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1.
Gac Med Mex ; 156(5): 412-417, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33372936

RESUMO

INTRODUCTION: Older adults constitute the most vulnerable population group to the COVID-19 pandemic. In Mexico, their biopsychosocial conditions might intensify their vulnerability. METHOD: Affiliation to health systems, health conditions and gerontological evaluation of 3,218 older adults were analyzed following the methodology of the PAHO-Mexico Health, Well-being and Aging Survey. RESULTS: 88.6 % of older adults referred being affiliated to health systems; 30.2 %, 52.4 %, 10.3 %, 4.1 % and 5.6 % referred suffering from diabetes mellitus, high blood pressure, chronic obstructive pulmonary disease, heart disease and cerebrovascular disease, respectively; 15.6 % reported urinary incontinence, and 11.3%, fecal incontinence; 12.1 % of the women referred having suffered from breast cancer at some point, and 6.3 %, cervical cancer. The habit of smoking tobacco was observed in 11.1 %, risk of malnutrition in 32.8 %, established malnutrition in 4.1 %, functional dependence for basic and instrumental activities of daily life in 16.3 % and 17.6 %, respectively. CONCLUSION: Comprehensive gerontological evaluation is essential for efficient care of older adults who suffer from COVID-19, and for adequate care of the effects or health conditions at the conclusion of the confinement imposed by the pandemic.


INTRODUCCIÓN: Los adultos mayores constituyen el grupo más vulnerable ante la pandemia por COVID-19; en México, sus condiciones biopsicosociales podrían potenciar su vulnerabilidad. MÉTODO: Se analizó afiliación a sistemas de salud, condiciones de salud y evaluación gerontológica de 3218 adultos mayores conforme a la metodología de la Encuesta Salud, Bienestar y Envejecimiento OPS-México. RESULTADOS: 88.6 % de los adultos mayores refirió afiliación a un sistema de salud; 30.2, 52.4, 10.3, 4.1 y 5.6 % indicaron padecer diabetes mellitus, hipertensión arterial, enfermedad pulmonar obstructiva crónica, enfermedad cardiaca y evento vascular cerebral, respectivamente; 15.6 % reportó incontinencia urinaria y 11.3 %, fecal; 12.1 % de las mujeres indicó haber padecido en algún momento cáncer de mama y 6.3 %, cáncer cervicouterino. Se observó hábito de fumar tabaco en 11.1 %, riesgo de malnutrición en 32.8 %, malnutrición establecida en 4.1 %, dependencia funcional para las actividades básicas en 16.3 % e instrumentales de la vida diaria en 17.6 %. CONCLUSIÓN: La evaluación gerontológica integral es fundamental para la atención eficiente de los adultos mayores que padecen COVID-19 y para la adecuada atención por los efectos o condiciones de salud al terminar el confinamiento por la pandemia.


Assuntos
COVID-19 , Avaliação Geriátrica , Nível de Saúde , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade
2.
Cancer Cell Int ; 19: 214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427899

RESUMO

BACKGROUND: Gene expression profiles have demonstrated that miR-21 expression is altered in almost all types of cancers and it has been classified as an oncogenic microRNA. Persistent HPV infection is the main etiologic agent in cervical cancer and induces genetic instability, including disruption of microRNA gene expression. In the present study, we analyzed the underlying mechanism of how AP-1 transcription factor can active miR-21 gene expression in cervical cancer cells. METHODS: To identify that c-Fos and c-Jun regulate the expression of miR-21 we performed RT-qPCR and western blot assays. We analyzed the interaction of AP-1 with miR-21 promoter by EMSA and ChIP assays and determined the mechanism of its regulation by reporter construct plasmids. We identified the nuclear translocation of c-Fos and c-Jun by immunofluorescence microscopy assays. RESULTS: We demonstrated that c-Fos and c-Jun proteins are expressed and regulate the expression of miR-21 in cervical cancer cells. DNA sequence analysis revealed the presence of AP-1 DNA-binding sites in the human miR-21 promoter region. EMSA analyses confirmed the interactions of the miR-21 upstream transcription factor AP-1. ChIP assays further showed the binding of c-Fos to AP-1 sequences from the miR-21 core promoter in vivo. Functional analysis of AP-1 sequences of miR-21 in reporter plasmids demonstrated that these sequences increase the miR-21 promoter activation. CONCLUSIONS: Our findings suggest a physical interaction and functional cooperation between AP-1 transcription factor in the miR-21 promoter and may explain the effect of AP-1 on miR-21 gene expression in cervical cancer cells.

