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1.
bioRxiv ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39314389

RESUMO

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), infects approximately one-fourth of the world's population. While most infected individuals are asymptomatic, latent TB infection (LTBI) can progress to cause pulmonary TB (PTB). We recently reported an increased accumulation of mast cells (MCs) in lungs of macaques with PTB, compared with LTBI in macaques. MCs respond in vitro to Mtb exposure via degranulation and by inducing proinflammatory cytokines. In the current study, we show the dominant production of chymase by MCs in granulomas of humans and macaques with PTB. Using scRNA seq analysis, we show that MCs found in LTBI and healthy lungs in macaques are enriched in genes involved in tumor necrosis factor alpha, cholesterol and transforming growth factor beta signaling. In contrast, MCs clusters found in PTB express transcriptional signatures associated with interferon gamma, oxidative phosphorylation, and MYC signaling. Additionally, MC deficiency in the mouse model showed improved control of Mtb infection that coincided with reduced accumulation of lung myeloid cells and diminished inflammation at chronic stages. Thus, these collective results provide novel evidence for the pathological contribution of MCs during Mtb infection and may represent a novel target for host directive therapy for TB.

2.
Int J Mol Sci ; 25(16)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39201369

RESUMO

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG's role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells.


Assuntos
Catequina , Proliferação de Células , Heme , Fármacos Fotossensibilizantes , Protoporfirinas , Espécies Reativas de Oxigênio , Catequina/análogos & derivados , Catequina/farmacologia , Protoporfirinas/farmacologia , Protoporfirinas/metabolismo , Humanos , Heme/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fotoquimioterapia/métodos , Sobrevivência Celular/efeitos dos fármacos , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/análogos & derivados
3.
Obes Surg ; 34(8): 2897-2906, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39001982

RESUMO

INTRODUCTION: Metabolic and bariatric surgery (MBS) has experienced considerable growth, addressing the challenges of obesity and its complications. The lack of a comprehensive bibliometric analysis in Latin America motivates this study, highlighting the need to understand the evolution of research in this area and its impact on clinical decision-making and health policies. METHODOLOGY: A cross-sectional bibliometric study was carried out using the Scopus database. A structured search strategy was designed to identify articles related to bariatric surgery with authors affiliated with Latin American countries. Inclusion and exclusion criteria were applied, followed by a descriptive and bibliometric analysis of the scientific production found. RESULTS: A total of 3553 documents published between 1991 and 2024 were included. There was an annual growth of 11%, with an average age of documents of 7.5 years. A concentration was observed in some countries, notably Brazil, Mexico, and Chile. Although scientific output increased, the average number of citations per article showed a downward trend since 2003. DISCUSSION: Despite the growth in scientific production, the quality and relevance of research is questioned, especially given the decrease in the impact received. It highlights the lack of meaningful regional collaboration, which could limit the sharing of knowledge and resources. Questions are raised about gaps in research capacity and the economic and development implications are discussed. CONCLUSIONS: This study provides valuable information to strengthen future research in bariatric surgery in Latin America. It highlights the importance of promoting regional and international collaboration and improving research training in countries with less participation. Clinical intervention strategies can benefit from better understanding research trends and adopting evidence-based practices in a more informed manner.


Assuntos
Cirurgia Bariátrica , Bibliometria , Cirurgia Bariátrica/estatística & dados numéricos , Humanos , Estudos Transversais , América Latina , Pesquisa Biomédica , Obesidade Mórbida/cirurgia
4.
Mycorrhiza ; 34(1-2): 107-117, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38151658

