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1.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674494

RESUMO

Previously, we demonstrated that the administration of either geranylgeraniol (GGOH) or green tea polyphenols (GTP) improved bone health. This study examined the combined effects of GGOH and GTP on glucose homeostasis in addition to bone remodeling in obese mice. We hypothesized that GGOH and GTP would have an additive or synergistic effect on improving glucose homeostasis and bone remodeling possibly in part via suppression of proinflammatory cytokines. Forty-eight male C57BL/6J mice were assigned to a high-fat diet (control), HFD + 400 mg GGOH/kg diet (GG), HFD + 0.5% GTP water (TP), or HFD + GGOH + GTP (GGTP) diet for 14 weeks. Results demonstrated that GTP supplementation improved glucose tolerance in obese mice. Neither GGOH nor GTP affected pancreas insulin or bone formation procollagen type I intact N-terminal, bone volume at the lumbar vertebrae, or bone parameters at the trabecular bone and cortical bone of the femur. There was an interactive effect for serum bone resorption collagen type 1 cross-linked C-telopeptide concentrations, resulting in no-GGOH and no-GTP groups having the highest values. GGOH increased trabecular number and decreased trabecular separation at the lumbar vertebrae. GTP increased trabecular thickness at lumbar vertebrae. The GG group produced the greatest connectivity density and the lowest structure model index. Only GTP, not GGOH, decreased adipokines concentrations (resistin, leptin, monocyte chemoattractant protein-1, and interleukin-6). In an obese male mouse model, individual GGOH and GTP supplementation improved glucose homeostasis, serum CTX, and trabecular microstructure of LV-4. However, the combined GGOH and GTP supplementation compromises such osteoprotective effects on serum CTX and trabecular bone of obese mice.


Assuntos
Densidade Óssea , Polifenóis , Camundongos , Animais , Masculino , Camundongos Obesos , Polifenóis/farmacologia , Camundongos Endogâmicos C57BL , Antioxidantes/farmacologia , Remodelação Óssea , Dieta Hiperlipídica/efeitos adversos , Chá/química , Glucose/farmacologia , Homeostase , Biomarcadores
2.
Am J Physiol Heart Circ Physiol ; 315(3): H482-H491, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29750565

RESUMO

During pregnancy, the heart undergoes significant and numerous changes, including hypertrophy, that are usually described as physiological and reversible. Two aspects of the cardiac response to pregnancy are relatively understudied: advanced maternal age and multiple pregnancies (multiparity). Repeated breeder (RB) mice that have undergone five to seven consecutive pregnancies were euthanized 21 days after the weaning of their last pups and compared with age-matched primiparous, one-time pregnant (O1P) mice. The ages of the older mouse groups were similar (12 ± 1 mo). Pregnancy at a later age resulted in reduced fertility (40%); resorption was 29%, maternal mortality was 10%, and mortality of the pups was 17%. Contractile function as indicated by percent fractional shortening was significantly decreased in O1P and RB groups compared with the old nonpregnant control (ONP) group. There was no pathological induction of the fetal program of gene expression, with the exception of ß-myosin heavy chain mRNA, which was induced in O1P compared with ONP mice ( P < 0.05) but not in RB mice. MicroRNA-208a was significantly increased in O1P compared with ONP mice ( P < 0.05) but significantly decreased in RB compared with ONP mice ( P < 0.05). mRNA of genes regulating angiogenesis (i.e., vascular endothelial growth factor-A) were significantly downregulated, whereas proinflammatory genes [i.e., interleukin-6, chemokine (C-C motif) ligand 2, and Cd36] were significantly upregulated in O1P ( P < 0.05) but not in RB mice. Overall, our results suggest that rather than multiparity, pregnancy in advanced age is a much more stressful event in both pregnant dams and fetuses, as evidenced by increased mortality, lower fertility, downregulation of angiogenesis, upregulation of inflammation, and cardiac dysfunction. NEW & NOTEWORTHY Pregnancy in older mice significantly decreases cardiac function, although repeated breeder mice demonstrated increased wall hypertrophy and dilated chamber size compared with one-time pregnant mice. Interestingly, many of the molecular changes were altered in one-time pregnant mice but not in repeated breeder mice, which may contribute to adverse pregnancy outcomes in a first pregnancy at a later age.