3.
BMC Cancer ; 16: 215, 2016 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-26975392

RESUMO

BACKGROUND: Expression of the microRNA miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA or oncomir. Due to the critical functions of its target proteins in various signaling pathways, miR-21 is an attractive target for genetic and pharmacological modulation in various cancers. Cervical cancer is the second most common cause of death from cancer in women worldwide and persistent HPV infection is the main etiologic agent. This malignancy merits special attention for the development of new treatment strategies. In the present study we analyze the role of miR-21 in cervical cancer cells. METHODS: To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression in a cervical intraepithelial neoplasia-derived cell lines using siRNAs. The effect of miR-21 on gene expression was assessed in cervical cancer cells transfected with the siRNA expression plasmid pSIMIR21. We identified the tumor suppressor gene PTEN as a target of miR-21 and determined the mechanism of its regulation throughout reporter construct plasmids. Using this model, we analyzed the expression of miR-21 and PTEN as well as functional effects such as autophagy and apoptosis induction. RESULTS: In SiHa cells, there was an inverse correlation between miR-21 expression and PTEN mRNA level as well as PTEN protein expression in cervical cancer cells. Transfection with the pSIMIR21 plasmid increased luciferase reporter activity in construct plasmids containing the PTEN-3'-UTR microRNA response elements MRE21-1 and MRE21-2. The role of miR-21 in cell proliferation was also analyzed in SiHa and HeLa cells transfected with the pSIMIR21 plasmid, and tumor cells exhibited markedly reduced cell proliferation along with autophagy and apoptosis induction. CONCLUSIONS: We conclude that miR-21 post-transcriptionally down-regulates the expression of PTEN to promote cell proliferation and cervical cancer cell survival. Therefore, it may be a potential therapeutic target in gene therapy for cervical cancer.


Assuntos
Proliferação de Células/genética , MicroRNAs/biossíntese , PTEN Fosfo-Hidrolase/biossíntese , Neoplasias do Colo do Útero/genética , Apoptose/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células HeLa , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , RNA Interferente Pequeno , Neoplasias do Colo do Útero/patologia
4.
Mediators Inflamm ; 2014: 510846, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24808638

RESUMO

OBJECTIVE: The goal of the present study was to investigate the effect of IL-12 expressed in plasmid on the Th1 cytokine profile in an experimental HPV16-positive murine tumor model and the association with the IL-12's antitumor effect. METHODS: Mice were injected with BMK-16/myc cells to establish HPV16-positive tumor and then pNGVL3-mIL-12 plasmid; pcDNA3 plasmid or PBS was injected directly into tumor site. The antitumor effect of the treatment was evaluated and the cytokines expression profile in each tumor tissue was analyzed. RESULTS: Treatment with pNGVL3-mIL-12 plasmid had a significant antitumor effect, and a Th2-Th3-type cytokines prolife was detected in the murine tumor model with expression of the cytokines IL-10, IL-4, and TGF-ß1. However, after the tumor was treated with three intratumoral injections of plasmid containing IL-12 cDNA, it showed a cytokine profile associated with Th1 with expression of IL-2, IL-12, and IFN-γ cytokines and reduced expression of IL-10, IL-4, and TGF-ß1. CONCLUSIONS: The treatment with the IL-12 gene in the experimental HPV16-positive tumor model promoted the activation of the cellular immune response via expression of a Th1-type cytokine profile and was associated with the inhibition of tumor growth. Thus, IL-12 treatment represents a novel approach for gene therapy against cervical cancer.


