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Inspired by the potent inhibition activity of the c-Met (mesenchymal-epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limited side effects. Among them, compound 31e exhibited potent antiproliferative activity (IC50 (50% inhibitory concentration) = 0.026 µΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that 31e induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells.
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Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1ß) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1ß and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.
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Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Citocinas/metabolismo , Eleutherococcus/química , Polissacarídeos/farmacologia , Animais , Conotoxinas , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Peptídeos Cíclicos , Distribuição Aleatória , Transdução de SinaisRESUMO
We isolated three laccase-producing fungus strains from Taxus rhizosphere. Myrotheium verrucaria strain DJTU-sh7 had the highest laccase activity of 216.2 U/ml, which was increased to above 300 U/ml after optimization. DJTU-sh7 had the best decolorizing effect for three classes of reactive dyes. The DJTU-sh7-containing fungal consortium displayed the robust decolorizing ability. Both color removal efficiency and chemical oxygen demand were increased in the consortium mediated biotransformation. Transcriptome changes of M. verrucaria elicited by azo dye and phenolic were quantified by the high throughput transcriptome sequencing, and the activities of the selected oxidases and reductases were determined. The possible involvement of oxidases and reductases, especially laccase, aryl alcohol oxidase, and ferric reductase in the biotransformation of dye and phenolic compounds was revealed at both transcriptomic and phenotypic levels. Revealing the transcriptomic mechanisms of fungi in dealing with organic pollutants facilitates the fine-tuned manipulation of strains in developing novel bioremediation and biodegradation strategies.We isolated three laccase-producing fungus strains from Taxus rhizosphere. Myrotheium verrucaria strain DJTU-sh7 had the highest laccase activity of 216.2 U/ml, which was increased to above 300 U/ml after optimization. DJTU-sh7 had the best decolorizing effect for three classes of reactive dyes. The DJTU-sh7-containing fungal consortium displayed the robust decolorizing ability. Both color removal efficiency and chemical oxygen demand were increased in the consortium mediated biotransformation. Transcriptome changes of M. verrucaria elicited by azo dye and phenolic were quantified by the high throughput transcriptome sequencing, and the activities of the selected oxidases and reductases were determined. The possible involvement of oxidases and reductases, especially laccase, aryl alcohol oxidase, and ferric reductase in the biotransformation of dye and phenolic compounds was revealed at both transcriptomic and phenotypic levels. Revealing the transcriptomic mechanisms of fungi in dealing with organic pollutants facilitates the fine-tuned manipulation of strains in developing novel bioremediation and biodegradation strategies.
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Ascomicetos/genética , Ascomicetos/metabolismo , Corantes/metabolismo , Rizosfera , Taxus/microbiologia , Transcriptoma , Compostos Azo , Biodegradação Ambiental , Biotransformação , Sequenciamento de Nucleotídeos em Larga Escala , Lacase/biossíntese , Fenóis/metabolismo , Fenótipo , Microbiologia do SoloRESUMO
BACKGROUND: Recently genome-wide association studies identified that NCAN rs2228603 polymorphism was associated with non-alcoholic fatty liver disease (NAFLD) mainly in subjects of European ancestry. While no research have been conducted to demonstrate the relationship between NCAN rs2228603 and NAFLD in Chinese Han adults. The aim of this study was to investigate whether NCAN rs2228603 is associated with NAFLD in Chinese population. METHODS: Gene NCAN rs2228603 was genotyped in 182 patients with NAFLD and 195 healthy controls. The expression of NCAN was tested according to polymerase chain reaction analysis (PCR) and serum lipids were performed by biology techniques. RESULTS: No significant difference was found in genotype and allele frequencies of NCAN rs2228603 between the NAFLD group and the controls (P > 0.05). Subjects with the NCAN rs2228603 CT genotype showed a higher level of alkaline phosphatase (AKP) (P = 0.017) and a higher high-density lipoprotein (HDL) (P < 0.05). CONCLUSIONS: Our study for the first time identified that the gene NCAN rs2228603 is not a risk factor for the incidence of NAFLD in Chinese population. Also we found the dual and opposite role of T variant in protecting liver with a higher level of HDL and conferring risk for liver damage with a higher level of AKP. TRIAL REGISTRATION: Chinese Clinical Trial Register.gov Identifier: ChiCTR-ROC-15006447 .
