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Mouadh Mihoub, André Pichette, Balla Sylla, Charles Gauthier, Jean Legault
Betulin has a wide range of biological and pharmacological properties with its anticancer activity attracting most of the attention as it offers a possible alternative treatment to chemotherapy. However, betulin's in vivo biological effectiveness is limited by its poor solubility. As such, we synthesized polar glycosylated derivatives to increase its hydrosolubility and enhance its pharmacological properties. Among these synthesized compounds, 28-O-α-l-rhamnopyranosylbetulin 3β-O-α-l-rhamnopyranoside (Bi-L-RhamBet) was assessed for its cytotoxic effects against a suite of lung cancer cell lines...
2018: PloS One
Deepika Laddu, Neeta Parimi, Jane A Cauley, Peggy M Cawthon, Kristine E Ensrud, Eric Orwoll, Marcia Stefanick, Lisa Langsetmo
Background: The benefits of physical activity (PA) for health have primarily been evaluated during midlife. Whether patterns of change in late-life PA associate with overall and cause-specific mortality remains unclear. Methods: We examined the association between PA trajectories and subsequent mortality among 3,767 men aged ≥ 65 years. Men self-reported PA using the Physical Activity Scale for the Elderly scale (PASE) at up to 4 time points from 2000 through 2009 (Year 7); mortality was assessed over an average of 7...
February 26, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Claes Ohlsson, Maria Nethander, Magnus K Karlsson, Björn E Rosengren, Eva Ribom, Dan Mellström, Liesbeth Vandenput
The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. Many of the actions of DHEAS are considered to be mediated through metabolism into androgens and estrogens in peripheral target tissues. The predictive value of serum DHEA and DHEAS for the likelihood of falling is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEA and DHEAS levels and incident fall risk in a large cohort of older men...
March 12, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Flávia R G Carneiro, Alice Lepelley, John J Seeley, Matthew S Hayden, Sankar Ghosh
ECSIT is a mitochondrial complex I (CI)-associated protein that has been shown to regulate the production of mitochondrial reactive oxygen species (mROS) following engagement of Toll-like receptors (TLRs). We have generated an Ecsit conditional knockout (CKO) mouse strain to study the in vivo role of ECSIT. ECSIT deletion results in profound alteration of macrophage metabolism, leading to a striking shift to reliance on glycolysis, complete disruption of CI activity, and loss of the CI holoenzyme and multiple subassemblies...
March 6, 2018: Cell Reports
Yi Wen, Yi-Ran Liu, Tao-Tao Tang, Ming-Ming Pan, Sheng-Chun Xu, Kun-Ling Ma, Lin-Li Lv, Hong Liu, Bi-Cheng Liu
Ischemia/reperfusion (I/R) is a critical risk factor for acute kidney injury (AKI). Recent studies provided evidence that tubular epithelial cells (TEC)-associated inflammation aggravates kidney injury and impairs tissue repair after I/R injury. Here we demonstrated that the Nod-like receptor protein 3 (NLRP3) inflammasome is activated by mitochondrial reactive oxygen species (mROS) during I/R injury via direct interactions between the inflammasome and thioredoxin-interacting protein (TXNIP). Firstly, we found that NLRP3 inflammasome activation was induced by I/R injury, peaking at day 3 after reperfusion...
February 22, 2018: International Journal of Biochemistry & Cell Biology
T S Rogers, S Harrison, S Judd, E S Orwoll, L M Marshall, J Shannon, L Langsetmo, N E Lane, J M Shikany
Studying dietary patterns is often more informative than individual nutrients or foods. We found that a Prudent dietary pattern (rich in vegetables and fish) was associated with reduced loss of total hip BMD in older men. A Prudent dietary pattern may be a potential lifestyle strategy for minimizing bone loss. INTRODUCTION: This study aimed to identify baseline dietary patterns using factor analysis in a cohort of older men and to evaluate whether the dietary patterns were associated with bone mineral density change (%ΔBMD) at the total hip and femoral neck over time...
February 15, 2018: Osteoporosis International
Eric S Orwoll, Jack Wiedrick, Jon Jacobs, Erin S Baker, Paul Piehowski, Vladislav Petyuk, Yuqian Gao, Tujin Shi, Richard D Smith, Douglas C Bauer, Steven R Cummings, Carrie M Nielson, Jodi Lapidus
The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high-throughput proteomics approach to identify serum peptides and proteins associated with 5-year mortality in community-dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: MrOS). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography-ion mobility-mass spectrometry, and incident mortality in the subsequent 5 years was ascertained by tri-annual questionnaire...
