Management of Fluoropyrimidine-Induced Cardiac Adverse Outcomes Following Cancer Treatment.

Advancements in cancer treatments have improved survival rates but have also led to increased cardiotoxicities, which can cause adverse cardiovascular events or worsen pre-existing conditions. Herein, cardiotoxicity is a severe adverse effect of 5-fluorouracil (5-FU) therapy in cancer patients, with reported incidence rates ranging from 1 to 20%. Some studies have also suggested subclinical effects and there are reports which have documented instances of cardiac arrest or sudden death during 5-FU treatment, highlighting the importance of timely management of cardiovascular symptoms. However, despite being treated with conventional medical approaches for this cardiotoxicity, a subset of patients has demonstrated suboptimal or insufficient responses. The frequent use of 5-FU in chemotherapy and its association with significant morbidity and mortality indicates the need for a greater understanding of 5-FU-associated cardiotoxicity. It is essential to reduce the adverse effects of anti-tumor medications while preserving their efficacy, which can be achieved through drugs that mitigate toxicity associated with these drugs. Underpinning cardiotoxicity associated with 5-FU therapy also has the potential to offer valuable guidance in pinpointing pharmacological approaches that can be employed to prevent or ameliorate these effects. The present study provides an overview of management strategies for cardiac events induced by fluoropyrimidine-based cancer treatments. The review encompasses the underlying molecular and cellular mechanisms of cardiotoxicity, associated risk factors, and diagnostic methods. Additionally, we provide information on several available treatments and drug choices for angina resulting from 5-FU exposure, including nicorandil, ranolazine, trimetazidine, ivabradine, and sacubitril-valsartan, which have demonstrated potential in mitigating or protecting against chemotherapy-induced adverse cardiac effects.

Pediatric asthma exacerbation and COVID-19 pandemic: Impacts, challenges, and future considerations.

OBJECTIVE: Asthma, a common disease among children and adolescents, poses a great health risk when ignored; therefore, a thorough follow-up to prevent exacerbations is emphasized. The aim of the present study is to investigate asthma exacerbation in children during the Coronavirus disease 2019 (COVID-19) era. DATA SOURCES: This narrative review has been done by searching the PubMed and Embase databases using Asthma, COVID-19, Pandemic, and Symptom flare up as keywords. STUDY SELECTIONS: Studies related to asthma exacerbation in COVID-19 pandemic were included. RESULTS: Based on studies, controlled or mild to moderate asthma has not been considered a risk factor for COVID-19 severity and has not affected hospitalization, intensive care unit (ICU) admission, and mortality. Surprisingly, emergent and non-emergent visits and asthmatic attacks decreased during the pandemic. The three main reasons for decreased incidence and exacerbation of asthma episodes in the COVID-19 era included reduced exposure to environmental allergens, increasing the acceptance of treatment by pediatrics and caregivers, and decreased risk of other respiratory viral infections. Based on the available studies, COVID-19 vaccination had no serious side effects, except in cases of uncontrolled severe asthma, and can be injected in these children. Also, there was no conclusive evidence of asthma exacerbation after the injection of COVID-19 vaccines. CONCLUSION: Further studies are recommended to follow the pattern of asthma in the post-pandemic situation and to become prepared for similar future conditions.

Metabolomics profile and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score.

