The Effect of Rutin and Extracts of Uncaria guianensis (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study.

There is increasing interest in the potential of natural compounds to treat diseases, such as endometriosis, a gynecological disorder that affects 10-15% of women of reproductive age, and it is related to severe pelvic pain and infertility. We have evaluated the in vitro effects of rutin and the aqueous bark, roots, and leaf extracts (ABE, ARE, and ALE, respectively) and isolated components of Uncaria guianensis on stromal cells from eutopic endometrium and lesions of patients with endometriosis. Two- and three-dimensional cultures were used to assess the cell death and production of reactive oxygen species (ROS), cytokines and growth factors of cells following exposure to these natural products. The applied treatments did not reduce cellular viability, but ROS production did increase. In addition, significant increases in the levels of interleukin (IL)-15, IL-17A, IL-4, IL-6, tumor necrosis factor-α, and vascular endothelium growth factor were observed when 2D-cells from endometrium of patients with endometriosis were treated with ABE, while exposure to ALE induced significant increases in epidermal growth factor in lesion cells.

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-ß-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-ß-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-ß-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.

Interleukin in endometriosis-associated infertility-pelvic pain: systematic review and meta-analysis.

The objective is to study the significance of altered interleukin levels in endometriosis-related infertility or pelvic pain. The present systematic review and meta-analysis includes a discussion on the roles of interleukin in the physiopathology of endometriosis-associated infertility and/or pelvic pain. We included all studies in which interleukins in peritoneal fluid, follicular fluid or serum from patients were measured and that correlated the findings with either peritoneal or deep endometriosis-associated infertility or pelvic pain. For the meta-analysis, we selected studies on the following cytokines: interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8). Endometriosis is a chronic inflammatory disease. Inflammatory processes clearly participate in the etiology of endometriosis. Cytokines are mediators of inflammation, and increase in their concentration in plasma or other body fluids signals the presence and extent of tissue lesions. A number of studies have reported on the association between higher cytokine levels and progression or maintenance of endometriosis and coexisting infertility or pelvic pain. The results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility. Such association was not found for endometriosis-associated pain. In spite of accumulated evidence on the association of pro-inflammatory cytokines and endometriosis, it still is not clear if and how these mediators participate in the physiopathology of endometriosis-associated infertility or pelvic pain, in part due to poor quality of the evidence established in the vast majority of interleukins and challenges in endometriosis research reproducibility. In summary, the results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility.

Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review.

Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy due to multiple genetic alterations typically found in this cancer type. Natural products derived from plants often possess biological activities that may be valuable in the development of new therapeutic agents for cancer treatment. Several genera from the family Celastraceae have been studied in this context. This review reports studies on chemical constituents isolated from species from the Celastraceae family targeting cancer mechanisms studied to date. These results are then correlated with molecular characteristics of head and neck squamous cell carcinoma in an attempt to identify constituents with potential application in the treatment of this complex disease at the molecular level.

AKT inhibition interferes with the expression of immune checkpoint proteins and increases NK-induced killing of HL60-AML cells.

OBJECTIVE: To determine the role of the AKT pathway in the regulating of natural Killer-induced apoptosis of acute myeloid leukemia cells and to characterize the associated molecular mechanisms. METHODS: BALB/c nude mice were injected with HL60 cells to induce a xenogenic model of subcutaneous leukemic tumors. Mice were treated with perifosine, and their spleens were analyzed using biometry, histopathology, and immunohistochemistry. Gene expression analysis in leukemia cells was performed by real-time PCR. Protein analysis of leukemia and natural Killer cells was performed by flow cytometry. AKT inhibition in HL60 cells, followed by co-culture with natural Killer cells was performed to assess cytotoxicity. Apoptosis rate was quantified using flow cytometry. RESULTS: Perifosine treatment caused a reduction in leukemic infiltration in the spleens of BALB/c nude mice. In vitro , AKT inhibition reduced HL60 resistance to natural Killer-induced apoptosis. AKT inhibition suppressed the immune checkpoint proteins PD-L1, galectin-9, and CD122 in HL60 cells, but did not change the expression of their co-receptors PD1, Tim3, and CD96 on the natural Killer cell surface. In addition, the death receptors DR4, TNFR1, and FAS were overexpressed by AKT inhibition, thus increasing the susceptibility of HL60 cells to the extrinsic pathway of apoptosis. CONCLUSION: The AKT pathway is involved in resistance to natural Killer-induced apoptosis in HL60 cells by regulating the expression of immune suppressor receptors. These findings highlight the importance of AKT in contributing to immune evasion mechanisms in acute myeloid leukemia and suggests the potential of AKT inhibition as an adjunct to immunotherapy.

