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1.
Arch. Soc. Esp. Oftalmol ; 98(5): 265-269, mayo 2023. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-219934

RESUMO

Objetivo Aplicar técnicas de inteligencia artificial, mediante algoritmos de aprendizaje profundo, para el desarrollo y optimización de un sistema de predicción de la edad de una persona con base en una retinografía color, y estudiar una posible relación entre la evolución de la retinopatía diabética (RD) y un envejecimiento prematuro de la retina. Métodos Se entrenó una red convolucional para calcular la edad de una persona con base en una retinografía. Dicho entrenamiento fue realizado sobre un conjunto de retinografías de pacientes con diabetes previamente dividido en 3 subconjuntos (entrenamiento, validación y test). La diferencia entre la edad cronológica del paciente y la edad biológica de la retina se definió como gap de edad retiniano. Resultados Se utilizó un conjunto de 98.400 imágenes para la fase de entrenamiento, 1.000 imágenes para la fase de validación y 13.544 para la fase de test. El gap retiniano de los pacientes sin RD fue de 0,609 años y el de los pacientes con RD de 1,905 años (p<0,001), siendo la distribución por grado de RD de: RD leve 1,541 años; RD moderada 3,017 años; RD severa 3,117 años, y RD proliferativa 8,583 años. Conclusiones El gap de edad retiniano muestra una diferencia en positivo de media entre las personas diabéticas con RD frente a las que no tienen RD, y además aumenta progresivamente, de acuerdo con el grado de RD. Estos resultados podrían indicar la existencia de una relación entre la evolución de la enfermedad y un envejecimiento prematuro de la retina (AU)


Objective To apply artificial intelligence techniques, through deep learning algorithms, for the development and optimization of a system for predicting the age of a person based on a color retinography, and to study a possible relationship between the evolution of retinopathy diabetes (RD) and premature aging of the retina. Methods A convolutional network was trained to calculate the age of a person based on a retinography. Said training was carried out on a set of retinographies of patients with diabetes previously divided into 3 subsets (training, validation and test). The difference between the chronological age of the patient and the biological age of the retina was defined as the retinal age gap. Results A set of 98,400 images was used for the training phase, 1000 images for the validation phase and 13,544 for the test phase. The retinal gap of the patients without RD was 0.609 years and that of the patients with RD was 1905 years (p<0.001), with the distribution by degree of RD being: mild RD 1541 years; moderate RD 3017 years; RD severe 3117 years, and proliferative RD 8583 years. Conclusions The retinal age gap shows a positive mean difference between diabetics with RD versus those without RD, and it increases progressively, according to the degree of RD. These results could indicate the existence of a relationship between the evolution of the disease and premature aging of the retina (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Índice de Gravidade de Doença , Inteligência Artificial , Retinopatia Diabética/diagnóstico , Biomarcadores , Algoritmos , Fatores Etários
2.
Arch Soc Esp Oftalmol (Engl Ed) ; 98(5): 265-269, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37075840

RESUMO

OBJECTIVE: To apply artificial intelligence (AI) techniques, through deep learning algorithms, for the development and optimization of a system for predicting the age of a person based on a color retinography and to study a possible relationship between the evolution of retinopathy diabetes and premature ageing of the retina. METHODS: A convolutional network was trained to calculate the age of a person based on a retinography. Said training was carried out on a set of retinographies of patients with diabetes previously divided into three subsets (training, validation and test). The difference between the chronological age of the patient and the biological age of the retina was defined as the retinal age gap. RESULTS: A set of 98,400 images was used for the training phase, 1000 images for the validation phase and 13,544 for the test phase. The retinal gap of the patients without DR was 0.609 years and that of the patients with DR was 1905 years (p < 0.001), with the distribution by degree of DR being: mild DR: 1541 years, moderate DR: 3017 years, DR severe: 3117 years and proliferative DR: 8583 years. CONCLUSIONS: The retinal age gap shows a positive mean difference between diabetics with DR versus those without DR, and it increases progressively, according to the degree of DR. These results could indicate the existence of a relationship between the evolution of the disease and premature ageing of the retina.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Inteligência Artificial , Retina/diagnóstico por imagem , Algoritmos , Biomarcadores
3.
Viruses ; 15(2)2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36851539

