From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research ...protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day−1, 200 mg day−1, 150 mg day−1 and 2.5 mg kg−1) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day−1 for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Brassinosteroids (BRs) are the class of phytohormones with great importance in agriculture and potential diverse effects on human welfare, including skin disease treatment. In this sense, BRs are a ...promising tool for promoting skin regeneration.
Therefore, the objective of the present work was to analyze the effect of BRs in wound repair, mainly the inflammatory and proliferative phases, and their influence on migratory abilities in human dermal fibroblasts (HDFa), and consequently understand the mitochondrial metabolism.
We measured nine natural and synthetic BRs for the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We further evaluated the migration activity in HDFa modeling promotion of wound closure after BRs exposure. In addition, we evaluated the 84 gene profiles linked to wound healing response using RT2 Profiler PCR Array and examined cellular bioenergetics using an extracellular flux analyzer.
Results showed that LPS-induced cells had around 10 % lower reactive oxygen species and nitric oxide accumulation when treated with some BRs compounds. HDFa treated with homobrassinolide-based and homocastasterone-based compounds resulted in the greatest migratory activity and presents the best results for mitochondrial responses.
Together, these results provided strong evidence for BRs' ability to promote skin health, particularly through contributions to both reducing excessive oxidative stress and controlling the inflammation process resulting in the best HDFa cell migration through the control of mitochondrial function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride ...is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.
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•Finasteride and Minoxidil are approved drugs for androgenetic alopecia.•In the testis the drugs affect lead to male reproductive disorders.•In vivo and in vitro studies help to make decisions for new therapeutic approaches.•Systematic reviews has been listed as a high-level study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The presence of infections is one of the main factors that leads to delays in healing or non-closure of cutaneous wounds. Although the goal of antibiotic use is to treat or prevent infection, there ...is currently no agreement on the effectiveness of these products.
The aim of this study was to evaluate the efficacy of antibiotic use during the healing process of skin wounds in animal models not intentionally infected, as well as to analyze the advances and limitations of the studies carried out in this field.
This systematic review was performed according to the PRISMA guidelines, using a structured search on the MedLine (PubMed) and Scopus platforms to retrieve studies published until August 29, 2018, 13:35p.m. The studies included were limited to those that used excision or incision wound models and that were not intentionally infected. The data for the animal models, antibiotic used, and the main results of the studies were extracted, and compared where possible. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool.
Twenty-seven studies were selected. Overall, the effects of the antibiotic on the wound decreased inflammatory cell infiltration and promoted an increased number of fibroblasts, extracellular matrix constituents, re-epithelialization and tissue strength. A great deal of important information about the methodology was not presented, such as: the statistical analysis used, the animal model (sex and age), antibiotic dosage, blinding and randomization of the animals chosen.
Based on the results found, we believe that antibiotic therapy can be considered a viable alternative for the treatment of cutaneous wounds. However, current evidence obtained from the methodological quality analysis points towards a high risk of bias. This is due to the incomplete characterization of the experimental design and treatment protocol, which compromises the reproducibility of the studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
At the beginning of the process, the collagen exposed initiates the coagulation cascade forming the platelet cap, and as the process progresses occur, the release of many cytokines and growth factors ...promotes cell and vascular proliferation 3 The next stage is the proliferative phase, characterized by the synthesis of the granulation tissue rich in vessels, cells, and type III collagen. Thinking in the relationship among different phases of the wound healing process, different treatments, and redox metabolism, this special issue gathered 9 studies using in vivo and in vitro analyses to understand the cellular, immunological, and morphological bases associated with the recovery process of the injured tissue. Concerning new therapies, some studies have shown that external agents such as peptides obtained from animals, plant extract, and acidic electrolyzed water and antibiotics were considered as a rich source of active molecules with potential relevance and applicability indirect or complementary strategies focused on tissue repair.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The accentuated increase in the use of medicinal plants by the population to treat diseases makes it necessary to carry out pharmacological studies in order to contribute to the scientific knowledge ...and clarify the mechanisms involved in the main compounds present in these plants. Due to the difficulty of combating antimicrobial-resistant microorganisms, plants become a low-cost and effective alternative. The stem, fruit, and leaves of plants are used to measure antioxidant and antimicrobial capacity and to combat the oxidative degradation of free radicals produced in the presence of xenobiotics. A systematic review is a powerful tool that incorporates the variability among the studies, providing an overall estimate of the use of plant extracts as antioxidants and antimicrobial activities. In view of the controversies in the literature regarding the use of compounds from plants or the isolation and purification of the main substances for the prevention of bacterial various therapeutic actions, the aim