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1.
Environ Geochem Health ; 46(2): 45, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227264

RESUMO

In order to study the influence of water-rock interaction on the mass time-varying characteristics of coal rocks, coal was selected as the research object and subjected to chemical immersion tests with different pH aqueous solutions for 12 days. By experiment, the time-varying patterns of mass change fraction in coal samples, pH value in solution, and ions concentration of calcium and magnesium were obtained. Based on the gray correlation theory, the correlation degree between the mass change fraction and four influencing factors was analyzed. The gray prediction models for the mass time-varying characteristics of coal rocks have been established. The research shows that: (1) the influence ways and degree of different pH aqueous solutions on the mass changes of coal rocks are different, (2) during the process of water-rock interaction, the change law of pH value, ions concentration of calcium and magnesium in solution are obvious, (3) the multiple regression models can be used to predict the mass change of coal rocks accurately under water-rock interaction.


Assuntos
Cálcio , Magnésio , Carvão Mineral , Água
2.
BMC Oral Health ; 23(1): 137, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894905

RESUMO

BACKGROUND: The aim of this study was to investigate the protective effect and mechanism of oridonin in an in vitro lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs) model of periodontitis. METHODS: Primary hPDLSCs were isolated and cultured, and then the expression of surface antigens CD146, STRO-1 and CD45 of hPDLSCs was detected by flow cytometry. The mRNA expression level of Runx2, OPN, Col-1, GRP78, CHOP, ATF4 and ATF6 in the cells was tested by qRT-PCR. MTT was taken to determine the cytotoxicity of oridonin at different concentrations (0-4 µM) on hPDLSCs. Besides, ALP staining, alizarin red staining and Oil Red O staining were utilized to assess the osteogenic differentiation (ALP concentration, mineralized calcium nodule formation) and adipogenic differentiation abilities of the cells. The proinflammatory factors level in the cells was measured by ELISA. The protein expression level of NF-κB/NLRP3 pathway-related proteins and endoplasmic reticulum (ER) stress-related markers in the cells were detected by Western blot. RESULTS: hPDLSCs with positive CD146 and STRO-1 expression and negative CD45 expression were successfully isolated in this study. 0.1-2 µM of oridonin had no significant cytotoxicity on the growth of hPDLSCs, while 2 µM of oridonin could not only greatly reduce the inhibitory effect of LPS on the proliferation and osteogenic differentiation of hPDLSCs cells, but also inhibit LPS-induced inflammation and ER stress in hPDLSCs cells. Moreover, further mechanism research showed that 2 µM of oridonin suppressed NF-κB/NLRP3 signaling pathway activity in LPS-induced hPDLSCs cells. CONCLUSIONS: Oridonin promotes proliferation and osteogenic differentiation of LPS-induced hPDLSCs in an inflammatory environment, possibly by inhibiting ER stress and NF-κB/NLRP3 pathway. Oridonin may have a potential role in the repair and regeneration of hPDLSCs.


Assuntos
Lipopolissacarídeos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Ligamento Periodontal , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteogênese , Antígeno CD146/metabolismo , Antígeno CD146/farmacologia , Transdução de Sinais , Diferenciação Celular , Células-Tronco/metabolismo , Proliferação de Células , Células Cultivadas
3.
Int J Mol Sci ; 23(7)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35408818

