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OBJECTIVE: This paper employs network pharmacology and molecular docking to analyze the active components, targets, and molecular mechanisms of Scutellaria baicalensis in treating renal cell carcinoma (RCC). MATERIALS AND METHODS: The potential active target genes and components of Scutellaria baicalensis are obtained by searching the TCMSP database, and RCC targets are obtained using OMIM, Genecards, and Drugbank databases. The interaction of target proteins is analyzed thanks to STRING, and the component target disease network diagram is constructed through Cytoscape 3.8.2 software. Besides, KEGG, and GO enrichment analysis is performed using the Bioconductor bioinformatics R software package. AutoDock Vina 1.1.2, PyMol 2.5 and Maestro 12.9 software are used for molecular docking. RESULTS: According to the results, Scutellaria baicalensis, which has 36 active ingredients, 500 drug targets, and 85 drug-disease common targets in the treatment of RCC, relies mainly on active ingredients, including wogonin, baicalein, acacetin, oroxylin A, moslosooflavone, salvigenin, and neobaicalein. In addition, the core components within Scutellaria baicalensis that contribute to the treatment of renal cancer are TP53, CCND1, STAT3, CASP3, JUN, VEGFA, AKT1, and EGFR; while the main molecular mechanisms that helps relieve RCC include PI3K-Akt, Ras, MAPK, p53, VEGF, and JAK-STAT signaling pathway. Molecular docking suggested that wogonin had a good binding affinity with core proteins CASP3, CCND1, JUN, STAT3, TP53, and VEGFA. CONCLUSIONS: This study confirms that Scutellaria baicalensis can treat RCC in a multi-component, multi-target, and multi-way manner.
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Carcinoma de Células Renais , Medicamentos de Ervas Chinesas , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Caspase 3 , Simulação de Acoplamento Molecular , Scutellaria baicalensis , Fosfatidilinositol 3-Quinases , Neoplasias Renais/tratamento farmacológicoRESUMO
OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of enhanced external counter pulsation (EECP) plus sacubitril/valsartan in the treatment of patients with chronic heart failure (CHF) and the effect on ankle-arm index and cardiac function. PATIENTS AND METHODS: In this retrospective study, 106 patients with chronic heart failure treated in our hospital from September 2020 to April 2022 were recruited and randomly assigned to receive either sacubitril/valsartan (observation group) or EECP plus sacubitril/valsartan (combination group) alternately at the point of admission, with 53 patients in each group. Outcome measures included clinical efficacy, ankle brachial index (ABI), cardiac function indices [N-terminal brain natriuretic peptide precursor (NT-proBNP), 6 min walking distance (6MWD), left ventricular ejection fraction (LVEF)], and adverse events. RESULTS: EECP plus sacubitril/valsartan resulted in significantly higher treatment efficiency and ABI levels vs. sacubitril/valsartan (p<0.05). Patients receiving combined therapy showed significantly lower NT-proBNP levels than those given monotherapy (p<0.05). EECP plus sacubitril/valsartan resulted in longer 6MWD and higher LVEF than sacubitril/valsartan alone (p<0.05). No significant differences were observed in the adverse events between the two groups (p>0.05). CONCLUSIONS: EECP plus sacubitril/valsartan substantially improves the ABI levels, cardiac functions, and exercise tolerance of patients with chronic heart failure, with a high safety profile. EECP improves blood supply to myocardial ischemic tissues by increasing ventricular diastolic blood return and blood perfusion to ischemic myocardium, raises aortic diastolic pressure, restores pumping function, improves LVEF, and reduces NT-proBNP secretion.
