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1.
Artigo em Inglês | MEDLINE | ID: mdl-38737924

RESUMO

Introduction: Residential stability is increasingly recognized as a significant factor influencing youth positive development. While the existing body of research provides valuable insights, gaps remain regarding the determinants of residential stability and how its outcomes may vary by gender and race. This study aims to investigate the relationship between residential stability, substance use, and behavioral issues among children aged 9-10 years, with a focus on the mediating role of trauma exposure. Methods: This research utilizes data from the Adolescent Brain Cognitive Development (ABCD) study, a longitudinal project initiated in 2016 with a sample of 11,849 participants. It explores the links between residential stability, socioeconomic factors, stress, and emotional and behavioral outcomes using the Child Behavior Checklist (CBCL). Structural equation modeling was employed to analyze the data. Results: Findings indicate that higher household income, living in a household with married parents, and residing in areas with greater household incomes correlate with residential stability. In turn, residential stability is linked to lower levels of life stress and reduced substance use in the future. Furthermore, the impact of residential stability on substance uses and CBCL scores was entirely mediated by trauma exposure. Conclusions: The findings advocate for the implementation of economic, social, and public policies aimed at fostering stable living environments for children and families to mitigate the emotional and behavioral challenges future generations may face. Enhancing socioeconomic status and supporting structures that promote married family living arrangements emerge as effective strategies to improve residential stability and the well-being of young people in the United States.

2.
Cost Eff Resour Alloc ; 21(1): 84, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932767

RESUMO

BACKGROUND: Prostate cancer is the second most common cancer in males worldwide and the third most common among Iran's male population. However, there is a lack of evidence regarding its direct and indirect costs in low and middle-income countries. This study intends to bridge the gap using a cost of illness approach, assessing the costs of prostate cancer from the perspectives of patients, society, and the insurance system. METHODS: Two hundred ninety seven patients were included in the study. Data for a 2-month period were obtained from patients registered at two hospitals (Tabriz, Tehran) in Iran in 2017. We applied a prevalence-based, bottom-up approach to assess the costs of the illness. We used the World Health Organization methods to measure the prevalence and investigate the determinants of catastrophic and impoverishing health expenditures. RESULTS: We determined the total costs of the disease for the patients to be IRR 68 million (PPP $ 5,244.44). Total costs of the disease from the perspective of the society amounted to IRR 700,000 million (PPP $ 54 million). Insurance companies expended IRR 20 million (PPP $ 1,558.80) per patient. Our findings show that 31% of the patients incurred catastrophic health expenditure due to the disease. Five point forty-four percent (5.44%) of the patients were impoverished due to the costs of this cancer. CONCLUSION: We found an alarmingly high prevalence of catastrophic health expenditures among prostate cancer patients. In addition, prostate cancer puts a substantial burden on both the patients and society.

3.
Am J Mens Health ; 17(6): 15579883231205845, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37978812

RESUMO

Obesity prevalence in the United States has increased drastically in the last two decades. Racial differences in obesity have emerged with the increase in obesity, with temporal trends because of individual, socioeconomic, and environmental factors, eating behaviors, lack of exercise, etc., raising questions about understanding the mechanisms driving these racial differences in the prevalence of obesity among non-Hispanic Black (NHB) and non-Hispanic White (NHW) men. Although many studies have measured obesity using body mass index (BMI), little is known about waist circumference (WC). This study examines variations in obesity among NHW and NHB using BMI and WC. We used National Health and Nutrition Examination Surveys (1999-2016) with a sample of 9,000 NHW and 3,913 NHB men aged 20 years or older. To estimate the association between the prevalence of obesity (BMI ≥30) and race, we applied modified Poisson regression; to explore and decompose racial differences, we used Oaxaca-Blinder decomposition (OBD). We found that NHW had higher abdominal obesity (WC ≥102) than NHB, but NHB were more likely to be obese (BMI ≥30) during most years, with some fluctuations. Modified Poisson regression showed that NHB had a higher prevalence of obesity (prevalence ratio [PR]: 1.11, 95% confidence interval [CI] = [1.04, 1.18]) but lower abdominal obesity (PR: 0.845; 95% CI = [0.801, 0.892]) than NHW. OBD showed that age, access to health care, smoking, and drinking contributed to the differences in abdominal obesity. The study identifies a significant increase in obesity among men over the last two decades; generalized obesity (based on BMI) was more problematic for NHB men, but abdominal obesity was more problematic for NHW men.


