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Androgenetic alopecia (AGA) is the most common hair loss disorder, affecting millions of men and women worldwide. Current formulations used to treat this condition often lead to a wide variety of side effects, ranging from allergies to sexual disfunction, especially when those drugs are administered orally. In this study, we developed and tested unique formulations containing nanostructured lipid carriers (NLC) composed of lipids extracted from fruit seeds, carrying finasteride to enhance efficacy of AGA treatment. By stabilizing the hydrophobic compounds in the solid matrix, three formulations of NLC were engineered and successfully prepared. Further an in vivo model of AGA was induced in rats by the administration of testosterone, as a platform to evaluate the efficiency of the formulations. The chosen formulation exhibited high bioavailability, medium size of 124.5 nm and PdI of 0.143, without systemic absorption. In addition, it promoted efficient and significant follicle restoration in AGA induced rats by increasing number of active bulbs and showed to be a safe formulation for topical application. The results of this research indicate that the presented formulation has significant potential to yield improved outcomes in AGA treatment., 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 © 2024 Elsevier B.V. All rights reserved.)

Introduction: Research in tumor treatment has shown promising results using extracellular vesicles (EVs) derived from immune cells. EVs derived from M1 macrophages (proinflammatory), known as M1-EVs, have properties that suppress tumor growth, making them a promising treatment tool for immune susceptible tumors such as melanoma. Here, small unaltered M1-EVs (M1-sEVs) were employed in a 3D mouse melanoma model (melanospheres) to evaluate such activity., Methods: Macrophages were polarized and EVs were isolated by ultracentrifugation. The EVs obtained were characterized based on size, with measurements performed by dynamic light scattering and electron microscopy, and the expression profiles of microRNAs were analyzed by microarray and PCR. Melanospheres were used to evaluate the cytotoxicity of M1-sEVs. Pondering a possible future transposition from the animal model to the human, human melanoma cells were transfected with a specific miRNA, and the impact on cell proliferation was evaluated., Results: The isolated EVs showed a size distribution between 50-400 nm in diameter, but preeminently in a range of 70-90 nm. M1-sEVs demonstrated a remarkable ability to reduce cell proliferation and viability in the melanospheres, leading to a decrease in their volume. M1-sEVs contained unique miRNAs, including miR-29a-3p, which exhibited significant antitumor activities according to bioinformatics analysis. Validation of the antitumor effects of miR-29a-3p was obtained by a functional evaluation, i.e., by inducing miRNA overexpression in human melanoma cells (SK-MEL-28)., Conclusion: Although further research would be advisable, the study provides evidence supporting the potential of M1-sEVs and their miRNA load as a possible targeted immune therapy for melanoma.

Background: Considering that microRNAs (miRNAs), extracellular vesicles and particles (EVPs) and the amyloid precursor protein (APP) processing have been shown to be altered in oral squamous cells carcinoma (OSCC), it is possible that miRNAs that target APP processing pathways in EVPs are impacted in tumor cells. Our aim was to evaluate miRNAs that target APP itself or disintegrin and metalloproteinase domain 10 (ADAM10), which generate a trophic compound, sAPPα, in EVPs derived from OSCC cell lines, an aggressive and non-invasive, compared to normal keratinocytes., Methods: We used two OSCC cell lines, an aggressive human oral squamous cell carcinoma cell line (SCC09) and a less aggressive cell line (CAL27) compared with a keratinocyte lineage (HaCaT). Cells were maintained in cell media, from which we isolated EVPs. EVPs were evaluated regarding their size and concentration using Nanotracking Analysis. We measured the levels of miRNAs which had as potential downstream target APP or ADAM10, specifically miR-20a-5p, miR-103a-3p, miR-424-5p, miR-92b-3p, miR-31-5p, and miR-93-5., Results: There were no differences on size distributions and concentration of isolated EVPs. OSCC cell lines-derived EVPs miR-20a-5p, miR-92b-3p, and miR-93-5p were upregulated in comparison to HaCaT-derived EVPs; while miR-31-5p was reduced in EVPs obtained from CAL27 cells., Conclusion: Our results indicate changes in miRNAs that target APP machinery processing in EVPs derived from OSCC cell lines of different aggressiveness, which may be involved with abnormal miRNA expression in OSCC tissue and/or releasing tumor suppressor miRNA., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bone metastatic prostate cancer (PCa) is associated with a high risk of mortality. Changes in the expression pattern of miRNAs seem to be related to early aspects of prostate cancer, as well as its establishment and proliferation, including the necessary steps for metastasis. Here we compiled, for the first time, the important roles of miRNAs in the development, diagnosis, and treatment of bone metastasis, focusing on recent in vivo and in vitro studies. PCa exosomes are proven to promote metastasis-related events, such as osteoblast and osteoclast differentiation and proliferation. Aberrant miRNA expression in PCa may induce abnormal bone remodeling and support tumor development. Furthermore, miRNAs are capable of binding to multiple mRNA targets, a dynamic property that can be harnessed for the development of treatment tools, such as antagomiRs and miRNA mimics, which have emerged as promising candidates in PCa treatment. Finally, miRNAs may serve as noninvasive biomarkers, as they can be detected in tissue and bodily fluids, are highly stable, and show differential expression between nonmetastatic PCa and bone metastatic samples. Taken together, the findings underscore the importance of miRNA expression profiles and miRNA-based tools as rational technologies to increase the quality of life and longevity of patients.

