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1.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473963

RESUMO

The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we demonstrated that C1QBP is an essential promoter of migration, chemoresistance, clonogenic, and tumorigenic capacity in colon cancer cells. However, the mechanisms underlying these functions and the effects of specific C1QBP protein inhibitors remain unexplored. Here, we show that the specific pharmacological inhibition of C1QBP with the small molecule M36 significantly decreased the viability rate, clonogenic capacity, and proliferation rate of different colon cancer cell lines in a dose-dependent manner. The effects of the inhibitor of C1QBP were cytostatic and non-cytotoxic, inducing a decreased activation rate of critical pro-malignant and mitogenic cellular pathways such as Akt-mTOR and MAPK in RKO colon cancer cells. Additionally, treatment with M36 significantly affected the mitochondrial integrity and dynamics of malignant cells, indicating that p32/C1QBP plays an essential role in maintaining mitochondrial homeostasis. Altogether, our results reinforce that C1QBP is an important oncogene target and that M36 may be a promising therapeutic drug for the treatment of colon cancer.


Assuntos
Neoplasias do Colo , Citostáticos , Humanos , Citostáticos/farmacologia , Mitógenos/farmacologia , Transdução de Sinais , Proteínas Mitocondriais/metabolismo , Proliferação de Células , Proteínas de Transporte/metabolismo
2.
Int J Mol Sci ; 24(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36982333

RESUMO

The presence of cancer stem cells (CSCs) has been associated with the induction of drug resistance and disease recurrence after therapy. 5-Fluorouracil (5FU) is widely used as the first-line treatment of colorectal cancer (CRC). However, its effectiveness may be limited by the induction of drug resistance in tumor cells. The Wnt pathway plays a key role in the development and CRC progression, but it is not clearly established how it is involved in CSCs resistance to treatment. This work aimed to investigate the role played by the canonical Wnt/ß-catenin pathway in CSCs resistance to 5FU treatment. Using tumor spheroids as a model of CSCs enrichment of CRC cell lines with different Wnt/ß-catenin contexts, we found that 5FU induces in all CRC spheroids tested cell death, DNA damage, and quiescence, but in different proportions for each one: RKO spheroids were very sensitive to 5FU, while SW480 were less susceptible, and the SW620 spheroids, the metastatic derivative of SW480 cells, displayed the highest resistance to death, high clonogenic capacity, and the highest ability for regrowth after 5FU treatment. Activating the canonical Wnt pathway with Wnt3a in RKO spheroids decreased the 5FU-induced cell death. But the Wnt/ß-catenin pathway inhibition with Adavivint alone or in combination with 5FU in spheroids with aberrant activation of this pathway produced a severe cytostatic effect compromising their clonogenic capacity and diminishing the stem cell markers expression. Remarkably, this combined treatment also induced the survival of a small cell subpopulation that could exit the arrest, recover SOX2 levels, and re-grow after treatment.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Via de Sinalização Wnt , beta Catenina/metabolismo , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/patologia , Neoplasias do Colo/metabolismo , Linhagem Celular , Fluoruracila/uso terapêutico , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proliferação de Células , Células-Tronco Neoplásicas/metabolismo
3.
J Trop Pediatr ; 67(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33313750

RESUMO

We report diagnosis, treatment and evolution of cases of ocular toxocariasis in specialized consultation in Quindío, Colombia. No cases were seen during the 2000-17 period, but five cases were confirmed from November 2017 to March 2019; two children resulted with definitive loss of vision on the affected eye. Studies in contacts found that 12 of 19 (63%) family members and 15 of 25 (60%) children <15 years of age living on the same street were positive for IgG Toxocara antibodies. Epidemiological studies are necessaries to establish the reasons for the increase in cases at this region.


Assuntos
Infecções Oculares Parasitárias , Toxocaríase , Animais , Anticorpos Anti-Helmínticos , Criança , Colômbia/epidemiologia , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/epidemiologia , Humanos , Encaminhamento e Consulta , Toxocaríase/diagnóstico , Toxocaríase/epidemiologia
4.
Dermatol Ther ; 33(6): e14319, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32949180

