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1.
Mol Biol Rep ; 51(1): 148, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236307

RESUMO

BACKGROUND: ESR1 is expressed by 60-70% of breast tumours. it's a good prognosis factor and the target of hormone therapy. Optimization of ESR1 reactivation therapy is currently ongoing. Here we probe if the transcription factor CTCF plays a role in the differential expression of ESR1 in the breast cancer cell lines MCF-7 (ESR1+) and MDA-MB-231 (ESR1-). METHODS AND RESULTS: Knockdown of CTCF in MCF-7 resulted in decreased ESR1 gene expression. CTCF binds to the promoter of ESR1 in MCF-7 but not in MDA-MB-231 cells. CTCF ESR1 binding sites are unmethylated in MCF7 but methylated in MDA-MB-231 cells. CONCLUSION: ESR1 expression in MCF7 cells is dependent on CTCF expression. CTCF can bind to specific regions of the promotor of ESR1 gene in MCF-7 cells but not in MDA-MB-231 cells, this correlates with the methylation status of these regions and could be involved in the transcriptional regulation of ESR1.


Assuntos
Neoplasias da Mama , Fator de Ligação a CCCTC , Metilação de DNA , Receptor alfa de Estrogênio , Humanos , DNA , Metilação de DNA/genética , Células MCF-7 , Células MDA-MB-231 , Neoplasias da Mama/genética , Regiões Promotoras Genéticas , Fator de Ligação a CCCTC/genética , Receptor alfa de Estrogênio/genética
2.
Eur J Nutr ; 62(3): 1479-1492, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36651990

RESUMO

PURPOSE: The high-meat, low-fibre Western diet is strongly associated with colorectal cancer risk. Mycoprotein, produced from Fusarium venanatum, has been sold as a high-fibre alternative to meat for decades. Hitherto, the effects of mycoprotein in the human bowel have not been well considered. Here, we explored the effects of replacing a high red and processed meat intake with mycoprotein on markers of intestinal genotoxicity and gut health. METHODS: Mycomeat (clinicaltrials.gov NCT03944421) was an investigator-blind, randomised, crossover dietary intervention trial. Twenty healthy male adults were randomised to consume 240 g day-1 red and processed meat for 2 weeks, with crossover to 2 weeks 240 g day-1 mycoprotein, separated by a 4-week washout period. Primary end points were faecal genotoxicity and genotoxins, while secondary end points comprised changes in gut microbiome composition and activity. RESULTS: The meat diet increased faecal genotoxicity and nitroso compound excretion, whereas the weight-matched consumption of mycoprotein decreased faecal genotoxicity and nitroso compounds. In addition, meat intake increased the abundance of Oscillobacter and Alistipes, whereas mycoprotein consumption increased Lactobacilli, Roseburia and Akkermansia, as well as the excretion of short chain fatty acids. CONCLUSION: Replacing red and processed meat with the Fusarium-based meat alternative, mycoprotein, significantly reduces faecal genotoxicity and genotoxin excretion and increases the abundance of microbial genera with putative health benefits in the gut. This work demonstrates that mycoprotein may be a beneficial alternative to meat within the context of gut health and colorectal cancer prevention.


Assuntos
Neoplasias Colorretais , Carne , Adulto , Masculino , Humanos , Carne/efeitos adversos , Dieta , Ácidos Graxos Voláteis , Dano ao DNA , Compostos Nitrosos
3.
Eur J Nutr ; 62(8): 3349-3359, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37624376

