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1.
Int J Mol Sci ; 22(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299206

RESUMO

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-ß-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.


Assuntos
Cistationina beta-Sintase/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/patologia , Animais , Hipertrofia/genética , Hipertrofia/metabolismo , Hipertrofia/patologia , Masculino , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Proteínas Quinases S6 Ribossômicas/genética , Proteínas Quinases S6 Ribossômicas/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuínas/antagonistas & inibidores , Sirtuínas/genética , Sirtuínas/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
2.
Plast Reconstr Surg ; 148(1): 31-43, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34181602

RESUMO

BACKGROUND: Reduction mammaplasty for macromastia is one of the most common operations performed by plastic surgeons. There remains hesitancy in operating on adolescents, as there is ongoing debate about breast regrowth and potential impact on breastfeeding. The goal of this study was to analyze these concerns by reviewing the current literature. METHODS: A systematic review of MEDLINE, Scopus, and Google Scholar was conducted using the following terms: "breast reduction" or "mammaplasty" or "breast reconstruction" and "adolescent" or "youth" or "pediatric" or "child" or "teen." Primary outcomes were success of breastfeeding after the procedure and procedure-related complications. RESULTS: Twenty-three studies (87 percent retrospective), consisting of 2926 patients with preoperative cup sizes of C to KK (mean, DDD), met inclusion criteria. Mean age at the time of surgery ranged from 16 to 21 years, with the youngest patient being 12 years old. The overall complication rate was 27.3 percent (95 percent CI, 14.4 to 42.5 percent). Minor complications (22.8 percent; 95 percent CI, 10.2 to 38.5 percent) were more common than major (4.2 percent; 95 percent CI, 1.6 to 7.9 percent). Eighteen percent of patients (95 percent CI, 2.2 to 43.8 percent) reported regrowth of their breast tissue postoperatively, with 2.7 percent (95 percent CI, 0.9 to 5.5 percent) undergoing a second revision mammaplasty. Fifty-three percent of patients (95 percent CI, 36.0 to 69.3 percent) did not attempt breastfeeding. Of those who attempted, 55.1 percent (95 percent CI, 34.4 to 74.9 percent) were successful. CONCLUSIONS: Prospective data are lacking. Patient counseling should focus on encouraging a trial of breastfeeding, despite surgical history. One-fifth of adolescent patients may notice breast regrowth postoperatively; however, the amount of regrowth is likely small and unlikely to reexacerbate symptoms, as the rate of revision surgery is small.


Assuntos
Mama/anormalidades , Hipertrofia/cirurgia , Mamoplastia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Guias de Prática Clínica como Assunto , Tempo para o Tratamento/normas , Adolescente , Fatores Etários , Mama/crescimento & desenvolvimento , Mama/patologia , Mama/cirurgia , Aleitamento Materno , Criança , Aconselhamento , Feminino , Humanos , Hipertrofia/diagnóstico , Hipertrofia/patologia , Mamoplastia/métodos , Educação de Pacientes como Assunto , Complicações Pós-Operatórias/etiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Exacerbação dos Sintomas , Resultado do Tratamento , Adulto Jovem
3.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064664

RESUMO

Rutin is a flavonoid with antioxidant property. It has been shown to exert cardioprotection against cardiomyocyte hypertrophy. However, studies regarding its antihypertrophic property are still lacking, whether it demonstrates similar antihypertrophic effect to its metabolite, quercetin. Hence, this study aimed to investigate the effects of both flavonoids on oxidative stress and mitogen-activated protein kinase (MAPK) pathway in H9c2 cardiomyocytes that were exposed to angiotensin II (Ang II) to induce hypertrophy. Cardiomyocytes were exposed to Ang II (600 nM) with or without quercetin (331 µM) or rutin (50 µM) for 24 h. A group given vehicle served as the control. The concentration of the flavonoids was chosen based on the reported effective concentration to reduce cell hypertrophy or cardiac injury in H9c2 cells. Exposure to Ang II increased cell surface area, intracellular superoxide anion level, NADPH oxidase and inducible nitric oxide synthase activities, and reduced cellular superoxide dismutase activity and nitrite level, which were similarly reversed by both rutin and quercetin. Rutin had no significant effects on phosphorylated proteins of extracellular signal-related kinases (ERK1/2) and p38 but downregulated phosphorylated c-Jun N-terminal kinases (JNK1/2), which were induced by Ang II. Quercetin, on the other hand, had significantly downregulated the phosphorylated proteins of ERK1/2, p38, and JNK1/2. The quercetin inhibitory effect on JNK1/2 was stronger than the rutin. In conclusion, both flavonoids afford similar protective effects against Ang II-induced cardiomyocyte hypertrophy, but they differently modulate MAPK pathway.