RESUMO

Some studies have demonstrated that neurotransmitters are involved in the pathogenesis of numerous skin conditions, including psoriasis, addressing the close correlation between the skin and the central nervous system. There are reports showing psoriasis improvement after peripheral nervous system injury. In addition, botulinum toxin has been reported as a treatment for several diseases, including psoriasis. This is a proof-of-concept study of botulinum toxin and psoriasis, involving eight patients with stable and recalcitrant plaques of psoriasis vulgaris. The lesions were 5 cm2 at the maximum. Botulinum toxin Dysport (Ipsen Biopharm, Wrexham, UK), 5 units per cm2 , was administered in one subcutaneous application. Patients were then evaluated at 2 and 4 weeks after treatment. Our results indicated a substantial improvement in all patients, 4 weeks after treatment, with no significant side effects. Our preliminary conclusion is that botulinum toxin represents a novel mechanism for interfering with the immunopathogenesis of psoriasis and improving the quality of life of our patients.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Psoríase , Toxinas Botulínicas Tipo A/efeitos adversos , Humanos , Fármacos Neuromusculares/efeitos adversos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento
5.
J Environ Sci Health B ; 55(11): 968-973, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32897838

RESUMO

The aim of this study was to identify organochlorine (OC) and organophosphorus (OP) pesticides levels in water samples collected in secondary water bodies in agricultural area planted with coffee and plantain. A descriptive cross-sectional study was carried out. A validated method for microwave-assisted extraction and gas chromatography with electron microcapture detector (MAE-GC-µECD) was used to analyze pesticide residues in samples. The determinations were based on certified reference material, Organochlorine Pesticide Mix AB #3, Canadian Drinking Organophosphorus Pesticides Mix, and pentachloronitrobenzene (ISTD) Internal Standard Mix 508.1. Pesticide residues were found in 81.3% of the samples, including OCs: 4.4'-DDT (38%), endosulfan II (19.7%), endosulfan sulfate, and endrin (11.7% and 8.8%), and others identified as 4.4'-DDE, Delta-HCB, parathion, chlorpyrifos, endrin aldehyde, heptachlor, heptachlor epoxide, endrin ketone, and methoxychlor. Parathion and/or chlorpyrifos were found in 5.8-8% of samples; the water bodies most heavily affected were those in Filandia and Quimbaya in which 100% of samples were contaminated, followed by those in Calarcá, Córdoba, Pijao, and Génova, with contamination found in over 75% of samples. The results indicated that surface waters from Quindío municipalities are contaminated with pesticide residues hazardous to human health, which are still in use despite being either restricted or prohibited.


Assuntos
Coffea , Hidrocarbonetos Clorados/análise , Organofosfatos/análise , Resíduos de Praguicidas/análise , Poluentes Químicos da Água/análise , Agricultura , Cromatografia Gasosa , Colômbia , Estudos Transversais , Monitoramento Ambiental/métodos , Humanos , Plantago
6.
Dermatol Online J ; 22(9)2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28329605

RESUMO

During the last few decades, management of psoriasis has changed worldwide, owing to a better understanding of its pathophysiology and the introduction of new treatments. As experts in the field of dermatology, specialists from Latin America collaborated to develop this review and further provide an update on the current state of psoriasis management in Latin America. With the goal of summarizing the latest information on psoriasis in most countries in Latin America, we conducted a literature search to obtain relevant articles published in the medical/scientific literature in Latin American countries over the last 10 years; in addition, we completed a questionnaire comprised of 20 questions on important issues related to psoriasis. The aim of this final document isto help improve understanding and management of the disease and to help patients gain better access to new approaches and medical solutions.


Assuntos
Antibacterianos/uso terapêutico , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Fototerapia , Psoríase/terapia , Acessibilidade aos Serviços de Saúde , Humanos , América Latina/epidemiologia , Terapia PUVA , Cooperação do Paciente , Psoríase/epidemiologia , Terapia Ultravioleta
7.
Stem Cell Rev Rep ; 20(1): 25-51, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37922108

RESUMO

CD133 protein has been one of the most used surface markers to select and identify cancer cells with stem-like features. However, its expression is not restricted to tumoral cells; it is also expressed in differentiated cells and stem/progenitor cells in various normal tissues. CD133 participates in several cellular processes, in part orchestrating signal transduction of essential pathways that frequently are dysregulated in cancer, such as PI3K/Akt signaling and the Wnt/ß-catenin pathway. CD133 expression correlates with enhanced cell self-renewal, migration, invasion, and survival under stress conditions in cancer. Aside from the intrinsic cell mechanisms that regulate CD133 expression in each cellular type, extrinsic factors from the surrounding niche can also impact CD33 levels. The enhanced CD133 expression in cells can confer adaptive advantages by amplifying the activation of a specific signaling pathway in a context-dependent manner. In this review, we do not only describe the CD133 physiological functions known so far, but importantly, we analyze how the microenvironment changes impact the regulation of CD133 functions emphasizing its value as a marker of cell adaptability beyond a cancer-stem cell marker.


