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1.
Zhongguo Zhong Yao Za Zhi ; 45(4): 755-763, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237475

RESUMO

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.

2.
Phytomedicine ; 67: 153156, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901568

RESUMO

BACKGROUND: Baihu-Guizhi decoction (BHGZD) has been extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic effect. However, the material basis and the underlying mechanisms of BHGZD against RA have not been fully elucidated. PURPOSE: To investigate the chemical profile and the pharmacological mechanisms of BHGZD against RA. METHODS: The chemical constituents containing in BHGZD were identified using UFLC-Q-TOF-MS/MS system, and the corresponding putative targets were predicted. Then, the differentially expressed genes (DEGs) between adjuvant-induced arthritis (AIA) and normal control groups were identified using microarray analysis. After constructing the interaction network of "RA-related gene-BHGZD putative target", BHGZD candidate targets against RA were screened by topological analysis and further experimentally validated based on AIA rat model. RESULTS: A total of 41 chemical constituents were identified in the water extract of BHGZD, which were predicted to hit 1312 putative targets. Additionally, 26 DEGs between the AIA and normal control groups were defined as "RA-related genes", which were functionally involved into the imbalance of "inflammation-immune" system during RA progression. On the basis of the topological importance in the network of "RA-related gene-BHGZD putative target", 177 BHGZD candidate targets against RA were identified. Among them, TLR4, c-Fos/AP-1, IL2 and TNF had direct interactions with each other and also function as crucial components of toll-like receptor and T cell receptor signaling pathways, which may play important roles in maintaining the balance of "inflammation-immune" system. Experimentally, we verified that BHGZD dose-dependently attenuated the severity, pathological changes, as well as mechanical, cold, and heat hypersensitivities during RA progression based on the AIA rat model. Further western blot analysis demonstrated that BHGZD significantly reduced the protein levels of TLR4, c-Fos/AP-1, IL2 and TNF, which were induced by RA modeling, in the inflamed joints of AIA rats (all p<0.05). CONCLUSION: This study combining the chemical and transcriptomic profilings, target prediction, network calculation and experimental validations identifies the chemical constituents containing in BHGZD and offers the convincing evidence that BHGZD may ameliorate RA partially by restoring the balance of "inflammation-immune" system and subsequently reversing the pathological events during RA progression through regulating the TLR4-c-Fos-IL2-TNF axis.

3.
Cell Rep ; 29(10): 3212-3222.e4, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31801084

RESUMO

Hepatocytes are the primary functional cells of the liver, performing its metabolic, detoxification, and endocrine functions. Functional hepatocytes are extremely valuable in drug discovery and evaluation, as well as in cell therapy for liver diseases. However, it has been a long-standing challenge to maintain the functions of hepatocytes in vitro. Even freshly isolated hepatocytes lose essential functions after short-term culture for reasons that are still not well understood. In the present study, we find that mechanical tension-induced yes-associated protein activation triggers hepatocyte dedifferentiation. Alleviation of mechanical tension by confining cell spreading is sufficient to inhibit hepatocyte dedifferentiation. Based on this finding, we identify a small molecular cocktail through reiterative chemical screening that can maintain hepatocyte functions over the long term and in vivo repopulation capacity by targeting actin polymerization and actomyosin contraction. Our work reveals the mechanisms underlying hepatocyte dedifferentiation and establishes feasible approaches to maintain hepatocyte functions.

4.
Oxid Med Cell Longev ; 2019: 9151067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583050

RESUMO

Background/Aims: Obesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males. Methods: An obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor κB (NF-κB) was assessed by immunofluorescence. Results: High-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-κB activity in Sertoli cells (SCs). Conclusion: Metformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.

