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1.
Immunity ; 56(9): 1991-2005.e9, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37659413

RESUMO

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.


Assuntos
Antivirais , Drosophila , Animais , Drosophila melanogaster , GMP Cíclico , Mamíferos
2.
Micromachines (Basel) ; 14(6)2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37374727

RESUMO

Complex optical elements have the advantages of improving image quality and optical performance and expanding the field of view. Therefore, it is widely used in X-ray scientific devices, adaptive optical elements, high-energy laser systems, and other fields and is a hot research direction in precision optics. Especially for precision machining, there is a greater need for high-precision testing technology. However, how to measure complex surfaces efficiently and accurately is still an important research topic in optical metrology technology. In order to verify the ability of optical metrology for complex optical surfaces with wavefront sensing based on image information of the focal plane, some experiment platforms in different types of optical surfaces were set up. In order to validate the feasibility and validity of wavefront-sensing technology based on image information of focal planes, a large number of repetitive experiments were carried out. The measurement results with wavefront sensing based on image information of the focal plane were compared with the measurement results with the ZYGO interferometer. The experimental results demonstrate that good agreement is obtained among the error distribution, PV value, and RMS value of the ZYGO interferometer, which shows the feasibility and validity of wavefront sensing based on image information of focal plane technology in optical metrology for the complex optical surface.

3.
bioRxiv ; 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37214844

RESUMO

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP. This CDN binds to and activates the protein STING to trigger immunity. We recently discovered in the model organism Drosophila melanogaster two cGAS-like receptors (cGLRs) that activate STING-dependent antiviral immunity and can produce 3'2'-cGAMP, in addition to 2'3'-cGAMP. Here we explore CDN-mediated immunity in 14 different Drosophila species covering 50 million years of evolution and report that 2'3'-cGAMP and 3'2'-cGAMP fail to control infection by Drosophila C virus in D. serrata, D. sechellia and D. mojavensis . Using an accurate and sensitive mass spectrometry method, we discover an unexpected diversity of CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster , including a novel CDN, 2'3'-c-di-GMP. We show that 2'3'-c-di-GMP is the most potent STING agonist identified so far in D. melanogaster and that this molecule also activates a strong antiviral transcriptional response in D. serrata . Our results shed light on the evolution of cGLRs in flies and provide a basis for the understanding of the function and regulation of this emerging family of PRRs in animal innate immunity.

4.
Kidney Int ; 103(3): 529-543, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36565808

RESUMO

Chronic kidney disease (CKD) is a common cause of morbidity in human immunodeficiency virus (HIV)-positive individuals. HIV infection leads to a wide spectrum of kidney cell damage, including tubular epithelial cell (TEC) injury. Among the HIV-1 proteins, the pathologic effects of viral protein R (Vpr) are well established and include DNA damage response, cell cycle arrest, and cell death. Several in vitro studies have unraveled the molecular pathways driving the cytopathic effects of Vpr in tubular epithelial cells. However, the in vivo effects of Vpr on tubular injury and CKD pathogenesis have not been thoroughly investigated. Here, we use a novel inducible tubular epithelial cell-specific Vpr transgenic mouse model to show that Vpr expression leads to progressive tubulointerstitial damage, interstitial inflammation and fibrosis, and tubular cyst development. Importantly, Vpr-expressing tubular epithelial cells displayed significant hypertrophy, aberrant cell division, and atrophy; all reminiscent of tubular injuries observed in human HIV-associated nephropathy (HIVAN). Single-cell RNA sequencing analysis revealed the Vpr-mediated transcriptomic responses in specific tubular subsets and highlighted the potential multifaceted role of p53 in the regulation of cell metabolism, proliferation, and death pathways in Vpr-expressing tubular epithelial cells. Thus, our study demonstrates that HIV Vpr expression in tubular cells is sufficient to induce HIVAN-like tubulointerstitial damage and fibrosis, independent of glomerulosclerosis and proteinuria. Additionally, as this new mouse model develops progressive CKD with diffuse fibrosis and kidney failure, it can serve as a useful tool to examine the mechanisms of kidney disease progression and fibrosis in vivo.