Assuntos
Fosfatidilinositol 3-Quinases , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética , Células-Tronco Neoplásicas/metabolismo , Autorrenovação Celular
8.
Artigo em Inglês | MEDLINE | ID: mdl-38314980

RESUMO

Background The Dermatology Life Quality Index (DLQI) is a valuable tool for assessing the quality of life in adult patients with psoriasis. Aims To analyse the reliability and validity of the DLQI to measure the quality of life in patients with mild to moderate-severe psoriasis. Methods This was a secondary validation study nested in a follow-up study. The Rasch-Andrich model was utilised to perform response function, item and person fit, differential item functioning, dimensionality, and reliability analyses. Results A total of 1439 patients were analysed, 52.1% male, mean age of 48.7 years (SD 16.1). Psoriasis vulgaris was the phenotype in 43.1% of patients, and 86% had a mild Psoriasis Area Severity Index (PASI). Adequate adjustment of the response function and the items was observed in the best-fit sample, except for item 7 (work and study). The measure explained 60.9% of the variance and presented a reliability of 0.86. Differential item functioning was identified by age, with a relevant bias in the estimation for older adults. Item-person maps are provided. Limitations This study was performed at a single centre, with most patients presenting a mild PASI score, limiting generalisation of the findings. Conclusion The validity evidence favours the use of the DLQI in moderate-severe psoriasis. However, the instrument biases the estimate of older adults. This population group should consider a specific version of the instrument.

9.
Biomedica ; 43(1): 107-120, 2023 03 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37167466

RESUMO

Introduction: Atopic dermatitis, also known as eczema or atopic eczema, is a chronic inflammatory skin disorder characterized by the presence of pruritus accompanied by itching. In Colombia, epidemiological and healthcare resource utilization information regarding this pathology is limited. Objective: To describe atopic dermatitis epidemiological characteristics and healthcare resource utilization patterns in Colombia. Material and methods: A retrospective database study using real-world data obtained from the national claims database SISPRO (Sistema de Información para la Protección Social) for the 2015-2020 period was carried out. Sociodemographic (age, and health services delivery), epidemiological (incidence, prevalence, and comorbidities), and healthcare resource utilization data were extracted from the SISPRO database. Results: The epidemiological results showed increased incidence and prevalence of atopic dermatitis in Colombia in the 2018-2019 period compared to 2015-2017. Accordingly, the number of medical consultations (particularly with specialists), the number of procedures, and the number of hospitalizations of patients with atopic dermatitis increased. Topic and systemic corticoids were the most frequently prescribed drugs. Conclusions: Diagnoses of atopic dermatitis in Colombia increased with a concomitant increase in healthcare resource utilization during 2015-2020, which was possibly slowed down by the arrival of the Covid-19. This study may help physicians gaining a better understanding of the disease, improving atopic dermatitis patient management.


Introducción. La dermatitis atópica, también conocida como eczema o eczema atópico, es un trastorno inflamatorio crónico de la piel caracterizado por la presencia de prurito acompañado de picor. En Colombia, la información epidemiológica y de utilización de recursos sanitarios sobre esta enfermedad es limitada. Objetivo. Describir las características epidemiológicas y los patrones de utilización de recursos sanitarios para la dermatitis atópica en Colombia. Material y métodos. Se trata de un estudio retrospectivo en el cual se utilizan datos de la práctica clínica real obtenidos del registro nacional SISPRO (Sistema de Información para la Protección Social) en el período 2015-2020. Se extrajeron datos sociodemográficos (incluida la edad y la prestación de servicios de salud), epidemiológicos (incluidos la incidencia, la prevalencia y las comorbilidades) y los correspondientes a la utilización de los recursos sanitarios. Resultados. Los resultados epidemiológicos han demostrado un aumento de la incidencia y prevalencia de la dermatitis atópica en Colombia en el periodo 2018-2019, en comparación con el periodo 2015-2017. Aumentó el número de consultas médicas (particularmente, con especialistas) de pacientes con dermatitis atópica, el de procedimientos y el de hospitalizaciones. Los corticoides tópicos y sistémicos fueron los medicamentos más prescritos. Conclusiones. Los diagnósticos de dermatitis atópica en Colombia aumentaron con un incremento concomitante en la utilización de recursos sanitarios durante 2015-2020, que posiblemente se vio atenuado por la llegada del Covid-19. Este estudio puede ayudar a los médicos a tener un mejor conocimiento de la enfermedad y, por lo tanto, mejorar el tratamiento de los pacientes con dermatitis atópica.