Assuntos
Angiotensina II/toxicidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipertrofia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mioblastos Cardíacos/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Animais , Antioxidantes/farmacologia , Células Cultivadas , Hipertrofia/induzido quimicamente , Hipertrofia/tratamento farmacológico , Hipertrofia/patologia , Proteínas Quinases Ativadas por Mitógeno/genética , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/efeitos dos fármacos , NADPH Oxidases/metabolismo , Óxido Nítrico/metabolismo , Fosforilação , Ratos , Espécies Reativas de Oxigênio/metabolismo , Vasoconstritores/toxicidade
4.
BMC Neurol ; 21(1): 210, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034682

RESUMO

BACKGROUND: Primary right brachium pontis germinoma with hypertrophic olivary degeneration (HOD) is extremely rare. A preoperative diagnosis is challenging due to the absence of characterized clinical and neuroimaging features, and biopsy should be considered. CASE PRESENTATION: A 20-year-old male patient presented with a case of primary intracranial germinoma originating from right brachium pontis with HOD manifesting as ocular myoclonus, nystagmus in both eyes, ataxic gait and incoordination of the limbs. Magnetic resonance imaging (MRI) revealed an irregular patchy lesion with hyperintensity on T2-weighted images (T2WI) and T2 fluid-attenuated inversion recovery (FLAIR) without enhancement by gadolinium (Gd). Furthermore, a focal hyperintense nodule on T2WI in the left inferior olive nucleus (ION) of the medulla oblongata was considered hypertrophic olivary degeneration (HOD) based on the patient's symptoms and neuroimaging findings. Due to suspected demyelinating disease and low-grade glioma (LGG), a biopsy was planned. The pathological diagnosis was germinoma. Subsequently, he received chemoradiation therapy, resulting in the improvement of neurological deficits and the disappearance of the lesion on MRI. CONCLUSION: A case of "Primary right brachium pontis germinoma with HOD" is reported for the first time. A preoperative diagnosis is challenging due to the fact of absence of clinical signs and symptoms and neuroimaging characteristics. However, patients can have favourable prognoses with appropriate evaluation and treatment.


Assuntos
Neoplasias Encefálicas/patologia , Germinoma/patologia , Pedúnculo Cerebelar Médio/patologia , Núcleo Olivar/patologia , Humanos , Hipertrofia/etiologia , Hipertrofia/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Bulbo/patologia , Mioclonia/etiologia , Adulto Jovem
5.
FASEB J ; 35(6): e21676, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34042220

RESUMO

Ligamentum flavum hypertrophy (LFH) leads to lumbar spinal stenosis (LSS) caused by LF tissue inflammation and fibrosis. Emerging evidence has indicated that dysregulated microRNAs (miRNAs) have an important role in inflammation and fibrosis. Mechanical stress (MS) has been explored as an initiating step in LFH pathology progression; the inflammation-related miRNAs induced after mechanical stress have been implicated in fibrosis pathology. However, the pathophysiological mechanism of MS-miRNAs-LFH remains to be elucidated. Using miRNAs sequencing analysis and subsequent confirmation with qRT-PCR assays, we identified the decreased expression of miR-10396b-3p and increased expression of IL-11 (interleukin-11) as responses to the development of LSS in hypertrophied LF tissues. We also found that IL-11 is positively correlated with fibrosis indicators of collagen I and collagen III. The up-regulation of miR-10396b-3p significantly decreased the level of IL-11 expression, whereas miR-10396b-3p down-regulation increased IL-11 expression in vitro. Luciferase reporter assay indicates that IL-11 is a direct target of miR-10396b-3p. Furthermore, cyclic mechanical stress inhibits miR-10396b-3p and induces IL-11, collagen I, and collagen III in vitro. Our results showed that overexpression of miR-10396b-3p suppresses MS-induced LFH by inhibiting collagen I and III via the inhibition of IL-11. These data suggest that the MS-miR-10396b-3p-IL-11 axis plays a key role in the pathological progression of LFH.


