RESUMO
BACKGROUND: Exposure to secondhand tobacco smoke (SHS) and child maltreatment are preventable threats to child health. Few evidence-based interventions target both SHS and child maltreatment risk. The purpose of this paper is to describe the systematic braiding process of two evidence-based programs to address child SHS in the home and maltreatment perpetration risk, and present results from the formative work and pilot study. METHODS: The first 4 steps of the systematic braiding process were completed, including the following: (1) the identification of core elements of both programs, (2) the development of an initial draft of the braided curriculum (Smoke-Free Home SafeCare - SFH-SC), (3) an acceptability and feasibility pilot of SFH-SC with caregivers of young children who reported a smoker living in the home (N = 8), and (4) feedback collection on the braided curriculum from SafeCare Providers (N = 9). RESULTS: Experts identified common pedagogical and theoretical underpinnings for the two programs and braided Smoke-Free Homes: Some Things Are Better Outside into two SafeCare modules. Caregiver feedback from the pilot demonstrated that participants were engaged with SFH-SC and felt supported and comfortable discussing SHS intervention content with the SFH-SC Provider. Caregiver self-reports indicated a slight increase in smoke-free home rules from baseline to follow-up and a notable reduction in parent stress on the Parent Stress Index of 5.9 points (SD = 10.2). SafeCare Provider feedback following intensive review of the curriculum indicated high feasibility for SFH-SC delivery. CONCLUSIONS: Parent and Provider findings suggest SFH-SC is a viable intervention that has potential to reduce the public health impact of SHS and child maltreatment for at-risk families. PROTOCOL: The protocol for the pilot is not published elsewhere; however, the full protocol for the hybrid trial can be found here: https://clinicaltrials.gov/ct2/show/NCT05000632 . TRIAL REGISTRATION: NCT, NCT05000632. Registered 14 July 2021, there is not a separate registration number for the pilot.
RESUMO
Estradiol is essential for the development of female sex characteristics and fertility. Postmenopausal women and breast cancer patients have high levels of estradiol. Aromatase catalyzes estradiol synthesis; however, the factors regulating aromatase activity are unknown. We identified a new 22-kDa protein, aromatase interacting partner in breast (AIPB), from the endoplasmic reticulum of human breast tissue. AIPB expression is reduced in tumorigenic breast and further reduced in triple-negative tumors. Like that of aromatase, AIPB expression is induced by nonsteroidal estrogen. We found that AIPB and aromatase interact in nontumorigenic and tumorigenic breast tissues and cells. In tumorigenic cells, conditional AIPB overexpression decreased estradiol, and blocking AIPB availability with an AIPB-binding antibody increased estradiol. Estradiol synthesis is highly increased in AIPB knockdown cells, suggesting that the newly identified AIPB protein is important for aromatase activity and a key modulator of estradiol synthesis. Thus, a change in AIPB protein expression may represent an early event in tumorigenesis and be predictive of an increased risk of developing breast cancer.
Assuntos
Aromatase/metabolismo , Neoplasias da Mama/patologia , Mama/metabolismo , Estradiol/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Neoplasias/metabolismo , Sequência de Aminoácidos/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Retículo Endoplasmático/metabolismo , Feminino , Humanos , Células MCF-7 , Progesterona/biossíntese , Interferência de RNA , RNA Interferente Pequeno/genéticaRESUMO
After cholesterol is transported into the mitochondria of steroidogenic tissues, the first steroid, pregnenolone, is synthesized in adrenal and gonadal tissues to initiate steroid synthesis by catalyzing the conversion of pregnenolone to progesterone, which is mediated by the inner mitochondrial enzyme 3ß-hydroxysteroid dehydrogenase 2 (3ßHSD2). We report that the mitochondrial translocase Tom22 is essential for metabolic conversion, as its knockdown by small interfering RNA (siRNA) completely ablated progesterone conversion in both steroidogenic mouse Leydig MA-10 and human adrenal NCI cells. Tom22 forms a 500-kDa complex with mitochondrial proteins associated with 3ßHSD2. Although the absence of Tom22 did not inhibit mitochondrial import of cytochrome P450scc (cytochrome P450 side chain cleavage enzyme) and aldosterone synthase, it did inhibit 3ßHSD2 expression. Electron microscopy showed that Tom22 is localized at the outer mitochondrial membrane (OMM), while 3ßHSD2 is localized at the inner mitochondrial space (IMS), where it interacts through a specific region with Tom22 with its C-terminal amino acids and a small amino acid segment of Tom22 exposed to the IMS. Therefore, Tom22 is a critical regulator of steroidogenesis, and thus, it is essential for mammalian survival.