Assuntos
Envelhecimento/fisiologia , Coração/fisiologia , Gravidez/fisiologia , Animais , Citocinas/genética , Citocinas/metabolismo , Feminino , Coração/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Contração Miocárdica , Miocárdio/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Eur J Appl Physiol ; 117(5): 989-1004, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28321637

RESUMO

BACKGROUND: It has been proposed that the increase in skeletal muscle mass observed during the initial weeks of initiating a resistance training program is concomitant with eccentric muscle damage and edema. PURPOSE: We examined the time course of muscle hypertrophy during 4 weeks of concentric-only resistance training. METHODS: Thirteen untrained men performed unilateral concentric-only dumbbell curls and shoulder presses twice per week for 4 weeks. Sets of 8-12 repetitions were performed to failure, and training loads were increased during each session. Subjects consumed 500 ml of whole milk during training. Assessments of soreness, lean mass, echo intensity, muscle thickness, relaxed and flexed arm circumference, and isokinetic strength were performed every 72 or 96 h. RESULTS: Soreness, echo intensity, relaxed circumference, and peak torque data did not significantly change. Significant increases in lean mass, muscle thickness, and flexed circumference were observed within seven training sessions. Lean mass was elevated at tests #7 (+109.3 g, p = .002) and #8 (+116.1 g, p = .035), with eight different subjects showing changes above the minimal difference of 139.1 g. Muscle thickness was elevated at tests #6 (+0.23 cm, p = .004), #7 (+0.31 cm, p < .001), and #8 (+0.27 cm, p < .001), with ten subjects exceeding the minimal difference of 0.24 cm. There were no changes for the control arm. CONCLUSION: In individuals beginning a resistance training program, small but detectable increases in hypertrophy may occur in the absence of eccentric muscle damage within seven training sessions.


Assuntos
Músculo Esquelético/fisiologia , Mialgia/etiologia , Treinamento Resistido/efeitos adversos , Adulto , Humanos , Hipertrofia/diagnóstico por imagem , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Mialgia/diagnóstico por imagem , Tempo de Reação
4.
BMC Musculoskelet Disord ; 17: 181, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27113571

RESUMO

BACKGROUND: Very few studies have investigated differences in musculoskeletal health due to gender in a large rural population. The aim of this study is to investigate factors affecting musculoskeletal health in terms of hand grip strength, musculoskeletal discomfort, and gait disturbance in a rural-dwelling, multi-ethnic cohort. METHODS: Data for 1117 participants (40 years and older, 70% female) of an ongoing rural healthcare study, Project FRONTIER, were analyzed. Subjects with a history of neurological disease, stroke and movement disorder were excluded. Dominant hand grip strength was assessed by dynamometry. Gait disturbance including stiff, spastic, narrow-based, wide-based, unstable or shuffling gait was rated. Musculoskeletal discomfort was assessed by self-reported survey. Data were analyzed by linear, logistic regression and negative binomial regressions as appropriate. Demographic and socioeconomic factors were adjusted in the multiple variable analyses. RESULTS: In both genders, advanced age was a risk factor for weaker hand grip strength; arthritis was positively associated with musculoskeletal discomfort, and fair or poor health was significantly associated with increased risk of gait disturbance. Greater waist circumference was associated with greater musculoskeletal discomfort in males only. In females, advanced age is the risk factor for musculoskeletal discomfort as well as gait disturbance. Females with fair or poor health had weaker hand grip strength. Higher C-reactive protein and HbA1c levels were also positively associated with gait disturbance in females, but not in males. CONCLUSION: This cross-sectional study demonstrates how gender affects hand grip strength, musculoskeletal discomfort, and gait in a rural-dwelling multi-ethnic cohort. Our results suggest that musculoskeletal health may need to be assessed differently between males and females.