Assuntos
Hipertrofia/prevenção & controle , Interleucina-11/antagonistas & inibidores , Ligamento Amarelo/crescimento & desenvolvimento , MicroRNAs/genética , Estenose Espinal/prevenção & controle , Estresse Mecânico , Feminino , Humanos , Hipertrofia/etiologia , Hipertrofia/patologia , Interleucina-11/genética , Interleucina-11/metabolismo , Ligamento Amarelo/metabolismo , Ligamento Amarelo/patologia , Masculino , Pessoa de Meia-Idade , Estenose Espinal/etiologia , Estenose Espinal/patologia
6.
J Orthop Surg (Hong Kong) ; 29(2): 23094990211012846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33926334

RESUMO

OBJECTIVE: This study was designed to investigate the relationship between the laminar slope angle (LSA) and the lumbar disc degenerative grade, the cross-section area (CSA) of multifidus muscle, the muscle-fat index, and the thickness of the ligamentum flavum. METHODS: Retrospective analysis of 122 patients who were scheduled to undergo a lumbar operation for diagnoses associated with degenerative lumbar disease between January and December 2017. The L4-L5 disc grade was evaluated from preoperative sagittal T2-weighed magnetic resonance imaging of the lumber region; the CSA of the multifidus and muscle-fat index were measured at the L4 level, while the thickness of the ligamentum flavum was measured at the L4-L5 facet level from axis T2-weighed magnetic resonance imaging. The slope of the laminar was evaluated from preoperative three-dimensional computer tomography at the tip level of the facet joints and selected by the axis plane. Independent-sample T-tests were used to assess the association between age and measurement indices. RESULTS: Our results showed that age was positively connected with the LSA of L4 and L5 in different patients, although there was no significant difference between age and the difference of the two segment LSA. Partial correlation analysis, excluding the interference of age, revealed a strong negative relationship between the LSA of L4 and the thickness of the ligamentum flavum, irrespective of whether we considered the left or right. However, there was no correlation with lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. CONCLUSION: The thickness of the ligamentum flavum showed changes with anatomical differences in the LSA, but not the lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. A small change in LSA may cause large mechanical stress; this may be one of the causative factors responsible for lumbar spinal stenosis.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Ligamento Amarelo/diagnóstico por imagem , Vértebras Lombares , Estenose Espinal/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertrofia/complicações , Hipertrofia/diagnóstico por imagem , Hipertrofia/patologia , Imageamento Tridimensional , Degeneração do Disco Intervertebral/diagnóstico por imagem , Ligamento Amarelo/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estenose Espinal/etiologia , Estenose Espinal/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
FASEB J ; 35(5): e21587, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33891350

RESUMO

We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2 ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10-7 for rs4675569, 1.7 × 10-6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.


Assuntos
Hipertrofia/patologia , Íntrons , Fibras Musculares Esqueléticas/patologia , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Treinamento de Força/efeitos adversos , Proteína Gli3 com Dedos de Zinco/genética , Adulto , Estudo de Associação Genômica Ampla , Humanos , Hipertrofia/etiologia , Hipertrofia/metabolismo , Masculino , Fibras Musculares Esqueléticas/metabolismo , Adulto Jovem
8.
Aging (Albany NY) ; 13(8): 10891-10919, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864446

RESUMO

Alzheimer's disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon long-term challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by 1H-magnetic-resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD-related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis.


Assuntos
Adipócitos/patologia , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Fígado Gorduroso/diagnóstico , Intolerância à Glucose/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/patologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/administração & dosagem , Sacarose na Dieta/efeitos adversos , Modelos Animais de Doenças , Metabolismo Energético/genética , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Humanos , Hipertrofia/diagnóstico , Hipertrofia/etiologia , Hipertrofia/metabolismo , Hipertrofia/patologia , Fígado/patologia , Camundongos , Camundongos Transgênicos , Índice de Gravidade de Doença
9.
Abdom Radiol (NY) ; 46(8): 4046-4055, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33779787

RESUMO

PURPOSE: Preoperative hypertrophy induction of future liver remnant (FLR) reduces the risk of postoperative liver insufficiency after partial hepatectomy. One of the most commonly used methods to induce hypertrophy of FLR is portal vein embolization (PVE). Recent studies have shown that transarterial radioembolization (TARE) also induces hypertrophy of the contralateral liver lobe. The aim of our study was to evaluate contralateral hypertrophy after TARE versus after PVE taking into account the effect of cirrhosis. METHODS: Forty-nine patients undergoing PVE before hemihepatectomy and 24 patients with TARE as palliative treatment for liver malignancy were retrospectively included. Semi-automated volumetry of the FLR/contralateral liver lobe before and after intervention (20 to 65 days) was performed on CT or MRI, and the relative increase in volume was calculated. Cirrhosis was evaluated independently by two radiologists on CT/MRI, and interrater reliability was calculated. RESULTS: Hypertrophy after PVE was significantly more pronounced than after TARE (25.3% vs. 7.4%; p < 0.001). In the subgroup of patients without cirrhosis, the difference was also statistically significant (25.9% vs. 8.6%; p = 0.002), whereas in patients with cirrhosis, the difference was not statistically significant (18.2% vs. 7.4%; p = 0.212). After PVE, hypertrophy in patients without cirrhosis was more pronounced than in patients with cirrhosis (25.9% vs. 18.2%; p = 0.203), while after TARE, hypertrophy was comparable in patients with and without cirrhosis (7.4% vs. 8.6%; p = 0.928). CONCLUSION: TARE induces less pronounced hypertrophy of the FLR compared to PVE. Cirrhosis seems to be less of a limiting factor for hypertrophy after TARE, compared to PVE.