5.
Onco Targets Ther ; 12: 8117-8123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632064

RESUMO

Purpose: The oncogenic roles of lncRNA LINC01116 have been reported in several types of cancer, while its involvement in gastric cancer is unknown. This study aimed to investigate the involvement of LINC01116 in gastric cancer. Methods: Gene expression was detected by qPCR. Correlations were analyzed by linear regression. Overexpression and siRNA silencing techniques were used to analyze gene functions. Cell invasion and migration were analyzed by Transwell assays. Results: LINC01116 and lncRNA CASC11 were both upregulated in cancer tissues compared to cancer-adjacent tissues. Expression levels of LINC01116 and CASC11 were increased with the increase in clinical stages. Expression levels of LINC01116 and CASC11 were positively correlated. Overexpression of LINC01116 mediated the upregulated CASC11 in gastric cancer cells, and CASC11 overexpression also led to overexpressed LINC01116. Overexpression of LINC01116 and CASC11 led to promoted invasion and migration of gastric cancer cells. Rescue experiments showed that CASC11 knockdown attenuated the effects of LINC01116 overexpression. Overexpression of LINC01116 failed to significantly affect cancer cell proliferation. Conclusion: LINC01116 promoted cancer cell invasion and migration in gastric cancer by positively interacting with CASC11.

6.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3399-3405, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602901

RESUMO

Tripterygium wilfordii is widely used in the treatment of rheumatism with curative effect. However,its toxicity and adverse reactions,especially the hepatotoxicity,rank the first in the herbs induced liver injury,is the key factors hindering its clinical application. This paper reviewed the literatures related to the hepatotoxicity of T. wilfordii in recent 20 years,and summarized the characteristic of hepatotoxicity induced by T. wilfordii,the factors causing liver injury,the mechanism of toxicity,and the measures to reduce toxicity. In animal experiments,the T. wilfordii induced-hepatotoxicity in physiological state was more serious than pathological state. The T. wilfordii induced-hepatotoxicity is related to various toxic components contained in it,but alkaloids are the most toxic one.Overdose and cumulative overdose are the lead causing of hepatotoxicity induced by T. wilfordii. The theory of oxidative stress is still an important mechanism of T. wilfordii induced-hepatotoxicity,and Nrf2,as a key regulatory enzyme of oxidative stress,has become an important target for drugs to against T. wilfordii induced-hepatotoxicity. Mitochondrial autophagy and liver hypersensitivity are new mechanisms of liver injury induced by T. wilfordii. The measures such as dosage control,drug compatibility and dosage form variations can help to reduce the hepatotoxicity induced by T. wilfordii. This paper clarified the current situation and shortcomings of safety research on T. wilfordii,so as to propose new research strategies and provide ideas for rational evaluation of safety and clinical safe drug use of T. wilfordii.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Tripterygium/toxicidade , Animais
7.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3441-3447, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602907

RESUMO

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 µg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Tripterygium/química , Inibidores da Angiogênese/farmacologia , Angiotensina I/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial/efeitos dos fármacos , Comprimidos , Fator A de Crescimento do Endotélio Vascular
8.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3486-3493, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602913

RESUMO

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/toxicidade , Genitália Feminina/efeitos dos fármacos , Glicosídeos/toxicidade , Tripterygium/química , Animais , Apoptose , Aromatase/metabolismo , Artrite Experimental/induzido quimicamente , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Glicosídeos/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Comprimidos
9.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3502-3511, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602915

RESUMO

The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/toxicidade , Glicosídeos/administração & dosagem , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , Relação Dose-Resposta a Droga , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Comprimidos
10.
Front Immunol ; 10: 1881, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507583

RESUMO

Growing evidence suggests that obesity is associated with the susceptibility and disease severity of multiple sclerosis. The chronic inflammation induced by obesity is believed to contribute to this process. However, the immune mechanisms connecting obesity to the prevalence and pathogenesis of MS are poorly defined. In this study, we show that high fat diet (HFD)-induced obese mice developed an exacerbated EAE as indicated by higher clinical scores and more severe pathological changes in spinal cord than the control mice fed with normal diet (ND), following immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. The exacerbation of EAE in HFD mice was associated with enhanced microglial activation and increased expansion of Th1 and Th17 cells. The HFD mice also showed aggravated disease in an adoptive T cell transfer EAE model. Mechanistically, HFD augmented the expression level of IL-6 and CCL-2 both in serum and brain, and blockade of IL-6 and CCL-2 signal ameliorated EAE with reduced T cells infiltration in CNS. Taken together, our results suggest that obesity promotes CNS inflammation in EAE through IL-6 and CCL-2 mediated the inflammatory cells infiltration.

