RESUMO
BACKGROUND: Yeast biomass, encompassing fatty acids, terpenoids, vitamins, antioxidants, enzymes, and other bioactive compounds have been extensively utilized in food-related fields. The safety and potential bioactivities of Scheffersomyces segobiensis DSM 27193, an oleaginous yeast strain, are unclear. RESULTS: Scheffersomyces segobiensis DSM 27193 accumulated large palmitoleic acid (POA) levels (43.4 g kg-1 biomass) according to the results of whole-cell components. We annotated the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and predicted the categories and host of the pathogen-host interactions (PHI) genes in S. segobiensis DSM 27193. However, S. segobiensis DSM 27193 did not exert toxic effects in mice. Administration of S. segobiensis DSM 27193 led to substantial weight reduction by diminishing food intake in an obesity mouse model. Additionally, it reversed hepatic steatosis and adipose tissue hypertrophy, and improved abnormalities in serum biochemical profiles such as triglyceride, total cholesterol, low-density lipoprotein cholesterol, lipopolysaccharide, tumor necrosis factor-α, interleukin-1ß, and interleukin-6. CONCLUSION: This study is the first to illustrate the safety and effects of S. segobiensis DSM 27193 against obesity and offers a scientific rationale for its application in functional food supplements. © 2023 Society of Chemical Industry.
Assuntos
Ácidos Graxos Monoinsaturados , Fígado Gorduroso , Saccharomycetales , Animais , Camundongos , Fígado Gorduroso/tratamento farmacológico , Obesidade/tratamento farmacológico , Tecido Adiposo , Hipertrofia/patologia , Colesterol , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , FígadoRESUMO
BACKGROUND: ShuGan-QieZhi capsule (SGQZC) is a traditional Chinese preparation used to treat hyperlipidemia and obesity, even non-alcoholic fatty liver disease (NAFLD). However, its therapeutic effects, main bioactive ingredients, as well as potential mechanisms for NAFLD are still unclear. PURPOSE: To investigate the pharmacological effect, main active ingredients, and mechanisms of SGQZC against high-fat diet (HFD)-induced NAFLD in mice. METHODS: NAFLD models were established by feeding C57BL/6 J mice an HFD for 24 weeks. From the 12th week, HFD-fed mice received daily gavage of either SGQZC or silibinin for 12 weeks. Hepatic hypertrophy parameters, along with hepatic and systemic lipid metabolism changes in NAFLD mice, were assessed. Oil red O and histopathological staining techniques determined lipid accumulation and liver injury severity. qRT-PCR analysis measured the expression of genes tied to liver lipid metabolism and inflammation. HPLC-MS/MS identified the primary components of SGQZC in the serum. Human normal hepatocytes (LO2) and hepatic stellate cells (LX-2) were used to screen SGQZC's bioactive ingredients. Network pharmacological analysis, transcriptomics, and western blotting delved into SGQZC's synergistic mechanisms against NAFLD. RESULTS: SGQZC ameliorated abnormal lipid metabolism and liver hypertrophy in mice with HFD-induced NAFLD, consequently reducing hepatic lipid accumulation, inflammatory cell infiltration, and liver impairment. Eight crucial components of SGQZC were detected in serum using HPLC-MS/MS and were found to effectively attenuate lipid accumulation and inflammation in liver cells. Further investigation indicated that SGQZC modulates MAPK pathway and AKT/NF-κB pathway, subsequently improving lipid metabolism and inflammation. CONCLUSION: SGQZC alleviates NAFLD by synergistically modulating the MAPK-mediated lipid metabolism and inhibiting AKT/NF-κB pathways-mediated inflammation. Our findings reveal the enormous potential of SGQZC for the treatment of NAFLD, providing a possible new clinical therapeutic strategy.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espectrometria de Massas em Tandem , Camundongos Endogâmicos C57BL , Fígado , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos , Dieta Hiperlipídica/efeitos adversos , Lipídeos , Hipertrofia/patologiaRESUMO
The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized were characterized by different physical and chemical methods. The in vivo investigation evaluated Wistar rats (n = 20, 11 days, adult male with 21 weeks) subdivided into untreated (HGLI diet), conventional treatment (nutritionally adequate diet), treatment 1 (HGLI + crude extract (12.5 mg/kg)), and treatment 2 (HGLI + EPG (50 mg/kg)) groups. Dietary intake, caloric intake and efficiency, weight, inflammatory cytokines tissue concentration, visceral adipose tissue (VAT) weight, histopathological analysis, and antioxidant activity in plasma and VAT were investigated. EPG showed the same physical and chemical characteristics as previous batches (95.2 nm, smooth surface, and chemical interactions between materials). The EPG-treated group was the only group promoting negative ∆dietary intake, ∆caloric efficiency, and ∆weight. In addition, it presented a significant reduction (p < 0.05) in IL-6 and leptin levels and a greater presence of multilocular adipocytes. The results suggest that EPG can act as a nutraceutical in adjuvant therapy for treating inflammatory diseases associated with adipose tissue accumulation.