Assuntos
Nefropatia Associada a AIDS , Produtos do Gene vpr , Infecções por HIV , HIV-1 , Insuficiência Renal Crônica , Animais , Humanos , Camundongos , Nefropatia Associada a AIDS/genética , Modelos Animais de Doenças , Produtos do Gene vpr/genética , Produtos do Gene vpr/metabolismo , Produtos do Gene vpr/farmacologia , Infecções por HIV/complicações , HIV-1/genética , HIV-1/metabolismo , Proteínas do Vírus da Imunodeficiência Humana , Camundongos Transgênicos , Insuficiência Renal Crônica/complicações
5.
J Int Med Res ; 50(8): 3000605221118702, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35983672

RESUMO

OBJECTIVE: Renal impairment is a significant complication of systemic lupus erythematosus (SLE). Additionally, infection in patients with end-stage renal disease (ESRD) attributable to SLE is common, and it increases the risk of mortality. This study explored the infection profile and risk factors for mortality in patients with ESRD attributable to SLE. METHODS: In this retrospective, observational study of 125 hospitalized patients, demographic, clinical, laboratory, treatment, and prognosis data were retrieved and analyzed. RESULTS: The 125 cases included 98 pulmonary infections (78.4%), 14 urinary infections (11.2%), and 13 intestinal infections (10.4%). Twenty-six patients died within 1 month after enrollment. Univariate Cox regression and Kaplan-Meier analyses revealed several possible indicators potentially influencing patient survival. Furthermore, multivariate Cox regression analysis identified a higher SLE Disease Activity Index-2000 score, recent higher-dose glucocorticoid use, hypertension, and catheter indwelling as risk factors for higher mortality. CONCLUSIONS: Infections were common in patients with advanced SLE and ESRD, and several risk factors might increase the risk of mortality. Once infection is identified, empiric antibiotics should be initiated immediately, and subsequent antibiotics should be applied per the results of drug sensitivity testing to clear the infection.


Assuntos
Falência Renal Crônica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Antibacterianos , Humanos , Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Estudos Retrospectivos , Fatores de Risco
6.
Front Psychol ; 13: 859324, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846600

RESUMO

The manufacturing process is defined by the synchronous matching and mutual support of the event logic and the task context, so that the work task can be completed perfectly, by executing each step of the manufacturing process. However, during the manufacturing process of the traditional production environment, on-site personnel are often faced with the situation that on-site advice is required, due to a lack of experience or knowledge. Therefore, the function of the manufacturing process should be more closely connected with the workers and tasks. To improve the manufacturing efficiency and reduce the error rate, this research proposes a set of manufacturing work knowledge frameworks, to integrate the intelligent assisted learning system into the manufacturing process. Through Augmented Reality (AR) technology, object recognition technology is used to identify the components within the line of sight, and the assembly steps are presented visually. During the manufacturing process, the system can still feedback to the user in animation, so as to achieve the function equivalent to on-the-spot guidance and assistance when a particular problem is solved by a specialist. Research experiments show that the operation of this intelligent assisted learning interface can more quickly recognize how the manufacturing process works and can solve problems, which greatly resolves the issue of personnel with insufficient experience and knowledge.

7.
Materials (Basel) ; 14(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34640195

RESUMO

The plastic deformation processes and fracture behavior of a Ti-5Al-5Mo-5V-1Cr-1Fe alloy with bimodal and lamellar microstructures were studied by room-temperature tensile tests with in situ scanning electron microscopy (SEM) observations. The results indicate that a bimodal microstructure has a lower strength but higher ductility than a lamellar microstructure. For the bimodal microstructure, parallel, deep slip bands (SBs) are first noticed in the primary α (αp) phase lying at an angle of about 45° to the direction of the applied tension, while they are first observed in the coarse lath α (αL) phase or its interface at grain boundaries (GBs) for the lamellar microstructure. The ß matrix undergoes larger plastic deformation than the αL phase in the bimodal microstructure before fracture. Microcracks are prone to nucleate at the αp/ß interface and interconnect, finally causing the fracture of the bimodal microstructure. The plastic deformation is mainly restricted to within the coarse αL phase at GBs, which promotes the formation of microcracks and the intergranular fracture of the lamellar microstructure.