RESUMO

PURPOSE: Mycoprotein is a relatively novel food source produced from the biomass of Fusarium venenatum. It has previously been shown to improve CVD risk markers in intervention trials when it is compared against total meat. It has not hitherto been assessed specifically for benefits relative to red and processed meat. METHODS: We leveraged samples from Mycomeat, an investigator-blind randomised crossover controlled trial in metabolically healthy male adults (n = 20), randomised to consume 240 g/day of red and processed meat for 14 days followed by mycoprotein, or vice versa. Blood biochemical indices were a priori defined secondary endpoints. RESULTS: Mycoprotein consumption led to a 6.74% reduction in total cholesterol (P = 0.02) and 12.3% reduction in LDL cholesterol (P = 0.02) from baseline values. Change in fasted triglycerides was not significantly different between diets (+ 0.19 ± 0.11 mmol/l with mycoprotein, P = 0.09). There was a small but significant reduction in waist circumference for mycoprotein relative to meat (- 0.95 ± 0.42 cm, P = 0.04). Following the mycoprotein diet, mean systolic (- 2.41 ± 1.89 mmHg, P = 0.23) and diastolic blood pressure (- 0.80 ± 1.23 mmHg, P = 0.43) were reduced from baseline. There were no statistically significant effects of the intervention on urinary sodium, nitrite or TMAO; while urinary potassium (+ 126.12 ± 50.30 mmol/l, P = 0.02) and nitrate (+ 2.12 ± 0.90 mmol/l, P = 0.04) were both significantly higher with mycoprotein relative to meat. The study population comprised metabolically healthy adults, therefore, changes in plasma lipids had little effect on cardiovascular risk scores (- 0.34% FRS for mycoprotein P = 0.24). CONCLUSIONS: These results confirm potential cardiovascular benefits when displacing red and processed meat with mycoprotein in the diet. Longer trials in higher risk study populations are needed to fully elucidate suggested benefits for blood pressure and body composition. CLINICALTRIALS: gov Identifier: NCT03944421.


Assuntos
Doenças Cardiovasculares , Carne Vermelha , Adulto , Humanos , Masculino , Biomarcadores , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol , Fatores de Risco de Doenças Cardíacas , Carne , Fatores de Risco , Estudos Cross-Over
4.
Nutr Health ; : 2601060231187516, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37461824

RESUMO

Purpose: No dietary interventional studies have reported the impact of olive oil on cardiovascular risk markers in groups of different ethnic origins. We report a pilot randomised controlled trial of an intervention supplementing extra virgin olive oil (EVOO) on markers of cardiovascular risk among East Asian Chinese, and European Caucasian individuals. Methods: A cross-over, randomised controlled dietary intervention for 2 weeks was undertaken. Thirty-two adults, healthy, individuals of Chinese and European origin took part in this study. 24-h ambulatory systolic and diastolic blood pressure (SBP, DBP), and blood lipids, were assessed. Results: Positive benefits of EVOO consumption were observed in all participants. Lower 24-h ambulatory SBP (-4.3 mmHg; p = 0.020), and day-time SBP (5.528 mmHg; p = 0.008), night-time DBP (-3.784 mmHg; p = 0.008) and night-time MAP (-3.747 mmHg; p = 0.007) were seen in all participants independently of covariates. In addition, total cholesterol (7.9 mg/dL; p = 0.017) and LDL-cholesterol (6.5 mg/dL; p = 0.028) were increased with butter but not with olive oil. No significant difference in other cardiovascular risk factors were observed. However, differences were observed between Caucasians and East Asian individuals in the absence of significant differences in lifestyle. Conclusion: This pilot study suggests that consumption of EVOO should be advocated as a healthier dietary fat and recommended to replace butter as a dietary strategy to improve cardiovascular health in both Caucasians and East Asian individuals.

5.
BMC Med ; 20(1): 79, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35655214

RESUMO

BACKGROUND: The associations of cancer with types of diets, including vegetarian, fish, and poultry-containing diets, remain unclear. The aim of this study was, therefore, to investigate the association of type of diet with all cancers and 19 site-specific incident cancers in a prospective cohort study and then in a meta-analysis of published prospective cohort studies. METHODS: A total of 409,110 participants from the UK Biobank study, recruited between 2006 and 2010, were included. The outcomes were incidence of all cancers combined and 19 cancer sites. Associations between the types of diets and cancer were investigated using Cox proportional hazards models. Previously published prospective cohort studies were identified from four databases, and a meta-analysis was conducted using random-effects models. RESULTS: The mean follow-up period was 10.6 years (IQR 10.0; 11.3). Compared with meat-eaters, vegetarians (hazard ratio (HR) 0.87 [95% CI: 0.79 to 0.96]) and pescatarians (HR 0.93 [95% CI: 0.87 to 1.00]) had lower overall cancer risk. Vegetarians also had a lower risk of colorectal and prostate cancers compared with meat-eaters. In the meta-analysis, vegetarians (Risk Ratio (RR): 0.90 [0.86 to 0.94]) and pescatarians (RR 0.91 [0.86; 0.96]) had lower risk of overall and colorectal cancer. No associations between the types of diets and prostate, breast, or lung cancers were found. CONCLUSIONS: Compared with meat-eaters, vegetarians and pescatarians had a lower risk of overall, colorectal, and prostate cancer. When results were pooled in a meta-analysis, the associations with overall and colorectal cancer persisted, but the results relating to other specific cancer sites were inconclusive.