Assuntos
Embolização Terapêutica , Neoplasias Hepáticas , Hepatectomia , Humanos , Hipertrofia/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Veia Porta/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
10.
Rev. argent. cir. plást ; 27(1): 21-24, jan.-mar. 2021. ilus
Artigo em Espanhol | LILACS | ID: biblio-1223520

RESUMO

Introducción. La hipertrofia de los labios menores se define como tejido labial que sobresale más allá de los labios mayores, puede afectar de manera uni- o bilateral y resultar en dispareunia, interferencia con los deportes, dificultades con la limpieza, irritación e infecciones crónicas del tracto urinario, incomodidad para el uso de prendas ajustadas, además de trastornos psicológicos. Todos estos motivos llevan a las mujeres a la consulta. La reducción de labios menores es el procedimiento estético genital femenino más común. Este trabajo tiene como objetivo presentar técnicas de baja complejidad para resolver diferentes grados de hipertrofia de labios menores. Materiales y métodos. Estudio retrospectivo, observacional que comprendió 3 pacientes entre el periodo de marzo del 2019 a febrero 2020 que Incluyó a pacientes con hipertrofias leves y moderadas. Resultados. En 2 pacientes se realizó escisión directa y en 1, técnica del desepitelizado más lipotransferencia de labios mayores, sin evidenciar complicaciones mayores. Discusión. Si bien en la literatura se han reportado un gran número de técnicas quirúrgicas, cada una de ellas debe adecuarse al tipo de hipertrofia labial. La técnica del desepitelizado permite conservar un borde natural, con conservación de la coloración y textura original de la paciente, aporte neurovascular, pero no es conveniente utilizarla en pacientes de grados mayores de hipertrofia. La escisión directa proporciona una técnica simple para la escisión del exceso de tejido en pacientes con mayor tamaño de sus labios menores, pero elimina el contorno, la coloración y la textura naturales del borde libre, aun así, las pacientes resultan conformes con su nuevo aspecto. Conclusión. La reconstrucción de los labios menores, utilizando las técnicas de desepitelización y escisión directa, es confiable y da un resultado cosmético y funcional exitoso. Estas técnicas son de baja complejidad, tiempo operatorio breve, técnicamente reproducibles, dando gran conformidad y resultando un método seguro


Introduction. Hypertrophy of the labia minora is defined as lip tissue that protrudes beyond the labia majora, can affect unilaterally or bilaterally and result in dyspareunia, interference with sports, difficulties with cleaning, irritation and chronic infections of the urinal tract, discomfort for wearing tight clothes, in addition to psychological disorders. All these reasons lead women to the consultation. Labia minora reduction is the most common female genital cosmetic procedure. This work aims to present low complexity techniques to resolve different degrees of hypertrophy of the labia minora. Materials and methods: retrospective, observational study that comprised 3 patients between the period of March 2019 to February 2020 that included patients with mild and moderate hypertrophy. Results: Direct excision was performed in 2 patients and in 1, de-epithelialization technique plus lipotransference of the labia majora. Without showing major complications. Discussion: Although a large number of surgical techniques have been reported in the literature, each of them must be adapted to the type of lip hypertrophy. The de-epithelialization technique allows a natural border to be preserved, with preservation of the patient's original color and texture, neurovascular supply, but it is not convenient to use it in patients with higher degrees of hypertrophy. Direct excision provides a simple technique for excision of excess tissue in patients with larger labia minora, but removes the natural contour, coloration and texture of the free edge, yet patients are still satisfied with their new appearance. Conclusion. The reconstruction of the labia minora, using de-epithelialization and direct excision techniques is reliable and gives a successful cosmetic and functional result. These are low complexity techniques, short operating time, technically reproducible, giving great conformity and resulting in a safe method


Assuntos
Humanos , Feminino , Procedimentos Cirúrgicos Operatórios/métodos , Vulva/patologia , Estudos Retrospectivos , Hipertrofia/patologia
11.
Molecules ; 26(4)2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561994