RESUMO

Persistent high-risk human papillomavirus infection is the main risk factor for cervical cancer establishment, where the viral oncogenes E6 and E7 promote a cancerous phenotype. Metabolic reprogramming in cancer involves alterations in glutamine metabolism, also named glutaminolysis, to provide energy for supporting cancer processes including migration, proliferation, and production of reactive oxygen species, among others. The aim of this work was to analyze the effect of HPV16 E6 and E7 oncoproteins on the regulation of glutaminolysis and its contribution to cell proliferation. We found that the E6 and E7 oncoproteins exacerbate cell proliferation in a glutamine-dependent manner. Both oncoproteins increased the levels of transporter SNAT1, as well as GLS2 and GS enzymes; E6 also increased LAT1 transporter protein levels, while E7 increased ASCT2 and xCT. Some of these alterations are also regulated at a transcriptional level. Consistently, the amount of SNAT1 protein decreased in Ca Ski cells when E6 and E7 expression was knocked down. In addition, we demonstrated that cell proliferation was partially dependent on SNAT1 in the presence of glutamine. Interestingly, SNAT1 expression was higher in cervical cancer compared with normal cervical cells. The high expression of SNAT1 was associated with poor overall survival of cervical cancer patients. Our results indicate that HPV oncoproteins exacerbate glutaminolysis supporting the malignant phenotype.


Assuntos
Glutamina , Neoplasias do Colo do Útero , Feminino , Humanos , Proliferação de Células , Papillomavirus Humano 16/genética , Proteínas E7 de Papillomavirus/genética , Sistema A de Transporte de Aminoácidos/metabolismo
4.
Pathogens ; 11(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36558861

RESUMO

BACKGROUND: Worldwide prevalence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has increased, affecting mostly young males. OPSCC associated with Human Papillomavirus (HPV) infection exhibits particular characteristics in terms of response to treatment, hence HPV has been proposed as a prognostic factor. The impact of HPV positivity and associated biomarkers on OPSCC in the Mexican population has not been addressed. Therefore, the analysis of OPSCC prognostic markers in the Mexican population is necessary. METHODS: Retrolective study in Mexican OPSCC patients, where HPV prevalence, p16 and EGFR levels were assessed using INNO-LiPA and immunohistochemistry. RESULTS: We found an HPV prevalence of 57.6% in OPSCC cases treated at a reference center in Mexico. HPV and p16 positivity, as well as EGFR, associate with better outcomes in OPSCC patients, and they also promote reduced death risk. Notably, HPV presence and p16 positivity showed a significant association with disease-free survival (DFS), with a HR of 0.15 (p = 0.006) and a HR of 0.17 (p = 0.012), respectively, indicating a possible role as predictive biomarkers in Mexican OPSCC patients. CONCLUSIONS: Our results reflect the clinical utility of p16 analysis to improve overall survival (OS) and to predict recurrence in oropharyngeal cancer. These results position p16 and HPV as predictive biomarkers for OPSCC.

5.
Cells ; 11(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36497200

RESUMO

High-risk human papillomavirus (HPV) infection is the main risk factor for cervical cancer (CC) development, where the continuous expression of E6 and E7 oncoproteins maintain the malignant phenotype. In Mexico, around 70% of CC cases are diagnosed in advanced stages, impacting the survival of patients. The aim of this work was to identify biomarkers affected by HPV-16 E6 and E7 oncoproteins that impact the prognosis of CC patients. Expression profiles dependent on E6 and E7 oncoproteins, as well as their relationship with biological processes and cellular signaling pathways, were analyzed in CC cells. A comparison among expression profiles of E6- and E7-expressing cells and that from a CC cohort obtained from The Cancer Genome Atlas (TCGA) demonstrated that the expression of 13 genes impacts the overall survival (OS). A multivariate analysis revealed that the downregulated expression of RIPOR2 was strongly associated with a worse OS. RIPOR2, including its transcriptional variants, were overwhelmingly depleted in E6- and E7-expressing cells. Finally, in a Mexican cohort, it was found that in premalignant cervical lesions, RIPOR2 expression decreases as the lesions progress; meanwhile, decreased RIPOR2 expression was also associated with a worse OS in CC patients.