Assuntos
Neoplasias Colorretais , Neoplasias da Próstata , Animais , Bancos de Espécimes Biológicos , Dieta/efeitos adversos , Peixes , Humanos , Masculino , Carne/efeitos adversos , Aves Domésticas , Estudos Prospectivos , Reino Unido/epidemiologia , Vegetarianos
6.
Microsurgery ; 42(4): 305-311, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34812535

RESUMO

INTRODUCTION: Physiologic microsurgical procedures to treat lymphedema include vascularized lymph node transfer (VLNT) and lymphovenous bypass (LVB). The purpose of this study was to assess 30-day outcomes of VLNT and LVB using the National Surgical Quality Improvement Program (NSQIP) database. METHODS: NSQIP was queried (2012-2018) for lymphatic procedures for upper extremity lymphedema after mastectomy. Prophylactic lymphatic procedures and those for lower extremity lymphedema were excluded. Outcomes were assessed for three groups: LVB, VLNT, and patients who had procedures simultaneously (VLNA+LVB). Primary outcomes measured were operative time, 30-day morbidities, and hospital length of stay. RESULTS: The study included 199 patients who had LVB (n = 43), VLNT (n = 145), or VLNT+LVB (n = 11). There was no difference in co-morbidities between the groups (p = 0.26). 30-day complication rates including unplanned reoperation (6.9% VLNT vs. 2.3% LVB) and readmission (0.69% VLNT vs. none in LVB) were not statistically significant (p = 0.54). Surgical site infection, wound complications, deep vein thromboembolism, and cardiac arrest was also similar among the three groups. Postoperative length of stay for VLNT (2.5 days± 2.3), LVB (1.9 days± 1.9), and VLNT+LVB (2.8 days± 0.3) did not differ significantly (p = 0.20). Operative time for LVB (305.4 min ± 186.7), VLNT (254 min ± 164.4), and VLNT+LVB (295.3 min ± 43.2) was not significantly different (p = 0.21). CONCLUSIONS: Our analysis of the NSQIP data revealed that VLNT and LVB are procedures with no significant difference in perioperative morbidity. Our results support that choice of VLNT versus LVB can be justifiably made per the surgeon's preference and experience as the operations have similar complication rates.


Assuntos
Neoplasias da Mama , Linfedema , Neoplasias da Mama/cirurgia , Feminino , Humanos , Linfonodos/irrigação sanguínea , Linfedema/etiologia , Mastectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Melhoria de Qualidade , Estados Unidos , Extremidade Superior/cirurgia
7.
J Surg Res ; 258: 8-16, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32971339

RESUMO

BACKGROUND: Resident burnout is associated with increased adverse patient events and increased incidence of resident depression and suicide when compared to the general population. We hypothesized that resident-driven assessment and implementation of wellness measures would allow implementation of desired interventions and facilitate improvement in wellness. METHODS: A wellness intervention team was established to address resident wellness and job satisfaction. A needs assessment to determine desired interventions as well as a three-part anonymous 5-point Likert scale survey was developed and distributed to general surgery residents. Following implementation of three measures, a postintervention survey was administered at 6 and 15 mo to the same cohort. Analysis of variance test was used to evaluate for significant difference between preintervention and postintervention surveys. RESULTS: Three interventions were implemented: two protected weekday personal days per year, modernization of resident workspace, and additional meal funds. There were statistically significant changes in perceptions of wellness opportunities (3.14 versus 3.88 and 3.7; P < 0.05), time for wellness (2.53 versus 3.42 and 3.2; P < 0.05), work/life balance satisfaction (2.86 versus 3.71 and 3.41; P < 0.05), and improved quality of life (2.67 versus 3.3 and 3.0; P < 0.05) in both 6-mo and 15-mo postintervention responses. CONCLUSIONS: Implementation of resident-selected wellness measures was found to influence overall resident satisfaction and improved perception of the working environment. Several scores of wellness items showed sustained improvement at 15 mo. These results suggest that resident-driven wellness interventions can positively affect working conditions for residents.