Assuntos
Citocinas/metabolismo , Papillomavirus Humano 16/patogenicidade , Interleucina-12/metabolismo , Células Th1/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Terapia Genética , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-12/genética , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
J Interferon Cytokine Res ; 44(6): 281-289, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38516906

RESUMO

Chronic low-grade inflammation (CLI) is implicated in the development of multiple metabolic diseases. The gut microbiota (GM) activates different signaling pathways and induces phenotypic changes, offering an exciting opportunity to treat CLI. We evaluated the mediation of waist circumference on the association of GM with serum cytokines. In this cross-sectional study of 331 children, we measured 5 gut bacterial species, namely, Lactobacillus (L.) casei, L. paracasei, L. reuteri, Staphylococcus (S.) aureus, and Akkermansia (A.) muciniphila, as well as anthropometry, serum cytokines, and other covariates. We evaluated adjusted regression models, path analysis, and structural equation modeling to obtain path coefficients (PCs) for direct, indirect (waist circumference-mediated), and total effects. We found that L. paracasei was directly associated with lower interleukin-10 (IL-10) levels (PC = -173.5 pg/mL). We also observed indirect associations between S. aureus with lower adiponectin levels (PC = -0.1 µg/mL and -0.09 µg/mL). Finally, A. muciniphila was indirectly associated with higher adiponectin levels (PC = 0.1 µg/mL). Our findings suggest the importance of considering the GM composition and waist circumference when evaluating inflammatory-related factors, providing a basis for future research to identify potential strategies to intervene in inflammatory processes and prevent metabolic diseases in childhood. [Figure: see text].


Assuntos
Microbioma Gastrointestinal , Inflamação , Circunferência da Cintura , Humanos , Masculino , Feminino , Criança , Estudos Transversais , Análise de Mediação , Citocinas/sangue , Citocinas/metabolismo , Adolescente
6.
In Vivo ; 37(6): 2517-2523, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905606

RESUMO

BACKGROUND/AIM: Resistant triple-negative breast cancer (TNBC) is a subtype of this disease that is resistant to conventional chemotherapy agents. IFN-τ is a cytokine that has recently been shown to have immunoregulatory and antitumor effects. The present study aimed to examine the antiproliferative and apoptosis effects of IFN-τ in breast cancer cells and the antitumor effect in a murine tumor model of TNBC. MATERIALS AND METHODS: Murine breast cancer 4T1 cells were cultured and treated with ovine IFN-τ and through MTT and Caspase-Glo 3/7 assays, viability and cell death were determined. In addition, the antitumor effect of IFN-τ was determined in a murine tumor model of TNBC. RESULTS: Ovine IFN-τ showed a concentration-dependent antiproliferative effect on 4T1 murine breast cancer cells. Also, treatment of 4T1 cells with IFN-τ induced the activation of caspase 3 and 7, which is indicative of apoptotic cell death. Moreover, we detected an increase in the expression of type I interferon receptor (IFNAR1/2) in cells treated with IFN-. The intratumoral application of IFN-τ in mice inhibited tumor growth compared to the control non-treated group, and the effect was associated with the increased expression of GM-CSF. CONCLUSION: Ovine IFN-τ may be an effective immunotherapeutic cytokine for the treatment of TNBC.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Ovinos , Camundongos , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Apoptose , Antineoplásicos/farmacologia , Citocinas , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células
7.
Children (Basel) ; 10(8)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37628382

