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1.
Cell ; 161(4): 762-73, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25957684

RESUMO

Transcription through immunoglobulin switch (S) regions is essential for class switch recombination (CSR), but no molecular function of the transcripts has been described. Likewise, recruitment of activation-induced cytidine deaminase (AID) to S regions is critical for CSR; however, the underlying mechanism has not been fully elucidated. Here, we demonstrate that intronic switch RNA acts in trans to target AID to S region DNA. AID binds directly to switch RNA through G-quadruplexes formed by the RNA molecules. Disruption of this interaction by mutation of a key residue in the putative RNA-binding domain of AID impairs recruitment of AID to S region DNA, thereby abolishing CSR. Additionally, inhibition of RNA lariat processing leads to loss of AID localization to S regions and compromises CSR; both defects can be rescued by exogenous expression of switch transcripts in a sequence-specific manner. These studies uncover an RNA-mediated mechanism of targeting AID to DNA.


Assuntos
Citidina Desaminase/metabolismo , Switching de Imunoglobulina , RNA Guia de Cinetoplastídeos/metabolismo , Animais , Quadruplex G , Íntrons , Proteínas Ligantes de Maltose/metabolismo , Camundongos , Processamento Pós-Transcricional do RNA , RNA Guia de Cinetoplastídeos/genética
2.
J Transl Med ; 22(1): 282, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491529

RESUMO

BACKGROUND: Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. METHODS: Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC. RESULTS: A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1ß, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group. CONCLUSIONS: OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed at https://smuonco.shinyapps.io/OralExplorer/  (Alternate URL: http://robinl-lab.com/OralExplorer ).


Assuntos
Biologia Computacional , Software , Humanos , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Transcriptoma/genética , Bases de Dados Factuais , Fatores de Troca de Nucleotídeo Guanina Rho
3.
Cancer Cell Int ; 24(1): 177, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773440

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors worldwide, with extremely aggressive and complicated biology. Krüppel-like factors (KLFs) encode a series of transcriptional regulatory proteins and play crucial roles in a variety of processes, including tumor cell differentiation and proliferation. However, the potential biological functions and possible pathways of KLFs in the progression of PDAC remain elusive. METHODS: We systematically evaluated the transcriptional variations and expression patterns of KLFs in pancreatic cancer from the UCSC Xena. Based on difference analysis, the non-negative matrix factorization (NMF) algorithm was utilized to identify the immune characteristics and clinical significance of two different subtypes. The multivariate Cox regression was used to construct the risk model and then explore the differences in tumor immune microenvironment (TIME) and drug sensitivity between high and low groups. Through single-cell RNA sequencing (scRNA-seq) analysis, we screened KLF6 and further investigated its biological functions in pancreatic cancer and pan-cancer. RESULTS: The KLFs exhibited differential expression and mutations in the transcriptomic profile of PDAC. According to the expression of KLFs, patients were classified into two distinct subtypes, each exhibiting significant differences in prognosis and TIME. Moreover, the KLF signature was developed using univariate Cox and Lasso regression, which proved to be a reliable and effective prognostic model. Furthermore, the KLF_Score was closely associated with immune infiltration, response to immunotherapy, and drug sensitivity and we screened small molecule compounds targeting prognostic genes separately. Through scRNA-seq analysis, KLF6 was selected to further demonstrate its role in the malignance of PC in vitro. Finally, pan-cancer analysis emphasized the biological significance of KLF6 in multiple types of tumors and its clinical utility in assessing cancer prognosis. CONCLUSION: This study elucidated the pivotal role of KLF family genes in the malignant development of PC through comprehensive analysis and revealed that KLF6 would be a novel diagnostic biomolecule marker and potential therapeutic target for PDAC.

4.
Pharmacol Res ; 202: 107141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490314

RESUMO

Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments,alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.