Assuntos
Esgotamento Profissional/prevenção & controle , Promoção da Saúde , Internato e Residência , Médicos/psicologia , Local de Trabalho/psicologia , Cirurgia Geral/educação , Humanos , Percepção
8.
Eur J Nutr ; 60(2): 615-639, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32535781

RESUMO

PURPOSE: This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors. METHODS: PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020. Forty-five chronic (≥ 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included. RESULTS: Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10). Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI - 6.79 to - 0.58; P = 0.02) and DBP by 1.52 mmHg (95% CI - 2.87 to - 0.18, P = 0.04). In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI - 2.97 to - 0.07; P = 0.05], DBP by 1.78 mmHg [95% CI - 3.43 to - 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI - 4.06 to - 2.15; P = 0.02]). Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02). CONCLUSION: These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure. No other significant improvements were observed for other specified fruits. More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.


Assuntos
Mirtilos Azuis (Planta) , Doenças Cardiovasculares , Citrus , Frutas , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Dieta , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Ann Plast Surg ; 86(6S Suppl 5): S517-S520, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33833159

RESUMO

INTRODUCTION: The incidence of high-pressure injection injuries of the hand is low. Although the occurrence is rare, the precarious progression of the injury exacts prompt surgical evaluation in order to avoid complications and amputation. The current study was devised in order to make comparisons to the current data, in addition to supplementing the literature with observations regarding clinical course and management. METHODS: A multisurgeon, retrospective chart review from a single institution was performed. Inclusion criteria included cases involving a high-pressure injection injury to the hand that underwent surgical management. Patient demographics, injury details, and hospital course were all reviewed and recorded. RESULTS: This retrospective review identified 20 cases meeting criteria, all of which involved males. The average age at time of injury was 39.7 years (range, 21-71 years). The incidence of injection injuries over a 10-year time period was 2.1 cases per year. The nondominant hand was injured in 11 cases (63%). The most common site of injury was the index finger with 11 recorded incidents (55%). Other reported locations included the metacarpal (40%) and small finger (5%). Occupational data included 10 construction workers, 5 painters, and 2 cleaning crew members, and 3 had nonmanual occupations. Paint was the most commonly injected substance with 17 reported cases (85%). On average, the delay until surgery was observed to be 21.9 hours (n = 16). Only 1 patient underwent surgery at 6 hours after surgery. The average number of procedures performed was 1.8 (range, 1-4). Hospitalization duration was on average 3.9 days (range, 1-9 days), and the average follow-up length was 69 days (range, 7-112 days). There were no identified cases that necessitated amputation. CONCLUSIONS: This form of injury most commonly affects male, middle-aged laborers. Our study found very low amputation rates when compared with the current literature, despite observing longer delays to surgery according to current recommendations. Limited comparisons can be made from data regarding clinical course and management because of the small sample size of the current study and the limited published data. This indicates a need for further exploration and collection of data involving parameters such as clinical course and management.


Assuntos
Traumatismos da Mão , Mãos , Amputação Cirúrgica , Traumatismos da Mão/epidemiologia , Traumatismos da Mão/etiologia , Traumatismos da Mão/cirurgia , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Ann Plast Surg ; 86(6S Suppl 5): S603-S605, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34100820

RESUMO

INTRODUCTION: The National Resident Matching Program and Electronic Residency Application Service provide data for tracking trends among applicants in each specialty over the past 5 years. The purpose of this study was to examine this information and determine sex and race/ethnicity distribution over the past 5 years. METHODS: The National Resident Matching Program and Electronic Residency Application Service databases were surveyed for trends in the following categories: number of positions, number of applicants, percent of applicants per position, and number of applicants by sex and self-identified race/ethnicity. This information was analyzed graphically for visual representation of the changes in the field. RESULTS: While there has been a steady increase in number of positions offered, there has also been a significant decrease in number of applicants, resulting in an increase in number of positions offered per applicant. While female and Asian applicants have increased in number, rates of applications from other diverse groups have remained stagnant. CONCLUSIONS: The number of plastic surgery positions offered has increased, whereas the number of applicants has decreased, resulting in a reduction in the number of applicants per position. Lack of racial diversity remains a significant issue in the applicant pool.