RESUMO

The homeostasis of NAD+ anabolism is indispensable for maintaining the NAD+ pool. In mammals, the mainly synthetic pathway of NAD+ is the salvage synthesis, a reaction catalyzed by nicotinamide mononucleotide adenylyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNATs) successively, converting nicotinamide (NAM) to nicotinamide mononucleotide (NMN) and NMN to NAD+, respectively. However, the relationship between NAD+ anabolism disturbance and diabetic nephropathy (DN) remains elusive. Here our study found that the disruption of NAD+ anabolism homeostasis caused an elevation in both oxidative stress and fibronectin expression, along with a decrease in Sirt1 and an increase in both NF-κB P65 expression and acetylation, culminating in extracellular matrix deposition and globular fibrosis in DN. More importantly, through constitutively overexpressing NMNAT1 or NAMPT in human mesangial cells, we revealed NAD+ levels altered inversely with NMN levels in the context of DN and, further, their changes affect Sirt1/NF-κB P65, thus playing a crucial role in the pathogenesis of DN. Accordingly, FK866, a NAMPT inhibitor, and quercetin, a Sirt1 agonist, have favorable effects on the maintenance of NAD+ homeostasis and renal function in db/db mice. Collectively, our findings suggest that NMN accumulation may provide a causal link between NAD+ anabolism disturbance and diabetic nephropathy (DN) as well as a promising therapeutic target for DN treatment.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , NAD , Nicotinamida-Nucleotídeo Adenililtransferase , Animais , Nefropatias Diabéticas/metabolismo , Humanos , Células Mesangiais/metabolismo , Camundongos , NAD/metabolismo , NF-kappa B/metabolismo , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Nicotinamida Fosforribosiltransferase/metabolismo , Nicotinamida-Nucleotídeo Adenililtransferase/genética , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo , Sirtuína 1/metabolismo
4.
Exp Mol Pathol ; 117: 104546, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32976820

RESUMO

RNA binding motif protein 3 (RBM3) has been shown to be upregulated in several types of human tumors. Using tissue microarrays and immunohistochemistry, we showed here that both nuclear and cytoplasmic RBM3 expression levels were higher in hepatocellular carcinoma (HCC) tissues than in adjacent non-tumorous tissues. High nuclear RBM3 was found to be correlated with larger tumor size (P = 0.030), high serum AFP levels (P = 0.011), and advanced Edmonson grading (P = 0.006). Cytoplasmic RBM3 was associated with advanced Edmonson grading (P = 0.003). Kaplan-Meier survival analysis revealed that, although not statistically significant, there was a trend toward shortened overall survival in the subset of HCC patients with high RBM3 expression (both nuclear and cytoplasmic). In addition, we found that RBM3 could promote YAP1 expression in HCC cells. Moreover, we found that YAP1 played an essential part in RBM3-induced proliferation of HCC cells. Furthermore, we demonstrated that Verteporfin, a YAP1 inhibitor, could repress RBM3-induced proliferation of HCC cells. Our findings provide a new experimental basis for further understanding of the possible role of RBM3-YAP1 in the regulation of HCC proliferation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Transdução de Sinais , Fatores de Transcrição/antagonistas & inibidores , Verteporfina/farmacologia , Proteínas de Sinalização YAP , alfa-Fetoproteínas/genética
5.
Sensors (Basel) ; 20(15)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751475

RESUMO

With the increase of mining depth and strength, the evolution of bolt axial force is increasingly becoming important for ensuring the reliability and safety of support. To improve the problem of the existing coal mine roadway pressure-monitoring method, whereby it is difficult to continuously monitor the axial force of the bolt over a long period of time, a full rod fiber bragg grating (FBG) force-measuring bolt and system were designed based on the principle of fiber grating sensing. It was found that a trapezoidal groove is a relatively better groove. The linearity between the center wavelength offset of the fiber grating and the axial force was more than 0.99, and the conversion formula between the axial force of the bolt rod and the wavelength change of the fiber grating were obtained. The real-time monitoring revealed that the axial force of the bolt obviously changed before and after compression. The axial force distribution curve can be divided into the stable zone, growth zone, and peak zone. The influence of the roadway abutment pressure was approximately 130 m ahead of the working face, and the peak area was within the 25-35 m range of the advance working face. The axial force of the bolt rod at the end of the anchorage linearly increased with the tail end of the bolt, the axial force of the free segment was the largest, and the overall stress was essentially the same. The application results demonstrate the feasibility and effectiveness of the FBG full-length force bolt.