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Proteoglicanas de Sulfatos de Condroitina/genética , Predisposição Genética para Doença , Lectinas Tipo C/genética , Proteínas do Tecido Nervoso/genética , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Lipoproteínas HDL/sangue , Lipoproteínas HDL/genética , Masculino , Pessoa de Meia-Idade , Neurocam , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
BACKGROUND: Previous observational studies have shown that the prevalence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) is associated with socioeconomic status. However, due to the methodological limitations of traditional observational studies, it is challenging to definitively establish causality. AIM: To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization (MR). METHODS: We initially screened single nucleotide polymorphisms (SNPs) to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis. The inverse variance weighted (IVW) method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE. We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR (MVMR) analyses based on the IVW MVMR model. Furthermore, a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index, major depressive disorder (MDD), smoking, alcohol consumption, and sleep duration. RESULTS: The study identified three socioeconomic statuses that had a significant impact on GERD. These included household income [odds ratio (OR): 0.46; 95% confidence interval (95%CI): 0.31-0.70], education attainment (OR: 0.23; 95%CI: 0.18-0.29), and the Townsend Deprivation Index at recruitment (OR: 1.57; 95%CI: 1.04-2.37). These factors were found to independently and predominantly influence the genetic causal effect of GERD. Furthermore, the mediating effect of educational attainment on GERD was found to be mediated by MDD (proportion mediated: 10.83%). Similarly, the effect of educational attainment on BE was mediated by MDD (proportion mediated: 10.58%) and the number of cigarettes smoked per day (proportion mediated: 3.50%). Additionally, the mediating effect of household income on GERD was observed to be mediated by sleep duration (proportion mediated: 9.75%). CONCLUSION: This MR study shed light on the link between socioeconomic status and GERD or BE, providing insights for the prevention of esophageal cancer and precancerous lesions.
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The transformation of solid wastes from industrial production into effective adsorbents could significantly contribute to wastewater treatment. In this study, after acidizing and burning soft scale (SS) from coal gasification system, two magnetic adsorbents (mag-ASS and mag-BASS) were prepared via the combination of magnetite with ultrasonic, respectively. The treatment effects of mag-ASS and mag-BASS were then investigated for simulated wastewater containing macromolecular organic matter [i.e., methylene blue (MB)] and Ca2+. The results indicated that the pseudo second order kinetic, Elovich, Freundlich, Langmuir and Temkin model could well describe the adsorption behavior of MB and Ca2+ onto mag-ASS and mag-BASS. The maximum adsorption capacities of mag-ASS for MB and mag-BASS for Ca2+ were 600.53 mg/g and 102.54 mg/g, respectively. Surprisingly, the adsorption abilities of mag-ASS for MB and mag-BASS for Ca2+ show significantly higher than the others. The adsorption mechanisms of MB mainly included electrostatic interaction, π-π conjugate interaction and cation exchange, while those of Ca2+ were mainly electrostatic interaction and cation exchange. The diffusion of MB and Ca2+ onto the magnetic adsorbents might be controlled by the combined effects of intraparticle and liquid film diffusion. There was no significant reduction in adsorption capacity after 8 cycles of adsorption and desorption, indicating that SS-based magnetic adsorbents had good recyclability and stability. Moreover, the removal efficiency of mag-BASS for total hardness and total organic carbon in real coal gasification gray water (CGGW) was 82.60 and 64.10%, respectively. The treatment of CGGW and the resource of wastes would significantly promote the reasonable disposal of coal gasification scales.