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Índice Tornozelo-Braço , Insuficiência Cardíaca , Humanos , Volume Sistólico , Estudos Retrospectivos , Tornozelo , Tetrazóis/uso terapêutico , Função Ventricular Esquerda , Valsartana/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Resultado do Tratamento , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
OBJECTIVE: We aimed to explore the associations of the ATP2B1 gene polymorphisms with eclampsia. PATIENTS AND METHODS: A total of 150 patients with eclampsia (disease group) and 150 healthy pregnant women (control group) were taken as the subjects of study. The peripheral blood of the two groups of subjects was collected to extract deoxyribonucleic acids (DNAs), and the ATP2B1 gene rs71454161, rs73196661 and rs73196675 polymorphisms were detected by sequencing the Polymerase Chain Reaction (PCR) products, and then, analyzed combined with gene expression determined via Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and clinical indicators, such as 24-h urine protein, platelets, and LDH. RESULTS: A difference was observed in the allele distribution of ATP2B1 gene rs71454161 (p=0.000) and rs73196661 (p=0.011) between the disease group and control group. Disease group exhibited higher frequencies of allele G of rs71454161 and allele T of rs73196661 than control group. Besides, there was a difference in the genotype distribution of ATP2B1 gene rs71454161 (p=0.000), rs73196661 (p=0.000) and rs73196675 (p=0.000) between disease group and control group. Disease group exhibited higher frequencies of genotype GG of rs71454161, genotype TT of rs73196661 and genotype CG of rs73196675 than control group. Moreover, a difference in the distributions of ATP2B1 gene rs71454161 (p=0.000) and rs73196661 (p=0.014) was found between the two groups in the dominant model. Disease group exhibited lower frequencies of AA+AG of rs71454161 and CC+CT of rs73196661 than control group in the dominant model. Differences in the distributions of haplotypes ACC (p=0.000), ATC (p=0.047) and GTC (p=0.000) of ATP2B1 gene rs71454161, rs73196661 and rs73196675 were observed between disease group and control group. Furthermore, a high degree of linkage disequilibrium was detected between rs71454161 and rs73196661 (D'=0.329). The ATP2B1 gene rs73196675 polymorphism was evidently correlated with the gene expression of ATP2B1 (p<0.05), and the patients with genotype GG had a lower expression level of ATP2B1. The ATP2B1 gene rs71454161 was evidently correlated with the 24-h urinary protein in eclampsia patients (p=0.021), and the patients with genotype AG had a higher level of 24-h urinary proteins. The rs73196661 polymorphism was significantly correlated with LDH (p=0.000), and the patients with genotype CC had a higher level of LDH. CONCLUSIONS: The ATP2B1 gene polymorphism was significantly correlated with the occurrence and progression of eclampsia.
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Eclampsia , Alelos , Eclampsia/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , GravidezRESUMO
OBJECTIVE: To elucidate the biological role of miR-4282 in influencing metastasis of epithelial ovarian cancer (EOC) by regulating MIER1. PATIENTS AND METHODS: MiR-4282 expressions in 45 cases of EOC specimens and normal controls were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miR-4282 and clinical features in EOC patients, including pathological indicators and overall survival, was analyzed. After intervening miR-4282 level in SKOV3 and 3AO cells by plasmid transfection, changes in migratory and invasive abilities were determined by transwell assay and wound healing assay. The target gene of miR-4282 was observed by Dual-Luciferase reporter assay, followed by exploration of its involvement in EOC progression via rescue experiments. RESULTS: MiR-4282 was downregulated in EOC specimens than normal controls. EOC patients expressing low level of miR-4282 had higher incidences of lymphatic metastasis and distant metastasis, as well as worse prognosis than those overexpressing miR-4282. Overexpression of miR-4282 in SKOV3 cells weakened metastatic ability, and conversely, knockdown of miR-4282 in 3AO cells yielded the promotive trends. MIER1 was confirmed to be the target gene binding miR-4282, which was highly expressed in EOC specimens. MIER1 was able to reverse the regulatory effect of miR-4282 on EOC cell metastasis. CONCLUSIONS: Lowly expressed miR-4282 in EOC specimens is closely linked to the incidence of metastasis and overall survival. MiR-4282 prevents EOC metastasis by a negative regulation on MIER1.