Assuntos
Etnicidade , Força da Mão/fisiologia , Doenças Musculoesqueléticas/diagnóstico , População Rural , Caracteres Sexuais , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Doenças Musculoesqueléticas/epidemiologia
5.
Pediatr Int ; 57(3): 393-400, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25330041

RESUMO

BACKGROUND: Although oseltamivir is a common influenza treatment, there is a lack of data on the economic benefits of timely oseltamivir treatment. METHODS: From February 2004 through June 2007, 116 hospitalized children ≤ 15 years of age with laboratory-confirmed influenza who received oseltamivir were identified via retrospective medical chart review. Demographic, clinical, and cost data were abstracted and multivariate linear regression was used to assess the association between oseltamivir time to treatment and treatment-related costs among hospitalized children with laboratory-confirmed influenza. RESULTS: Overall, 28% (n = 33) of patients were treated with oseltamivir ≥ day 3 of admission. Rapid influenza diagnostic test was used in a significantly lower proportion of patients treated with oseltamivir ≥ day 3 of admission compared with those who received oseltamivir earlier. On multivariate linear regression, initiation of oseltamivir ≥ day 3 of admission was associated with a 60.84% increase (95%CI: 32.59-95.11) in treatment-related hospital costs, compared with initiation on admission. CONCLUSION: Delayed initiation of oseltamivir was found to be associated with increased treatment-related hospital costs among children hospitalized with laboratory-confirmed influenza.


Assuntos
Custos Hospitalares/tendências , Hospitalização/economia , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Adolescente , Antivirais/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Influenza Humana/economia , Influenza Humana/epidemiologia , Masculino , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento
6.
Prev Chronic Dis ; 12: E217, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26652217

RESUMO

The objective of this study was to examine population-based prevalence of walking in the United States among pregnant women. Objectively measured walking data on 197 pregnant women who participated in the National Health and Nutrition Examination Survey 2005-2006 were analyzed. In general, pregnant women showed a level of walking below the recommendation; most walking was at low-intensity levels. These findings suggest that walking, particularly at higher intensity than usual, should be promoted among pregnant women.


Assuntos
Gestantes , Caminhada/estatística & dados numéricos , Adolescente , Adulto , Feminino , Promoção da Saúde , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Gravidez , Prevalência , Estados Unidos/epidemiologia , Adulto Jovem
7.
Nucleic Acids Res ; 40(15): 7303-18, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22638570

RESUMO

The sarcomeric myosin gene, Myh7b, encodes an intronic microRNA, miR-499, which regulates cardiac and skeletal muscle biology, yet little is known about its transcriptional regulation. To identify the transcription factors involved in regulating Myh7b/miR-499 gene expression, we have mapped the transcriptional start sites and identified an upstream 6.2 kb region of the mouse Myh7b gene whose activity mimics the expression pattern of the endogenous Myh7b gene both in vitro and in vivo. Through promoter deletion analysis, we have mapped a distal E-box element and a proximal Ikaros site that are essential for Myh7b promoter activity in muscle cells. We show that the myogenic regulatory factors, MyoD, Myf5 and Myogenin, bind to the E-box, while a lymphoid transcription factor, Ikaros 4 (Eos), binds to the Ikaros motif. Further, we show that through physical interaction, MyoD and Eos form an active transcriptional complex on the chromatin to regulate the expression of the endogenous Myh7b/miR-499 gene in muscle cells. We also provide the first evidence that Eos can regulate expression of additional myosin genes (Myosin 1 and ß-Myosin) via the miR-499/Sox6 pathway. Therefore, our results indicate a novel role for Eos in the regulation of the myofiber gene program.