8.
Foodborne Pathog Dis ; 18(12): 859-866, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34415782

RESUMO

Antibiotic resistance genes (ARGs) are emerging contaminants that pose a health risk to humans worldwide. Little information on ARGs in bee honey is available. This study profiles ARGs in bee honey samples produced in China, the biggest producer in the world. Of 317 known ARGs encoding resistance to 8 classes of antibiotics, 212 were found in collected honey samples by a real-time quantitative polymerase chain reaction approach. Occurrence frequencies of genes providing resistance to FCA (fluoroquinolone, quinolone, florfenicol, chloramphenicol, and amphenicol) and aminoglycosides were 21.0% and 18.5%, respectively. Frequencies of genes encoding efflux pumps were 42.5% and those of destructase genes 36.6%, indicating that these two mechanisms were predominant for resistance. Nine plasmid-mediated quinolone resistance genes were detected. Of the nine transposase genes known to be involved in antibiotic resistance, eight were found in the samples examined, with tnpA-4, tnpA-5, and tnpA-6 being more abundant. The abundance of the transposase genes was associated with genes conferring resistance to tetracyclines (r = 0.648, p < 0.01), macrolide-lincosamide-streptogramin B (r = 0.642, p < 0.01), FCA (r = 0.517, p < 0.01), and aminoglycosides (r = 0.401, 0.01 < p < 0.05). This is the first study on the abundance and diversity of ARGs in Chinese bee honey products. These findings suggest that bee honey may be a significant source of ARGs that might pose threat to public health. Further research is required to collect more samples in diverse geographic regions in China to make a more comprehensive judgment of ARG in bee honey.


Assuntos
Antibacterianos , Mel , Animais , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos , Genes Bacterianos , Tetraciclinas
9.
Nanoscale Res Lett ; 16(1): 131, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34390420

RESUMO

X-ray computed tomography (CT) has been widely used in clinical practice, and contrast agents such as Iohexol are often used to enhance the contrast of CT imaging between normal and diseased tissue. However, such contrast agents can have some toxicity. Thus, new CT contrast agents are urgently needed. Owing to the high atomic number (Z = 83), low cost, good biological safety, and great X-ray attenuation property (5.74 cm2 kg-1 at 100 keV), bismuth has gained great interest from researchers in the field of nano-sized CT contrast agents. Here, we synthesized BiF3: Ln@PVP nanoparticles (NPs) with an average particle size of about 380 nm. After coating them with polyvinylpyrrolidone (PVP), the BiF3: Ln@PVP NPs possessed good stability and great biocompatibility. Meanwhile, compared with the clinical contrast agent Iohexol, BiF3: Ln@PVP NPs showed superior in vitro CT imaging contrast. Subsequently, after in situ injection with BiF3: Ln@PVP NPs, the CT value of the tumor site after the injection was significantly higher than that before the injection (the CT value of the pre-injection and post-injection was 48.9 HU and 194.58 HU, respectively). The morphology of the gastrointestinal (GI) tract can be clearly observed over time after oral administration of BiF3: Ln@PVP NPs. Finally, the BiF3: Ln@PVP NPs were completely discharged from the GI tract of mice within 48 h of oral administration with no obvious damage to the GI tract. In summary, our easily synthesized BiF3: Ln@PVP NPs can be used as a potential clinical contrast agent and may have broad application prospects in CT imaging.

10.
Nature ; 597(7874): 109-113, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34261127

RESUMO

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'-5']pA[3'-5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells1-5. Animal genomes typically encode multiple proteins with predicted homology to cGAS6-10, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.