Assuntos
COVID-19 , Dermatite , Humanos , Colômbia/epidemiologia , Dermatite/epidemiologia , Estudos Retrospectivos
10.
Front Oncol ; 13: 1121787, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969011

RESUMO

Introduction: Cancer Stem Cells (CSC) are responsible for maintaining tumor growth, chemoresistance, and metastasis. Therefore, understanding their characteristics is critical to progress in cancer therapy. While the contribution of the canonical Wnt/b-catenin signaling in both normal and CSCs had been well established, the function of non-canonical Wnt signaling cascades in stem cells is unclear. Recently, we reported that Wnt ligands trigger complex signaling in which the canonical and non-canonical responses can be simultaneously activated by one ligand in colon cancer cells, suggesting, therefore, that noncanonical Wnt pathways may also be important in CSCs. Methods: The present work aimed to know the role of the Wnt/Ca2+ pathway in colon CSCs. We used tumorspheres as a model of CSCs enrichment of CRC cell lines with different Wnt/b-catenin contexts. Results: Using Wnt3a and Wnt5a as prototype ligands to activate the canonical or the non-canonical pathways, respectively, we found that both Wnt3a and Wnt5a promote sphere-formation capacity and proliferation without stimulating b-catenin-dependent transcription. Upregulation of sphere formation by Wnt5a or Wnt3a requires the downstream activation of Phospholipase C and transcriptional factor NFAT. Moreover, the single specific inhibition of PLC or NFAT, using U73122 and 11R-VIVIT, respectively, leads to impaired sphere formation. Discussion: Our results indicate that both types of ligands activate the Wnt/Ca2+ signaling axis to induce/maintain the self-renewal efficiency of CSCs, demonstrating to be essential for the functions of CSC in colon cancer.

11.
Rev Chilena Infectol ; 29(4): 395-400, 2012 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-23096538

RESUMO

OBJECTIVE: to identify the risk factors for surgical site infections (SSI) in patients with surgical management fractures with internal fixation or prosthetic material. MATERIALS AND METHODS: a cross-sectional study was conducted in a tertiary institution in Armenia-Colombia in 2008 and 2009 in 223 patients. RESULTS: The superficial incisional infection frequency was 9,4% (n: 21), and deep incisional infection was 7,6% (n: 17); there were no organ/space SSI.; the highest rates of infection were observed in patella fractures (50%), acromio-clavicular joint (25%), and femur (23,7%). The infections were caused by: S. aureus, Enterobactergergoviae y Enterobacteraerogenes. There was an association with clean-contaminated wounds compared to clean wounds (OR 2,2), comminuted fractures (OR 2,1) multiple fractures (OR 2,9) and patella surgery (OR 3,1). CONCLUSIONS: the severity of the fracture and the degree of contamination were predisposing factors to infection.


Assuntos
Infecções Bacterianas/epidemiologia , Fixação Interna de Fraturas/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Antibacterianos/uso terapêutico , Cefazolina/uso terapêutico , Colômbia/epidemiologia , Estudos Transversais , Feminino , Humanos , Controle de Infecções , Masculino , Infecções Relacionadas à Prótese/microbiologia , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Infecção da Ferida Cirúrgica/microbiologia
12.
J Dermatolog Treat ; 33(6): 2821-2826, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35583354

RESUMO

BACKGROUND: Psoriasis is a chronic disease that seriously impacts quality of life. There are known genetic and environmental factors that influence its onset and progression. Even though there is no cure for it, there are a variety of treatments available today to control its symptoms, although many of them fail to do so substantially. OBJECTIVE: To identify the association of multiple sociodemographic, clinical, and pharmacological factors with therapeutic failure. METHODS: Observational, descriptive, cross-sectional, retrospective, and analytical study of therapeutic failure in patients with moderate or severe psoriasis between 2020 and 2021 was performed. RESULTS: In total 1051 patients with moderate or severe psoriasis were evaluated. Gender (ORa: 0.579 CI 95%: 0.382-0.878), type of therapy (biologic or non-biologic; ORa: 1.939 CI 95%: 1.242-3.027), age (ORa: 1.018 CI 95%: 1.003-1.034), days of treatment (ORa: 1 CI 95%: 0.999-1) and DLQI (ORa: 1.212 CI 95%: 1.172-1.253) are significantly associated with therapeutic failure. CONCLUSION: Being male and receiving biologic therapy are associated with a higher incidence of therapeutic failure in the treatment of moderate or severe psoriasis. The increase in DLQI increase in the probability of failure, and mayor age or days of treatment decrease in the probability of failure.


