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PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle. RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3ß activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.
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MicroARNs , Músculo Esquelético , Osteoporosis , Sarcopenia , Humanos , MicroARNs/metabolismo , Sarcopenia/metabolismo , Sarcopenia/genética , Osteoporosis/genética , Osteoporosis/metabolismo , Músculo Esquelético/metabolismo , Remodelación Ósea , Factor I del Crecimiento Similar a la Insulina/metabolismo , Transducción de Señal , Miostatina/metabolismoRESUMEN
PURPOSE: To evaluate clinical, laboratory, radiological, therapeutic, and prognostic characteristics of patients with acromegaly according to the size of the growth hormone (GH)-secreting pituitary adenoma at diagnosis. METHODS: Observational, retrospective, single-center study of patients with acromegaly followed at a tertiary center. Data were collected regarding clinical presentation, characteristics of the adenoma in the magnetic resonance imaging, GH and IGF-1 levels, and disease control after surgery or adjuvant treatment (normal IGF-1 levels). Patients were divided according to the adenoma size at diagnosis in: group I < 10 mm; II 10-19 mm; III 20-29 mm; IV 30-39 mm; and V ≥ 40 mm. Comparisons were made between the groups, and correlations of tumor size with disease parameters, ROC curves, and logistic regression analyses were performed to investigate tumor size and confounding factors that could impact the outcomes. RESULTS: 117 patients were studied [59 women, age at diagnosis 43 ± 13 years; group I = 11 patients (9%); group II 54 (46%); group III 34 (29%); group IV 10 (9%); group V 8 (7%)]. Hypopituitarism, cavernous sinus invasion, GH levels, and use of somatostatin receptor ligands had their prevalence increased according to the adenoma size. Age showed a negative correlation with tumor size. A tumor diameter around 20 mm was the best predictor for the presence of hypopituitarism, invasiveness, need of adjuvant therapies, and poorer disease control. CONCLUSION: Adenomas < 20 mm showed lower morbidity and better therapeutic response in acromegaly, while those ≥ 20 mm had similar clinical, therapeutic, and prognostic behavior.
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Acromegalia , Humanos , Acromegalia/patología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Hormona de Crecimiento Humana/metabolismo , Imagen por Resonancia Magnética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adenoma/patología , Adenoma/terapia , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Adenoma Hipofisario Secretor de Hormona del Crecimiento/terapia , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/terapiaRESUMEN
Astrocytes play key roles in the brain. When astrocyte support fails, neurological disorders follow, resulting in disrupted synaptic communication, neuronal degeneration, and cell death. We posit that astrocytes overexpressing neurotrophic factors, such as Insulin Like Growth Factor 1 (IGF1), prevent the onset of neurodegeneration. We overexpressed IGF1 and the reporter TdTomato (TOM) in hippocampal astrocytes with bicistronic Adeno-Associated Virus (AAV) harboring the Glial Fibrillary Acidic Protein (GFAP) promoter and afterwards induced neurodegeneration by the intracerebroventricular (ICV) injection of streptozotocin (STZ), a rat model of behavioral impairment, neuroinflammation and shortening of hippocampal astrocytes. We achieved a thorough transgene expression along the hippocampus with a single viral injection. Although species typical behavior was impaired, memory deficit was prevented by IGF1. STZ prompted astrocyte shortening, albeit the length of these cells in animals injected with GFP and IGF1 vectors did not statistically differ from the other groups. In STZ control animals, hippocampal microglial reactive cells increased dramatically, but this was alleviated in IGF1 rats. We conclude that overexpression of IGF1 in astrocytes prevents neurodegeneration onset. Hence, individuals with early neurotrophic exhaustion would be vulnerable to age-related neurodegeneration.