RESUMO

The Andean paramo, hereafter "paramo", is a Neotropical high-mountain region between the treeline and permanent snowline (3500-4800 m) and is considered the world's coolest biodiversity hotspot. Because of paramo's high humidity, solar radiation and temperature variation, mycorrhizal symbiosis is expected to be essential for plants. Existing theory suggests that replacement of arbuscular mycorrhizal (AM) by ectomycorrhizal (ECM) and then ericoid mycorrhizal plants (ERM) can be expected with increasing elevation. Previous findings also suggest that non-(NM) and facultatively mycorrhizal (FM) species predominate over obligatory mycorrhizal (OM) species at high elevations. However, these expectations have never been tested outside of the northern temperate zone. We addressed the distribution and environmental drivers of plant mycorrhizal types (AM, ECM and ERM) and statuses (NM, FM and OM) along the paramo's elevational gradient. We used vegetation plots from the VegParamo database, climatic and edaphic data from online repositories, and up-to-date observation information about plant mycorrhizal traits at species and genus level, the latter being proposed as hypotheses. AM plants were dominant along the entire gradient, and ERM plants were most abundant at the lowest elevations (2500-3000 m). The share of FM plants increased and that of OM plants decreased with elevation, while NM plants increased above 4000 m. Temperature and soil pH were positively related to the abundance of AM plants and negatively to ERM plants. Our results reveal patterns that contrast with those observed in temperate northern-hemisphere ecosystems.


Assuntos
Micorrizas , Simbiose , Ecossistema , Plantas , Biodiversidade , Solo , Microbiologia do Solo
5.
Cureus ; 15(10): e47119, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021873

RESUMO

Brain abscesses are localized infections in the brain's parenchyma, characterized by inflammation, pus formation, and the development of a surrounding capsule. These lesions typically occur due to underlying factors such as immunosuppression, ear and sinus infections, and contamination during neurosurgery. While brain abscesses are a life-threatening complication of cyanotic heart defects, they are rarely reported, with only sporadic cases previously documented. This article presents the case of an eight-year-old male patient with an uncorrected transposition of the great arteries, who was evaluated for symptoms including headache, fever, and neurological focalization. Diagnostic imaging revealed three lesions consistent with brain abscesses. Furthermore, the causal agents were identified as Streptococcus intermedius and Fusobacterium spp., representing oral microorganisms. Additionally, the patient exhibited poor oral hygiene and dental caries in multiple teeth. This article discusses and integrates the possible pathophysiological mechanisms that allowed a localized dental infection to spread hematogenously and cause brain abscesses in this patient. Prompt management of the infectious source is crucial to prevent a poor prognosis associated with brain abscesses. Therefore, this case emphasizes the importance of regular dental assessments and thromboprophylaxis for patients with underlying cardiomyopathies that cause right-to-left shunting to prevent potential complications.

6.
Chempluschem ; 88(5): e202300028, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37134299

RESUMO

Cysteine-based perfluoroaromatic (hexafluorobenzene (HFB) and decafluorobiphenyl (DFBP)) were synthesized and established as a chemoselective and available core to construct molecular systems ranging from small molecules to biomolecules with interesting properties. The DFBP was found more effective than HFB for the monoalkylation of decorated thiol molecules. As proof of concept of the potential application of perfluorinated derivatives as non-cleavable linkers, some antibody-perfluorinated conjugates were prepared via thiol through two different strategies, i) using thiol from reduced cystamine coupling to carboxylic acids from mAb by amide bond, and ii) using thiols from reduction of mAb disulfide bond. Conjugates cell binding analysis demonstrated that the bioconjugation does not affect the macromolecular entity. Besides, some molecular properties of synthesized compounds are evaluated through spectroscopic characterization (FTIR and 19 F NMR chemical shifts) and theoretical calculations. The comparison of calculated and experimental 19 F NMR shifts and IR wavenumbers give excellent correlations, asserting as powerful tools in structurally identifying HFB and DFBP derivatives. Moreover, molecular docking was also developed to predict cysteine-based perfluorated derivatives' affinity against topoisomerase Il and cyclooxygenase 2 (COX-2). The results suggested that mainly cysteine-based DFBP derivatives could be potential topoisomerase II α and COX-2 binders, becoming potential anticancer agents and candidates for anti-inflammatory treatment.


