RESUMO
Neighborhood environments significantly influence the development of diabetes risk factors, morbidity, and mortality throughout an individual's life. The social, economic, and physical environments of a neighborhood all affect the health risks of individuals and communities and also affect population health inequities. Factors such as access to healthy food, green spaces, safe housing, and transportation options can impact the health outcomes of residents. Social factors, including social cohesion and neighborhood safety, also play an important role in shaping neighborhood environments and can influence the development of diabetes. Therefore, understanding the complex relationships between neighborhood environments and diabetes is crucial for developing effective strategies to address health disparities and promote health equity. This review presents landmark findings from studies that examined associations between neighborhood socioeconomic, built and physical, and social environmental factors and diabetes-related risk and outcomes. Our framework emphasizes the historical context and structural and institutional racism as the key drivers of neighborhood environments that ultimately shape diabetes risk and outcomes. To address health inequities in diabetes, we propose future research areas that incorporate health equity principles and place-based interventions.
Assuntos
Diabetes Mellitus , Equidade em Saúde , Humanos , Meio Social , Promoção da Saúde , Habitação , Características de Residência , Diabetes Mellitus/epidemiologiaAssuntos
Anti-Helmínticos/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Praziquantel/uso terapêutico , Esquistossomose Urinária/tratamento farmacológico , Adulto , Animais , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Schistosoma haematobium/isolamento & purificação , Esquistossomose Urinária/complicações , Esquistossomose Urinária/diagnóstico , Esquistossomose Urinária/parasitologia , Resultado do TratamentoRESUMO
PURPOSE: To characterize the expression patterns of tenascin-C (TN-C) splice variants in normal corneas and in those affected by pseudophakic-aphakic bullous keratopathy (PBK-ABK). METHODS: Alternatively spliced variants of TN-C mRNA from normal and age-matched human corneas with PBK-ABK were analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization, using beta2-microglobulin as a housekeeping gene to normalize the samples. Normal and PBK-ABK corneas were studied by immunofluorescence and western blot analysis with antibodies to specific fibronectin type III-like (FN-III) repeats of TN-C. RESULTS: Tenascin-C mRNA expression was detected in epithelial, stromal, and endothelial cells of normal and PBK-ABK central corneas, although the protein was seen only in diseased corneas. Assessed by RT-PCR, PBK-ABK corneas expressed approximately three times more total TN-C mRNA than did normal corneas. Four major TN-C mRNA variants (with no FN-III insertional repeats or with retained insertional repeats D, A1, or A1+D) and three minor variants (with retained repeats A1+A2, A1+A2+D, or A1+A2+B+D) were much more abundant in PBK-ABK than in normal corneas. Repeat A1 was more abundant in PBK-ABK TN-C protein than repeats A2, A3, B, or D. Major TN-C variants in PBK-ABK corneas were in the range of 190 kDa to 240 kDa. CONCLUSIONS: Expression of TN-C mRNA and protein is higher in PBK-ABK corneas than in normal corneas. This increase mainly concerns relatively small TN-C splice variants that may affect corneal cell adhesion and migration and contribute to the exacerbation of PBK-ABK.
Assuntos
Processamento Alternativo , Córnea/metabolismo , Doenças da Córnea/metabolismo , RNA Mensageiro/metabolismo , Tenascina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Doenças da Córnea/patologia , Primers do DNA/química , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Pessoa de Meia-Idade , Sondas de Oligonucleotídeos/química , Reação em Cadeia da Polimerase , Tenascina/genéticaRESUMO
PURPOSE: Pseudophakic/aphakic bullous keratopathy (PBK/ABK) human corneas accumulate an extracellular matrix glycoprotein tenascin-C (TN-C), an important modulator of cell adhesion and migration. Here, the purpose was to identify specific TN-C mRNA splice variants in normal and PBK/ABK human corneas. METHODS: Conventional and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) with primers to alternatively spliced (insertional) and constitutive fibronectin type II-like repeats of TN-C was used. Splice variants were identified by cloning and sequencing of RT-PCR products or by Southern blot analysis. RESULTS: The majority of corneal TN-C mRNA species corresponded to relatively small forms of the protein. Four previously unidentified TN-C mRNA splice variants were found in normal and PBK/ABK corneas that contained insertional repeats A1+A2+B+D, A1+A2+D, A1+B+D, or A1+D. Variants with insertional repeats A1+A2 or A1, previously described in mouse and rat, were also identified in human corneas. Semiquantitative RT-PCR showed that novel TN-C mRNA variants were dramatically elevated in PBK/ABK compared to normal corneas. CONCLUSION: TN-C protein was found in PBK/ABK but not in normal corneas; however, both normal and diseased corneas contained mRNA for 15 different TN-C isoforms. PBK/ABK corneas had elevated levels of six relatively small TN-C mRNA variants including five novel ones. These specific isoforms may adversely affect adhesion and migration of corneal cells thus contributing to the exacerbation of PBK/ABK.
Assuntos
Processamento Alternativo/genética , Córnea/química , Doenças da Córnea/genética , RNA Mensageiro/análise , Tenascina/genética , Southern Blotting , Primers do DNA/química , Humanos , Sondas de Oligonucleotídeos/química , Reação em Cadeia da Polimerase , Transcrição GênicaRESUMO
Type VI collagen and gelatinase A are synthesized by human keratocytes in vitro. Keratoconus is a corneal disease that has increased gelatinase A activity. Normal keratocyte culture media analyzed by Western blotting with polyclonal antibody to type VI collagen showed a single 140 kDa band that increased in intensity after phorbol ester treatment. The same 140 kDa band was absent in media collected from keratoconus keratocytes cultured with or without phorbol ester. We speculate that in keratoconus keratocyte cultures, type VI collagen may be degraded or modified by the increased gelatinase A activity so as not to be recognized by the type VI antibody.