6.
Cell Biochem Funct ; 37(5): 385-394, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31140646

RESUMO

To explore the molecular mechanism of insulin on proliferation and differentiation of MC3T3-E1 cell under high glucose conditions. We first investigated the effect of different concentrations of insulin on the osteoblast cell proliferation and cell differentiation at various time points by MTT analysis, cell cycle analysis, and expression detection of differentiation genes. Then, we used 200 ng/mL of insulin to treat the osteoblast cell at different time points for identifying the common differentially expressed mRNAs among various time points by RNA sequencing. Thirdly, we performed the gene ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis to explore the biological function of these common differentially expressed mRNAs. The results showed that insulin promoted the cell proliferation and differentiation of osteoblast cell. In RNA sequencing, a total of 31 common differentially expressed mRNAs were identified between different time points. Mt1, Tmem135, Avp, and Dlg2 were found to be associated with the new bone formation. In addition, three important signalling pathways, namely, lysosome, glutamatergic synapse, and chemokine signalling pathways, were found in the KEGG enrichment analysis. Our work demonstrated that insulin could promote the osteoblast cell proliferation and cell differentiation, which may play a key role in bone formation. SIGNIFICANCE OF THE STUDY: Our result showed that insulin could promote the proliferation and differentiation of osteoblast at both cellular and molecular levels, which may promote the new bone formation in the osteoblasts.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Glucose/metabolismo , Insulina/farmacologia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Células 3T3 , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Camundongos , Osteoblastos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
J Craniofac Surg ; 30(8): e723-e727, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31261342

RESUMO

In the repair of unilateral cleft lip, the Cupid's bow, and vermilion on the affected side are sometimes lowered excessively. Methods involving skin and mucosa flaps have been used to correct this issue, but they pose some risk of scarring. The authors here describe a layered muscle flap technique that was based on the anatomical research of nasal-labial muscles, especially the levator labii superioris alaeque nasi muscle. This technique can be used to suspend the Cupid's bow and vermilion in secondary unilateral cleft lip repair. Forty-five patients with secondary unilateral cleft lip with excessively lowered Cupid's bows and vermilion on the affected side were included in this study, which lasted 3 years. These patients were treated using the layered muscle flap surgical technique. The heights of specific bilateral landmarks were measured on patient photos and used to define the symmetry of bilateral Cupid's bow and vermilion. The comparison between post-operative and pre-operative symmetries was used to evaluate the post-operative results, and most of them were satisfactory. The results were also mostly well retained in follow-up investigations. This layered muscle flap technique could be effective in selected cases.


Assuntos
Fenda Labial/cirurgia , Retalhos Cirúrgicos , Adolescente , Adulto , Procedimentos Cirúrgicos Dermatológicos , Músculos Faciais/cirurgia , Feminino , Humanos , Lábio/cirurgia , Masculino , Nariz/cirurgia , Período Pós-Operatório , Procedimentos de Cirurgia Plástica/métodos , Pele , Adulto Jovem
8.
Sensors (Basel) ; 19(7)2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974913

RESUMO

The authors wish to correct the affiliation of co-author Guangyao Si, due to name changes of which he was unaware during his leave of absence [...].

9.
Sensors (Basel) ; 18(6)2018 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-29865264

RESUMO

Fiber Bragg grating (FBG) measuring bolts, as a useful tool to evaluate the behaviors of steel bolts in underground engineering, can be manufactured by gluing the FBG sensors inside the grooves, which are usually symmetrical cuts along the steel bolt rod. The selection of the cut shape and the glue types could perceivably affect the final supporting strength of the bolts. Unfortunately, the impact of cut shape and glue type on bolting strength is not yet clear. In this study, based on direct tension tests, full tensile load⁻displacement curves of rock bolts with different groove shapes were obtained and analyzed. The effects of groove shape on the bolt strength were discussed, and the stress redistribution in the cross-section of a rock bolt with different grooves was simulated using ANSYS. The results indicated that the trapezoidal groove is best for manufacturing the FBG bolt due to its low reduction of supporting strength. Four types of glues commonly used for the FBG sensors were assessed by conducting tensile tests on the mechanical testing and simulation system and the static and dynamic optical interrogators system. Using linear regression analysis, the relationship between the reflected wavelength of FBG sensors and tensile load was obtained. Practical recommendations for glue selection in engineering practice are also provided.