February 5, 2018: Aging Cell
Gregory J Tranah, Kristine Yaffe, Caroline M Nievergelt, Neeta Parimi, M Maria Glymour, Kristine E Ensrud, Jane A Cauley, Sonia Ancoli-Israel, Sara Mariani, Susan Redline, Katie L Stone
Slow wave (or stage N3) sleep has been linked to a variety of cognitive processes. However, the role of stage N3 in the elderly is debated. The link between stage N3 and episodic memory may be weakened or changed in the older adult population, possibly due to several altered mechanisms impacting the cellular structure of the brain. The bases for the age-related dissociation between stage N3 and cognition are not understood. Since APOEε4 status is the strongest genetic risk factor for cognitive decline, we assessed whether the ε4 allele is associated with stage N3 sleep...
2018: PloS One
Paul J Collini, Martin A Bewley, Mohamed Mohasin, Helen M Marriott, Robert F Miller, Anna-Maria Geretti, Apostolos Beloukas, Athanasios Papadimitropoulos, Robert C Read, Mahdad Noursadeghi, David H Dockrell
Rationale People living with HIV (PLWH) are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined. Objectives We hypothesized apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed. Methods Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from healthy donors or HIV-1-seropositive donors on long-term ART with undetectable plasma viral load...
January 24, 2018: American Journal of Respiratory and Critical Care Medicine
N C Wright, E R Hooker, C M Nielson, K E Ensrud, S L Harrison, E S Orwoll, E Barrett-Connor
There is limited wrist fracture information on men. Our goal was to calculate frequency and identify risk factors for wrist fracture in the Osteoporotic Fractures in Men (MrOS) study. We confirmed that fracture history and certain medications are predictors, and identified novel predictors including markers of kidney function and physical performance. INTRODUCTION: To calculate the incidence of wrist fractures and their risk factors in older community-dwelling men from the US Osteoporotic Fractures in Men (MrOS) study...
January 17, 2018: Osteoporosis International
Jianping Sun, Karim Oualkacha, Vincenzo Forgetta, Hou-Feng Zheng, J Brent Richards, Daniel S Evans, Eric Orwoll, Celia M T Greenwood
Performance of a recently developed test for association between multivariate phenotypes and sets of genetic variants (MURAT) is demonstrated using measures of bone mineral density (BMD). By combining individual-level whole genome sequenced data from the UK10K study, and imputed genome-wide genetic data on individuals from the Study of Osteoporotic Fractures (SOF) and the Osteoporotic Fractures in Men Study (MrOS), a data set of 8810 individuals was assembled; tests of association were performed between autosomal gene-sets of genetic variants and BMD measured at lumbar spine and femoral neck...
January 9, 2018: Scientific Reports
Małgorzata Wojtkowska, Dorota Buczek, Yutaka Suzuki, Victoria Shabardina, Wojciech Makałowski, Hanna Kmita
BACKGROUND: The existence of mitochondria-related organelles (MROs) is proposed for eukaryotic organisms. The Amoebozoa includes some organisms that are known to have mitosomes but also organisms that have aerobic mitochondria. However, the mitochondrial protein apparatus of this supergroup remains largely unsampled, except for the mitochondrial outer membrane import complexes studied recently. Therefore, in this study we investigated the mitochondrial inner membrane and intermembrane space complexes, using the available genome and transcriptome sequences...
December 29, 2017: BMC Genomics
B Rita Alevriadou, Santhanam Shanmughapriya, Akshar Patel, Peter B Stathopulos, Muniswamy Madesh
Calcium (Ca2+ ) transport by mitochondria is an important component of the cell Ca2+ homeostasis machinery in metazoans. Ca2+ uptake by mitochondria is a major determinant of bioenergetics and cell fate. Mitochondrial Ca2+ uptake occurs via the mitochondrial Ca2+ uniporter (MCU) complex, an inner mitochondrial membrane protein assembly consisting of the MCU Ca2+ channel, as its core component, and the MCU complex regulatory/auxiliary proteins. In this review, we summarize the current knowledge on the molecular nature of the MCU complex and its regulation by intra- and extramitochondrial levels of divalent ions and reactive oxygen species (ROS)...
