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1.
Neurourol Urodyn ; 43(2): 516-526, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38108523

RESUMO

BACKGROUND: Partial bladder outlet obstruction (pBOO) may lead to bladder remodeling, including fibrosis and extracellular matrix (ECM) deposition. Despite the extensive research on the mechanisms underlying pBOO, potential therapeutic targets for the treatment of pBOO require further research. Dysregulated expression of thrombospondin-1 (Thbs1) has been reported in various human fibrotic diseases; however, its relationship with pBOO remains unclear. AIMS: Investigate the effects of Thbs1 on bladder remodeling caused by pBOO. METHODS: We established a pBOO model in Sprague-Dawley rats and performed urodynamic analyses to estimate functional changes in the bladder, validated the histopathological changes in the bladder by using haematoxylin-eosin and Masson's trichrome staining, identified key target genes by integrating RNA sequencing (RNA-seq) and bioinformatics analyses, validated the expression of related factors using Western blot analysis and RT-qPCR, and used immunofluorescence staining to probe the potential interaction factors of Thbs1. RESULTS: Urodynamic results showed that pressure-related parameters were significantly increased in rats with pBOO. Compared with the sham group, the pBOO group demonstrated significant increases in bladder morphology, bladder weight, and collagen deposition. Thbs1 was significantly upregulated in the bladder tissues of rats with pBOO, consistent with the RNA-seq data. Thbs1 upregulation led to increased expression of matrix metalloproteinase (MMP) 2, MMP9, and fibronectin (Fn) in normal human urinary tract epithelial cells (SV-HUC-1), whereas anti-Thbs1 treatment inhibited the production of these cytokines in TGF-ß1-treated SV-HUC-1. Further experiments indicated that Thbs1 affected bladder remodeling in pBOO via the fibroblast growth factor receptor 3 (FGFR3) pathway. CONCLUSIONS: Thbs1 plays a crucial role in bladder remodeling caused by pBOO. Targeting Thbs1 might alleviate ECM damage. Mechanistically, Thbs1 may function via the FGFR signaling pathway by regulating the FGFR3 receptor, identified as the most relevant disease target of pBOO, and FGF2 may be a mediator. These findings suggest that Thbs1 plays a role in BOO development and is a therapeutic target for this condition.


Assuntos
Obstrução do Colo da Bexiga Urinária , Bexiga Urinária , Animais , Humanos , Ratos , Modelos Animais de Doenças , Ratos Sprague-Dawley , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/farmacologia , Transdução de Sinais
2.
Cardiovasc Diabetol ; 22(1): 290, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891550

RESUMO

BACKGROUND: A comprehensive network meta-analysis comparing the effects of individual sodium-glucose cotransporter 2 (SGLT2) inhibitors on patients with and without comorbidities including diabetes mellitus (DM), heart failure (HF), and chronic kidney disease (CKD) has not been previously conducted. METHODS: We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomized controlled trials up to March 28, 2023. Network meta-analysis using a random-effects model was conducted to calculate risk ratios (RRs). Risk of Bias tool 2.0 was used to assess bias, and CINeMA to assess the certainty of evidence. In the subgroup analysis, the SGLT2 inhibitors were classified into highly (dapagliflozin, empagliflozin, and ertugliflozin) and less selective SGLT2 inhibitors (canagliflozin and sotagliflozin). RESULTS: A total of fourteen trials with 75,334 patients were analyzed. Among these, 40,956 had taken SGLT2 inhibitors and 34,378 had not. One of the main results with particular findings was empagliflozin users had a significantly lower risk of all-cause death compared to dapagliflozin users in DM population (RR: 0.81, 95% CI 0.69-0.96). In HF population, sotagliflozin users had a borderline significantly lower risk of CV death or hospitalization for HF (HHF) than dapagliflozin users (RR: 0.90, 95% CI 0.80-1.01). In non-HF population, those who used canagliflozin had a significantly lower risk of CV death or HHF compared with those who used dapagliflozin (RR: 0.75, 95% CI 0.58-0.98). At last, for HF patients, those who used less selective SGLT2 inhibitors had a significantly lower risk of MACEs compared to those who used highly selective SGLT2 inhibitors (RR: 0.75, 95% CI 0.62-0.90). CONCLUSIONS: Our network meta-analysis revealed that empagliflozin users with diabetes experienced a lower risk of dying from any cause than those using dapagliflozin. Additionally, canagliflozin users demonstrated a reduced risk of cardiovascular death or HHF compared to dapagliflozin users in those without HF. In HF patients, less selective SGLT2 inhibitors showed superior CV composite outcomes, even surpassing the performance of highly selective SGLT2 inhibitors. TRIAL REGISTRATION: PROSPERO [CRD42022361906].