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Astrocitos , Dependovirus , Hipocampo , Factor I del Crecimiento Similar a la Insulina , Animales , Astrocitos/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Hipocampo/metabolismo , Dependovirus/genética , Ratas , Masculino , Ratas Wistar , Proteína Ácida Fibrilar de la Glía/metabolismoRESUMEN
PURPOSE: The insulin-like growth factor (IGF) system includes IGF-I, IGF-II insulin and their membrane receptors. IGF system also includes a family of proteins namely insulin-like growth factor-binding proteins (IGFBPs) composed for six major members (IGFBP-1 to IGFBP6), which capture, transport and prolonging half-life of IGFs. However, it has been described that IGFBPs can also have other functions. METHODS: IGFBP5 expression was inhibited by shRNAs, migration was analyzed by scratch-wound assays, invasion assays were performed by the Boyden chamber method, spheroids formation assays were performed on ultra-low attachment surfaces, expression and phosphorylation of proteins were analyzed by Western blot. RESULTS: IGFBP5 is a repressor of IGF-IR expression, but it is not a repressor of IR in MCF-7 breast cancer cells. In addition, IGFBP5 is a suppressor of migration and MMP-9 secretion induced by IGF-I and insulin, but it does not regulate invasion in MCF-7 cells. IGFBP5 also is a repressor of MCF-7 spheroids formation. However treatment with 340 nM rescues the inhibitory effect of IGFBP in the MCF-7 spheroids formation. CONCLUSION: IGFBP5 regulates IGF-IR expression, migration and MMP-9 secretion induced by IGF-I and/or insulin, and the spheroids formation in MCF-7 breast cancer cells.
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Neoplasias de la Mama , Movimiento Celular , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina , Insulina , Invasividad Neoplásica , Esferoides Celulares , Humanos , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Células MCF-7 , Insulina/metabolismo , Femenino , Metaloproteinasa 9 de la Matriz/metabolismo , Receptor IGF Tipo 1/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , FosforilaciónRESUMEN
Context A maternal high-fat diet is thought to pose a risk to spermatogenesis in the progeny. Aims We tested whether a maternal high-fat diet would affect Sertoli cell expression of transcription factors (insulin-like growth factor I (IGF-I); glial-cell line-derived neurotrophic factor (GDNF); Ets variant 5 (ETV5)) and cell proliferation and apoptotic proteins, in the testis of adult offspring. Methods Pregnant rats were fed ad libitum with a standard diet (Control) or a high-fat diet (HFat) throughout pregnancy and lactation. After weaning, male pups were fed the standard diet until postnatal day 160. Males were monitored daily from postnatal day 34 to determine onset of puberty. On postnatal day 160, their testes were processed for morphometry and immunohistochemistry. Key results The HFat diet increased seminiferous-tubule diameter (P P P P P P P P Conclusions A maternal high-fat diet alters the balance between spermatogonia proliferation and spermatid apoptosis. Implications A maternal high-fat diet seems to 'program' adult male fertility.
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Apoptosis , Proliferación Celular , Dieta Alta en Grasa , Lactancia , Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Testículo , Animales , Femenino , Masculino , Embarazo , Apoptosis/fisiología , Lactancia/fisiología , Testículo/metabolismo , Testículo/patología , Ratas , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , Espermatogénesis/fisiología , Células de Sertoli/metabolismo , Células de Sertoli/patología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Ratas WistarRESUMEN
OBJECTIVE: To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. METHODS: 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. RESULTS: GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 µg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. CONCLUSION: GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.
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Asma , Ensayo de Inmunoadsorción Enzimática , Trastornos del Crecimiento , Hormona de Crecimiento Humana , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina , Índice de Severidad de la Enfermedad , Humanos , Asma/sangre , Masculino , Femenino , Niño , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Trastornos del Crecimiento/sangre , Trastornos del Crecimiento/etiología , Hormona de Crecimiento Humana/sangre , Estudios de Casos y Controles , Preescolar , Valores de Referencia , Estadísticas no Paramétricas , AdolescenteRESUMEN
Feeding high-gain diets and an inadequate energy and protein ratio during pre-puberty may lead to impaired growth and mammary gland development of heifers. Thus, frequent application of bovine somatotropin (bST) may prevent future losses in productivity, improve mammary development and animal performance. We aimed to evaluate the effects of bST on digestibility, performance, blood metabolites, mammary gland development, and carcass composition of high-performance prepubertal Holstein × Gyr heifers. Thirty-four Holstein × Gyr heifers with an average initial body weight of 218 ± 49 kg and 14 ± 4 months of age were submitted to an 84-day trial evaluating the effects of no bST or bST injections. Treatments were randomly assigned to each animal within one of the tree blocks. The bST did not influence digestibility or performance parameters. Regarding blood results, IGF1 concentration presented an interaction between treatment and day, where bST heifers had the highest IGF1 concentration. Heifers receiving bST also showed increased ribeye area; however, only an experimental day effect for backfat thickness was observed, with greater accumulation of carcass fat on day 84. Heifers receiving bST had lower pixels/mm² on parenchyma, characteristic of greater parenchymal tissue. Moreover, heifers on bST treatment also had reduced pixels/mm2, characteristic of reduced fat pad tissue. Lastly, bST injections did not influence liver and muscle gene expression, nor most genes evaluated in mammary gland tissue, except for IGFBP3 expression, which was greater for bST heifers. In summary, we confirm the efficacy of bST injections to overcome the detrimental effects of high-gain diets on mammary gland growth and to improve lean carcass gain of prepubertal Holstein × Gyr heifers.