of this was to present a systematic review on the antimicrobial and antioxidant properties of cashew (Anacardium occidentale), cajui (Anacardium microcarpum), and pequi (Caryocar brasiliense). The following databases were analyzed: PubMed/Medline, Virtual Health Library (LILACS and SciELO), and Science Direct. Out of 425 articles, 33 articles have been used in this study, which were also represented in the Prisma Statement. In vitro antioxidant tests were conducted in 28 studies using different methodologies. Most of the tests involving the studied species demonstrated positive antioxidant potential and antimicrobial properties. The results provide important data and perspectives into the use of natural products that can contribute to the treatment of various diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Type 2 diabetes mellitus (T2DM) is among the most prevalent diseases in the world, affecting over 420 million people. The disease is marked by a poor metabolic effect of insulin leading to chronic ...hyperglycaemia, which can result in microvascular complications. It is widely known that postprandial glycaemia is reliant on the total carbohydrate content of a meal. However, the importance of the amount and the source of these carbohydrates remains controversial due to mechanisms other than insulin secretion. Oxidative stress, inflammation, pyruvate production and the quality of the intestinal microbiota, resulting in plasma lipopolysaccharides and short-chain fatty acids production, play an important role in blood sugar control and consequently in type 2 diabetes. Thus, we systematically reviewed the preclinical evidences on the impact of the amount and type of carbohydrate found in different diets and its influence on blood glucose levels in diabetic animals. We used a comprehensive and structured search in biomedical databases Medline (PubMed), Scopus and Web of Science, recovering and analyzing 27 original studies. Results showed that sucrose-rich diets deteriorated diabetic condition in animal models regardless of the total dietary carbohydrate content. On the other hand, fiber, particularly resistant starch, improved blood glucose parameters through direct and indirect mechanisms, such as delayed gastric emptying and improved gut microbiota. All studies used rodents as animal models and male animals were preferred over females. Improvements in T2DM parameters in animal models were more closely related to the type of dietary carbohydrate than to its content on a diet, i. e., resistant starch seems to be the most beneficial source for maintaining normoglycemia. Results show that current literature is at high risk of bias due to neglecting experimental methods.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The excess of proinflammatory mediators promotes the increase of the peroxide of hydrogen (H2O2) and nitric oxide content, which accelerate the peroxidation of the component cells 7, 8. ...a ...controlled inflammation process is necessary to avoid persistent tissue damage through the continued action of free radicals and reactive oxygen species (ROS) 7. ...disruptors of redox balance (e.g., inductors of oxidative stress or inhibitors of antioxidant molecules) have been proposed as candidates for new healing drugs. The former study showed that nutrient intake and malnutrition can act as predictors of oxidative uremic toxicity. ...they provided evidence that age and sex exhibited a limited association with malnutrition and cardiometabolic risk factors in haemodialysis patients. The latter study evaluated glutamine supplementation for the treatment of acute pancreatitis and showed that the use of glutamine might be promising for the future management of acute pancreatitis by relieving the intracellular energy stress, thereby attenuating the predominance of necrosis over apoptosis. ...one review summarized the role of macroautophagy in the heart following myocardial infarction and showed that some noncoding RNAs and their easy manipulation exposed their potential as new targets for clinical development to treat autophagy-related diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Considering the efficacy of rapamycin in increasing lifespan and healthspan, attenuating the aging-dependent immunological decline, we compared the evolution of Trypanosoma cruzi infection and acute ...myocarditis in young and elderly mice untreated and chronically treated with this drug. Five groups were investigated: young uninfected and infected, elderly uninfected and infected with Trypanosoma cruzi untreated and treated with rapamycin (4 mg/kg every 3 days) from the 8th to the 96th week of age. Seven days after the last treatment, elderly mice were inoculated with T. cruzi. Young animals were infected at 8-weeks-old. Untreated elderly mice exhibited increase parasitemia, parasite load and myocarditis, which were associated to down-regulation in IL-2, IL-6, IFN-γ, TNF, anti-T. cruzi immunoglobulin G (IgG) total, IgG1 and IgG2a plasma levels, inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) cardiac production, as well as upregulation in Arginase-1 gene expression and arginase activity compared to young animals. These parameters were improved in rapamycin-pretreated elderly mice, which exhibited a better parasitological control, reduced heart inflammation and microstructural damage. These responses were associated with a better balance between Th1 and Th2 effectors similar to that observed in young animals, including an improved activation of Th1 cytokines and the iNOS pathway that positively regulates NO biosynthesis, contradicting the predominant activation of the arginase pathway in untreated elderly animals. Thus, our findings suggest that chronic pretreatment with rapamycin can attenuate immunosenescence in mice, contributing to prolong parasite resistance and attenuate acute myocarditis in elderly host challenged by T. cruzi.
•The effect of rapamycin on T. cruzi-infected young and elderly mice was analyzedE.•Elderly mice developed Th1/Th2 and iNOS/Arg imbalance and a severe infection.•Rapamycin reversed age-dependent Th1 and iNOS down-regulation in elderly animals.•Rapamycin attenuated systemic and heart inflammation in elderly animals.•Rapamycin attenuated T. cruzi-infection by restrict immunosenescence in mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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