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Objective: To evaluate the efficacy and safety of Ophiocordyceps sinensis (OS) preparations for the treatment of Hashimoto's thyroiditis (HT). Methods: We searched eight databases to collect randomized controlled trials (RCTs) of OS combined with a low-iodine diet or levothyroxine for HT. The search period was from inception to June 2023. Meta-analysis was performed using Revman 5.3 software after two evaluators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. The GRADE system was used to assess the certainty of evidence. Results: A total of 14 RCTs involving 1,014 patients with HT were included. Meta-analysis showed that OS preparations combined with a low-iodine diet were more effective in reducing thyroid peroxidase antibody (TPOAb) [SMD = -3.81, 95% CI (-5.07, -2.54), p < 0.00001] and thyroglobulin antibody (TgAb) [SMD = -4.73, 95% CI (-6.86, -2.61), p < 0.00001] compared to a low-iodine diet. Compared with levothyroxine treatment alone, OS preparations combined with levothyroxine further reduced TPOAb [SMD = -2.04, 95% CI (-2.82, -1.26), p < 0.00001], TgAb [SMD = -2.01, 95% CI (-2.68, -1.33), p < 0.00001], tumor necrosis factor alpha (TNF-α) [SMD = -3.40, 95% CI (-5.66, -1.14), p = 0.003], interleukin-2 (IL-2) [SMD = -2.31, 95% CI (-3.98, -0.65), p = 0.006], and interleukin-6 (IL-6) [MD = -4.16, 95% CI (-6.17, -2.15), p < 0.0001], and elevated free thyroxine (FT4) [SMD = 1.34, 95% CI (0.59, 2.08), p = 0.0004], but no significant effect on free triiodothyronine (FT3) [SMD = 0.83, 95% CI (-0.12, 1.78), p = 0.09] and thyroid stimulating hormone (TSH) [SMD = -0.80, 95% CI (-1.71, 0.11), p = 0.08]. In terms of safety, three studies reported adverse reactions in 10 patients in each of the experimental and control groups. Conclusion: OS preparations in combination with other treatments (low-iodine diet or levothyroxine) may decrease thyroid autoantibodies and inflammatory responses in patients with HT. In HT patients with hypothyroidism, the combination of the OS preparations with levothyroxine also improved FT4. However, the quality of the included studies was generally low. Moreover, the safety of OS preparations remains unclear. Therefore, more high-quality, multicenter, large-sample RCTs are needed in the future to validate the efficacy and safety of OS preparations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023432663.
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Kaolinite supported cerium oxide (CeOx/Kaol) was successfully prepared via a deposition method and used to improve the mechanical and aging properties of styrene-butadiene rubber (SBR) composite. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results showed that cerium oxide has a successfully loading and fine distribution on the edge and surface of kaolinite. Fourier transform infrared (FT-IR) spectroscopy indicated that cerium oxide may interact with the surface hydroxyls of kaolinite. The CeOx/Kaol material had a uniform dispersion in the resulting SBR composite. The loading of cerium oxide on Kaol increases the scorch time (t10) and curing time (t90) of the filled SBR composites relative to the pure SBR. The mechanical parameters of the filled SBR composites were increased significantly. The tensible strength and tear strength at 40 phr content with 4% CeOx loading reached 12.85 Mpa and 51.16 kN/m, which were increases of 35.9% and 38.3%, respectively, relative to that of the SBR filled with raw Kaol. The anti-ageing characteristic of the resulting composite showed an obvious improvement with the loading of CeOx. Meanwhile, the reinforcement and anti-ageing mechanisms of the CeOx/Kaol were proposed. These results were attributed to the complexation between Ce elements on the surface of Kaol and rubber chains through a double bond. This could improve the incorporation between rubber molecules and filler particles, and restrict rubber chain motion via trapping rubber chains.