Assuntos
Citocinas , Obesidade , Ratos , Animais , Masculino , Ratos Wistar , Obesidade/patologia , Citocinas/farmacologia , Gelatina/farmacologia , Tecido Adiposo/patologia , Adipócitos , Hipertrofia/patologia , Carotenoides/farmacologiaRESUMO
BACKGROUND: Aloe-emodin (AE), a natural anthraquinone extract from traditional Chinese medicinal plants, has been certified to protect against acute myocardial ischemia. However, its effect on cardiac remodeling after chronic myocardial infarction (MI) and the possible mechanism remain unclear. PURPOSE: This study investigated the effect of AE on cardiac remodeling and oxidative damage induced by myocardial infarction (MI) in vitro and explored the underlying mechanisms. METHODS: Echocardiography and Masson staining were used to demonstrate myocardial dysfunction and fibrosis. Cell apoptosis was detected by TUNEL staining. The expressions of fibrosis-related factors such as type I collagen, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) were detected by Western blot. RESULTS: Our data demonstrated that AE treatment significantly improved cardiac function, reduced structural remodeling, and reduced cardiac apoptosis and oxidative stress in mice with myocardial infarction. In vitro, AE could protect neonatal mouse cardiomyocytes (NMCM) from angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and apoptosis, and significantly inhibited (p < 0.05) Ang II-induced reactive oxygen species (ROS) increase. Furthermore, AE treatment significantly reversed the Ang ii-induced upregulation. CONCLUSION: In summary, our work reveals for the first time that AE activates the TGF-ß signaling pathway by up-regulating Smad7 expression, which in turn regulates the expression of fibrosis-related genes, ultimately improving cardiac function, inhibiting the development of cardiac fibrosis and hypertrophy in rats with chronic MI.
Assuntos
Aloe , Cardiomiopatias , Emodina , Infarto do Miocárdio , Camundongos , Ratos , Animais , Emodina/farmacologia , Remodelação Ventricular , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos , Cardiomiopatias/metabolismo , Hipertrofia/patologia , Fibrose , Miocárdio/metabolismo , Angiotensina II/farmacologia , Proteína Smad7/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Initially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear. AIM OF THE STUDY: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. MATERIALS AND METHODS: Network pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. RESULTS: Network pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including TnfÉ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. CONCLUSIONS: QGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.
Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Qigong , Animais , Feminino , Humanos , Camundongos , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Modelos Animais de Doenças , Estradiol , Hipertrofia/patologia , Inflamação/metabolismo , Insulina , Resistência à Insulina/fisiologia , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator 2 Relacionado a NF-E2/metabolismo , Obesidade/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológicoRESUMO
The purpose of the study was to identify potential predictors of muscle hypertrophy responsiveness following neuromuscular electrical stimulation resistance training (NMES-RT) in persons with chronic spinal cord injury (SCI). Data for twenty individuals with motor complete SCI who completed twice weekly NMES-RT lasting 12-16 weeks as part of their participation in one of two separate clinical trials were pooled and retrospectively analyzed. Magnetic resonance imaging (MRI) was used to measure muscle cross-sectional area (CSA) of the whole thigh and knee extensor muscle before and after NMES-RT. Muscle biopsies and fasting biomarkers were also measured. Following the completion of the respective NMES-RT trials, participants were classified into either high-responders (n = 8; muscle CSA > 20%) or low-responders (n = 12; muscle CSA < 20%) based on whole thigh muscle CSA hypertrophy. Whole thigh muscle and knee extensors CSAs were significantly greater (P < 0.0001) in high-responders (29 ± 7% and 47 ± 15%, respectively) compared to low-responders (12 ± 3% and 19 ± 6%, respectively). There were no differences in total caloric intake or macronutrient intake between groups. Extensor spasticity was lower in the high-responders compared to the low-responders as was the dosage of baclofen. Prior to the intervention, the high-responders had greater body mass compared to the low-responders with SCI (87.8 ± 13.7 vs. 70.4 ± 15.8 kg; P = 0.012), body mass index (BMI: 27.6 ± 2.7 vs. 22.9 ± 6.0 kg/m2; P = 0.04), as well as greater percentage in whole body and regional fat mass (P < 0.05). Furthermore, high-responders had a 69% greater increase (P = 0.086) in total Akt protein expression than low-responders. High-responders also exhibited reduced circulating IGF-1 with a concomitant increase in IGFBP-3. Exploratory analyses revealed upregulation of mRNAs for muscle hypertrophy markers [IRS-1, Akt, mTOR] and downregulation of protein degradation markers [myostatin, MurF-1, and PDK4] in the high-responders compared to low-responders. The findings indicate that body composition, spasticity, baclofen usage, and multiple signaling pathways (anabolic and catabolic) are involved in the differential muscle hypertrophy response to NMES-RT in persons with chronic SCI.
Assuntos
Terapia por Estimulação Elétrica , Treinamento Resistido , Traumatismos da Medula Espinal , Humanos , Baclofeno/metabolismo , Treinamento Resistido/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estudos Retrospectivos , Músculo Esquelético/fisiologia , Espasticidade Muscular , Traumatismos da Medula Espinal/metabolismo , Hipertrofia/patologia , Terapia por Estimulação Elétrica/métodosRESUMO
Hypertension affects 1 in 3 adults in the United States and leads to left ventricular (LV) concentric hypertrophy, interstitial fibrosis, and increased stiffness. The treatment of cardiac fibrosis remains challenging and empiric. Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that is highly effective in reducing cardiovascular events in patients and cardiac fibrosis and hypertrophy in animals when administered before pressure overload by promoting the increase of anti-inflammatory M1 macrophages. In this study, we investigated whether EPA mitigates the exacerbation of cardiac remodeling and fibrosis induced by established hypertension, a situation that closely recapitulates a clinical scenario. Twelve-week-old spontaneously hypertensive rats were randomized to eat an EPA-enriched or control diet for 20 weeks. We report that rats eating the EPA-enriched diet exhibited a reduction of interstitial cardiac fibrosis and ameliorated LV diastolic dysfunction despite the continuous increase in blood pressure. However, we found that EPA did not have an impact on cardiac hypertrophy. Interestingly, the EPA diet increased mRNA expression of M2 macrophage marker Mrc1 and interleukin-10 in cardiac tissue. These findings indicated that the antifibrotic effects of EPA are mediated in part by phenotypic polarization of macrophages toward anti-inflammatory M2 macrophages and increases of the anti-inflammatory cytokine, interleukin-10. In summary, EPA prevents the exacerbation of cardiac fibrosis and LV diastolic dysfunction during sustained pressure overload. EPA could represent a novel treatment strategy for hypertensive cardiomyopathy.