Assuntos
Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica , Fator de Transcrição Ikaros/metabolismo , MicroRNAs/genética , Fatores de Regulação Miogênica/metabolismo , Cadeias Pesadas de Miosina/genética , Miosina Tipo II/genética , Proteínas do Tecido Nervoso/metabolismo , Transcrição Gênica , Animais , Sequência de Bases , Proteínas de Transporte/química , Proteínas de Transporte/fisiologia , Células Cultivadas , Proteínas de Ligação a DNA , Elementos E-Box , Humanos , Fator de Transcrição Ikaros/fisiologia , Camundongos , MicroRNAs/biossíntese , Dados de Sequência Molecular , Músculo Esquelético/metabolismo , Proteína MyoD/metabolismo , Miocárdio/metabolismo , Fatores de Regulação Miogênica/fisiologia , Cadeias Pesadas de Miosina/biossíntese , Miosina Tipo II/biossíntese , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/fisiologia , Regiões Promotoras Genéticas , Domínios e Motivos de Interação entre Proteínas , Sítio de Iniciação de Transcrição
8.
Med Sci Sports Exerc ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38595204

RESUMO

PURPOSE: Maternal and postnatal overnutrition has been linked to an increased risk of cardiometabolic diseases in offspring. This study investigated the impact of adult-onset voluntary wheel running to counteract cardiometabolic risks in female offspring exposed to a life-long high-fat, high-sucrose (HFHS) diet. METHODS: Dams were fed either a HFHS or a low-fat, low-sucrose (LFLS) diet starting from 8 weeks prior to pregnancy and continuing throughout gestation and lactation. Offspring followed their mothers' diets. At 15 weeks of age, they were divided into sedentary (Sed) or voluntary wheel running (Ex) groups, resulting in four groups: LFLS/Sed (n = 10), LFLS/Ex (n = 5), HFHS/Sed (n = 6), HFHS/Ex (n = 5). Cardiac function was assessed at 25 weeks, with tissue collection at 26 weeks for mitochondrial respiratory function and protein analysis. Data were analyzed using two-way ANOVA. RESULTS: While maternal HFHS diet did not affect the offspring's body weight at weaning, continuous HFHS feeding post-weaning resulted in increased body weight and adiposity, irrespective of the exercise regimen. HFHS/Sed offspring showed increased left ventricular wall thickness and elevated expression of enzymes involved in fatty acid transport (CD36, FABP3), lipogenesis (DGAT), glucose transport (GLUT4), oxidative stress (protein carbonyls, nitrotyrosine), and early senescence markers (p16, p21). Their cardiac mitochondria displayed lower oxidative phosphorylation (OXPHOS) efficiency and reduced expression of OXPHOS complexes and fatty acid metabolism enzymes (ACSL5, CPT1B). However, HFHS/Ex offspring mitigated these effects, aligning more with LFLS/Sed offspring. CONCLUSIONS: Adult-onset voluntary wheel running effectively counteracts the detrimental cardiac effects of a lifelong HFHS diet, improving mitochondrial efficiency, reducing oxidative stress, and preventing early senescence. This underscores the significant role of physical activity in mitigating diet-induced cardiometabolic risks.

9.
bioRxiv ; 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38328143

RESUMO

The heart is a highly plastic organ that responds to diverse stimuli to modify form and function. The molecular mechanisms of adaptive physiological cardiac hypertrophy are well-established; however, the regulation of hypertrophy regression is poorly understood. To identify molecular features of regression, we studied Burmese pythons which experience reversible cardiac hypertrophy following large, infrequent meals. Using multi-omics screens followed by targeted analyses, we found forkhead box protein O1 (FoxO1) transcription factor signaling, and downstream autophagy activity, were downregulated during hypertrophy, but re-activated with regression. To determine whether these events were mechanistically related to regression, we established an in vitro platform of cardiomyocyte hypertrophy and regression from treatment with fed python plasma. FoxO1 inhibition prevented regression in this system, while FoxO1 activation reversed fed python plasma-induced hypertrophy in an autophagy-dependent manner. We next examined whether FoxO1 was implicated in mammalian models of reversible hypertrophy from exercise and pregnancy and found that in both cases FoxO1 was activated during regression. In these models, as in pythons, activation of FoxO1 was associated with increased expression FoxO1 target genes involved in autophagy. Taken together, our findings suggest FoxO1-dependent autophagy is a conserved mechanism for regression of physiological cardiac hypertrophy across species.