Assuntos
Glucose , Osteoartrite , Sirtuína 1 , Animais , Humanos , Cartilagem Articular/patologia , Glucose/metabolismo , Osteoartrite/metabolismo , Sirtuína 1/metabolismo , Sirtuínas/metabolismo
5.
Pestic Biochem Physiol ; 203: 106009, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39084775

RESUMO

Fall armyworm, Spodoptera frugiperda (J. E. Smith), is a widely recognized global agricultural pest that has significantly reduced crop yields all over the world. S. frugiperda has developed resistance to various insecticides. Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides, leading to increased resistance in insect populations. However, the function of the specific P450 gene for lambda-cyhalothrin resistance in S. frugiperda was unclear. Herein, the expression patterns of 40 P450 genes in the susceptible and lambda-cyhalothrin-resistant populations were analyzed. Among them, CYP321A7 was found to be overexpressed in the resistant population, specifically LRS (resistance ratio = 25.38-fold) derived from a lambda-cyhalothrin-susceptible (SS) population and FLRS (a population caught from a field, resistance ratio = 63.80-fold). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for LRS (2.76-fold) and the FLRS (4.88-fold) as compared to SS, while no significant differences were observed in the activities of glutathione S-transferases and esterases. Furthermore, the knockdown of CYP321A7 gene by RNA interference significantly increased the susceptibility to lambda-cyhalothrin. Remarkably, the knockdown of CYP321A7 reduced the enzymatic activity of P450 by 43.7%, 31.9%, and 22.5% in SS, LRS, and FLRS populations, respectively. Interestingly, fourth-instar larvae treated with lambda-cyhalothrin at the LC30 dosage had a greater mortality rate due to RNA interference-induced suppression of CYP321A7 (with increases of 61.1%, 50.0%, and 45.6% for SS, LRS, and FLRS populations, respectively). These findings suggest a link between lambda-cyhalothrin resistance and continual overexpression of CYP321A7 in S. frugiperda larvae, emphasizing the possible importance of CYP321A7 in lambda-cyhalothrin detoxification in S. frugiperda.


Assuntos
Sistema Enzimático do Citocromo P-450 , Resistência a Inseticidas , Inseticidas , Nitrilas , Piretrinas , Spodoptera , Animais , Piretrinas/farmacologia , Piretrinas/toxicidade , Spodoptera/efeitos dos fármacos , Spodoptera/genética , Nitrilas/toxicidade , Nitrilas/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Inseticidas/farmacologia , Inseticidas/toxicidade , Resistência a Inseticidas/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Interferência de RNA , Inativação Metabólica , Larva/efeitos dos fármacos , Larva/genética
6.
Environ Res ; 222: 115346, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36702189

RESUMO

Large amounts of microplastics (MPs) enter the soil along with the amendment of sludge to soil. However, it is still unclear about the response of MPs occurrence and the adsorption behaviors of cadmium (Cd)on MPs to typical agricultural environmental scenarios. In present work, three kinds of MPs (polyethylene, polypropylene, and polystyrene) were chosen to investigate that response in three agricultural environmental scenarios with sludge-amended soil, including dry-wet alteration (7 d, five cycles), microbial addition (Bacillus subtilis, 0.05 g/g soil), and Ultraviolet (UV) irradiation (340 nm, 4 × 15 W, 4 d). The results showed that there was the highest adsorption capacity of Cd on MPs (36.21, 45.15, 12.43 µg/g for PE, PP, PS, respectively) after UV irradiation exceeding those from MPs triggered by other two scenarios). UV irradiation caused an increase in the abundance of Streptomyces, an expansion in specific surface area, a significant change in surface morphologies, an improvement in crystallinity or the formation of new crystals, and an enhancement in C-O and CO content, and then resulted in the incremental adsorption capacity of Cd on MPs. The findings are important of significance for controlling the environmental risks from sludge MPs via carrying heavy metals in the soil-plant systems.