Assuntos
Ácido Eicosapentaenoico , Hipertensão , Animais , Ratos , Anti-Inflamatórios , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Ácido Eicosapentaenoico/metabolismo , Fibrose , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Hipertrofia/metabolismo , Hipertrofia/patologia , Inflamação/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Miocárdio/metabolismo , Ratos Endogâmicos SHRRESUMO
OBJECTIVE: The objective of this study was to determine the matrix metalloproteinase-10 (MMP-10) expression pattern and to assess how it contributes to endochondral osteogenesis in Kashin-Beck disease (KBD). DESIGN: The cartilages of KBD patients, Sprague-Dawley rats fed with selenium (Se)-deficient diet and/or T-2 toxin, and ATDC5 cells were used in this study. ATDC5 cells were induced into hypertrophic chondrocytes using a 1% insulin-transferrin-selenium (ITS) culture medium for 21 days. The expressions of MMP-10 in the cartilages were visualized by immunohistochemistry. The messenger RNA (mRNA) and protein expression levels were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting. MMP-10 short hairpin RNA (shRNA) was transfected into hypertrophic chondrocytes to knock down the gene expression of MMP-10. Meanwhile, the cell death of MMP-10-knockdown chondrocyte was detected using flow cytometry. RESULTS: The expression of MMP-10 was decreased in the growth plates of children with KBD. A decreased expression of MMP-10 also was observed in the growth plates of rats fed with an Se-deficient diet and/or T-2 toxin exposure. The mRNA and protein expression levels of MMP-10 increased during the chondrogenic differentiation of ATDC5 cells. MMP-10 knockdown in hypertrophic chondrocytes significantly decreased the gene and protein expression of collagen type II (Col II), Col X, Runx2, and MMP-13. Besides, the percentage of cell apoptosis was significantly increased after MMP-10 knockdown in hypertrophic chondrocytes. CONCLUSION: MMP-10 deficiency disrupts chondrocyte terminal differentiation and induces the chondrocyte's death, which impairs endochondral osteogenesis in the pathogenesis of KBD.
Assuntos
Doença de Kashin-Bek , Metaloproteinase 10 da Matriz , Osteoartrite , Animais , Condrócitos/metabolismo , Humanos , Hipertrofia/metabolismo , Hipertrofia/patologia , Metaloproteinase 10 da Matriz/genética , Metaloproteinase 10 da Matriz/metabolismo , Camundongos , Osteoartrite/metabolismo , Osteogênese , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Selênio , Toxina T-2RESUMO
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/metabolismoRESUMO
BACKGROUND: Osthole has been widely reported to have pharmacological activities such as anti-cancer, anti-inflammation and anti-hyperlipidemic effects. Klotho was identified as an anti-senescence protein in a variety of tissues. Loss of klotho has been associated with chronic kidney disease. However, potential roles and molecular events for osthole and klotho in diabetic nephropathy remain unclear. PURPOSE: In the current study, we undertook to study the effect of osthole on klotho expression in advanced glycation end products (AGE)-cultured human renal proximal tubular cells, and to investigate the molecular mechanisms of osthole and exogenous klotho against AGE-induced renal tubular hypertrophy. METHODS: Cell viability was elucidated by MTT assay. Protein expression was measured by Western blotting. mRNA level was analyzed by real-time PCR. Cellular hypertrophy growth was evaluated by hypertrophy index. Relative cell size was detected by flow cytometry. RESULTS: We found that raising the ambient AGE concentration causes a dose-dependent decrease in klotho synthesis. Osthole significantly increased AGE-inhibited klotho mRNA and protein expression. Osthole and exogenous klotho treatments significantly attenuated AGE-induced Janus kinase 2 (JAK2)-signal transducers and activators of transcription 1 (STAT1) and STAT3 activation. Moreover, protein levels of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 were augmented by osthole and exogenous klotho. The abilities of osthole and exogenous klotho to reverse AGE-induced cellular hypertrophy were verified by the observation that osthole and exogenous klotho inhibited p21Waf1/Cip1/collagen IV/RAGE expression, total protein content, and cell size. CONCLUSION: Consequently, we found that osthole attenuated AGE-induced renal tubular hypertrophy via induction of klotho expression and suppression of the JAK2-STAT1/STAT3 signaling. These results also showed that klotho might be used as a unique molecular target for the treatment of diabetic nephropathy.
