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1.
Int Immunopharmacol ; 135: 112223, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38772295

RESUMO

Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Fator 2 Relacionado a NF-E2 , Nicotina , Osteomielite , Transdução de Sinais , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Nicotina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Osteomielite/microbiologia , Osteomielite/tratamento farmacológico , Osteomielite/metabolismo , Camundongos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Camundongos Endogâmicos C57BL , Humanos , Masculino , Fagocitose/efeitos dos fármacos , Modelos Animais de Doenças
2.
Health Equity ; 6(1): 767-776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225666

RESUMO

Introduction: Although a requirement for the health and hygiene of young children, millions of US families with low-incomes have unmet needs for diapers. The present study explored retail options in Durham County, NC for purchasing diapers in low-income neighborhoods in effort to increase our understanding of the overall context of diaper need. Methods: During June 2018, we visited 63 retailers selling 2460 child diaper products in 29 census tracts with a median household income ≤200% of the federal poverty guideline. Corner stores were the only retailers to sell products without original packaging, including one corner store selling loose diapers for $1.49 each. Next, we calculated bus routes to determine accessibility of the retailer with the lowest prices and greatest selection. One-way bus travel from all other census tracts to a big-box store required taking two buses combined with an average of 11 min walking for an average travel time of 43 min. We deemed census tracts as "priority areas for diaper access" when they were characterized as: (1) low income and (2) low access with no retailer selling all of the 10 most common child diaper sizes. Results: Nearly half (n=13) of the census tracts in our sample met our criteria for priority areas. We compared neighborhood characteristics of priority areas with all other county census tracts. Families living in priority areas were statistically significantly more likely to: identify as Black or African American, face challenges affording housing costs, have homes or automobiles in need of repair, experience neighborhood violence, and have less educational attainment.

3.
Plant Cell ; 34(6): 2266-2285, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35294019

RESUMO

B-box containing proteins (BBXs) integrate light and various hormonal signals to regulate plant growth and development. Here, we demonstrate that the photomorphogenic repressors BBX28 and BBX29 positively regulate brassinosteroid (BR) signaling in Arabidopsis thaliana seedlings. Treatment with the BR brassinolide stabilized BBX28 and BBX29, which partially depended on BR INSENSITIVE1 (BRI1) and BIN2. bbx28 bbx29 seedlings exhibited larger cotyledon aperture than the wild-type when treated with brassinazole in the dark, which partially suppressed the closed cotyledons of brassinazole resistant 1-1D (bzr1-1D). Consistently, overexpressing BBX28 and BBX29 partially rescued the short hypocotyls of bri1-5 and bin2-1 in both the dark and light, while the loss-of-function of BBX28 and BBX29 partially suppressed the long hypocotyls of bzr1-1D in the light. BBX28 and BBX29 physically interacted with BR-ENHANCED EXPRESSION1 (BEE1), BEE2, and BEE3 and enhanced their binding to and activation of their target genes. Moreover, BBX28 and BBX29 as well as BEE1, BEE2, and BEE3 increased BZR1 accumulation to promote the BR signaling pathway. Therefore, both BBX28 and BBX29 interact with BEE1, BEE2, and BEE3 to orchestrate light and BR signaling by facilitating the transcriptional activity of BEE target genes. Our study provides insights into the pivotal roles of BBX28 and BBX29 as signal integrators in ensuring normal seedling development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brassinosteroides/metabolismo , Brassinosteroides/farmacologia , Regulação da Expressão Gênica de Plantas/genética , Proteínas Quinases/metabolismo , Plântula/genética , Plântula/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
J Pharm Biomed Anal ; 193: 113636, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33221574

RESUMO

The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency.


Assuntos
Antioxidantes , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida
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