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1.
Hepatobiliary Surg Nutr ; 13(2): 273-292, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617479

RESUMO

Colorectal cancer represents the third most common cancer and about 20% are diagnosed with synchronous metastatic disease. From a historical point of view, surgery remains the mainstream treatment for resectable colorectal liver metastases (CRLM). Furthermore, disease outcomes are improving due significant advances in systemic treatments and diagnostic methods. However, the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question. Thus, patient selection combining image workouts, time of recurrence, positive lymph nodes, and molecular biomarkers can improve the decision-making process. Nevertheless, molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment. Tumor biomakers, genetic profiling, and circulating tumor DNA have been used to offer as much personalized treatment as possible, based on the precision oncology concept of tailored care rather than a guideline-based therapy. This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

2.
Microorganisms ; 12(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38674664

RESUMO

The SARS-CoV-2 P.1 variant, responsible for an outbreak in Manaus, Brazil, is distinguished by 12 amino acid differences in the S protein, potentially increasing its ACE-2 affinity and immune evasion capability. We investigated the innate immune response of this variant compared to the original B.1 strain, particularly concerning cytokine production. Blood samples from three severe COVID-19 patients were analyzed post-infection with both strains. Results showed no significant difference in cytokine production of mononuclear cells and neutrophils for either variant. While B.1 had higher cytopathogenicity, neither showed viral replication in mononuclear cells. Structural analyses of the S protein highlighted physicochemical variations, which might be linked to the differences in infectivity between the strains. Our studies point to the increased infectivity of P.1 could stem from altered immunogenicity and receptor-binding affinity.

3.
rev. udca actual. divulg. cient ; 26(2): e2428, jul.-dic. 2023. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1576975

RESUMO

RESUMEN El río Hacha ubicado en Florencia-Caquetá, Colombia, abastece agua para el consumo humano y proporciona otros servicios ecosistémicos. Las actividades antrópicas han generado una presión en este recurso natural. Se realizó una valoración económica de la calidad de agua y los servicios recreativos en los balnearios del corredor vial del río. Se establecieron cuatro puntos en el tramo para medir indicadores fisicoquímicos del agua. Se realizó una encuesta en una muestra de 460 personas, cuyo análisis empleó los métodos de costo-viaje y valoración contingente. Se encontró que los indicadores de calidad de agua no exceden los límites permisibles para contacto primario. La recreación en los sitios genera beneficios económicos para la demanda local: la variación del excedente del consumidor ante un proyecto hipotético de mejora en la calidad del agua fue positiva. La disposición a pagar por hogar por una mejora en la calidad del agua asciende a $9.984,04 por año. Esto implica que existe un potencial de aprovechamiento sostenible en los servicios ecosistémicos asociados a la recreación en el recurso hídrico.


ABSTRACT The Hacha river located in Florencia-Caquetá, supplies water for human consumption and provides other ecosystem services. Anthropic activities have generated pressure on this natural resource. An economic valuation was made of water quality and recreational services in the river's road corridor resorts. Four points were established along the stretch to measure physicochemical water indicators. A survey was conducted on a sample of 460 people whose analysis employed the Cost-Travel and Contingent Valuation methods. It was found that the water quality indicators do not exceed the permissible limits for primary contact. Recreation at the sites generates economic benefits for local demand: the variation in consumer surplus for a hypothetical water quality improvement project was positive. The willingness to pay (WTP) per household for an improvement in water quality amounts to $2.12 dollars per year. This implies that there is a potential for sustainable use of the ecosystem services associated with water resource recreation.

