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1.
Sports Med ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900358

RESUMEN

BACKGROUND: 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). Two different systematic literature searches were conducted in PubMed, Scopus and Web of Science, retrieving 36 and 16 reports for humans and animal models, respectively. RESULTS: In humans, areal bone mineral density (aBMD) was similar between swimmers and non-athletic controls at the lumbar spine, hip and femoral neck. Swimmers' tibia diaphysis showed a higher cross-sectional area but lower cortical thickness. Inconsistent findings at the femoral neck cortical thickness were found. Due to the small number of studies, trabecular microarchitecture in human swimmers was not assessed. In rodent models, aBMD was found to be lower at the tibia, but similar at the femur. Inconsistent findings in femur diaphysis cross-sectional area were observed. No differences in femur and tibia trabecular microarchitecture were found. CONCLUSION: Swimming seems to affect bone health differently according to anatomical region. Studies in both humans and rodent models suggest that tibia cortical bone is negatively affected by swimming. There was no evidence of a negative effect of swimming on other bone regions, both in humans and animal models.

2.
JCI Insight ; 9(12)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38780544

RESUMEN

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. Whereas dual-energy x-ray absorptiometry measures of bone mineral density were unchanged after 10 days of fasting, high-resolution peripheral quantitative CT demonstrated remodeling of bone microarchitecture. Pathway analysis of longitudinal metabolomics data identified one-carbon metabolism as fasting dependent. In cultured osteoblasts, we tested the functional significance of one-carbon metabolites modulated by fasting, finding that methionine - which surged after 3 days of fasting - affected markers of osteoblast cell state in a concentration-dependent manner, in some instances exhibiting a U-shaped response with both low and high concentrations driving putative antibone responses. Administration of methionine to mice for 5 days recapitulated some fasting effects on bone, including a reduction in serum P1NP. In conclusion, a 10-day fast in humans led to remodeling of bone microarchitecture, potentially mediated by a surge in circulating methionine. These data support an emerging model that points to a window of optimal methionine exposure for bone health.


Asunto(s)
Densidad Ósea , Remodelación Ósea , Ayuno , Metionina , Metionina/metabolismo , Metionina/administración & dosificación , Animales , Humanos , Remodelación Ósea/efectos de los fármacos , Remodelación Ósea/fisiología , Ratones , Masculino , Femenino , Densidad Ósea/efectos de los fármacos , Osteoblastos/metabolismo , Procolágeno/metabolismo , Procolágeno/sangre , Persona de Mediana Edad , Adulto , Absorciometría de Fotón , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/sangre , Restricción Calórica
3.
Biol Open ; 13(2)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38288785

RESUMEN

Bone 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. Among the many initiatives supported by BMAS, there is the BMAS Summer School, inaugurated in 2021 and now at its second edition. The aim of the BMAS Summer School 2023 was to educate and train students by disseminating the latest advancement on BMA. Moreover, Summer School 2023 provided suggestions on how to write grants, deal with negative results in science, and start a laboratory, along with illustrations of alternative paths to academia. The event was animated by constructive and interactive discussions between early-career researchers and more senior scientists. In this report, we highlight key moments and lessons learned from the event.


Asunto(s)
Adiposidad , Médula Ósea , Humanos , Tejido Adiposo , Instituciones Académicas
4.
Psychoneuroendocrinology ; 157: 106365, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37573628

RESUMEN

Famine 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. We review the time-course of these adaptations by describing studies involving the short-term fasting of healthy individuals as well as studies describing the hormonal changes in states of chronic undernutrition, using individuals with anorexia nervosa as a model of chronic starvation. Lastly, we review representative clinical effects of chronic undernutrition.