Assuntos
Cumarínicos/farmacologia , Glucuronidase/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Hipertrofia/tratamento farmacológico , Túbulos Renais/efeitos dos fármacos , Antígenos de Neoplasias/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Glucuronidase/farmacologia , Produtos Finais de Glicação Avançada/toxicidade , Humanos , Hipertrofia/induzido quimicamente , Hipertrofia/patologia , Janus Quinase 2/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Proteínas Klotho , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro. MATERIALS AND METHODS: In vivo OA model was established by intra-articular injection (1.5â¯mg) of monosodium iodoacetate (MIA) into rats and weekly treated by intra-articular administration of EAA at a dose range from 0.3 to 0.9â¯g/kg for four weeks. The pain behavior parameters, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were tested before and after the treatment. Then histopathologic, immunohistochemical and TUNEL analyses of the articular cartilage were conducted, followed by Mankin's scoring. In vitro, the effects of EAA on chondrocytes were evaluated via assays of cell viability, immunofluorescence, real time PCR, and Western blot. UPLC-MS was applied to determine the chemical composition of EAA. RESULTS: The animal data showed that EEA not only attenuated the pain hypersensitivity but also blocked the cartilage degeneration by improving chondrocyte survival and suppressing chondrocyte apoptosis at a dose-dependent manner in OA rats. Furthermore, EAA remarkably restored the abnormal expression of collagen type II (Col2) and matrix metalloproteinase-13 (MMP13) in cartilage of OA rats. The cellular data showed that EAA significantly increased the cell viability of chondrocytes against OA-like damage and restored the abnormal expressions of Col2 and MMP13 in damaged chondrocytes. The molecular data showed that EAA significantly restored the abnormal mRNA expressions of Col2, Col10, MMP2 and MMP13 as well as the abnormal protein expressions of MMP13, PARP (total and cleaved) in chondrocytes under pathological condition. UPLC-MS analysis showed the known main components of EAA, including amino acides (glycine, L-aspartic acid, L-glutamic acid, and L-hydroxyproline), nucleoside (uridine), purines (xanthine and hypoxanthine), and pyrimidine (uracil). CONCLUSIONS: Our data demonstrate that EAA exerts antinociceptive and chondroprotective effects on OA through suppressing chondrocyte hypertrophy and apoptosis with restoration of the molecular expressions of anabolism and catabolism in chondrocytes. It provides a promising TCM candidate of novel agent for OA therapy.
Assuntos
Agkistrodon , Analgésicos/uso terapêutico , Misturas Complexas/uso terapêutico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Hipertrofia/induzido quimicamente , Hipertrofia/tratamento farmacológico , Hipertrofia/patologia , Ácido Iodoacético , Masculino , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Dor/induzido quimicamente , Dor/patologia , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine in the treatment of adenoid hypertrophy in children. METHOD: Screening standard articles, extracting relevant data from meta-analysis, were analyzed by Revman5.1 software, by searching PubMed, Medline, VIP, Wan Fang and Chinese HowNet database 2006-2016 in traditional Chinese medicine treatment of children with adenoid literature. RESULTS: 206 articles met the inclusion criteria, of which ten were selected and included in the meta-analysis, and there were 803 patients. The results showed that the remission rate of the Chinese medicine treatment group was better than that of the Western medicine group. The combined effect of the amount of OR 2.06, 95% Cl (1.45, 2.96) and the combined effect of the amount of the test Z = 4.12, P < 0.00001 showed the recurrence of the disease was lower in traditional Chinese medicine treatment group than the Western medicine group. The combined effect of the amount of OR 3.05, 95% Cl (2.11, 4.56) and the combined effect of the amount of the test Z = 5.86, P < 0.00001 showed the total effective rate is high in the traditional Chinese medicine treatment group than the Western medicine group. The difference between the combined effect of the amount of OR 2.79, 95% Cl (1.78, 5.03) and the combined effect of the amount of the test of Z = 4.54, P < 0.00001 was statistically significant, which showed the treatment effect of Chinese medicine group is obviously better than the Western medicine group. CONCLUSION: The use of Chinese medicine for the treatment of children with adenoid hypertrophy has good clinical efficacy.