Assuntos
Obesidade Abdominal , Obesidade , Humanos , Masculino , Negro ou Afro-Americano , Obesidade/epidemiologia , Obesidade Abdominal/etnologia , Fatores Raciais , Fatores de Risco , Estados Unidos/epidemiologia , Brancos
4.
Public Health Pract (Oxf) ; 6: 100425, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37711501

RESUMO

Objectives: Educational attainment is a protective factor against poor health, but high educational attainment has a weaker effect on black people than on white people; this pattern has been called marginalization-related diminished returns (MDRs). Using a national sample of white people and black people 25 years and above, this study estimates the association between high educational attainment and allostatic load between black people and white people, and within each group. Study design: This cross-sectional study uses data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016, including 2761 black people and 7058 white people. The outcome variable of interest was the Allostatic Load Scale (AL). We created the allostatic load scale by using 8 biomarkers, then created a binary variable (if ALS≥4 as 1 and ALS<4 as 0) to present elevated AL. Methods: We used several weighted modified Poisson regression models controlling for educational attainment (a predictor) and race (a moderator variable), age, sex, and marital status. We also controlled the models for smoking and drinking status as health behavior variables. As a sensitivity analysis, we ran several sets of regression analysis using the AL scale as a continuous outcome variable. Results: We found an inverse association between AL and educational attainment. The interaction between race and education has resulted in an inverse association between AL and educational attainment, with a weaker association in black people than in white people. We found similar findings by running regression models with AL as a continuous variable. Conclusions: We observed a weaker association between educational attainment and AL in black people than in white people, suggesting that educational attainment has more robust protection against allostatic load for white people than black people.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37490210

RESUMO

BACKGROUND: COVID-19 pandemic has immensely impacted the social and personal lives of individuals around the globe. Marginalized-related diminished returns (MDRs) theory suggests that educational attainment shows a weaker protective effect for health and behavioral outcomes for Black individuals compared to White individuals. Previous studies conducted before the COVID-19 pandemic demonstrated diminished returns of educational attainment for Black individuals compared to White individuals. OBJECTIVES: The study has three objectives: First, to test the association between educational attainment and cigarette smoking, e-cigarette vaping, presence of chronic medical conditions (CMC), self-rated health (SRH), depressive symptoms, and obesity; second, to explore racial differences in these associations in the USA during the COVID-19 pandemic; and third, to compare the interaction of race and return of educational attainment pre- and post-COVID-19 pandemic. METHODS: This study utilized data from the Health Information National Trends Survey (HINTS) 2020. Total sample included 1313 adult American; among them, 77.4% (n = 1017) were non-Hispanic White, and 22.6% (n = 296) were non-Hispanic Black. Educational attainment was the independent variable operationalized as years of education. The main outcomes were cigarette smoking, e-cigarette vaping, CMC, SRH, depressive symptoms, and obesity. Age, gender, and baseline physical health were covariates. Race/ethnicity was an effect modifier. RESULTS: Educational attainment was significantly associated with lower CMC, SRH, depressive symptoms, obesity, cigarette smoking, and e-cigarette vaping. Educational attainment did not show a significant interaction with race on any of our outcomes, suggesting that the health returns of education is similar between non-Hispanic White and non-Hispanic Black individuals. CONCLUSION: COVID-19 may have operated as an equalizer of the returns of educational attainment. This observation may be because White may have more to lose; Black communities may be more resilient or have economic and social policies that buffered unemployment and poverty regardless of historical anti-Black oppression.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35564878