Asunto(s)
Anorexia Nerviosa , Hormona de Crecimiento Humana , Hipogonadismo , Desnutrición , Humanos , Sistemas Neurosecretores
5.
bioRxiv ; 2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-37205600

RESUMEN

While 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. Pathway analysis implicated ~12h rhythms in RNA and protein metabolism, with strong homology to the circatidal gene programs previously identified in Cnidarian marine species. We further observed ~12h rhythms of intron retention events of genes involved in MHC class I antigen presentation, synchronized to expression of mRNA splicing genes in all three participants. Gene regulatory network inference revealed XBP1, and GABP and KLF transcription factor family members as potential transcriptional regulators of human ~12h rhythms. These results suggest that human ~12h biological rhythms have a primordial evolutionary origin with important implications for human health and disease.

6.
Biomedicines ; 12(1)2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38255142

RESUMEN

Considering the conflicting evidence regarding the potential long-term detrimental effect of swimming during growth on femur quality and fracture risk, our aim was to investigate the effect of eight months of swimming on femur quality. Twenty male eight-week-old Wistar rats were assigned into a swimming (SW; n = 10; 2 h/day, 5 days/week) or active control group (CG; n = 10, housed with running wheel) for eight months. Plasma osteocalcin and C-terminal telopeptide of type I collagen concentrations (ELISA) were assessed at baseline, four, and eight months of protocol. Femur structure (micro-computed tomography), biomechanical properties (three-point bending), and cellular density (histology) were determined after the protocol. SW displayed a lower uncoupling index, suggesting higher bone resorption, lower empty lacunae density, cortical and trabecular femur mass, femur length and cortical thickness, and higher cortical porosity than CG (p < 0.05). Although both biomarkers' concentrations decreased in both groups throughout the experiment (p < 0.001), there were no significant differences between groups (p > 0.05). No differences were also found regarding biomechanical properties, bone marrow adiposity, and osteocyte and osteoclast densities (p > 0.05). Long-term swimming was associated with unbalanced bone turnover and compromised femur growth, lower femur mass, and deteriorated cortical bone microarchitecture. However, femur trabecular microarchitecture and biomechanical properties were not affected by swimming.

7.
Nutrients ; 14(14)2022 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-35889794

RESUMEN

Osteoporosis 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 (7.5 µg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 µg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.


Asunto(s)
Densidad Ósea , Osteoporosis , Alendronato/farmacología , Animales , Peso Corporal , Bovinos , Calostro/metabolismo , Suplementos Dietéticos , Femenino , Humanos , Osteoporosis/tratamiento farmacológico , Ovariectomía , Embarazo , Ratas , Ratas Sprague-Dawley
8.
Neoplasia ; 28: 100785, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35390742

RESUMEN

In multiple myeloma (MM), communication via Notch signaling in the tumor niche stimulates tumor progression and bone destruction. We previously showed that osteocytes activate Notch, increase Notch3 expression, and stimulate proliferation in MM cells. We show here that Notch3 inhibition in MM cells reduced MM proliferation, decreased Rankl expression, and abrogated the ability of MM cells to promote osteoclastogenesis. Further, Notch3 inhibition in MM cells partially prevented the Notch activation and increased proliferation induced by osteocytes, demonstrating that Notch3 mediates MM-osteocyte communication. Consistently, pro-proliferative and pro-osteoclastogenic pathways were upregulated in CD138+ cells from newly diagnosed MM patients with high vs. low NOTCH3 expression. These results show that NOTCH3 signaling in MM cells stimulates proliferation and increases their osteoclastogenic potential. In contrast, Notch2 inhibition did not alter MM cell proliferation or communication with osteocytes. Lastly, mice injected with Notch3 knock-down MM cells had a 50% decrease in tumor burden and a 50% reduction in osteolytic lesions than mice bearing control MM cells. Together, these findings identify Notch3 as a mediator of cell communication among MM cells and between MM cells and osteocytes in the MM tumor niche and warrant future studies to exploit Notch3 as a therapeutic target to treat MM.


