Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment.

Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.

Investigating thyroid dysfunction in the context of COVID-19 infection.

COVID-19 is a contagious viral infection caused by severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2). One of the key features of COVID-19 infection is inflammation. There is increasing evidence pointing to an association between cytokine storm and autoimmunity. One autoimmune disease of interest in connection to COVID-19 is hyperthyroidism. COVID-19 has been shown to decrease TSH levels and induce thyrotoxicosis, destructive thyroiditis, and de novo Graves' disease. It has also been suggested that the immune response against SARS-CoV-2 antigens following vaccination can cross-react through a mechanism called molecular mimicry which can elicit autoimmune reactivity, potentially leading to potential thyroid disease post vaccine. However, if the COVID-19 vaccine is linked to reduced COVID-19 related serious disease, it could potentially play a protective role against post COVID-19 hyperthyroidism (de novo disease and exacerbations). Further studies investigating the complex interplay between COVID-19 or COVID-19 vaccine and thyroid dysfunction can help provide substantial evidence and potential therapeutic targets that can alter prognosis and improve COVID-19 related outcomes in individuals with or without preexisting thyroid disease.

Vulnerable in silence: Paediatric health in the Ukrainian crisis.

The Russian invasion of Ukraine is a humanitarian disaster. It has a wide-ranging impact on the livelihood and the health of those affected by the war. In the midst of constant shelling and casualties, children are more vulnerable to injuries, infections, malnutrition, and trauma, all of which can have serious consequences for their physical and mental health. Children, unlike adults, are simply subjected to the horrors of war with no pre-existing ability to deal with the consequences. We hope to highlight the effects of the current Ukrainian war on the health of the paediatric population, with a particular emphasis on surgical care, cancer care, infectious disease, to name a few. We hope to help contextualize future data and encourage the development of a system to protect and serve the war's most vulnerable population.

Exploring the role of Nrf2 signaling in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the most aggressive glial cell tumors in adults. Although current treatment options for GBM offer some therapeutic benefit, median survival remains poor and does not generally exceed 14 months. Several genes, such as isocitrate dehydrogenase (IDH) enzyme and O6-methylguanine-DNA methyltransferase (MGMT), have been implicated in pathogenesis of the disease. Treatment is often adapted based on the presence of IDH mutations and MGMT promoter methylation status. Recent GBM cell line studies have associated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) expression with high-grade tumors. Increased Nrf2 expression is often found in tumors with IDH-1 mutations. Nrf2 is an important transcription factor with anti-apoptotic, antioxidative, anti-inflammatory, and proliferative properties due to its complex interactions with multiple regulatory pathways. In addition, evidence suggests that Nrf2 promotes  GBM cell survival in hypoxic environment,by up-regulating hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Downregulation of Nrf2 has been shown to improve GBM sensitivity to chemotherapy drugs such as Temozolomide. Thus, Nrf2 could be a key regulator of GBM pathways and potential therapeutic target.  Further research efforts exploring an interplay between Nrf2 and major molecular signaling mechanisms could offer novel GBM drug candidates with a potential to significantly improve patients prognosis.

Elective surgeries during and after the COVID-19 pandemic: Case burden and physician shortage concerns.

The COVID-19 pandemic had a significant impact on several aspects of global healthcare systems, particularly surgical services. New guidelines, resource scarcity, and an ever-increasing demand for care have posed challenges to healthcare professionals, resulting in the cancellation of many surgeries, with short and long-term consequences for surgical care and patient outcomes. As the pandemic subsides and the healthcare system attempts to reestablish a sense of normalcy, surgical recommendations and advisories will shift. These changes, combined with a growing case backlog (postponed surgeries + regularly scheduled surgeries) and a physician shortage, can have serious consequences for physician health and, as a result, surgical care. Several initiatives are already being implemented by governments to ensure a smooth transition as surgeries resume. Newer and more efficient steps aimed at providing adequate surgical care while preventing physician burnout, on the other hand, necessitate a collaborative effort from governments, national medical boards, institutions, and healthcare professionals. This perspective aims to highlight alterations in surgical recommendations over the course of the pandemic and how these changes continue to influence surgical care and patient outcomes as the pandemic begins to soften its grip.

OMICs Technologies for Natural Compounds-based Drug Development.

Compounds isolated from natural sources have been used for medicinal purposes for many centuries. Some metabolites of plants and microorganisms possess properties that would make them effective treatments against bacterial infection, inflammation, cancer, and an array of other medical conditions. In addition, natural compounds offer therapeutic approaches with lower toxicity compared to most synthetic analogues. However, it is challenging to identify and isolate potential drug candidates without specific information about structural specificity and limited knowledge of any specific physiological pathways in which they are involved. To solve this problem and find a way to efficiently utilize natural sources for the screening of compounds candidates, technologies, such as next-generation sequencing, bioinformatics techniques, and molecular analysis systems, should be adapted for screening many chemical compounds. Molecular techniques capable of performing analysis of large datasets, such as whole-genome sequencing and cellular protein expression profile, have become essential tools in drug discovery. OMICs, as genomics, proteomics, and metabolomics, are often used in targeted drug discovery, isolation, and characterization. This review summarizes technologies that are effective in natural source drug discovery and aid in a more precisely targeted pharmaceutical approach, including RNA interference or CRISPR technology. We strongly suggest that a multidisciplinary effort utilizing novel molecular tools to identify and isolate active compounds applicable for future drug discovery and production must be enhanced with all the available computational tools.