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Hormona del Crecimiento , Animales , Bovinos , Femenino , Hormona del Crecimiento/sangre , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/crecimiento & desarrollo , Glándulas Mamarias Animales/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Dieta/veterinaria , Alimentación Animal/análisis , Maduración Sexual/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Fenómenos Fisiológicos Nutricionales de los Animales , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismoRESUMEN
Introduction: Chronic obstructive pulmonary disease is a systemic disease characterized not only by respiratory symptoms but also by physical deconditioning and muscle weakness. One prominent manifestation of this disease is the decline in respiratory muscle strength. Previous studies have linked the genotypes of insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) to muscle weakness in other populations without this disease. However, there is a notable knowledge gap regarding the biological mechanisms underlying respiratory muscle weakness, particularly the role of IGF-1 and IGF-2 genotypes in this pulmonary disease. Therefore, this study aimed to investigate, for the first time, the association between IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with chronic obstructive pulmonary disease. In addition, we analyzed the relationship between oxidative stress, chronic inflammation, and vitamin D with respiratory muscle strength. Methods: A cross sectional study with 61 individuals with chronic obstructive pulmonary disease. Polymerase chain reaction of gene polymorphisms IGF-1 (rs35767) and IGF-2 (rs3213221) was analyzed. Other variables, related to oxidative stress, inflammation and Vitamin D were dosed from peripheral blood. Maximal inspiratory and expiratory pressure were measured. Results: The genetic polymorphisms were associated with respiratory muscle strength ( 3.0 and 3.5; = 0.57). Specific genotypes of IGF-1 and IGF-2 presented lower maximal inspiratory and expiratory pressure (<0.05 for all). Oxidative stress, inflammatory biomarkers, and vitamin D were not associated with respiratory muscle strength. Conclusion: The polymorphisms of IGF-1 and IGF-2 displayed stronger correlations with respiratory muscle strength compared to blood biomarkers in patients with chronic obstructive pulmonary disease. Specific genotypes of IGF-1 and IGF-2 were associated with reduced respiratory muscle strength in this population.
Introducción: La enfermedad pulmonar obstructiva crónica es una enfermedad sistémica caracterizada no solo por síntomas respiratorios, sino también por el deterioro físico y la debilidad muscular. Una manifestación destacada de esta enfermedad es el declive en la fuerza de los músculos respiratorios. Estudios previos han vinculado los genotipos de factor de crecimiento insulínico 1 y 2 (IGF-1 e IGF-2) con la debilidad muscular en poblaciones sin esta enfermedad. Sin embargo, existe un vacío de conocimiento con respecto a los mecanismos biológicos subyacentes a la debilidad de los músculos respiratorios, en particular el papel de los genotipos IGF-1 e IGF-2 en esta enfermedad pulmonar. Por lo tanto, este estudio tuvo como objetivo investigar, por primera vez, la asociación de los genotipos IGF-1 e IGF-2 con la fuerza de los músculos respiratorios en individuos con enfermedad pulmonar obstructiva crónica. Además, analizamos la relación entre el estrés oxidativo, la inflamación crónica y la vitamina D con la fuerza de los músculos respiratorios. Métodos: Un estudio transversal con 61 individuos con enfermedad pulmonar obstructiva crónica. Se analizó la reacción en cadena de la polimerasa de los polimorfismos genéticos IGF-1 (rs35767) e IGF-2 (rs3213221). Otras variables relacionadas con el estrés oxidativo, la inflamación y la vitamina D se dosificaron a partir de muestras de sangre periférica. Se midieron las presiones inspiratorias y espiratorias máximas. Resultados: Los polimorfismos genéticos están asociados con la fuerza de los músculos respiratorios (F: 3.0 y 3.5; R2= 0.57). Genotipos específicos de IGF-1 e IGF-2 presentaron bajos valores en las presiones inspiratorias y espiratorias (p<0.05 en todos los casos). El estrés oxidativo, los biomarcadores inflamatorios y la vitamina D no se asociaron con la fuerza de los músculos respiratorios. Conclusión: Los polimorfismos de IGF-1 e IGF-2 mostraron correlaciones más sólidas con la fuerza de los músculos respiratorios en pacientes con enfermedad pulmonar obstructiva crónica en comparación con los biomarcadores sanguíneos. Genotipos específicos de IGF-1 e IGF-2 se asociaron con una disminución de la fuerza de los músculos respiratorios en esta población.