Asunto(s)
Comunicación Celular , Mieloma Múltiple , Osteocitos , Osteólisis , Receptor Notch3 , Animales , Humanos , Ratones , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Osteocitos/metabolismo , Osteocitos/patología , Osteogénesis , Receptor Notch3/genética , Receptor Notch3/metabolismo , Transducción de Señal
9.
Int J Exerc Sci ; 15(2): 103-112, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36895796

RESUMEN

Caffeine 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 [n = 18; age: 22.1 ± 2.6 years; BMI: 26.9 ± 4.3 kg/m2; estimated maximal oxygen consumption (VO2max): 45.1 ± 8.3 ml·kg-1·min-1] participated in a repeated-measures, double-blind, placebo-controlled trial. During the experimental trials, participants were fitted with a heart rate monitor and a mouthpiece with a one-way nonrebreathing valve and then rested for 10 min during baseline HRV and expired gas assessments. Participants chewed either caffeine (~170mg) or placebo gum for 5 min. Following expectoration and a 5 min warmup, participants walked on a treadmill for 20 min at 60% of estimated VO2max and then rested for 30 min. HRV indices were calculated from 10 min measurements during baseline and post-exercise (post 1, 2, and 3). A main effect of treatment was found for standard deviation of RR intervals (SDNN), absolute power of low frequency band (LF), absolute power of high frequency band (HF), and the standard deviation perpendicular to the line-of-identity in Poincaré plot (SD1) (p < 0.05). Further, a trend for higher root mean square of successive RR interval differences (RMSSD) with caffeine was observed (p = 0.066). Post hoc t-tests revealed that post-exercise SDNN, LF, HF, and SD1 were higher with caffeine compared to placebo (p ≤ 0.012). Results demonstrated that low dose caffeine did not delay the recovery of HRV indices reflective of parasympathetic nervous system activity following an acute bout of moderate exercise.

10.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34638536

RESUMEN

Glucocorticoid-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. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0-700 µM). Colostrum co-treated with DEX was executed at 0.1-5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Calostro/metabolismo , Fármacos Neuroprotectores/farmacología , Osteoblastos/efectos de los fármacos , Osteoporosis/prevención & control , Animales , Apoptosis/fisiología , Caspasa 3/metabolismo , Bovinos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Dexametasona/farmacología , Femenino , Glucocorticoides , Glutatión/análisis , Inflamación/inducido químicamente , Ratones , Fármacos Neuroprotectores/metabolismo , Osteoblastos/fisiología , Osteoporosis/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Embarazo
11.
Nutrients ; 13(9)2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34578859

RESUMEN

Osteoporosis 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: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.


Asunto(s)
Calostro/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Animales , Densidad Ósea , Huesos/efectos de los fármacos , Huesos/metabolismo , Bovinos , Suplementos Dietéticos , Modelos Animales de Enfermedad , Femenino , Ovariectomía , Ratas , Ratas Wistar
12.
Arch Osteoporos ; 16(1): 141, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34561723

RESUMEN

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. PURPOSE: To determine whether risk factors normally associated with low bone mass in athletic populations (i.e. nutrition intake, energy expenditure and energy availability) are significant predictors of bone mass changes in vocational dance students. METHODS: The total of 101 vocational dancers (63 females, 12.8 ± 2.2 years; 38 males, 12.7 ± 2.2 years) and 115 age-matched controls (68 females, 13.0 ± 2.1 years; 47 males, 13.0 ± 1.8 years) were monitored for 3 consecutive years. Bone mass parameters were measured annually at impact sites (femoral neck, FN; lumber spine, LS) and non-impact site (forearm) using DXA. Nutrition (3-day record), energy expenditure (accelerometer), energy availability and IGF-1 serum concentration (immunoradiometric assays) were also assessed. RESULTS: Female and male vocational dancers had consistently reduced bone mass at all anatomical sites (p < 0.001) than controls. IGF-1 did not differ between male vocational dancers and controls, but female dancers showed it higher than controls. At baseline, calcium intake was significantly greater in female vocational dancers than controls (p < 0.05). Male vocational dancers' fat and carbohydrate intakes were significantly lower than matched controls (p < 0.001 and p < 0.05, respectively). Energy availability of both female and male vocational dancers was within the normal range. A significant group effect was found at the FN regarding energy intake (p < 0.05) in female dancers. No significant predictors were found to explain bone mass differences in males. CONCLUSION: Our 3-year study revealed that both female and male vocational dancers displayed lower bone mass compared to controls, at both impact and non-impact sites. The aetiology of these findings may be grounded on factors different than those usually considered in athletic populations.