RESUMO

Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. Resveratrol is a nutraceutical with anti-inflammatory properties. Previous studies have shown high doses (100-400 mg/kg bodyweight/day) benefit mdx mice. We treated 4-week-old mdx and wildtype mice with a lower dose of resveratrol (5 mg/kg bodyweight/day) for 15 weeks. Voluntary exercise was used to test if a lower dosage than previously tested could reduce exercise-induced damage where a greater inflammatory infiltrate is present. We found resveratrol promoted skeletal muscle hypertrophy in wildtype mice. In dystrophic muscle, resveratrol reduced exercise-induced muscle necrosis. Gene expression of immune cell markers, CD86 and CD163 were reduced; however, signalling targets associated with resveratrol's mechanism of action including Sirt1 and NF-κB were unchanged. In conclusion, a lower dose of resveratrol compared to the dosage used by other studies reduced necrosis and gene expression of inflammatory cell markers in dystrophic muscle suggesting it as a therapeutic candidate for treating DMD.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Resveratrol/farmacologia , Animais , Biomarcadores/metabolismo , Hipertrofia/induzido quimicamente , Hipertrofia/metabolismo , Hipertrofia/patologia , Inflamação/metabolismo , Camundongos , Necrose/tratamento farmacológico , Resveratrol/uso terapêutico
12.
Aging (Albany NY) ; 13(4): 6025-6040, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568575

RESUMO

Lumbar spinal stenosis (LSS) is a condition wherein patients exhibit age-related fibrosis, elastin-to-collagen ratio reductions, and ligamentum flavum hypertrophy. This study was designed to assess the relationship between SIRT6 and telomerase activity in hypertrophic ligamentum flavum (LFH) cells from LSS patients. We observed significant reductions in SIRT6, TPP1, and POT1 protein levels as well as increases in telomerase reverse transcriptase (TERT) levels and telomerase activity in LFH tissues relative to non- hypertrophic ligamentum flavum (LFN) tissues. When SIRT6 was overexpressed in these LFH cells, this was associated with significant increases in telomerase activity and a significant reduction in fibrosis-related protein expression. These effects were reversed, however, when telomerase activity was inactivated by hTERT knockdown in these same cells. SIRT6 overexpression was further found to reduce the frequency of senescence-associated ß-galactosidase (SA-ß-Gal)-positive LFH cells and to decrease p16, MMP3, and L1 mRNA levels and telomere dysfunction-induced foci (TIFs) in LFH cells. In contrast, hTERT knockdown-induced telomerase inactivation eliminated these SIRT6-dependent effects. Overall, our results indicate that SIRT6 functions as a key protective factor that prevents cellular senescence and telomere dysfunction in ligamentum flavum cells, with this effect being at least partially attributable to SIRT6-dependent telomerase activation.


Assuntos
Dano ao DNA , Hipertrofia , Ligamento Amarelo/patologia , Fatores de Proteção , Sirtuínas/genética , Estenose Espinal/patologia , Telomerase , Envelhecimento , Senescência Celular , Feminino , Fibrose , Humanos , Hipertrofia/patologia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade
13.
Mol Biol Rep ; 48(1): 645-655, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33394230

RESUMO

Cardiomyocytes possess the ability to respond to mechanical stimuli by reprogramming their gene expression. This study investigated the effects of different loading protocols on signaling and expression responses of myogenic, anabolic, inflammatory, atrophy and pro-apoptotic genes in cardiomyocyte-like H9C2 cells. Differentiated H9C2 cells underwent various stretching protocols by altering their elongation, frequency and duration, utilizing an in vitro cell tension system. The loading-induced expression changes of MyoD, Myogenin, MRF4, IGF-1 isoforms, Atrogin-1, Foxo1, Fuca and IL-6 were measured by Real Time-PCR. The stretching-induced activation of Akt and Erk 1/2 was also evaluated by Western blot analysis. Low strain (2.7% elongation), low frequency (0.25 Hz) and intermediate duration (12 h) stretching protocol was overall the most effective in inducing beneficial responses, i.e., protein synthesis along with the suppression of apoptosis, inflammation and atrophy, in the differentiated cardiomyocytes. These findings demonstrated that varying the characteristics of mechanical loading applied on H9C2 cells in vitro can regulate their anabolic/survival program.