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/efeitos adversos , Metanálise em Rede , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia
3.
Neurourol Urodyn ; 42(7): 1506-1521, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37455557

RESUMO

AIMS: N6-methyladenosine (m6A) modification is a critical posttranscriptional event in gene regulation. Thus, identifying methyltransferase, demethylase, or m6A binding protein-mediated m6A modifications in cancer or noncancer transcriptomes has become a promising novel strategy for disease therapy development. However, novel insights into m6A modification in partial bladder outlet obstruction (pBOO) and detailed information about the drivers of bladder remodeling remain to be elucidated. Here, we first characterized the m6A modification landscape in pBOO and investigated potential actionable pharmaceutical targets for future therapies. METHODS: We generated an improved animal model of pBOO in SD rats with urethral meatus stricture induced by suturing. Urodynamic investigations and cystometry were carried out to evaluate the physiologic changes elicited by pBOO. Whole-transcriptome sequencing (RNA-seq) and m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) were subsequently performed to analyze the expression pattern associated with bladder remodeling in pBOO. RESULTS: The cystometric evaluation of bladder function demonstrated obvious increases in pressure-related parameters in the pBOO group. Hematoxylin and eosin staining and Masson's trichrome staining validated the occurrence of bladder remodeling. A global elevation in m6A RNA methylation levels was observed in parallel to a increased expression of METTL3 in the pBOO group. High-throughput sequencing revealed the differences in expression patterns between the pBOO and sham-operated groups. Furthermore, potential m6A-modified genes, including CCN2, may serve as new pharmaceutical targets to reverse bladder remodeling. CONCLUSIONS: Exploring the roles of m6A-modified genes identified as associated with bladder remodeling by integrating RNA-seq and MeRIP-seq data can offer new insights for developing promising treatments for pBOO patients.


Assuntos
Estreitamento Uretral , Obstrução do Colo da Bexiga Urinária , Animais , Ratos , Modelos Animais de Doenças , Metiltransferases/genética , Metiltransferases/metabolismo , Preparações Farmacêuticas/metabolismo , Ratos Sprague-Dawley , RNA , Bexiga Urinária
4.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(5): 528-532, 2023 Sep 30.
Artigo em Zh | MEDLINE | ID: mdl-37753892

RESUMO

In order to solve the problems of quality control and traceability of medical test lung for meeting the calibration conditions of JJF 1234-2018 Calibration Specification for Ventilators, the calibration device and method are researched for compliance and airway resistance of medical test lung in this paper. A calibration device for medical test lung is designed using constant volume active piston technology to simulate human breathing. Through comparison experiment, the deviation between this device and the similar foreign device can be found. The deviation is lower than 0.4% for lung compliance and lower than 0.7% for airway resistance. The calibration of lung compliance and airway resistance can be completed by this device. This device has a clear and complete traceability path to ensure quality control from the source. The calibration of ventilator is improved. This paper provides a reference for related metrology departments and medical institutions to study on quality inspection of respiratory medical instruments.


Assuntos
Respiração , Ventiladores Mecânicos , Humanos , Calibragem , Controle de Qualidade , Pulmão
5.
Crit Care ; 26(1): 349, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371256

RESUMO

BACKGROUND: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. METHODS: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. CONCLUSIONS: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.