Assuntos
Microplásticos , Poluentes do Solo , Plásticos , Cádmio , Solo , Esgotos , Poluentes do Solo/análise
7.
Sleep Breath ; 27(6): 2155-2163, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36940015

RESUMO

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease and may lead to a loss of kidney function. However, it remains unclear whether or not continuous positive airway pressure (CPAP) treatment improves the estimated glomerular filtration rate (eGFR) in patients with OSA. This meta-analysis was designed to investigate the effect of CPAP therapy on eGFR in patients with OSA. METHODS: We searched the electronic databases Web of Science, Cochrane Library, PubMed, and Embase through June 1, 2022. Information about patients, CPAP duration, gender distribution, pre- and post-CPAP treatment eGFR, and age of patients were collected for further analysis. We applied the standardized mean difference (SMD) with a 95%confidence interval (CI) to analyze the pooled effects. Both Stata 12.0 software and Review Manager 5.2 software were employed for all statistical analyses. RESULTS: A sample of 13 studies with 519 patients was included in the meta-analysis. There was no significant change of eGFR levels before and after CPAP usage for patients with OSA (SMD = - 0.05, 95%CI: - 0.30 to 0.19, Z = 0.43, p = 0.67). However, subgroup analysis revealed that the level of eGFR was obviously decreased after CPAP therapy in patients with OSA and CPAP use duration > 6 months (SMD = - 0.30, 95% CI = - 0.49 to - 0.12, z = 3.20, p = 0.001), and elderly patients (> 60 years) (SMD = - 0.32, 95% CI = - 0.52 to - 0.11, z = 3.02, p = 0.002). CONCLUSIONS: Meta-analysis confirmed that OSA treatment with CPAP has no clinically significant effect on eGFR.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Humanos , Idoso , Taxa de Filtração Glomerular , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Modalidades de Fisioterapia
8.
Molecules ; 28(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37959704

RESUMO

The flavonoids from Perilla leaves were extracted using flash extraction assisted by ultrasonic extraction with ethanol. Subsequently, macroporous resin was employed for the isolation and purification of these flavonoids, followed by an investigation into their antioxidant activity. The process conditions for the extraction of flavonoids from Perilla leaves were designed and optimized using a one-way experiment combined with a response surface methodology. The optimal extraction conditions were determined as follows: the liquid-solid ratio was 20:1, ethanol volume fraction of 60%, ultrasound temperature of 60 °C, ultrasound time of 10 min and flash evaporation time of 60 s. The optimal extraction rate of flavonoids is 9.8 mg/g. In terms of separation and purification, a high-performance macroporous resin (HPD450 resin) with high purification efficiency was selected through static analysis and adsorption experiments. The optimal enrichment conditions were as follows: loading concentration of 0.06 mg/mL, optimal loading concentration of 20 mL, elution concentration of 70% and 76 mL, providing a reference for the further development and utilization of Perilla leaf flavonoids.


Assuntos
Flavonoides , Perilla , Antioxidantes/farmacologia , Folhas de Planta , Extratos Vegetais , Etanol
9.
J Transl Med ; 20(1): 218, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562743

RESUMO

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.


Assuntos
Células Acinares , Endorribonucleases , Animais , Humanos , Camundongos , Células Acinares/metabolismo , Ácido Araquidônico/metabolismo , Proteínas de Transporte/metabolismo , Endorribonucleases/metabolismo , Fibrose , Radioisótopos de Gálio , Camundongos Knockout , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteínas Serina-Treonina Quinases , Tripsina/metabolismo , Proteínas Supressoras de Tumor/metabolismo
10.
Clin Oral Investig ; 26(4): 3747-3764, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35029749