RESUMO

Education continues to be a key factor contributing to increased access to critical life-improving opportunities and has been found to be protective against Allostatic Load (AL). The purpose of this study was to assess AL among Non-Hispanic (NH) White and NH Black men with the same level of education. We used 1999-2016 National Health and Nutrition Examination Surveys (NHANES) data with an analytical sample of 6472 men (1842 NH Black and 4630 NH White), and nine biomarkers to measure AL, controlling for various demographic and health-related factors. NH Black men had a higher AL score than NH White men (39.1%, 842 vs. 37.7%, 1,975). Racial disparities in AL between NH Black and NH White men who have a college degree or above (PR: 1.49, CI: [1.24-1.80]) were observed. Models posited similar AL differences at every other level of education, although these were not statistically significant. The findings reveal that socioeconomic returns to education and the societal protective mechanisms associated with education vary greatly between White and Black men.


Assuntos
Alostase , Negro ou Afro-Americano , Escolaridade , Humanos , Masculino , Inquéritos Nutricionais , Fatores Raciais
7.
Artigo em Inglês | MEDLINE | ID: mdl-34734120

RESUMO

BACKGROUND: While socioeconomic status (SES) indicators such as educational attainment and employment are among the major drivers of health and illness, the health returns of SES indicators may differ across racial groups. Built on Marginalization related Diminished Returns framework (MDRs) that refers to weaker health effects of SES indicators for marginalized and minoritized groups than non-Hispanic White people, we conducted this study with two aims: First to test the association between educational attainment and employment with cardiometabolic diseases (CMDs), and second, to test racial variation in these associations. METHODS: This cross-sectional study used the National Health and Nutrition Examination Survey (NHANES 1999-2016) data. Participants included 29,230 adults who were either non-Hispanic White or non-Hispanic Black. Race, demographic factors (age and sex, and marital status), SES (educational attainment and employment), behaviors (smoking, drinking, and exercise), health insurance, and CMDs (diabetes, stroke, hypertension, and congestive heart failure) were measured. Weighted Poisson regression models were used in Stata to adjust for the complex sample design of the NHANES. Models without and with interactions were performed in the pooled sample. We also ran race-stratified models. RESULTS: Overall, high educational attainment and employment showed inverse associations with some CMDs. As documented by statistical interactions between race and our SES indicators, we observed weaker inverse associations between educational attainment and employment with some CMDs. Race-stratified models also confirmed our main analysis. However, the results varied across CMD conditions. CONCLUSION: We observe that SES indicators such as educational attainment and employment have differential associations for racial groups. Compared to non-Hispanic White people, non-Hispanic Black people remain at CMDs risk across the full SES spectrum. This finding is in line with the MDRs framework and may be due to the structural racism, social stratification, and Marginalization of non-Hispanic Black Americans.

8.
Healthcare (Basel) ; 9(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34828490

RESUMO

Obesity is a major public health problem both globally and within the U.S. It varies by multiple factors, including but not limited to income and sex. After controlling for potential covariates, there is little evidence to determine the association between income and obesity and how obesity may be moderated by sex and family income. We examined the association between income and obesity in U.S. adults aged 20 years and older, and tested whether this relationship differs by race or ethnicity groups. For this analysis, we used data from the 1999-2016 National Health and Nutrition Examination Surveys (NHANES). Obesity was determined using Body Mass Index ≥ 30 kg/m2; the Gini coefficient (GC) was calculated to measure income inequality using the Poverty Income Ratio (PIR). We categorized the PIR into five quintiles to examine the relationship between income inequality and obesity. For the first set of analyses, we used a modified Poisson regression in a sample of 36,665 adults, with an almost equal number of men and women (women's ratio was 50.6%), including 17,303 white non-Hispanics (WNH), 7475 black non-Hispanics (BNHs), and 6281 Mexican Americans. The models included age, racial/ethnic groups, marital status, education, health behaviors (smoking and drinking status and physical activities), health insurance coverage, self-reported health, and household structure (live alone and size of household). Adjusting for potential confounders, our findings showed that the association between PIR and obesity was positive and significant more frequently among WNH and BNH in middle and top PIR quintiles than among lower-PIR quintiles; this association was not significant in Mexican Americans (MAs). Results of GC in obese women showed that in comparison with WNHs (GC: 0.34, S.E.: 0.002), BNHs (GC: 0.38, S.E.: 0.004) and MAs (GC: 0.41, S.E.: 0.006) experienced higher income inequality, and that BNH obese men experienced the highest income inequality (GC: 0.45, S.E.: 0.011). The association between PIR and obesity was significant among WNHs and BNHs men in the 3rd, 4th and 5th PIR quintiles. The same association was not found for women. In treating obesity, policymakers should consider not only race/ethnicity and sex, but also strategies to reduce inequality in income.