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Carcinoma Epitelial do Ovário/genética , Proteínas de Ligação a DNA/genética , Genes Supressores de Tumor , MicroRNAs , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: The efficacy and safety of IL-17 inhibitors for patients with Psoriatic arthritis (PsA) is still a controversial issue. MATERIALS AND METHODS: We systematically searched MEDLINE, EMBASE and Cochrane for randomized controlled trials that compared IL-17 inhibitors with placebo or TNF inhibitor adalimumab in patients with PsA. RESULTS: Eleven studies with 5327 patients were included in the meta-analysis. IL-17 inhibitors were effective in achieving response rates of American College of Rheumatology (ACR) 20, ACR50 and ACR70 compared with the control group. The results of subgroup analyses showed that IL-17 inhibitors had significant advantages in increasing the response rates of ACR20, ACR50 and ACR70 over placebo. IL-17 inhibitors did not show advantages in the responses of ACR20 and ACR50, but they were associated with a higher rate of ACR70 when compared with adalimumab. The longer the follow-up time, the higher the response rates of ACR20, ACR50 and ACR70 in IL-17 inhibitors group. IL-17 inhibitors treatment also significantly increased the rates of PASI75 and PASI90 compared with controls. Additionally, IL-17 inhibitors were associated with higher risks of any Candida infections and injection site reactions and with a lower rate of allergic reactions or hypersensitivities compared with the control group. CONCLUSIONS: This study provided a clear proof of beneficial effects of IL-17 inhibitors in improving joint disease activity in patients with PsA with an acceptable safety profile.
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Antirreumáticos/farmacologia , Artrite Psoriásica/tratamento farmacológico , Interleucina-17/antagonistas & inibidores , Artrite Psoriásica/metabolismo , Humanos , Interleucina-17/metabolismoRESUMO
AIMS: The aims of this study were to investigate the effects of probiotics and antibiotics on microbial composition, short chain fatty acids (SCFAs) concentration and free fatty acid receptor 2/3 (FFAR2/3) expression in boiler chickens. METHODS AND RESULTS: A total of 150 1-day-old male broilers were randomly allocated into three groups, control (CON) group, probiotics (PB) group and antibiotics (ATB) group. Results indicated that PB improved the average body weight from 1 to 21 days and feed intake from 21 to 42 days (P < 0·05), while ATB improved the feed efficiency from 1 to 42 days (P < 0·05). Based on 16s rRNA sequencing, PB treatment increased the amount of kingdom bacteria, and the relative abundance of the main bacteria including acetate and butyrate producing bacteria of phylum Firmicutes, family Ruminococcaceae and genus Faecalibacterium. ATB treatment also increased the relative abundance of phylum Firmicutes, family Ruminococcaceae and Lachnospiraceae, however, it introduced some pathogenic bacteria, such as bacteria of family Rikenellaceae and Enterobacteriaceae. Gas chromatography and mass spectrometry (GC-MS) assay revealed that PB increased acetate and butyrate concentrations at both 21 and 42 days, and propionate at 42 days in the colorectum. Moreover qRT-PCR analysis showed PB treatment significantly activated the FFAR2/3 mRNA expressions. On the contrast, ATB treatment lowered the colorectal propionate at 21 days, and decreased acetate, propionate and butyrate concentrations at 42 days, accompanied with decreased FFAR2/3 mRNA expressions. CONCLUSIONS: Compared to the CON birds, an enriched SCFAs producing bacteria with higher SCFAs contents and activated FFAR2/3 expressions are prominent features of PB birds. However, antibiotics treatment plays the reverse effect compared to PB treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study brings a significant idea that less SCFAs concentration may be another reason why the antibiotics inhibit the immune system development and immunity of the body.
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Microbiota , Probióticos , Animais , Antibacterianos/farmacologia , Galinhas , Ácidos Graxos Voláteis , Masculino , RNA Mensageiro/genética , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: Thyroid cancer (TC) is a common malignant tumor of the endocrine system, and its morbidity and mortality are in the high places. Recent studies have focused on exploring biological markers and targeted therapy for TC. This research aims to elucidate the role of LINC00106 in the progression of TC and the regulatory mechanisms. PATIENTS AND METHODS: Differential level of LINC00106 in a downloaded profile containing TC and normal tissues from GEPIA database was analyzed. Subsequently, its level in TC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between LINC00106 level and clinical data of TC patients was assessed, including age, tumor staging, lymphatic metastasis, and overall survival. After transfection of si-LINC00106, TC cell metastasis was evaluated by wound healing and transwell assay. Relative levels of E-cadherin, N-cadherin, ß-catenin, and Vimentin regulated by LINC00106 were determined using qRT-PCR and Western blot. RESULTS: LINC00106 was downregulated in TC tissues than normal ones. Its level was correlated to tumor staging, lymphatic metastasis and overall survival in TC patients. The knockdown of LINC00106 in BCPCP and TPC-1 cells enhanced migratory and invasive abilities and triggered the process of epithelial-mesenchymal transition (EMT). CONCLUSIONS: LINC00106 is lowly expressed in TC specimens, which attenuates migratory and invasive abilities in TC by inhibiting EMT as a tumor suppressor.