10.
Biochim Biophys Acta ; 1863(11): 2690-2699, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27526674

RESUMO

Podocyte injury or loss plays a major role in the pathogenesis of proteinuric kidney disease including diabetic nephropathy (DN). High basal level of autophagy is critical for podocyte health. Recent studies have revealed that hepatocyte growth factor (HGF) can ameliorate podocyte injury and proteinuria. However, little is known about the impact of HGF on podocyte autophagy. In this study, we investigated whether and how HGF affects autophagy in podocytes treated with high glucose (HG) conditions. HGF significantly diminishes apoptosis, oxidative stress and autophagy impairment inflicted by HG in podocytes. These beneficial effects of HGF disappear once HGF receptor is blocked by SU11274, a specific inhibitor of c-Met. Moreover, HGF markedly suppresses HG-stimulated glycogen synthase kinase 3beta (GSK3ß) activity. Accordingly, exogenous constitutively-active GSK3ß overexpression using an adenoviral vector system (Ad-GSK3ß-S9A) abrogates the ability of HGF to ameliorate HG-mediated podocyte injury while neither adenoviral-mediated overexpression of wild-type GSK3ß (Ad-GSK3ß-WT) nor adenoviral transduction of inactive GSK3ß mutant (Ad-GSK3ß-K85A) can counteract the protective effects of HGF on HG-treated podocytes. Collectively, these results suggest that HGF prevents HG-induced podocyte injury via an autophagy-promoting mechanism, which involves GSK3ß inhibition.


Assuntos
Autofagia/efeitos dos fármacos , Glucose/toxicidade , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Fator de Crescimento de Hepatócito/farmacologia , Podócitos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Citoproteção , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Podócitos/enzimologia , Podócitos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transfecção
11.
Exp Mol Pathol ; 100(3): 441-50, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27112839

RESUMO

Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Transforming growth factor beta 1 (TGFß1) is a well-distinguished mediator of progressive renal fibrosis in DN. However, the molecular mechanisms contributing to enhanced TGFß1 expression in the progression of DN are not fully understood. Herein, we reported that c-Jun and specificity protein 1 (SP1) were critical upstream regulators of TGFß1 expression in DN. The increase in c-Jun and SP1 expressions was positively correlated with TGFß1 in both high glucose-treated human renal mesangial cells (HRMCs) and diabetic kidneys. Furthermore, c-Jun dose-dependently promoted SP1-mediated TGFß1 transcription and vice versa. The synergistic effects of c-Jun and SP1 were attributed to their auto-regulation and cross-activation. Moreover, enhanced phosphorylation levels of c-Jun and SP1 were accompanied with increased TGFß1 expression in diabetic kidneys. Accordingly, dephosphorylation of c-Jun and SP1 by the specific c-Jun N-terminal kinase (JNK) inhibitor SP600125 prevented the increase in TGFß1 expression. These results suggested that c-Jun and SP1 synergistically activated profibrotic TGFß1 expression in the development of DN by auto-regulation, cross-activation and phospho-modification.


Assuntos
Nefropatias Diabéticas/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fator de Transcrição Sp1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Idoso , Animais , Antracenos/farmacologia , Western Blotting , Linhagem Celular , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Progressão da Doença , Feminino , Glucose/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Pessoa de Meia-Idade , Mutação , Fosforilação , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-jun/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-jun/genética , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição Sp1/genética , Fator de Crescimento Transformador beta1/genética
12.
Sensors (Basel) ; 16(10)2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27775657

RESUMO

Monitoring of roof activity is a primary measure adopted in the prevention of roof collapse accidents and functions to optimize and support the design of roadways in underground coalmines. However, traditional monitoring measures, such as using mechanical extensometers or electronic gauges, either require arduous underground labor or cannot function properly in the harsh underground environment. Therefore, in this paper, in order to break through this technological barrier, a novel monitoring system for roof safety control in underground coal mining, using fiber Bragg grating (FBG) material as a perceived element and transmission medium, has been developed. Compared with traditional monitoring equipment, the developed, novel monitoring system has the advantages of providing accurate, reliable, and continuous online monitoring of roof activities in underground coal mining. This is expected to further enable the prevention of catastrophic roof collapse accidents. The system has been successfully implemented at a deep hazardous roadway in Zhuji Coal Mine, China. Monitoring results from the study site have demonstrated the advantages of FBG-based sensors over traditional monitoring approaches. The dynamic impacts of progressive face advance on roof displacement and stress have been accurately captured by the novel roadway roof activity and safety monitoring system, which provided essential references for roadway support and design of the mine.