Scientists of Tomorrow/ Cientistas do Amanhã : a project to inspire, stimulate scientific thinking, and introduce scientific methodology for young students.

The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health. In Brief Rangel et al. enumerated the Scientists of Tomorrow/Cientistas do Amanhã program, an immersive science initiative conducted in collaboration with a public school. The program, which involved 15 students, aimed to promote science, share knowledge, inspire academic paths, and underscore societal impacts. Led by postgraduates, professors, and healthcare experts, the program included diverse lectures and practical laboratory activities. Highlights Every research endeavor commences with a fundamental question. Sharing of findings by researchers and students contributes toward the expansion of knowledge. Teaching scientific methodology is a pivotal step in nurturing critical thinking skills. Science permeates our daily lives and plays a crucial role in addressing societal issues.

Overview of miRNAs for the non-invasive diagnosis of endometriosis: evidence, challenges and strategies. A systematic review.

OBJECTIVE: The aim of the study was to assess the evidence on miRNAs as biomarkers for the diagnosis of endometriosis, as well as to provide insights into the challenges and strategies associated with the use of these molecules as accessible tools in clinical practice. METHODS: Systematic review conducted on PubMed®, Latin American and Caribbean Health Sciences Literature (LILACS), MEDLINE® and Web of Science databases using the search terms endometriosis (all fields) AND miRNA (all fields), evaluating all publication up to May 2019. RESULTS: Most miRNAs found to be dysregulated in this study were harvested from tissue samples, which precludes their use as a non-invasive diagnostic test. However, differential expression of 62 miRNAs was reported in samples that may be used for non-invasive diagnosis of endometriosis, such as blood, serum and plasma. CONCLUSION: Despite the identification of several candidates, studies are investigatory in nature and have been conducted with small number of samples. Also, no particular miRNA has been validated for diagnostic purposes so far. Studies based primarily on biological samples and applicable to translational research are warranted. Large databases comprising information on sample type and the use of saliva and vaginal fluid for miRNAs identification may prove essential to overcome current barriers to diagnosis of endometriosis.

Swab pooling: A new method for large-scale RT-qPCR screening of SARS-CoV-2 avoiding sample dilution.

To minimize sample dilution effect on SARS-CoV-2 pool testing, we assessed analytical and diagnostic performance of a new methodology, namely swab pooling. In this method, swabs are pooled at the time of collection, as opposed to pooling of equal volumes from individually collected samples. Paired analysis of pooled and individual samples from 613 patients revealed 94 positive individuals. Having individual testing as reference, no false-positives or false-negatives were observed for swab pooling. In additional 18,922 patients screened with swab pooling (1,344 pools), mean Cq differences between individual and pool samples ranged from 0.1 (Cr.I. -0.98 to 1.17) to 2.09 (Cr.I. 1.24 to 2.94). Overall, 19,535 asymptomatic patients were screened using 4,400 RT-qPCR assays. This corresponds to an increase of 4.4 times in laboratory capacity and a reduction of 77% in required tests. Therefore, swab pooling represents a major alternative for reliable and large-scale screening of SARS-CoV-2 in low prevalence populations.