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Cálcio , Carvão Mineral , Azul de Metileno , Azul de Metileno/química , Adsorção , Cálcio/química , Águas Residuárias/química , Cinética , Poluentes Químicos da Água/química , Purificação da Água/métodosRESUMO
BACKGROUND: Achalasia is associated with high risk of esophageal carcinoma. However, the optimal endoscopic surgery for patients with early esophageal carcinoma concomitant with achalasia remains unclear. CASE SUMMARY: A combination of concurrent endoscopic submucosal dissection (ESD) and modified peroral endoscopic myotomy (POEM) was performed on a 62-year-old male, who presented with multiple early esophageal carcinomas concomitant with achalasia. The patient exhibited an improvement in feeding obstruction, and presented no evidence of disease during the 3-year follow-up. CONCLUSION: The combination of ESD and POEM is a feasible treatment modality for patients with early esophageal carcinoma concomitant with achalasia.
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BACKGROUND: Many studies have focused on the femoral tunnel technique and fixation method, but few studies have involved the tibial tunnel technique and fixation method. The all-inside technique is one of the new techniques that has been described in recent years. All-inside anterior cruciate ligament (ACL) reconstruction is based on a tibial socket instead of a full tunnel. This method has many potential advantages. AIM: To compare clinical outcomes of knee ACL autograft reconstruction using all-inside quadrupled semitendinosus (AIST) and traditional hamstring tendon (TBT) techniques. METHODS: From January 2017 to October 2019, the clinical data of 80 patients with ACL reconstruction were retrospectively analyzed, including 67 males and 13 females. The patients had an average age of 24.3 ± 3.1 years (age range: 18-33 years). The AIST technique was used in 42 patients and the TBT technique was used in 38 patients. The time between operation and injury, operative duration, postoperative visual analogue scale (VAS) score and knee functional recovery were recorded and compared between the two groups. The International Knee Documentation Committee (IKDC) and Lysholm scoring system were used to comprehensively evaluate clinical efficacy. RESULTS: Eighty patients were followed for 24-36 mo, with an average follow-up duration of 27.5 ± 1.8 mo. There were no significant differences in the time between surgery and injury, operative duration, IKDC and Lysholm scores of the affected knee at the last follow-up evaluation between the two groups. There were significant differences in VAS scores 1 d, 3 d, 7 d, 2 wk and 1 mo after surgery (P < 0.05). There was no significant difference in VAS score at 3 mo, 6 mo and 1 year after operation. CONCLUSION: The efficacy of the AIST ACL reconstruction technique was comparable to the TBT technique, but the postoperative pain was less with the AIST technique. Thus, the AIST technique is an ideal treatment choice for ACL reconstruction.
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To prevent the scale formation in the equipments and pipelines after pre-treated coal gasification gray water (CGGW) entering the reuse system and reduce the influence of various pollutants in the effluent on subsequent biochemical treatment, this study presented a coupled use of pulse electrocoagulation (PEC) and chemical precipitation (CP) coupling method for the pretreatment of coal gasification gray water (CGGW). In addition, the operation parameters of PEC and the reaction conditions of PEC-CP were optimized based on iron plate as electrode and total hardness, turbidity and sludge yield as assessment indicators. Due to the formation of multi-hydroxyl iron by several minutes of pulse current, and the addition of pH regulator and coagulant aid, the efficient removal of various ions, hardness and turbidity was significantly reduced via various mechanism such as redox, precipitation, adsorption and coagulation reaction. The result indicated that under the optimal operation conditions, the total hardness, turbidity, and Fen+ of PEC-CP effluents were 275.0 mg/L, 3.0 NTU and 5.6 mg/L, respectively and sludge amount was 0.88 kg/m3. The removal rates of Si, B, Mn, Ba, COD, NPOC and NH4+-N by PEC-CP reached 80.0%, 75.4%, 97.0%, 99.8%, 35.0%, 33.6% and 23.8%, respectively. The present results suggested that the CGGW pretreatment effluents could be not only reused directly, but also greatly alleviate the scaling problem of water pipeline and coal gasification production facilities.