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Genotipo , Factor II del Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina , Fuerza Muscular , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica , Músculos Respiratorios , Humanos , Estudios Transversales , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/genética , Fuerza Muscular/fisiología , Masculino , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculos Respiratorios/fisiopatología , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Anciano , Femenino , Persona de Mediana Edad , Inflamación/fisiopatología , Inflamación/genética , Vitamina D/sangre , Debilidad Muscular/fisiopatología , Debilidad Muscular/genéticaRESUMEN
INTRODUCTION: Chronic obstructive pulmonary disease is a systemic disease characterized not only by respiratory symptoms but also by physical deconditioning and muscle weakness. One prominent manifestation of this disease is the decline in respiratory muscle strength. Previous studies have linked the genotypes of insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) to muscle weakness in other populations without this disease. However, there is a notable knowledge gap regarding the biological mechanisms underlying respiratory muscle weakness, particularly the role of IGF-1 and IGF-2 genotypes in this pulmonary disease. Therefore, this study aimed to investigate, for the first time, the association between IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with chronic obstructive pulmonary disease. In addition, we analyzed the relationship between oxidative stress, chronic inflammation, and vitamin D with respiratory muscle strength. METHODS: A cross sectional study with 61 individuals with chronic obstructive pulmonary disease. Polymerase chain reaction of gene polymorphisms IGF-1 (rs35767) and IGF-2 (rs3213221) was analyzed. Other variables, related to oxidative stress, inflammation and Vitamin D were dosed from peripheral blood. Maximal inspiratory and expiratory pressure were measured. RESULTS: The genetic polymorphisms were associated with respiratory muscle strength ( 3.0 and 3.5; = 0.57). Specific genotypes of IGF-1 and IGF-2 presented lower maximal inspiratory and expiratory pressure (<0.05 for all). Oxidative stress, inflammatory biomarkers, and vitamin D were not associated with respiratory muscle strength. CONCLUSION: The polymorphisms of IGF-1 and IGF-2 displayed stronger correlations with respiratory muscle strength compared to blood biomarkers in patients with chronic obstructive pulmonary disease. Specific genotypes of IGF-1 and IGF-2 were associated with reduced respiratory muscle strength in this population.
INTRODUCCIÓN: La enfermedad pulmonar obstructiva crónica es una enfermedad sistémica caracterizada no solo por síntomas respiratorios, sino también por el deterioro físico y la debilidad muscular. Una manifestación destacada de esta enfermedad es el declive en la fuerza de los músculos respiratorios. Estudios previos han vinculado los genotipos de factor de crecimiento insulínico 1 y 2 (IGF-1 e IGF-2) con la debilidad muscular en poblaciones sin esta enfermedad. Sin embargo, existe un vacío de conocimiento con respecto a los mecanismos biológicos subyacentes a la debilidad de los músculos respiratorios, en particular el papel de los genotipos IGF-1 e IGF-2 en esta enfermedad pulmonar. Por lo tanto, este estudio tuvo como objetivo investigar, por primera vez, la asociación de los genotipos IGF-1 e IGF-2 con la fuerza de los músculos respiratorios en individuos con enfermedad pulmonar obstructiva crónica. Además, analizamos la relación entre el estrés oxidativo, la inflamación crónica y la vitamina D con la fuerza de los músculos respiratorios. MÉTODOS: Un estudio transversal con 61 individuos con enfermedad pulmonar obstructiva crónica. Se analizó la reacción en cadena de la polimerasa de los polimorfismos genéticos IGF-1 (rs35767) e IGF-2 (rs3213221). Otras variables relacionadas con el estrés oxidativo, la inflamación y la vitamina D se dosificaron a partir de muestras de sangre periférica. Se midieron las presiones inspiratorias y espiratorias máximas. RESULTADOS: Los polimorfismos genéticos están asociados con la fuerza de los músculos respiratorios (F: 3.0 y 3.5; R2= 0.57). Genotipos específicos de IGF-1 e IGF-2 presentaron bajos valores en las presiones inspiratorias y espiratorias (p<0.05 en todos los casos). El estrés oxidativo, los biomarcadores inflamatorios y la vitamina D no se asociaron con la fuerza de los músculos respiratorios. CONCLUSIÓN: Los polimorfismos de IGF-1 e IGF-2 mostraron correlaciones más sólidas con la fuerza de los músculos respiratorios en pacientes con enfermedad pulmonar obstructiva crónica en comparación con los biomarcadores sanguíneos. Genotipos específicos de IGF-1 e IGF-2 se asociaron con una disminución de la fuerza de los músculos respiratorios en esta población.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Músculos Respiratorios/fisiopatología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/genética , Fuerza Muscular/fisiología , Genotipo , Vitamina D/sangre , Estudios Transversales , Debilidad Muscular/fisiopatología , Debilidad Muscular/genética , Inflamación/fisiopatología , Inflamación/genéticaRESUMEN