Assuntos
Antineoplásicos , Cisteína , Cisteína/química , Simulação de Acoplamento Molecular , Ciclo-Oxigenase 2/metabolismo , Antineoplásicos/química , Compostos de Sulfidrila/química
7.
Rev Med Inst Mex Seguro Soc ; 61(2): 239-244, 2023 Mar 01.
Artigo em Espanhol | MEDLINE | ID: mdl-37205605

RESUMO

Background: Acute hemorrhagic leukoencephalitis (AHLE) is an inflammatory disease of the brain, with a fulminant course that leads to a hemorrhagic demyelination of the central nervous system, having a poor prognosis and high mortality. Most of the times associated to crossed reactivity and molecular mimicry. Clinical case: : We present a case report of a previously healthy young woman with an acute and multifocal clinical course, preceded by a viral respiratory tract infection, followed by a rapid disease progression and a delay in the diagnosis. The clinical, neuroimaging and cerebrospinal fluid featured suggested the diagnosis of AHLE, despite efforts and management with immunosuppression and intensive care, the response to treatment was poor leaving the patient with a severe neurological impairment. Conclusion: There is little evidence regarding the clinical course and treatment of this disease, and more studies are needed to better characterize it and to provide further information about its prognosis and management. This paper gives a systematic review of the literature.


Introducción: la leucoencefalitis hemorrágica aguda (AHLE, por sus siglas en inglés) es una enfermedad inflamatoria del cerebro que conduce a una desmielinización hemorrágica del sistema nervioso central (SNC), de mal pronóstico y alta mortalidad. Muchas veces se asocia a diferentes patógenos que provocan un mimetismo molecular. Caso clínico: presentamos un caso de origen mexicano, que presento una clínica de una evolución aguda de tipo multifocal. Inicialmente asociado a un cuadro de origen infeccioso, aparentemente viral. Posterior a ese cuadro el paciente presenta una evolución tórpida, con retraso del diagnóstico. Acude con las manifestaciones clínicas, radiológicas y en líquido cefalorraquídeo compatibles con la enfermedad, aunque se da tratamiento inmunosupresor de manera energética la paciente presenta poca respuesta al tratamiento, con muchas secuelas por la enfermedad. Conclusión: existen poca evidencia sobre la evolución clínica y el manejo médico de la enfermedad y se necesitan más estudios para caracterizarla mejor y brindar más información sobre su pronóstico y manejo. En este artículo se provee una revisión sistemática de la bibliografía.


Assuntos
Leucoencefalite Hemorrágica Aguda , Feminino , Humanos , Leucoencefalite Hemorrágica Aguda/diagnóstico , Leucoencefalite Hemorrágica Aguda/tratamento farmacológico , Leucoencefalite Hemorrágica Aguda/etiologia , Encéfalo
8.
Endocrinol Diabetes Nutr (Engl Ed) ; 69(10): 888-896, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36446709

RESUMO

INTRODUCTION: One of the main goals of prescribing physical activity for people with type 2 diabetes is to reduce hyperglycaemia, as it is a risk factor for the development of chronic complications. As less time spent each day in sedentary behaviour would lead to higher glucose consumption by skeletal muscle tissue, this could have significant positive effects on blood glucose control parameters. For this reason, the aim of this study was to analyse the information from different protocols for breaking sedentary behaviour and the association with blood glucose control parameters in patients with type 2 diabetes. MATERIAL AND METHODS: A systematic search was carried out for randomised controlled studies on this topic published in the scientific literature. The following databases were considered: PubMed, Cochrane, EBSCO, WoS, ScienceDirect and Medline. RESULTS: 24 studies were identified and analysed using the COVIDENCE platform. Seven articles were selected for the final analysis, comprising 138 patients. The results show that breaks in sedentary behaviour with light physical activity in people with type 2 diabetes are effective in reducing insulin resistance, the area under the glucose curve, fasting and postprandial blood glucose, and blood glucose variability. CONCLUSIONS: Acute interruption of sedentary behaviour, through light-intensity and short-duration exercise, can improve blood glucose indicators in patients with type 2 diabetes, including short term blood glucose variability.