Assuntos
Tonsila Faríngea/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Doenças Faríngeas/tratamento farmacológico , Criança , Humanos , Hipertrofia/tratamento farmacológico , Hipertrofia/patologia , Doenças Faríngeas/patologia , Resultado do TratamentoRESUMO
Fucosylated chondroitin sulfate from Isostichopus badionotus (fCS-Ib) is a kind of sulfated polysaccharides with well-repeated structure. In our former publications, fCS-Ib has been reported to be a functional food ingredient with hypoglycemic and antilipemic activities. However, there is no systematic study to investigate the effects of fCS-Ib on metabolic syndromes. In the present study, C57BL/6 mice fed on a high-fat and high sucrose diet (HFSD) for 6â¯weeks was used to cause metabolic syndromes. The final results showed that fCS-Ib alleviated obesity, hyperlipidemia, hyperglycemia, inflammation, liver steatosis, and adipocyte hypertrophy caused by HFSD. Meanwhile, fCS-Ib showed powerful effects on moderating gut microbiota dysbiosis in the HFSD-fed mice. Supplement of fCS-Ib could reduce ratio of Firmicutes to Bacteroidetes by decreasing abundance of Lachnospiraceae and Allobaculum while increasing abundance of Porphyromonadaceae, Barnesiella, and Bacteroides. Our results showed that fCS-Ib could be further developed as a potential pharmaceutical agent to prevent metabolic syndromes and gut microbiota dysbiosis.
Assuntos
Sulfatos de Condroitina/administração & dosagem , Disbiose/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Pepinos-do-Mar/química , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Animais , Sulfatos de Condroitina/química , Sulfatos de Condroitina/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Disbiose/induzido quimicamente , Disbiose/microbiologia , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/patologia , Frutose/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/patologia , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/patologia , Hipertrofia/induzido quimicamente , Hipertrofia/tratamento farmacológico , Hipertrofia/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/patologia , Camundongos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/patologiaRESUMO
PURPOSE: Experimental laboratory data have indicated a protective effect of vitamin D on breast cancer progression, while epidemiological evidence is growing. Using pharmacy claims data, this study investigates the association between vitamin D supplement use initiated after a breast cancer diagnosis and associated mortality. METHODS: Women aged 50-80 years with a record of invasive breast cancer were identified on the National Cancer Registry Ireland database (n = 5417). Initiation of de novo vitamin D post-diagnosis was identified from linked national prescription data (n = 2581, 49%). Multivariate Cox proportional hazards models were used to estimate adjusted HRs (95% CIs) for breast cancer-specific mortality. RESULTS: There was a 20% reduction in breast cancer-specific mortality in de novo vitamin D users (modelled as a time-varying variable) compared to non-users (HR 0.80; 95% CI 0.64-0.99, p = 0.048) and the reduction was greater at 49% (HR 0.51; 95% CI 0.34-0.74, p < 0.001), if vitamin D was initiated soon after the breast cancer diagnosis (within 6 months). CONCLUSIONS: In this large national breast cancer cohort, de novo vitamin D use post-diagnosis was found to be associated with a reduction in breast cancer-specific mortality. Vitamin D, therefore, has the potential as a non-toxic and inexpensive agent to improve survival in breast cancer patients. Findings support the need for RCTs exploring the effect of vitamin D supplementation on breast cancer survival.
Assuntos
Neoplasias da Mama/dietoterapia , Sobreviventes de Câncer , Suplementos Nutricionais , Vitamina D/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Mama/anormalidades , Mama/patologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Hipertrofia/dietoterapia , Hipertrofia/epidemiologia , Hipertrofia/patologia , Irlanda/epidemiologia , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
We investigated the effects of regular leucine intake and/or resistance exercise training on skeletal muscle hypertrophy and satellite cell activity after the administration of different doses of leucine. Ten-week-old Sprague-Dawley rats were assigned to six groups (n = 7 per group): a control group (Con), two groups receiving either 10% (0.135 g/kg.wt) (Leu10) or 50% (0.675 g/kg.wt) (Leu50) leucine supplementation, and three exercise groups receiving 0% (Ex), 10% (Leu10Ex), and 50% (Leu50Ex) leucine supplementation. The rats performed ladder climbing exercises thrice per week for 8 weeks, and received leucine supplements at the same time daily. Muscle phenotypes were assessed by immunohistochemistry. MyoD, myogenin, and IGF1 protein levels were determined by western blot. The Leu50Ex group displayed significantly higher numbers of positive embryonic myosin fibers (0.35 ± 0.08, 250%) and myonuclei (3.29 ± 0.3, 118.7%) than all other groups. And exercise training groups increased the cross-sectional area, the number of satellite cells and protein expression of MyoD, myogenin, and IGF1alpha relative to the Control group (P < 0.05). However, Only leucine supplementation group did not increase skeletal muscle hypertrophy and satellite cell activity, regardless of the dose (P > 0.05). Leucine intake accompanied by regular exercise training may increase satellite cell activation in skeletal muscles, and improve muscle quality more effectively than continuous leucine ingestion alone.