10.
J Am Coll Health ; : 1-7, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36877632

RESUMO

OBJECTIVE: To examine food insecurity (FI) prevalence among college students during the COVID-19 pandemic (April 2021) using cross-sectional design, and the moderating role of the first-generation student status in the relationship between FI and grade point average (GPA). PARTICIPANTS: Three-hundred sixty students recruited mostly from upper-level kinesiology courses. METHODS: General linear model was used to predict GPA based on food security status, psychological health, and bodily pain, with subgroup analysis performed by first-generation student status. RESULTS: Approximately 19% were classified as having FI. Those with FI showed lower GPA and poor health compared to those without FI. The link between FI and GPA was moderated by first-generation student status, with the negative impact of FI on GPA more clearly observed among non-first-generation students. CONCLUSION: First-generation student status could play a role in determining the impact of FI on academic performance.

11.
Integr Med Res ; 12(2): 100949, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37214317

RESUMO

Background: Accelerated skeletal muscle wasting is a shared trait among many pathologies and aging. Acupuncture has been used as a therapeutic intervention to control pain; however, little is known about its effects on skeletal muscle atrophy and function. The study's purpose was to compare the effects of acupuncture, electro-acupuncture, and electrical stimulation on cast-induced skeletal muscle atrophy. Methods: Forty female Sprague Dawley rats were randomly divided into groups: Control, casted (CAST), CAST+Acupuncture (CAST-A), 4) CAST+Electro-acupuncture (CAST-EA), and CAST+Electrical stimulation (CAST-ES) (n = 8). Plaster casting material was wrapped around the left hind limb. Acupuncture and electro-acupuncture (10 Hz, 6.4 mA) treatments were applied by needling acupoints (stomach-36 and gallbladder-34). Electrical stimulation (10 Hz, 6.4 mA) was conducted by needling the lateral and medial gastrocnemius muscles. Treatments were conducted for 15 min, three times/week for 14 days. Muscle atrophy F-box (MAFbx), muscle RING finger 1 (MuRF1), and contractile properties were assessed. Results: Fourteen days of cast-immobilization decreased muscle fiber CSA by 56% in the CAST group (p = 0.00); whereas, all treatment groups demonstrated greater muscle fiber CSA than the CAST group (p = 0.00). Cast-immobilization increased MAFbx and MuRF1 protein expression in the CAST group (p<0.01) while the CAST-A, CAST-EA, and CAST-ES groups demonstrated lower levels of MAFbx and MuRF1 protein expression (p<0.02) compared to the CAST group. Following fourteen days of cast-immobilization, peak twitch tension did not differ between the CAST-A and CON groups (p = 0.12). Conclusion: Skeletal muscle atrophy, induced by 14 days of cast-immobilization, was significantly attenuated by acupuncture, electro-acupuncture, or electrical stimulation.

12.
Metabolites ; 12(6)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35736495

RESUMO

Cardiac mitochondrial dysfunction contributes to obesity-associated heart disease. Maternal and postnatal diet plays an important role in cardiac function, yet the impacts of a mismatch between prenatal and postweaning diet on cardiometabolic function are not well understood. We tested the hypothesis that switching to a standard chow diet after weaning would attenuate systemic metabolic disorders and cardiac and mitochondrial dysfunction associated with maternal and postnatal high-fat/high-sucrose (HFHS) diet in mice. Six-month-old male CD1 offspring from dams fed a HFHS diet and weaned to the same HFHS diet (HH) or switched to a standard chow diet (HC) were compared to offspring from dams fed a low-fat/low-sucrose diet and maintained on the same diet (LL). HC did not decrease body weight (BW) but normalized glucose tolerance, plasma cholesterol, LDL, and insulin levels compared to the HH. Systolic function indicated by the percent fractional shortening was not altered by diet. In freshly isolated cardiac mitochondria, maximal oxidative phosphorylation-linked respiratory capacity and coupling efficiency were significantly higher in the HC in the presence of fatty acid substrate compared to LL and HH, with modification of genes associated with metabolism and mitochondrial function. Switching to a standard chow diet at weaning can attenuate the deleterious effects of long-term HFHS in adult male mouse offspring.