13.
Biochim Biophys Acta ; 1839(11): 1110-20, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25046864

RESUMO

Diabetic nephropathy (DN) is one of the major complications in diabetes patients. Reactive oxygen species (ROS) play key roles in DN progression. As a primary transcription factor, Nrf2 controls the antioxidant response to maintain cellular redox homeostasis. Herein we systemically examined the role of Nrf2 in DN progression and its regulatory mechanism in a mouse model bearing type II diabetes and in cultured human renal mesangial cells (HRMCs). We found that Nrf2 could ameliorate DN progression by transcriptional repression of TGFß1 in vivo and in vitro. Moreover, Nrf2 bound to the specific region in TGFß1 promoter by interactions with transcription factors c-Jun and SP1. Significant abolishment of Nrf2-mediated TGFß1 transcriptional repression could be accomplished by knockdown of either c-Jun or SP1, and site-directed mutagenesis of c-Jun and SP1 binding sites in the TGFß1 promoter specific region. Moreover, after interacting with c-Jun and SP1, Nrf2 inhibited c-Jun and SP1 activations, and thus reversed c-Jun- and SP1-promoted TGFß1 transcription. In all, Nrf2 could slow down DN progression by repression of TGFß1 in a c-Jun and SP1-dependent way. Our findings may provide novel clues for DN preventions and interventions in clinic.


Assuntos
Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Fator 2 Relacionado a NF-E2/fisiologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fator de Transcrição Sp1/metabolismo , Fator de Crescimento Transformador beta1/genética , Animais , Sequência de Bases , Células Cultivadas , Nefropatias Diabéticas/patologia , Progressão da Doença , Regulação para Baixo/genética , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Ligação Proteica
14.
Zhonghua Bing Li Xue Za Zhi ; 44(11): 778-82, 2015 Nov.
Artigo em Zh | MEDLINE | ID: mdl-26888387

RESUMO

OBJECTIVE: To study the effects of p38 MAPK signaling pathway and aldose reductase (AR) on the transforming growth factor (TGF)-ß1-induced expression of fibronectin (FN). METHODS: Human mesangial cells (HMCs) were cultured, and transfected with pCDNA3-AR. AR gene silencing was induced by small interfering RNA (siRNA). AR expression in HMCs was examined by immunofluorescence analysis. RT-PCR and real-time PCR were performed to detect the mRNA expression of AR in the HMCs and Western blotting was used to detect the protein expression of AR, FN and p38. AR inhibitors (ARIs), Sorbinil and Zopolrestat were added and co-incubated, followed by addition of TGF-ß1. Western blotting was used to document protein expression of FN and p38 mitogen-activated protein kinases (p38 MAPKs) in the HMCs. RESULTS: Immunofluorescence analysis showed a stronger expression of AR in HMCs transfected with AR than that of normal HMCs and HMCs transfected with blank vector. In comparison with normal HMCs and those transfected with blank vector, HMCs transfected with AR showed stronger protein expression of FN (P<0.05). After incubation of ARIs, protein expression of FN decreased in HMCs transfected with AR (P<0.05). After stimulation of TGF-ß1, FN protein expression increased in both normal HMCs and those transfected with AR (P<0.05). After preincubation with ARI, FN protein expression in HMCs transfected decreased significantly (P<0.05). After stimulation of TGF-ß1, naïve HMCs showed increased expression of phosphor-p38. In contrast, HMCs preincubated with ARIs showed reduced expression of phosphor-p38, and HMCs transfected with AR showed increased expression of phosphor-p38 (P<0.05). CONCLUSIONS: AR regulates the expression of FN through the stimulation of TGF-ß1, which may involve the activation of p38-MAPK signaling pathway. AR may play a role in the pathogenesis of glomerulosclerosis.