Assuntos
Diabetes Mellitus Tipo 2 , Comportamento Sedentário , Humanos , Glicemia , Exercício Físico/fisiologia , Controle Glicêmico
9.
Artigo em Inglês | MEDLINE | ID: mdl-35764387

RESUMO

BACKGROUND: Published evidence on self-rated health's capacity to predict mortality and its variability across subpopulations lacks consistency. Our objective is to evaluate this predictive association and whether/how it varies by sex, age and educational attainment at the population level in Spain. METHODS: Data came from a prospective longitudinal study based on 42 645 individuals aged ≥15 years who participated in the 2011-2012 and 2014 Spanish Health Surveys. Median follow-up time for mortality was 5.4 years. Cox proportional hazards models adjusted for sociodemographic, lifestyle and chronic disease variables were used to estimate the predictive capacity of self-rated health on mortality. RESULTS: Self-rated health was associated with mortality with a dose-response effect (p value for linear trend <0.001). Compared with respondents who rated their health as very good, those rating it as very poor presented an HR of 3.33 (95% CI 2.50 to 4.44). Suboptimal self-rated health was a stronger predictor of mortality among 15-44 year-olds (HR 2.87; 95% CI 1.59 to 5.18), compared with the estimate for 45-64 year-olds (HR 1.86; 95% CI 1.45 to 2.39) (p value for interaction=0.001) and for those 65 and older (HR 1.51; 95% CI 1.36 to 1.68) (p value for interaction <0.001). Regarding educational attainment, the association was stronger for individuals with university studies (HR 2.51; 95% CI 1.67 to 3.76) than for those with only primary or no studies (HR 1.31; 95% CI 1.17 to 1.48) (p value for interaction=0.010). No statistically significant differences were observed between men and women. CONCLUSIONS: Self-rated health may be considered a good predictor of all-cause mortality in the population of Spain, although the magnitude of this predictive association varies by age and educational level.

10.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1385892

RESUMO

ABSTRACT: Oral mucosal melanoma is an unusual and aggressive malignant tumor that mainly affects the palate of men aged between 50 and 60 years. We present a literature review focusing on the etiopathogenesis and the clinicopathologic features of this entity. In addition, we reported a rare case of an oral mucosal melanoma arising in the left cheek of a 60-yea r- old man. Computed tomography scan revealed infiltration of the tumor to other anatomic structures including the maxillary sinus, the zygomatic bone and the pterygoid processes. Based on its extension, the lesion was considered inoperable and treatment with three-dimensional conformal radiation therapy was proposed but the patient only attended to the first session and died from cancer progression 6 months after the diagnosis. This paper reinforces the importance of inclusion of this malignant tumor in the differential diagnosis of pigmented lesions of the oral mucosa.


RESUMEN: El melanoma de la mucosa oral es un tumor maligno inusual y agresivo que afecta principalmente al paladar de hombres de entre 50 y 60 años. Presentamos una revisión bibliográfica centrada en la etiopatogenia y las características clínico-patológicas de esta entidad. Además, reportamos un caso raro de melanoma de la mucosa oral que surgió en la mejilla izquierda de un hombre de 60 años. La tomografía computarizada reveló la infiltración del tumor a otras estructuras anatómicas, incluido el seno maxilar, el hueso cigomático y los procesos pterigoideos. En base a su extensión, la lesión se consideró inoperable y se propuso tratamiento con radioterapia conformada tridimensional pero el paciente solo asistió a la primera sesión y falleció por progresión del cáncer 6 meses después del diagnóstico. Este trabajo refuerza la importancia de la inclusión de este tumor maligno en el diagnóstico diferencial de las lesiones pigmentadas de la mucosa oral.