Assuntos
Moléculas de Adesão Celular , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano 16 , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/genética , Prognóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Moléculas de Adesão Celular/genética , Infecções por Papillomavirus/genética
6.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955700

RESUMO

Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including those of the anus, oropharynx, and penis are also related to HPV infection. In CC, HPV-16 is the most prevalent high-risk HPV type, followed by HPV-18, both being responsible for 70% of cases. HPV intratype variant lineages differ in nucleotide sequences by 1-10%, while sublineages differ by 0.5-1%. Several studies have postulated that the nucleotide changes that occur between HPV intratype variants are reflected in functional differences and in pathogenicity. Moreover, it has been demonstrated that HPV-16 and -18 intratype variants differentially affect molecular processes in infected cells, changing their biological behavior that finally impacts in the clinical outcome of patients. Mexico has participated in providing knowledge on the geographical distribution of intratype variants of the most prevalent HPVs in premalignant lesions of the cervix and cervical cancer, as well as in other HPV-related tumors. In addition, functional studies have been carried out to assess the cellular effects of intratype variations in HPV proteins. This review addresses the state of the art on the epidemiology of HPV-16 and HPV-18 intratype variants in the Mexican population, as well as their association with persistence, precancer and cervical cancer, and functional aspects related to their biological behavior.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18/genética , Humanos , México/epidemiologia , Biologia Molecular , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/patologia
7.
Cells ; 11(3)2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35159157

RESUMO

Mast cells (MCs) are tissue-resident immune cells that are important players in diseases associated with chronic inflammation such as cancer. Since MCs can infiltrate solid tumors and promote or limit tumor growth, a possible polarization of MCs to pro-tumoral or anti-tumoral phenotypes has been proposed and remains as a challenging research field. Here, we review the recent evidence regarding the complex relationship between MCs and tumor cells. In particular, we consider: (1) the multifaceted role of MCs on tumor growth suggested by histological analysis of tumor biopsies and studies performed in MC-deficient animal models; (2) the signaling pathways triggered by tumor-derived chemotactic mediators and bioactive lipids that promote MC migration and modulate their function inside tumors; (3) the possible phenotypic changes on MCs triggered by prevalent conditions in the tumor microenvironment (TME) such as hypoxia; (4) the signaling pathways that specifically lead to the production of angiogenic factors, mainly VEGF; and (5) the possible role of MCs on tumor fibrosis and metastasis. Finally, we discuss the novel literature on the molecular mechanisms potentially related to phenotypic changes that MCs undergo into the TME and some therapeutic strategies targeting MC activation to limit tumor growth.


Assuntos
Transtornos Mieloproliferativos , Neoplasias , Animais , Mastócitos/metabolismo , Transtornos Mieloproliferativos/metabolismo , Neoplasias/metabolismo , Transdução de Sinais , Microambiente Tumoral
8.
J Insect Sci ; 21(6)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723332