Assuntos
Suplementos Nutricionais , Leucina/administração & dosagem , Músculo Esquelético/patologia , Treinamento Resistido/métodos , Animais , Diferenciação Celular/efeitos dos fármacos , Terapia Combinada , Relação Dose-Resposta a Droga , Hipertrofia/metabolismo , Hipertrofia/patologia , Hipertrofia/prevenção & controle , Leucina/farmacologia , Leucina/uso terapêutico , Masculino , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/metabolismo , Força Muscular/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Condicionamento Físico Animal/fisiologia , Ratos Sprague-Dawley , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Células Satélites de Músculo Esquelético/patologia , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/fisiologia , Suporte de Carga/fisiologiaRESUMO
The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.
Assuntos
Miocárdio/patologia , Neuropeptídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Secretogranina II/farmacologia , Animais , Catalase/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipertrofia/tratamento farmacológico , Hipertrofia/metabolismo , Hipertrofia/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Neuropeptídeos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Secretogranina II/uso terapêutico , Superóxido Dismutase/metabolismoRESUMO
The present study was conducted to evaluate the influence of oral administration of black seed (Nigella sativa) oil on histomorphometrical characteristics of testes and testosterone profile in adult rabbits. Twenty adult male rabbits aged seven months were divided into two groups: control and treated. Black seed oil was administrated orally for 60 days at 5ml/kg body weight/day on daily basis in addition to the food and water ad lib to the treated group. Biometric parameters of the testes were recorded immediately after their removal. Tissue samples of testes were processed with paraffin tissue preparation technique. Histometrical parameters of testes were measured with the help of automated image analysis software Image J®. Serum testosterone concentration was determined with Radioimmunoassay technique. Statistical analysis revealed significant (P<0.05) rise in weight, length, circumference and volume of testis in treated group than control group. The values of histometrical parameters studied viz., thickness of spermatogenic epithelium, diameter and area of seminiferous tubules, diameter of lumen of seminiferous tubules, number of spermatogenic layers of testes and serum testosterone concentration were found significantly (P<0.05) higher in treated group than control group. Based on the data it is conceivable that the oral administration of black seed oil has potential to stimulate testicular function in adult rabbits.
Assuntos
Nigella sativa , Óleos de Plantas/farmacologia , Testículo/efeitos dos fármacos , Testosterona/sangue , Administração Oral , Animais , Hipertrofia/patologia , Masculino , Coelhos , Testículo/patologiaRESUMO
Qiliqiangxin (QLQX), a traditional Chinese herbs medication, exerted protective effect in chronic heart failure patients in a multicenter randomized double-blind study. QLQX has also been found to improve cardiac function and reduce cardiac fibrosis in spontaneously hypertension animal model. However, the effect of longterm treatment with QLQX in such a condition and the related molecular mechanisms remain largely unknown. In the present study, thirteen-week-old spontaneously hypertensive rats (SHRs) were treated by daily intragastric administration of QLQX or saline for one year. Echocardiography, electron microscopy, and Masson's trichrome staining were used to determine cardiac function, mitochondria ultrastructure, and cardiac fibrosis, respectively. Quantitative reverse transcription polymerase chain reactions (qRT-PCRs) and Western blotting were used to determine gene expressions. We found that QLQX significantly improved cardiac function and reduced gene markers of pathological hypertrophy including ANP, BNP, and Myh7. QLQX also attenuated cardiac fibrosis and apoptosis in SHRs as evidenced by downregulation of α-SMA, collagen I, collagen III, and TGF-ß expressions and reduction of Bax to Bcl-2 ratio. Moreover, the damage of mitochondrial ultrastructure was greatly improved and the reduction of PPAR-α, PPAR-γ, and PGC-1α expression levels was significantly restored in SHRs by treatment with QLQX. In conclusion, longterm treatment with QLQX protects against cardiac remodeling and dysfunction in hypertension by increasing PPARs and PGC-1α.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Hipertensão/tratamento farmacológico , Medicina Tradicional Chinesa , Infarto do Miocárdio/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Ecocardiografia , Humanos , Hipertensão/fisiopatologia , Hipertrofia/diagnóstico por imagem , Hipertrofia/tratamento farmacológico , Hipertrofia/genética , Hipertrofia/patologia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Remodelação VentricularRESUMO
