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Spirulina phycocyanin triggers differential protein term and apoptosis inside SKOV-3 cellular material.
ment employees and is in the public domain in the US.CONTEXT Congenital pituitary hormone deficiencies with syndromic phenotypes, and/or familial occurrence suggest genetic hypopituitarism; however, in many such patients the underlying molecular basis of the disease remains unknown. OBJECTIVE To describe patients with syndromic hypopituitarism due to biallelic loss-of-function variants in TBC1D32, a gene implicated in Sonic hedgehog (Shh) signaling. SETTING Referral center. PATIENTS A Finnish family of two siblings with panhypopituitarism, absent anterior pituitary, and mild craniofacial dysmorphism, and a Pakistani family with a proband with growth hormone deficiency, anterior pituitary hypoplasia, and developmental delay. INTERVENTIONS The patients were investigated by whole genome sequencing. Expression profiling of TBC1D32 in human fetal brain was performed through in situ hybridization. Stable and dynamic protein-protein interaction partners of TBC1D32 were investigated in HEK cells followed by mass spectrometry analyses. MAIN OUTCOME MEASURES Genetic and phenotypic features of patients with biallelic loss-of-function mutations in TBC1D32. RESULTS The Finnish patients harboured compound heterozygous loss-of-function variants (c.1165_1166dup p.(Gln390Phefs*32), and c.2151del p.(Lys717Asnfs*29)) in TBC1D32; the Pakistani proband carried a known pathogenic homozygous TBC1D32 splice-site variant c.1372+1G>A p.(Arg411_Gly458del), as did a fetus with cleft lip and partial intestinal malrotation from a terminated pregnancy within the same pedigree. TBC1D32 was expressed in the developing hypothalamus, Rathke's pouch and areas of the hindbrain. TBC1D32 interacted with proteins implicated in cilium assembly, Shh signaling, and brain development. CONCLUSIONS Biallelic TBC1D32 variants underlie syndromic hypopituitarism, and the underlying mechanism may be via disrupted Shh signaling. © Endocrine Society 2020.Bone loss in aging is linked with chronic low-grade inflammation and the accumulation of marrowfat in animals and humans. Peroxisome proliferator-activated receptor gamma (PPARγ), an adipogenic regulator, plays key roles in these biological processes. However, studies of the roles of PPARγ in age-related bone loss and inflammation are lacking. We hypothesized that deletion of PPARγ in bone marrow mesenchymal lineage cells would reduce bone loss with aging, potentially through a reduction in fat-generated inflammatory responses and an increase in osteoblastic activity. In the present study, we show that mice deficient of PPARγ in Dermo1-expressing mesenchymal lineage cells (Dermo1-CrePPARγfl/fl) have reduced fat mass and increased cortical bone thickness, but that deficiency of PPARγ had limited effect on protection of trabecular bone with aging as demonstrated by DXA, µ-CT, and histomorphometric analyses. Conditional knockout of PPARγ reduced serum concentrations of adipokines including adiponectin, resistin and leptin and reduced marrow stromal cell expression levels of inflammation-related genes. Inflammation genes involved in the interferon (IFN) signaling pathway were reduced the most. These results demonstrate that disruption of the master adipogenic regulator, PPARγ, has a certain protective effect on aging-induced bone loss, suggesting that regulation of adipose function and modulation of IFN signaling are among the key mechanisms by which PPARγ regulates bone homeostasis during aging process. find more © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail [email protected] The association between high selenium (Se) intake and metabolic disorders such as type 2 diabetes has raised great concern, but the underlying mechanism remains unclear. OBJECTIVE Through targeted metabolomics analysis, we examined the liver sugar and acylcarnitine metabolism responses to supranutritional selenomethionine (SeMet) supplementation in pigs. METHODS Thirty-six castrated male pigs (Duroc-Landrace-Yorkshire, 62.0 ± 3.3 kg) were fed SeMet adequate (Se-A, 0.25 mg Se/kg) or SeMet supranutritional (Se-S, 2.5 mg Se/kg) diets for 60 d. The Se concentration, biochemical, gene expression, enzyme activity, and energy-targeted metabolite profiles were analyzed. RESULTS The Se-S group had greater fasting serum concentrations of glucose (1.9-fold), insulin (1.4-fold), and free fatty acids (FFAs,1.3-fold) relative to the Se-A group (P less then 0.05). The liver total Se concentration was 4.2-fold that of the Se-A group in the Se-S group (P less then 0.05), but expression of most selenoprotein gensugar metabolism and elevation of lipid synthesis in pig livers. Our research provides novel insights into high SeMet intake-induced type 2 diabetes. Copyright © The Author(s) 2020.INTRODUCTION eScreening is a mobile health technology resource for veterans and staff to support Veterans Health Administration initiatives such as early identification of health problems, shared decision-making, and measurement-based care. METHODS We conducted an exploratory mixed methods retrospective study with newly enrolling post-9/11 veterans to (1) understand eScreening user experience and obtain practical feedback on the technology to guide improvements, (2) assess veteran satisfaction with eScreening following improvements to the technology, and (3) examine veteran characteristics associated with eScreening satisfaction. Focus group data were collected on user experience with eScreening from a sample of veterans who participated in an eScreening pilot. Guided by a user-centered design approach, findings informed improvements to the technology. Survey data were subsequently collected from a large cohort of veterans to assess satisfaction with the improved program. Questionnaire data were also collectey significant, though not clinically meaningful relationships between health-related characteristics and satisfaction with eScreening. However, millennials showed significantly higher satisfaction ratings compared with non-millennials. CONCLUSIONS These findings support the use of patient experiences and feedback to aide product development. In addition, post-9/11 veterans support the use of eScreening to assist health screening. However, evaluating the eScreening program in more diverse veteran groups and Veterans Affairs settings is needed to improve the generalizability of these findings to the larger veteran population. © Association of Military Surgeons of the United States 2020. All rights reserved. For permissions, please e-mail [email protected].
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