Assuntos
Injúria Renal Aguda , Interleucina-18 , Adulto , Humanos , Lipocalina-2/urina , Inibidor Tecidual de Metaloproteinase-2 , Creatinina , Injúria Renal Aguda/terapia , Biomarcadores , Hospitais
6.
Mol Cancer ; 20(1): 75, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985545

RESUMO

BACKGROUND: Cirrhosis is a recognized risk factor for developing hepatocellular carcinoma (HCC). Few studies have reported the expression profile of circRNAs in HCC samples compared to paratumour dysplastic nodule (DN) samples. METHODS: The Arraystar Human circRNA Array combined with laser capture microdissection (LCM) was used to analyse the expression profile of circRNAs in HCC samples compared to paratumour DN samples. Then, both in vitro and in vivo HCC models were used to determine the role and mechanism of key circRNA in HCC progression and treatment sensitivity. RESULTS: We found that circMEMO1 was significantly downregulated in HCC samples and that the level of circMEMO1 was closely related to the OS and disease-free survival (DFS) of HCC patients. Mechanistic analysis revealed that circMEMO1 can modulate the promoter methylation and gene expression of TCF21 to regulate HCC progression by acting as a sponge for miR-106b-5p, which targets the TET family of genes and increases the 5hmC level. More importantly, circMEMO1 can increase the sensitivity of HCC cells to sorafenib treatment. CONCLUSION: Our study determined that circMEMO1 can promote the demethylation and expression of TCF21 and can be considered a crucial epigenetic modifier in HCC progression.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Carcinoma Hepatocelular/patologia , Metilação de DNA , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/patologia , RNA Circular/metabolismo , Antineoplásicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Metilação de DNA/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Regiões Promotoras Genéticas/genética , RNA Circular/genética , Sorafenibe/uso terapêutico
7.
Hepatology ; 72(3): 923-939, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31867749

RESUMO

BACKGROUND AND AIMS: Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB-EGF to promote angiogenesis and HCC progression. APPROACH AND RESULTS: A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB-EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia-inducible factor 1 α signaling pathway. In addition, HB-EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3-kinase/Akt signaling pathway. The level of HB-EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence-free survival, which suggests that HB-EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB-EGF inhibitor cross-reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression. CONCLUSIONS: HB-EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB-EGF inhibitor cross-reacting material 197 with sorafenib might be used for individualized treatment of HCC.


Assuntos
Proteínas de Bactérias/farmacologia , Carcinoma Hepatocelular , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Neoplasias Hepáticas , Proteínas de Membrana/metabolismo , Serina Endopeptidases/metabolismo , Inibidores da Angiogênese/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/prevenção & controle , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Transdução de Sinais , Sorafenibe/farmacologia
8.
Environ Sci Technol ; 55(11): 7615-7623, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34014661

RESUMO

Feammox, that is, Fe(III) reduction coupled to anaerobic ammonium oxidation, has been reported to play an important role in the nitrogen cycle in natural environments. However, the application of Feammox in wastewater treatment is limited because continuous Fe(III) supplementation is required for achieving continuous nitrogen removal, which is not feasible in practice. In this study, air was aerated intermittently into the Feammox system containing iron and high-content ammonium for oxidizing Fe(II) generated from Feammox to Fe(III), then, the produced Fe(III) participated in the next round of Feammox, leading to continuous nitrogen removal through the Fe(II)/Fe(III) cycle. The results showed that after each 10 min of aeration (150 mL/min), every 6-7 days, dissolved oxygen (DO) increased from 0 to about 0.4 mg/L, accompanied by a decrease in Fe(II) and an increase in Fe(III). One day after the aeration, DO was undetectable, and then, Fe(II) content increased and Fe(III) content decreased. On day 90, NH4+-N content in the aerated reactor was only 10.2 mg/L, while it remained at around 288.3 mg/L in the aeration-free group. X-ray diffraction showed that the generated Fe(III) through air aeration was Fe(OH)3. Microbial analysis showed that anammox and nitrification/denitrification could be excluded in the system. This NH4+ removal process, driven by the Fe(II)/Fe(III) cycle with O2 as the terminal electron acceptor, might be used as an in situ remediation method for treating high-content NH4+.


Assuntos
Compostos de Amônio , Anaerobiose , Reatores Biológicos , Desnitrificação , Compostos Férricos , Compostos Ferrosos , Nitrogênio , Oxirredução
9.
J Gastroenterol Hepatol ; 36(6): 1487-1496, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33393670

RESUMO

BACKGROUND AND AIM: The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC. METHODS: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. RESULTS: Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC. CONCLUSION: Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/genética , Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Prognóstico , Taxa de Sobrevida
10.
Opt Express ; 28(21): 30362-30378, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33115040

RESUMO

Ring artifacts seriously deteriorate the quality of CT images. Intensity-dependence of detector responses will result in intensity-dependent ring artifacts and time-dependence of CT hardware systems will result in time-dependent ring artifacts. However, only the intensity-dependent ring artifacts are taken into consideration in most post-processing methods. Therefore, the purpose of this study is to propose a general post-processing method, which has a significant removal effect on the intensity-dependent ring artifacts and the time-dependent ring artifacts. First in the proposed method, transform raw CT images into polar coordinate images, and the ring artifacts will manifest as stripe artifacts. Secondly, obtain structure images by smoothing the polar coordinate images and acquire texture images containing some details and stripe artifacts by subtracting the structure images from the polar coordinate images. Third, extract the stripe artifacts from the texture images using mean extraction and texture classification, and obtain the extracted ring artifacts by transforming the extracted stripe artifacts from polar coordinates into Cartesian coordinates. Finally, obtain corrected CT images by subtracting the extracted ring artifacts from the raw CT images, and iterate the corrected CT images in above steps until the ring artifacts extracted in the last iteration are weak enough. Simulation and real data show that the proposed method can remove the intensity-dependent ring artifacts and the time-dependent ring artifacts effectively while preserving image details and spatial resolution. In particular, real data prove that the method is suitable for new CT systems such as the photon counting CT.

11.
BMC Med Inform Decis Mak ; 20(1): 64, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252745

RESUMO

BACKGROUND: In this study, we focus on building a fine-grained entity annotation corpus with the corresponding annotation guideline of traditional Chinese medicine (TCM) clinical records. Our aim is to provide a basis for the fine-grained corpus construction of TCM clinical records in future. METHODS: We developed a four-step approach that is suitable for the construction of TCM medical records in our corpus. First, we determined the entity types included in this study through sample annotation. Then, we drafted a fine-grained annotation guideline by summarizing the characteristics of the dataset and referring to some existing guidelines. We iteratively updated the guidelines until the inter-annotator agreement (IAA) exceeded a Cohen's kappa value of 0.9. Comprehensive annotations were performed while keeping the IAA value above 0.9. RESULTS: We annotated the 10,197 clinical records in five rounds. Four entity categories involving 13 entity types were employed. The final fine-grained annotated entity corpus consists of 1104 entities and 67,799 tokens. The final IAAs are 0.936 on average (for three annotators), indicating that the fine-grained entity recognition corpus is of high quality. CONCLUSIONS: These results will provide a foundation for future research on corpus construction and named entity recognition tasks in the TCM clinical domain.


Assuntos
Medicina Tradicional Chinesa
12.
Cell Biol Int ; 43(3): 323-332, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30632644

RESUMO

Calycosin has been reported to have a strong osteogenic activity and a positive correlation with anti-osteoporosis effects. However, its precise mechanism of action remains unclear. Since insulin-like growth factor 1 receptor (IGF1R) signaling and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling have been shown to play a pivotal role in regulating osteogenesis, we hypothesized that the osteogenic activity of calycosin is mediated by these signaling pathways. Rat calvarial osteoblasts (ROBs) were cultured in osteogenic medium containing calycosin with or without GSK1904529A (GSK) or LY294002 (LY) (inhibitors of IGF1R and PI3K, respectively). The effects on cell proliferation, alkaline phosphatase (ALP) activity, calcified nodules, mRNA or protein expression of osteogenic genes [alkaline phosphatase (Alpl), collagen type I (Col1a1), runt-related transcription factor 2 (Runx2), Osterix, and bone morphogenetic protein 2 (Bmp2)], and phosphorylation of IGF1R and Akt were examined. The present results showed that calycosin enhanced cell proliferation, ALP activity and Alizarin Red-S staining in a dose-dependent manner in the range of 10-8 -10-6 M, while an inhibitory effect was observed at 10-5 M. Treatment at the optimal concentration (10-6 M, a physiologically achievable concentration) increased mRNA levels of osteogenic genes and phosphorylation of IGF1R and Akt. Furthermore, treatment with GSK or LY partly reversed the effects of calycosin on ROBs, as indicated by the decreases in calycosin-induced ALP activity, calcified nodules and osteogenic gene expression. These results suggest that the osteogenic effect of calycosin partly involves the IGF1R/PI3K/Akt signaling pathway.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Isoflavonas/farmacologia , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Crânio/citologia , Fosfatase Alcalina/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imidazóis/farmacologia , Isoflavonas/química , Morfolinas/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
13.
J Environ Sci (China) ; 81: 34-42, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30975327