INTRODUCTION: Insulin-like growth factor type I (IGF-I) has gained considerable notoriety in military training, primarily because it is responsible for energy deficits and sensitive to an inadequate protein intake, which are situations that are commonly experienced in specific military operations. Therefore, this study aimed to assess the kinetics of IGF-I and insulin-like growth factor binding protein type 3 (IGFBP-3) in a 4-day military field training exercise. MATERIALS AND METHODS: The sample comprised 12 male soldiers (21.71 ± 1.64 years). Changes were assessed at 3 times: time 1-basal (control week); time 2-after specific military field training; and time 3-1 week after the specific training (control week). Changes in body composition and serum levels of IGF-I and IGFBP-3 were observed. RESULTS: The main finding of this study was it verified the biphasic kinetics of both IGF-I and IGFBP-3 at the 3 times observed, that is, a significant drop from time 1 (basal-IGF-I: 189 ng/mL and IGFBP-3: 4.71 mg/L) to time 2 (immediately after military training-IGF-I: 162 ng/mL and IGFBP-3: 4.08 mg/L) and a subsequent recovery of these markers, with a significant increase from time 2 (immediately after military training) to time 3 (a week after military training-IGF-I: 199 ng/mL and IGFBP-3: 4.96 mg/L). CONCLUSIONS: It can be concluded that IGF-I and IGFBP-3 levels respond quickly to the stimuli caused by military training, especially after specific field training. However, the same markers quickly return to their basal values after this type of training finishes, simply by following the daily routine of the battalion in the control weeks, with no specific intervention being necessary.
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Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina , Personal Militar , Humanos , Masculino , Adulto Joven , Brasil , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Cinética , Personal Militar/estadística & datos numéricosRESUMEN
BACKGROUND: Human subjects with generalized growth hormone (GH) insensitivity due to GH receptor deficiency (GHRD)/Laron syndrome display a very low incidence of insulin resistance, diabetes, and cancer, as well as delayed age-related cognitive decline. However, the risk of cardiovascular disease (CVD) in these subjects is poorly understood. Here, we have assessed cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. METHODS: We measured markers of CVD in two phases: one in a cohort of 30 individuals (GHRD = 16, control relatives = 14) brought to USC (in Los Angeles, CA) and one in a cohort including additional individuals examined in Ecuador (where the subjects live) for a total of 44 individuals (GHRD = 21, control relatives = 23). Data were collected on GHRD and control groups living in similar geographical locations and sharing comparable environmental and socio-economic circumstances. RESULTS: Compared to controls, GHRD subjects displayed lower serum glucose, insulin, blood pressure, smaller cardiac dimensions, similar pulse wave velocity, lower carotid artery intima-media thickness, lower creatinine, and a non-significant but major reduction in the portion of subjects with carotid atherosclerotic plaques (7% GHRDs vs. 36%, Controls p = 0.1333) despite elevated low-density lipoprotein cholesterol levels. CONCLUSION: The current study indicates that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors as compared to their relatives. FUNDING: This study was funded in part by NIH/NIA grant P01 AG034906 to V.D.L.
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Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Síndrome de Laron , Humanos , Masculino , Femenino , Adulto , Enfermedades Cardiovasculares/epidemiología , Síndrome de Laron/genética , Persona de Mediana Edad , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/deficiencia , Grosor Intima-Media Carotídeo , Ecuador/epidemiología , Receptores de Somatotropina/genética , Receptores de Somatotropina/deficiencia , Análisis de la Onda del Pulso , Factores de Riesgo , Glucemia/metabolismo , Glucemia/análisis , Presión Sanguínea , Estudios de Casos y ControlesRESUMEN
OBJECTIVE: To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood. STUDY DESIGN: A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24 months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2 years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1]). RESULTS: After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6 months and continued through 12-24 months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12 months, and a lower mean IGF-1 levels at birth and 6 months. CONCLUSION: This study demonstrates a delayed impact of PAE on growth that manifested around 6 months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay.