Assuntos
Internato e Residência , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Eletrônica , Feminino , Humanos , Inquéritos e Questionários , Estados Unidos
11.
J Hand Surg Am ; 46(1): 54-59, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32948347

RESUMO

Raynaud phenomenon (RP) is a condition causing vasospasm in the fingers and toes of patients that can have a significant negative impact on quality of life. This can lead to pain, ulceration, and possible loss of digits. Several pharmacological options are available for treatment. However, RP can often be refractory to traditional modalities, leaving surgery or injections as the next available options. This article provides a review and update on the use of botulinum toxin as an effective therapy for the treatment of RP refractory to medical management.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Doença de Raynaud , Toxinas Botulínicas Tipo A/uso terapêutico , Dedos , Humanos , Fármacos Neuromusculares/uso terapêutico , Qualidade de Vida , Doença de Raynaud/tratamento farmacológico
12.
Medicina (Kaunas) ; 57(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34946297

RESUMO

Background and Objectives: Healthcare workers (HCWs) play important roles in mitigating the COVID-19 pandemic and are more likely to become infected with COVID-19. Mexico, among other countries, had a high incidence and prevalence of cases and deaths from this disease. Material and Methods: This retrospective study evaluated the clinical characteristics as well as the geographical distribution of cases, deaths, and active cases of COVID-19 in HCWs and non-HCWs using official information from the Ministry of Health of Mexico. Results: A total of 235,343 cases of COVID-19 were reported in healthcare workers, and 2,094,191 cases were reported in non-healthcare workers. A total of 76.0% of cases in healthcare workers occurred in those who were between 25 and 50 years of age, and 71.4% of deaths occurred in those who were 50 to 69 years of age. Among healthcare workers, the most frequent comorbidities were obesity (15.2%), hypertension (10.9%), and diabetes (6.8%). Nurses were the group with the most cases (39.7%), followed by other healthcare workers (30.6%), physicians (26%), and dentists (1.6%). Physicians were the group with the most deaths (46%), followed by other professionals (30%), nurses (19%), and dentists (3%). Conclusion: These findings are likely the result of healthcare workers in Mexico being at a greater risk of exposure to SARS-CoV-2.


Assuntos
COVID-19 , Pandemias , Idoso , Pessoal de Saúde , Humanos , México/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
13.
Cell Immunol ; 355: 104146, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32702524

RESUMO

The lipopolysaccharide (LPS) of Gram-negative bacteria is recognized on human monocytes and macrophages by TLR4 and MD2 and induces the production of inflammatory cytokines; the LPS + IgG complexes co-stimulation increases the cytokine production, mediated by the Fc-γRIIa (CD32a). We stimulated human CD14 + monocytes or THP-1 cells with LPS or LPS + soluble human IgG (sIgG) and TNF-α transcription and production, assessed RT-qPCR, ELISA, or flow cytometry, was enhanced by 30% upon LPS + sIgG compared to LPS stimulation. LPS + sIgG co-stimulation affected the NF-κB pathway (p65 phosphorylation and nucleus translocation, and IkB- α degradation). The biochemical inhibition of IRAK 1/4 and Syk kinases suppressed the enhancer effect of LPS + sIgG on TNF- α production, suggesting the involvement of both MyD88 dependent and independent pathways. Our results suggest that during LPS activation, sIgG may participate in a TLR4 - Fc-γR crosstalk.


Assuntos
Imunoglobulina G/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Receptores de IgG/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Células Cultivadas , Citocinas/metabolismo , Humanos , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Interleucina-2/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Antígeno 96 de Linfócito/imunologia , Antígeno 96 de Linfócito/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , NF-kappa B/metabolismo , Receptor Cross-Talk/fisiologia , Receptores de IgG/imunologia , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
14.
BMC Cancer ; 19(1): 356, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987626