Deep Infiltrating Endometriosis and Activation and Memory Surface Markers and Cytokine Expression in Isolated Treg Cells.

It is not yet clear whether regulatory T (Treg) cells are active, and whether they play a favorable or adverse effect on endometrial foci implantation. Our aim was to evaluate activation and memory surface markers in Treg isolated from peritoneal fluid (PF) and peripheral blood (PB) of women with deep endometriosis and to assess its cytokine mRNA expression. This case-control study included 49 women with deep infiltrating endometriosis and 20 healthy controls. It was analyzed PF and PB of both groups. Cell surface markers GITR, TNFRII, HLA-DR, ICOS, CTLA-4, CD45RA, and CD45RO were evaluated in Treg (CD3+CD4+CD25+CD127lowFoxp3+) cells by flow cytometry. Additionally, Foxp3, TGF-beta, IL-10, IL-6, and TNF-alpha mRNA expression was assessed by real-time PCR in Treg cells (CD4+CD25+CD127dim/-) isolated using magnetic microbeads. Women with endometriosis had higher percentages of TNFRII+ Treg and CTLA-4+ Treg in their PB, and lower percentages of ICOS+ Treg and CD45RO+ Treg in their PF. The groups displayed no differences in mRNA expression. Regardless of the group, in PF, the percentage of Treg cells overall and of CD45RA+ Treg cells were significantly lower, whereas the percentage of TNFRII+ Treg and CD45RO+ Treg were significantly higher than in PB. Foxp3 and TGF-beta mRNA expression were also higher in PF than in PB. Our results indicated that Treg cells in women with endometriosis have a distinct profile of activation and memory markers, but similar cytokine expression. Moreover, we could observe clearly that Treg cells have distinct profile regarding their origin site.

Regulatory T cells isolated from endometriotic peritoneal fluid express a different number of Toll-like receptors.

OBJECTIVE: To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. METHODS: Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. RESULTS: Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. CONCLUSION: Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.

Microbiome Profile of Deep Endometriosis Patients: Comparison of Vaginal Fluid, Endometrium and Lesion.

This work aimed to identify and compare the bacterial patterns present in endometriotic lesions, eutopic endometrium and vaginal fluid from endometriosis patients with those found in the vaginal fluid and eutopic endometrium of control patients. Vaginal fluid, eutopic endometrium and endometriotic lesions were collected. DNA was extracted and the samples were analyzed to identify microbiome by high-throughput DNA sequencing of the 16S rRNA marker gene. Amplicon sequencing from vaginal fluid, eutopic endometrium and endometriotic lesion resulted in similar profiles of microorganisms, composed most abundantly by the genus Lactobacillus, Gardnerella, Streptococcus and Prevotella. No significant differences were found in the diversity analysis of microbiome profiles between control and endometriotic patients; however deep endometriotic lesions seems to present different bacterial composition, less predominant of Lactobacillus and with more abundant Alishewanella, Enterococcus and Pseudomonas.

One year cross-sectional study in adult and neonatal intensive care units reveals the bacterial and antimicrobial resistance genes profiles in patients and hospital surfaces.

Several studies have shown the ubiquitous presence of bacteria in hospital surfaces, staff, and patients. Frequently, these bacteria are related to HAI (healthcare-associated infections) and carry antimicrobial resistance (AMR). These HAI-related bacteria contribute to a major public health issue by increasing patient morbidity and mortality during or after hospital stay. Bacterial high-throughput amplicon gene sequencing along with identification of AMR genes, as well as whole genome sequencing (WGS), are biotechnological tools that allow multiple-sample screening for a diversity of bacteria. In this paper, we used these methods to perform a one-year cross sectional profiling of bacteria and AMR genes in adult and neonatal intensive care units (ICU and NICU) in a Brazilian public, tertiary hospital. Our results showed high abundances of HAI-related bacteria such as S. epidermidis, S. aureus, K. pneumoniae, A. baumannii complex, E. coli, E. faecalis, and P. aeruginosa in patients and hospital surfaces. Most abundant AMR genes detected throughout ICU and NICU were mecA, blaCTX-M-1 group, blaSHV-like, and blaKPC-like. We found that NICU environment and patients were more widely contaminated with pathogenic bacteria than ICU. Patient samples, despite the higher bacterial load, have lower bacterial diversity than environmental samples in both units. Finally, we also identified contamination hotspots in the hospital environment showing constant frequencies of bacterial and AMR contamination throughout the year. Whole genome sequencing (WGS), 16S rRNA oligotypes, and AMR identification allowed a high-resolution characterization of the hospital microbiome profile.