Background: The intermediate metabolites associated with the development of atherosclerotic cardiovascular disease (ASCVD) remain largely unknown. Thus, we conducted a large panel of metabolomics profiling to identify the new candidate metabolites that were associated with 10-year ASCVD risk. Methods: Thirty acylcarnitines and twenty amino acids were measured in the fasting plasma of 1,102 randomly selected individuals using a targeted FIA-MS/MS approach. The 10-year ASCVD risk score was calculated based on 2013 ACC/AHA guidelines. Accordingly, the subjects were stratified into four groups: low-risk (n = 620), borderline-risk (n = 110), intermediate-risk (n = 225), and high-risk (n = 147). 10 factors comprising collinear metabolites were extracted from principal component analysis. Results: C4DC, C8:1, C16OH, citrulline, histidine, alanine, threonine, glycine, glutamine, tryptophan, phenylalanine, glutamic acid, arginine, and aspartic acid were significantly associated with the 10-year ASCVD risk score (p-values ≤ 0.044). The high-risk group had higher odds of factor 1 (12 long-chain acylcarnitines, OR = 1.103), factor 2 (5 medium-chain acylcarnitines, OR = 1.063), factor 3 (methionine, leucine, valine, tryptophan, tyrosine, phenylalanine, OR = 1.074), factor 5 (6 short-chain acylcarnitines, OR = 1.205), factor 6 (5 short-chain acylcarnitines, OR = 1.229), factor 7 (alanine, proline, OR = 1.343), factor 8 (C18:2OH, glutamic acid, aspartic acid, OR = 1.188), and factor 10 (ornithine, citrulline, OR = 1.570) compared to the low-risk ones; the odds of factor 9 (glycine, serine, threonine, OR = 0.741), however, were lower in the high-risk group. "D-glutamine and D-glutamate metabolism", "phenylalanine, tyrosine, and tryptophan biosynthesis", and "valine, leucine, and isoleucine biosynthesis" were metabolic pathways having the highest association with borderline/intermediate/high ASCVD events, respectively. Conclusions: Abundant metabolites were found to be associated with ASCVD events in this study. Utilization of this metabolic panel could be a promising strategy for early detection and prevention of ASCVD events.

Metabolomics Signatures of SARS-CoV-2 Infection.

For a very long time, viral infections have been considered as one of the most important causes of death and disability around the world. Through the viral infection, viruses as small pathogens enter the host cells and use hosts' biosynthesis machinery to replicate and collect infectious lineages. Moreover, they can modify hosts' metabolic pathways in order to their own purposes. Nowadays (in 2019-2020), the most famous type of viral infection which was caused by a novel type of coronavirus is called COVID-19 disease. It has claimed the lives of many people around the world and is a very serious threat to health. Since investigations of the effects of viruses on host metabolism using metabolomics tools may have given focuses on novel appropriate treatments, in the current review the authors highlighted the virus-host metabolic interactions and metabolomics perspective in COVID-19.

COVID-19 Pathology on Various Organs and Regenerative Medicine and Stem Cell-Based Interventions.

Severe acute respiratory syndrome-coronavirus 2, a novel betacoronavirus, has caused the global outbreak of a contagious infection named coronavirus disease-2019. Severely ill subjects have shown higher levels of pro-inflammatory cytokines. Cytokine storm is the term that can be used for a systemic inflammation leading to the production of inflammatory cytokines and activation of immune cells. In coronavirus disease-2019 infection, a cytokine storm contributes to the mortality rate of the disease and can lead to multiple-organ dysfunction syndrome through auto-destructive responses of systemic inflammation. Direct effects of the severe acute respiratory syndrome associated with infection as well as hyperinflammatory reactions are in association with disease complications. Besides acute respiratory distress syndrome, functional impairments of the cardiovascular system, central nervous system, kidneys, liver, and several others can be mentioned as the possible consequences. In addition to the current therapeutic approaches for coronavirus disease-2019, which are mostly supportive, stem cell-based therapies have shown the capacity for controlling the inflammation and attenuating the cytokine storm. Therefore, after a brief review of novel coronavirus characteristics, this review aims to explain the effects of coronavirus disease-2019 cytokine storm on different organs of the human body. The roles of stem cell-based therapies on attenuating cytokine release syndrome are also stated.

Stem cell-based models and therapies: a key approach into schizophrenia treatment.