RESUMO

BACKGROUND: Persistent gut microbiota (GM) imbalance has been associated with metabolic disease development. This study evaluated the mediating role of waist circumference in the association between GM and insulin resistance (IR) in children. METHODS: This cross-sectional study included 533 children aged between 6 and 12. The anthropometry, metabolic markers, and relative abundance (RA) of five intestinal bacterial species were measured. Path coefficients were estimated using path analysis to assess direct, indirect (mediated by waist circumference), and total effects on the association between GM and IR. RESULTS: The results indicated a positive association mediated by waist circumference between the medium and high RA of S. aureus with homeostatic model assessments for insulin resistance (HOMA-IR) and for insulin resistance adiponectin-corrected (HOMA-AD). We found a negative association mediated by waist circumference between the low and medium RA of A. muciniphila and HOMA-IR and HOMA-AD. Finally, when we evaluated the joint effect of S. aureus, L. casei, and A. muciniphila, we found a waist circumference-mediated negative association with HOMA-IR and HOMA-AD. CONCLUSIONS: Waist circumference is a crucial mediator in the association between S. aureus and A. muciniphila RA and changes in HOMA-IR and HOMA-AD scores in children.

8.
Children (Basel) ; 10(11)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38002890

RESUMO

BACKGROUND: Imbalance in the intestinal microbiota can lead to chronic low-grade inflammation. Diet may influence this association. In this study, we aimed to evaluate the interaction between Akkermansia muciniphila (A. muciniphila) and dietary patterns using a proinflammatory index. METHODS: We conducted a cross-sectional study with school-aged children. We quantified the relative abundance (RA) of A. muciniphila in feces using a polymerase chain reaction. We collected dietary information through employing a food frequency questionnaire and generated dietary patterns using principal component analysis. We generated a proinflammatory index from serum levels of interleukin-6, interleukin-10, tumor necrosis factor alpha, and adiponectin validated by receptor operating characteristic curves. We evaluated the association between A. muciniphila and the proinflammatory index using logistic regression, including an interaction term with dietary patterns. RESULTS: We found that children with a low RA of A. muciniphila and a high intake of simple carbohydrates and saturated fats had increased odds of being high on the proinflammatory index. However, when the consumption of this dietary pattern is low, children with a low RA of A. muciniphila had decreased odds of being high on the proinflammatory index. CONCLUSIONS: Our results suggest that the simultaneous presence of A. muciniphila and diet have a more significant impact on the presence of being high on the proinflammatory index compared to both factors separately.

9.
Metab Syndr Relat Disord ; 20(5): 303-311, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35325575

RESUMO

Background: The alteration in the composition of the gut microbiota has been associated with an increased risk of developing cardiovascular and metabolic diseases. The present study evaluated the association between the relative abundance (RA) of intestinal Staphylococcus aureus and the inflammatory response with cardiometabolic alterations in children. Methods: This cross-sectional study included 1142 children (age 6-12 years), which were classified by degree of adiposity. Anthropometry, cardiometabolic markers, and RA of intestinal S. aureus were measured. Cytokine concentrations were available in 626 children. Path coefficients (PC) were estimated by path analysis. Results: RA of S. aureus was positively associated with cholesterol PC = 24.98 (95% CI 10.76 to 39.21) and negatively with triglycerides PC = -13.10 (95% CI -22.73 to -3.48). Body mass index (BMI) Z-scores had significant mediation effects on the association between RA of S. aureus with waist circumference PC = 2.87 (95% CI 0.58 to 5.16), triglycerides PC = 6.63 (95% CI 1.29 to 11.98), low-density lipoproteins (LDL) PC = 1.73 (95% CI 0.27 to 3.18), and high-density lipoproteins PC = -1.20 (95% CI -2.19 to -0.22). Interleukin 6 (IL-6) was negatively associated with glucose PC = -3.01 (95% CI -5.85 to -0.17) and LDL PC = -8.65 (95% CI -16.54 to -0.77), and interleukin 10 (IL-10) was positively associated with glucose PC = 3.37 (95% CI 0.47 to 6.26). Conclusions: It is suggested that the RA of S. aureus, IL-6, and IL-10 are associated with cardiometabolic alterations in children, where BMI Z-scores have an important mediating effect for the development of these.