RESUMO

OBJECTIVES: Improper orthodontic force often causes root resorption or destructive bone resorption. There is evidence that T helper 17 (Th17) cells and regulatory T (Treg) cells may be actively involved in bone remodeling during tooth movement. In a combination of in vitro and in vivo studies, we investigated the effect of human periodontal ligament cells (hPDLCs) on Th17/Treg cells under different orthodontic forces and corticotomy. MATERIAL AND METHODS: hPDLCs were cultured in vitro and subjected to different mechanical forces. The expression of interleukin (IL)-6 and transforming growth factor (TGF)-ß in the supernatant and the mRNA levels of hypoxia inducible factor (HIF)-1α, Notch1, and TGF-ß in hPDLCs were investigated. Supernatants were collected and co-cultured with activated CD4+T cells, and the differentiation of Th17/Treg cells was analyzed by flow cytometry. We also established an animal model of tooth movement with or without corticotomy. The tooth movement distance, alveolar bone height, and root resorption were analyzed using micro-computed tomography. Expression of interleukin (IL)-17A, forkhead Box P3 (Foxp3), and IL-6 were analyzed using immunohistochemistry, while osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of IL-17A, IL-6, Foxp3, IL-10, HIF-1α, notch1, and C-X-C motif chemokine ligand 12 (CXCL12) in alveolar bone and gingiva were investigated. RESULTS: Heavy force repressed cell viability and increased the mortality rate of hPDLCs; it also improved the expression of IL-6, declined the expression of TGF-ß, and promoted the mRNA expression level of HIF-1α. The expression of TGF-ß and Notch1 mRNA decreased and then increased. The supernatant of hPDLCs under heavy force promotes the polarization of Th17 cells. The heavy force caused root resorption and decreased alveolar bone height and increased the positive area of IL-17A immunohistochemical staining and the expression of IL-17A, IL-6, HIF-1α, and Notch1 mRNA. Corticotomy accelerated tooth movement, increased the proportion of Foxp3-positive cells, and up-regulated the expression of Foxp3, IL-10, and CXCL12 mRNA. CONCLUSIONS: During orthodontic tooth movement, the heavy force causes root resorption and inflammatory bone destruction, which could be associated with increased expression of Th17 cells and IL-6. Corticotomy can accelerate tooth movement without causing root resorption and periodontal bone loss, which may be related to the increased expression of Treg cells. CLINICAL RELEVANCE: Altogether, this report provides a new perspective on the prevention of inflammatory injury via the regulation of Th17/Treg cells in orthodontics.


Assuntos
Perda do Osso Alveolar , Linfócitos T Reguladores , Perda do Osso Alveolar/prevenção & controle , Animais , Diferenciação Celular , Homeostase , Ligamento Periodontal , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Técnicas de Movimentação Dentária , Microtomografia por Raio-X
11.
J Environ Manage ; 322: 116113, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36055089

RESUMO

The complicated contamination of microplastics (MPs) and heavy metals in sludge has garnered substantial attention in recent years; however, research on the behavior of MPs loading of heavy metals in sludge after sludge treatment methods is limited. Four representative sludge treatment methods were selected herein: anaerobic digestion, thermal drying, thermal hydrolysis (TH), and aerobic composting. Before and after sludge treatment, the chemical bonding of MPs, cadmium (Cd) adsorption properties, and metabolic changes in the microbial community succession was analyzed, and the factors influencing differences in Cd sorption by sludge MPs were explored. The results revealed that Cd adsorption by MPs occurs as multilayer physical adsorption that can be well fitted by Freundlich isotherms. Compared with the other three treatments, TH led to the most significant effect on the chemical bonding properties of the MPs, with a more than two-fold increase in C-O single bonds and CO double bonds, as well as adsorption of the highest amount of Cd at 767 µg/g. In addition, sludge conductivity and water content also affected Cd sorption capacity, with correlation coefficients of 0.405 and -0.384. Pedobacter, Flavobacterium, Lysobacter, and Sphingobacterium in the sludge presented a high degree of coupling with adsorption capacity, it was inferred that the above dominant species of bacteria may affect the adsorption of Cd by microplastics through the production of extracellular enzyme forms.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Adsorção , Cádmio/química , Microplásticos , Plásticos/química , Esgotos , Água , Poluentes Químicos da Água/análise
12.
Environ Res ; 199: 111271, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34010623