Assuntos
Apoptose/genética , Reprogramação Celular/genética , Hipertrofia/genética , Mecanotransdução Celular/genética , Miócitos Cardíacos/metabolismo , Animais , Morte Celular/genética , Linhagem Celular , Sobrevivência Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Hipertrofia/patologia , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Fator de Crescimento Insulin-Like I/genética , Sistema de Sinalização das MAP Quinases/genética , Proteínas Musculares/genética , Proteína MyoD/genética , Miócitos Cardíacos/patologia , Fatores de Regulação Miogênica/genética , Miogenina/genética , Ratos , Proteínas Ligases SKP Culina F-Box/genética
14.
J Oral Maxillofac Surg ; 79(5): 1122-1132, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33493432

RESUMO

PURPOSE: Our current understanding of unilateral condylar hyperplasia (UCH) was put forth by Obwegeser. He hypothesized that UCH is 2 separate conditions: hemimandibular hyperplasia and hemimandibular elongation. This hypothesis was based on the following 3 assumptions: 1) the direction of overgrowth, in UCH, is bimodal-vertical or horizontal, with rare cases growing obliquely; 2) UCH can expand a hemimandible with and without significant condylar enlargement; and 3) there is an association between the condylar expansion and the direction of overgrowth-minimal expansion resulting in horizontal growth and significant enlargement causing vertical displacement. The purpose of this study was to test these assumptions. PATIENTS AND METHODS: We analyzed the computed tomography scans of 40 patients with UCH. First, we used a Silverman Cluster analysis to determine how the direction of overgrowth is distributed in the UCH population. Next, we evaluated the relationship between hemimandibular overgrowth and condylar enlargement to confirm that overgrowth can occur independently of condylar expansion. Finally, we assessed the relationship between the degree of condylar enlargement and the direction of overgrowth to ascertain if condylar expansion determines the direction of growth. RESULTS: Our first investigation demonstrates that the general impression that UCH is bimodal is wrong. The growth vectors in UCH are unimodally distributed, with the vast majority of cases growing diagonally. Our second investigation confirms the observation that UCH can expand a hemimandible with and without significant condylar enlargement. Our last investigation determined that in UCH, there is no association between the degree of condylar expansion and the direction of the overgrowth. CONCLUSIONS: The results of this study disprove the idea that UCH is 2 different conditions: hemimandibular hyperplasia and hemimandibular elongation. It also provides new insights about the pathophysiology of UCH.


Assuntos
Assimetria Facial , Côndilo Mandibular , Assimetria Facial/diagnóstico por imagem , Assimetria Facial/etiologia , Assimetria Facial/patologia , Humanos , Hiperplasia , Hipertrofia/patologia , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/patologia
15.
Lasers Med Sci ; 36(4): 791-802, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32638240

RESUMO

Compensatory hypertrophy (CH) occurs due to excessive mechanical load on a muscle, promoting an increase in the size of muscle fibers. In clinical practice, situations such as partial nerve injuries, denervation, and muscle imbalance caused by trauma to muscles and nerves or diseases that promote the loss of nerve conduction can induce CH in muscle fibers. Photobiomodulation (PBM) has demonstrated beneficial effects on muscle tissue during CH. The aim of the present study was to evaluate the effect of PBM on the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) as well as type 2 metalloproteinases (MMP-2) during the process of CH due to excessive load on the plantaris muscle in rats. Forty-five Wistar rats weighing 250 g were divided into three groups: control group (n = 10), hypertrophy (H) group (n = 40), and H + PBM group (n = 40). CH was induced through the ablation of synergist muscles of the plantaris muscle. The tendons of the gastrocnemius and soleus muscles were isolated and sectioned to enable the partial removal of each of muscle. The preserved plantaris muscle below the removed muscles was submitted to excessive functional load. PBM was performed with low-level laser (AsGaAl, λ = 780 nm; 40 mW; energy density: 10 J/cm2; 10 s on each point, 8 points; 3.2 J). Animals from each group were euthanized after 7 and 14 days. The plantaris muscles were carefully removed and sent for analysis of the gene and protein expression of IL-6 and TNF-α using qPCR and ELISA, respectively. MMP-2 activity was analyzed using zymography. The results were submitted to statistical analysis (ANOVA + Tukey's test, p < 0.05). The protein expression analysis revealed an increase in IL-6 levels in the H + PBM group compared to the H group and a reduction in the H group compared to the control group. A reduction in TNF-α was found in the H and H + PBM groups compared to the control group at 7 days. The gene expression analysis revealed an increase in IL-6 in the H + PBM group compared to the H group at 14 days as well as an increase in TNF-α in the H + PBM group compared to the H group at 7 days. Increases in MMP-2 were found in the H and H + PBM groups compared to the control group at both 7 and 14 days. Based on findings in the present study, it is concluded that PBM was able to modulate pro-inflammatory cytokines that are essential for the compensatory hypertrophy process. However, it has not shown a modulation effect directly in MMP-2 activity during the same period evaluated.


