Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene

Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits. However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice. Remarkably, its ability to inhibit the growth of this aggressive form of cancer occurred with the mouse equivalent of a recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling. Additional studies investigating TNJ-induced tumor growth suppression and modified reproductive responses are needed to characterize its potential as a CAM therapy for women with and without HER2+ breast cancer

Mechanism of aortic medial matrix remodeling is distinct in patients with bicuspid aortic valve

ObjectivesPatients with bicuspid aortic valves (BAV) are predisposed to developing ascending thoracic aortic aneurysms (TAA) at an earlier age than patients who develop degenerative TAAs and have a tricuspid aortic valve (TAV). The hypothesis tested is that BAV-associated aortopathy is mediated by a mechanism of matrix remodeling that is distinct from that seen in TAAs of patients with tricuspid aortic valves.MethodsAortic specimens were collected during ascending aortic replacement, aortic valve replacement, and heart transplants from nonaneurysmal (NA) donors and recipients. Matrix architecture of the aortic media was assessed qualitatively using multiphoton microscopy followed by quantification of collagen and elastin fiber orientation. α-Elastin was determined and matrix maturity was assessed by quantifying immature and mature collagen and lysyl oxidase (Lox) expression and activity in aortic specimens. Matrix metalloproteinase-2/9 activity was quantified in aortic smooth muscle cells.ResultsElastin and collagen fibers were more highly aligned in BAV-NA and BAV-TAA cases than in TAV-TAA cases, whereas TAV-TAA cases were more disorganized than TAV-NA cases. α-Elastin content was unchanged. Immature collagen was reduced in BAV-NA and BAV-TAA cases when compared with TAV-NA and TAV-TAA cases. Mature collagen was elevated in TAV-TAA cases compared with TAV-NA and BAV-TAA cases. There was a trend toward elevated Lox gene expression and activity and matrix metalloproteinase-2/9 activity for TAV-TAA, BAV-NA, and BAV-TAA specimens.ConclusionsThe highly aligned matrix architecture in patients with BAVs indicates that wall remodeling is distinct from TAV-TAA. Altered matrix architecture and reduced collagen maturity suggest that the effector molecules mediating the remodeling of TAAs are different in BAV and TAV cases

Diabetes Mellitus is Associated with Poor Bone Microarchitecture in Older Adults Residing in Long-Term Care Facilities

Objectives. Both diabetes mellitus (DM) and osteoporosis are very common in older adults who reside in long-term care (LTC) facilities. Nevertheless, few studies have examined the relationship between diabetes and bone quality in this population. The purpose of this study is to determine if bone mineral density (BMD) or trabecular bone score (TBS) is a better measure of bone quality and skeletal health, in LTC residents with and without a history of DM. Methodology. In this longitudinal cohort study, we examined baseline BMD (lumbar spine, total hip, and femoral neck), TBS, DM, and functional status in 511 LTC residents who were enrolled in two ongoing randomized placebo-controlled osteoporosis clinical trials. Results. On average, participants were older than 80 years and majority were prefrail or frail. Women with DM had greater lumbar spine BMD (1.106 vs 1.017, adjusted difference ± standard error = 0.084 ± 0.023 g/cm2, p=0.0003) and femoral neck BMD (0.695 vs 0.651, 0.027 ± 0.013 g/cm2, p=0.0463), but lesser lumbar spine TBS (1.211 vs 1.266, −0.036 ± 0.016, p=0.0299) compared to women without DM. Total hip BMD was also higher based on descriptive statistics (0.780 vs 0.734, p=0.6255) in diabetic women, although the difference was not statistically significant. Men had similar but attenuated findings. Conclusions. Among LTC residents, those with DM have greater BMD but lower bone quality measured by TBS. TBS should be considered in assessing older patients with DM. However, further studies are required to confirm the findings with respect to fractures

Personal and Environmental Contributors to Sedentary Behavior of Older Adults in Independent and Assisted Living Facilities

Sedentary behavior is associated with negative health outcomes and unhealthy aging. Older adults are the most sedentary age group, and decreasing sitting time represents an intervention target for improving health. Determinants of sedentary behavior have been examined in older adults living in their own homes, yet less is known about sedentary behavior of older adults in residential care facilities. The purpose of this study was to explore factors contributing to sedentary behavior among residents of independent and assisted living facilities. We conducted eight focus groups with residents (n = 44) and semi-structured interviews with staff (n = 6) across four living facilities. Audio recordings were transcribed and analyzed using an iterative, inductive approach. Three salient themes were identified. Residents and staff both viewed sedentary behavior negatively unless it was in the context of social engagement. Additionally, fear of falling was discussed as a significant contributor to sedentary behavior. Finally, residents felt the community living environment contributed to their sedentary behavior while staff did not. Our findings provide valuable insight for designing targeted interventions for older adults in residential facilities and suggest thinking beyond the individual and considering environmental influences on sedentary behavior in the residential care setting