RESUMO

Despite numerous interventions, the ectoparasitic mite Varroa (Varroa destructor Anderson and Trueman [Mesostigmata: Varroidae]) and the pathogens it vectors remain a primary threat to honey bee (Apis mellifera Linnaeus [Hymenoptera: Apidae]) health. Hygienic behavior, the ability to detect, uncap, and remove unhealthy brood from the colony, has been bred for selectively for over two decades and continues to be a promising avenue for improved Varroa management. Although hygienic behavior is expressed more in Varroa-resistant colonies, hygiene does not always confer resistance to Varroa. Additionally, existing Varroa resistance selection methods trade efficacy for efficiency, because those achieving the highest levels of Varroa resistance can be time-consuming, and thus expensive and impractical for apicultural use. Here, we tested the hypothesis that hygienic response to a mixture of semiochemicals associated with Varroa-infested honey bee brood can serve as an improved tool for predicting colony-level Varroa resistance. In support of our hypothesis, we demonstrated that a mixture of the compounds (Z)-10-tritriacontene, (Z)-8-hentriacontene, (Z)-8-heptadecene, and (Z)-6-pentadecene triggers hygienic behavior in a two-hour assay, and that high-performing colonies (hygienic response to ≥60% of treated cells) have significantly lower Varroa infestations, remove significantly more introduced Varroa, and are significantly more likely to survive the winter compared to low-performing colonies (hygienic response to <60% of treated cells). We discuss the relative efficacy and efficiency of this assay for facilitating apiary management decisions and selection of Varroa-resistant honey bees, as well as the relevance of these findings to honey bee health, pollination services, and social insect communication.


Assuntos
Abelhas , Feromônios , Varroidae , Animais , Criação de Abelhas , Abelhas/química , Abelhas/parasitologia
9.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 48(3): [100661], Jul-Sep. 2021. tab
Artigo em Espanhol | IBECS | ID: ibc-219574

RESUMO

Objetivo: Determinar la frecuencia, la evolución clínica, el tratamiento y el desenlace de la lesión renal aguda (LRA) en pacientes embarazadas con preeclampsia severa (PS) menores de 20años de edad. Material y método: Estudio observacional, transversal, retrospectivo y analítico en una serie de 23 pacientes embarazadas menores de 20años de edad con PS atendidas en la UCI de un hospital de alta especialidad de la ciudad de México durante los años 2018 y 2019. Se consultaron los expedientes para conocer la frecuencia de enfermas que desarrollaron LRA (creatinina sérica ≥1,1mg/dl), complicaciones, diuresis, tratamiento con fármacos, terapia de reemplazo, desenlace (recuperación, hemodiálisis) y mortalidad. Los resultados se compararon con los de enfermas de la serie que no presentaron LRA. Se utilizó estadística descriptiva, prueba U de Mann Whitney y prueba exacta de Fisher con el programa SPSS versión 20. Resultados: Veintidós enfermas tenían riñones nativos y una portaba injerto renal. La frecuencia de pacientes con LRA fue del 43,47% (n=10) con media de la creatinina sérica de 1,59±0,63mg/dl (límites 1,1 a 3,2) y diuresis de 0,91±0,74ml/kg/h. Las 23 enfermas recibieron furosemida como fármaco individual intravenoso (60,87%; n=14) o posterior a la infusión de solución NaCl 0,9% (39,13%; n=9). La LRA se recuperó en el 39,13% (n=9) y se precisó hemodiálisis en la paciente trasplantada (4,34%), con muerte materna del 0%. Conclusiones: La frecuencia de LRA fue elevada, con un solo caso que requirió hemodiálisis, sin mortalidad materna. El uso irrestricto de furosemida en todos los casos resultó relevante.(AU)


Objective: To determine the frequency, clinical course, treatment and outcome of acute kidney injury (AKI) in pregnant patients under 20years of age with severe preeclampsia (SP). Material and method: Observational, cross-sectional, retrospective and analytical study in a series of 23 pregnant patients under 20years of age with SP attended in the Intensive Care Unit (ICU) of a high specialty hospital in Mexico City during the years 2018 and 2019. Records were consulted to determine the frequency of patients that developed AKI (serum creatinine ≥1.1mg/dL), complications, diuresis, drug treatment, replacement therapy, outcome (recovery, haemodialysis), and mortality. The results were compared with those of the patients in the series that did not present with an AKI. Descriptive statistics, Mann Whitney U test and Fisher's exact test, using SPSS version 20, were used. Results: Twenty-two patients had native kidneys and one had a kidney graft. The frequency of patients with AKI was 43.47% (n=10) with mean serum creatinine 1.59±0.63mg/dL (range 1.1 to 3.2) and urine volume 0.91±0.74ml/kg/hour. All 23 patients received furosemide, as an individual drug intravenously 60.87% (n=14), and 39.13% (n=9) after the infusion of 0.9% NaCl solution. AKI recovered in 39.13% (n=9), and haemodialysis was performed in the transplanted patient (4.34%), with 0% maternal death. Conclusions: The frequency of AKI was high with only one case requiring haemodialysis, and no maternal mortality. The unrestricted use of furosemide in all cases was relevant.(AU)