13.
Steroids ; 178: 108952, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34968450

RESUMO

Mice that lack the gene for expression of cytochrome P450 8B1 (P450 8B1) resist weight gain and improve glucose tolerance when fed a high-fat diet. Thus, the inhibition of P450 8B1 is a target to treat obesity-associated metabolic disorders. P450 8B1 is the enzyme that hydroxylates its substrate, 7α-hydroxy-cholest-4-en-3-one to 7α-,12α-dihydroxycholest-4-en-3-one, which ultimately results in the formation of cholic acid. Cholic acid is the 12α-hydroxylated bile acid implicated in enhanced absorption of cholesterol. The synthesis of a rationally designed inhibitor for P450 8B1 was achieved through the incorporation of a C12-pyridine in the C-ring of a steroid molecule. Seven days of new inhibitor treatment showed attenuation of glucose intolerance in mice that were fed a high fat and a high sucrose diet (HFHS) without affecting body weight. Taken together, these promising results will lead to a P450 8B1 inhibitor as a potential therapeutic strategy to treat obesity-associated insulin resistance.


Assuntos
Obesidade , Esteroide 12-alfa-Hidroxilase , Animais , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/uso terapêutico , Colesterol/metabolismo , Ácido Cólico/metabolismo , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Esteroide 12-alfa-Hidroxilase/antagonistas & inibidores , Esteroide 12-alfa-Hidroxilase/metabolismo
14.
Metabolites ; 12(10)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36295815

RESUMO

Natural bioactive compounds are proposed as alternatives in mitigating obesity-associated skeletal muscle dysfunction. The objective of this study was to test the hypothesis that the combination of geranylgeraniol (GGOH) and green tea polyphenols (GTPs) can alleviate high-fat-diet (HFD)-induced muscle atrophy and alter gut microbiome composition. Male C57BL/6J mice fed an HFD were assigned to four groups (12 mice each) in a 2 (no GGOH vs. 400 mg GGOH/kg diet) × 2 (no GTPs vs. 0.5% weight/volume GTPs in water) factorial design. After 14 weeks of diet intervention, skeletal muscle and cecal samples were collected and examined. Compared to the control groups, the group that consumed a combination of GGOH and GTPs (GG + GTPs) had significantly decreased body and fat mass but increased skeletal muscle mass normalized by body weight and cross-sectional area. In soleus muscle, the GG + GTP diet increased citrate synthase activity but decreased lipid peroxidation. Gut microbiome beta-diversity analysis revealed a significant difference in the microbiome composition between diet groups. At the species level, the GG + GTP diet decreased the relative abundance of Dorea longicatena, Sporobacter termitidis, and Clostridium methylpentosum, and increased that of Akkermansia muciniphila and Subdoligranulum variabile. These results suggest that the addition of GGOH and GTPs to an HFD alleviates skeletal muscle atrophy, which is associated with changes in the gut microbiome composition.