4.
J Hepatocell Carcinoma ; 10: 1923-1933, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37933267

RESUMO

Purpose: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare primary liver malignancy often diagnosed at advanced stages. While there are limited data on the efficacy of specific agents, we aim to report outcomes of patients treated with systemic therapies and explore prognostic factors. Patients and Methods: Medical records of patients treated between 2010 and 2022 were reviewed. Treatments were defined after multidisciplinary assessment. Descriptive statistics were used for baseline demographics. Time-to-event outcomes were estimated using the Kaplan-Meier method, compared by log-rank and adjusted by a regression model. Radiomic features (including size, shape, and texture) of the primary lesion were extracted and dimensionality reduced. An unsupervised Gaussian Mixture Model (GMM) clustering was performed, and survival was compared between clusters. Results: We identified 23 patients: 12 males, with a median age of 23.6 years. At diagnosis, 82.6% had metastases, most frequently to the lungs (39.1%), lymph nodes (39.1%), and peritoneum (21.7%). Patients received a median of three lines (1-8) of treatment, including different regimens. Sorafenib (39.1%), capecitabine (30.4%), and capecitabine/interferon (13%) were the most used first-line regimens. The median time-to-failure was 3.8 months (95% CI: 3.2-8.7). Capecitabine + interferon (42.1%) and platinum combinations (39.1%) were the most used second-line regimens, with a time-to-failure of 3.5 months (95% CI: 1.5-11.6). Median overall survival was 26.7 months (95% CI: 15.1-40.4). A high baseline neutrophil-to-lymphocyte ratio (NLR) was associated with worse survival (p=0.02). Radiomic features identified three clusters, with one cluster (n=6) having better survival (40.4 vs 22.6 months, p=0.039). Tumor sphericity in the arterial phase was the most relevant characteristic associated with a better prognosis (accuracy=0.93). Conclusion: FLHCC has unique features compared to conventional HCC, including young onset, gender balance, and absence of hepatopathy. Systemic therapies can provide encouraging survival, but lack of uniformity precludes defining a preferable regimen. Radiomics and NLR were suggested to correlate with prognosis and warrant further validation.

5.
Medicines (Basel) ; 10(6)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37367731

RESUMO

Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis.

6.
JCO Glob Oncol ; 9: e2200416, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37348031

RESUMO

The incidence of hepatocellular carcinoma (HCC) is expected to increase in the coming years, and strategies to mitigate the burden of this disease are needed in different regions. Geographic variations in epidemiology and risk factors, such as viral hepatitis and metabolic disease, pose challenges in adopting programs for early detection programs and management of patients with HCC. Brazil, like other countries, has high economic and social inequality, with heterogeneous access to health care. Viral hepatitis is the main risk factor but there is growing awareness of fatty liver disease. Risk factor monitoring and screening programs are unmet priorities because patients are often diagnosed at later stages. Advances in the management of patients with HCC have been made in recent years, including new tools for selecting patients for liver transplantation, sophisticated surgical techniques, and new systemic agents. High-volume academic centers often achieve favorable results through the adoption and application of established treatments, but this is not a reality in most regions of Brazil, because of disparities in wealth and resources. As HCC management requires a coordinated and multidisciplinary team, the role of local referral centers in decentralizing access to treatments and promoting health education in different regions should be encouraged and supported.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Brasil/epidemiologia , Fatores de Risco , Incidência
7.
Arq Gastroenterol ; 60(1): 106-131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37194769

RESUMO

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.


Assuntos
Carcinoma Hepatocelular , Gastroenterologia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Brasil , Sociedades Médicas
8.
Ann Hepatol ; 28(4): 101110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37100385

RESUMO

INTRODUCTION AND OBJECTIVES: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. CONCLUSIONS: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Prognóstico , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
9.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047018

RESUMO

Multidrug resistance (MDR) and induction of metastasis are some of the puzzles encountered during cancer chemotherapy. The MDR phenotype is associated with overexpression of ABC transporters, involved in drug efflux. Metastasis originates from the epithelial-mesenchymal transition (EMT), in which cells acquire a migratory phenotype, invading new tissues. ABC transporters' role during EMT is still elusive, though cells undergoing EMT exhibit enhanced ABCB1 expression. We demonstrated increased ABCB1 expression but no change in activity after TGF-ß-induced EMT in A549 cells. Moreover, ABCB1 inhibition by verapamil increased snail and fibronectin expression, an event associated with upregulation of ABCB1, evidencing coincident cell signaling pathways leading to ABCB1 and EMT-related markers transcription, rather than a direct effect of transport. Additionally, for the first time, increased ABCC1 expression and activity was observed after EMT, and use of ABCC1 inhibitors partially inhibited EMT-marker snail, although increased ABCC1 function translated into collateral sensibility to daunorubicin. More investigations must be done to evaluate the real benefits that the gain of ABC transporters might have on the process of metastasis. Considering ABCC1 is involved in the stress response, affecting intracellular GSH content and drug detoxification, this transporter could be used as a therapeutic target in cancer cells undergoing EMT.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Fator de Crescimento Transformador beta
10.
Life (Basel) ; 13(4)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37109592