Assuntos
Humanos , Feminino , Adulto , Gestantes , Pré-Eclâmpsia , Ginecologia , Injúria Renal Aguda , Síndrome HELLP , Eclampsia , Diálise Renal , Estudos Transversais , Estudos Retrospectivos , México
10.
Rev Esp Anestesiol Reanim (Engl Ed) ; 68(2): 114-116, 2021 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33371977
11.
Artigo em Espanhol | IBECS | ID: ibc-196755
12.
Sci Rep ; 10(1): 22046, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33328560

RESUMO

The role of the Androgen Receptor (AR) expression and its activity in the prognosis of hepatocellular carcinoma (HCC) remains inconclusive. The aim of this study is to analyze the role of the AR expression and its activity as prognostic biomarkers in HCC. Three-hundred and thirty-seven patients from The Cancer Genome Atlas (TCGA) (107 females; 59.42 years [SD = 13.0]) were included. To infer AR activity, the expression-profile of previously validated androgen responsive genes (ARGs) was included. AR activity was shown by the AR-Score-21 (21 ARGs) and AR-Score-13 (13 ARGs) that were computed based on the expression of the selected ARGs. Those ARGs whose expression was significantly different between histological grades were used for computing two new AR-Scores. HCC patients with higher AR expression showed a higher median overall survival (OS). AR-Score 21 and AR-Score-13 did not show any association with prognosis. Six of the 21 ARGs of the AR-Score-21 and 7 of the 13 ARGs of the AR-Score-13 showed a significant different expression profile among histological grades. Based on these differences, another two AR-Scores were computed (AR-Score-6 and AR-Score-7). They showed the relative increase of upregulated to downregulated ARGs in high-grade HCC. Higher AR activity inferred by these AR-Scores was associated with worse outcomes. The expression of AR is associated with a better prognosis in HCC. However, the activity of the AR seems to be qualitatively different among histological grades. The AR activity inferred by the shifted ARGs is associated with a worse prognosis in HCC patients.


Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Proteínas de Neoplasias/biossíntese , Receptores Androgênicos/biossíntese , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
13.
Cell Signal ; 76: 109815, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33148514

RESUMO

The persistent infection with high-risk human papillomavirus (HPV) is an etiologic factor for the development of different types of cancers, mainly attributed to the continuous expression of E6 and E7 HPV oncoproteins, which regulate several cell signalling pathways including the Hippo pathway. It has been demonstrated that E6 proteins promote the increase of the Hippo elements YAP, TAZ and TEAD, at protein level, as well as their transcriptional targets. Also, E6 and E7 oncoproteins promote nuclear YAP localization and a decrease in YAP negative regulators such as MST1, PTPN14 or SOCS6. Interestingly, Hippo signalling components modulate HPV activity, such as TEAD1 and the transcriptional co-factor VGLL1, induce the activation of HPV early and late promoters, while hyperactivation of YAP in specific cells facilitates virus infection by increasing putative HPV receptors and by evading innate immunity. Additionally, alterations in Hippo signalling elements have been found in HPV-related cancers and particularly, the involvement of HPV oncoproteins on the regulation of some of these Hippo components has been also proposed, although the precise mechanisms remain unclear. The present review addresses the recent findings describing the interplay between HPV and Hippo signalling in HPV-related cancers, a fact that highlights the importance of developing more in-depth studies in this field to establish key therapeutic targets.