15.
J Mol Cell Cardiol ; 51(1): 41-50, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21539845

RESUMO

Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models of heart failure. The efficacious compounds target class I, class IIb and, to a lesser extent, class IIa HDACs. It is hypothesized that a selective inhibitor of a specific HDAC class (or an isoform within that class) will provide a favorable therapeutic window for the treatment of heart failure, although the optimal selectivity profile for such a compound remains unknown. Genetic studies have suggested that class I HDACs promote pathological cardiac remodeling, while class IIa HDACs are protective. In contrast, nothing is known about the function or regulation of class IIb HDACs in the heart. We developed assays to quantify catalytic activity of distinct HDAC classes in left and right ventricular cardiac tissue from animal models of hypertensive heart disease. Class I and IIa HDAC activity was elevated in some but not all diseased tissues. In contrast, catalytic activity of the class IIb HDAC, HDAC6, was consistently increased in stressed myocardium, but not in a model of physiologic hypertrophy. HDAC6 catalytic activity was also induced by diverse extracellular stimuli in cultured cardiac myocytes and fibroblasts. These findings suggest an unforeseen role for HDAC6 in the heart, and highlight the need for pre-clinical evaluation of HDAC6-selective inhibitors to determine whether this HDAC isoform is pathological or protective in the setting of cardiovascular disease.


Assuntos
Histona Desacetilases/metabolismo , Hipertensão/enzimologia , Miocárdio/enzimologia , Adenoviridae/genética , Animais , Doenças Cardiovasculares , Células Cultivadas , Ventrículos do Coração/enzimologia , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/biossíntese , Histona Desacetilases/genética , Hipertensão/patologia , Masculino , Camundongos , Miócitos Cardíacos/enzimologia , Reação em Cadeia da Polimerase , Isoformas de Proteínas , Interferência de RNA , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Remodelação Ventricular
16.
Sci Rep ; 11(1): 18057, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508150

RESUMO

Cardiovascular disease is the leading cause of death in women during pregnancy and the postpartum period. Obesity is an independent risk factor for cardiovascular diseases. Nearly 60% of women of reproductive age are considered overweight or obese, cardiovascular disease morbidity and mortality continue to be pervasive. The objective of this study was to determine the effects of an obesogenic diet on the cardiometabolic health of dams during pregnancy and postpartum. Female mice were fed either a high-fat, high-sucrose diet (HFHS) or a refined control diet (CON) for 8 weeks before initiation of pregnancy and throughout the study period. Mice in the HFHS showed two distinct phenotypes, obesity-prone (HFHS/OP) and obesity resistance (HFHS/OR). Pre-pregnancy obesity (HFHS/OP) induced glucose intolerance before pregnancy and during postpartum. Systolic function indicated by the percent fractional shortening (%FS) was significantly decreased in the HFHS/OP at late pregnancy (vs. HFHS/OR) and weaning (vs. CON), but no differences were found at 6 weeks of postpartum among groups. No induction of pathological cardiac hypertrophy markers was found during postpartum. Plasma adiponectin was decreased while total cholesterol was increased in the HFHS/OP. Our results suggested that obesity, not the diet alone, negatively affected cardiac adaptation during pregnancy and postpartum.


Assuntos
Intolerância à Glucose/metabolismo , Cardiopatias/etiologia , Cardiopatias/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Complicações Cardiovasculares na Gravidez/etiologia , Complicações Cardiovasculares na Gravidez/metabolismo , Biomarcadores , Glicemia , Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/efeitos adversos , Suscetibilidade a Doenças , Feminino , Intolerância à Glucose/etiologia , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Testes de Função Cardíaca , Humanos , Resistência à Insulina , Lipídeos/sangue , Obesidade/diagnóstico , Obesidade/etiologia , Período Pós-Parto , Gravidez , Complicações Cardiovasculares na Gravidez/fisiopatologia
17.
Nutr Res ; 93: 27-37, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34352722