RESUMO

BACKGROUND: Glucocorticoid receptor (GR) activation has been associated with breast cancer cell survival in vitro. Glucocorticoid (GC)-dependent protection against tumor necrosis factor (TNF)-induced cell death has been well characterized in MCF7 luminal A breast cancer cells. The GR activates a variety of protective mechanisms, such as inhibitors of apoptosis proteins (IAPs). However, the relative contribution of the GR-dependent expression of IAPs in the protection of cell death has not, to our knowledge, been evaluated. METHODS: MCF7 cells were used for all experiments. GR was activated with cortisol (CORT) or dexamethasone (DEX) and inhibited with mifepristone (RU486). Cell viability was determined in real-time with the xCELLigence™ RTCA System and at specific endpoints using crystal violet stain. The mRNA levels of the eight members of the IAP family were measured by qRT-PCR. The protein levels of GR, PR, ERα, HER2, PARP1, c-IAP1 and XIAP were evaluated by Western blot analysis. The knockdown of c-IAP1 and XIAP was accomplished via transient transfection with specific siRNAs. GR activation was verified by a gene reporter assay. Via the cBioportal interphase we queried the mRNA levels of GR and IAPs in breast cancer tumors. RESULTS: RU486 significantly inhibited the anti-cytotoxic effect of both GCs. PARP1 processing was diminished in the presence of both GCs. The combined treatments of GCs + TNF increased the relative mRNA levels of Survivin>c-IAP1 > NAIP>Apollon>XIAP>Ts-IAP > ML-IAP > c-IAP2. Additionally, GR mRNA content increased with the combined treatments of GCs + TNF. Sustained levels of the proteins c-IAP1 and XIAP were observed after 48 h of the combined treatments with GCs + TNF. With c-IAP1 and XIAP gene silencing, the GC-mediated protection was diminished. In the breast tumor samples, the GR mRNA was coexpressed with Apollon and XIAP with a Pearson coefficient greater than 0.3. CONCLUSIONS: The effect of GCs against TNF-mediated cytotoxicity involves increased mRNA expression and sustained protein levels of c-IAP1 and XIAP. The antagonist effects of RU486 and the qRT-PCR results also suggest the role of the GR in this process. This finding may have clinical implications because the GR and IAPs are expressed in breast tumor samples.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Proteínas Inibidoras de Apoptose/genética , Fator de Necrose Tumoral alfa/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Genes Reporter , Humanos , Células MCF-7 , RNA Mensageiro/genética
16.
Horm Behav ; 89: 189-192, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28161388

RESUMO

Estrogen receptor-alpha (ERα) dimerizes with unliganded progesterone receptor (PR) in target tissues to trigger genomic and non-genomic effects. In ovariectomized rats the antiprogestin RU486 or antisense nucleotides against PR antagonize estradiol-induced sexual receptivity. We determined the relevance of unliganded PR for the expression of estrogen-dependent scent-marking (chinning) and sexual receptivity by injecting RU486 to: a) ovariectomized (ovx) rabbits given estradiol benzoate (EB; 5µg/day); b) intact rabbits. Chinning and lordosis were quantified in ovx animals before (5days; baseline) and during hormonal treatments: EB+RU486 (20mg/day; n=18) or EB+vehicle (n=18). On treatment day 4 LQ (lordosis quotient) increased in both groups, relative to baseline (mean±se): LQ=1±5 (baseline) vs 25±21 (EB+RU486) and 2±6 (baseline) vs 37±29 (EB+vehicle). On day 9 LQ values were: 22±23 (EB+RU486) and 54±39 (EB+vehicle). Chinning increased only in the EB+vehicle group (day 9=55±46 vs baseline=17±20 marks/10min). In intact rabbits one RU486 injection: reduced the LQ from 72±7to 36±8 five hrs later, increased the latency to receive first ejaculation from 45 to 98s, and decreased the number of ejaculations received in the test from 3 to 2 but did not modify mounting latency or chinning. Results support a participation of unliganded PR for the induction (ovx) and maintenance (intact) of rabbit estrous behavior by estrogens.


Assuntos
Estrogênios/fisiologia , Estro/efeitos dos fármacos , Estro/fisiologia , Antagonistas de Hormônios/farmacologia , Mifepristona/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Sexual Animal/fisiologia , Animais , Estradiol/análogos & derivados , Estradiol/farmacologia , Receptor alfa de Estrogênio/efeitos dos fármacos , Receptor alfa de Estrogênio/fisiologia , Feminino , Injeções , Masculino , Postura , Coelhos , Receptores de Progesterona/efeitos dos fármacos , Receptores de Progesterona/fisiologia
17.
Euro Surveill ; 22(24)2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28661394