Assuntos
Drosophila melanogaster/metabolismo , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/metabolismo , RNA de Cadeia Dupla/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Sistemas do Segundo Mensageiro , Sequência de Aminoácidos , Animais , Cristalografia por Raios X , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/imunologia , Drosophila melanogaster/virologia , Feminino , Humanos , Imunidade Inata , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Modelos Moleculares , Nucleotidiltransferases/química , Nucleotidiltransferases/imunologia , RNA de Cadeia Dupla/análise , RNA de Cadeia Dupla/imunologia , Receptores de Reconhecimento de Padrão/química , Receptores de Reconhecimento de Padrão/imunologia , Vírus/imunologia
11.
Nature ; 597(7874): 114-118, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34261128

RESUMO

In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes1 and eukaryotes2-5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections6-8. Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-κB-dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce the cyclic dinucleotide 3'2'-cGAMP, whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2'-cGAMP in response to an as-yet-unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors that sense different types of nucleic acids and trigger immunity through the production of cyclic dinucleotides beyond 2'3'-cGAMP.


Assuntos
Drosophila melanogaster/imunologia , Nucleotidiltransferases/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Vírus/imunologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Drosophila melanogaster/virologia , Feminino , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Ligantes , Masculino , Proteínas de Membrana/metabolismo , Modelos Moleculares , NF-kappa B/metabolismo , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/classificação , Nucleotidiltransferases/deficiência , Nucleotidiltransferases/metabolismo , RNA de Cadeia Dupla/análise , RNA de Cadeia Dupla/imunologia , RNA de Cadeia Dupla/metabolismo , Receptores de Reconhecimento de Padrão/classificação , Receptores de Reconhecimento de Padrão/deficiência , Receptores de Reconhecimento de Padrão/imunologia
12.
ACS Omega ; 6(16): 10723-10734, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-34056226

RESUMO

High-efficiency nanotheranostic agents with multimodal imaging guidance have attracted considerable interest in the field of cancer therapy. Herein, novel silver-decorated bismuth-based heterostructured polyvinyl pyrrolidone nanoparticles (NPs) with good biocompatibility (Bi-Ag@PVP NPs) were synthesized for accurate theranostic treatment, which can integrate computed tomography (CT)/photoacoustic (PA) imaging and photodynamic therapy/photothermal therapy (PDT/PTT) into one platform. The Bi-Ag@PVP NPs can enhance light absorption and achieve a better photothermal effect than bismuth NPs. Moreover, after irradiation under an 808 nm laser, the Bi-Ag@PVP NPs can efficiently induce the generation of reactive oxygen species (ROS), thereby synergizing PDT/PTT to exert an efficient tumor ablation effect both in vitro and in vivo. Furthermore, Bi-Ag@PVP NPs can also be employed to perform enhanced CT/PA imaging because of their high X-ray absorption attenuation and enhanced photothermal conversion. Thus, they can be utilized as a highly effective CT/PA imaging-guided nanotheranostic agent. In addition, an excellent antibacterial effect was achieved. After irradiation under an 808 nm laser, the Bi-Ag@PVP NPs can destroy the integrity of Escherichia coli, thereby inhibiting E. coli growth, which can minimize the risk of infection during cancer therapy. In conclusion, our study provides a novel nanotheranostic platform that can achieve CT/PA-guided PDT/PTT synergistic therapy and have potential antibacterial properties. Thus, this work provides an effective strategy for further broad clinical application prospects.