9.
Mol Biol Rep ; 48(7): 5707-5722, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34275112

RESUMO

CD47, a member of the immunoglobulin superfamily, is an important "Don't Eat-Me" signal in phagocytosis process [clearance of apoptotic cells] as well as a regulator of the adaptive immune response. The lower level of CD47 on the cell surface leads to the clearance of apoptotic cells. Dysregulation of CD47 plays a critical role in the development of disorders, particularly cancers. In cancers, recognition of CD47 overexpression on the surface of cancer cells by its receptor, SIRPα on the phagocytic cells, inhibits phagocytosis of cancer cells. Thus, blocking of CD47-SIRPα signaling axis might be as a promising therapeutic target, which promotes phagocytosis of cancer cells, antigen-presenting cell function as well as adaptive T cell-mediated anti-cancer immunity. In this respect, it has been reported that CD47 expression can be regulated by microRNAs (miRNAs). MiRNAs can regulate phagocytosis of macrophages apoptotic process, drug resistance, relapse of disease, radio-sensitivity, and suppress cell proliferation, migration, and invasion through post-transcriptional regulation of CD47-SIRPα signaling axis. Moreover, the regulation of CD47 expression by miRNAs and combination with conventional cytotoxic drugs together with the help of nano-delivery represent a valuable opportunity for effective cancer treatment. In this review, we review studies that evaluate the role of miRNAs in the regulation of CD47-SIRPα in disorders to achieve a novel preventive, diagnostic, and therapeutic strategy.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct. Confirmed.Journal standard instruction requires a structured abstract; however, none was provided. Please supply an Abstract with subsections..Not confirmed. This is a review article. According to submission guidelines: "The abstract should be presented divided into subheadings (unless it is a mini or full review article)". Kindly check and confirm whether the corresponding authors and mail ID are correctly identified. Confirmed.


Assuntos
Antígenos de Diferenciação/metabolismo , Antineoplásicos/farmacologia , Antígeno CD47/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Interferência de RNA , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antígenos de Diferenciação/genética , Antineoplásicos/administração & dosagem , Antígeno CD47/genética , Gerenciamento Clínico , Suscetibilidade a Doenças , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Especificidade de Órgãos , Fagocitose/efeitos dos fármacos , Receptores Imunológicos/genética
10.
Int J Nanomedicine ; 16: 1681-1706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688185

RESUMO

The unique properties of carbon nanotubes (CNTs) (such as their high surface to volume ratios, enhanced conductivity and strength, biocompatibility, ease of functionalization, optical properties, etc.) have led to their consideration to serve as novel drug and gene delivery carriers. CNTs are effectively taken up by many different cell types through several mechanisms. CNTs have acted as carriers of anticancer molecules (including docetaxel (DTX), doxorubicin (DOX), methotrexate (MTX), paclitaxel (PTX), and gemcitabine (GEM)), anti-inflammatory drugs, osteogenic dexamethasone (DEX) steroids, etc. In addition, the unique optical properties of CNTs have led to their use in a number of platforms for improved photo-therapy. Further, the easy surface functionalization of CNTs has prompted their use to deliver different genes, such as plasmid DNA (PDNA), micro-RNA (miRNA), and small interfering RNA (siRNA) as gene delivery vectors for various diseases such as cancers. However, despite all of these promises, the most important continuous concerns raised by scientists reside in CNT nanotoxicology and the environmental effects of CNTs, mostly because of their non-biodegradable state. Despite a lack of widespread FDA approval, CNTs have been studied for decades and plenty of in vivo and in vitro reports have been published, which are reviewed here. Lastly, this review covers the future research necessary for the field of CNT medicine to grow even further.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Nanotubos de Carbono/química , Endocitose , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/terapia
11.
JAMA Psychiatry ; 78(4): 426-432, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566072