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Poluentes Ambientais , Poluentes Químicos da Água , Carvão Mineral , Águas Residuárias , Esgotos , Água , Precipitação Química , Eletrocoagulação , Ferro , Poluentes Químicos da Água/análise , Eliminação de Resíduos Líquidos/métodosRESUMO
Boron-doped graphitized carbon nanofibers (CNFs) were prepared by optimizing CNFs preparation, surface treatment, graphitization and boron-added graphitization. The interlayer spacing (d002) of the boron-doped graphitized CNFs reached 3.356 Å, similar to that of single-crystal graphite. Special platelet CNFs (PCNFs), for which d002 is less than 3.400 Å, were selected for further heat treatment. The first heat treatment of PCNFs at 2800 °C yielded a d002 between 3.357 and 3.365 Å. Successive nitric acid treatment and a second heat treatment with boric acid reduced d002 to 3.356 Å. The resulting boron-doped PCNFs exhibited a high discharge capacity of 338 mAh g⻹ between 0 and 0.5 V versus Li/Li⺠and 368 mAh g⻹ between 0 and 1.5 V versus Li/Liâº. The first-cycle Coulombic efficiency was also enhanced to 71-80%. Such capacity is comparable to that of natural graphite under the same charge/discharge conditions. The boron-doped PCNFs also exhibited improved rate performance with twice the capacity of boron-doped natural graphite at a discharge rate of 5 C.
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OBJECTIVE: To evaluate the repair of rotator cuff tear by allogenic cortical bone anchors with the technique of suture bridge. METHODS: A total of 18 patients with rotator cuff tear were recruited during the period of June 2006 to June 2009. There were 7 males and 11 females with an average age of 45.2 years old (range: 34 - 65). The locations included left shoulder (n = 11) and right shoulder (n = 7). Rotator cuff tear was repaired by allogenic cortical bone anchors with the technique of suture bridge under arthroscopy. The efficacy was evaluated by University of California Los Angeles (UCLA) standard score. RESULTS: The average follow-up period was 17.6 months (range: 12 - 36). The excellent rate of treatment was 100%. All rotator cuff tears were healed. Only 2 cases had minor pain and there was no limitation of joint activity. The bone anchor fully integrated with the subject area at Month 3 post-operation. CONCLUSION: The advantages of repairing rotator cuff tear by allograft cortical bone anchors with the technique of suture bridge includes minimal trauma, a large tendon bone area, firm fixation and a low cost. It is a better approach of repairing rotator cuff tear.
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Transplante Ósseo , Lesões do Manguito Rotador , Técnicas de Sutura , Traumatismos dos Tendões/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões do Ombro , Articulação do Ombro/cirurgia , Âncoras de Sutura , Suturas , Transplante Homólogo , Resultado do TratamentoRESUMO
This study comprehensively investigated the potential roles of soil mineralogy identified by the automated mineral liberation analysers (MLA) in the prediction of geochemical behavior of toxic metals in the smelter polluted soils. The results from modal mineralogy revealed that the non-reactive silicate phases such as quartz (42.05%) and biotite (40.43%) were the major mineralogical phases. The element deportment showed that fayalite, lead oxide, apatite, galena and wollastonite were identified as the dominant As, Cd, Pb and Zn bearing minerals. Furthermore, MLA analysis also confirmed that Pb was most concentrated in the smaller particles of lead oxide, which significantly enhanced Pb release in reaction with the chemical extractant during chemical kinetic tests. The results from pH-dependent leaching tests indicated that the leaching concentrations of As, Pb and Zn increased at low and high pH values, but were lowest at the neutral pH range. In addition, the results from the kinetic study demonstrated that the second order model provided the best description for the release patterns of the main metal contaminants in the bioavailability and bioaccessibility tests. The integrated geochemical analysis demonstrated that among these studied elements, As showed a typical geochemical pattern, which was predominantly controlled by 90.09% of fayalite. The above study results would have significant implications for soil remediation and risk management of smelter contaminated sites.