RESUMO

BACKGROUND: Ozone has adverse effects on human health, it is necessary to obtain the refined ozone exposure concentration. At present, most of existing ozone exposure research is based on ground air quality monitoring station (MS) which gather urban area information only. It is diffcult to estimate the ozone in the areas where MSs are scarce. OBJECTIVE: By combining accurate but uneven data of outdoor ozone exposure concentrations based on MSs and unbiased coverage data based on RS in China, we can improve the accuracy of simulation of average monthly ozone exposure concentrations in monitor-free area. Since ozone concentrations are usually low at night, ozone exposure is assessed during the day (e.g., 10:00-18:00). METHODS: We proposed a space-time geostatistical kriging interpolation based on the composite space/time mean trend model (CSTM) to predict ozone exposure in mainland China, having obtained a refined ozone exposure concentration interpolation map from an MS. We verified the accuracy of the interpolation results and remote sensing (RS) data, while simultaneously determining the distance threshold (according to the data accuracy) to improve the accuracy of the hybrid map. RESULTS: We used a refined smoothing filter to reduce the influence of spatial and seasonal trends on ozone concentration. We found a cutoff separation distance of 175 km at which the two data showed an equal estimation accuracy, and the estimation result was fused with RS data through the distance threshold. Finally, The multi-source data with the best accuracy were fused to obtain the refined map. In China, ozone exposure concentration mainly gathers in the northern and eastern regions as well as part of the central mainland. CONCLUSIONS: RS data can be used to characterize ground ozone exposure concentrations when 24th-layer data and MS data for monitoring ozone exposure concentrations are combined to estimate temporal and spatial ozone exposure in China. Ozone exposure in China can be explored further to provide suggestions for human health and regional economic development.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Humanos , Ozônio/análise , Análise Espacial
13.
J Cell Biochem ; 121(2): 1431-1440, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31502329

RESUMO

It is well characterized that activated hepatic stellate cells (HSCs) exert critical functions in accelerating the progression of liver fibrosis. Previous studies have indicated that Dahuang Zhechong pill (DHZCP), a traditional Chinese herbal medicine, is capable of inactivating HSCs and thus attenuate the formation of liver fibrosis in rats. However, pharmacological mechanisms of DHZCP in alleviating liver fibrosis remain unclear. This study aims to investigate the antifibrotic role of DHZCP through inhibiting the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway. DHZCP was found to significantly suppresses extracellular matrix formation and immune cell infiltration, thus alleviating liver fibrosis symptoms in the in vivo model. Moreover, DHZCP reduced serum levels of transforming growth factor ß1 and tumor necrosis factor-α in rats with liver fibrosis. DHZCP treatment remarkably downregulated protein levels of PI3K and phosphorylated Akt, as well as fibrosis markers. In vitro experiments further demonstrated that DHZCP markedly suppressed HSCs proliferation by downregulating PI3K/Akt, which exerted a synergistic effect with the PI3K inhibitor LY294002. To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury.


Assuntos
Tetracloreto de Carbono/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley
14.
Endocr J ; 67(4): 397-408, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31875589

RESUMO

It has been shown that circular RNAs, a class of non-coding RNA molecules, play an important role in the regulation of glucose and lipid homeostasis. In the present study, we sought to investigate the function of circular RNA HIPK3 (circHIPK3) in diabetes-associated metabolic disorders, including hyperglycemia and insulin resistance. Results show that oleate stimulated circHIPK3 increase, and that circHIPK3 enhanced the stimulatory effect of oleate on adipose deposition, triglyceride (TG) content, and cellular glucose content in HepG2 cells. MiR-192-5p was the potential target of circHIPK3, since circHIPK3 significantly decreased miR-192-5p mRNA level, whereas anti-circHIPK3 significantly increased miR-192-5p mRNA level. Further study shows that transcription factor forkhead box O1 (FOXO1) was a downstream regulator of miR-192-5p, since miR-192-5p significantly decreased FOXO1 expression, whereas circHIPK3 significantly increased FOXO1 expression. Notably, the inhibitory effect of miR-192-5p was significantly reversed by circHIPK3. In vivo study shows that anti-miR-192-5p significantly increased blood glucose content, which was significantly inhibited by FOXO1 shRNA. MiR-192-5p significantly decreased adipose deposition and TG content in HepG2 cells, which was significantly reversed by the co-treatment with circHIPK3. Forskolin/dexamethasone (FSK/DEX) significantly increased cellular glucose, mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), and this stimulatory effect of FSK/DEX was significantly inhibited by miR-192-5p. In the presence of circHIPK3, however, the inhibitory effect of miR-192-5p was totally lost. In summary, the present study demonstrated that circHIPK3 contributes to hyperglycemia and insulin resistance by sponging miR-192-5p and up-regulating FOXO1.