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Factor I del Crecimiento Similar a la Insulina , Estado Nutricional , Efectos Tardíos de la Exposición Prenatal , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Femenino , Filipinas/epidemiología , Embarazo , Lactante , Masculino , Recién Nacido , Estudios Longitudinales , Preescolar , Consumo de Bebidas Alcohólicas/efectos adversos , Desarrollo Infantil/efectos de los fármacos , Adulto , Sangre Fetal/metabolismo , Sangre Fetal/química , Glicerofosfolípidos/sangre , Péptidos Similares a la InsulinaRESUMEN
The role of the insulin-like growth factor (IGF) system has attracted close attention. The activity of IGF binding proteins (IGFBPs) within the ovary has not been fully elucidated to date. These proteins bind to IGF with an equal, or greater, affinity than to the IGF1 receptor, thus being in the main position to regulate IGF signalling, in addition to extending the half-life of IGFs within the bloodstream and promoting IGF storage in specific tissue niches. IGF1 has an important part in cell proliferation, differentiation and apoptosis. Considering the importance of IGFs in oocyte maturation, this review sought to elucidate aspects including: IGF production mechanisms; constituent members of their family and their respective functions; the role that these factors play during folliculogenesis, together with their functions during oocyte maturation and apoptosis, and their performance during luteal development. This review also explores the role of IGFs in biotechnological applications, focusing specifically on animal genetic gain.
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Factor I del Crecimiento Similar a la Insulina , Femenino , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Transducción de Señal/fisiología , Unión Proteica , FosforilaciónRESUMEN
OBJECTIVE: The aim of this study was to investigate the levels of leptin, growth hormone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 and their relations with clinical parameters in patients with primary fibromyalgia and healthy controls. METHODS: Our study was performed on 30 female patients with primary fibromyalgia and 30 healthy controls. The levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by a two-site immunoradiometric assay. The serum level of leptin was measured by the ELISA kit. RESULTS: The serum level of leptin was significantly higher, but the serum levels of insulin-like growth factor-1 were significantly lower in patients with fibromyalgia syndrome than healthy controls (p<0.001). The leptin level was positively correlated with the Visual Analog Scale, Fibromyalgia Impact Questionnaire score, Beck Depression Inventory score, tender point count, age, and duration of disease (p<0.001), but it was negatively correlated with insulin-like growth factor-1 (p<0.001). The insulin-like growth factor-1 level was negatively correlated with age, Visual Analog Scale, Fibromyalgia Impact Questionnaire and Beck Depression Inventory scores, duration of disease, and tender point count (p<0.001). CONCLUSION: Our results indicate that high levels of serum leptin and low levels of serum insulin-like growth factor-1 may play a role in the physiopathogenesis of fibromyalgia and may be related to some symptoms.
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Fibromialgia , Leptina , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Dolor , Pacientes , Encuestas y CuestionariosRESUMEN
Limited information exists on the use of zinc-l-selenomethionine (Zn-L-SeMet) in broiler diets and its effects on the growth performance, body temperature, mortality rates, blood profile, and gene expression, especially when animals are reared under cyclic heat stress conditions. This study aimed to investigate the impact of Zn-L-SeMet in broiler diets from 1 to 42 days of age reared under cyclic heat stress and its effects on growth performance, cloacal temperatures, mortality rate, blood parameters, and insulin-like growth factor 1 (IGF-1) and growth hormone receptor (GHR) gene expression in the breast muscle. A total of 1000 male Cobb 500® broiler chicks were randomly assigned to five treatments: 0, 0.15, 0.23, 0.47, and 1.30 mg/kg of Zn-L-SeMet. Each treatment consisted of 10 replicates with 20 birds each. No statistically significant differences in growth performance were observed from 1 to 21 days of age (P > 0.05). However, from 1 to 42 days, feed intake (FI) and feed conversion ratio (FCR) decreased linearly (P < 0.05). Cloacal temperatures showed no significant effects (P > 0.05), while overall mortality rate exhibited a quadratic response (P < 0.05), with the optimal inclusion level predicted to reduce broiler mortality at 0.71 mg/kg. Triglyceride (TRG) levels increased with 0.97 mg/kg (P < 0.05), and gama-glutamil transferase (GGT) levels decreased with the inclusion of 1.19 mg/kg (P < 0.05). No significant effects on IGF-1 and GHR gene expression were found (P > 0.05). In conclusion, the inclusion of 1.30 mg/kg of Zn-L-SeMet in diets of heat-stressed broilers improved growth performance from 1 to 42 days of age. An inclusion of 0.71 mg/kg reduced mortality rate, while 0.97 mg and 1.19 mg increased and reduced TRG and GGT levels, respectively.