Assuntos
Alphapapillomavirus/metabolismo , Neoplasias/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Via de Sinalização Hippo , Humanos , Transdução de Sinais
14.
Heliyon ; 6(6): e04174, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32551395

RESUMO

In this work, multiwall carbon nanotubes (MWCNTs) developed from cobalt-ferrite catalyst on activated carbon (from castor seed), was used as an adsorbent for the removal of cadmium and hexavalent chromium ions. The effectiveness of the adsorbent for the uptake of Cd(II) and Cr(VI)ions from aqueous solution was investigated in a process batch adsorption study. The developed activated carbon and MWCNTs were characterized by Brunauer-Emmett-Teller (BET) surface area analysis, Fourier Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM) for the determination of surface area, functional group, and surface morphology, respectively. The BET surface area of activated carbon and developed adsorbent from Co-Fe/AC was 230.24 and 372.42 m2/g, respectively. The operational parameters evaluated on the adsorption efficiency were solution pH, temperature, adsorbent dosage initial metal ions concentration, and contact time. The adsorption of Cd(II) and Cr(VI) were found to have attained equilibrium positions in 60 min for the concentration range tested, respectively. The four linearized adsorption isotherm models; Langmuir, Freundlich, Temkin and Dubinin Radushkevich (D-R) tested, when compared, revealed that Langmuir isotherm fitted well to the experimental data judging from the higher correlation coefficient values (R2) and lower values of the error functions (chi-square (χ2), the sum of square error (ERRSQ/SSE) and the sum of absolute error (EABS))with monolayer adsorption capacities of 404.858 and 243.902 mg/g for Cd(II) and Cr(VI) ions, respectively. Adsorption kinetic models investigated by pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion showed the conformity of pseudo-second-order model to the process adsorption as informed by the higher values R2 and Adj, R2, maximum log-likelihood and smaller ERRSQ/SSE, χ2, Akaike information criterion (AIC), Bayesian information criterion (BIC), and Hannan-Quinn information criterion (HQIC). The intraparticle diffusion model plots indicated that intraparticle diffusion was not the only rate-limiting step. Thermodynamic adsorption parameters (ΔHo and ΔGo, ΔSo) showed that the adsorption of Cd (II) and Cr (VI) ions was spontaneous, endothermic, and increased in randomness between the adsorbate-adsorbent. The mean adsorption energy (E), the heat of adsorption (ΔHo), and activation energy (Ea) values, revealed the adsorption mechanism of Cd(II) and Cr(VI) onto MWCNTs as a combination of chemical and physical adsorption but dominated more by chemical adsorption.

15.
Int J Mol Sci ; 21(8)2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32326003

RESUMO

Cancer cells exhibit exacerbated metabolic activity to maintain their accelerated proliferation and microenvironmental adaptation in order to survive under nutrient-deficient conditions. Tumors display an increase in glycolysis, glutaminolysis and fatty acid biosynthesis, which provide their energy source. Glutamine is critical for fundamental cellular processes, where intermediate metabolites produced through glutaminolysis are necessary for the maintenance of mitochondrial metabolism. These include antioxidants to remove reactive oxygen species, and the generation of the nonessential amino acids, purines, pyrimidines and fatty acids required for cellular replication and the activation of cell signaling. Some cancer cells are highly dependent on glutamine consumption since its catabolism provides an anaplerotic pathway to feed the Krebs cycle. Intermediate members of the glutaminolysis pathway have been found to be deregulated in several types of cancers and have been proposed as therapeutic targets and prognostic biomarkers. This review summarizes the main players in the glutaminolysis pathway, how they have been found to be deregulated in cancer and their implications for cancer maintenance. Furthermore, non-coding RNAs are now recognized as new participants in the regulation of glutaminolysis; therefore, their involvement in glutamine metabolism in cancer is discussed in detail.


