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Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology. Methods: The scoping review was conducted according to the Arksey and O'Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021. Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies. Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cavalcante, Freitas, Siquara da Rocha, Santos, Souza, Ramos, Rocha and Gurgel Rocha.)

Background: Coronavirus-19 disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory viruses damage not only the upper respiratory tract in humans, but also several different organs such as the brain. Some of the neurological consequences of COVID-19 reported are anosmia, headache, stroke, declined cognitive function, and impaired mental health, among others. People who had COVID-19 have a higher risk of sequelae in the central nervous system (CNS). However, it is not known which are all possible sequelae and how long will last the long-term effects of the COVID-19 pandemic on behavioral patterns and quality of life., Aim: We intend to address the long-term impacts of COVID-19 on mental health and the relevance of physical exercise during the pandemic., Methods: We conducted a literature search using PubMed to find the articles that were related to these themes., Results: We found 23,489 papers initially, and then we applied the inclusion/exclusion criteria to narrow down our search to 3617 articles and selected 1380 eligible articles after a thorough reading of titles and abstracts. The findings indicated that COVID-19 impacted general mental health and led many not only hospitalized patients to develop cognitive decline, memory impairment, anxiety, sleep alterations, and depressive-like behavior. Furthermore, the fear of vaccines and their effects had negatively affected mental health and directly impacted mortality rates in unvaccinated COVID-19 patients., Conclusions: Preventive measures must be undertaken, such as the vaccination of the entire population, vaccination hesitancy discouragement by creating awareness among individuals, and people's engagement in a physically active lifestyle, since being physically active is a low-cost and effective measure to restore or inhibit the negative outcomes from COVID-19 on mental health., (© 2023. The Author(s).)

Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and the inhibition of the Hedgehog (HH) pathway in OSCC. Initially, ATO cytotoxicity was assessed in a panel of cell lines. Cell viability, cell cycle, death patterns, and cell morphology were analyzed, as well as the effect of ATO on the expression of HH pathway components. After the cytotoxic assay, HSC3 cells were chosen for all in vitro assays. ATO increased apoptotic cell death and nuclear fragmentation in the sub-G1 cell cycle phase and promoted changes in cell morphology. In addition, the reduced expression of GLI1 indicated that ATO inhibits HH activity. The present study provides evidence of ATO as an effective cytotoxic drug for oral cancer treatment in vitro.

Drug repurposing has been applied in the biomedical field to optimize the use of existing drugs, leading to a more efficient allocation of research resources. In oncology, this approach is particularly interesting, considering the high cost related to the discovery of new drugs with therapeutic potential. Computational methods have been applied to predict associations between drugs and their targets. However, drug repurposing has not always been promising and its efficiency has yet to be proven. Therefore, the present scoping review protocol was developed to screen the literature on how in silico strategies can be implemented in drug repurposing in oncology. The scoping review will be conducted according to the Arksey and O'Malley framework (2005) and the Joanna Briggs Institute recommendations. We will search the PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We will include peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between January 1, 2003, and December 31, 2021. Data will be charted and findings described according to review questions. We will report the scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines (PRISMA-ScR)., Competing Interests: The authors have declared that no competing interests exist.

Overweight and obesity (OBT) is a serious health condition worldwide, and one of the major risk factors for cardiovascular disease (CVD), the main reason for morbidity and mortality worldwide. OBT is the proportional increase of Adipose Tissue (AT) compared with other tissue and fluids, associated with pathological changes in metabolism, hemodynamic overload, cytokine secretion, systemic inflammatory profile, and cardiac metabolism. In turn, AT is heterogeneous in location, and displays secretory capacity, lipolytic activation, insulin sensitivity, and metabolic status, performing anatomic, metabolic, and endocrine functions. Evidence has emerged on the bidirectional crosstalk exerted by miRNAs as regulators between the heart and AT on metabolism and health conditions. Here, we discuss the bidirectional endocrine role of miRNAs between heart and AT, rescuing extracellular vesicles' (EVs) role in cell-to-cell communication, and the most recent results that show the potential of common therapeutic targets through the elucidation of parallel and ⁄or common epigenetic mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Soci, Cavalcante, Improta-Caria and Roever.)