Assuntos
Aldeído Redutase/metabolismo , Fibronectinas/metabolismo , Sistema de Sinalização das MAP Quinases , Células Mesangiais/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Células Cultivadas , Humanos , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Biochim Biophys Acta ; 1832(5): 674-84, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23416120

RESUMO

3, 5-Diiodothyronine (T2), a natural metabolite of triiodothyronine (T3) from deiodination pathway, can mimic biologic effects of T3 without inducing thyrotoxic effects. Recent studies revealed T3 acted as a protective factor against diabetic nephropathy (DN). Nevertheless, little is known about the effect of T2 on DN. This study was designed to investigate whether and how T2 affects experimental models of DN in vivo and in vitro. Administration of T2 was found to prevent significant decrease in SIRT1 protein expression and activity as well as increases in blood glucose, urine albumin excretion, matrix expansion, transforming growth factor-ß1 expression, fibronectin and type IV collagen deposition in the diabetic kidney. Concordantly, similar effects of T2 were exhibited in the cultured rat mesangial cells (RMC) exposed to high glucose and that could be abolished by a known SIRT1 inhibitor, sirtinol. Moreover, enhanced NF-κB acetylation and JNK phosphorylation present in both diabetic rats and high glucose-treated RMC were distinctly dampened by T2. Collectively, these results suggested that T2 was a protective agent against renal damage in diabetic nephropathy, whose action involved regulation of SIRT1.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/prevenção & controle , Di-Iodotironinas/farmacologia , Rim/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Animais , Western Blotting , Linhagem Celular , Colágeno/genética , Colágeno/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Imuno-Histoquímica , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Rim/metabolismo , Rim/fisiopatologia , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
16.
Kidney Int ; 85(2): 333-343, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24025640

RESUMO

The generation of reactive oxygen species has a pivotal role in both acute and chronic glomerular injuries in patients with lupus nephritis. As the transcription factor Nrf2 is a major regulator of the antioxidant response and is a primary cellular defense mechanism, we sought to determine a role of Nrf2 in the progression of lupus nephritis. Pathological analyses of renal biopsies from patients with different types of lupus nephritis showed oxidative damage in the glomeruli, accompanied by an active Nrf2 antioxidant response. A murine lupus nephritis model using Nrf2(+/+) and Nrf2(-/-) mice was established using pristine injection. In this model, Nrf2(-/-) mice suffered from greater renal damage and had more severe pathological alterations in the kidney. In addition, Nrf2(+/+) mice showed ameliorative renal function when treated with sulforaphane, an Nrf2 inducer. Nrf2(-/-) mice had higher expression of transforming growth factor ß1 (TGFß1), fibronectin, and iNOS. In primary mouse mesangial cells, the nephritogenic monoclonal antibody R4A activated the nuclear factor-kappa B (NF-κB) pathway and increased the level of reactive oxygen species, iNOS, TGFß1, and fibronectin. Knockdown of Nrf2 expression aggravated all aforementioned responses induced by R4A. Thus, these results suggest that Nrf2 improves lupus nephritis by neutralizing reactive oxygen species and by negatively regulating the NF-κB and TGFß1 signaling pathways.


Assuntos
Mediadores da Inflamação/metabolismo , Glomérulos Renais/metabolismo , Nefrite Lúpica/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Adulto , Animais , Anticorpos Monoclonais/farmacologia , Estudos de Casos e Controles , Células Cultivadas , Dano ao DNA , Modelos Animais de Doenças , Feminino , Fibronectinas/metabolismo , Fulerenos , Humanos , Isotiocianatos/farmacologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais , Sulfóxidos , Transfecção , Fator de Crescimento Transformador beta1/metabolismo
17.
Exp Cell Res ; 319(19): 3051-7, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23973665

RESUMO

During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions.