Asunto(s)
Baile , Adolescente , Densidad Ósea , Niño , Metabolismo Energético , Femenino , Humanos , Estudios Longitudinales , Masculino , Estudiantes
13.
Cancer Res ; 81(19): 5102-5114, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34348968

RESUMEN

Systemic 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. In mice with established human or murine multiple myeloma, treatment with BT-GSI decreased tumor burden and prevented the progression of multiple myeloma-induced osteolytic disease by inhibiting bone resorption more effectively than unconjugated GSI at equimolar doses. These findings show that BT-GSI has dual anti-myeloma and anti-resorptive properties, supporting the therapeutic approach of bone-targeted Notch inhibition for the treatment of multiple myeloma and associated bone disease. SIGNIFICANCE: Development of a bone-targeted Notch inhibitor reduces multiple myeloma growth and mitigates cancer-induced bone destruction without inducing the gastrointestinal toxicity typically associated with inhibition of Notch.


Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Huesos/metabolismo , Huesos/patología , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Receptores Notch/antagonistas & inhibidores , Animales , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/farmacología , Línea Celular Tumoral , Ácido Clodrónico/análogos & derivados , Ácido Clodrónico/química , Ácido Clodrónico/farmacología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Ratones , Mieloma Múltiple/etiología , Osteólisis , Transducción de Señal/efectos de los fármacos , Microtomografía por Rayos X , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Artículo en Inglés | MEDLINE | ID: mdl-34200783

RESUMEN

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. Continuous core body temperature, mean skin temperature, heart rate, and labor productivity were collected from the beginning to the end of all work-shifts. RESULTS: In workplaces where self-pacing is not feasible or very limited, we found that occupational heat stress is associated with the heat strain experienced by workers. Strategies focusing on hydration, work-rest cycles, and ventilated clothing were able to mitigate the physiological heat strain experienced by workers. Increasing mechanization enhanced labor productivity without increasing workers' physiological strain. CONCLUSIONS: Empowering laborers to self-pace is the basis of heat mitigation, while tailored strategies focusing on hydration, work-rest cycles, ventilated garments, and mechanization can further reduce the physiological heat strain experienced by workers under certain conditions.


Asunto(s)
Trastornos de Estrés por Calor , Enfermedades Profesionales , Exposición Profesional , Chipre , Grecia , Trastornos de Estrés por Calor/epidemiología , Trastornos de Estrés por Calor/etiología , Trastornos de Estrés por Calor/prevención & control , Respuesta al Choque Térmico , Calor , Humanos , Qatar , España
15.
Cancer Res ; 81(3): 713-723, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33288657

RESUMEN

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. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI (acute kidney injury, AKI) in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease. SIGNIFICANCE: These results reveal and highlight an unexpected role of APE2 via its interaction with MYH9 and suggest that APE2 has the potential to prevent acute kidney injury in patients with cisplatin-treated cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/3/713/F1.large.jpg.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Endonucleasas/metabolismo , Túbulos Renales Proximales/efectos de los fármacos , Enzimas Multifuncionales/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Lesión Renal Aguda/prevención & control , Animales , Carboplatino/efectos adversos , Daño del ADN , ADN Mitocondrial/efectos de los fármacos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/efectos de los fármacos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Endonucleasas/efectos de los fármacos , Endonucleasas/genética , Pérdida Auditiva Sensorineural/inducido químicamente , Humanos , Túbulos Renales Proximales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , Enzimas Multifuncionales/efectos de los fármacos , Enzimas Multifuncionales/genética , Mutación , Cadenas Pesadas de Miosina/genética , Nefritis/inducido químicamente , Oxaliplatino/efectos adversos , Fenotipo , Trombocitopenia/inducido químicamente , Regulación hacia Arriba/efectos de los fármacos
16.
Arch Osteoporos ; 14(1): 46, 2019 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-30968227