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Metais Pesados , Poluentes do Solo , Monitoramento Ambiental , Chumbo , Metais Pesados/análise , Solo , Poluentes do Solo/análise , Zinco/análiseRESUMO
BACKGROUND: Recurrent anterior shoulder instability is a common traumatic injury, the main clinical manifestation of which is recurrent anteroinferior dislocation of the humeral head. The current follow-up study showed that the effect of arthroscopic Bankart repair is unreliable. AIM: To evaluate the clinical efficacy of arthroscopy with subscapularis upper one-third tenodesis for treatment of anterior shoulder instability, and to develop a method to further improve anterior stability and reduce the recurrence rate. METHODS: Between January 2015 and December 2018, male patients with recurrent anterior shoulder instability were selected. One hundred and twenty patients had a glenoid defect < 20% and 80 patients had a glenoid defect > 20%. The average age was 25 years (range, 18-45 years). Patients with a glenoid defect < 20% underwent arthroscopic Bankart repair with a subscapularis upper one-third tenodesis. The patients with a glenoid defect > 20% underwent an arthroscopic iliac crest bone autograft with a subscapularis upper one-third tenodesis. All patients were assessed with Rowe and Constant scores. RESULTS: The average shoulder forward flexion angle was 163.6° ± 8.3° and 171.8° ± 3.6° preoperatively and at the last follow-up evaluation, respectively. The average external rotation angle when abduction was 90° was 68.4° ± 13.6° and 88.5° ± 6.2° preoperatively and at the last follow-up evaluation, respectively. The mean Rowe scores preoperatively and at the last follow-up evaluation were 32.6 ± 3.2 and 95.2 ± 2.2, respectively (P < 0.05). The mean Constant scores preoperatively and at the last follow-up evaluation were 75.4 ± 3.5 and 95.8 ± 3.3, respectively (P < 0.05). No postoperative dislocations were recorded by the end of the follow-up period. CONCLUSION: Arthroscopy with subscapularis upper one-third tenodesis was effective for treatment of recurrent anterior shoulder instability independent of the size of the glenoid bone defect, enhanced anterior stability of the shoulder, and did not affect postoperative range of motion of the affected limb.
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MiR-27 prevents atherosclerosis by inhibiting inflammatory responses induced by lipoprotein lipase. Overexpression of miR-27b attenuates angiotensin-induced atrial fibrosis. Nevertheless, studies have rarely investigated on the effect of miR-27 in cardiomyocyte injury. H9c2 cells were transfected with miR-27 mimic/inhibitor. Then the cell proliferation was tested by MTT assay and the cell apoptosis was detected by flow cytometry. The luciferase activity assay was utilized to analyze the relationship between miR-27 and TGFBR1. Quantificational real-time polymerase chain reaction and western blot were utilized to detect the cardiomyocyte differentiation marker and nuclear factor kappa B (NF-κB) pathway. Our outcomes demonstrated that miR-27 expression was downregulated cardiomyocyte injury subjected to hypoxia/reoxygenation (H/R). Additionally, overexpression of miR-27 could significantly alleviate cardiomyocyte injury by regulating cell activity and apoptosis. The luciferase activity assay confirmed that transforming growth factor ß receptor 1 (TGFBR1) is a direct hallmark of miR-27. Besides, overexpression of miR-27 promoted the expression of TGFBR1 in H/R model. After transfection with miR-27 mimic/inhibitor, the expression of NF-κB pathway-related proteins was decreased/increased. Taken together, our data manifested that miR-27 repressed cardiomyocyte injury induced by H/R via mediating TGFBR1 and inhibiting NF-κB signaling pathway. Furthermore, miR-27/ TGFBR1 might be utilized as hopeful biomarkers for myocardial ischemia diagnosis and treatment.