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BACKGROUND AND AIMS: High-fat diet (HFD) is reported to induce atherosclerosis and insulin resistance. Macrophage lipid accumulation has been implicated as key mediators during the development of HFD-induced atherosclerosis. Traditional Chinese formula, which has long been used to improve disorder of glucose and lipid metabolism of patients, is now gradually being used as complementary therapy. This study aimed to investigate the effect of Danhong injection (DHI), a Chinese medicine used for the treatment of coronary artery disease, on atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: We observed the effects of DHI on HFD-induced atherosclerosis in a mice model, macrophage lipid accumulation in an ox-LDL-stimulated macrophage model, and the role of PI3K/AKT insulin pathway in the process of DHI ameliorating atherosclerosis. The data demonstrated that DHI attenuated atherosclerosis by ameliorating blood lipids, reducing the atherosclerotic index and atherosclerotic plaque area in HFD-induced atherosclerotic mice, and inhibiting TC levels in an ox-LDL-induced macrophage model. By estimating the levels of serum insulin resistance-related indexes and protein expression of GLUT-4, DHI treatment dramatically inhibited the levels of fasting serum NEFA and fasting serum insulin and promoted the protein expression of GLUT-4 in aortas of the HFD-induced atherosclerotic mice. Moreover, according to the hints provided by microarray-based transcriptional profiling, the results demonstrated that DHI treatment also promoted the activation of PI3K/AKT insulin signaling pathway induced by IRS-1 in aortas of HFD-induced atherosclerotic mice. Furthermore, in an ox-LDL-induced macrophage model, the activation of PI3k/AKT signaling pathway also effectively functioned in the process of DHI inhibiting macrophage lipid accumulation. CONCLUSIONS: These results highlight that DHI treatment attenuates atherosclerosis and macrophage lipid accumulation by promoting the activation of PI3K/AKT insulin signaling pathway. It provides new insights into the molecular mechanism of DHI and its therapeutic potential in the treatment of atherosclerosis.
Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Medicamentos de Ervas Chinesas/administração & dosagem , Hipolipemiantes/administração & dosagem , Insulina/metabolismo , Lipídeos/sangue , Macrófagos/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Aorta/enzimologia , Aorta/patologia , Doenças da Aorta/enzimologia , Doenças da Aorta/genética , Doenças da Aorta/patologia , Aterosclerose/enzimologia , Aterosclerose/genética , Aterosclerose/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação da Expressão Gênica , Injeções Intraperitoneais , Insulina/genética , Macrófagos/enzimologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Fosfatidilinositol 3-Quinase/genética , Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-akt/genética , Células RAW 264.7 , Transdução de SinaisRESUMO
PURPOSE: Long noncoding RNAs (lncRNAs) play an important role in the tumorigenesis and progression of human cancer. This research was performed to investigate the role of LINC01296 in clinical characteristics, biological functions and molecular mechanisms of bladder cancer. MATERIALS AND METHODS: In this study, expressions of LINC01296 in cancer tissues and normal tissues were firstly compared using the Gene Expression Profiling Interactive Analysis database. Subsequently, a microarray data analysis was performed to compare lncRNA and mRNA expression profiles in four pairs of human bladder cancer samples. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC01296 in bladder cancer tissues. The association between LINC01296 expressions and clinicopathological characteristics of bladder cancer was analyzed by Kaplan-Meier analysis and the Cox proportional-hazard model. The biological functions and molecular mechanisms of LINC01296 in bladder cancer were studied by MTT assay, colony-formation assay, cell cycle analysis, transwell migration assay, wound healing assay, qRT-PCR analysis and Western blot assay. RESULTS: The expression of LINC01296 was significantly higher in most cancer tissues than that in adjacent normal tissues, and was positively correlated with clinical stages of the cancer (P=0.016), lymph node metastasis (P=0.034), and pathologic grades (P=0.012). The increased level of LINC01296 was associated with a poorer prognosis and shorter survival of the patients. Multivariate analysis showed that the LINC01296 expression was an independent predictor of overall survival in bladder cancer. Additionally, LINC01296 knockdown inhibited the proliferation, migration and progression of cell cycle of bladder cancer cells, and was involved in the regulation of epithelial-mesenchymal transition. CONCLUSION: The findings of this study suggested that LINC01296 promotes progression of bladder cancer, and potentially acts as a biomarker and therapeutic target of bladder cancer.