RESUMEN

Less is known on bone mass gains in dancers involved in vocational dance training. The present study found that, as young vocational dancers progress on their professional training, their bone health remains consistently lower compared to non-exercising controls. Endocrine mechanisms do not seem to explain these findings. PURPOSE: Little is known on bone mass development in dancers involved in vocational training. The aim of the present study was to model bone mineral content (BMC) accruals and to determine whether circulating levels of oestrogens, growth hormone (GH), and insulin-like growth factor I (IGF-1) explain differences in bone mass gains between vocational dance students and matched controls. METHODS: The total of 67 vocational female dancers (VFDs) and 68 aged-matched controls (12.1 ± 1.9 years and 12.7 ± 2.0 years at baseline, respectively) were followed for two consecutive years (34 VFD and 31 controls remained in the study for the full duration). BMC was evaluated annually at impact [femoral neck (FN); lumbar spine (LS)] and non-impact sites (forearm) using DXA. Anthropometry, age at menarche (questionnaire), and hormone serum concentrations (immunoradiometric assays) were also assessed for the same period. RESULTS: VFD demonstrated consistently reduced body weight (p < 0.001) and BMC at all three anatomical sites (p < 0.001) compared to controls throughout the study period. Menarche, body weight, GH, and IGF-1 were significantly associated with bone mass changes over time (p < 0.05) but did not explain group differences in BMC gains at impact sites (p > 0.05). However, body weight did explain the differences between groups in terms of BMC gains at the forearm (non-impact site). CONCLUSION: Two consecutive years of vocational dance training revealed that young female dancers demonstrate consistently lower bone mass compared to controls at both impact and non-impact sites. The studied endocrine parameters do not seem to explain group differences in terms of bone mass gains at impact sites.


Asunto(s)
Densidad Ósea/fisiología , Baile/fisiología , Estrógenos/sangre , Hormona del Crecimiento/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Absorciometría de Fotón , Adolescente , Antropometría , Peso Corporal , Niño , Femenino , Cuello Femoral/fisiopatología , Antebrazo/fisiopatología , Humanos , Vértebras Lumbares/fisiopatología , Menarquia
17.
J Sports Sci ; 37(1): 82-89, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29912627

RESUMEN

Given 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. A 3D-DXA software was used to analyse trabecular and cortical bone. Anthropometry, maturation (Tanner staging), menstrual parameters (age at menarche and primary amenorrhea), energy availability and nutritional analysis (3-day record) were also assessed.Compared to non-exercising participants, dancers exhibited significantly higher volumetric density for integral, cortical and trabecular bone, and thicker cortex at the femur. Ballet dancers demonstrated lower body weight compared to controls (p < 0.01). Female dancers had their menarche later than controls, and the prevalence of primary amenorrhea were significantly higher in dancers than controls (p < 0.01). Dancer's energy availability was below the normal range (<30 kcal/kgFFM/day). Despite the presence of certain osteoporosis risk factors such as low energy availability, primary amenorrhoea and lower body weight, professional ballet dancers revealed higher bone density for both cortical and trabecular bone compartments compared to controls.


Asunto(s)
Absorciometría de Fotón , Densidad Ósea/fisiología , Hueso Esponjoso/anatomía & histología , Hueso Esponjoso/diagnóstico por imagen , Hueso Cortical/anatomía & histología , Hueso Cortical/diagnóstico por imagen , Baile/fisiología , Adulto , Amenorrea , Antropometría , Peso Corporal , Estudios de Casos y Controles , Dieta , Metabolismo Energético , Femenino , Fémur/anatomía & histología , Fémur/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Masculino , Menstruación , Persona de Mediana Edad , Osteoporosis , Factores de Riesgo , Maduración Sexual
18.
J Toxicol Environ Health A ; 80(13-15): 797-804, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28696896