Psychiatric disorders such as schizophrenia can generate distress and disability along with heavy costs on individuals and health care systems. Different genetic and environmental factors play a pivotal role in the appearance of the mentioned disorders. Since the conventional treatment options for psychiatric disorders are suboptimal, investigators are trying to find novel strategies. Herein, stem cell therapies have been recommended as novel choices. In this context, the preclinical examination of stem cell-based therapies specifically using appropriate models can facilitate passing strong filters and serious examination to ensure proper quality and safety of them as a novel treatment approach. Animal models cannot be adequately helpful to follow pathophysiological features. Nowadays, stem cell-based models, particularly induced pluripotent stem cells reflected as suitable alternative models in this field. Accordingly, the importance of stem cell-based models, especially to experiment with the regenerative medicine outcomes for schizophrenia as one of the severe typing of psychiatric disorders, is addressed here.

Auxiliary role of mesenchymal stem cells as regenerative medicine soldiers to attenuate inflammatory processes of severe acute respiratory infections caused by COVID-19.

Acute respiratory infections as one of the most common problems of healthcare systems also can be considered as an important reason for worldwide morbidity and mortality from infectious diseases. Coronaviruses are a group of well-known respiratory viruses that can cause acute respiratory infections. At the current state, the 2019 novel coronavirus is cited as the most worldwide problematic agent for the respiratory system. According to investigations, people with old age and underlying diseases are at higher risk of 2019 novel coronavirus infection. Indeed, they may show a severe form of the disease (with severe acute respiratory infections). Based on the promising role of cell therapy and regenerative medicine approaches in the treatment of several life-threatening diseases, it seems that applying cell-based approaches can also be a hopeful strategy for improving subjects with severe acute respiratory infections caused by the 2019 novel coronavirus. Herein, due to the amazing effects of mesenchymal stem cells in the treatment of various diseases, this review focuses on the auxiliary role of mesenchymal stem cells to reduce inflammatory processes of acute respiratory infections caused by the 2019 novel coronavirus.

Cellular Dust as a Novel Hope for Regenerative Cancer Medicine.

Although stem cells have the most therapeutic potential, the advantages of regenerative medicine may be best provided using extracellular vesicles which also known in the past as "cellular dust." These microparticles are substances released by cells and play a pivotal role in pathophysiology of tumor progression and metastasis, thrombosis, and inflammation. Extracellular vesicles including exosomes and cell-derived microparticles supporting many physiological and disease processes which are relevant to immunology, hemostasis, thrombosis, neurobiology, cell signaling, angiogenesis, and cancer. While they have not any value for many years, this cellular dust has been studied and shows therapeutic properties similar to their mother cells (stem cells) but without their disadvantages. These vesicles do not divide, limiting the risk of cancer, and do not differentiate either. Therefore, they prevent tumor progression and development of poor function. Furthermore, it appears that they can be produced by a single donor for several patients, and have already confirmed their therapeutic potential in animals in repairing heart, liver and kidney lesions. The present study was aimed to introduce cellular dust as a new horizon for regenerative cancer medicine and also new hope for potential therapeutic applications of cancer and associated diseases.

The Horizon of Gene Therapy in Modern Medicine: Advances and Challenges.

Gene therapy as a novel study in molecular medicine will have a significant impact on human health in the near future. In recent years, the scope of gene therapy has been developed and is now beginning to revolutionize therapeutic approaches. Accordingly, many types of diseases are now being studied and treated in clinical trials through various gene delivery vectors. The emergence of recombinant DNA technology which provides the possibility of fetal genetic screening and genetic counseling is a good case in point. Therefore, gene therapy advances are being applied to correct inherited genetic disorders such as hemophilia, cystic fibrosis, and familial hypercholesterolemia as well as acquired diseases like cancer, AIDS, Alzheimer's disease, Parkinson's disease, and infectious diseases like HIV. As a result, gene therapy approaches have the ability to help the vast majority of newborns with different diseases. Since these ongoing treatments and clinical trials are being developed, many more barriers and challenges have been created. In order to continue this positive growth, these challenges need to be recognized and addressed. Accordingly, safety, efficiency and also risks and benefits of gene therapy trials for each disease should be considered. As a result, sustained manufacturing of the therapeutic gene product without any harmful side effects is the least requirement for gene therapy. Herein, different aspects of gene therapy, an overview of the progress, and also the prospects for the future have been discussed for the successful practice of gene therapy.