RESUMO

Importance: Depression is one of the leading causes of disability in the United States. African American women of low socioeconomic status with uncontrolled hypertension are at risk of having severe depressive symptoms, yet there is limited research about the mental health of this vulnerable population. Data from the Prime Time Sister Circles randomized clinical trial (PTSC-RCT) study can shed light on the prevalence of depressive symptoms among low-socioeconomic-status older African American women with hypertension. Objective: To determine the prevalence of depressive symptoms among low-socioeconomic-status African American women aged 40 to 75 years with uncontrolled hypertension who receive their care from a federally qualified health center (FQHC) and to identify risk factors associated with depressive symptoms. Design, Setting, and Participants: Cross-sectional analysis of data from the PTSC-RCT of depressive symptomology, measured using an adapted version of the 10-item Center for Epidemiological Studies Depression Scale Revised (CES-D-10). Descriptive statistics were used to characterize the study population. We used logistic regression models to investigate the factors associated with participants with or without symptoms of depression. We used baseline data from the PTSC-RCT study, including 316 African American English-speaking women between ages 40 and 75 years with hypertension (systolic blood pressure ≥140 mm Hg or diastolic ≥90 mm Hg), who received their primary care at a FQHC in Washington, DC, in 2017 and 2018 and were flagged by the FQHC as uncontrolled. Main Outcomes and Measures: We used the CES-D-10 from the Center for Epidemiologic Studies Depression Scale to measure presence of depressive symptoms. Results: A total of 57.0% of the women in the study (180 of 316) scored greater than or equal to 10 on the CES-D-10. Depressive symptoms had a negative association with a postsecondary education (adjusted odds ratio [aOR], 0.492; 95% CI, 0.249-0.968) and a positive association with the number of chronic conditions (aOR, 1.235; 95% CI, 1.046-1.460) and smoking (aOR, 1.731; 95% CI, 1.039-2.881). Conclusions and Relevance: In this study of low-income African American women with uncontrolled hypertension, more than half had symptoms of depression that was associated with less than high-school education, chronic conditions, and smoking. Low-income African American women with uncontrolled hypertension should be screened and adequately treated for depressive symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04371614.


Assuntos
Negro ou Afro-Americano/etnologia , Depressão/etnologia , Hipertensão/etnologia , Classe Social , Adulto , Idoso , Comorbidade , Estudos Transversais , Depressão/diagnóstico , Feminino , Humanos , Hipertensão/terapia , Renda , Pessoa de Meia-Idade , Pobreza , Prevalência , Estados Unidos/etnologia , Saúde da Mulher
12.
J Cell Biochem ; 119(7): 5834-5842, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29575235

RESUMO

Acute liver failure (ALF) is a lethal disease with limited life-saving therapy. Because lack of whole organ donors for liver transplantation, a substitute treatment strategy is needed for these patients. Preclinical and clinical findings have proved that treatment with mesenchymal stem cells (MSCs) is beneficial for recovery from ALF. In this approach, however, the appropriate sources of these cells are unclear. In the present study, we investigated and compared the therapeutic potentials of bone marrow-mesenchymal stem cells (BM-MSC) with those of adipose tissue (AT-MSC) in carbon tetrachloride (CCL4)-induced acute liver failure in mice. Murine BM- and AT-MSCs obtained from normal mice were cultured and labelled. The cells were transplanted to CCL4-induced ALF mice models intravenously. After cell transplantation, blood samples and liver tissues were collected daily for 72 h to analyze liver enzymes and liver histopathology, respectively. We found that survival rate of AT-MSC transplanted (AT-TR) mice was significantly higher than that of control (ALF) group. Liver histopathology was superior in the AT-TR mice, but not significantly, compared to that in BM-MSC transplanted (BM-TR) ones. Furthermore, in the AT-TR mice the level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), in some time points were significantly less than those of BM-TR. Taken together, these data suggest that in comparison to BM-MSC, AT-MSCs is an appropriate choice for cell therapy in the case of acute liver failure.