11.
J Cell Mol Med ; 23(10): 6859-6871, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373170

RESUMO

OBJECTIVE: The high-fat diet (HFD)-induced obesity is responsible for the testosterone deficiency (TD). However, the mechanism remains unknown. Mitochondrial homeostasis is proved to be important for maintaining the function of steroidogenic acute regulatory protein (StAR), the first rate-limiting enzyme in testosterone synthesis. As the key regulator of mitochondrial membrane permeability, cyclophilin D (CypD) plays a crucial role in maintaining mitochondrial function. In this study, we sought to elucidate the role of CypD in the expression of StAR affected by HFD. METHODS: To analyse the influence of CypD on StAR in vivo and in vitro, mouse models of HFD, CypD overexpression and CypD knockout (Ppif-/- ) as well as Leydig cells treated with palmitic acid (PA) and CypD overexpression plasmids were examined with an array of metabolic, mitochondrial function and molecular assays. RESULTS: Compared with the normal diet mice, consistent with reduced testosterone in testes, the expressions of StAR in both mRNA and protein levels in HFD mice were down-regulated, while expressions of CypD were up-regulated. High-fat intake impaired mitochondrial function with the decrease in StAR in Leydig cells. Overexpression of CypD inhibited StAR expressions in vivo and in vitro. Compared with C57BL/6 mice with HFD, expressions of StAR were improved in Ppif-/- mice with HFD. CONCLUSIONS: Mitochondrial CypD involved in the inhibitory effect of HFD on StAR expression in testes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30813535

RESUMO

Dyeing wastewater is very hard to treat, and adsorption could be a good choice. Spent substrate of Pleurotus eryngii (SSPE) was first used to adsorb malachite green, safranine T and methylene blue from aqueous solutions, and the corresponding adsorption isotherm, thermodynamics and dynamics models were simulated. More than 93% of the dyes were removed with solutions with 100 mg/L of initial dye concentration, 1 g of SSPE and pH of 6.0 after adsorption for 4 h. Freundlich isotherm models fit better the adsorption data than Langmuir models. Adsorption of the dyes onto SSPE was a spontaneous exothermic process based on an adsorption thermodynamics model. SSPE could adsorb the dyes rapidly, and a second-order kinetics model fit better with the adsorption data than a pseudo first-order kinetics model. Accordingly, SSPE could be a good bio-adsorbent for the removal of malachite green, safranine T and methylene blue from the aqueous solution.


Assuntos
Corantes/isolamento & purificação , Pleurotus/metabolismo , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Adsorção , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Corantes/química , Concentração de Íons de Hidrogênio , Modelos Químicos , Termodinâmica , Poluentes Químicos da Água/química
13.
Biol Trace Elem Res ; 187(1): 59-64, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29730749

RESUMO

Both Shanghai and Switzerland are developed regions with long-standing salt iodization programs and periodic monitoring. However, the two regions have their own approach to the implementation of the iodized salt policy. In Shanghai, monitoring was carried out every few years, using probability-proportional-to-size sampling technique to select 30 sampling units. Each unit consisted of more than 12 pregnant women and one randomly selected primary school. Urine samples were then taken from the chosen pregnant women and randomly recruited students of that school for iodine test. Data of Switzerland used in this comparative study was extracted from published researches. In Shanghai, the median urinary iodine concentration (UIC) in 2014 was 20% lower than in 1999 (P < 0.05). The median UIC of pregnant women in 2014 was 9.5% lower than that in 2011 (P < 0.05). In terms of iodized salt concentration, opposite to the increasing in Switzerland, it has exhibited a downward trend in Shanghai (P < 0.05). For the years monitored, the iodized salt concentration in Shanghai was significantly (P < 0.05) higher than in Switzerland. Though the UIC of children exhibited a downward trend in Shanghai (P < 0.05), it was still significantly (P < 0.05) higher than in Switzerland over the same monitoring period. However, the UIC in pregnant women was a totally different story, which was significantly (P < 0.05) lower in Shanghai than in Switzerland. Iodized salt is very important for maintaining sufficient iodine level in the population. Appropriate concentration of iodine in fortified salt needs to be decided according to local conditions. Special attention should be paid to the iodine level of pregnant women in Shanghai, and more education about iodine is necessary for the public health.