11.
Eur Radiol ; 32(11): 7480-7487, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35536390

RESUMO

OBJECTIVES: We compared the compression force, breast thickness, and glandular dose, as well as the severity of discomfort and women's experience between the patient-assisted compression (PAC) and standard compression (SC) modes. MATERIALS AND METHODS: We conducted a prospective randomized controlled study at Hospital del Mar in Barcelona, Spain. We included 448 asymptomatic women aged 50 to 69 years old, attending their screening round from December 2017 to December 2019. Mammograms included the two bilateral views. In each woman, one breast was studied with SC and the other with PAC. The mode used in each breast was selected following a randomized list. Compression force, breast thickness, and average glandular dose were obtained for each of the 1792 images. We also recorded the degree of discomfort and women's experience, after mammogram acquisitions, using a predefined survey. RESULTS: Higher compression forces were obtained with PAC than with SC (99.27 N vs 83.25 N, p < 0.001). Breast thickness mode (56.11 mm vs 57.52 mm, p = 0.015) and glandular dose (1.34 mGy vs 1.37 mGy, p = 0.018) were lower in PAC. The discomfort score was slightly higher with PAC (mean 3.94 vs 3.69, p = 0.042), but in the satisfaction survey, more women reported that PAC caused less discomfort. Additionally, 63.2% of women (289/448) preferred PAC. CONCLUSION: PAC achieved higher compression forces without impairing the other technical imaging parameters and enhanced women's experience of screening mammography. We believe there were no clinically significant differences in the severity of discomfort between the two modes. KEY POINTS: • Self-compression allows higher compression forces than the standard compression mode. • Self-compression does not affect technical imaging parameters. • Self-compression improved women's experience of screening mammography when standard compression was used on one breast and self-compression on the other.


Assuntos
Neoplasias da Mama , Mamografia , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Mamografia/métodos , Detecção Precoce de Câncer , Método Simples-Cego , Estudos Prospectivos , Neoplasias da Mama/diagnóstico por imagem
12.
Eur Radiol ; 32(11): 7470-7479, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35536391

RESUMO

OBJECTIVES: Evaluate the image quality of a mammography screening device using the patient-assisted compression (PAC) compared with the standard compression (SC) mode. METHODS: This prospective within-woman, randomized controlled trial was conducted between September 2017 and December 2019. Participants were asymptomatic women aged 50 to 69 years attending their second or subsequent screening mammography round. By random assignment, one breast underwent the SC and the other breast, the PAC. Image quality was evaluated as perfect, good, moderate, or inadequate (PGMI) on 10 criteria for the craniocaudal (CC) view and 8 criteria for the mediolateral oblique (MLO) view. Pearson's chi-square test, with Yates' correction if pertinent, was performed to compare image quality between compression modes. RESULTS: A total of 444 participants were included (mean [± standard deviation] age, 60 [± 4.9] years). There were no differences in the percentages of PGMI between the PAC and SC modes for the CC view (perfect, 37% [162/444] vs 37% [163/444]; good, 1% [5/444] vs 2% [9/444]; moderate, 62% [277/444] vs 61% [271/444]; inadequate, 0% vs 0.2% [1/444]; p = .88) or for the MLO view (perfect, 53% [237/444] vs 56% [247/444]; good, 22% [99/444] vs 22% [97/444]; moderate, 23% [102/444] vs 22% [98/444]; inadequate, 1% [6/444] vs 0.5% [2/444]; p = .72). No differences were found when we stratified by laterality or when analyzed by PGMI criteria. CONCLUSION: PAC does not seem to impair mammographic image quality. Future research should focus in a daily practice setting. KEY POINTS: No differences were found in the distribution of the PGMI classification, a tool for quality assessment, between patient-assisted compression and standard compression. Similar results were found on stratification of image quality by mammographic view and breast laterality for both types of compression. None of the PGMI criteria had significantly more errors in patient-assisted compression than in standard compression.