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Urothelial Carcinoma Antigen 1 (UCA1) is a cell and tissue specific long non-coding RNA (lncRNA) associated with the tumorigenesis and invasion of bladder cancer. However, the mechanism driving the over-transcription of UCA1 in bladder cancer cells remains unclear. It has been reported that C/EBPß has a significant role of regulation in tumorigenesis. Here we report that the expression of UCA1 was dramatically inhibited in 5637â¯cells with C/EBPß down-regulation. Additionally, the function tests indicated that C/EBPß could promote 5637â¯cells growth and colony formation by inducing the expression level of UCA1. These data suggest that C/EBPß was involved in transcriptional regulation of UCA1 and contributed substantially to its high expression and proliferation promoting in bladder cancer cells.
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Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , RNA Longo não Codificante/genética , Transcrição Gênica , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Regiões Promotoras Genéticas/genética , Ligação Proteica , RNA Longo não Codificante/metabolismoRESUMO
Long non-coding RNA urothelial carcinoma associated 1 (UCA1) was first identified in bladder cancer tissues. High expression of UCA1 in bladder cancer has suggested it may serve as a potential diagnostic molecular marker for bladder cancer. Subsequent research in bladder cancer cell lines showed that UCA1 can promote cell proliferation, but the underlying mechanism remains unknown. In the present study, we identified BRG1 as a UCA1 binding partner using an in vitro RNA pull-down assay, and RNA-binding protein immunoprecipitation assay confirmed UCA1-BRG binding in bladder cancer cells in vivo. BRG1 is a chromatin remodeling factor with reported tumor suppressor activities that directly upregulates levels of the p21 cell cycle inhibitor by binding sequences in the p21 promoter. Depletion of UCA1 by RNAi resulted in upregulated p21 levels and inhibition of cell replication, while overexpressed UCA1 reduced p21 protein and promoted cell growth. Notably, UCA1 downregulation of p21 and induction of cell proliferation antagonized the function of BRG1. UCA1 highly expressed tissue samples are often with BRG1 high expression. Furthermore, we found that UCA1 impairs both binding of BRG1 to the p21 promoter and chromatin remodeling activity of BRG1. Collectively, these results demonstrate that UCA1 promotes bladder cancer cell proliferation by inhibiting BRG1.
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Inibidor de Quinase Dependente de Ciclina p21/genética , DNA Helicases/genética , Proteínas Nucleares/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Proliferação de Células , Montagem e Desmontagem da Cromatina , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , DNA Helicases/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Proteínas Nucleares/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/metabolismoRESUMO
OBJECTIVE: To study the DNA methylation of human telomerase reverse transcriptase (hTERT) promoter in ameloblastoma (AB) and investigate its clinical biological significance. METHODS: DNA methylation of hTERT promoter in 12 cases of AB and 11 cases of normal oral mucosa were detected by methylation-specific PCR. RESULTS: The positive cases of unmethylated hTERT promoter region in AB and normal oral mucosa were 4 (4/12) and 6 (6/11), respectively (P < 0.001). The positive cases of methylated hTERT promoter region in AB and normal oral mucosa were 11 (11/12) and 3 (3/11), respectively. Four cases of AB and 1 case of normal oral mucosa showed both DNA methylation and unmethylation of hTERT promoter region in the same time. CONCLUSIONS: DNA methylation of of hTERT promoter region in AB was more common than that in normal oral mucosa. The DNA methylation in hTERT promoter maybe regulate hTERT gene expression.
