Estrogen deficiency and low-calcium diet increased bone loss and urinary calcium excretion but did not alter arterial stiffness in young female rats

Many epidemiological studies have reported that the severity of arterial diseases such as arterial calcification and stiffness is inversely related to bone loss, i.e., osteoporosis. However, the nature of this relationship is unclear. The purpose of the present study was to examine the influences of estrogen deficiency and/or low-calcium diet (0.1% Ca) on bone metabolism and calcium balance, as well as aortic wall composition and stiffness in young female rats. Twenty-eight 6-week-old female rats were randomized into four groups: OVX-Low calcium (OL) and OVX-Normal calcium groups (ON) were ovariectomized, and Sham-Low calcium (SL) and Sham-Normal calcium groups (SN) were sham-operated. After 12 weeks, the bone mineral density of the lumbar spine and tibial proximal metaphysis were significantly lower in ON than in SN, and also significantly lower in OL than in ON. Additionally, OL rats had significant higher (vs. SN and SL) urinary deoxypyridinoline, but not urinary calcium, excretion at 4 weeks after ovariectomy. However, at 12 weeks after ovariectomy, urinary calcium excretion was significantly higher in OL than in SL, with corresponding increases in two bone turnover markers, bone-type alkaline phosphatase and tartrate-resistant acid phosphatase. Neither estrogen deficiency nor low-calcium diet affected aortic stiffness or elastin degeneration and calcium deposition over the course of the present study, although changes of bone metabolism occurred rapidly. Taken together, these results show that bone loss and arterial stiffness did not progress simultaneously in the present experimental protocol

Tumor size and proliferative marker geminin levels associated with SUVmax levels on PET for breast cancers

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67- high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53

Molecular identification of 1-Cys peroxiredoxin and anthocyanidin/flavonol 3-O-galactosyltransferase from proanthocyanidin-rich young fruits of persimmon (Diospyros kaki Thunb.)

Fruits of persimmon (Diospyros kaki Thunb.) accumulate large amounts of proanthocyanidins (PAs) in the early stages of development. Astringent (A)-type fruits remain rich in soluble PAs even after they reach full-mature stage, whereas non-astringent (NA)-type fruits lose these compounds before full maturation. As a first step to elucidate the mechanism of PA accumulation in this non-model species, we used suppression subtractive hybridization to identify transcripts accumulating differently in young fruits of A- and NA-type. Interestingly, only a few clones involved in PA biosynthesis were identified in A–NA libraries. Represented by multiple clones were those encoding a novel 1-Cys peroxiredoxin and a new member of family 1 glycosyltransferases. Quantitative RT-PCR analyses confirmed correlation of the amount of PAs and accumulation of transcripts encoding these proteins in young persimmon fruits. Furthermore, the new family 1 glycosyltransferase was produced in Escherichia coli and shown to efficiently catalyze galactosylation at 3-hydroxyl groups of several anthocyanidins and flavonols. These findings suggest a complex mechanism of PA accumulation in persimmon fruits

Tumor size and proliferative marker geminin rather than Ki67 expression levels significantly associated with maximum uptake of 18F-deoxyglucose levels on positron emission tomography for breast cancers.

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67-high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53

Multiple ETS family proteins regulate PF4 gene expression by binding to the same ETS binding site.