Assuntos
Regulação Neoplásica da Expressão Gênica , Glutamina/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , RNA não Traduzido/genética , Animais , Antineoplásicos/farmacologia , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , MicroRNAs/genética , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Interferência de RNA , RNA Circular/genética
16.
Int J Immunopathol Pharmacol ; 34: 2058738420907186, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32138573

RESUMO

The goals of our study were to determine the possible association of interleukin (IL)-31 with Th17 cytokine profile in serum and to quantify retinoic acid-related orphan receptor C (RORC) mRNA expression in psoriatic arthritis (PsA) patients. This cross-sectional study was conducted in 50 patients with PsA and 30 control subjects (CS) matched by age and gender. The cytokine serum levels were quantified by magnetic bead-based assay using the Bio-Plex MAGPIX system, and RORC mRNA expression was determined by quantitative polymerase chain reaction (qPCR). As a result, significant differences in IL-31 were observed between study groups (77.23 pg/mL in PsA vs 64.4 pg/mL in CS, P < 0.001) and Th17 cytokine profile serum levels (IL-17A: 6.36 pg/mL in PsA vs 2.97 pg/mL in CS, P = 0.02; IL-17F: 44.15 pg/mL in PsA vs 23.36 pg/mL in PsA, P = 0.01; IL-17E: 3.03 pg/mL in PsA vs 0.82 pg/mL in CS, P < 0.001; IL-21: 36.45 pg/mL in PsA vs 12.44 pg/mL in CS, P = 0.02); however, significant differences were not observed for IL-23 (31.2 pg/mL in PsA vs 53.26 pg/mL in CS, P = 0.58). Furthermore, positive correlations between IL-31 and Th17 cytokine profile serum levels were found (IL-17A: rs = 0.64, P < 0.001; IL-17F: rs = 0.73, P < 0.001; IL-17E: rs = 0.70, P < 0.001; IL-21: rs = 0.54, P = 0.002; IL-23: rs = 0.5, P < 0.01). Regarding RORC gene expression, the PsA group showed an increase of 6.85-fold compared to the CS group. We did not find any association between the serum levels of cytokines and RORC gene expression. In conclusion, in PsA, there are increased serum levels of IL-31, IL-17A, IL-17F, IL-17E, and IL-21, but not IL-23. Moreover, there was a positive correlation of IL-31 with the Th17 cytokine profile and a high RORC gene expression. Altogether, these findings suggest a proinflammatory contribution of IL-31 in close association with the Th17 cytokine profile in PsA.


Assuntos
Artrite Psoriásica/metabolismo , Artrite Psoriásica/patologia , Citocinas/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interleucinas/metabolismo , Células Th17/metabolismo , Adulto , Idoso , Estudos Transversais , Citocinas/sangue , Feminino , Humanos , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo
17.
AJNR Am J Neuroradiol ; 41(2): 364-368, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31831466

RESUMO

BACKGROUND AND PURPOSE: Differentiation between tuberculous and pyogenic spondylodiscitis is a diagnostic challenge because imaging often does not reliably distinguish the 2 entities and percutaneous biopsies are often culture-negative. The purpose of this study was to determine whether violation of the anterior meningovertebral ligament in the setting of anterior epidural abscess discriminates between these entities. MATERIALS AND METHODS: This was a retrospective cohort study of all patients with acid-fast bacillus testing and anterior epidural abscess diagnosed on spinal MR imaging between May 2014 and September 2019, with a final diagnosis of tuberculous or pyogenic spondylodiscitis. Six cases of tuberculous spondylodiscitis (mean age, 45.5 years; 80% male) and 35 cases of pyogenic spondylodiscitis were evaluated (mean age, 56.6 years; 49% male). Demographic characteristics were recorded. Cases were assessed for anterior meningovertebral ligament destruction on MR imaging, as demonstrated by the shape of the epidural collection. Segmental location of the infection was also assessed. Independent 2-sample t tests and χ2 tests of independence were performed to evaluate the significance of the difference between the groups. RESULTS: Five of 6 (83.3%) cases of tuberculous epidural abscess had an intact anterior meningovertebral ligament, and 0/35 cases of pyogenic epidural abscess demonstrated an intact ligament (P < .001). The presence of an intact anterior meningovertebral ligament had 83.3% sensitivity and 100% specificity for tuberculous spondylodiscitis, a 100% positive predictive value, and a 97.2% negative predictive value. CONCLUSIONS: The presence of an intact anterior meningovertebral ligament has high sensitivity and specificity for tuberculous spondylodiscitis-associated epidural abscess, though these results should be validated in a larger sample.