Assuntos
Neoplasias da Mama , Mamografia , Feminino , Humanos , Pessoa de Meia-Idade , Mamografia/métodos , Estudos Prospectivos , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Mama/diagnóstico por imagem , Hiperplasia
13.
Campbell Syst Rev ; 18(3): e1253, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36913200

RESUMO

Immunisation is one of the most cost-effective interventions to prevent and control life-threatening infectious diseases. Nonetheless, rates of routine vaccination of children in low- and middle-income countries (LMICs) are strikingly low or stagnant. In 2019, an estimated 19.7 million infants did not receive routine immunisations. Community engagement interventions are increasingly being emphasised in international and national policy frameworks as a means to improve immunisation coverage and reach marginalised communities. This systematic review examines the effectiveness and cost-effectiveness of community engagement interventions on outcomes related to childhood immunisation in LMICs and identifies contextual, design and implementation features that may be associated with effectiveness. We identified 61 quantitative and mixed methods impact evaluations and 47 associated qualitative studies related to community engagement interventions for inclusion in the reteview. For cost-effectiveness analysis 14 of the 61 studies had the needed combination of cost and effectiveness data. The 61 included impact evaluations were concentrated in South Asia and Sub-Saharan Africa and spread across 19 LMICs. The review found that community engagement interventions had a small but significant, positive effect on all primary immunisation outcomes related to coverage and their timeliness. The findings are robust to exclusion of studies assessed as high risk of bias. Qualitative evidence indicates appropriate intervention design, including building in community engagement features; addressing common contextual barriers of immunisation and leveraging facilitators; and accounting for existing implementation constraints and practicalities on the ground are consistently cited as reasons for intervention success. Among the studies for which we were able to calculate cost-effectiveness, we find that the median non-vaccine cost per dose of intervention to increase immunisation coverage by 1% was US $3.68. Given the broad scope of the review in terms of interventions and outcomes, there is significant variation in findings. Among the various types of community engagement interventions, those that involve creation of community buy-in or development of new cadres of community-based structures were found to have consistent positive effect on more primary vaccination coverage outcomes than if the engagement is limited to the design or delivery of an intervention or is a combination of the various types. The evidence base for sub-group analysis for female children was sparse (only two studies) and the effect on coverage of both full immunisation and third dose of diphtheria pertussis tetanus for this group was insignificant.

15.
Cancers (Basel) ; 13(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34283059

RESUMO

Cancer remains a leading cause of death worldwide despite decades of intense efforts to understand the molecular underpinnings of the disease. To date, much of the focus in research has been on the cancer cells themselves and how they acquire specific traits during disease development and progression. However, these cells are known to secrete large numbers of extracellular vesicles (EVs), which are now becoming recognized as key players in cancer. EVs contain a large number of different molecules, including but not limited to proteins, mRNAs, and miRNAs, and they are actively secreted by many different cell types. In the last two decades, a considerable body of evidence has become available indicating that EVs play a very active role in cell communication. Cancer cells are heterogeneous, and recent evidence reveals that cancer cell-derived EV cargos can change the behavior of target cells. For instance, more aggressive cancer cells can transfer their "traits" to less aggressive cancer cells and convert them into more malignant tumor cells or, alternatively, eliminate those cells in a process referred to as "cell competition". This review discusses how EVs participate in the multistep acquisition of specific traits developed by tumor cells, which are referred to as "the hallmarks of cancer" defined by Hanahan and Weinberg. Moreover, as will be discussed, EVs play an important role in drug resistance, and these more recent advances may explain, at least in part, why pharmacological therapies are often ineffective. Finally, we discuss literature proposing the use of EVs for therapeutic and prognostic purposes in cancer.

16.
Cancers (Basel) ; 13(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073836

RESUMO

The Epstein-Barr virus (EBV) is a globally dispersed pathogen involved in several human cancers of B-cell and non-B-cell origin. EBV has been classified into EBV-1 and EBV-2, which have differences in their transformative ability. EBV-1 can transform B-cells into LCL more efficiently than EBV-2, and EBV-2 preferentially infects T-cell lymphocytes. The EBNA3A oncoprotein is a transcriptional regulator of virus and host cell genes, and is required in order to transform B-cells. EBNA3A has six peptide motifs called nuclear localization signals (NLSs) that ensure nucleocytoplasmic protein trafficking. The presence of multiple NLSs has been suggested to enhance EBNA3 function or different specificities in different cell types. However, studies about the NLS variability associated with EBV types are scarce. Based on a systematic sequence analysis considering more than a thousand EBNA3A sequences of EBV from different human clinical manifestations and geographic locations, we found differences in NLSs' nucleotide structures among EBV types. Compared with the EBNA3A EBV-1, EBNA3A EBV-2 has two of the six NLSs altered, and these mutations were possibly acquired by recombination. These genetic patterns in the NLSs associated with EBV-1 and EBV-2 provide new information about the traits of EBNA3A in EBV biology.