13.
Micron ; 144: 103031, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33618202

RESUMO

Lightweight Al2NbTi3V2Zrx (x = 1.0, 0.8, 0.6, 0.4, 0.2, 0) high entropy alloys are produced by mechanical milling and vacuum hot pressing. The microstructure, phase evolution and mechanical properties of the alloys are analyzed. The microstructure of the alloys with x = 1.0, 0.8, 0.6 consists of BCC solid solution matrix and two intermetallics (i.e., α and ß), and then ß phase disappears in Al2NbTi3V2Zr0.4 alloy. Further decreasing Zr content to below 0.2, α phase vanishes and γ and δ intermetallics emerge in Al2NbTi3V2Zr0.2 and Al2NbTi3V2 alloys. The Al2NbTi3V2Zrx alloys cannot obtain a single phase structure by decreasing Zr content with current fabrication process, which is likely because that the mixing entropy of the HEA system is not large enough to prohibit the formation of the secondary phases at hot pressing temperature of 1250 °C. All the bulks possess low density ranging from 4.93 to 5.21 g/cm3. Hardness of the Al2NbTi3V2Zrx alloys decreases from 781 HV to 697 HV and then increases to 814 HV with the decrease of Zr from x = 1 to 0. This varying tendency is closely related with the content of secondary intermetallic phases. The compressive test shows the Al2NbTi3V2Zr0.4 alloy has a yield strength of 1742 MPa, fracture strength of 2420 MPa, compressive strain of 38.2 %, which is probably related to its simplest microstructure. The comprehensive mechanical property of Al2NbTi3V2Zr0.4 alloy is superior to the majority of other HEAs and Ti64 alloy.

14.
PhytoKeys ; 171: 25-35, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33510573

RESUMO

Fenghwaia, a new monotypic genus, along with the new species Fenghwaia gardeniicarpa, is described from Guangdong Province, China. The combined features of inferior ovary, cylindrical drupaceous fruits and orbicular and dorsiventrally-compressed seeds with an elongate and pronounced basal appendage make the new genus significantly different from other genera of the family. In addition, its pollen morphology also showed great similarity to other species of this stenopalynous family. The molecular phylogenetic analysis, based on nuclear ribosomal internal transcribed spacer (ITS) and plastid trnL-F intron spacer (trnL-F) DNA sequence data from the new genus and the other 375 species representing 58 genera of Rhamnaceae, indicates that Fenghwaia is nested within the 'rhamnoid' group and sister to the tribe Rhamneae and then both sister to the tribe Maesopsideae. A taxonomic classification key to the 'rhamnoid' group is provided, based on morphological characters. A global conservation assessment is also performed and classifies Fenghwaia gardeniicarpa as Near Threatened (NT).

15.
Kidney Int ; 99(4): 914-925, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33359498

RESUMO

With the widespread use combination antiretroviral therapy, there has been a dramatic decrease in HIV-associated nephropathy. However, although the patients living with HIV have low or undetectable viral load, the prevalence of chronic kidney disease (CKD) in this population remains high. Additionally, improved survival is associated with aging-related comorbidities such as diabetes and cardiovascular disease. A faster progression of CKD is associated with concurrent HIV infection and diabetes than with HIV infection or diabetes alone. To explore the potential pathogenic mechanisms that synergistically drive CKD progression by diabetes and HIV infection, we generated a new mouse model with a relatively low expression of HIV-1 proviral genes specifically in podocytes (pod-HIV mice) to better mimic the setting of kidney injury in patients living with HIV. While no apparent kidney phenotypes were observed at baseline in pod-HIV mice, the induction of mild diabetic kidney disease with streptozotocin led to significant worsening of albuminuria, glomerular injury, podocyte loss, and kidney dysfunction as compared to the mice with diabetes alone. Mechanistically, diabetes and HIV-1 synergistically increased the glomerular expression of microRNA-34a (miR-34a), thereby reducing the expression of Sirtuin-1 (SIRT1) deacetylase. These changes were also associated with increased acetylation and activation of p53 and p65 NF-κB and with enhanced expression of senescence and inflammatory markers. The treatment of diabetic pod-HIV mice with the specific Sirtuin-1 agonist BF175 significantly attenuated albuminuria and glomerulopathy. Thus, our study highlights the reduction in Sirtuin-1 as a major basis of CKD progression in diabetic patients living with HIV and suggests Sirtuin-1 agonists as a potential therapy.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Infecções por HIV , Podócitos , Albuminúria/genética , Animais , Nefropatias Diabéticas/genética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Glomérulos Renais , Camundongos
16.
Ann Clin Lab Sci ; 49(5): 661-665, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31611211