Sesquiterpene lactone (SL) subtypes including hirsutinolide and cadinanolide have a controversial genesis. Metabolites of these classes are either described as natural products or as artifacts produced via the influence of solvents, chromatographic mobile phases, and adsorbents used in phytochemical studies. Based on this divergence, and to better understand the sensibility of these metabolites, different pH conditions were used to prepare semisynthetic SLs and evaluate the anti-inflammatory and antiproliferative activities. Therefore, glaucolide B ( 1 ) was treated with various Brønsted-Lowry and Lewis acids and bases-the same approach was applied to some of its derivatives-allowing us to obtain 14 semisynthetic SL derivatives, 10 of which are hereby reported for the first time. Hirsutinolide derivatives 7a (CC 50 = 5.0 µM; SI = 2.5) and 7b (CC 50 = 11.2 µM; SI = 2.5) and the germacranolide derivative 8a (CC 50 = 3.1 µM; SI = 3.0) revealed significant cytotoxic activity and selectivity against human melanoma SK-MEL-28 cells when compared with that against non-tumoral HUVEC cells. Additionally, compounds 7a and 7c.1 showed strongly reduced interleukin-6 (IL-6) and nitrite (NOx) release in pre-treated M1 macrophages J774A.1 when stimulated with lipopolysaccharide. Despite the fact that hirsutinolide and cadinanolide SLs may be produced via plant metabolism, this study shows that acidic and alkaline extraction and solid-phase purification processes can promote their formation., Competing Interests: The authors declare no conflicts of interest.

Senecio spp. is one of the most frequent plant-related poisonings in cattle. Its ingestion generates the disease seneciosis, characterized by hepatic damages. Liver biopsies and serum markers dosage are tools used in diagnosis; however, many breeding cattle are undiagnosed. MicroRNAs are non-coding RNA, stable in biological fluids. Their difference in expression levels may indicate the presence of the poisoning. We analyzed the miRNA profiling to identify potential diagnostic biomarkers for Senecio brasiliensis poisoning. The expression of miR-21, miR-885, miR-122, miR-181b, miR-30a, miR-378, and let-7 f were evaluated in the serum of exposed cattle. At least one histological change was found in liver and lower quantity of albumin and high AST and ALP were also detected. MiRNAs miR-30a, miR-378, miR-21, miR-885, and miR-122 presented significantly higher expression in intoxicated animals than in healthy animals. Furthermore, miR-122, miR-885, and, especially, miR-21 signatures demonstrated high sensitivity and specificity, with potential application for detecting poisoning., (Copyright © 2022 Elsevier B.V. All rights reserved.)

MicroRNA (miRNAs) are small non-coding RNA molecules involved in a wide range of biological processes through the post-transcriptional regulation of gene expression. Most studies evaluated microRNA expression in human, and despite fewer studies in veterinary medicine, this topic is one of the most exciting areas of modern veterinary medicine. miRNAs showed to be part of the pathogenesis of diseases and reproduction physiology in animals, making them biomarkers candidates. This review provides an overview of the current knowledge regarding miRNAs' role in reproduction and animal diseases, diagnostic and therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Acanthamoeba spp. are the causative agents of a sight-threatening infection of the cornea known as Acanthamoeba keratitis (AK). Amphotericin B - deoxycholate (AB) is used in the treatment of infectious keratitis, however, its topical administration has side effects as blepharitis, iritis, and painful instillation. In this context, the preheating of AB can decrease its toxicity by the formation of super aggregates (hAB). hAB associated with a thermoreversible in situ gelling ophthalmic system is a promising option due to the latter biocompatibility, low toxicity, and high residence time on the ocular surface. Our objective was to develop a topical ocular formulation of hAB for the treatment of AK. After heating at 70°C for 20 min, hAB was incorporated into a thermoreversible gelling system. The amebicidal activity of AB and hAB was evaluated against trophozoites and cysts of A. castellanii (ATCC 50492) and a regional clinical isolate (IC01). The results showed that the preheating of AB did not change the pharmacological action of the drug, with the amebicidal effect of AB and hAB under trophozoites and cysts of Acanthamoeba spp. The thermoreversible system remained stable, allowing the increase of drug retention time. For assessment of cytotoxicity, HUVEC (ATCC® CRL-1730) cells were challenged with AB and hAB for 48h. Cell viability was assessed, and hAB did not show cytotoxicity for HUVEC cells. As far as we know this was the first study that showed the preheated AB associated with a thermoreversible in situ gelling ophthalmic system as a promising system for topical ocular topical administration of hAB for AK therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)