Assuntos
Iodo/urina , Cloreto de Sódio na Dieta/urina , China , Feminino , Humanos , Iodo/deficiência , Gravidez , Suíça
14.
Bioresour Technol ; 266: 134-138, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29960243

RESUMO

Spent substrate of Ganodorma lucidum (SSGL), waste from cultivation of Ganoderma lucidum, was firstly used as a bio-adsorbent to adsorb three typical dyes malachite green, safranine T and methylene blue, and the adsorption thermodynamics and dynamics were also studied. SSGL was rich of hydroxyl group and carbonyl group, which had the potential to be an efficient bio-adsorbent for the three dyes removal from water and wastewater, and the treatment model should be eco-friendly. The experimental data fit well with the Langmuir and Freundlich isotherm, and the adsorption of dyes took place mainly on monolayer surface of SSGL. The experimental data fit also well with the adsorption thermodynamics, the adsorption were spontaneous and mainly a chemical adsorption. SSGL could adsorb the dyes rapidly and achieve an equilibrium in a short time, and the experimental data fit well with the second-order kinetics model.


Assuntos
Corantes/química , Purificação da Água , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Azul de Metileno , Corantes de Rosanilina , Termodinâmica , Poluentes Químicos da Água
15.
Biomed Pharmacother ; 103: 1592-1601, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29864947

RESUMO

Atomic force microscopy (AFM) is appropriately applied to the examination of hard surfaces and soft samples with extremely high resolution and ultrasensitive force, which cannot be obtained by other imaging techniques, including optical and electron microscopy. In the current study, AFM was employed to evaluate the anti-arthritic effect of licochalcone A (LCA), a flavonoid isolated from the root of Chinese medicinal herb Glycyrrhiza inflate, on rheumatoid arthritis synovial fibroblasts (RASFs) at the nanoscale for the first time. The morphology, ultrastructure and stiffness of RASFs was modified by LCA as determined by AFM, suggesting that LCA most likely exerts an anti-arthritic effect based on the key role of RASFs in the progression of RA. Further studies showed that the inhibitory effect of LCA on IκBα phosphorylation and degradation as well as on p65 nuclear translocation and phosphorylation contributed to altering the morphology, ultrastructure and stiffness of the RASF membrane. Interestingly, IKKß phosphorylation was not detectable in RASFs, indicating that LCA altered the morphology, ultrastructure and stiffness of the RASF membrane by inhibiting NF-κB activation independent of IKKß phosphorylation. Antigen-induced arthritis (AIA) was established in Sprague Dawley (SD) rats to validate the anti-arthritic effect of LCA, and LCA significantly decreased both the arthritis scores and paw swelling in the AIA rats, suggesting that LCA inhibits the progression and development of arthritis in vivo. Collectively, AFM provides evidence at the nanoscale to predict the anti-arthritic effect of drugs on RASFs, and LCA should be further investigated as a candidate agent for the treatment of arthritis.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Chalconas/uso terapêutico , Microscopia de Força Atômica , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Chalconas/química , Chalconas/farmacologia , Módulo de Elasticidade , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibroblastos/ultraestrutura , Masculino , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Ratos Sprague-Dawley , Membrana Sinovial/patologia
16.
Br J Nutr ; 119(11): 1245-1253, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29580306