Assuntos
Psoríase , Qualidade de Vida , Humanos , Masculino , Feminino , Estudos Transversais , Estudos Retrospectivos , Prevalência , Índice de Gravidade de Doença , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Psoríase/diagnóstico
13.
Biomedica ; 42(2): 278-289, 2022 06 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35867921

RESUMO

Introduction: About 80-95% of patients infected with the human immunodeficiency virus (HIV) develop skin manifestations, which are markers of the patients' immune status. Objective: To describe the dermatologic manifestations and the clinical and sociodemographic factors of hospitalized patients diagnosed with HIV and their correlation with CD4 T-lymphocyte count. Materials and methods: We conducted an observational, cross-sectional, and retrospective study of the medical records of 227 adult patients with HIV diagnosis evaluated by dermatology in a hospital in Medellín, Colombia. Results: We included 227 patient records with 433 dermatologic manifestations, 64.4% of them infectious. The most frequent manifestations were oral candidiasis, condylomata acuminata, and drug reactions. Moreover, a statistically significant relationship was found between disseminated herpes zoster virus and secondary syphilis with a CD4 count between 200-499 cells/mm3 (p=0.04 and 0.028, respectively). There was also a statistically significant relationship between oral candidiasis and a CD4 count of less than 100 cells/mm3 (p=0.008). Conclusions: The relationship between disseminated herpes zoster with CD4 between 200-499 cells/mm3 suggests that, despite having high CD4 counts, severe forms of the disease may occur due to possible T-cell dysfunction and depletion of the immune system. Additionally, the relationship between oral candidiasis and CD4 less than 100 cells/mm3 indicates the potential role of oral candidiasis as an essential marker of weakened immune status in HIV patients.


Introducción. Entre el 80 y el 95 % de los pacientes infectados por el virus de inmunodeficiencia humana (HIV) desarrollan manifestaciones en la piel que sirven como marcadores de su estado inmunológico. Objetivos. Describir las manifestaciones dermatológicas y los factores clínicos y sociodemográficos de los pacientes hospitalizados con diagnóstico de HIV y su correlación con el recuento de linfocitos T CD4. Materiales y métodos. Se hizo un estudio observacional de corte transversal y retrospectivo a partir del registro de las historias clínicas de 227 pacientes mayores de edad con diagnóstico de HIV, evaluados por dermatología en un hospital de Medellín, Colombia. Resultados. Los 227 registros daban cuenta de 433 manifestaciones dermatológicas, el 64,4 % de ellas infecciosas. Las tres manifestaciones más frecuentes fueron candidiasis oral, condilomas acuminados y reacciones a medicamentos. Se encontró una relación estadísticamente significativa entre el virus del herpes zóster (HZ) diseminado y la sífilis secundaria, con un recuento de CD4 entre 200 y 499 células/mm3 (p=0,04 y 0,028, respectivamente), y entre la candidiasis oral y un recuento de CD4 menor de 100 células/mm3 (p=0,008). Conclusiones. La relación entre el herpes zóster diseminado y un recuento de CD4 entre 200 y 499 células/mm3 sugiere que, a pesar de los recuentos altos, se pueden presentar formas graves de la enfermedad debido a una posible disfunción de las células T y el agotamiento del sistema inmunológico. La relación entre la candidiasis oral y un recuento de CD4 menor de 100 células/mm3 plantea la posibilidad de considerar esta infección micótica como un marcador importante de debilitamiento inmunológico de los pacientes con HIV.


Assuntos
Candidíase , Infecções por HIV , Herpes Zoster , Colômbia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos
14.
Biomedica ; 41(2): 234-239, 2021 06 29.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34214264

RESUMO

Exogenous pigmentation by silver nitrate is a rare disease whose clinical manifestations appear even years after the contact, making its diagnosis difficult on occasions. It is characterized by the presence of blue-gray macules or plaques on the skin or mucosa in the contact area, sometimes very similar to melanocytic lesions and melanoma, which constitute the main differential diagnosis. We report the case of a male patient from Medellín, Colombia, with a family history of melanoma and the presence of these lesions throughout his body.


La pigmentación exógena por nitrato de plata es una enfermedad poco frecuente, cuyas manifestaciones clínicas pueden aparecer años después del contacto, lo que en ocasiones dificulta su diagnóstico. Se caracteriza por la presencia de máculas o placas azul-grisáceas en la piel o las mucosas de la zona de contacto que, en ocasiones, son muy similares a las lesiones melanocíticas y al melanoma, sus principales diagnósticos diferenciales. Se reporta el caso de un paciente de Medellín, Colombia, con antecedentes familiares de melanoma y presencia de estas lesiones en todo el cuerpo.