Uncovering the hidden microbiota in hospital and built environments: New approaches and solutions.

IMPACT STATEMENT: Research concerning the microbiome of indoor environments like hospitals, houses or buildings could have several implications for human health. Today, there is an ongoing shift in the paradigm of microbial analysis, from single isolated bacterial samples to entire microbiome profiles using high-throughput DNA sequencing methods. The use of sequencing methods in several studies has revealed an unprecedented microbial diversity in indoor environments, leading to a larger comprehension of the entire microbiome context. Here, we present a review of these microbiome studies using high-throughput DNA sequencing, including some new approaches and ideas that can be broadly applied in microbial tracking and epidemiological surveillance of indoor environments.

Hormone treatment as first line therapy is safe and relieves pelvic pain in women with bowel endometriosis.

OBJECTIVE: To evaluate clinical features and complications in patients with bowel endometriosis submitted to hormonal therapy. METHODS: Retrospective study based on data extracted from medical records of 238 women with recto-sigmoid endometriosis treated between May 2010 and May 2016. RESULTS: Over the course of follow-up, 143 (60.1%) women remained in medical treatment while 95 (39.9%) presented with worsening of pain symptoms or intestinal lesion growth (failure of medical treatment group), with surgical resection performed in 54 cases. Women in the Medical Treatment Group were older (40.5±5.1 years versus 37.3±5.8 years; p<0.0001) and had smaller recto sigmoid lesions (2.1±1.9 versus 3.1±2.2; p=0.008) compared to those who had failed to respond to medical treatment. Similar significant reduction in pain scores for dysmenorrhea, chronic pelvic pain, cyclic dyschezia and dysuria was observed in both groups; however greater reduction in pain scores for dyspareunia was noted in the Surgical Group. Subjective improvement in pain symptoms was also similar between groups (100% versus 98.2%; p=0.18). Major complications rates were higher in the Surgical Group (9.2% versus 0.6%; p=0.001). CONCLUSION: Patients with recto-sigmoid endometriosis who failed to respond to medical treatment were younger and had larger intestinal lesions. Hormonal therapy was equally efficient in improving pain symptoms other than dyspareunia compared to surgery, and was associated with lower complication rates in women with recto-sigmoid endometriosis. Medical treatment should be offered as a first-line therapy for patients with bowel endometriosis. Surgical treatment should be reserved for patients with pain symptoms unresponsive to hormonal therapy, lesion growth or suspected intestinal subocclusion.

Short-Term Effects of Sepsis and the Impact of Aging on the Transcriptional Profile of Different Brain Regions.

Among the clinical manifestations observed in septic patients, sepsis-associated encephalopathy (SAE) is probably the most obscure and poorly explored. It is well established, however, that SAE is more prevalent in aged individuals and related to a worse outcome. In this context, we decided to investigate the acute effects of sepsis, induced by cecal ligation and puncture (CLP), on the cerebral transcriptional profile of young and old rats. The idea was to highlight important signaling pathways possibly implicated in the early stages of SAE. Global gene expression analysis of three different brain regions (hippocampus, cerebellum, and cortex) indicated a relatively small interference of sepsis at the transcriptional level. Cerebellum tissue was the least affected by sepsis in aged rats. The increased expression of S100a8, Upp1, and Mt2a in all three brain regions of young septic rats indicate that these genes may be involved in the first line of response to sepsis in the younger brain. On the other hand, altered expression of a network of genes involved in sensory perception of smell in the cortex of aged rats, but not in young ones, indicates an earlier disruption of cortex function, possibly more sensitive to the systemic inflammation. The expression of S100a8 at the protein level was confirmed in all brain regions, with clear-up regulation in septic aged cortex. Taken together, our results indicate that the transcriptional response of the central nervous system to early sepsis varies between distinct brain regions and that the cortex is affected earlier in aged animals, in line with early neurological manifestations observed in older patients.

Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease.

The aim of this study was to evaluate Treg and NK cells related cytokines in deep infiltrating endometriosis lesions and its relationship with clinical symptoms of the disease. mRNA expression of Transforming Growth Factor Beta (TGFB), Interleukin (IL)10, Interferon Gamma (IFNG), IL7, and IL15 was analyzed by Real-Time PCR in eutopic endometrium and rectosigmoid lesions from 11 women with deep infiltrating endometriosis and in eutopic endometrium from 11 healthy women. IL10, IFNG, and IL7 expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from women with endometriosis. IL10 and TGFB expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from healthy women. In addition, TGFB and IL15 levels correlated positively with deep dyspareunia and cyclic dyschezia, respectively, while IL7 levels correlated negatively with dysmenorrhea. Deep infiltrating rectosigmoid endometriosis displays alterations in Treg and NK cells related cytokine, and TGFB, IL7 and IL15 expression is related with dyspareunia, dysmenorrhea and cyclic dyschezia, respectively, in patients with the disease.

AKT inhibition interferes with the expression of immune checkpoint proteins and increases NK-induced killing of HL60-AML cells

ABSTRACT Objective To determine the role of the AKT pathway in the regulating of natural Killer-induced apoptosis of acute myeloid leukemia cells and to characterize the associated molecular mechanisms. Methods BALB/c nude mice were injected with HL60 cells to induce a xenogenic model of subcutaneous leukemic tumors. Mice were treated with perifosine, and their spleens were analyzed using biometry, histopathology, and immunohistochemistry. Gene expression analysis in leukemia cells was performed by real-time PCR. Protein analysis of leukemia and natural Killer cells was performed by flow cytometry. AKT inhibition in HL60 cells, followed by co-culture with natural Killer cells was performed to assess cytotoxicity. Apoptosis rate was quantified using flow cytometry. Results Perifosine treatment caused a reduction in leukemic infiltration in the spleens of BALB/c nude mice. In vitro , AKT inhibition reduced HL60 resistance to natural Killer-induced apoptosis. AKT inhibition suppressed the immune checkpoint proteins PD-L1, galectin-9, and CD122 in HL60 cells, but did not change the expression of their co-receptors PD1, Tim3, and CD96 on the natural Killer cell surface. In addition, the death receptors DR4, TNFR1, and FAS were overexpressed by AKT inhibition, thus increasing the susceptibility of HL60 cells to the extrinsic pathway of apoptosis. Conclusion The AKT pathway is involved in resistance to natural Killer-induced apoptosis in HL60 cells by regulating the expression of immune suppressor receptors. These findings highlight the importance of AKT in contributing to immune evasion mechanisms in acute myeloid leukemia and suggests the potential of AKT inhibition as an adjunct to immunotherapy.

Genetic diversity and chemical variability of Lippia spp. (Verbenaceae).