December 2017: Journal of the Royal Society, Interface
Nicholas C Harvey, Anders Odén, Eric Orwoll, Jodi Lapidus, Timothy Kwok, Magnus K Karlsson, Björn E Rosengren, Östen Ljunggren, Cyrus Cooper, Eugene McCloskey, John A Kanis, Claes Ohlsson, Dan Mellström, Helena Johansson
Although prior falls are a well-established predictor of future fracture, there is currently limited evidence regarding the specific value of falls history in fracture risk assessment relative to that of other clinical risk factors and bone mineral density (BMD) measurement. We therefore investigated, across the three Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted future fracture independently of FRAX and whether these associations varied with age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong, and USA...
March 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Upasana Sah, Kajal Sharma, Nivedita Chaudhri, Muniappan Sankar, P Gopinath
Due to the excessive use of antibiotics over the years, the microorganisms have developed resistance to numerous drugs. The growth of multi-resistant organisms (MROs) heads due to the insufficient treatment with the currently available medications which present a great threat to the biotic component of the environment as well as to the food technology sectors. The goal of this research was to develop a nano-composite made up of single-walled carbon nanotubes (SWCNTs) and amine-functionalized porphyrin, which could further be used for the anti-microbial studies in presence of visible light showing photodynamic effect to inactivate cells...
February 1, 2018: Colloids and Surfaces. B, Biointerfaces
Tara S Rogers, Stephanie Harrison, Christine Swanson, Jane A Cauley, Elizabeth Barrett-Connor, Eric Orwoll, Katie L Stone, Nancy E Lane
Background: Disrupted rest-activity circadian rhythm (RAR) patterns have been associated with poor health outcomes (i.e. diminished cognitive function, increased risk of dementia and falls). Circadian time cues in bone influence the differentiation of osteoblasts and osteoclasts, and bone turnover markers exhibit circadian variation; relationships between bone outcomes and RAR are emerging areas of research. We evaluated associations between RAR and areal bone mineral density (aBMD) at the total hip and femoral neck in older men from the Osteoporotic Fractures in Men (MrOS) cohort...
December 2017: Bone Reports
L Yang, N Parimi, E S Orwoll, D M Black, J T Schousboe, R Eastell
Finite element model can estimate bone strength better than BMD. This study used such a model to determine its association with hip fracture risk and found that the strength estimate provided limited improvement over the hip BMDs in predicting femoral neck (FN) fracture risk only. INTRODUCTION: Bone fractures occur only when it is loaded beyond its ultimate strength. The goal of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of DXA scans, with incident hip fracture as a single condition or with femoral neck (FN) and trochanter (TR) fractures separately in older men...
November 22, 2017: Osteoporosis International
Meredith L Wallace, Katie Stone, Stephen F Smagula, Martica H Hall, Burcin Simsek, Deborah M Kado, Susan Redline, Tien N Vo, Daniel J Buysse
Study Objectives: Sleep is multidimensional, with domains including duration, timing, continuity, regularity, rhythmicity, quality, and sleepiness/alertness. Individual sleep characteristics representing these domains are known to predict health outcomes. However, most studies consider sleep characteristics in isolation, resulting in an incomplete understanding of which sleep characteristics are the strongest predictors of health outcomes. We applied three multivariable approaches to robustly determine which sleep characteristics increase mortality risk in the osteoporotic fractures in men sleep study...
January 1, 2018: Sleep
Peggy M Cawthon, Sheena Patel, Susan K Ewing, Li-Yung Lui, Jane A Cauley, Jennifer G Lyons, Lisa Fredman, Deborah M Kado, Andrew R Hoffman, Nancy E Lane, Kristine E Ensrud, Steven R Cummings, Eric S Orwoll
Low bone mineral density (BMD) is associated with increased mortality risk, yet the impact of BMD loss on mortality is relatively unknown. We hypothesized that greater BMD loss is associated with increased mortality risk in older men. Change in femoral neck BMD was assessed in 4400 Osteoporotic Fractures in Men (MrOS) study participants with two to three repeat dual-energy X-ray absorptiometry scans over an average of 4.6 ± 0.4 (mean ± SD) years. Change in femoral neck BMD was estimated using mixed effects models; men were grouped into three categories of BMD change: maintenance (n = 1087; change ≥ 0 g/cm(2)); expected loss (n = 2768; change between 0 g/cm(2) and <1 SD below mean change [>-0...
August 2017: JBMR Plus
Margaret L Gourlay, Victor S Ritter, Jason P Fine, Robert A Overman, John T Schousboe, Peggy M Cawthon, Eric S Orwoll, Tuan V Nguyen, Nancy E Lane, Steven R Cummings, Deborah M Kado, Jodi A Lapidus, Susan J Diem, Kristine E Ensrud
Owing to an oversight by the authors, the acknowledgments were incomplete.
November 7, 2017: Archives of Osteoporosis
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