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Transição Epitelial-Mesenquimal/genética , RNA Longo não Codificante , Neoplasias da Glândula Tireoide/genética , Linhagem Celular , Movimento Celular , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , CicatrizaçãoRESUMO
Osteoporosis (OP) is one of the most common chronic metabolic bone diseases in the seniors and postmenopausal women. Plenty of microRNAs (miRNAs) have been confirmed to be involved in OP progression. However, the role of miR-655-3p in osteogenic differentiation and bone formation was still unclear. In this study, we aimed to investigate the cellular function of miR-655-3p and its underlying mechanism in OP. We found that miR-655-3p expression was downregulated in both ovariectomized (OVX) mice bone tissues and MC3T3-E1 cells treated with simulated microgravity (MG). MiR-655-3p overexpression facilitated cell differentiation but suppressed cell apoptosis of MC3T3-E1 cells induced by simulated MG. Mechanistically, we confirmed that lysine-specific histone demethylase 1 (LSD1) is a downstream target gene of miR-655-3p. Furthermore, overexpression of miR-655-3p activated the bone morphogenetic protein 2 (BMP-2)/decapentaplegic homolog (Smad) signaling pathway by suppressing LSD1 expression. Moreover, LSD1 knockdown accelerated osteogenic differentiation and inhibited apoptosis in MC3T3-E1 cells under simulated MG. Additionally, the OVX mouse model was established to investigate the role of miR-655-3p/LSD1 axis in vivo. The results demonstrated that LSD1 could reverse the effects triggered by the injection of adeno-associated virus-miR-655-3p on OP development. Further investigations revealed that miR-655-3p boosted osteogenic differentiation through LSD1/BMP-2/Smad signaling pathway. In summary, these findings implied a potential value of miR-655-3p in OP therapy.
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MicroRNAs , Osteoporose/genética , Animais , Apoptose , Proteína Morfogenética Óssea 2/metabolismo , Linhagem Celular , Progressão da Doença , Feminino , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Humanos , Camundongos , Osteoblastos/metabolismo , Osteogênese/genética , Osteoporose/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismoRESUMO
The effects of Bi incorporation on the recombination process in wurtzite (WZ) GaBiAs nanowires are studied by employing micro-photoluminescence (µ-PL) and time-resolved PL spectroscopies. It is shown that at low temperatures (T < 75 K) Bi-induced localization effects cause trapping of excitons within band-tail states, which prolongs their lifetime and suppresses surface nonradiative recombination (SNR). With increasing temperature, the trapped excitons become delocalized and their lifetime rapidly shortens due to facilitated SNR. Furthermore, Bi incorporation in the GaBiAs NW is found to have a minor influence on the surface states responsible for SNR.
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OBJECTIVES: Despite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown. METHODS: A cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013-2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control. RESULTS: A total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4+ and CD8+ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17-6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02-3.57) and MN (3.33, 1.26-9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08-2.63), underlying medical conditions (1.94, 95% CI 1.09-3.46) and lack of antiviral therapy (2.08, 95% CI 1.04-4.17) were predictors for higher T-cell responses. CONCLUSIONS: Survivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.
