Toxicity Assessment of New Ag-ZnO/AgO Nanocomposites: An In Vitro and In Vivo Approach.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

The Influence of IL-11 on Cardiac Fibrosis in Experimental Models: A Systematic Review.

Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.

Metallic nanoparticles and treatment of cutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous leishmaniasis (LC) is an infectious vector-borne disease caused by parasites belonging to the genus Leishmania. Metallic nanoparticles (MNPs) have been investigated as alternatives for the treatment of LC owing to their small size and high surface area. Here, we aimed to evaluate the effect of MNPs in the treatment of LC through experimental, in vitro and in vivo investigations. METHODS: The databases used were MEDLINE/ PubMed, Scopus, Web of Science, Embase, and Science Direct. Manual searches of the reference lists of the included studies and grey literature were also performed. English language and experimental in vitro and in vivo studies using different Leishmania species, both related to MNP treatment, were included. This study was registered in PROSPERO (CRD42021248245). RESULTS: A total of 93 articles were included. Silver nanoparticles are the most studied MNPs, and L. tropica is the most studied species. Among the mechanisms of action of MNPs in vitro, we highlight the production of reactive oxygen species, direct contact of MNPs with the biomolecules of the parasite, and release of metal ions. CONCLUSION: MNPs may be considered a promising alternative for the treatment of LC, but further studies are needed to define their efficacy and safety.

RNA vaccines in infectious diseases: A systematic review.

Infectious diseases are a major health concern worldwide, especially as they are one of the main causes of mortality in underdeveloped and developing countries. Those that are considered emerging and re-emerging are characterized by unpredictability, high morbidity and mortality, exponential spread, and substantial social impact. These characteristics highlight the need to create an "on demand" control method, with rapid development, large-scale production, and wide distribution. In view of this, RNA vaccines have been investigated as an effective alternative for the treatment and prevention of infectious diseases since they can meet those needs and are considered safe, affordable, and totally synthetic. Therefore, this systematic review aimed to evaluate the use of RNA vaccines for infectious diseases from experimental, in vivo, and in vitro studies. PubMed, Web of Science, and Embase were searched for suitable studies. Additionally, further investigations, such as grey literature checks, were performed. A total of 723 articles were found, of which only 41 met the inclusion criteria. These studies demonstrated the potential of using RNA vaccines to control 19 different infectious diseases, of which COVID-19 was the most studied. Similarly, viruses comprised the largest number of reported vaccine targets, followed by protozoa and bacteria. The mRNA vaccines were the most widely used, and the intramuscular route of administration was the most reported. Regarding preclinical experimental models, mice were the most used to evaluate the impact and safety of the RNA vaccines developed. Thus, although further studies and evaluation of the subject are necessary, it is evident that RNA vaccines can be considered a promising alternative in the treatment and prophylaxis of infectious diseases.

Cannabis sativa: A look at protozoa, helminths, insect vectors, and pests.

Active principles extracted from plants, such as essential oils, have been commonly described in the literature as therapeutic targets for numerous pathological conditions. Cannabis sativa, which has an ancient and peculiar history, has been used for various purposes, from recreational to compounds of pharmacotherapeutic and industrial importance, such as pesticides based on this plant. It is a plant that contains approximately 500 described cannabinoid compounds and is the target of in vitro and in vivo studies at different locations. This review clarifies the role of cannabinoid compounds in parasitic infections caused by helminths and protozoa. In addition, this study briefly presented the use of C. sativa constituents in the formulation of pesticides for vector control, as the latter topic is justified by the economic burden faced by several regions where vector-borne diseases are a troubling reality. Studies involving cannabis compounds with pesticidal potential should be encouraged, especially those that evaluate their effectiveness against the different life cycles of insects, seeking to interrupt vector proliferation after egg laying. Actions aimed at the management and cultivation of plant species with ecologically correct pharmacotherapeutic and pesticide potentials are becoming urgent.

Revisiting the hallmarks of cancer: A new look at long noncoding RNAs in breast cancer.

