The outbreak of Coronavirus disease 2019 (COVID-19) is the current world health concern, presenting a public health dilemma with ascending morbidity and mortality rates exceeding any previous viral spread, without a standard effective treatment yet. SARS-CoV-2 infection is distinguished with multiple epidemiological and pathological features, one of them being the elevated levels of cytokine release, which in turn trigger an aberrant uncontrolled response known as “cytokine storm”. This phenomenon contributes to severe acute respiratory distress syndrome (ARDS), leading to pneumonia and respiratory failure, which is considered a major contributor to COVID-19-associated fatality rates. Taking into account that the vast majority of the COVID-19 cases are aggravated by the respiratory and multiorgan failure triggered by the sustained release of cytokines, implementing therapeutics that alleviate or diminish the upregulated inflammatory response would provide a therapeutic advantage to COVID-19 patients. Indeed, dexamethasone, a widely available and inexpensive corticosteroid with anti-inflammatory effects, has shown a great promise in reducing mortality rates in COVID-19 patients. In this review, we have critically compared the clinical impact of several potential therapeutic agents that could block or interfere with the cytokine storm, such as IL-1 inhibitors, IL-6 inhibitors, mast cell targeting agents, and corticosteroids. This work focused on highlighting and contrasting the current success and limitations towards the involvement of these agents in future treatment protocols.
The devastating pandemic of coronavirus disease 2019 (COVID-19) has caused thousands of deaths and left millions of restless patients suffering from its complications. Increasing data indicate that the disease presents in a severe form in patients with pre-existing chronic conditions like cardiovascular diseases, diabetes, respiratory system diseases, and renal diseases. This indicates that these patients seem to be more susceptible to COVID-19 and have higher mortality rates compared to patients with no comorbid conditions. Several factors can explain the heightened susceptibility to and fatal presentation of COVID-19 in these patients, for example, the enhanced expression of the angiotensin-converting enzyme-2 receptor (ACE2) in specific organs, cytokine storm, and drug interactions contribute to the increased morbidity and mortality. Adding to the findings that individuals with pre-existing conditions may be more susceptible to COVID-19, it has also been shown that COVID-19 can induce chronic diseases in previously healthy patients. Therefore, understanding the interlinked relationship between COVID-19 and chronic diseases helps in optimizing the management of susceptible patients. This review comprehensively described the molecular mechanisms that contribute to worse COVID-19 prognosis in patients with pre-existing comorbidities such as diabetes, cardiovascular diseases, respiratory diseases, gastrointestinal and renal diseases, blood disorders, autoimmune diseases and finally, obesity. It also focused on how COVID-19 could, in some cases, lead to chronic conditions as a result of long-term multi-organ damage. Lastly, this work carefully discusses the tailored management plans for each specific patient population, aiming to achieve the best therapeutic outcome with minimum complications.
Objectives
Cancer is a leading cause of disabling morbidities and death worldwide. Although there are various strategies for the management of cancer, the severe adverse effects negatively impact the patient’s quality of life. In addition, the development of resistance limits the efficacy of many chemotherapeutics. Many natural agents are capable of reducing the adverse effects associated with chemotherapy and improving the therapeutic outcome. Tangeretin, a polymethoxy flavone, is one of the promising natural anticancer agents.
Key findings
Tangeretin not only targets various malignancies but also synergizes chemotherapeutic agents and reverses cancer resistance. Hence, the application of tangeretin as an adjuvant in cancer chemotherapy would be a promising strategy.
Summary
This work critically highlighted the proposed anticancer activity of tangeretin and discussed its potential combination with various chemotherapeutic agents. Additionally, it shed light on tangeretin chemical derivatives with improved pharmacokinetic and pharmacodynamic activity. Finally, this review described flavonoid biosynthetic pathways and how bioengineering can be employed to enhance the production yield of tangeretin. Thus, this work paves the way for the rational clinical utilization of tangeretin as a safe and effective adjuvant in chemotherapeutic protocols.
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