Assuntos
Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Músculo Esquelético/patologia , Músculo Esquelético/efeitos da radiação , Animais , Hipertrofia/metabolismo , Hipertrofia/patologia , Hipertrofia/radioterapia , Interleucina-6/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Músculo Esquelético/metabolismo , Ratos , Ratos Wistar , Tendões/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Ann N Y Acad Sci ; 1490(1): 42-56, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32978775

RESUMO

During osteoarthritis (OA), articular chondrocytes undergo phenotypic changes that resemble developmental patterns characteristic of growth plate chondrocytes. These phenotypic alterations lead to a hypertrophy-like phenotype characterized by altered production of extracellular matrix constituents and increased collagenase activity, which, in turn, results in cartilage destruction in OA disease. Recent studies have shown that the phenotypic instability and dysregulated gene expression in OA are associated with changes in DNA methylation patterns. Subsequent efforts have aimed to identify changes in DNA methylation with functional impact in OA disease, to potentially uncover therapeutic targets. Here, we paired an in vitro 3D/pellet culture system that mimics chondrocyte hypertrophy with RNA sequencing (RNA-Seq) and enhanced reduced representation of bisulfite sequencing (ERRBS) to identify transcriptomic and epigenomic changes in murine primary articular chondrocytes undergoing hypertrophy-like differentiation. We identified hypertrophy-associated changes in DNA methylation patterns in vitro. Integration of RNA-Seq and ERRBS datasets identified associations between changes in methylation and gene expression. Our integrative analyses showed that hypertrophic differentiation of articular chondrocytes is accompanied by transcriptomic and epigenomic changes in vitro. We believe that our integrative approaches have the potential to uncover new targets for therapeutic intervention.


Assuntos
Condrogênese/genética , Metilação de DNA/genética , Epigênese Genética/genética , Osteoartrite/genética , Osteoartrite/patologia , Animais , Cartilagem Articular/crescimento & desenvolvimento , Cartilagem Articular/patologia , Diferenciação Celular/fisiologia , Células Cultivadas , Condrócitos/citologia , Condrócitos/patologia , Condrogênese/fisiologia , Expressão Gênica , Humanos , Hipertrofia/genética , Hipertrofia/patologia , Camundongos , Camundongos Endogâmicos C57BL
17.
Spine (Phila Pa 1976) ; 46(9): E520-E527, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33273443

RESUMO

STUDY DESIGN: Experimental animal study. OBJECTIVE: The aim of this study was to clarify chronological effects of mechanical stress on ligamentum flavum (LF) using a long-term fusion rabbit model. SUMMARY OF BACKGROUND DATA: LF hypertrophy is a major pathology of lumbar spinal stenosis (LSS), but its mechanism remains unclear. We previously demonstrated mechanical-stress-induced LF hypertrophy with a rabbit model. However, we only investigated LFs at a single time point in the short-term; the effects of long-term mechanical stress have not been elucidated. METHODS: Eighteen-week-old male New Zealand White rabbits were randomly divided into two groups: the mechanical stress group underwent L2-3 and L4-5 posterolateral fusion and resection of the L3-4 supraspinal muscle, whereas the control group underwent only surgical exposure. Rabbits were sacrificed 16 and 52 weeks after the procedure. Axial specimens of LFs at L3-4 were evaluated histologically. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) was performed to assess the numbers of vessels and myofibroblasts. RESULTS: In the mechanical stress group, LFs at the L3-4 level exhibited hypertrophy with elastic fiber disruption and cartilage matrix production at 16 and 52 weeks. A trend test indicated that mechanical stress induced LF hypertrophy, elastic fiber disruption, and cartilage matrix production in a time-dependent manner, with the lowest levels before treatment and the highest at 52 weeks. Immunostaining for α-SMA showed similar numbers of vessels in both groups, whereas the percentage of myofibroblasts was significantly larger at 16 and 52 weeks in the mechanical stress group than in the control group. CONCLUSION: We demonstrated that long-term mechanical stress caused LF hypertrophy with progressive elastic fiber disruption and cartilage matrix production accompanied by enhanced myofibroblasts. In addition, the reported rabbit model could be extended to elucidate the mechanism of LF hypertrophy and to develop new therapeutic strategies for LSS by preventing LF hypertrophy.Level of Evidence: SSSSS.