RESUMO

Cathodic reduction of CO2 and anodic oxidation of organic matters are crucial to methane-producing microbial electrolysis cell (MEC) applied in anaerobic digestion of waste activated sludge. However, cathodic CO2 reduction is usually restrained by slow metabolism rates of H2-utilizing methanogens and low electron-capturing capacity of CO2, which consequently slows down the anodic oxidation that participates to sludge disintegration. Herein, a strategy with adding nitrate as electron acceptor to foster electronic transfer between the anode and cathode was proposed to improve anodic oxidation. Results showed that the average efficiency of anodic oxidation in the nitrate-added MEC increased by 55.9%. Accordingly, volatile suspended solid removal efficiency in the nitrate-added MEC was 21.9% higher than that of control MEC. Although the initial cumulative methane production in the nitrate-added MEC was lower than that of control MEC, the cumulative methane production in 24 days was 8.9% higher. Fourier transform infrared spectroscopy analysis indicated that anodic oxidation of MEC with nitrate accelerated the disintegration of sludge flocs and cell walls. Calculation on current signal further revealed that anodic oxidation driven by cathodic nitrate reduction was the main mechanism responsible for the improved sludge digestion.


Assuntos
Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Biocombustíveis , Reatores Biológicos , Eletrodos , Elétrons , Nitratos , Óxidos de Nitrogênio , Oxirredução , Esgotos
14.
Mol Carcinog ; 57(6): 807-814, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29500880

RESUMO

Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response.


Assuntos
Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Dano ao DNA , Diterpenos/farmacologia , Doxorrubicina/farmacologia , Fenantrenos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Compostos de Epóxi/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7
15.
Neurourol Urodyn ; 37(7): 2088-2096, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29953650

RESUMO

AIMS: Open surgery is the most commonly used methodological approach for generating a partial bladder outlet obstruction (pBOO) animal model. Surgical suturing closing a part of the urethral meatus induces comparable pathophysiological changes in bladder and renal functions, but the optimum degree of obstruction that closely mimics the clinical pathology of pBOO has not been elucidated. We investigated the optimum obstruction level by performing a comprehensive time-dependent analysis of the stability and reliability of this novel animal model. METHODS: Six- to eight-week-old female BALB/c mice were divided into three groups according to the degree of urethral meatus stricture (UMS). Non-operated mice served as controls, and a pBOO model generated using the traditional method served as a positive control. A cystometric evaluation and long-term studies were performed to evaluate the validity and reliability of this novel animal model. An additional 35 mice were used to investigate the protein expression levels and histopathological features 24 h and 14 days postoperatively, respectively. RESULTS: The characteristic cystometry features in the UMS group revealed increased changes in pressure-related parameters compared with the control. The 1/3 UMS model is an optional pBOO animal model because the cystometric evaluation and histopathological studies revealed a striking resemblance between the 1/3 UMS model and the model generated using the traditional open-surgery method. CONCLUSIONS: The minimally invasive UMS model required less time and produced minimal alterations in pathophysiologically relevant processes compared with the traditional surgery model. Suturing to cause UMS produced effective and repeatable patterns in bladder function investigations in mice.