RESUMO

OBJECTIVE: Gout is a type of inflammatory arthritis that can be complicated with bone erosion through several inflammatory factors. Mean platelet volume (MPV) is regarded as a marker in many inflammatory disorders, but despite this, the metric has not been used for gout. MATERIAL AND METHODS: This study evaluates the relationship between MPV and bone erosion in patients with gout. In total, 299 patients were evaluated retrospectively, and 120 patients were ultimately included based on inclusion criteria. RESULTS: Both the duration of this disease and mean platelet volume were related to bone erosion in gout and may be regarded as independent predictors of bone erosion. CONCLUSION: These results suggest that mean platelet volume can be a predictor of bone erosion in gout.


Assuntos
Artrite/sangue , Osso e Ossos/patologia , Gota/sangue , Volume Plaquetário Médio , Artrite/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Feminino , Gota/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão
17.
Mol Cell Endocrinol ; 495: 110507, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31315024

RESUMO

Clinical studies have demonstrated that cigarette smoking is strongly associated with insulin resistance and heart disease. Nicotine is considered the primary toxin constituent associated with smoking. However, the distinct molecular mechanism of nicotine-induced cardiac dysfunction remains unclear. Cardiomyocytes with nicotine-induced insulin resistance are characterized by decreased glucose uptake, as measured by 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG), a fluorescent derivative of glucose, and reactive oxygen species (ROS) generation. Immunoblotting was used to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), extracellular signal-related kinase (ERK) and phosphoinositide 3-kinase (PI3K, p85, Y607). We determined the impact of nicotine on insulin resistance and Nrf2, phospho-ERK and phospho-PI3K expression in the myocardial tissue of a mouse model. Nicotine increased ROS production and depressed insulin-induced glucose uptake in cardiomyocytes. Pretreatment with N-acetyl-L-cysteine (NAC), an antioxidant, reversed nicotine-inhibited glucose uptake induced by insulin. Nicotine exposure directly inhibited Nrf2 and increased ERK phosphorylation in cardiomyocytes, which were obstructed by NAC. Further exploration of signaling cascades revealed nicotine-induced ROS involved in inhibiting PI3K/Nrf2 and activating ERK in cardiomyocytes. Moreover, the mouse model treated with nicotine showed glucose intolerance and impaired insulin tolerance accompanied by inhibited PI3K/Nrf2 and increased ERK in myocardial tissues. Thus, nicotine induces insulin resistance via the downregulation of Nrf2 activity in cardiomyocytes, which is a potential mechanism of the pharmacological effects of nicotine. This study identified potential therapeutic targets against nicotine-related cardiovascular diseases.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Resistência à Insulina , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Nicotina/farmacologia , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Animais , Linhagem Celular , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Heme Oxigenase-1/metabolismo , Insulina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptor de Insulina/metabolismo
18.
Parasit Vectors ; 12(1): 302, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200771

RESUMO

BACKGROUND: Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma infection has not been established. RESULTS: This study investigated the link between tTG and IL-33/ST2 in the induction of liver fibrogenesis during Sj infection in mice. The extent of liver fibrosis coincided with an increase in tTG and IL-33/ST2 expression in the liver of infected mice between five to eight weeks, with a peak of correlation at six weeks after Sj infection. The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-κB pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj infection. CONCLUSIONS: These results indicate that during Sj infection tTG may control liver fibrosis at least partially through TLR4, NF-κB pathway activation and then IL-33/ST2. tTG, IL-33 or ST2 might be promising drug targets against liver fibrosis induced by Sj infection.