OBJECTIVE: The aim of this study was to verify how a pair of monozygotic twins would respond to light-emitting diode therapy (LEDT) or placebo combined with a strength-training program during 12 weeks. DESIGN: This case-control study enrolled a pair of male monozygotic twins, allocated randomly to LEDT or placebo therapies. Light-emitting diode therapy or placebo was applied from a flexible light-emitting diode array (λ = 850 nm, total energy = 75 J, t = 15 seconds) to both quadriceps femoris muscles of each twin immediately after each strength training session (3 times/wk for 12 weeks) consisting of leg press and leg extension exercises with load of 80% and 50% of the 1-repetition maximum test, respectively. Muscle biopsies, magnetic resonance imaging, maximal load, and fatigue resistance tests were conducted before and after the training program to assess gene expression, muscle hypertrophy and performance, respectively. Creatine kinase levels in blood and visual analog scale assessed muscle damage and delayed-onset muscle soreness, respectively, during the training program. RESULTS: Compared with placebo, LEDT increased the maximal load in exercise and reduced fatigue, creatine kinase, and visual analog scale. Gene expression analyses showed decreases in markers of inflammation (interleukin 1ß) and muscle atrophy (myostatin) with LEDT. Protein synthesis (mammalian target of rapamycin) and oxidative stress defense (SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT, together with increases in thigh muscle hypertrophy. CONCLUSIONS: Light-emitting diode therapy can be useful to reduce muscle damage, pain, and atrophy, as well as to increase muscle mass, recovery, and athletic performance in rehabilitation programs and sports medicine.
Assuntos
Exercício Físico/fisiologia , Terapia com Luz de Baixa Intensidade/métodos , Mialgia/terapia , Treinamento Resistido/métodos , Gêmeos Monozigóticos , Estudos de Casos e Controles , Creatina Quinase , Tolerância ao Exercício/fisiologia , Humanos , Hipertrofia/sangue , Hipertrofia/patologia , Hipertrofia/terapia , Interleucina-1beta/sangue , Masculino , Fadiga Muscular/fisiologia , Mialgia/sangue , Mialgia/patologia , Miostatina/sangue , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Superóxido Dismutase/fisiologia , Serina-Treonina Quinases TOR/fisiologia , Coxa da Perna/patologia , Regulação para Cima , Adulto JovemRESUMO
Angiotensin II (Ang II) is a very important cardiovascular disease inducer and may cause cardiac pathological hypertrophy and remodeling. We evaluated a Chinese traditional medicine, alpinate oxyphyllae fructus (AOF), for therapeutic efficacy for treating Ang II-induced cardiac hypertrophy. AOF has been used to treat patients with various symptoms accompanying hypertension and cerebrovascular disorders in Korea. We investigated its protective effect against Ang II-induced cytoskeletal change and hypertrophy in H9c2 cells. The results showed that treating cells with Ang II resulted in pathological hypertrophy, such as increased expression of transcription factors NFAT-3/p-NFAT-3, hypertrophic response genes (atrial natriuretic peptide [ANP] and b-type natriuretic peptide [BNP]), and Gαq down-stream effectors (PLCß3 and calcineurin). Pretreatment with AOF (60-100 µg/mL) led to significantly reduced hypertrophy. We also found that AOF pretreatment significantly suppressed the cardiac remodeling proteins, metalloproteinase (MMP9 and MMP2), and tissue plasminogen activator (tPA), induced by Ang II challenge. In conclusion, we provide evidence that AOF protects against Ang II-induced pathological hypertrophy by specifically inhibiting the insulin-like growth factor (IGF) II/IIR-related signaling pathway in H9c2 cells. AOF might be a candidate for cardiac hypertrophy and ventricular remodeling prevention in chronic cardiovascular diseases.