Assuntos
Suturas/efeitos adversos , Estreitamento Uretral/etiologia , Obstrução do Colo da Bexiga Urinária/etiologia , Animais , Peso Corporal , Constrição Patológica , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão , Pressão , Antígeno Nuclear de Célula em Proliferação/biossíntese , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estreitamento Uretral/patologia , Estreitamento Uretral/fisiopatologia , Obstrução do Colo da Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Urodinâmica , Procedimentos Cirúrgicos Urológicos
16.
J Xray Sci Technol ; 26(2): 227-240, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29036876

RESUMO

This study aims to investigate and test a new image reconstruction algorithm applying to the low-signal projections to generate high quality images by reducing the artifacts and noise in the cone-beam computed tomography (CBCT). For the low-signal and noisy projections, a multiple sampling method is first utilized in projection domain to suppress environmental noise, which guarantees the accuracy of the data for reconstruction, simultaneously. Next, a fuzzy entropy based method with block matching 3D (BM3D) filtering algorithm is employed to improve the image quality to reduce artifacts and noise in image domain. Then, simulation studies on polychromatic spectrum were performed to evaluate the performance of the proposed new algorithm. Study results demonstrated significant improvement in the signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of the images reconstructed using the new algorithm. SNRs and CNRs of the new images were averagely 40% and 20% higher than those of the previous images reconstructed using the traditional algorithms, respectively. As a result, since the new image reconstruction algorithm effectively reduced the artifacts and noise, and produced images with better contour and grayscale distribution, it has the potential to improve image quality using the original CBCT data with the low and missing signals.


Assuntos
Algoritmos , Artefatos , Tomografia Computadorizada de Feixe Cônico/métodos , Imageamento Tridimensional/métodos , Lógica Fuzzy , Imagens de Fantasmas
17.
Zhongguo Zhong Yao Za Zhi ; 43(11): 2261-2268, 2018 Jun.
Artigo em Zh | MEDLINE | ID: mdl-29945377

RESUMO

In this study, complex enzymes combined with ultrasonic extraction technology(MC) were used, to select optimal extraction combinations by single factor and orthogonal test, with Hedysarum polysaccharides yield and content as the comprehensive indexes. The components, physicochemical properties and antioxidant activity of Hedysarum polysaccharides from complex enzyme combined with ultrasonic extraction(HPS-MC)and the Hedysarum polysaccharides from hot water extraction(HPS-R)were analyzed. The results showed that:complex enzymes had significant effect on the yield and content of Hedysarum polysaccharides, and the ultrasonic power could significantly improve the content of Hedysarum polysaccharides. The optimum technological parameters were as follows: complex enzyme ratio 1:1, ultrasonic power 105 W, ultrasonic time 60 min, and enzymatic hydrolysis pH 5, achieving (14.01±0.64)% and (92.45±1.47)% respectively for the yield and content of Polysaccharides. As compared with HPS-R, the molecular weight, absolute viscosity and protein content of HPS-MC were decreased, while the content of uronic acid was increased. In the antioxidant system, the concentration of polysaccharide was within the range of 1-7 g·L⁻¹; the antioxidant activity of HPS-MC was higher than that of HPS-R, and HPS-MC (80%) with the lowest molecular weight showed a significant dose effect relationship with the increase of the experimental concentration. In conclusion, MC is a simple, convenient, economical and environmentally friendly extraction technology, and the Hedysarum polysaccharides extracted by this method have obvious antioxidant activity.


Assuntos
Antioxidantes/farmacologia , Fabaceae/química , Polissacarídeos/farmacologia , Enzimas , Hidrólise , Peso Molecular , Extratos Vegetais , Ultrassonografia , Água
18.
Biochem Biophys Res Commun ; 491(3): 862-868, 2017 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-28390898