RESUMO

The international maritime traffic of people and goods has often contributed to the spread of pathogens affecting public health. The Maritime Declaration of Health (MDH), according to the International Health Regulations (IHR) (2005), is a document containing data related to the state of health on board a ship during passage and on arrival at port. It is a useful tool for early detection of public health risks. The main objective of our study was to evaluate compliance with the model provided in the IHR, focusing on the format and degree of completion of MDH forms received at Spanish ports. We reviewed the content of 802 MDH forms submitted to nine Spanish ports between October 2014 and March 2015. Study results show that 22% of MDH forms presented did not comply with the recommended model and 39% were incomplete. The proportion of cargo ships with correct and complete MDH forms was lower than passenger ships; thus, the nine health questions were answered less frequently by cargo ships than passenger ships (63% vs 90%, p value < 0.001). The appropriate demand and usage of MDH forms by competent authorities should improve the quality of the document as a tool and improve risk assessment.


Assuntos
Surtos de Doenças/prevenção & controle , Saúde Global , Vigilância da População/métodos , Saúde Pública/normas , Navios/normas , Viagem , Humanos , Saúde Pública/legislação & jurisprudência , Medição de Risco , Espanha , Organização Mundial da Saúde
19.
Proc Natl Acad Sci U S A ; 110(24): 9824-9, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23703908

RESUMO

The Cyanobacteria Prochlorococcus and Synechococcus account for a substantial fraction of marine primary production. Here, we present quantitative niche models for these lineages that assess present and future global abundances and distributions. These niche models are the result of neural network, nonparametric, and parametric analyses, and they rely on >35,000 discrete observations from all major ocean regions. The models assess cell abundance based on temperature and photosynthetically active radiation, but the individual responses to these environmental variables differ for each lineage. The models estimate global biogeographic patterns and seasonal variability of cell abundance, with maxima in the warm oligotrophic gyres of the Indian and the western Pacific Oceans and minima at higher latitudes. The annual mean global abundances of Prochlorococcus and Synechococcus are 2.9 ± 0.1 × 10(27) and 7.0 ± 0.3 × 10(26) cells, respectively. Using projections of sea surface temperature as a result of increased concentration of greenhouse gases at the end of the 21st century, our niche models projected increases in cell numbers of 29% and 14% for Prochlorococcus and Synechococcus, respectively. The changes are geographically uneven but include an increase in area. Thus, our global niche models suggest that oceanic microbial communities will experience complex changes as a result of projected future climate conditions. Because of the high abundances and contributions to primary production of Prochlorococcus and Synechococcus, these changes may have large impacts on ocean ecosystems and biogeochemical cycles.


Assuntos
Ecossistema , Prochlorococcus/crescimento & desenvolvimento , Água do Mar/microbiologia , Synechococcus/crescimento & desenvolvimento , Algoritmos , Oceano Atlântico , Previsões , Geografia , Oceano Índico , Biologia Marinha/tendências , Modelos Biológicos , Oceano Pacífico , Densidade Demográfica , Dinâmica Populacional , Prochlorococcus/citologia , Análise de Regressão , Estações do Ano , Synechococcus/citologia , Temperatura
20.
Gac Med Mex ; 151(2): 206-15, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-25946532

RESUMO

Inflammation is recognized as part of the etiology of numerous diseases. The interaction among cells of the immunological system with local cells and molecules, such as cytokines and chemokines, allows cellular activation and response amplification. The importance of several physicochemical factors like frictional force, vascular flow, shear stress, and pressure is now recognized because they are known to modulate genetic expression and endothelial activation; however, there are very few studies that recreate such cellular microenvironments. Hence, it is of paramount importance to develop new models that will mimic physiological conditions. Our aim was to improve a human vein ex vivo model that would allow endothelial activation in flow conditions, to study the molecular components during adhesion, taking into consideration physicochemical parameters such as flow and shear stress. Endothelial umbilical human vein was used and activated with TNF-a in order to determine U937 monocytic cells adhesion, as well as cytokines secretion and ICAM-1 expression. This model will allow leukocyte adhesion studies, using different inflammatory stimulus, along with the signaling pathways involved in several pathologies.


Assuntos
Endotélio Vascular/fisiologia , Hemodinâmica , Modelos Cardiovasculares , Fator de Necrose Tumoral alfa/fisiologia , Humanos , Técnicas In Vitro , Veias Umbilicais
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