Assuntos
Apoptose/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Macrófagos/metabolismo , Células Mesangiais/efeitos dos fármacos , Receptor fas/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Inflamação/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Células Mesangiais/citologia , Células Mesangiais/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Heliyon ; 10(1): e23990, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38268605

RESUMO

The dense conventional combined support hardly controls the overall subsidence of the roadway roof in extra-thick coal seam and affects the excavation efficiency, leading to the technical problem of mining proportion imbalance in the mine. In this study, the typical mining roadway with extra-thick coal seams in the Yanzhou mining area was taken as the engineering background, the roof stress distribution of the development face during the extra-thick coal seam mining was simulated, the deformation and failure characteristics of the roof at different layers under different thicknesses of the top coal were analyzed, and the progressive fragmentation and discontinuous deformation and failure mechanism of the top coal were revealed. Furthermore, the reinforced support technique of the thick anchorage and high preload in roof was put forward,and the reinforced technique was successful applied in the typical roadway in of Baodian Coal Mine, the experimental results showed that the fracture damage of the top coal in the mining roadway was effectively controlled, the deformation of the surrounding rock under the proposed support scheme was reduced by 40 %-50 % and the excavation speed was increased by 33 %.

19.
Sci Rep ; 13(1): 2381, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36765191

RESUMO

Since the western region of China, which is typical of extraordinary resource endowments, has gradually emerged as the major mining zone in China, the mining of thick coal seams and roadways with coal-rock composite roof have become more and more common in this region. However, it is extremely difficult to realize safe and effective maintenance and control of such roadways due to the differences in natural endowments of coal-rock masses. With the roadway with coal-rock composite roof of Hulusu Coal Mine in western China as the engineering background, experiment research on large-scale similarity model was conducted through comprehensive measures such as the pneumatic loading system, the surrounding rock stress monitoring system, the roadway deformation monitoring system, the bolt load monitoring system, and the displacement field monitoring system in this paper. According to the results of the experiment, the control effects of the three support systems on the roadway with coal-rock composite roof were significantly different. When the single support of short anchor bolts was applied, the comparatively low initial anchor-hold failed to constrain the initial micro deformation of the roof. Consequently, wide-range fractures of the roof were triggered at a loading pressure of 0.8 MPa. In the meanwhile, the deep surrounding rocks witnessed a downward inflection point in stress, accompanied by the possibility of the collapse of the thin-layer anchorage zone at any time. As for the support combining both short anchor bolts and long anchor cables, though a reinforced effect on the bolt anchorage zone could be achieved with the help of the cables, the active reinforcement capacity of the bolt was limited. The bolt anchorage zone was the first to be damaged at a loading pressure of 0.9 MPa, which would subsequently affect the effective bearing capacity of the deep surrounding rocks. In the application of the single support of high-strength long anchor bolts, the long bolts with high pre-tightening force were able to lock multiple groups of coal-rock strata to form a thick-layer anchorage bearing structure capable of withstanding a load as high as 1.0 MPa. The crash and collapse of the coal wall eventually caused the subsidence of the roof. Based on the intense dynamic load experiment and the feedbacks of engineering application outcomes in the field, it was concluded that the high-pretension thick-layer (HPTL) anchoring technology can effectively constrain the deformation of roadways with coal-rock composite roof with favorable application outcomes.

20.
Transl Oncol ; 36: 101740, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37487432

RESUMO

Genetically abnormal fibroblasts are notably more prevalent in colorectal cancer (CRC) than in adjacent normal tissue, emphasizing their significance in driving the heterogeneity of the tumor microenvironment. Functioning as a significant regulatory gene in the context of fibrosis, FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) has exhibited abnormal expression in colorectal cancer and interstitial localization in our experiments. However, current research on the role of FENDRR in cancer has focused solely on its impact on cancer cells. Its crucial role in the tumor stroma is yet to be explored. The goal of this study was to understand the relationship between atypical FENDRR expression, its distinct localization, and genetically abnormal fibroblasts in CRC. We aimed to establish the function of FENDRR within the stromal compartment of patients through bioinformatics. Our study confirmed that FENDRR suppresses cancer-associated fibroblasts by inhibiting their activation and collagen generation in CRC. Furthermore, our findings suggest that low FENDRR expression indicates a poor prognosis. Therefore, we propose that FENDRR is a promising therapeutic target for future studies in CRC.

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