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Anticorpos Antivirais/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Influenza Humana/imunologia , Adulto , Anticorpos Antivirais/imunologia , Estudos de Casos e Controles , China , Estudos Transversais , Feminino , Humanos , Subtipo H7N9 do Vírus da Influenza A , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Parkinson's disease is a neurodegenerative disease that typically results in the loss of dopaminergic neurons, especially in an area of the brain known as the substantia nigra. Here, we investigated the roles of two important neuronal development proteins, dysbindin-1 and SATB2, at different stages of Parkinson's disease. MATERIALS AND METHODS: Using various concentrations of a neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we established the mouse models at initial and advanced stages of the Parkinson's disease. The pole and rotarod tests were used to assess behavioral response and motor function, respectively. Histology was used to assess the disease pathology. Immunohistochemistry and Western blotting were used to analyze dysbindin-1 and SATB2 expression levels. RESULTS: Compared with controls, the mice in the initial and advanced stages of Parkinson's disease required 2.3-fold and 3.8-fold longer to reach the floor in the pole test. Similarly, in the rotarod test, mice in the initial (168 ± 3.73 s) and advanced stages (91 ± 5.62 s) of Parkinson's disease were less able to maintain motor stability, compared with control mice (214 ± 4.18 s). The expression levels of dysbindin-1 and SATB2 in substantia nigra tissue from control mice were limited but were substantially increased (2.4-fold and 3.6-fold, respectively) in mice in the initial stage of the Parkinson's disease. However, in the mice in the advanced stage of Parkinson's disease, dysbindin-1 expression was 1.7-fold lower, and the SATB2 expression was 1.8-fold higher, than that in the control mice. CONCLUSIONS: The increased expression levels of dysbindin-1 and SATB2 in the initial stage of Parkinson's disease may be due to their protective roles. However, the reduced expression levels in the advanced stage of Parkinson's disease may contribute to irreversible neuronal degeneration.
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Disbindina/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Doença de Parkinson/fisiopatologia , Fatores de Transcrição/metabolismo , Regulação para Cima , Animais , Modelos Animais de Doenças , Progressão da Doença , Masculino , Camundongos , Doença de Parkinson/metabolismo , Teste de Desempenho do Rota-Rod , Substância Negra/metabolismoRESUMO
OBJECTIVE: The aim of this study was to analyze the correlations of the sodium channel, voltage-gated, type V, alpha subunit (SCN5A) gene polymorphisms with the onset of atrial fibrillation (AF), and its clinical significance. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (QRT-PCR) amplification and the TaqMan analysis were utilized to analyze the composition of SCN5A genotypes and alleles in the peripheral blood mononuclear cells of 48 normal controls and 115 AF patients. Meanwhile, the differences in single nucleotide polymorphisms (SNPs), 1673 A>G, and 3666+69 G>C, between the AF group and the control group were analyzed using the χ2-test. The high-risk factors influencing the AF attack were analyzed via logistic regression analysis, as well as univariate and multivariate analyses. In addition, the correlations of gene polymorphisms with high-risk factors (drinking and hypertension) for AF were verified by the χ2-test. RESULTS: There were statistically significant differences in the incidence rate of hypertension, the times of smoking and drinking, and the frequencies of palpitation and syncope between the AF group and the control group (p<0.05). The composition of genotypes and alleles of 1673 A>G and 3666+69 G>C in the AF group was significantly different from that of the control group (p<0.05). According to the results of the logistic regression analysis, as well as the univariate and multivariate analyses, drinking, and hypertension were associated with the occurrence of AF (p<0.05). Furthermore, statistically significant differences were observed in the composition of the gene polymorphisms 1673 A>G and 3666+69 G>C between patients with and without histories of drinking and hypertension (p<0.05). CONCLUSIONS: There are significant differences in SCN5A gene polymorphisms 1673 A>G and 3666+69 G>C between AF patients and normal controls. Moreover, drinking and hypertension can influence the changes in the gene polymorphisms.
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Fibrilação Atrial/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: A thermostable endo-mannanase from the fungus Talaromyces cellulolyticus was identified to facilitate manno-oligosaccharide preparation from Konjac (Amorphophallus konjac) flour. METHODS AND RESULTS: A putative endo-1,4-ß-mannanase from the T. cellulolyticus was obtained and efficiently expressed by improving its gene dosage in the genome of the host. After cultivation in a bench-top bioreactor for about 120 h, the protein content and enzyme activity of mannanase increased to 3·4 g l-1 and 17 500 U ml-1 respectively. Enzymatic characterization showed that this enzyme has an optimal temperature of 80°C, optimal pH of 5·0. Under the optimized hydrolysis conditions of pH 5·0, 70°C, and an enzyme concentration of 200 U l-1 solution, this enzyme could efficiently hydrolyse 0·5% konjac flour into manno-oligosaccharides (MOSs) with the degree of polymerization range from 3 to 7. The possible mechanism by which the enzyme produced MOSs was also discussed. CONCLUSION: Talaromyces cellulolyticus endo-mannanase is thermostable and has a broad pH range adaptability. Method of improving the dosage of mannanase gene in the genome could realized its high-level impression. This enzyme could efficiently hydrolyse konjac flour into manno-oligosaccharide products. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has enriched endo-mannanase resources, facilitated its bulk production and provided a strong reference for its application in manno-oligosaccharide preparation from the natural glucomannan of konjac flour.