Assuntos
Discite/diagnóstico , Discite/microbiologia , Tuberculose/complicações , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Diagnóstico Diferencial , Discite/patologia , Abscesso Epidural/diagnóstico , Abscesso Epidural/microbiologia , Abscesso Epidural/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose/patologia , Adulto Jovem
18.
Heliyon ; 5(11): e02821, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31844736

RESUMO

The inhibiting effects of Chicken Nails Extract (CNE) on Mild Steel corrosion in 2M H2SO4 were investigated in this study. The effect of the concentration of inhibitor (0.5-1.5 g/l), time (5-8 h) and temperature (40-70oc) on Inhibition efficiency were investigated using Response Surface Methodology. The Physiochemical analysis and proximate analysis of the CNE were investigated; the result showed that organic constituents were present which made the Chicken nails extract a good inhibitor. The rate of corrosion increases as time and temperature increase while the Inhibition efficiency was discovered to increase as the inhibitor concentration increases. The optimum conditions obtained were temperature 63.63 °C, time 5 h and inhibitor concentration of 0.1 g/l. The optimum Inhibition Efficiency at these optimum conditions was predicted to be 74.04%. The micrographs result of Scanning Electron Micrographs analysis showed that in the presence of the inhibitor, there was a passive layer of a film formed on the surface. This study revealed that Chicken Nails Extract is a potentially good green inhibitor for Mild steel corrosion in 2M H2SO4.

19.
Front Oncol ; 9: 998, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612116

RESUMO

Solid tumors carry out the formation of new vessels providing blood supply for growth, tumor maintenance, and metastasis. Several processes take place during tumor vascularization. In angiogenesis, new vessels are derived from endothelial cells of pre-existing vessels; while in vasculogenesis, new vessels are formed de novo from endothelial progenitor cells, creating an abnormal, immature, and disorganized vascular network. Moreover, highly aggressive tumor cells form structures similar to vessels, providing a pathway for perfusion; this process is named vasculogenic mimicry (VM), where vessel-like channels mimic the function of vessels and transport plasma and blood cells. VM is developed by numerous types of aggressive tumors, including ovarian carcinoma which is the second most common cause of death among gynecological cancers. VM has been associated with poor patient outcome and survival in ovarian cancer, although the involved mechanisms are still under investigation. Several signaling molecules have an important role in VM in ovarian cancer, by regulating the expression of genes related to vascular, embryogenic, and hypoxic signaling pathways. In this review, we provide an overview of the current knowledge of the signaling molecules involved in the promotion and regulation of VM in ovarian cancer. The clinical implications and the potential benefit of identification and targeting of VM related molecules for ovarian cancer treatment are also discussed.

20.
Sci Rep ; 9(1): 13620, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541186

RESUMO

The Human Papillomavirus (HPV) E1 protein is the only viral protein with enzymatic activity. The main known function of this protein is the regulation of the viral DNA replication. Nevertheless, it has been demonstrated that the ablation of HPV18 E1 mRNA in HeLa cells promotes a deregulation of several genes, particularly those involved in host defense mechanisms against viral infections; however, the specific contribution of E1 protein in HPV-independent context has not been studied. The aim of this work was to determine the effect of the HPV E1 protein in the regulation of cellular gene expression profiles evaluated through RNA-seq. We found that E1 proteins from HPV16 and 18 induced an overexpression of different set of genes associated with proliferation and differentiation processes, as well as downregulation of immune response genes, including IFNß1 and IFNλ1 and Interferon-stimulated gene (ISG), which are important components involved in the antiviral immune response. Together, our results indicate that HR-(High-Risk) and LR-(Low-Risk) HPV E1 proteins play an important role in inhibiting the anti-viral immune response.


Assuntos
Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Replicação do DNA/genética , DNA Viral/genética , Expressão Gênica/genética , Regulação Viral da Expressão Gênica/genética , Células HeLa , Interações Hospedeiro-Patógeno , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/imunologia , Infecções por Papillomavirus/genética , Proteínas Virais/genética , Replicação Viral/genética
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