Assuntos
Argiria , Melanoma , Argiria/etiologia , Humanos , Masculino , Pigmentação , Nitrato de Prata/toxicidade , Pele
15.
Front Endocrinol (Lausanne) ; 12: 627745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828530

RESUMO

Cancer cells characteristically have a high proliferation rate. Because tumor growth depends on energy-consuming anabolic processes, including biosynthesis of protein, lipid, and nucleotides, many tumor-associated conditions, including intermittent oxygen deficiency due to insufficient vascularization, oxidative stress, and nutrient deprivation, results from fast growth. To cope with these environmental stressors, cancer cells, including cancer stem cells, must adapt their metabolism to maintain cellular homeostasis. It is well- known that cancer stem cells (CSC) reprogram their metabolism to adapt to live in hypoxic niches. They usually change from oxidative phosphorylation to increased aerobic glycolysis even in the presence of oxygen. However, as opposed to most differentiated cancer cells relying on glycolysis, CSCs can be highly glycolytic or oxidative phosphorylation-dependent, displaying high metabolic plasticity. Although the influence of the metabolic and nutrient-sensing pathways on the maintenance of stemness has been recognized, the molecular mechanisms that link these pathways to stemness are not well known. Here in this review, we describe the most relevant signaling pathways involved in nutrient sensing and cancer cell survival. Among them, Adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway, mTOR pathway, and Hexosamine Biosynthetic Pathway (HBP) are critical sensors of cellular energy and nutrient status in cancer cells and interact in complex and dynamic ways.


Assuntos
Metabolismo Energético/fisiologia , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais/fisiologia , Animais , Hexosaminas/metabolismo , Humanos , Estresse Oxidativo/fisiologia , Serina-Treonina Quinases TOR/metabolismo
16.
Heliyon ; 7(7): e07358, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34278015

RESUMO

During the last years, in the sub-basin of the Chicú river, the agricultural and cattle exploitation has intensified and has depleted the water resources, thereby causing a deficit that has limited the continuity of such agricultural activity. Therefore, it is necessary to quantify land use and land cover changes contribute to the hydrological response to achieve sustainable management of the water resources in the sub-basin. In this sense, an integrated approach was used, which includes the SWAT (Soil and Water Assessment Tool) hydrological model and the different LUCC (Land use and cover change) maps obtained through tele-detection by using Landsat images to decide the hydrological response in the basin with the changes in land cover and uses in 1997, 2001, 2006, 2011, and 2016. As a result of the SWAT modeling, it can be noticed that the surface run-off varies according to the type of cover and extension, increasing or decreasing the water flow according to the characteristics of each cover, as in the case of bare lands (AGRL). While in 2006 it represented an area of 7.32% with a run-off of 39.25 mm, in 2001 its area decreased to 5.66% with a run-off of 44.9 mm. Moreover, in 1997 a flow of 4.45 m 3 / s can be observed, whereas in 2001 it decreases by 15% in the main current, which can be justified by a decrease of 8.8% in dense (FRSD) and fragmented (FRDT) forests. For 2006 and 2011 scenarios, the flow increases 13% and 50%, respectively, which corresponds to an increase of 36% and 48% concerning 2001 in clean grasses (PAST); despite the increase in clean grasses (PAST), the surface run-off was maintained almost constant above 9 mm, and it is thus considered a more stable vegetation cover.

17.
Front Oncol ; 11: 642940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136383

RESUMO

p32 is a multifunctional and multicompartmental protein that has been found upregulated in numerous adenocarcinomas, including colorectal malignancy. High levels of p32 expression have been correlated with poor prognosis in colorectal cancer. However, the functions performed by p32 in colorectal cancer have not been characterized. Here we show that p32 is overexpressed in colorectal cancer cell lines compared to non-malignant colon cells. Colon cancer cells also display higher nuclear levels of p32 than nuclear levels found in non-malignant cells. Moreover, we demonstrate that p32 regulates the expression levels of genes tightly related to malignant phenotypes such as HAS-2 and PDCD4. Remarkably, we demonstrate that knockdown of p32 negatively affects Akt/mTOR signaling activation, inhibits the migration ability of colon malignant cells, and sensitizes them to cell death induced by oxidative stress and chemotherapeutic agents, but not to cell death induced by nutritional stress. In addition, knockdown of p32 significantly decreased clonogenic capacity and in vivo tumorigenesis in a xenograft mice model. Altogether, our results demonstrate that p32 is an important promoter of malignant phenotype in colorectal cancer cells, suggesting that it could be used as a therapeutic target in colorectal cancer treatment.