Assuntos
Doenças Cardiovasculares , Staphylococcus aureus , Adiposidade/fisiologia , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Criança , Estudos Transversais , Citocinas , Glucose , Humanos , Interleucina-10 , Interleucina-6 , Fatores de Risco , Triglicerídeos , Circunferência da Cintura
10.
Arch Med Res ; 53(4): 407-415, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35382951

RESUMO

AIM: To evaluate the taxonomic profile of the gut microbiota using metagenomics and the association with diet-dependent childhood obesity. METHODS: A cross-sectional study of a subsample of 46 children was conducted. The children were classified as normal-weight, overweight, and obese according to their age and sex and the World Health Organization (WHO) guidelines. Dietary patterns were determined through principal component analysis. The profile of the human gut microbiota was determined by bioinformatic analysis using whole metagenome shotgun sequencing. The association of gut microbiota and z-BMI, waist circumference and hip circumference, and the possible modifying effect of diet were analyzed using multiple regression models. RESULTS: Children with an abundance of Holdemania spp. and high protein and complex carbohydrate consumption had a lower z-BMI (ß -19.06, p = 0.011), waist circumference (ß -171.92, p = 0.003), and hip circumference (ß -157.57, p = 0.004). In contrast, observed a positive association between Coprococcus catus and the low intake of this dietary pattern with hip circumference (ß 147.87, p = 0.025). Furthermore, the presence of Bilophila spp. and Paraprevotella xylaniphila with high saturated fat and simple carbohydrate consumption we observed a positive association between z-BMI (ß 47.5, p = 0.002), hip circumference (ß 44.54, p = 0.025), and waist circumference (ß 44.34, p = 0.004). CONCLUSION: We suggest that the synergism between diet and the profile of children's gut microbiota can be a factor that could be associated with the development of obesity and its complications in childhood.


Assuntos
Microbioma Gastrointestinal , Obesidade Infantil , Índice de Massa Corporal , Carboidratos , Criança , Estudos Transversais , Dieta , Humanos , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia
11.
Front Immunol ; 12: 593161, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717073

RESUMO

HPV E5 is an oncoprotein mainly expressed in premalignant lesions, which makes it an important target for a vaccine to prevent or cure cervical cancer (CC). In this study, we evaluated whether E5 targeted to DEC-205, present in dendritic cells (DCs), could induce a therapeutic protection against HPV16-induced tumor cells in a mouse model. The HPV-16 E5 (16E5) protein was cross-linked to a monoclonal antibody (mAb) specific to mouse DEC-205 (anti-DEC-205:16E5) or to an isotype control mAb (isotype:16E5). Rotavirus VP6 was cross-linked to the mouse anti-DEC-205 mAb (anti-DEC-205:VP6) as a non-specific antigen control. BALB/c mice were inoculated subcutaneously (s.c.) with the 16E5-expressing BMK-16/myc tumor cells, and 7 and 14 days later the mice were immunized s.c. with the conjugates, free 16E5 or PBS in the presence of adjuvant. Tumor growth was monitored to evaluate protection. A strong protective immune response against the tumor cells was induced when the mice were inoculated with the anti-DEC-205:16E5 conjugate, since 70% of the mice controlled the tumor growth and survived, whereas the remaining 30% developed tumors and died by day 72. In contrast, 100% of the mice in the control groups died by day 30. The anti-DEC-205:16E5 conjugate was found to induce 16E5-specific memory T cells, with a Th1/Th17 profile. Both CD4+ and CD8+ T cells contributed to the observed protection. Finally, treating mice that had developed tumors with an anti-PD-1 mAb, delayed the tumor growth for more than 20 days. These results show that targeting 16E5 to DEC-205, alone or combined with an immune checkpoint blockade, could be a promising protocol for the treatment of the early stages of HPV-associated cancer.