Assuntos
Proteína Forkhead Box O1/genética , Hepatócitos/metabolismo , Hiperglicemia/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Circular/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Colforsina/farmacologia , Dexametasona/farmacologia , Proteína Forkhead Box O1/metabolismo , Glucocorticoides/farmacologia , Glucose/metabolismo , Glucose-6-Fosfatase/efeitos dos fármacos , Glucose-6-Fosfatase/genética , Células Hep G2 , Humanos , Hiperglicemia/metabolismo , Resistência à Insulina , Camundongos , Ácido Oleico/farmacologia , Fosfoenolpiruvato Carboxiquinase (ATP)/efeitos dos fármacos , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Triglicerídeos/metabolismo , Regulação para Cima
15.
Med Sci Monit ; 25: 87-97, 2019 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-30606998

RESUMO

BACKGROUND The uncoupling protein 1 (UCP1) gene has a role in mitochondrial energy expenditure in brown adipose tissue. This study aimed to investigate the effects of berberine, a benzylisoquinoline alkaloid used in traditional Chinese medicine, on energy expenditure, expression of the UCP1 gene, the cell stress protein inositol-requiring enzyme 1α (IRE1α), apoptosis genes, and macrophage phenotype (M1 and M2) in white and brown adipose tissue in an obese mouse model fed a high-fat diet. MATERIAL AND METHODS Four-week-old C57BL/6J male mice (n=20) were divided into a high-fat diet group, a normal diet group, a group treated with berberine at 100 mg/kg/d in 0.9% normal saline, and a non-treated group. Whole-body fat mass, blood glucose, insulin resistance, and oxygen expenditure during physical activity were measured. After 16 weeks, the mice were euthanized for examination of liver and adipose tissue. The expression of pro-inflammatory cytokines, apoptosis genes, thermogenic genes (including UCP1), and IRE1α, were investigated using immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR), in white and brown adipose tissue. Magnetic cell sorting harvested M1 and M2 macrophages in adipose tissue. Clodronate liposomes were used to inhibit macrophage recruitment. RESULTS Berberine treatment in mice fed a high-fat diet increased energy metabolism, glucose tolerance, and expression of UCP1, and reduced expression of pro-inflammatory cytokines, macrophage recruitment, and resulted in M2 macrophage polarization in white adipose tissue. Polarized M2 macrophages showed reduced expression of apoptotic genes and IRE1α. CONCLUSIONS Berberine improved metabolic function in a mouse model fed a high-fat diet.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Berberina/farmacologia , Tecido Adiposo/efeitos dos fármacos , Animais , China , Dieta Hiperlipídica , Endorribonucleases/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Inflamação/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteína Desacopladora 1/efeitos dos fármacos
16.
Opt Express ; 24(5): 5125-5135, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29092340

RESUMO

Aluminum-doped zinc oxide (AZO) is well known as transparent conducting material for electro-optical devices, but is rarely used as plasmonic material, particularly on the localized surface plasmon resonance (LSPR) behavior of AZO nanostructure and its plasmonic devices. In this study, we systematically investigate the plasmonic behaviors of AZO thin films and patterned AZO nanostructures with various structural dimensions under different annealing treatments. We find that AZO film can possess highly-tunable, metal-like, and low-loss plasmonic property and the LSPR characteristic of AZO nanostructure is observed in the near-infrared (NIR) region under proper annealing conditions. Finally, environmental index sensing is performed to demonstrate the capability of AZO nanostructure for optical sensing application. High index sensitivity of 873 nm per refractive index unit (RIU) variation is obtained in experiment.