In previous studies on the mechanism underlying megakaryocyte-specific gene expression, several ETS motifs were found in each megakaryocyte-specific gene promoter. Although these studies suggested that several ETS family proteins regulate megakaryocyte-specific gene expression, only a few ETS family proteins have been identified. Platelet factor 4 (PF4) is a megakaryocyte-specific gene and its promoter includes multiple ETS motifs. We had previously shown that ETS-1 binds to an ETS motif in the PF4 promoter. However, the functions of the other ETS motifs are still unclear. The goal of this study was to investigate a novel functional ETS motif in the PF4 promoter and identify proteins binding to the motif. In electrophoretic mobility shift assays and a chromatin immunoprecipitation assay, FLI-1, ELF-1, and GABP bound to the -51 ETS site. Expression of FLI-1, ELF-1, and GABP activated the PF4 promoter in HepG2 cells. Mutation of a -51 ETS site attenuated FLI-1-, ELF-1-, and GABP-mediated transactivation of the promoter. siRNA analysis demonstrated that FLI-1, ELF-1, and GABP regulate PF4 gene expression in HEL cells. Among these three proteins, only FLI-1 synergistically activated the promoter with GATA-1. In addition, only FLI-1 expression was increased during megakaryocytic differentiation. Finally, the importance of the -51 ETS site for the activation of the PF4 promoter during physiological megakaryocytic differentiation was confirmed by a novel reporter gene assay using in vitro ES cell differentiation system. Together, these data suggest that FLI-1, ELF-1, and GABP regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors

Adolescent Health Promotion Interventions Using Well-Care Visits and a Smartphone Cognitive Behavioral Therapy App: Randomized Controlled Trial

BackgroundAdolescent health promotion is important in preventing risk behaviors and improving mental health. Health promotion during adolescence has been shown to contribute to the prevention of late onset of the mental health disease. However, scalable interventions have not been established yet. ObjectiveThis study was designed to test the efficacy of two adolescent health promotion interventions: a well-care visit (WCV) with a risk assessment interview and counseling and self-monitoring with a smartphone cognitive behavioral therapy (CBT) app. Our hypothesis was that participants who had received both WCV and the CBT app would have better outcomes than those who had received only WCV or those who had not received any intervention. We conducted a prospective multi-institutional randomized controlled trial. MethodsParticipants were 217 adolescents aged 13-18 years. They were randomly divided into two intervention groups (WCV group and WCV with CBT app group) and a nonintervention group. WCV comprised a standardized physical examination along with a structured interview and counseling for youth risk assessment, which was designed with reference to the Guideline for Health Supervision of Adolescents of Bright Futures. A smartphone-based CBT program was developed based on the CBT approach. The CBT app comprised a 1-week psychoeducation component and a 1-week self-monitoring component. During the CBT program, participants created several self-monitoring sheets based on the CBT model with five window panels: event, thoughts, feelings, body response, and actions. The primary outcome was the change in scores for depressive symptoms. Secondary outcomes included changes in scores for self-esteem, quality of life, self-monitoring, and an adolescent health promotion scale. These outcomes were evaluated at baseline and at 1, 2, and 4 months after baseline. The exploratory outcome was the presence of suicidal ideation during the observation period. Intervention effects were estimated using mixed effect models. ResultsIn total, 94% (204/217) of the participants completed the 4-month evaluation. Both intervention groups showed a significant effect in the form of reduced scores for depressive symptoms at 1 month in high school students; however, these effects were not observed at 2 and 4 months. The intervention effect was significantly more predominant in those scoring above cutoff for depressive symptoms. There was significantly less suicidal ideation in the intervention groups. As for secondary outcomes, there was significant increase in health promotion scale scores at the 4-month follow-up among junior high school students in the WCV group. Moreover, the CBT app was significantly effective in terms of obtaining self-monitoring skills and reducing depressive symptoms. ConclusionsAlthough adolescent health promotion interventions may have short-term benefits, the frequency of WCV and further revision of the CBT app should be considered to evaluate long-term effectiveness. Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry UMIN 000036343; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R00004124

Comparison of SUVmax levels after combination of tumor size and geminin levels.

<p>SUVmax levels for groups with tumor size ≤2cm and geminin-low (G-L), ≤2cm and geminin-high (G-H), >2cm and geminin-low (G-L) and >2cm and geminin-high (G-H). Boxes represent median values and upper and lower quartiles.</p

SUVmax levels according to tumor size and geminin expression levels.

<p>SUVmax levels according to tumor size and geminin expression levels.</p