Assuntos
Tecido Adiposo/transplante , Falência Hepática Aguda/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Tecido Adiposo/citologia , Animais , Tetracloreto de Carbono/toxicidade , Terapia Baseada em Transplante de Células e Tecidos , Modelos Animais de Doenças , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Masculino , Camundongos
13.
Nat Commun ; 8(1): 1707, 2017 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-29167426

RESUMO

Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia.


Assuntos
Caquexia/prevenção & controle , Neoplasias Experimentais/terapia , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Azepinas/farmacologia , Caquexia/genética , Caquexia/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Epigênese Genética , Proteína Forkhead Box O3/metabolismo , Regulação da Expressão Gênica , Humanos , Interleucina-6/metabolismo , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/prevenção & controle , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Triazóis/farmacologia
14.
Nanoscale ; 9(4): 1356-1392, 2017 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28067384

RESUMO

Nanocages (NCs) have emerged as a new class of drug-carriers, with a wide range of possibilities in multi-modality medical treatments and theranostics. Nanocages can overcome such limitations as high toxicity caused by anti-cancer chemotherapy or by the nanocarrier itself, due to their unique characteristics. These properties consist of: (1) a high loading-capacity (spacious interior); (2) a porous structure (analogous to openings between the bars of the cage); (3) enabling smart release (a key to unlock the cage); and (4) a low likelihood of unfavorable immune responses (the outside of the cage is safe). In this review, we cover different classes of NC structures such as virus-like particles (VLPs), protein NCs, DNA NCs, supramolecular nanosystems, hybrid metal-organic NCs, gold NCs, carbon-based NCs and silica NCs. Moreover, NC-assisted drug delivery including modification methods, drug immobilization, active targeting, and stimulus-responsive release mechanisms are discussed, highlighting the advantages, disadvantages and challenges. Finally, translation of NCs into clinical applications, and an up-to-date assessment of the nanotoxicology considerations of NCs are presented.


Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas/química , Nanoestruturas/toxicidade , Nanomedicina Teranóstica , Animais , Materiais Biocompatíveis , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Ouro , Humanos , Neoplasias/tratamento farmacológico
15.
Autophagy ; 12(8): 1240-58, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27171064

RESUMO

The activation of transcription factors is critical to ensure an effective defense against pathogens. In this study we identify a critical and complementary role of the transcription factors TFEB and TFE3 in innate immune response. By using a combination of chromatin immunoprecipitation, CRISPR-Cas9-mediated genome-editing technology, and in vivo models, we determined that TFEB and TFE3 collaborate with each other in activated macrophages and microglia to promote efficient autophagy induction, increased lysosomal biogenesis, and transcriptional upregulation of numerous proinflammatory cytokines. Furthermore, secretion of key mediators of the inflammatory response (CSF2, IL1B, IL2, and IL27), macrophage differentiation (CSF1), and macrophage infiltration and migration to sites of inflammation (CCL2) was significantly reduced in TFEB and TFE3 deficient cells. These new insights provide us with a deeper understanding of the transcriptional regulation of the innate immune response.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Imunidade Inata , Macrófagos/metabolismo , Animais , Autofagia , Núcleo Celular/metabolismo , Citosol/metabolismo , Feminino , Regulação da Expressão Gênica , Células HEK293 , Humanos , Inflamação , Ativação de Macrófagos , Masculino , Camundongos , Microglia/metabolismo , Células RAW 264.7
16.
Development ; 143(11): 1971-80, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27068104

