is thought to do so through the rich supply of blood vessels and nerve supply following the neural pathway which could bypass the varied physiological barriers and permit the direct transport of drug from the vermillion border to the target site. Herein, authors tried to highlight the prominent aspects and key findings relevant to drug delivery system for targeting drug delivery via transvermillion route of drug administration. Anatomy and physiology of lips, key benefits offered by lips drug delivery system, mechanism of drug absorption across lip skin. The intrinsic advantage of this system results in administration of required drug with its reduced dose and reducing its side effect. This innate advantage of targeted drug delivery system is under high deliberation of research and development in clinical and pharmaceutical fields as backbone of therapeutics and diagnostics too. The goal of a targeted drug delivery system is to extend, localize, target and have a protected drug interaction with the diseased tissue.

Clinical Efficacy of Remdesivir and Favipiravir in the Treatment of Covid-19 Patients: Scenario So Far

: 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.

IL-23/Th17 Axis: A Potential Therapeutic Target of Psoriasis

: 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 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.

Pyrazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer – An In-Silico Approach

Background: Breast cancer is one of the malignant tumours which mainly affect the female population. Total 20% of the cases of breast cancer are due to overexpression of Human epidermal growth factor receptor-2 (HER2), which is the dominant tyrosine kinase receptor. In general, 9-anilinoacridine derivatives play an important role as antitumor agents 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 evaluated 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-MM-GBSA module was used for free binding energy calculations. Using 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 have a good binding affinity with Glide scores in the range of -4.9 to -9.75 compared to the standard drugs CK0403(-4.105) and Tamoxifen (-3.78). From the results of in-silico ADMET properties, most of the compounds fall within the recommended values. MM-GBSA binding calculations of the most potent inhibitors are more favourable. Conclusion: The results of in-silico studies provide strong evidence for the consideration of valuable ligands in pyrazole substituted 9-anilinoacridines as potential HER2 inhibitors, and the compounds, 1v,s,r,d, a,o with significant Glide scores may produce significant anti-breast cancer activity for further development.