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Amorphophallus/química , Manosidases/metabolismo , Oligossacarídeos/metabolismo , Talaromyces/enzimologia , Estabilidade Enzimática , Farinha , Concentração de Íons de Hidrogênio , Hidrólise , Mananas/metabolismo , Manosidases/genética , Polimerização , TemperaturaRESUMO
OBJECTIVE: Bone marrow is full of mitochondria. However, the role of bone marrow mitochondrial protein in bone marrow damage and related signal transduction mechanism remains to be further studied. OPA is a newly discovered mitochondrial transmembrane protein. Its expression pattern and function in the physiological and pathological conditions of bone marrow are still elusive. The purpose of this study is to investigate the potential role of OPA in osteoporosis. PATIENTS AND METHODS: A mouse osteoporosis model was established by radiation. The OPA expression was tested by Western blot and qRT-PCR. The P38 signaling activity was evaluated by enzymatic activity kit. The mitochondrial ATP production was determined by flow cytometry. The bone marrow cell apoptosis was detected by flow cytometry. U0126 was used to pretreat mouse before modeling. Bone marrow tissue was collected from patients who received osteoporosis surgery to test the OPA expression, P38 activation and cell apoptosis. The OPA and P38 levels were analyzed by correlation. RESULTS: The mouse osteoporosis model was successfully established by radiation induction. In this osteoporosis model, the expression of OPA was increased. The P38 signaling was activated while the mitochondrial ATP production was reduced, with the increase of apoptosis of bone marrow cells. By contrast, U0126 pretreatment markedly inhibited the OPA expression, restrained the P38 signaling pathway, enhanced mitochondrial ATP production and suppressed the bone marrow cell apoptosis in mouse osteoporosis model. A significantly positive correlation was found between OPA and P38. CONCLUSIONS: The down-regulation of OPA inhibits cell apoptosis and improves osteoporosis via inducing mitochondrial ATP production and suppressing the P38 signaling pathway.
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Medula Óssea/enzimologia , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Osteoporose/enzimologia , Lesões por Radiação/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Animais , Apoptose , Medula Óssea/patologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Metabolismo Energético , Ativação Enzimática , Humanos , Camundongos , Pessoa de Meia-Idade , Mitocôndrias/patologia , Proteínas Mitocondriais/genética , Osteoporose/genética , Osteoporose/patologia , Lesões por Radiação/genética , Lesões por Radiação/patologia , Transdução de SinaisRESUMO
OBJECTIVE: The aim of this study was to investigate the effect of long non-coding RNA (lncRNA) HOTAIR on hepatic insulin resistance and to explore the possible underlying mechanism. PATIENTS AND METHODS: Liver tissues of type 2 diabetes mellitus (T2D) patients, healthy controls, C57BL/6J mice fed with a high-fat diet and db/db mice were harvested. Meanwhile, the expressions of HOTAIR and SIRT1 were detected. Subsequently, We HepG2 cells were treated with tumor necrosis factor α (TNF-α), and the insulin resistance model was constructed in vitro. The mRNA expression levels of HOTAIR and SIRT1 in the insulin resistance model were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Insulin sensitivity in HepG2 cells transfected with lentivirus was evaluated by relative commercial kits. In addition, protein expression levels of key factors in the AKT/GSK pathway were detected by Western blot. RESULTS: HOTAIR was significantly upregulated in T2D patients, C57BL/6J mice fed with a high-fat diet and db/db mice. However, SIRT1 expression presented an opposite changing trend. Moreover, upregulated HOTAIR remarkably promoted hepatic insulin resistance via the AKT/GSK pathway, which could be reversed by SIRT1 overexpression. CONCLUSIONS: Upregulated HOTAIR promotes hepatic insulin resistance by inhibiting SIRT1 expression and AKT/GSK pathway.