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Selenometionina , Zinc , Animales , Masculino , Selenometionina/metabolismo , Pollos , Suplementos Dietéticos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Dieta/veterinaria , Respuesta al Choque Térmico , Alimentación Animal/análisisRESUMEN
The relationship between growth hormone (GH) excess and cancer is a controversial matter. Until 2016, most studies in patients with acromegaly found links with colon and thyroid neoplasms. However, recent studies found increased risks in gastric, breast, and urinary tract cancer also. Concordantly, clinical situations where GH and insulin-like growth facto-I deficits exist are indeed associated with diminished malignancy incidence. In line with these observations, gain-of-function mutations of various enzymes belonging to the GH and IGF-I signaling pathways have been associated with increased carcinogenesis; similarly, loss-of-function mutations of other enzymes that usually work as tumor repressors are also associated with augmented cancer risk. In a study performed in Ecuador, it was demonstrated that subjects in the Ecuadorian cohort with Laron syndrome (ELS), who have a mutant GH receptor and greatly diminished GH and IGF-I signaling, display diminished incidence of cancer. Along with absent action of GH and IGF-I, ELS individuals also have low serum insulin levels and decreased insulin resistance. Furthermore, hyperglycemia and hyperinsulinemia are indispensable for fast cell mitosis, including that of those cells present in the benign and malignant neoplasms. Notably, and despite their obesity, subjects with the ELS display normoglycemia and hypo-insulinemia, along with diminished incidence of malignancies. We believe that the dual low-IGF-I/low insulin serum levels are responsible for the cancer protection, especially considering that the insulin/INSR signaling is a central site for energy generation in the form of ATP and GDP, which are indispensable for all and every GH/IGF-I physiologic as well as pathologic events.
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Acromegalia , Hormona de Crecimiento Humana , Neoplasias , Humanos , Hormona del Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , InsulinaRESUMEN
Diabetic nephropathy (DN) is a prevalent diabetic microvascular condition. It is the leading cause of kidney disease in the advanced stages. There is no currently effective treatment available. This research aimed to investigate the curative potentials of exosomes isolated from mesenchymal stem cells affecting DN. This study was performed on 70 male adult albino rats. Adult rats were randomized into seven groups: Group I: Negative control group, Group II: DN group, Group III: Balanites treated group, Group IV: MSCs treated group, Group V: Exosome treated group, Group VI: Balanites + MSCs treated group and Group VII: Balanites + exosome treated group. Following the trial period, blood and renal tissues were subjected to biochemical, gene expression analyses, and histopathological examinations. Results showed that MDA was substantially increased, whereas TAC was significantly decreased in the kidney in the DN group compared to normal health rats. Undesired elevated values of MDA levels and a decrease in TAC were substantially ameliorated in groups co-administered Balanites aegyptiacae with MSCs or exosomes compared to the DN group. A substantial elevation in TNF-α and substantially diminished concentration of IGF-1 were noticed in DN rats compared to normal health rats. Compared to the DN group, the co-administration of Balanites aegyptiacae with MSCs or exosomes substantially improved the undesirable elevated values of TNF-α and IGF-1. Furthermore, in the DN group, the mRNA expression of Vanin-1, Nephrin, and collagen IV was significantly higher than in normal healthy rats. Compared with DN rats, Vanin-1, Nephrin, and collagen IV Upregulation were substantially reduced in groups co-administered Balanites aegyptiacae with MSCs or exosomes. In DN rats, AQP1 expression was significantly lower than in normal healthy rats. Furthermore, the groups co-administered Balanites aegyptiacae with MSCs or exosomes demonstrated a substantial increase in AQP1 mRNA expression compared to DN rats.