BACKGROUND: The genus Lippia comprises 150 species, most of which have interesting medicinal properties. Lippia sidoides (syn. L. origanoides) exhibits strong antimicrobial activity and is included in the phytotherapy program implemented by the Brazilian Ministry of Health. Since species of Lippia are morphologically very similar, conventional taxonomic methods are sometimes insufficient for the unambiguous identification of plant material that is required for the production of certified phytomedicines. Therefore, genetic and chemical analysis with chemotype identification will contribute to a better characterization of Lippia species. METHODS: Amplified Length Polymorphism and Internal Transcribed Spacer molecular markers were applied to determine the plants' genetic variability, and the chemical variability of Lippia spp. was determined by essential oil composition. RESULTS: Amplified Length Polymorphism markers were efficient in demonstrating the intra and inter-specific genetic variability of the genus and in separating the species L. alba, L. lupulina and L. origanoides into distinct groups. Phylogenetic analysis using Amplified Length Polymorphism and markers produced similar results and confirmed that L. alba and L. lupulina shared a common ancestor that differ from L. origanoides. Carvacrol, endo-fenchol and thymol were the most relevant chemical descriptors. CONCLUSION: Based on the phylogenetic analysis it is proposed that L. grata should be grouped within L. origanoides due to its significant genetic similarity. Although Amplified Length Polymorphism and Internal Transcribed Spacer markers enabled the differentiation of individuals, the genotype selection for the production of certified phytomedicines must also consider the chemotype classification that reflects their real medicinal properties.

Scientists of Tomorrow/ Cientistas do Amanhã : a project to inspire, stimulate scientific thinking, and introduce scientific methodology for young students

ABSTRACT The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health.

Overview of miRNAs for the non-invasive diagnosis of endometriosis: evidence, challenges and strategies. A systematic review / Visão geral de miRNAs como diagnóstico não invasivo de endometriose: evidências, desafios e estratégias. Uma revisão sistemática

ABSTRACT Objective The aim of the study was to assess the evidence on miRNAs as biomarkers for the diagnosis of endometriosis, as well as to provide insights into the challenges and strategies associated with the use of these molecules as accessible tools in clinical practice. Methods Systematic review conducted on PubMed®, Latin American and Caribbean Health Sciences Literature (LILACS), MEDLINE® and Web of Science databases using the search terms endometriosis (all fields) AND miRNA (all fields), evaluating all publication up to May 2019. Results Most miRNAs found to be dysregulated in this study were harvested from tissue samples, which precludes their use as a non-invasive diagnostic test. However, differential expression of 62 miRNAs was reported in samples that may be used for non-invasive diagnosis of endometriosis, such as blood, serum and plasma. Conclusion Despite the identification of several candidates, studies are investigatory in nature and have been conducted with small number of samples. Also, no particular miRNA has been validated for diagnostic purposes so far. Studies based primarily on biological samples and applicable to translational research are warranted. Large databases comprising information on sample type and the use of saliva and vaginal fluid for miRNAs identification may prove essential to overcome current barriers to diagnosis of endometriosis.

RESUMO Objetivo O objetivo do estudo foi analisar as evidências sobre miRNAs como biomarcadores para o diagnóstico de endometriose, bem como levantar informações sobre os desafios e as estratégias necessárias para tornar essas moléculas ferramentas acessíveis para uso na prática clínica. Métodos Revisão sistemática conduzida nos bancos de dados PubMed®, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), MEDLINE® e Web of Science utilizando os termos de pesquisa "endometriosis" (todos os campos) AND "miRNA" (todos os campos), avaliando todas as publicações até maio de 2019. Resultados A maioria dos miRNAs desregulados foram analisados a partir de amostras de tecido, o que inviabiliza seu uso como teste diagnóstico não invasivo. Todavia, 62 miRNAs foram identificados como diferencialmente expressos em amostras que poderiam ser usadas para o diagnóstico pouco invasivo de endometriose, como sangue, soro e plasma. Conclusão Apesar de todos esses candidatos, os trabalhos são exploratórios, realizados com números pequenos de amostras, sem miRNAs específicos validados para fins diagnósticos. Estudos envolvendo principalmente amostras biológicas, visando à pesquisa translacional, deveriam ser mais explorados. O desenvolvimento de grandes bancos de dados sobre amostras, bem como o uso de saliva e fluido vaginal para identificação de miRNAs, poderia servir como recursos essenciais para as barreiras atuais no diagnóstico da endometriose.