RESUMO

Although the genetic interactions between signaling pathways and transcription factors have been largely decoded, much remains to be learned about the epigenetic regulation of cerebellar development. Here, we report that cerebellar deletion of Ezh2, the methyltransferase subunit of the PRC2 complex, results in reduced H3K27me3 and profound transcriptional dysregulation, including that of a set of transcription factors directly involved in cerebellar neuronal cell-type specification and differentiation. Such transcriptional changes lead to increased GABAergic interneurons and decreased Purkinje cells. Transcriptional changes also inhibit the proliferation of granule precursor cells derived from the rhombic lip. The loss of both cell types ultimately results in cerebellar hypoplasia. These findings indicate Ezh2/PRC2 plays crucial roles in regulating neurogenesis from both cerebellar germinal zones.


Assuntos
Linhagem da Célula , Cerebelo/embriologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/metabolismo , Animais , Contagem de Células , Linhagem da Célula/genética , Proliferação de Células , Cerebelo/metabolismo , Cerebelo/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Loci Gênicos , Genoma , Histonas/metabolismo , Interneurônios/metabolismo , Lisina/metabolismo , Metilação , Camundongos Knockout , Fator de Transcrição PAX7/metabolismo , Células de Purkinje/metabolismo , Células de Purkinje/patologia , Transcrição Gênica , Proteínas Supressoras de Tumor/metabolismo
17.
Cell Rep ; 14(5): 1156-1168, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26832413

RESUMO

Histone variants complement and integrate histone post-translational modifications in regulating transcription. The histone variant macroH2A1 (mH2A1) is almost three times the size of its canonical H2A counterpart, due to the presence of an ∼25 kDa evolutionarily conserved non-histone macro domain. Strikingly, mH2A1 can mediate both gene repression and activation. However, the molecular determinants conferring these alternative functions remain elusive. Here, we report that mH2A1.2 is required for the activation of the myogenic gene regulatory network and muscle cell differentiation. H3K27 acetylation at prospective enhancers is exquisitely sensitive to mH2A1.2, indicating a role of mH2A1.2 in imparting enhancer activation. Both H3K27 acetylation and recruitment of the transcription factor Pbx1 at prospective enhancers are regulated by mH2A1.2. Overall, our findings indicate a role of mH2A1.2 in marking regulatory regions for activation.


Assuntos
Elementos Facilitadores Genéticos/genética , Histonas/metabolismo , Proteínas de Homeodomínio/metabolismo , Músculo Esquelético/metabolismo , Fatores de Transcrição/metabolismo , Acetilação , Animais , Diferenciação Celular/genética , Cromatina/metabolismo , Epigênese Genética , Redes Reguladoras de Genes , Genoma , Células HEK293 , Humanos , Camundongos , Células Musculares/citologia , Células Musculares/metabolismo , Desenvolvimento Muscular/genética , Proteína MyoD/metabolismo , Fator de Transcrição 1 de Leucemia de Células Pré-B , Ligação Proteica/genética , Transcrição Gênica , Transcriptoma/genética
18.
Health Serv Res ; 51(3): 910-36, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26418717

RESUMO

OBJECTIVE: To explore the association between quality of care for surgical and pneumonia patients and the racial/ethnic composition of hospitals' patients. DATA SOURCE: Our primary data were surgical and pneumonia processes of care indicators from the 2012 Medicare Hospital Compare Data. We merged this data with information from the 2011 American Hospital Association Annual Survey of Hospitals. We computed the racial and ethnic composition of hospital patients using 2008 data from the Healthcare Costs and Utilization Project. STUDY DESIGN: The sample included 1,198 acute care general hospitals from 11 states: AZ, CA, FL, IA, MA, MD, NC, NJ, NY, WA, and WI. We compared quality across minority-serving, racially integrated, and majority-white hospitals using unconditional quantile regression models controlling for hospital and market characteristics. PRINCIPAL FINDINGS: We found quality differences between the lowest performing minority-serving, racially integrated, and majority-white hospitals. As we moved from 10th to 90th quantile, the quality differences between hospitals by patients' racial composition disappeared. In other words, the best minority-serving and racially integrated hospitals performed as well as the best majority hospitals. CONCLUSIONS: Efforts to improve quality of care for patients in minority-serving and racially integrated hospitals should focus on the lowest performers.