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Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina/fisiologia , RNA Longo não Codificante/fisiologia , Sirtuína 1/biossíntese , Animais , Estudos de Casos e Controles , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Feminino , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Mutantes , Pessoa de Meia-Idade , Mutação , RNA Longo não Codificante/biossíntese , Receptores Mitogênicos/genética , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: In recent decades, the death rate from lung cancer appears to be an increasing yearly trend, particularly for non-small-cell lung cancer (NSCLC). Curcumin is a yellow pigment found in turmeric rhizomes, reported to exhibit various anti-inflammatory, anti-angiogenic, anti-proliferative, and antioxidant properties. Many reports have suggested that curcumin could induce apoptosis in malignant cells, and therefore, has great potential in tumor treatment. However, little is known about the effect of curcumin on NSCLC or its associated mode of action. Therefore, in this study, we explored curcumin's effect on NSCLC and investigated its associated mechanism. MATERIALS AND METHODS: The non-small-cell lung cancer (NSCLC) cell line A549 was cultured and subjected to MTT and clonogenic survival assays to assess cell proliferation. Reactive oxygen species (ROS) levels were measured using a Fluostar Omega Spectrofluorimeter. Superoxide dismutase (SOD) and γ-glutamyl cysteine synthetase (γ-GCS) activity in A549 cells were both determined by a commercial determination kit. Expression levels of p-GSK3ß (Ser9), c-Myc, cyclin D1, ß-catenin α-tubulin, and proliferating cell nuclear antigen (PCNA) were analyzed by Western blot. RESULTS: Results of the MTT and clonogenic survival assay indicated that curcumin reduced A549 proliferation. ROS levels and SOD and γ-GCS activities were detected. Curcumin decreased intracellular ROS levels and increased SOD and γ-GCS activity. Meanwhile, the ROS inhibitor N-Acetylcysteine (NAC) reversed the decrease in ROS levels and the increase in SOD and γ-GCS activity. These results indicate that oxidative stress is involved in the curcumin-induced reduction of A549 viability. Curcumin also strongly inhibited ß-catenin and p-GSK3ß (Ser9) protein expression, as well as the expression of downstream cyclin D1 and c-Myc. Similarly, NAC reversed the inhibition of ß-catenin and p-GSK3ß (Ser9) protein expression, as well as the expression of downstream cyclin D1 and c-Myc. CONCLUSIONS: We showed that curcumin inhibits NSCLC proliferation via the Wnt/ß-catenin pathway.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Curcumina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/fisiologia , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: The occurrence rate of delayed fracture healing in diabetes mellitus patients is high. Transforming growth factor ß1 (TGF-ß1) is an important regulatory factor in bone tissue repair and regeneration. However, TGF-ß1 expression and its function in diabetic patient fracture have not been fully elucidated. PATIENTS AND METHODS: Type 2 diabetes fracture patients (T2DM group), fracture patients without diabetes (non-T2DM group), and healthy volunteers (Control group) were selected for the research. TGF-ß1 expression in peripheral blood was detected by using enzyme-linked immunosorbent assay (ELISA). Osteoblast cell line, MG-63 cells, were randomly divided into Control, high glucose group, and TGF-ß1 group. TGF-ß1 expression was evaluated by using Real Time-PCR (RT-PCR). Cell proliferation was evaluated by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis activity was determined with caspase-3 activity and flow cytometry assay. The effect of TGF-ß1 on NF-κB was detected by using Western blot. RESULTS: TGF-ß1 was significantly reduced in patients of T2DM and non-T2DM groups compared with Control (p<0.05), while it was lower in T2DM group (p<0.05). TGF-ß1 expression was declined, cell proliferation was inhibited, caspase-3 activity was enhanced, cell apoptosis was elevated, and NF-κB expression was reduced in MG-63 cells of high glucose group compared to Control group (p<0.05). TGF-ß1 significantly promoted cell proliferation, suppressed caspase-3 activity, alleviated cell apoptosis, and elevated NF-κB expression in MG-63 cells compared with high glucose group (p<0.05). CONCLUSIONS: TGF-ß1 decreased in diabetes fracture patients. Up-regulation of TGF-ß1 regulates cell apoptosis and caspase-3 activity, and it facilitates osteoblasts proliferation.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Consolidação da Fratura , Fraturas Ósseas/metabolismo , Osteoblastos/metabolismo , Fator de Crescimento Transformador beta1/sangue , Adulto , Idoso , Apoptose , Estudos de Casos e Controles , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Consolidação da Fratura/efeitos dos fármacos , Fraturas Ósseas/patologia , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Transdução de Sinais , Fatores de Tempo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