Obesity is associated with changes in memory. Thus, the aim of this systematic review was to investigate the physical exercise consequences on memory in obesity. A search was carried out in the PubMed, Lilacs, and Scielo databases with the following descriptors: "physical exercise," "memory," and "obesity." A total of 16 studies were analyzed in this review. Low, moderate, and high intensity exercise training showed positive effects on memory in patients with obesity (100%). The animal models of obesity used in their physical exercise protocols: treadmill (72.7%) or wheel running (27.3%). Most of the animal studies (81.8%) revealed positive effects of the physical exercise protocol on memory in obesity. Mouse was the most commonly used animal (54.5%), and a 60% high-fat diet (HFD) was the most commonly method used to induce obesity (82%). We did not identify any knockout model of obesity that was used to evaluate memory and used physical exercise as the main intervention. Thus, exercise training, independently if it is resistance or endurance training, seems to be an excellent intervention to prevent and inhibit cognitive impairment and memory loss on obese patients and animal models of obesity., (© 2021 World Obesity Federation.)

Objective: Epilepsy is a brain disorder that leads to seizures and neurobiological, cognitive, psychological, and social consequences. Physical inactivity can contribute to worse epilepsy pathophysiology. Here, we review how physical exercise affects epilepsy physiopathology., Methods: An extensive literature search was performed and the mechanisms of physical exercise on epilepsy were discussed. The search was conducted in Scopus and PubMed. Articles with relevant information were included. Only studies written in English were considered., Results: The regular practice of physical exercise can be beneficial for individuals with neurodegenerative diseases, such as epilepsy by decreasing the production of pro-inflammatory and stress biomarkers, increasing socialization, and reducing the incidence of epileptic seizures. Physical exercise is also capable of reducing the symptoms of depression and anxiety in epilepsy. Physical exercise can also improve cognitive function in epilepsy. The regular practice of physical exercise enhances the levels of brain-derived neuro factor (BDNF) in the hippocampi, induces neurogenesis, inhibits oxidative stress and reactive gliosis, avoids cognitive impairment, and stimulates the production of dopamine in the epileptic brain., Conclusion: Physical exercise is an excellent non-pharmacological tool that can be used in the treatment of epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic, caused by the rapid global spread of the novel coronavirus (SARS-CoV-2), has caused healthcare systems to collapse and led to hundreds of thousands of deaths. The clinical spectrum of COVID-19 is not only limited to local pneumonia but also represents multiple organ involvement, with potential for systemic complications. One year after the pandemic, pathophysiological knowledge has evolved, and many therapeutic advances have occurred, but mortality rates are still elevated in severe/critical COVID-19 cases. Mesenchymal stromal cells (MSCs) can exert immunomodulatory, antiviral, and pro-regenerative paracrine/endocrine actions and are therefore promising candidates for MSC-based therapies. In this review, we discuss the rationale for MSC-based therapies based on currently available preclinical and clinical evidence of safety, potential efficacy, and mechanisms of action. Finally, we present a critical analysis of the risks, limitations, challenges, and opportunities that place MSC-based products as a therapeutic strategy that may complement the current arsenal against COVID-19 and reduce the pandemic's unmet medical needs., (© 2021. The Author(s).)

Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barré syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2 + NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2 + and Casp3 + NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs., (Copyright © 2020 Cavalcante, Aragão-França, Sampaio, Nonaka, Oliveira, Campos, Sardi, Dias, Menezes, Rocha, Rossi, Paredes, Martins, Allahdadi, Peixoto, Barbosa-Filho, Souza and Soares.)

Alzheimer disease (AD) is one of the most common neurodegenerative diseases, affecting middle-aged and elderly individuals worldwide. AD pathophysiology involves the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain, along with chronic neuroinflammation and neurodegeneration. Physical exercise (PE) is a beneficial non-pharmacological strategy and has been described as an ally to combat cognitive decline in individuals with AD. However, the molecular mechanisms that govern the beneficial adaptations induced by PE in AD are not fully elucidated. MicroRNAs are small non-coding RNAs involved in the post-transcriptional regulation of gene expression, inhibiting or degrading their target mRNAs. MicroRNAs are involved in physiological processes that govern normal brain function and deregulated microRNA profiles are associated with the development and progression of AD. It is also known that PE changes microRNA expression profile in the circulation and in target tissues and organs. Thus, this review aimed to identify the role of deregulated microRNAs in the pathophysiology of AD and explore the possible role of the modulation of microRNAs as a molecular mechanism involved in the beneficial actions of PE in AD.

Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC ( n = 28), CD indeterminate form ( n = 10) and healthy controls ( n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.