Assuntos
Células Dendríticas/imunologia , Papillomavirus Humano 16/imunologia , Neoplasias/etiologia , Neoplasias/terapia , Proteínas Oncogênicas Virais/imunologia , Infecções por Papillomavirus/complicações , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Biomarcadores Tumorais , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunização , Memória Imunológica , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Neoplasias/diagnóstico , Infecções por Papillomavirus/virologia , Linfócitos T/imunologia , Linfócitos T/metabolismo
12.
Biomarkers ; 15(5): 470-4, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20507260

RESUMO

The AKNA gene is part of the 9q32 susceptibility locus for cervical cancer. A single-nucleotide polymorphism at codon 1119 of AKNA, yields a biologically relevant amino acid change (R1119Q) at the DNA binding AT-hook motif. Genotype frequencies in 97 allele pairs were: R/R = 0.597, R/Q = 0.278, Q/Q = 0.123. Q/Q homozygosity was present in 8.33% of healthy controls, 16.67% of patients with cervical intraepithelial neoplasia and 75% of cervical cancer patients. These differences are highly significant for the presence of Q/Q in cervical cancer (p = 0.01, odds ratio 3.66, 95% confidence interval 1.35-9.94). Therefore, AKNA appears to be an important genetic factor associated with the risk cervical cancer.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Motivos AT-Hook/genética , Adulto , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Adulto Jovem
13.
Rev Invest Clin ; 62(1): 63-80, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20415061

RESUMO

RNAi (RNA interference) is a natural process by which eukaryotic cells silence gene expression through small interference RNAs (siRNA) which are complementary to messenger RNA (mRNA). In this process, the siRNA that are 21-25 nucleotides long and are known as microRNA (miRNA), either associate with the RNA-induced silencing complex (RISC), which targets and cleaves the complementary mRNAs by the endonucleolytic pathway, or repress the translation. It is also possible to silence exogenous gene expression during viral infections by using DNA templates to transcribe siRNA with properties that are identical to those of bioactive microRNA. Persistent human papillomavirus (HPV) infection is the main etiological agent during cervical cancer development and the HPV E6 and E7 oncogenes, which induce cellular transformation and immortalization, represent strategic targets to be silenced with siRNA. In several in vitro and in vivo studies, it has been demonstrated that the introduction of siRNA directed against the E6 and E7 oncogenes in human tumoral cervical cells transformed by HPV, leads to the efficient silencing of HPV E6 and E7 oncogene expression, which induces the accumulation of the products of the p53 and pRb tumor suppressor genes and activates the mechanism of programmed cell death by apoptosis; thus, the progression of the tumoral growth process may be prevented. The goal of this review is to analyze the microRNA biogenesis process in the silencing of gene expression and to discuss the different protocols for the use of siRNA as a potential gene therapy strategy for the treatment of cervical cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Terapia Genética/métodos , MicroRNAs/genética , Interferência de RNA , RNA Mensageiro/genética , RNA Neoplásico/genética , Neoplasias do Colo do Útero/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Transformação Celular Viral , Terapia Combinada , Desenho de Fármacos , Feminino , Gammapapillomavirus/genética , Gammapapillomavirus/patogenicidade , Gammapapillomavirus/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/genética , Humanos , MicroRNAs/biossíntese , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/fisiologia , Oncogenes , Infecções por Papillomavirus/genética , Biossíntese de Proteínas , RNA Mensageiro/antagonistas & inibidores , RNA Neoplásico/antagonistas & inibidores , RNA Neoplásico/biossíntese , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Telomerase/antagonistas & inibidores , Telomerase/genética , Transcrição Gênica , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia
14.
Obes Res Clin Pract ; 14(3): 271-278, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32518007

RESUMO

This study examined the association between intestinal lactobacilli and obesity dependent on dietary patterns in children. A cross-sectional study was conducted including 1111 children, 6-12 years old. Obesity was determined according to the WHO cut-off points. Diet information from a Food Frequency Questionnaire identified three dietary patterns. Lactobacillus sp. were determined by a real-time polymerase chain reaction (PCR). The consumption of complex carbohydrates and a high abundance of L. paracasei were associated with a lower risk of obesity (0.35, Confidence Interval 95% 0.19-0.65). The same happened with a medium consumption of fats and a medium abundance of L. paracasei (0.43, CI95% 0.24-0.78). In contrast, an increased risk of obesity is observed with a medium and high consumption of simple carbohydrates (2.37, CI95% 1.29-4.34 and 2.52, CI95% 1.36-4.66, respectively, p-trend<0.05), and low consumption of complex carbohydrates (2.49, CI95% 1.35-4.58), in the presence of a high relative abundance of L. reuteri. A high relative abundance of L. paracasei decreased the risk of obesity, even when high-fat and simple carbohydrate diets were consumed; while a high relative abundance of L. reuteri was associated with a greater possibility of obesity with these types of diets. Our results provide evidence of diet implication in metabolism regulators like lactobacilli. This is helpful in strategies development to promote healthy diets during early stages of life.