Assuntos
Proteínas de Ligação ao GTP/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Cirrose Hepática/enzimologia , Esquistossomose Japônica/imunologia , Transglutaminases/genética , Animais , Cistamina/administração & dosagem , Sistemas de Liberação de Medicamentos , Feminino , Proteínas de Ligação ao GTP/imunologia , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 2 Glutamina gama-Glutamiltransferase , Schistosoma japonicum , Esquistossomose Japônica/patologia , Transglutaminases/imunologia
19.
Mol Cell Probes ; 43: 80-83, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30414896

RESUMO

Budgerigar fledgling disease virus (BFDV) infection causes sudden death, abdominal distention, and feather abnormality in psittacine birds. In this study, we developed a TaqMan Real-time PCR assay to detect BFDV by targeting a conserved region in VP1 gene. The detection limit of the assay was 30 DNA gene copies, 1000 times more sensitive than conventional PCR. The coefficients of variation were less than 1.09% in either intra- or inter-assays, indicating high reproducibility. By using this method, the prevalence of BFDV in China was evaluated. 56 feces samples were collected from four psittacine birds breeding facilities in China. The results showed 28 out of 56 samples were positive for BFDV in Real-Time PCR assay, while only 19 samples were positive in PCR assay. Three facilities were positive for BFDV with positive rates from 60% to 87.5%. Further sequence analysis of VP1 genes from the positive samples indicated that VP1 genes fell into two different lineages in phylogenetic tree, suggesting that different genotypes BFDV are co-circulating in China.


Assuntos
Melopsittacus/virologia , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/veterinária , Polyomavirus/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/veterinária , Animais , Fezes/virologia , Infecções por Polyomavirus/virologia , Vigilância da População , Padrões de Referência , Reprodutibilidade dos Testes , Infecções Tumorais por Vírus/virologia
20.
World Neurosurg ; 123: e141-e146, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30468923

RESUMO

OBJECTIVE: To discuss the effects of the hematocrit (Hct) in patients with traumatic brain injury after decompressive craniectomy (DC). METHODS: Demographic data, inspection and treatment procedures, and 30-day prognosis were obtained for 158 patients with head injury who underwent unilateral DC in our hospital between January 2013 and June 2018. Uni- and multivariate logistic regression was applied to analyze independent risk factors for 30-day outcome. The quantitative analysis of postoperative Hct, ΔHct (postoperative Hct minus initial Hct), and their combination for the prognosis of patients with TBI was displayed graphically using receiver operating characteristic (ROC) curves. Multiple linear regression was used to explore factors influencing postoperative Hct and ΔHct. RESULTS: Short-term mortality was 29.7%. Uni- and multivariate logistic regression analysis showed that age (odds ratio [OR], 1.064; P = 0.024), Glasgow Coma Scale score (OR, 0.711; P = 0.027), Injury Severity Score (ISS) (OR, 1.156; P = 0.047), midline shift in millimeters (OR, 1.809; P <0.001), postoperative Hct (OR, 0.743; P = 0.001), and ΔHct (OR, 1.242; P =0.048) were independent risk factors for short-term death. In ROC curves, a combination of postoperative Hct and ΔHct showed the highest sensitivity (77.5%) and highest specificity (89.4%). When using this combination to predict prognosis, we could achieve an accuracy of 94.5%. ISS (ß = -0.172, P = 0.022), initial Hct (ß = 0.243, P = 0.001), principal hematoma location (ß = -2.628, P < 0.001), hours of operation (ß = -0.884, P = 0.048), and colloid quantity (ß = -0.002, P = 0.001) were independent contributing factors for ΔHct, which was similar to postoperative Hct. CONCLUSIONS: A combination of postoperative Hct and ΔHct could better predict short-term survival of patients with TBI. Developing an appropriate treatment strategy to increase postoperative Hct and reduce the ΔHct may be good for the short-term prognosis of patients with TBI after DC.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/cirurgia , Craniectomia Descompressiva , Hematócrito , Adulto , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Humanos , Masculino , Prognóstico , Curva ROC , Estudos Retrospectivos
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