RESUMO

The interactions between cell and cellular matrix confers plasticity to each body tissue, influencing the cellular migratory capacity. Macrophages rely on motility to promote their physiological function. These phagocytes are determinant for the control of invasive infections, and their immunological role largely depends on their ability to migrate and adhere to tissue. Therefore, they interact with the components of the extracellular matrix through their adhesion receptors, conferring morphological modifications that change their shape during migration. Nevertheless, the need to use in vitro cell growth models with the conditioning of three-dimensional synthetic matrices to mimic the dynamics of cell-matrix interaction has been increasingly studied. This becomes more important to effectively understand the changes occurring in phagocyte morphology in the context of infection progression, such as in Chagas disease. This disease is caused by the intracellular pathogen Trypanosoma cruzi, capable of infecting macrophages, determinant cells in the anti-trypanosomatid immunity. In the present study, we sought to understand how an in vitro extracellular matrix model interferes with T. cruzi infection in macrophages. Using different time intervals and parasite ratios, we evaluated the cell morphology and parasite replication rate in the presence of 3D collagen I matrix. Nevertheless, microscopy techniques such as scanning electron microscopy were crucial to trace macrophage-matrix interactions. In the present work, we demonstrated for the first time that the macrophage-matrix interaction favors T. cruzi in vitro replication and the release of anti-inflammatory cytokines during macrophage infection, in addition to drastically altering the morphology of the macrophages and promoting the formation of migratory macrophages.

12.
Mol Clin Oncol ; 18(4): 29, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36908977

RESUMO

Prognostic markers in advanced hepatocellular carcinoma (HCC) are relevant for clinical decisions. Variations in inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), may correlate with outcomes. In the present study, it was aimed to assess the prognostic role of inflammation indexes in patients with HCC and the evolutionary behavior of these variables within the first month of treatment in a cohort of patients treated with sorafenib from 2009-2021. Subgroups were divided based on the median of each variable ('low' or 'high)'. Survival was estimated using the Kaplan-Meier method. Hazard Ratio (HR) with 95% confidence interval (CI) were estimated using Cox regression models. A total of 373 patients were included, most Child-Pugh-A (83.1%) and BCLC-C (74%). Child-Pugh-A (P=0.011), performance status 0 (P<0.001), no ascites (P<0.001) and NLR<2.6 (P<0.001) were independently associated with improved survival. Baseline PLR was not correlated with survival (P=0.137). Patients who maintained low NLR at baseline and at 1 month (reference subgroup) had improved survival (18.6 months, 95% CI:15.4-22.0) compared with the subgroup that maintained high NLR at baseline and at 1 month (4.2 months, 95% CI:3.6-5.9), with HR: 3.80 (95% CI: 2.89-4.96). The subgroup with low NLR at baseline and high NLR at 1 month had a worse prognosis compared with the reference group (HR:1.4, 95% CI: 1.1-2.0), whereas the subgroup with high NLR at baseline and low at 1 month had similar outcome (HR:1.2, 95% CI: 0.8-1.6). It was concluded that evolutionary variation of NLR has a prognostic role in HCC patients under systemic therapy. This finding suggested that systemic inflammation and early modulation of the immune environment during treatment may correlate with outcomes.

13.
Matrix Biol ; 118: 47-68, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36882122

RESUMO

Changes in protein glycosylation are a hallmark of transformed cells and modulate numerous phenomena associated with cancer progression, such as the acquisition of multidrug resistance (MDR) phenotype. Different families of glycosyltransferases and their products have already been described as possible modulators of the MDR phenotype. Among the glycosyltransferases intensively studied in cancer research, UDP-N-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase-6 (pp-GalNAc-T6), which is widely expressed in many organs and tissues, stands out. Its influence in several events associated with kidney, oral, pancreatic, renal, lung, gastric and breast cancer progression has already been described. However, its participation in the MDR phenotype has never been studied. Here, we demonstrate that human breast adenocarcinoma MCF-7 MDR cell lines, generated by chronic exposure to doxorubicin, in addition to exhibiting increased expression of proteins belonging to the ABC superfamily (ABCC1 and ABCG2), and anti-apoptotic proteins (Blcl-2 and Bcl-xL), also present high expression of pp-GalNAc-T6, the enzyme currently proposed as the main responsible for the biosynthesis of oncofetal fibronectin (onf-FN), a major extracellular matrix component expressed by cancer cells and embryonic tissues, but absent in healthy cells. Our results show that onf-FN, which is generated by the addition of a GalNAc unit at a specific threonine residue inside the type III homology connective segment (IIICS) domain of FN, is strongly upregulated during the acquisition of the MDR phenotype. Also, the silencing of pp-GalNAc-T6, not only compromises the expression of the oncofetal glycoprotein, but also made the MDR cells more sensitive to all anticancer drugs tested, partially reversing the MDR phenotype. Taken together, our results demonstrate for the first time the upregulation of the O-glycosylated oncofetal fibronectin, as well as the direct participation of pp-GalNAc-T6 during the acquisition of a MDR phenotype in a breast cancer model, giving credence to the hypothesis that in transformed cells, glycosyltransferases and/or their products, such as unusual extracellular matrix glycoproteins can be used as potential therapeutic targets for the treatment of cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Glicosilação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Glicosiltransferases , Resistência a Múltiplos Medicamentos/genética
14.
Medicines (Basel) ; 10(2)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36827215