RESUMO

Universal salt iodisation (USI) has been successfully implemented in China for more than 15 years. Recent evidence suggests that the definition of 'adequate iodine' (100-199 µg/l) be revised to 'sufficient iodine' (100-299 µg/l) based on the median urinary iodine concentration (MUI) in school-age children. The objective of this study was to determine the prevalence of thyroid dysfunction in populations after long-term salt iodisation and examine whether the definition of adequate iodine can be broadened to sufficient iodine based on the thyroid function in four population groups. A cross-sectional survey was conducted in six provinces in the northern, central and southern regions of China. Four population groups consisting of 657 children, 755 adults, 347 pregnant women and 348 lactating women were recruited. Three spot urinary samples were collected over a 10-d period and blood samples were collected on the 1st day. In the study, among the adults, pregnant women and lactating women, the prevalence rates of elevated thyroglobulin antibody and thyroid microsomal antibody levels were 12·4, 8·5 and 7·8 %, and 12·1, 9·1 and 9·1 %, respectively. Abnormally high thyroid dysfunction prevalence was not observed after more than 15 years of USI in China because the thyroid dysfunction rates were all <5 %. The recommended range should be cautiously broadened from adequate iodine to sufficient iodine according to the MUI of school-age children considering the high levels of hormones and antibodies in the other populations. Adults, particularly pregnant women positive for thyroid antibodies, should be closely monitored.


Assuntos
Autoanticorpos/sangue , Iodo/administração & dosagem , Lactação/fisiologia , Cloreto de Sódio na Dieta/administração & dosagem , Glândula Tireoide/efeitos dos fármacos , Adolescente , Adulto , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/prevenção & controle , Iodo/urina , Masculino , Pessoa de Meia-Idade , Gravidez , Tireoglobulina/imunologia , Glândula Tireoide/fisiologia , Adulto Jovem
17.
Biol Trace Elem Res ; 185(2): 275-281, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29541993

RESUMO

In Shanghai, a new iodized salt standard was implemented in 2012. To provide evidence to the government, we compared iodine status before (35 mg/kg) and after (30 mg/kg) adjustment in vulnerable populations living in Shanghai. The probability-proportional-to-size sampling technique was used to select at least 360 pregnant women for urine iodine test and at least 1200 students for thyroid measurement and the household salt test. Of these students, at least 360 performed urine iodine test. The median thyroid volume and the median household salt iodine concentration of children aged 8-10 years were 1.80 ml and 24.8 mg/kg in 2015, and 0.97 ml and 28.3 mg/kg in 2011. The median urine iodine concentration (UIC) of pregnant women was 126.52 and 139.77 µg/L in 2015 and 2011. All differences were statistically significant (P < 0.05). The median UIC of students was 171.40 and 181.63 µg/L in 2015 and 2011, the difference was not statistically significant. Multivariate linear regression analysis showed that thyroid volume in children was associated with sex, age, region, and household salt iodized concentration. The current iodized salt concentration meets the basic needs of the population's iodine requirements except for pregnant women. Periodic monitoring is necessary particularly in vulnerable groups.


Assuntos
Iodo/urina , Estado Nutricional , Gravidez/urina , Adulto , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Análise Multivariada , Sais/urina , Nódulo da Glândula Tireoide/diagnóstico
18.
Hepatology ; 68(1): 62-77, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29356058