Assuntos
Hospitais/estatística & dados numéricos , Pneumonia/terapia , Qualidade da Assistência à Saúde/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Diversidade Cultural , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Grupos Minoritários/estatística & dados numéricos , Pneumonia/etnologia , Indicadores de Qualidade em Assistência à Saúde , Estados Unidos
19.
Scand J Public Health ; 43(8): 786-95, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26261191

RESUMO

AIM: We examined the impact of different behavioral factors of health on the variations in the levels and rate of increase in life expectancy in Organization for Economic Co-operation and Development countries between 1985 and 2010. METHODS: Using the World Health Organization's conceptual framework of socio-economic determinants of health, we incorporated Organization for Economic Co-operation and Development, World Bank and United Nations data to estimate the impact of these variables on life expectancy for 30 Organization for Economic Co-operation and Development countries. We used a random effect model to control the fixed effect of year and each country. RESULTS: Results show that the level of health care spending is the most important factor predicting life expectancy. Other important factors are gross domestic product per capita, labor productivity, years of schooling and percentage of gross domestic product spending allocated for public services. Life expectancy was reduced by smoking and higher daily calorie consumption. Countries that were previously part of the Soviet Union had lower life expectancies. Political factors had only a minor impact on life expectancy. CONCLUSIONS: Life expectancy increased an average of 5.1 years in Organization for Economic Co-operation and Development countries between 1985 and 2010, but there was wide variation. Health spending per capita, economic factors and two behavioral factors - smoking and caloric intake - explained most of the variation and suggest where increased policy attention could have the greatest impact on life expectancy. Policymakers who consider our estimates recognize that they may see greater or less impact depending on the characteristics of their nation.


Assuntos
Países em Desenvolvimento/estatística & dados numéricos , Expectativa de Vida/tendências , Ingestão de Energia , Comportamentos Relacionados com a Saúde , Gastos em Saúde/tendências , Humanos , Fumar/epidemiologia , Fatores Socioeconômicos
20.
Int J Equity Health ; 13: 42, 2014 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-24885492

RESUMO

INTRODUCTION: Reducing inequalities in health care is one of the main challenges in all countries. In Iran as in other oil-exporting upper middle income countries, we expected to witness fewer inequalities especially in the health sector with the increase in governmental revenues. METHODS: This study presents an inequalities assessment of health care expenditures in Iran. We used data from the Household Income and Expenditure Survey (HIES) in Iran from 1984-2010. The analysis included 308,735 urban and 342,532 rural households. RESULTS: The results suggest heightened inequality in health care expenditures in Iran over the past three decades, including an increase in the gap between urban and rural areas. Furthermore, inflation has affected the poor more than the rich. The Kakwani progressivity index in all years is positive, averaging 0.436 in rural and 0.470 in urban areas during the time period of analysis. Compared to inequality in income distribution over the last 30 years, health expenditures continuously show more inequality and progressivity over the same period of time. CONCLUSIONS: According to the result of our study, during this period Iran introduced four National Development Plans (NDPs); however, the NDPs failed to provide sustainable strategies for reducing inequalities in health care expenditures. Policies that protect vulnerable groups should be prioritized.


Assuntos
Desenvolvimento Econômico , Financiamento Pessoal , Gastos em Saúde , Disparidades em Assistência à Saúde/economia , Renda , Pobreza , Características da Família , Disparidades em Assistência à Saúde/tendências , Humanos , Irã (Geográfico) , Programas Nacionais de Saúde , População Rural , Mudança Social , Classe Social
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