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Apoptose/fisiologia , NF-kappa B/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Apoptose/genética , Linhagem Celular , Citometria de Fluxo , Humanos , Hipóxia/metabolismo , MicroRNAs/metabolismo , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Clinical evidence gathered in Chinese communities suggested that acupoint sticking therapy could be an alternative treatment for asthma-related diseases. However, its underlying mechanism is still poorly understood. AIM/HYPOTHESIS: In this study, we aimed to investigate the mechanism of the anti-inflammatory effect of acupoint sticking application with 'Treatment of Winter Disease in Summer' (TWDS) prescription by using metabolomics. METHODS: Allergic asthma in guinea pig was sensitized and challenged by ovalbumin (OVA). Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The levels of Th2 cytokine and IgE level in serum were measured using enzyme-linked immunoassay (ELISA). The mRNA expression levels of IL-4, IL-5, IL-13 and orosomucoid-like 3 (ORMDL3) were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Proteins of NF-κB signaling pathway were measured using western blot. The serum metabolomics profiles were obtained by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS). RESULTS: The overall results confirmed that AST with TWDS prescription had a significant protective effect against OVA-induced allergic asthma in guinea pig. This treatment not only attenuated airway inflammation and collagen deposition in the airway, but also decreased the levels of IL-4, IL-5, IL-13 and IgE in serum. In addition, metabolomics results indicated that metabolisms of phospholipid, sphingolipid, purine, amino acid and level of epinephrine were restored back to the normal control level. Moreover, results of the gene expression of ORMDL3 in lung tissues indicated that AST using TWDS could alter the sphingolipid metabolism. Further western blotting analysis also showed that its anti-inflammatory mechanism was by decreasing the phosphorylation of p65 and IκB. CONCLUSION: The study demonstrated that metabolomics provides a better understanding of the actions of TWDS acupoint sticking therapy on OVA-induced allergic asthma.
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Terapia por Acupuntura/métodos , Antiasmáticos/farmacologia , Asma/terapia , Medicamentos de Ervas Chinesas/farmacologia , Hipersensibilidade/terapia , Animais , Asma/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Cobaias , Hipersensibilidade/metabolismo , Imunoglobulina E/sangue , Pulmão/metabolismo , Pulmão/patologia , Masculino , Proteínas de Membrana/genética , Metabolômica , NF-kappa B/metabolismo , Ovalbumina/efeitos adversos , Transdução de Sinais/efeitos dos fármacosRESUMO
INTRODUCTION: Melanin is synthesized by melanocytes, which are located in the basal layer of the skin. After synthesis, melanin is further deposited on the surface of the skin to form black spots or chloasma. Tyrosinase is a rate-limiting enzyme that plays an important role in melanogenesis. Currently, there are many drugs that inhibit tyrosinase expression to further reduce melanogenesis. Nevertheless, some of these could reverse the pharmacological effect of other drugs, when used simultaneously. MATERIALS AND METHODS: B16 mouse melanoma cells were treated with the tyrosinase inhibitors licochalcone A and ß-arbutin, alone or in combination with capsaicin, an alkaloid found in peppers. Cytotoxicity, melanin content, and tyrosinase activity and expression were determined. RESULTS: Licochalcone A/ß-arbutin inhibited tyrosinase expression and further hindered melanin synthesis when applied individually to B16 mouse melanoma cells. However, licochalcone A/ß-arbutin combined with 50 µmol/L capsaicin enhanced the expression of tyrosinase in these cells and further increased melanin content. CONCLUSION: Our data implied that capsaicin could reverse the inhibitory effect of licochalcone A/ß-arbutin on tyrosinase expression in B16 mouse melanoma cells. SUMMARY: B16 mouse melanoma cells were treated with the tyrosinase inhibitors licochalcone A and ß-arbutin, alone or in combination with capsaicin, an alkaloid found in peppers. Cytotoxicity, melanin content, and tyrosinase activity and expression were determined. Licochalcone A/ß-arbutin inhibited tyrosinase expression and further hindered melanin synthesis when applied individually to B16 mouse melanoma cells. However, licochalcone A/ß-arbutin combined with 50 µmol/L capsaicin enhanced the expression of tyrosinase in these cells and further increased melanin content. Our research implied that capsaicin could reverse the inhibitory effect of licochalcone A/ß-arbutin on tyrosinase expression in B16 mouse melanoma cells. Abbreviations used: B16: B16 mouse melanoma cells; L-DOPA: 3, 4-L-dihydroxyphenylalanine; TYR: Tyrosinase; USP: United States Pharmacopeia; FBS: Fetal bovine serum; EDTA: Ethylenediaminetetraacetic acid; DMSO: Dimethyl sulfoxide; RPMI: Roswell Park Memorial Institute; MTT3: 4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, NaOH: Sodium hydroxide; PBS: Phosphate-buffered saline; RIPA: Radio-immunoprecipitation assay; PMSF: Phenylmethanesulfonyl fluoride or phenylmethylsulfonyl fluoride; SDS: Sodium dodecyl sulfate, sodium salt; PVDF: Polyvinylidene fluoride; ECL: Enhanced chemiluminescence.