OBJECTIVE: To explore the effects of postoperative functional exercise on patients who underwent percutaneous transforaminal endoscopic discectomy for lumbar disc herniation. PATIENTS AND METHODS: From January to May 2011, patients who had a lumbar disc herniation and then underwent percutaneous transforaminal endoscopic discectomy were divided randomly into two groups: the intervention group (n=46) and the control group (n=46). The intervention group conducted early functional exercises of passive and autonomic activities after their operations, while the control group conducted routine functional exercises after their operations. Short-term and long-term curative effects and quality of life were compared; risk factors that might affect the rehabilitation effects on the patients were analyzed using logistic regression. RESULTS: The lumbar curvature, lumbar lordosis index and sacral inclination angle of the intervention group were better than that those same spinal stability factors in the control group six months after their operations (p<0.05). Scores for residual lumbocrural pain, straight leg raising, muscle strength (skin) sensory, nerve reflex and lumbar function of patients in the intervention group were better than those scores of the control group (p<0.05). The scores for physiological function, emotional function, activity and social function, mental health and quality of life of the intervention group were better than those of the control group (p<0.05). After 1 year of follow-up, the total effective rate for the intervention group was 82.6%, significantly higher than the control group, which had a total effective rate of 71.7% (p<0.05). After 3 years of follow-up, the score for the intervention group was 97.8%, significantly higher than the control group, which had an overall average score of 89.1% (p<0.05). Logistic regression analysis showed that the type of disc herniation, whether patients abided by their doctors' advice during treatment and protected their lumbar vertebra during treatment, and their age were all influential factors on patient rehabilitation. CONCLUSIONS: Early functional exercises of passive and autonomic activities can improve the postoperative quality of life of patients with lumbar disc herniation and provides a basis for inclusion in postoperative treatment of lumbar disc herniation. Importance should be placed on factors, such as postoperative exercise, that can improve the curative effect of rehabilitation.
Assuntos
Discotomia Percutânea/métodos , Endoscopia/métodos , Terapia por Exercício , Deslocamento do Disco Intervertebral/reabilitação , Vértebras Lombares/cirurgia , Adulto , Idoso , Feminino , Humanos , Deslocamento do Disco Intervertebral/psicologia , Deslocamento do Disco Intervertebral/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos RetrospectivosRESUMO
OBJECTIVE: Osteosarcoma is the most frequent primary bone malignancy that affects young adults and adolescents around the world. Increasing evidence suggests that dysfunctions of microRNAs (miRNAs) used to play an important role in human cancers. We aimed at evaluating the potential function of miR-16 and verify its influence on the function of RAB23 in osteosarcoma. PATIENTS AND METHODS: miR-16 expressions in osteosarcoma tissues and cell lines were examined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Transwell chambers were conducted to detect the miR-16 effects on osteosarcoma cells migration and invasion. Meanwhile, Western blot and luciferase assays were performed to validate RAB23 as miR-16 targets. RESULTS: miR-16 was down-regulated in osteosarcoma cell lines (MG63, SAOS-2, U2OS, and SOSP-9607) and osteosarcoma specimens, while RAB23 expression was higher in tumor tissues. Ectopic over-expression of miR-216 in osteosarcoma cells could inhibit cells migration and invasion. RAB23 was confirmed as a direct target of miR-16 and the inverse relationship between them was also observed. Over-expression of RAB23 ablates the inhibitory effects of miR-16. CONCLUSIONS: miR-16 inhibited cancer migration and invasion, and promoted the RAB23 expression in osteosarcoma. This newly identified miR-16/RAB23 axis may provide new insight into the pathogenesis and represents a potential therapeutic target for osteosarcoma.