RESUMO

In this article, we discuss the main aspects regarding the recognition of cell surface glycoconjugates and the immunomodulation of responses against the progression of certain pathologies, such as cancer and infectious diseases. In the first part, we talk about different aspects of glycoconjugates and delve deeper into the importance of N-glycans in cancer immunotherapy. Then, we describe two important lectin families that have been very well studied in the last 20 years. Examples include the sialic acid-binding immunoglobulin (Ig)-like lectins (siglecs), and galectins. Finally, we discuss a topic that needs to be better addressed in the field of glycoimmunology: the impact of oncofetal antigens on the cells of the immune system. New findings in this area are of great importance for advancement, especially in the field of oncology, since it is already known that cellular interactions mediated by carbohydrate-carbohydrate and/or carbohydrate proteins are able to modulate the progression of different types of cancer in events that compromise the functionality of the immune responses.

15.
Braz J Microbiol ; 54(2): 907-919, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36840821

RESUMO

Invasive fungal infections (IFI) are responsible for a large number of annual deaths. Most cases are closely related to patients in a state of immunosuppression, as is the case of patients undergoing chemotherapy. Cancer patients are severely affected by the worrisome proportions that an IFI can take during cancer progression, especially in an already immunologically and metabolically impaired patient. There is scarce knowledge about strategies to mitigate cancer progression in these cases, beyond conventional treatment with antifungal drugs with a narrow therapeutic range. However, in recent years, ample evidence has surfaced describing the possible interferences that IFI may have both on the progression of pre-existing cancers and in the induction of newly transformed cells. The leading gambit for modulation of tumor progression comes from the ability of fungal virulence factors to modulate the host's immune system, since they are found in considerable concentrations in the tumor microenvironment during infection. In this context, cryptococcosis is of particular concern, since the main virulence factor of the pathogenic yeast is its polysaccharide capsule, which carries constituents with high immunomodulatory properties and cytotoxic potential. Therefore, we open a discussion on what has already been described regarding the progression of cryptococcosis in the context of cancer progression, and the possible implications that fungal glycan structures may take in both cancer development and progression.


Assuntos
Criptococose , Cryptococcus neoformans , Neoplasias , Humanos , Criptococose/microbiologia , Polissacarídeos , Antifúngicos , Fatores de Virulência , Microambiente Tumoral
16.
Arq. gastroenterol ; Arq. gastroenterol;60(1): 106-131, Jan.-Mar. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1439403

RESUMO

ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.


RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.

17.
Immunol Res ; 71(1): 92-104, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36197587

RESUMO

Macrophage (Mϕ) polarization is an essential phenomenon for the maintenance of homeostasis and tissue repair, and represents the event by which Mϕ reach divergent functional phenotypes as a result to specific stimuli and/or microenvironmental signals. Mϕ can be polarized into two main phenotypes, M1 or classically activated and M2 or alternatively activated. These two categories diverge in many aspects, such as secreted cytokines, markers of cell surface, and biological functions. Over the last 10 years, many potential markers have been proposed for both M1 and M2 human Mϕ. However, there is scarce information regarding the glycophenotype adopted by these cells. Here, we show that M2- but not M1-polarized Mϕ expresses high levels of an unusual glycoform of fibronectin (FN), named O-glycosylated oncofetal FN (onf-FN), found in fetal/cancer cells, but not in healthy tissues. The onf-FN expression was confirmed in vitro by Western blot and real-time RT-qPCR in primary and cell line monocyte-derived Mϕ. onf-FN was induced by IL-4 and IL-13, but not by pro-inflammatory stimuli (LPS and INF-γ). RNA and protein analysis clearly demonstrated that it is specifically associated with the M2 polarization. In conclusion, we show by the first time that O-glycosylated onf-FN is expressed by M2-polarized Mϕ.