RESUMO

Physiological opening of the mitochondrial permeability transition pore (mPTP) is indispensable for maintaining mitochondrial function and cell homeostasis, but the role of the mPTP and its initial factor, cyclophilin D (CypD), in hepatic steatosis is unclear. Here, we demonstrate that excess mPTP opening is mediated by an increase of CypD expression induced hepatic mitochondrial dysfunction. Notably, such mitochondrial perturbation occurred before detectable triglyceride accumulation in the liver of high-fat diet-fed mice. Moreover, either genetic knockout or pharmacological inhibition of CypD could ameliorate mitochondrial dysfunction, including excess mPTP opening and stress, and down-regulate the transcription of sterol regulatory element-binding protein-1c, a key factor of lipogenesis. In contrast, the hepatic steatosis in adenoviral overexpression of CypD-infected mice was aggravated relative to the control group. Blocking p38 mitogen-activated protein kinase or liver-specific Ire1α knockout could resist CypD-induced sterol regulatory element-binding protein-1c expression and steatosis. Importantly, CypD inhibitor applied prior to or after the onset of triglyceride deposition substantially prevented or ameliorated fatty liver. CONCLUSION: CypD stimulates mPTP excessive opening, subsequently causing endoplasmic reticulum stress through p38 mitogen-activated protein kinase activation, and results in enhanced sterol regulatory element-binding protein-1c transcription and hepatic steatosis. (Hepatology 2018;68:62-77).


Assuntos
Ciclofilinas/metabolismo , Fígado Gorduroso/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Triglicerídeos/metabolismo , Animais , Cálcio/metabolismo , Ciclofilinas/antagonistas & inibidores , Estresse do Retículo Endoplasmático , Endorribonucleases/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Serina-Treonina Quinases/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Free Radic Biol Med ; 115: 471-483, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29233793

RESUMO

Licochalcone A (LCA) is derived from glycyrrhizae radix with antimicrobial, antitumor and anti-inflammatory activities. However, the anti-arthritic function of LCA and underlying mechanism has not been yet explored. The current study investigated the anti-arthritic effect of LCA and elucidated the underlying mechanism. The results showed that LCA significantly suppressed arthritis via the activation of SQSTM1 (p62)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling in the collagen-induced arthritis (CIA) model of DBA mice. In coincided with the results, this anti-arthritic effect of LCA was remarkably diminished in the collagen antibody-induced arthritis (CAIA) model of Nrf2-/- mice. These findings indicate that p62/Nrf2 signaling is a crucial pathway for the induction and treatment of arthritis. To further validate the effect of LCA on the arthritis, rheumatoid arthritis synovial fibroblasts (RASFs) isolated from the synovium of RA patients were employed in the study. In coincided with in vivo results, LCA inhibited the cell proliferation and arrested the cell cycle, induced apoptosis, suppressed pro-inflammatory cytokine secretion and increased expression of antioxidant enzymes via the activation of Keap1-Nrf2 signaling by enhancing p62 phosphorylation and expression, Nrf2 accumulation and Nrf2 nucleus translocation. Findings in the current study provide evidence that p62-Keap1-Nrf2 axis is a pivotal signaling pathway in development of arthritis and therapeutic efficacy of drugs, and LCA activates of Keap1-Nrf2 signaling to suppress arthritis by phosphorylation of p62 at Ser349. Collectively, LCA is valuable to be further investigated as a lead compound for application in anti-arthritis, and interference with the interaction between Nrf2 and Keap1 by phosphorylation of p62 may be a promising strategy for the discovery of anti-arthritic agents.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Chalconas/uso terapêutico , Fibroblastos/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Glycyrrhiza/imunologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Fosforilação , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais
20.
Cell Biol Int ; 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29087604

RESUMO

Altered glucose metabolism has been found in a variety of malignant diseases and recognized as one of the hallmarks of cancer. However, the molecular mechanism behind it is far from well understood. In current study, we found silencer of death domains (SODD) regulates glucose uptake of colorectal cancer cells. When cultured under low level of glucose, SODD overexpressing RKO and SW1417 cells generated more colonies, compared with control cells, in clonogenic assay. SODD upregulation enhanced RKO and SW1417 cells viability. Furthermore, SODD induced more GLUT1 (Glucose transporter 1) expression and enhanced glucose uptake. AKT phosphorylation was upregulated in SODD overexpression cells. Moreover, inhibition of GLUT1 or AKT could reverse SODD induced glucose uptake enhancement. In conclusion, our findings indicate that SODD positively regulates glucose uptake and may be a potential therapeutic target of colorectal cancer.

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