17.
Opt Express ; 23(19): A1245-52, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26406753

RESUMO

The contribution of graphene oxide (GO) on photocatalytic effects of Cu(x)O on plasmonic Au is investigated. It is found that the H(2) evolution rate from pure water is enhanced 1.4 fold using the visible-active Cu(x)O/GO photocatalyst, as compared with Cu(x)O without GO. In addition, the intensity of photoluminescence of Cu(x)O/GO can be enhanced as much as 2.85 fold as compared with Cu(x)O without GO. The enhancement is due to the negative fixed charge in GO, which can passivate the surface of Cu(x)O and suppress recombination of minority electrons at the surface. The results from optical characterization in this study can help to prove the proposed mechanism of passivation.

18.
PLoS Genet ; 7(9): e1002297, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21980301

RESUMO

Immense diversity of prion strains is observed, but its underlying mechanism is less clear. Three [PSI] prion strains--named VH, VK, and VL--were previously isolated in the wild-type yeast genetic background. Here we report the generation and characterization of eight new [PSI] isolates, obtained by propagating the wild-type strains with Sup35 proteins containing single amino-acid alterations. The VH strain splits into two distinct strains when propagated in each of the three genetic backgrounds, harboring respectively single mutations of N21L, R28P, and Gi47 (i.e. insertion of a glycine residue at position 47) on the Sup35 N-terminal prion-forming segment. The six new strains exhibit complex inter-conversion patterns, and one of them continuously mutates into another. However, when they are introduced back into the wild-type background, all 6 strains revert to the VH strain. We obtain two more [PSI] isolates by propagating VK and VL with the Gi47 and N21L backgrounds, respectively. The two isolates do not transmit to other mutant backgrounds but revert to their parental strains in the wild-type background. Our data indicate that a large number of [PSI] strains can be built on three basic Sup35 amyloid structures. It is proposed that the three basic structures differ by chain folding topologies, and sub-strains with the same topology differ in distinct ways by local structural adjustments. This "large number of variations on a small number of basic themes" may also be operative in generating strain diversities in other prion elements. It thus suggests a possible general scheme to classify a multitude of prion strains.


Assuntos
Fatores de Terminação de Peptídeos/química , Príons/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Alelos , Amiloide/química , Amiloide/genética , Variação Genética , Haploidia , Heterozigoto , Homozigoto , Fatores de Terminação de Peptídeos/genética , Príons/genética , Proteínas Recombinantes/genética , Proteínas de Saccharomyces cerevisiae/genética , Esferoplastos/genética
19.
Behav Sci (Basel) ; 14(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38667059

RESUMO

There is a growing tendency for mental health disorders to emerge during adolescence. These disorders impair emotional, cognitive, and behavioral functioning, such as unsatisfying peer relationships, disruptive behavior, and decreased academic performance. They also contribute to vulnerability in later adulthood which negatively influences life-long well-being. Thus, research into etiology is imperative to provide implications for prevention and intervention within family and school practices. It is suggested that the onset of psychological disorders, such as depression and anxiety, is closely related to stress levels and patterns of stress reaction. Therefore, considerable research has investigated the link between hereditary factors, economic status, dispositional vulnerability, social relationships, and stress levels. The current study examines existing evidence and identifies multifaceted risk factors for adolescents' mental problems across three layers, including individual traits and personality, family status and practices, as well as peer relationships, and school climate. It is also suggested that factors from these three perspectives interact and are closely interconnected, directly or indirectly contributing to adolescent psychopathology. The implications for future development of prevention and intervention programs, as well as therapy, are discussed.

20.
Phys Rev E ; 109(6-1): 064908, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39020922

RESUMO

The drag force acting on an intruder colliding with granular media is typically influenced by the impact velocity and the penetrating depth. In this paper, the investigation was extended to the dry and immersed scenarios through coupled simulations at different penetrating velocities. The drag force regime was clarified to exhibit velocity dependence in the initial contact stage, followed by the inertial transit stage with a F∼z^{2} (force-depth) relationship. Subsequently, it transitioned into the depth-dependent regime in both dry and immersed cases. The underlying rheological mechanism was explored, revealing that, in both dry and immersed scenarios, the granular bulk underwent a state relaxation process, as indicated by the granular inertial number. Additionally, the presence of the ambient fluid restricted the flow dynamics of the perturbed granular material, exhibiting a similar rheology as observed in the dry case.

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