Assuntos
Ligamento Amarelo/diagnóstico por imagem , Ligamento Amarelo/fisiologia , Estresse Mecânico , Experimentação Animal , Animais , Cartilagem/patologia , Tecido Elástico/diagnóstico por imagem , Tecido Elástico/patologia , Hipertrofia/diagnóstico por imagem , Hipertrofia/patologia , Ligamento Amarelo/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Vértebras Lombares/fisiologia , Masculino , Coelhos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/patologia , Fatores de Tempo
18.
Food Funct ; 12(1): 328-339, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33300913

RESUMO

The imbalance between the anabolism and catabolism of the extracellular matrix (ECM) is of great importance to osteoarthritis (OA) development. Aberrant inflammatory responses and hypertrophic changes of chondrocytes are the main contributors to these metabolic disorders. In the present study, we found that Oroxylin A (ORA), a flavonoid compound derived from Oroxylum indicum, maintained ECM hemostasis of chondrocytes by Interleukin-1ß (IL-1ß) stimulation. Besides, it was demonstrated that IL-1ß induced over-production of inflammatory mediators was attenuated by ORA treatment. Moreover, ORA could rescue IL-1ß mediated hypertrophic alterations of chondrocytes. Mechanistically, ORA's protective effects were found to be associated with both NF-κB and Wnt/ß-catenin signaling inhibition. Meanwhile, molecular docking analysis revealed that ORA could strongly bind to the inhibitor kappa B kinaseß (IKKß) and dishevelled, Dsh Homolog 2 (Dvl2), the upstream molecules of the NF-κB axis and ß-catenin axis, respectively. In addition, ORA driven chondroprotective effects were also affirmed in a surgically induced OA mouse model. Taken together, the current study suggested that ORA might be a promising therapeutic option for the treatment of OA.


Assuntos
Flavonoides/farmacologia , Hipertrofia/prevenção & controle , Inflamação/prevenção & controle , Osteoartrite/tratamento farmacológico , Animais , Modelos Animais de Doenças , Humanos , Hipertrofia/patologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite/patologia
19.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255398

RESUMO

Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-ß, 1-14 days) and thyroid hormone hypertrophic medium (T3, 15-28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-ß2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs' therapeutic effect on cartilage regeneration and hypertrophy suppression.


Assuntos
Cartilagem Hialina/crescimento & desenvolvimento , Hipertrofia/genética , Células-Tronco Mesenquimais/citologia , Osteoartrite/genética , Animais , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrogênese/genética , Humanos , Ácido Hialurônico/farmacologia , Hipertrofia/patologia , Hipertrofia/prevenção & controle , Hipertrofia/terapia , Proteínas Matrilinas/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Osteoartrite/terapia , Regeneração/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Tecidos Suporte , Fator de Crescimento Transformador beta/genética
20.
Sci Rep ; 10(1): 22314, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339902

RESUMO

Prevalence of major depression in people with chronic heart failure is higher than in normal populations. Depression in heart failure has become a major issue. Psilocybin-containing mushrooms commonly known as magic mushrooms, have been used since ancient times for their mind healing properties. Their safety in cardiovascular disease conditions is not fully known and may pose as a risk for users suffering from these illnesses. Study investigates the effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushrooms use from genus Psilocybe and Panaeolus respectively, in a pathological hypertrophy conditions in which endothelin-1 disorder is a contributor to pathogenesis. We examined the effects of the mushrooms extracts on endothelin-1-induced hypertrophy and tumor necrosis factor-α (TNF- α)-induced cell injury in H9C2 cardiomyocytes. Mushrooms were oven dried and extracted with cold and boiling-hot water. H9C2 cardiomyocytes were induced with endothelin-1 prior to treatment with extracts over 48 h. Cell injury was stimulated with TNF-α. Results proposed that the water extracts of Panaeolus cyanescens and Psilocybe cubensis did not aggravate the pathological hypertrophy induced by endothelin-1 and also protected against the TNF-α-induced injury and cell death in concentrations used. Results support medicinal safe use of mushrooms under controlled conditions and cautioned use of higher concentrations.


Assuntos
Agaricales/química , Endotelina-1/genética , Hipertrofia/tratamento farmacológico , Psilocybe/química , Receptor de Endotelina A/genética , Animais , Antagonistas do Receptor de Endotelina A/farmacologia , Alucinógenos/química , Alucinógenos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Hipertrofia/induzido quimicamente , Hipertrofia/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Fenilpropionatos/farmacologia , Psilocibina/química , Psilocibina/farmacologia , Piridazinas/farmacologia , Ratos , Receptor de Endotelina A/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
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