RESUMO

Ethylene regulates the plant's response to stress caused by iron (Fe) deficiency. However, specific roles of ERF proteins in response to Fe deficiency remain poorly understood. Here, we investigated the role of ERF72 in response to iron deficiency in Arabidopsis thaliana. In this study, the levels of the ethylene response factor AtERF72 increased in leaves and roots induced under the iron deficient conditions. erf72 mutant plants showed increased growth compared to wild type (WT) when grown in iron deficient medium for 5 d. erf72 mutants had increased root H+ velocity and the ferric reductase activity, and increase in the expression of the iron deficiency response genes iron-regulated transporter 1 (IRT1) and H+-ATPase (HA2) levels in iron deficient conditions. Compared to WT plants, erf72 mutants retained healthy chloroplast structure with significantly higher Fe and Mg content, and decreased chlorophyll degradation gene pheophorbide a oxygenase (PAO) and chlorophyllase (CLH1) expression when grown in iron deficient media. Yeast one-hybrid analysis showed that ERF72 could directly bind to the promoter regions of iron deficiency responses genes IRT1, HA2 and CLH1. Based on our results, we suggest that ethylene released from plants under iron deficiency stress can activate the expression of ERF72, which responds to iron deficiency in the negative regulation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Ferro/metabolismo , Doenças das Plantas , Folhas de Planta/fisiologia , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA
19.
Med Sci Monit ; 23: 2500-2507, 2017 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-28538709

RESUMO

BACKGROUND The abdominal straining pattern can act as a novel parameter for improving the prediction of bladder outlet obstruction (BOO). To preserve detrusor function in the early stage of urinary system impairment, such as BOO, we establish a novel method for cystometry and Intra-abdominal pressure (IAP) assessments in rodents without cystostomy. MATERIAL AND METHODS Twenty mice and rats were divided into three groups (control, sham-operated and BOO group) respectively. The cystometry and IAP assessments were measured by the pediatric venous indwelling sheath and coronary dilatation catheter connected to Laborie urodynamic system on postoperative day 7. Data was collected simultaneously through urethra and rectum in each group. In addition, bladder histology was assessed to confirm BOO. RESULTS The novel method can collect the urodynamic parameters successfully, including the BLPP, IAP, MBC, etc. IAP was elevated in BOO rats, but no significantly difference was found between the sham-operated rats and the control rats. The hypertrophy of detrusor muscle in bladder section was observed by Masson trichrome staining in BOO group compared with other groups. CONCLUSIONS Our novel method based on innovative research implement for cystometry and IAP assessments in rodents is a reliable and replicable approach for evaluating the lower urinary tract function. Especially it provides detailed information to evaluate lower urinary tract structures and function in the early stage of BOO.


Assuntos
Abdome/fisiopatologia , Pressão , Bexiga Urinária/fisiopatologia , Urologia/métodos , Animais , Feminino , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Coloração e Rotulagem , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Micção , Urodinâmica
20.
Nephrology (Carlton) ; 22(6): 436-440, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27149688

RESUMO

AIM: Prolonged QT interval is related to changes of electrolytes in haemodialysis (HD) and is associated with all-cause mortality in HD patients. It is unknown if prolonged QT interval is associated with all-cause mortality in peritoneal dialysis (PD) patients as the electrolytes were relatively stable in PD. We therefore investigated the association of prolonged QT interval and all-cause mortality in chronic PD patients. METHODS: The QT intervals were measured in 2003 and all patients were followed to December 2012. A prolonged QT interval was defined as a QT interval > 450 ms. The association of prolonged QT interval with all-cause and cardiac-specific mortality was analyzed using Cox regression and Kaplan-Meier analysis. RESULTS: Of 306 patients, 196 (64%) patients had prolonged QT interval. The incidence density rate was 9.7 per 100 persons-years for all-cause mortality and 5.6 for cardiac specific mortality in patients with prolonged QT interval. Prolonged QT interval was associated with all-cause mortality with a hazard ratio (HR) of 1.59 (95% confidence interval (CI): 1.06-2.39, P = 0.03] and cardiac mortality (HR: 1.66, 95% CI: 1.00-2.78, P = 0.05) with adjustments for age, gender, diabetes, and vintage of dialysis. Longer QT interval (>500 ms, 450-500 ms, and < 450 ms) was significantly associated with a worse overall survival (P = 0.03, log-rank test) and cardiac mortality free survival (P = 0.05, log-rank test). CONCLUSIONS: Prolonged QT interval was associated with all-cause and cardiac mortality in patients on peritoneal dialysis. The association is independent of patient's age and diabetes.


Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/mortalidade , Diálise Peritoneal , Adulto , Idoso , Causas de Morte , Estudos de Coortes , Eletrocardiografia , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/fisiopatologia , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
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