18.
Sci Rep ; 10(1): 19004, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149153

RESUMO

Ecuador is one of the most affected countries, with the coronavirus disease 2019 (COVID-19) infection, in Latin America derived from an ongoing economic crisis. One of the most important methods for COVID-19 detection is the use of techniques such as real time RT-PCR based on a previous extraction/purification of RNA procedure from nasopharyngeal cells using functionalized magnetic nanoparticles (MNP). This technique allows the processing of ~ 10,000 tests per day in private companies and around hundreds per day at local Universities guaranteeing to reach a wide range of the population. However, the main drawback of this method is the need for specialized MNP with a strong negative charge for the viral RNA extraction to detect the existence of the SARS-CoV-2 virus. Here we present a simplified low cost method to produce 10 g of nanoparticles in 100 mL of solution that was scaled to one litter by parallelizing the process 10 times in just two days and allowing for the possibility of making ~ 50,000 COVID-19 tests. This communication helps in reducing the cost of acquiring MNP for diverse biomolecular applications supporting developing country budgets constraints and chemical availability specially during the COVID-19 International Health Emergency.


Assuntos
Técnicas de Laboratório Clínico/métodos , Custos e Análise de Custo , Nanopartículas de Magnetita/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Teste para COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/diagnóstico , Países em Desenvolvimento , Humanos , Nanopartículas de Magnetita/economia , RNA Viral/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa/economia
19.
Int J Mol Sci ; 21(9)2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397263

RESUMO

Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.


Assuntos
Anticarcinógenos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Catequina/análogos & derivados , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Terapia Combinada/métodos , Fotoquimioterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Ácido Aminolevulínico/análogos & derivados , Ácido Aminolevulínico/farmacologia , Carcinoma de Células Escamosas/radioterapia , Catequina/farmacologia , Morte Celular/efeitos da radiação , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Hipóxia Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ferroquelatase/genética , Ferroquelatase/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Protoporfirinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Cutâneas/radioterapia , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos da radiação , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Survivina/genética , Survivina/metabolismo , Simportadores/genética , Simportadores/metabolismo
20.
New Phytol ; 226(4): 1117-1128, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31943225

RESUMO

The benefits of the arbuscular mycorrhizal (AM) symbiosis between plants and fungi are modulated by the functional characteristics of both partners. However, it is unknown to what extent functionally distinct groups of plants naturally associate with different AM fungi. We reanalysed 14 high-throughput sequencing data sets describing AM fungal communities associating with plant individuals (2427) belonging to 297 species. We examined how root-associating AM fungal communities varied between plants with different growth forms, photosynthetic pathways, CSR (competitor, stress-tolerator, ruderal) strategies, mycorrhizal statuses and N-fixing statuses. AM fungal community composition differed in relation to all studied plant functional groups. Grasses, C4 and nonruderal plants were characterised by high AM fungal alpha diversity, while C4 , ruderal and obligately mycorrhizal plants were characterised by high beta diversity. The phylogenetic diversity of AM fungi, a potential surrogate for functional diversity, was higher among forbs than other plant growth forms. Putatively ruderal (previously cultured) AM fungi were disproportionately associated with forbs and ruderal plants. There was phylogenetic correlation among AM fungi in the degree of association with different plant growth forms and photosynthetic pathways. Associated AM fungal communities constitute an important component of plant ecological strategies. Functionally different plants associate with distinct AM fungal communities, linking mycorrhizal associations with functional diversity in ecosystems.


Assuntos
Micobioma , Micorrizas , Ecossistema , Filogenia , Raízes de Plantas , Plantas , Microbiologia do Solo , Simbiose
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