RESUMO

Geranylgeraniol (GGOH) is found in edible oils such as olive, linseed, and sunflower oils, which have favorable metabolic effects. However, it is unknown whether these physiological benefits are mediated through the gut microbiome. Thus, the purpose of this study was to test the hypothesis that GGOH supplementation would improve glucose homeostasis and benefit the bone microstructure in obese mice through suppression of inflammation and modification of gut microbiota composition. Thirty-six male C57BL/6J mice were divided into 3 groups: a low-fat diet, a high-fat diet (HFD), and an HFD supplemented with 800 mg GGOH/kg diet (GG) for 14 weeks. Glucose and insulin tolerance tests were measured at baseline and end of study. The concentrations of adipokine cytokines (resistin, leptin, monocyte chemoattractant protein-1, interleukin-6) were measured via ELISA. Bone microarchitecture and quality were measured by micro-CT. Microbiome analysis was performed using 16S rRNA amplicon sequencing on cecal content. Relative to the HFD group, the GG group: (1) improved glucose tolerance and insulin sensitivity; (2) reduced production of pro-inflammatory adipokines, (3) increased serum procollagen I intact N-terminal propeptide (bone formation marker) concentrations, while decreasing serum collagen type 1 cross-linked C-telopeptide (bone resorption marker) levels, and (4) increased stiffness at both femur and LV-4 and cortical thickness at femoral midshaft. Compared to the HFD group, the GG group had an increased abundance of Butyricicoccus pullicaecorum and decreased Dorea longicatena in the cecal microbiome. Collectively, GGOH improves glucose homeostasis and bone microstructure in obese mice, probably via suppression of pro-inflammation and modification of microbiome composition.


Assuntos
Microbioma Gastrointestinal , Animais , Dieta Hiperlipídica/efeitos adversos , Diterpenos , Glucose , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , RNA Ribossômico 16S
18.
Artigo em Inglês | MEDLINE | ID: mdl-34065809

RESUMO

Body temperature is important for diagnosing illnesses. However, its assessment is often a difficult task, considering the large individual differences. Although 37 °C has been the gold standard of body temperature for over a century, the temperature of modern people is reportedly decreasing year by year. However, a mean axillary temperature of 36.89 ± 0.34 °C reported in 1957 is still cited in Japan. To assess the measured axillary temperature appropriately, understanding its distribution in modern people is important. This study retrospectively analyzed 2454 axillary temperature measurement data of healthy Japanese adults in 2019 (age range, 20-79 years; 2258 males). Their mean temperature was 36.47 ± 0.28 °C (36.48 ± 0.27 °C in males and 36.35 ± 0.31 °C in females). Approximately 5% of the 20-39-year-old males had body temperature ≥37 °C, whereas 8% had a temperature ≥ 37 °C in the afternoon. However, none of the subjects aged ≥50 years reported body temperature ≥37 °C. In multivariable regression analysis, age, blood pressure, pulse rate, and measurement time of the day were associated with axillary temperature. Our data showed that the body temperature of modern Japanese adults was lower than that reported previously. When assessing body temperature, the age, blood pressure, pulse rate, and measurement time of the day should be considered.


Assuntos
Temperatura Corporal , Termômetros , Adulto , Idoso , Eletrônica , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Temperatura , Adulto Jovem
19.
Artigo em Inglês | MEDLINE | ID: mdl-34444430

RESUMO

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in the older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in healthy older Japanese volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55-73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥65 years old) had higher CSF-TP concentration than the younger group (55-64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10-40 mg/dL). Conclusions: The reference interval of CSF-TP in the older population should be reconsidered for the precise diagnosis of neurological emergencies.


Assuntos
Proteínas do Líquido Cefalorraquidiano , Voluntários , Idoso , Líquido Cefalorraquidiano , Humanos , Japão , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos
20.
Artigo em Inglês | MEDLINE | ID: mdl-33916399

RESUMO

Coronavirus disease 2019 (COVID-19) has become a serious public health problem worldwide. In general, healthcare workers are considered to be at higher risk of COVID-19 infection. However, the prevalence of COVID-19 among healthcare workers in Japan is not well characterized. In this study, we aimed to examine the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among 2160 healthcare workers in hospitals and clinics that are not designated to treat COVID-19 patients in Japan. The prevalence of SARS-CoV-2 immunoglobulin G was 1.2% in August and October 2020 (during and after the second wave of the pandemic in Japan), which is relatively higher than that in the general population in Japan (0.03-0.91%). Because of the higher risk of COVID-19 infection, healthcare workers should be the top priority for further social support and vaccination against SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Pessoal de Saúde , Hospitais Gerais , Humanos , Japão/epidemiologia , Estudos Soroepidemiológicos
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