Accuracy of Objective Physical Activity Monitors in Measuring Steps in Older Adults

Objective: The aim of this study is to evaluate accuracy of research activity monitors in measuring steps in older adults with a range of walking abilities. Method: Participants completed an initial assessment of gait speed. The accuracy of each monitor to record 100 steps was assessed across two walking trials. Results: In all, 43 older adults (age 87 ± 5.7 years, 81.4% female) participated. Overall, the StepWatch had the highest accuracy (99.0% ± 1.5%), followed by the ActivPAL (93.7% ± 11.1%) and the Actigraph (51.4% ± 35.7%). The accuracy of the Actigraph and ActivPAL varied according to assistive device use, and the accuracy of all three monitors differed by gait speed category (all p < .05). StepWatch was highly accurate (⩾97.7) across all conditions. Discussion: The StepWatch and ActivPAL monitor were reasonably accurate in measuring steps in older adults who walk slowly and use an assistive device. The Actigraph significantly undercounted steps in those who walk slow or use an assistive device. Researchers should consider gait speed and the use of assistive devices when selecting an activity monitor

Co-administering melatonin with an estradiol-progesterone menopausal hormone therapy represses mammary cancer development in a mouse model of her2-positive breast cancer

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer. Individually, melatonin (MEL) and estradiol-progesterone therapy (EPT) did not significantly affect mammary cancer development through age 14 months, but, when combined, the melatonin-estradiol-progesterone therapy (MEPT) significantly repressed tumor formation. This repression was due to effects on tumor incidence, but not latency. These results demonstrate that melatonin and the HT cooperate to decrease the mammary cancer risk. Melatonin and EPT also cooperate to alter the balance of the progesterone receptor (PR) isoforms by significantly increasing PRA protein expression only in MEPT mammary glands. Melatonin significantly suppressed amphiregulin transcripts in MEL and MEPT mammary glands, suggesting that amphiregulin together with the higher PRA:PRB balance and other factors may contribute to reducing cancer development in MEPT mice. Melatonin supplementation influenced mammary morphology by increasing tertiary branching in the mouse mammary glands and differentiation in human mammary epithelial cell cultures. Uterine weight in the luteal phase was elevated after long-term exposure to EPT, but not toMEPT, indicating thatmelatonin supplementationmay reduce estrogen-induced uterine stimulation. Melatonin supplementation significantly decreased the incidence of grossly-detected lung metastases in MEL mice, suggesting that melatonin delays the formation of metastatic lesions and/or decreases aggressiveness in this model of HER2+ breast cancer. Mammary tumor development was similar in EPT and MEPT mice until age 8.6 months, but after 8.6 months, only MEPT continued to suppress cancer development. These data suggest that melatonin supplementation has a negligible effect in young MEPT mice, but is required in older mice to inhibit tumor formation. Sincemelatonin binding was significantly decreased in oldermammary glands, irrespective of treatment, melatonin supplementation may overcome reduced melatonin responsiveness in the agedMEPTmice. Sincemelatonin levels are known to decline near menopause, nocturnal melatonin supplementation may also be needed in aging women to cooperate with HT to decrease breast cancer risk

Co-administering Melatonin With an Estradiol-Progesterone Menopausal Hormone Therapy Represses Mammary Cancer Development in a Mouse Model of HER2-Positive Breast Cancer.

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer. Individually, melatonin (MEL) and estradiol-progesterone therapy (EPT) did not significantly affect mammary cancer development through age 14 months, but, when combined, the melatonin-estradiol-progesterone therapy (MEPT) significantly repressed tumor formation. This repression was due to effects on tumor incidence, but not latency. These results demonstrate that melatonin and the HT cooperate to decrease the mammary cancer risk. Melatonin and EPT also cooperate to alter the balance of the progesterone receptor (PR) isoforms by significantly increasing PRA protein expression only in MEPT mammary glands. Melatonin significantly suppressed amphiregulin transcripts in MEL and MEPT mammary glands, suggesting that amphiregulin together with the higher PRA:PRB balance and other factors may contribute to reducing cancer development in MEPT mice. Melatonin supplementation influenced mammary morphology by increasing tertiary branching in the mouse mammary glands and differentiation in human mammary epithelial cell cultures. Uterine weight in the luteal phase was elevated after long-term exposure to EPT, but not to MEPT, indicating that melatonin supplementation may reduce estrogen-induced uterine stimulation. Melatonin supplementation significantly decreased the incidence of grossly-detected lung metastases in MEL mice, suggesting that melatonin delays the formation of metastatic lesions and/or decreases aggressiveness in this model of HER