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BACKGROUND: Leptin receptor (LEPR) polymorphisms have been reported to be associated with lipid metabolism and insulin resistance in various populations. However, whether LEPR polymorphisms are associated with the risks of non-alcoholic fatty liver disease (NAFLD) and coronary atherosclerosis in the Chinese Han population remains unknown. OBJECTIVES: To investigate the association of LEPR polymorphisms at Q223R and K109R with the risks of NAFLD and coronary atherosclerosis in the Chinese Han population. PATIENTS AND METHODS: Genotypes of LEPR Q223R and K109R were determined by polymerase chain reaction followed by sequencing in patients with NAFLD (n = 554), coronary atherosclerosis (n = 421), and healthy controls (n = 550). Serum lipid profiles were determined using biochemical methods. Pearson's χ(2) test was used to check for Hardy-Weinberg equilibrium and to analyze the distributions of genotypes' alleles between groups. Baseline characteristics were analyzed using student's t-test, paired-samples t-test, or the χ(2) test where appropriate. RESULTS: The LEPR Q223R A allele significantly reduced the risks of both NAFLD and coronary atherosclerosis (OR = 0.683, 95% CI: 0.527 - 0.884, P = 0.004 and OR = 0.724, 95% CI: 0.548 - 0.955, P = 0.022, respectively). Compared to controls, no significant differences in the genotype and allele frequencies of K109R were found in the NAFLD and coronary atherosclerosis populations, respectively. However, there was a significantly increased risk of coronary atherosclerosis in NAFLD patients who carried the K109R A allele (OR = 2.283, 95% CI: 1.556 - 3.348, P < 0.001). CONCLUSIONS: LEPR Q223R polymorphisms may confer a significant risk of NAFLD and coronary atherosclerosis. The A allele in the K109R polymorphism might be considered an independent risk factor for coronary atherosclerosis in NAFLD patients.
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The precise design of Si-based materials at the nanometer scale is a quite complex issue but of utmost importance for their present and potential applications. This paper reports the first attempt to address the electrochemical reduction of SiO2 at the nanometer scale. SiO2 nanoparticles are first covered with a uniform carbon layer with controlled thickness at an accuracy of a few nanometers, by pressure-pulsed chemical vapor deposition. With appropriate thickness, the carbon layer plays significant roles as a current path and also as a physical barrier against Si-crystal growth, and the SiO2 nanoparticles are successfully converted into extremely small Si nanocrystals (<20 nm) inside the shell-like carbon layer whose morphology is derived from the original SiO2 nanoparticles. Thus, the proposed electroreduction method offers a new synthesis strategy of Si-C nanocomposites utilizing the morphology of SiO2 nanomaterials, which are well known for a wide variety of defined and regular nanostructures. Owing to the volume difference of SiO2 and the corresponding Si, nanopores are generated around the Si nanocrystals. It has been demonstrated that the nanopores around the Si nanocrystals are effective to improve cycle performance of Si as a negative electrode for lithium-ion batteries. The present method is in principle applicable to various SiO2 nanomaterials, and thus, offers production of a variety of Si-C composites whose carbon nanostructures can be defined by their parent SiO2 nanomaterials.