AIMS Medical Science最新文献

Extravillous trophoblast (EVT) invasion is required for remodeling uterine tertiary arteries and placenta development during pregnancy. Compromised EVT invasion may contribute to the pathology of placenta-related diseases. Metastasis -associated protein 3 (MTA3) is one of the subunits of nucleosome remodeling and deacetylation (NuRD) complex that represses transcription in a histone deacetylase-dependent manner. MTA3 is reported to be down-regulated in preeclamptic placentas, suggesting its potential role in EVT invasion. Here, we investigate the role of MTA3 in EVT invasion by studying its molecular mechanisms in EVT cells. First, we confirmed MTA3 expression in the EVT cells in human placenta using immunohistochemistry. We then used lentivirus-mediated MTA3 short hairpin RNA (shRNA) to knock down MTA3 expression in EVT-derived HTR8/SVneo cells and found higher invasion capacity in MTA3 knockdown cells. Using quantitative real-time PCR, we showed higher expression of invasion-related genes matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and transcription factor Snail in MTA3 knockdown compared with control cells. Co-immunoprecipitation-Western blot assay showed the protein-protein interaction of histone deacetylase 1 (HDAC1), a subunit of NuRD, with MTA3 in HTR8/SVneo cells. Co-immunoprecipitation-Mass spectrometry assay further identified 71 proteins interacting with MTA3, including NuRD subunits, heterochromatin proteins, epigenetics modifiers and transcription factors. This result not only indicated the involvement of NuRD complex in MTA3's function, but also demonstrated the complicated multiple co-players in MTA3 and NuRD complex mediated transcription repression in EVT. In summary, our data demonstrates that MTA3 regulates EVT invasion and related gene expression via NuRD complex in EVT.

Background: Asthma is one of the leading causes of emergency department visits and school absenteeism among school-aged children in the United States, but there is significant local-area variation in emergency department visit rates, as well as significant differences across racial-ethnic groups.

Analysis: We first calculated emergency department (ED) visit rates among Medicaid-enrolled children age 5-12 with asthma using a multi-state dataset. We then performed exploratory factor analysis using over 226 variables to assess whether they clustered around three county-level conceptual factors (socioeconomic status, healthcare capacity, and air quality) thought to be associated with variation in asthma ED visit rates. Measured variables (including ED visit rate as the outcome of interest) were then standardized and tested in a simple conceptual model through confirmatory factor analysis.

Results: County-level (contextual) variables did cluster around factors declared a priori in the conceptual model. Structural equation models connecting the ED visit rates to socioeconomic status, air quality, and healthcare system professional capacity factors (consistent with our conceptual framework) converged on a solution and achieved a reasonable goodness of fit on confirmatory factor analysis.

Conclusion: Confirmatory factor analysis offers an approach for quantitatively testing conceptual models of local-area variation and racial disparities in asthma-related emergency department use.

Purpose: This study examined secondary benefits of an individualized physical activity intervention on improving dementia family caregivers' subjective burden, depressive symptoms and positive affect.

Design and methods: A community-based randomized controlled trial (RCT) was implemented with family caregivers of persons with dementia (N = 211) who received the Enhanced Physical Activity Intervention (EPAI: treatment intervention, n = 106) or the Caregiver Skill Building Intervention (CSBI: control intervention, n = 105). Interventions were delivered over 12 months, including a baseline home visit and regularly spaced telephone calls. Data were collected in person at baseline, 6 and 12-months; and telephonically at 3 and 9-months. The EPAI integrated physical activity and caregiving content while the CSBI focused only on caregiving content. Descriptive, bivariate and intention-to-treat analyses using generalized estimating equations (GEE) were performed to examine secondary benefits of the EPAI on family caregiver burden, depressive symptoms and positive affect.

Results: Compared to caregivers in the CSBI group, caregivers in the EPAI significantly increased their overall and total moderate physical activity and showed a positive interaction between the intervention and time for positive affect at both six (p = 0.01) and 12-months (p = 0.03). The EPAI was significantly associated with improving burden at 3 months (p = 0.03) but had no significant effect on depressive symptoms.

Implications: Caregiver involvement in an individualized physical activity intervention was associated with increased overall and total moderate physical activity and improved positive affect from baseline to 12 months. Improved positive affect may help caregivers to feel better about themselves and their situation, and better enable them to continue providing care for their family member for a longer time at lower risk to their own mental health.

More than 0.5 million new cases of head and neck cancer are diagnosed worldwide each year, and approximately 75% of them are treated with radiation alone or in combination with other cancer treatments. A majority of patients treated with radiotherapy develop significant oral off-target effects because of the unavoidable irradiation of normal tissues. Salivary glands that lie within treatment fields are often irreparably damaged and a decline in function manifests as dry mouth or xerostomia. Limited ability of the salivary glands to regenerate lost acinar cells makes radiation-induced loss of function a chronic problem that affects the quality of life of the patients well beyond the completion of radiotherapy. The restoration of saliva production after irradiation has been a daunting challenge, and this review provides an overview of promising gene therapeutics that either improve the gland's ability to survive radiation insult, or alternately, restore fluid flow after radiation. The salient features and shortcomings of each approach are discussed.

Targeted α-particle therapy (TAT), in which an α-particle emitting radionuclide is specifically directed to a biological target, is gaining more attention to treat cancers as new targets are validated. Bio-vectors such as monoclonal antibodies are able to selectively transport α-particles to destroy targeted cancer cells. TAT has the potential for an improved therapeutic ratio over β-particle targeted conjugate therapy. The short path length and the intense ionization path generated render α-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking. ²¹²Pb is the longer-lived parent radionuclide of ²¹²Bi and serves as an in vivo generator of ²¹²Bi. ²¹²Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of ²¹²Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of ²¹²Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of ²¹²Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer.