Mechanisms underpinning signals from genome wide association studies remain poorly understood, particularly for non-coding variation and for complex diseases such as type 2 diabetes mellitus (T2D) where pathogenic mechanisms in multiple different tissues may be disease driving. One approach is to study relevant endophenotypes, a strategy we applied to the UBE2E2 locus where non-coding SNVs are associated with both T2D and visceral adiposity (a pathologic endophenotype). We integrated CRISPR targeting of SNV-containing regions and unbiased CRISPRi screening to establish candidate cis-regulatory regions, complemented by genetic loss of function in murine diet-induced obesity or ex vivo adipogenesis assays.
View Article and Find Full Text PDFMice and many marine organisms exhibit ~12-h ultradian rhythms, however, direct evidence of ~12-h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells from three healthy humans. All three participants independently exhibited robust ~12-h transcriptional rhythms in molecular programs involved in RNA and protein metabolism, with strong homology to circatidal gene programs previously identified in Cnidarian marine species.
View Article and Find Full Text PDFBackground: The effect of swimming on bone health remains unclear, namely due to discrepant findings between studies in humans and animal models.
Objective: The aim of this systematic review and meta-analysis is to identify the available evidence on the effects of swimming on bone mass, geometry and microarchitecture at the lumbar spine, femur and tibia in both humans and rodent animal models.
Methods: The study followed PRISMA guidelines and was registered at PROSPERO (CRD4202236347 and CRD42022363714 for human and animal studies).
Caloric restriction improves metabolic health but is often complicated by bone loss. We studied bone parameters in humans during a 10-day fast and identified candidate metabolic regulators of bone turnover. Pro-collagen 1 intact N-terminal pro-peptide (P1NP), a bone formation marker, decreased within 3 days of fasting.
View Article and Find Full Text PDFBone marrow adiposity (BMA) is a rapidly growing yet very young research field that is receiving worldwide attention based on its intimate relationship with skeletal and metabolic diseases, as well as hematology and cancer. Moreover, increasing numbers of young scientists and students are currently and actively working on BMA within their research projects. These developments led to the foundation of the International Bone Marrow Adiposity Society (BMAS), with the goal to promote BMA knowledge worldwide, and to train new generations of researchers interested in studying this field.
View Article and Find Full Text PDFFamine and starvation have punctuated the evolutionary past of the human species. As such, we have developed hormonal responses to undernutrition that minimize energy expenditure on processes that are not critical for the survival of the individual, such as reproduction. In this review, we discuss neuroendocrine adaptations to starvation including hypogonadotropic hypogonadism, growth hormone resistance, hypercortisolemia, and the downregulation of the hypothalamic-pituitary-thyroid axis.
View Article and Find Full Text PDFWhile circadian rhythms are entrained to the once daily light-dark cycle of the sun, many marine organisms exhibit ~12h ultradian rhythms corresponding to the twice daily movement of the tides. Although human ancestors emerged from circatidal environment millions of years ago, direct evidence of ~12h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells and identified robust ~12h transcriptional rhythms from three healthy participants.
View Article and Find Full Text PDFOsteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.
View Article and Find Full Text PDFCaffeine may impact post-exercise heart rate variability (HRV); although, studies have yielded inconsistent findings. We examined the effects of low dose caffeine on post-exercise HRV. Healthy, college-aged adults [ = 18; age: 22.
View Article and Find Full Text PDFGlucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis.
View Article and Find Full Text PDFOsteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.
View Article and Find Full Text PDFUnlabelled: Three years of study showed that female and male vocational dancers displayed lower bone mass compared to controls, at forearm, lumbar spine and femoral neck. Energy intake was found to positively predict bone mass accruals only in female dancers at femoral neck. Vocational dancers can be a risk population to develop osteoporosis.
View Article and Find Full Text PDFSystemic inhibition of Notch with γ-secretase inhibitors (GSI) decreases multiple myeloma tumor growth, but the clinical use of GSI is limited due to its severe gastrointestinal toxicity. In this study, we generated a GSI Notch inhibitor specifically directed to the bone (BT-GSI). BT-GSI administration decreased Notch target gene expression in the bone marrow, but it did not alter Notch signaling in intestinal tissue or induce gut toxicity.
View Article and Find Full Text PDFInt J Environ Res Public Health
June 2021
Background: Occupational heat exposure can provoke health problems that increase the risk of certain diseases and affect workers' ability to maintain healthy and productive lives. This study investigates the effects of occupational heat stress on workers' physiological strain and labor productivity, as well as examining multiple interventions to mitigate the problem.
Methods: We monitored 518 full work-shifts obtained from 238 experienced and acclimatized individuals who work in key industrial sectors located in Cyprus, Greece, Qatar, and Spain.
Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice.
View Article and Find Full Text PDFGiven the lack of relevant data, the aim of this study was to examine femur cortical and trabecular bone in female and male professional ballet dancers. 40 professional ballet dancers and 40 sex- and age-matched non-exercising controls volunteered. Femoral bone density was scanned by dual-energy X-ray absorptiometry (DXA) scan.
View Article and Find Full Text PDFJ Toxicol Environ Health A
October 2017
Despite the numerous health benefits of physical activity, some studies reported that increased intensity and duration may induce oxidative stress in several cellular components including DNA. The aim of this study was to assess the level of basal DNA damage as well as oxidative DNA damage in a group of professional dancers before and after a 10-month dancing season. A group of individuals from general population was also assessed as a control.
View Article and Find Full Text PDFBackground: Professional dancers are at risk of developing low bone mineral density (BMD). However, whether low BMD phenotypes already exist in pre-vocational dance students is relatively unknown.
Aim: To cross-sectionally assess bone mass parameters in female dance students selected for professional dance training (first year vocational dance students) in relation to aged- and sex-matched controls.
Background And Objective: While some authors report that dancers have reduced bone mineral density (BMD) and increased risk of osteoporosis, others have stressed the positive effects of dance training on developing healthy BMD. Given the existing controversy, the aim of this systematic review was to examine the best evidence-based information available in relation to female dancers.
Methods: Four databases (Web of Science, PubMed, EBSCO, Scopus) and two dance science journals (Journal of Dance Medicine and Science and Medical Problems of Performing Artists) were searched for relevant material using the keywords "dance", "ballet", "BMD", "bone density", "osteoporosis" and "female athlete triad syndrome".