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Acuaporinas , Diabetes Mellitus , Nefropatías Diabéticas , Exosomas , Células Madre Mesenquimatosas , Ratas , Masculino , Animales , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Exosomas/metabolismo , Exosomas/patología , Células Madre Mesenquimatosas/metabolismo , Acuaporinas/metabolismo , Colágeno/metabolismo , ARN Mensajero , Diabetes Mellitus/metabolismoRESUMEN
A high-protein hypercaloric diet enriched with glutamine and omega-3 polyunsaturated fatty acids was called an onco-diet. The goal was to verify the modulation of the inflammatory response and body composition of female dogs with mammary tumor after mastectomy, during onco-diet consumption, using a randomized, double-blinded, clinical trial. Six bitches (average age of 8.6 years) were allocated into Control Group-diet without glutamine, EPA and DHA supplementation; and six bitches (10.0 years) were allocated into Test-diet enriched with glutamine and omega-3. Serum measurements of TNF-α, IL-6, IL-10, IGF-1, C-reactive protein and determination of body composition were performed at pre- and post-surgical times. Statistical tests were used to compare the nutrient intake and dietary effects on inflammatory variables between the diets. No differences in concentrations of different cytokines (p>0.05) and C-reactive protein (CRP) (p = 0.51) were observed between the groups. The test group had a higher concentration of IGF-1 (p<0.05), higher percentage of muscle mass (p<0.01) and lower body fat (p<0.01), but the difference was present from initial and throughout the study. Onco-diet, enriched with glutamine and omega-3, in the amounts evaluated in this study, was not sufficient to modulate the inflammation and body composition of female dogs with mammary tumors submitted to unilateral mastectomy.
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Ácidos Grasos Omega-3 , Neoplasias , Animales , Perros , Femenino , Composición Corporal , Proteína C-Reactiva/metabolismo , Dieta/veterinaria , Ácidos Docosahexaenoicos , Ácidos Grasos Omega-3/metabolismo , Glutamina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Mastectomía , Proyectos PilotoRESUMEN
Growth hormone (GH) is a classic pituitary-derived hormone crucial to body growth and metabolism. In the pituitary gland, GH production is stimulated by GH-releasing hormone and inhibited by somatostatin. GH secretion can also be induced by other peptides, such as ghrelin, which interacts with receptors present in somatotropic cells. It is well established that GH acts directly on target cells or indirectly by stimulating the production of insulin-like growth factors (IGFs), particularly IGF-1. Notably, such somatotropic circuitry is also involved in the development and function of immune cells and organs, including the thymus. Interestingly, GH, IGF-1, ghrelin, and somatostatin are expressed in the thymus in the lymphoid and microenvironmental compartments, where they stimulate the secretion of soluble factors and extracellular matrix molecules involved in the general process of intrathymic T-cell development. Clinical trials in which GH was used to treat immunocompromised patients successfully recovered thymic function. Additionally, there is evidence that the reduction in the function of the somatotropic axis is associated with age-related thymus atrophy. Treatment with GH, IGF-1 or ghrelin can restore thymopoiesis of old animals, thus in keeping with a clinical study showing that treatment with GH, associated with metformin and dehydroepiandrosterone, could induce thymus regeneration in healthy aged individuals. In conclusion, the molecules of the somatotrophic axis can be envisioned as potential therapeutic targets for thymus regeneration in age-related or pathological thymus involution.
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Ghrelina , Factor I del Crecimiento Similar a la Insulina , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona del Crecimiento , Timo , SomatostatinaRESUMEN
CONTEXT: Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control. OBJECTIVE: As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed. METHODS: A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008). The main outcome measures were safety and biochemical control (age-adjusted IGF-I ≤ upper limit of normal). RESULTS: Patients (n = 50) entered 4 parental studies and 30 continued in the rollover; at data cutoff (June 2022), 27 were still receiving pasireotide. Overall, median (range) exposure was 58 (3-137) months. Normal IGF-I was achieved in 54%, and acromegaly symptoms and quality of life were improved with treatment. No predictors of pasireotide response were identified; however, controlled patients had smaller tumors and lower GH at baseline. Tumor volume reduction occurred in 63% of evaluable patients (n = 10/16). Most patients presented hyperglycemic events, including 63.2% of patients with normal glucose before treatment. Older patients and those with higher IGF-I, glucose, and HbA1c at baseline had higher glucose and HbA1c during pasireotide treatment. CONCLUSION: Pasireotide provided clinical benefit and was well tolerated for more than 11 years of treatment in acromegaly patients, most of whom were resistant to first-generation SRLs.