Assuntos
Dieta/efeitos adversos , Carboidratos da Dieta/análise , Lacticaseibacillus paracasei , Lactobacillus/metabolismo , Obesidade Infantil/microbiologia , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Estudos Transversais , Dieta/métodos , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Obesidade Infantil/epidemiologia , Fatores de Proteção
15.
J Cancer ; 11(16): 4754-4761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626522

RESUMO

The mechanisms of signal transduction by interferon-tau (IFN-τ) are widely known during the gestation of ruminants. In trophoblast cells, IFN-τ involves the activation of the JAK-STAT pathway, and it can have effects on other cell types, such as tumor cells. Here we report that the HPV16-positive BMK-16/myc cell treated with ovine IFN-τ, results in the activation of the canonical JAK-STAT and non-canonical JAK-STAT pathway. The MAPK signaling pathway was activated, we detected the proteins MEK1, MEK2, Raf1, STAT3, STA4, STAT5 and STAT6. Moreover, IFN-τ induced the expression of MHC Class I, MX and IP10 in the tumor cells and this response may be associated with the viral replication and with the anti-proliferative and the immunoregulatory effects of IFN-τ.

16.
J Clin Immunol ; 29(4): 532-44, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19259799

RESUMO

INTRODUCTION: Cervical cancer development from a squamous intraepithelial lesion is thought to be favored by an impaired T cell immunity. We evaluated parameters of T cell alterations such as proliferation, cytokine, and CD3zeta expression in peripheral blood and tumor-infiltrating T lymphocytes from women with squamous intraepithelial lesions (SIL) or cervical cancer (CC). RESULTS AND DISCUSSION: T cell proliferation and cytokine messenger RNA (mRNA) expression were similar in women with SIL and healthy donors, whereas low T cell proliferation and lower mRNA expression of IL-2, IL-10 and IFN-gamma were observed in women with CC. Moreover, infiltrating cells showed marginal responses. We also found that CD3zeta mRNA expression, whose protein is required for T cell activation, correlated with a decreased proliferation in advanced stages of the disease. CONCLUSION: Experiments with T cells from healthy donors in the presence TGF-beta1 or IL-10 suggest that these cytokines have a relevant role in T cell responses during CC progression.


Assuntos
Complexo CD3/biossíntese , Interleucina-10/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T/imunologia , Fator de Crescimento Transformador beta1/imunologia , Displasia do Colo do Útero/imunologia , Neoplasias do Colo do Útero/imunologia , Adulto , Idoso , Complexo CD3/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Feminino , Células HeLa , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-10/farmacologia , Interleucina-2/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologia , Linfócitos T/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia
17.
Salud Publica Mex ; 51 Suppl 3: S379-85, 2009.
Artigo em Espanhol | MEDLINE | ID: mdl-20464211

RESUMO

Genomics, as a scientific discipline responsible for genome maps, sequencing and functional analysis of genomes, allows for continually expanding knowledge of the structure and function of genomes. The influence of genomics on medicine generates a new perspective for how we perceive health and disease, knowing the influence of genetic variations on susceptibility to disease. In the area of public health, genetic epidemiology translates genetic knowledge into individual and public actions, evaluating the effect of the distribution of genetic determinants and their interaction with environmental factors involved in the etiology of human diseases. In addition, genomic medicine suggests new diagnostic systems, genetic associations and nutritional disorders, specific responses to diverse drugs, and the design of new drugs for susceptible groups. And yet, the greatest advances in genomic medicine in the field of health are forthcoming.