RESUMEN

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. The alkaline version of the comet assay was the method selected to measure both basal DNA damage and oxidative stress, since this method quantifies both endpoints. In order to measure oxidative stress, the comet assay was coupled with a lesion-specific endonuclease (formamidopyrimidine glycosylase) to detect oxidized purines. The levels of oxidative DNA damage in dancers were significantly increased after the dancing season. Pre-season levels of oxidative DNA damage were lower in dancers than those obtained from the general population, suggesting an adaptation of antioxidant system in dancers. Results of the present biomonitoring study indicate the need for more effective measures to protect ballet dancers from potentially occupational health risks related to regular intensive physical exercise.


Asunto(s)
Daño del ADN , Baile , Adulto , Estudios de Casos y Controles , Ensayo Cometa , Daño del ADN/fisiología , Baile/fisiología , Baile/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Estrés Oxidativo , Adulto Joven
19.
PLoS One ; 12(7): e0180639, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28678833

RESUMEN

BACKGROUND: 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. METHODS: 34 female selected for professional dance training (10.9yrs ±0.7) and 30 controls (11.1yrs ±0.5) were examined. Anthropometry, pubertal development (Tanner) and dietary data (3-day food diary) were recorded. BMD and bone mineral content (BMC) at forearm, femur neck (FN) and lumbar spine (LS) were assessed using Dual-Energy X-Ray Absorptiometry. Volumetric densities were estimated by calculating bone mineral apparent density (BMAD). RESULTS: Dancers were mainly at Tanner pubertal stage I (vs. stage IV in controls, p<0.001), and demonstrated significantly lower body weight (p<0.001) and height (p<0.01) than controls. Calorie intake was not different between groups, but calcium intake was significantly greater in dancers (p<0.05). Dancers revealed a significantly lower BMC and BMD values at all anatomical sites (p<0.001), and significantly lower BMAD values at the LS and FN (p<0.001). When adjusted for covariates (body weight, height, pubertal development and calcium intake), dance students continued to display a significantly lower BMD and BMAD at the FN (p<0.05; p<0.001) at the forearm (p<0.01). CONCLUSION: Before undergoing professional dance training, first year vocational dance students demonstrated inferior bone mass compared to controls. Longitudinal models are required to assess how bone health-status changes with time throughout professional training.


Asunto(s)
Densidad Ósea , Baile , Niño , Estudios Transversales , Femenino , Humanos
20.
Sports Med ; 45(2): 257-68, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25281333

RESUMEN

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". A total of 257 abstracts were screened using selected inclusion (studies involving bone measurements in dancers) and exclusion (editorials, opinion papers, chapters in books, narrative reviews and non-English language papers) criteria according to PRISMA guidelines. Following the above screening, a total of 108 abstracts were identified as potentially relevant. After the exclusion of conference proceedings, review papers, studies focusing only in male dancers and studies in which dancers' information were combined with other athletes, the eligible papers were subsequently assessed using the GRADE system and grouped according to: (1) prevalence of low BMD and associated factors, (2) incidence of low BMD and risk factors, (3) prevention/treatment of low BMD in dancers, and (4) other studies. RESULTS: Of the 257 abstracts that were initially screened, only 35 studies were finally considered. Only one of these 35 was of high quality, while the remaining 34 were of relatively low quality. Seven studies reported prevalence of low BMD and associated factors, 10 reported associated factors with no prevalence data, while one reported prevalence with no associated factors data. One study cited risk factors, while another one elaborated on the treatment of low BMD in dancers. The remaining 15 studies were classified as "other studies". CONCLUSIONS: It remains unclear whether low BMD is prevalent in female dancers. The present review highlights the need for high-quality BMD research in this area.


Asunto(s)
Densidad Ósea/fisiología , Baile/fisiología , Índice de Masa Corporal , Femenino , Humanos , Incidencia , Osteoporosis/epidemiología , Prevalencia , Factores de Riesgo
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