Breast cancer is one of the leading causes of death in women worldwide. The increasing understanding of the molecular mechanisms underlying its heterogeneity favors a better understanding of tumor biology and consequently the development of better diagnostic and treatment techniques. The advent of tumor genome sequencing techniques has highlighted more participants in the process, in addition to protein-coding genes. Thus, it is now known that long noncoding RNAs, previously described as transcriptional noise with no biological function, are intimately associated with tumor development. In breast cancer, they are abnormally expressed and closely associated with tumor progression, which makes them attractive diagnostic biomarkers and prognostic and specific therapeutic targets. Therefore, a thorough understanding of the regulatory mechanisms of long noncoding RNAs in breast cancer is essential for the search for new treatment strategies. In this review, we summarize the major long noncoding RNAs and their association with the cancer characteristics of the ability to sustain proliferative signaling, evasion of growth suppressors, replicative immortality, activation of invasion and metastasis, induction of angiogenesis, resistance to cell death, reprogramming of energy metabolism, genomic instability and sustained mutations, promotion of tumor inflammation, and evasion of the immune system. In addition, we report and suggest how they can be used as prognostic biomarkers and possible therapeutic targets.

Polymethylmethacrylate Microspheres are Immunologically Inert in Mouse Tissues.

Nowadays, aesthetic concerns have gained attention, especially by patients looking for a less invasive alternative to minor facial corrections. Polymethylmethacrylate (PMMA) is widely used as a soft tissue filler; the demand for this polymer has increased, and along with it, there are some reports of adverse reactions. Such adverse reactions stem from consequences of immune and inflammatory reactions to PMMA. Some animal models have been used to unravel the causes of these reactions, among other factors involving the management of PMMA. The aim of this study was to determine the immunogenic profile of PMMA implantation in different anatomical planes of mice, over up to 360 experimental days. In this study, BALB/c mice were divided into 30 groups for immune evaluation of the interaction between the organism and the polymer; 2% PMMA was implanted subcutaneously, 10% intramuscularly and 30% in periosteal juxtaposition and followed during five experimental days (7, 30, 90, 180 and 360 days after implantation-DAI). Pro- and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IFN-gamma, TNF, IL-17A, IL-10 and TGF-beta) were quantified in all experimental days. There was no statistical difference between the groups analyzed considering the evaluated parameters. Therefore, at all implanted depths, PMMA behaved inertly in a murine model.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Antitumor effect of melatonin on breast cancer in experimental models: A systematic review.

Breast cancer is the most frequent malignant neoplasm in females. While conventional treatments such as chemotherapy and radiotherapy are available, they are highly invasive and toxic to oncological patients. Melatonin is a promising molecule for the treatment of breast cancer with antitumor effects on tumorigenesis and tumor progression. The aim of this systematic review was to synthesize knowledge about the antitumor effect of melatonin on breast cancer in experimental models and propose the main mechanisms of action already described in relation to the processes regulated by melatonin. PubMed, Web of Science, and Embase databases were used. The inclusion criteria were in vitro and in vivo experimental studies that used different formulations of melatonin as a treatment for breast cancer, without year or language restrictions. Risk of bias for studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. Data from selected articles were presented as narrative descriptions and tables. Seventy-five articles on different breast cancer cell lines and experimental models treated with melatonin alone, or in combination with other compounds were included. Melatonin showed antitumor effects on proliferative pathways related to the cell cycle and tumorigenesis, tumor death, angiogenesis, and tumor metastasis, as well as on oxidative stress and immune regulatory pathways. These effects were either dependent or independent of melatonin receptors. Herein, we clarify the antitumor action of melatonin on different tumorigenic processes in breast cancer in experimental models. Systematic review registration: PROSPERO database (CRD42022309822/https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022309822).

A Revision of Polymeric Nanoparticles as a Strategy to Improve the Biological Activity of Melatonin.

Drug delivery systems based on nanotechnology exhibit a number of advantages over traditional pharmacological formulations. Polymeric nanoparticles are commonly used as delivery systems and consist of synthetic or natural polymers that protect drugs from degradation in physiological environments. In this context, indolamine melatonin has been associated with several biological functions, including antioxidant, antitumor, immunoregulatory, neuroprotective, and cardioprotective effects. However, its availability, half-life, and absorption depend upon the route of administration, and this can limit its therapeutic potential. An alternative is the use of polymeric nanoparticle formulations associated with melatonin to increase its bioavailability and therapeutic dose at sites of interest. Thus, the objective of this review is to provide a general and concise approach to the therapeutic association between melatonin and polymeric nanoparticles applied to different biological disorders and to also highlight its advantages and potential applications compared to those of the typical drug formulations that are available.