Assuntos
Genômica , Saúde Pública , Diagnóstico , Epidemiologia , Terapia Genética , Genoma Humano , Humanos , Vacinas
18.
Carbohydr Polym ; 215: 160-169, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981341

RESUMO

Inulin has interesting physicochemical and functional properties, and therefore a wide range of applications in the food and medical industries. It has gained great traction due to its ability to form nanoparticles and its possible application as nanovehicle for drug delivery. In this work, we demonstrated that the enzymatically-synthesized high molecular weight (HMW) inulin forms stable spherical nanoparticles with an average diameter of 112 ± 5 nm. The self-assemblage of HMW inulin nanoparticles is carried out during enzymatic synthesis of the polymer, and become detectable after a certain critical aggregation concentration (CAC) is reached. Both, the CAC and nanoparticle size are influenced by the reaction temperature. These nanoparticles are not toxic for peripheral blood mononuclear cells, at concentrations below 200 µg/mL; no significant prebiotic potential was detected in cultures of 13 probiotic strains. This work contributes to a better understanding of the formation of HMW inulin nanoparticles and their biological properties.


Assuntos
Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Hexosiltransferases/química , Inulina/síntese química , Inulina/toxicidade , Leuconostoc/enzimologia , Nanopartículas/química , Nanopartículas/toxicidade , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Inulina/química , Leucócitos Mononucleares/efeitos dos fármacos , Peso Molecular , Prebióticos , Probióticos
19.
Cancer Invest ; 26(10): 1037-43, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18798072

RESUMO

The present study was performed to determine IL-10 expression in cervical tissues in Mexican women according to the severity of the malignity and its association with HPV infection. IL-10 expression showed a clear tendency to increase during the different cervical cancer stages: 37% in LGSIL; 62% in HGSIL; and 84% in cancer. However, all the patients that expressed IL-10 were HPV positives; we found an association with HPV 16. These results suggest a clear relationship between IL-10, HPV and the stage of cervical cancer disease; this event could contribute to the immunosuppressive micro-environment in the tumor site.


Assuntos
Regulação Neoplásica da Expressão Gênica , Interleucina-10/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Primers do DNA , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Feminino , Humanos , México , Estadiamento de Neoplasias , Infecções por Papillomavirus/epidemiologia , Prevalência , RNA Mensageiro/genética , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/imunologia
20.
Nanomaterials (Basel) ; 7(8)2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28763050

RESUMO

This study underscores the development of Ag hydrogel nanocomposites, as smart substrates for antibacterial uses, via innovative in situ reactive and reduction pathways. To this end, two different synthetic strategies were used. Firstly thiol-acrylate (PSA) based hydrogels were attained via thiol-ene and radical polymerization of polyethylene glycol (PEG) and polycaprolactone (PCL). As a second approach, polyurethane (PU) based hydrogels were achieved by condensation polymerization from diisocyanates and PCL and PEG diols. In fact, these syntheses rendered active three-dimensional (3D) hydrogel matrices which were used as nanoreactors for in situ reduction of AgNO3 to silver nanoparticles. A redox chemistry of stannous catalyst in PU hydrogel yielded spherical AgNPs formation, even at 4 °C in the absence of external reductant; and an appropriate thiol-functionalized polymeric network promoted spherical AgNPs well dispersed through PSA hydrogel network, after heating up the swollen hydrogel at 103 °C in the presence of citrate-reductant. Optical and swelling behaviors of both series of hydrogel nanocomposites were investigated as key factors involved in their antimicrobial efficacy over time. Lastly, in vitro antibacterial activity of Ag loaded hydrogels exposed to Pseudomona aeruginosa and Escherichia coli strains indicated a noticeable sustained inhibitory effect, especially for Ag-PU hydrogel nanocomposites with bacterial inhibition growth capabilities up to 120 h cultivation.

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