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Ameloblastoma/genética , Metilação de DNA , Telomerase/genética , Adolescente , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Maxilomandibulares/genética , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Adulto JovemRESUMO
OBJECTIVE: To study the expression of HOXC13 mRNA in ameloblastoma (AB), and to investigate its biological significance. METHODS: HOXC13 mRNA was examined in 47 cases of AB (primary AB 29 cases, recurrent AB 14 cases, malignant AB 4 cases). 2 cases of fibrous dysplasia of bone, 10 cases of keratocystic odontogenic tumor (KCOT) and 7 cases of normal oral mucosa were selected as control. RESULTS: The positive rates of HOXC13 mRNA in AB, KCOT, and normal oral mucosa were 97.9% (46/47), 7/10 and 3/7, respectively. There was a significant difference among AB, OKC and normal mucosa (chi(2) = 21.665, P = 0.001). For HOXC13, the keratinizing cells and granulizing cells in AB were negative, some fibroblasts were positive, 2 cases of fibrous dysplasia of bone were positive. CONCLUSIONS: HOXC13 was highly expressed in AB. The expression of HOXC13 mRNA in AB had heterogeneity, which could improve the epithelial proliferation, and its loss may lead to the cornification and degeneration of epithelial cells.
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Ameloblastoma/genética , Proteínas de Homeodomínio/metabolismo , Adolescente , Adulto , Ameloblastoma/metabolismo , Ameloblastoma/patologia , Feminino , Expressão Gênica , Genes Homeobox , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Tumores Odontogênicos/genética , Tumores Odontogênicos/metabolismo , RNA Mensageiro/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To investigate the expression of cyclin E mRNA, p21(WAF1) mRNA and p27(KIP1) protein in human ameloblastoma (AB), and to explore the clinical and biological characteristics of AB. METHODS: The expression of cyclin E mRNA, p21(WAF1) mRNA and p27(KIP1) protein in 54 cases of human AB were detected by in situ hybridization or immunohistochemistry (SP method). RESULTS: The positive expression rate of cyclin E mRNA in the cytoplasm or cell nucleus of AB was 66.7% (36/54). The expression of cyclin E mRNA increased with AB recurrence and malignant transformation, and the difference of expression among primary AB, recurrent AB, and malignant AB, was statistically significant. The positive expression ratio of cyclin E mRNA in OKC was 50.0% (8/16). The p21(WAF1) mRNA expression in the cytoplasm or cell nucleus of AB decreased, and the positive ratio was 22.6% (12/54) in AB, 37.5% (6/16) in OKC, respectively. The p27(KIP1) protein expression in the cell nucleus of AB was positive in a small number of cases, and the positive rate was 16.7% (9/54) in AB, 6.3% (1/16) in OKC, respectively. CONCLUSIONS: The genesis and invasion of AB is associated with the cell proliferation and differentiation, and regulated by the higher expression of cyclin E and the lower expression of p21(WAF1) and p27(KIP1).
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Ameloblastoma/metabolismo , Ciclina E/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Proteínas Oncogênicas/metabolismo , Adolescente , Adulto , Idoso , Ameloblastoma/patologia , Criança , Ciclina E/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p27 , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Maxilomandibulares/patologia , Pessoa de Meia-Idade , Proteínas Oncogênicas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To study the oncogene transcriptor c-myc, stimulatory protein 1 (SP1) expression in ameloblastoma (AB) and their relation with telomerase reverse transcripase (hTERT), and to investigate the clinical biological characteristics of AB. METHODS: The expression was observed in AB by in situ hybridization and SP method. RESULTS: The positive rates of c-myc mRNA, hTERT mRNA and SP1 protein were 81.5% (44/54), 94.4% (51/54) and 83.3% (45/54), respectively. Their positive rates increased as AB recurred and transformed malignantly. A strong correlation was found between hTERT and c-myc, hTERT and SP1 (rs = 0.853, P < 0.001; rs = 0.900, P < 0.001). CONCLUSION: Activity of telomerase plays an important role in the tumorigenesis development of AB. Increasing of hTERT expression may be related to c-myc and SP1. The expression of these three parameters has a significant correlation with the clinical biological characteristics of AB.