Assuntos
Fibronectinas , Macrófagos , Humanos , Fibronectinas/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Linhagem Celular
19.
Artigo em Inglês | LILACS-Express | VETINDEX | ID: biblio-1513982

RESUMO

Abstract Studies that explore the use of lipids and their effects on animal nutrition have become increasingly abundant, producing a mass of information. The review was carried out on a parity basis through a survey of articles in the bibliographic databases: Web of Science and Periodicals Capes, using search terms associated or not, in the plural or singular, in English and Portuguese, such as: "lipids" AND "rabbits" AND "nutrition". After analyzing the files in the two scientific databases, certain files were excluded because they did not fit the theme or because they did not meet the inclusion criteria and repeated articles. A relevance test was carried out for the use of the articles, where they should deal with the subject: articles that report the use of lipids in the nutrition of non-ruminant animals; articles made available in complete form; articles that had at least one of the keywords; articles where the main subject is related to lipids. The articles were selected and tabulated in an Excel® spreadsheet with relevant information for exploration in the review. The use of oils and fats is a favorable point in the nutrition of non-ruminant animals, presenting benefits in the enrichment of final products such as: providing higher levels of omega-3 and omega-6, and thus obtaining meat products with lower levels of saturated fat and higher unsaturated fat contents promoting benefits to human health through its consumption, reduction of food costs, improvement in palatability and appearance of foods. These are nutritional strategies used in hot seasons of the year due to the low calorific increment produced.


Resumo Estudos que exploram o uso de lipídios e seus efeitos na nutrição animal têm se tornado cada vez mais abundantes, produzindo uma grande quantidade de informações. A revisão foi realizada de forma paritária por meio de uma pesquisa de artigos nas bases bibliográficas: Web of Science e Periódicos Capes, utilizando termos de busca associados ou não, no plural ou no singular, em inglês e português, tais como: "lipídios" E "coelhos" E "nutrição". Após analisar os arquivos nas duas bases científicas, determinados arquivos foram excluídos porque não se adequavam ao tema ou não atendiam aos critérios de inclusão, além de artigos repetidos. Um teste de relevância foi realizado para a seleção dos artigos, nos quais eles deveriam tratar do assunto: artigos que relatam o uso de lipídios na nutrição de animais não-ruminantes; artigos disponibilizados na forma completa; artigos que possuíam pelo menos uma das palavras-chave; artigos nos quais o assunto principal está relacionado a lipídios. Os artigos foram selecionados e tabulados em uma planilha do Excel® com informações relevantes para exploração na revisão. O uso de óleos e gorduras é um ponto favorável na nutrição de animais não-ruminantes, apresentando benefícios no enriquecimento de produtos finais, tais como: fornecer níveis mais altos de ômega-3 e ômega-6, e assim obter produtos de carne com menores teores de gordura saturada e maiores teores de gordura insaturada, promovendo benefícios para a saúde humana por meio do consumo, redução dos custos alimentares, melhoria na palatabilidade e aparência dos alimentos. Essas são estratégias nutricionais usadas nas estações quentes do ano devido ao baixo incremento calórico produzido.

20.
Trop Med Infect Dis ; 7(12)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36548658

RESUMO

Cancer and parasitic diseases, such as leishmaniasis and Chagas disease, share similarities that allow the co-development of new antiproliferative agents as a strategy to quickly track the discovery of new drugs. This strategy is especially interesting regarding tropical neglected diseases, for which chemotherapeutic alternatives are extremely outdated. We designed a series of (E)-3-aryl-5-(2-aryl-vinyl)-1,2,4-oxadiazoles based on the reported antiparasitic and anticancer activities of structurally related compounds. The synthesis of such compounds led to the development of a new, fast, and efficient strategy for the construction of a 1,2,4-oxadiazole ring on a silica-supported system under microwave irradiation. One hit compound (23) was identified during the in vitro evaluation against drug-sensitive and drug-resistant chronic myeloid leukemia cell lines (EC50 values ranging from 5.5 to 13.2 µM), Trypanosoma cruzi amastigotes (EC50 = 2.9 µM) and Leishmania amazonensis promastigotes (EC50 = 12.2 µM) and amastigotes (EC50 = 13.5 µM). In silico studies indicate a correlation between the in vitro activity and the interaction with tubulin at the colchicine binding site. Furthermore, ADMET in silico predictions indicate that the compounds possess a high druggability potential due to their physicochemical, pharmacokinetic, and toxicity profiles, and for hit 23, it was identified by multiple spectroscopic approaches that this compound binds with human serum albumin (HSA) via a spontaneous ground-state association with a moderate affinity driven by entropically and enthalpically energies into subdomain IIA (site I) without significantly perturbing the secondary content of the protein.

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