18.
Rev Salud Publica (Bogota) ; 20(2): 215-220, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30570004

RESUMO

OBJECTIVES: To establish the correlation between hypothyroidism and blood pesticide levels. MATERIALS AND METHODS: Cross-sectional study in agricultural workers and their permanent partners in plantain and coffee producing municipalities as reference population. A representative sample was estimated and thyroid function tests were performed using ELISA Stat Fax 303/Plus reader, at a wavelength of 450 nm. Organochlorine pesticide residuality was determined, a dispersive liquid-liquid microextraction (DLLME) assisted by sonication was implemented, and a gas chromatography-micro-electron capture detector (GC-pECD) was used for the analysis. RESULTS: 819 participants, 58.7% men and 41.3% women were included; their average age was 48.1 years. Prevalence of symptomatic hypothyroidism (1.2%) and subclinical hypothyroidism (6.7%) was observed, with a higher prevalence in people older than 60 years (2.6% and 8.9%, respectively). Non-causal association was found between subclinical hypothyroidism and the organochlorine pesticides 4,4'-DDE (sig.0,006), Heptachlor (sig.0,04), and Endosulfan I (sig.0,02). Antiperoxidase (Anti TPO) antibodies ≥60 lU/ml were associated with subclinical hypothyroidism (OR 2.6). CONCLUSIONS: The prevalence of hypothyroidism in the studied population is similar to that reported in the literature, and lower than in urban areas. In turn, the prevalence of subclinical hypothyroidism is higher and positive anti-TPO values are related to risk of progression to frank hypothyroidism, which is why follow-up is required in these patients. Three organochlorine pesticides were associated with subclinical hypothyroidism. TSH screening is recommended in people aged 40 and over, especially if they are exposed to the aforementioned agrochemicals.


OBJETIVOS: Determinar relación entre hipotiroidismo y plaguicidas en sangre. METODOLOGÍA: Estudio de corte transversal, en agricultores y sus compañeros(as) permanentes en municipios productores de plátano y café. Se calculó muestra representativa. Se realizaron pruebas de función tiroidea, se utilizó un lector de ELISA Stat Fax 303/Plus, en una longitud de onda 450 nm. Se determinó la residualidad de plaguicidas organoclorados, se implementó un método de microextracción dispersiva en fase líquida (DLLME) asistida por sonicación, y se empleó cromatografía de gases con detector de micro captura de electrones (GC-µECD) para el análisis. RESULTADOS: Se incluyeron 819 participantes, 58,7% hombres y 41,3% mujeres; promedio de edad 48,1 años. Prevalencia de hipotiroidismo manifiesto 1,2% y de hipotiroidismo subclínico 6,7%, mayor prevalencia en personas mayores de 60 años (2,6% y 8,9% respectivamente). Se encontró asociación no causal de hipotiroidismo subclínico con plaguicidas organoclorados 4,4'-DDE (sig.0,006), Heptacloro (sig.0,04), y Endosulfán I (sig.0,02). Los anticuerpos antiperoxidasa (Anti TPO) ≥ 60 lU/ml se asociaron con h. subclínico, OR 2,6. CONCLUSIONES: La prevalencia de hipotiroidismo hallada es similar a lo referido en la literatura, es menor que en áreas urbanas; la prevalencia de hipotiroidismo subclínico es mayor y con riesgo de progresión a hipotiroidismo franco cuando se relaciona con Anti-TPO positivos, razón por la cual se requiere seguimiento en estos pacientes. Se asociaron a h. subclínico 3 plaguicidas organoclorados. Se recomienda tamizaje de TSH en personas de 40 y más años sobre todo si están expuestas a los agroquímicos mencionados.


Assuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Café , Hidrocarbonetos Clorados/toxicidade , Hipotireoidismo/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Plantago , Adulto , Doenças dos Trabalhadores Agrícolas/sangue , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças Assintomáticas/epidemiologia , Cromatografia Gasosa , Colômbia/epidemiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hidrocarbonetos Clorados/sangue , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Praguicidas/sangue , Prevalência
19.
Biomédica (Bogotá) ; 43(1): 107-120, mar. 2023. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1533910

RESUMO

Introduction: Atopic dermatitis, also known as eczema or atopic eczema, is a chronic inflammatory skin disorder characterized by the presence of pruritus accompanied by itching. In Colombia, epidemiological and healthcare resource utilization information regarding this pathology is limited. Objective: To describe atopic dermatitis epidemiological characteristics and healthcare resource utilization patterns in Colombia. Materials and methods: A retrospective database study using real-world data obtained from the national claims database SISPRO (Sistema de Información para la Protección Social) for the 2015-2020 period was carried out. Sociodemographic (age, and health services delivery), epidemiological (incidence, prevalence, and comorbidities), and healthcare resource utilization data were extracted from the SISPRO database. Results: The epidemiological results showed increased incidence and prevalence of atopic dermatitis in Colombia in the 2018-2019 period compared to 2015-2017. Accordingly, the number of medical consultations (particularly with specialists), the number of procedures, and the number of hospitalizations of patients with atopic dermatitis increased. Topic and systemic corticoids were the most frequently prescribed drugs. Conclusions: Diagnoses of atopic dermatitis in Colombia increased with a concomitant increase in healthcare resource utilization during 2015-2020, which was possibly slowed down by the arrival of the Covid-19. This study may help physicians gaining a better understanding of the disease, improving atopic dermatitis patient management.


Introducción. La dermatitis atópica, también conocida como eczema o eczema atópico, es un trastorno inflamatorio crónico de la piel caracterizado por la presencia de prurito acompañado de picor. En Colombia, la información epidemiológica y de utilización de recursos sanitarios sobre esta enfermedad es limitada. Objetivo. Describir las características epidemiológicas y los patrones de utilización de recursos sanitarios para la dermatitis atópica en Colombia. Materiales y métodos. Se trata de un estudio retrospectivo en el cual se utilizan datos de la práctica clínica real obtenidos del registro nacional SISPRO (Sistema de Información para la Protección Social) en el período 2015-2020. Se extrajeron datos sociodemográficos (incluida la edad y la prestación de servicios de salud), epidemiológicos (incluidos la incidencia, la prevalencia y las comorbilidades) y los correspondientes a la utilización de los recursos sanitarios. Resultados. Los resultados epidemiológicos han demostrado un aumento de la incidencia y prevalencia de la dermatitis atópica en Colombia en el periodo 20182019, en comparación con el periodo 2015-2017. Aumentó el número de consultas médicas (particularmente, con especialistas) de pacientes con dermatitis atópica, el de procedimientos y el de hospitalizaciones. Los corticoides tópicos y sistémicos fueron los medicamentos más prescritos. Conclusiones. Los diagnósticos de dermatitis atópica en Colombia aumentaron con un incremento concomitante en la utilización de recursos sanitarios durante 2015-2020, que posiblemente se vio atenuado por la llegada del Covid-19. Este estudio puede ayudar a los médicos a tener un mejor conocimiento de la enfermedad y, por lo tanto, mejorar el tratamiento de los pacientes con dermatitis atópica.


Assuntos
Dermatite Atópica/epidemiologia , Revisão da Utilização de Recursos de Saúde , Colômbia , Tratamento Farmacológico , COVID-19
20.
Food Chem Toxicol ; 109(Pt 1): 143-154, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28870684

RESUMO

Cisplatin is an effective antineoplastic agent widely used in the treatment of solid tumors, however, it induces nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with increased reactive oxygen species (ROS) production and decreased antioxidant system defense in kidney. Isoliquiritigenin (IsoLQ) is a chalcone, which is characterized by its antioxidant and antiinflammatory properties. Herein, we investigated the protective effect of IsoLQ on LLC-PK1 proximal tubular cells against cisplatin-induced death and its effect on the antineoplastic activity of cisplatin on bladder cancer T24 cell line. It was found that pretreatment with IsoLQ attenuates cisplatin-induced cell death, ROS production, and activation of caspase-3. IsoLQ also induced heme oxygenase-1 (HO-1) expression that may be associated with nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation. The protective effect of IsoLQ was abrogated by tin mesoporphyrin (SnMP), an HO inhibitor. Further, bilirubin and carbon monoxide releasing molecule-2 also showed a protective effect against cisplatin-induced cell death. In addition, IsoLQ induced in a dose-dependent way, death of T24 cells and exacerbated cisplatin-induced cell death. These results suggest that IsoLQ has a protective effect on cisplatin-induced toxicity in LLC-PK1 cells, in part through induction of HO-1, without interfering with the antineoplastic activity of this agent in T24 cells.


Assuntos
Antineoplásicos/efeitos adversos , Chalconas/farmacologia , Cisplatino/efeitos adversos , Neoplasias da Bexiga Urinária/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Células LLC-PK1 , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Suínos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
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