Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 192
Filtrar
1.
Immunity ; 56(12): 2773-2789.e8, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37992711

RESUMO

Although the gut microbiota can influence central nervous system (CNS) autoimmune diseases, the contribution of the intestinal epithelium to CNS autoimmunity is less clear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2) promoted sex-specific disease progression in an animal model of multiple sclerosis. Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory response in the CNS and reduced disease progression. In contrast, overexpression or activation of IEC DRD2 by phenylethylamine administration exacerbated disease severity. This was accompanied by altered lysozyme expression and gut microbiota composition, including reduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived from Lactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our study indicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increases susceptibility to CNS autoimmune diseases in a female-biased manner, opening up future avenues for sex-specific interventions of CNS autoimmune diseases.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Esclerose Múltipla , Masculino , Feminino , Camundongos , Animais , Esclerose Múltipla/metabolismo , Modelos Animais de Doenças , Transdução de Sinais , Progressão da Doença , Receptores Dopaminérgicos
2.
Fish Shellfish Immunol ; 145: 109309, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142023

RESUMO

Heat Shock Proteins (HSPs) are a widely distributed family of proteins produced in response to heat and other stresses. To develop a deeper understanding of the mechanisms governing expression of HSPs in the bony fish Trachinotus ovatus, we carried out a whole genome analysis and identified 43 HSP genes. Based on their phylogenetic relationships with Danio rerio, Seriola dumerili, and Seriola lalandi, they were divided into four subfamilies: HSP20, HSP60, HSP70, and HSP90. We performed an analysis of the predicted physicochemical properties and subcellular localization of proteins encoded by these genes. The chromosomal localization results showed that the HSP genes are distributed across 20 chromosomes of T. ovatus.These genes were found to be expressed in different tissues, and they showed differential expression in the immune response against Streptococcus agalactiae. However, there was no significant differential expression in the different skin tissue locations of T. ovatus after infection by Cryptocaryon irritans Brown. This study provides basic information for further research on the evolution and structure and function of HSPs in teleosts.


Assuntos
Proteínas de Choque Térmico , Perciformes , Animais , Proteínas de Choque Térmico/genética , Filogenia , Peixes/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP90/genética
3.
Phys Chem Chem Phys ; 26(40): 25861-25869, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39359236

RESUMO

A new hard superconducting phase of RhB4 with the space group Cmca is predicted, and the phase transition and mechanical and superconducting properties of RhB4 under 300 GPa are studied using first principles. We predict a new high-pressure phase of RhB4 by substituting the most stable Cmca structure of OsB4, known for its excellent mechanical properties. The calculated enthalpy shows that above 112.6 GPa, Cmca is superior to Pmmn as was previously predicted by particle swarm optimization. The stability of the predicted phase is checked using formation enthalpy, elastic constant and phonon dispersion. Additionally, the convex hull of the Rh-B system confirms that the phase is expected to be synthesized experimentally. The Cmca phase is an incompressible hard material with a hardness of 23.75 GPa at 300 GPa attributed to strong intralayer covalent B-B bonds. Furthermore, the phase is a relatively pressure-insensitive superconductor, with a Tc of 8.6 K at 112.6 GPa and a pressure-dependent coefficient of -0.03 K GPa-1. The finding reveals a superconducting hard material that is well-suited for extreme high-pressure environments.

4.
Acta Pharmacol Sin ; 45(8): 1632-1643, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38627462

RESUMO

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.


Assuntos
HIV-1 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Humanos , HIV-1/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Latência Viral/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Retinoides/farmacologia , Retinoides/uso terapêutico
5.
J Fluoresc ; 33(3): 923-932, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36527543

RESUMO

Two chromenoquinoline-based fluorescent probes 1a-b have been synthesized and investigated. Photofading behaviors of compounds 1a-b showed that at least 89% absorption remained after 6 h irradiating, meanwhile, many of ions and amino acids had negligible impacts on their fluorescence intensity, which meant they had excellent photostability and selectivity. Probes 1a-b exhibited strong absorption and emission in organic solvents with large fluorescence quantum yields, even in water probe 1a still had a relatively large fluorescence quantum yield (20%). Combined with DFT calculation, the influence of alkylation on optical properties of 1b was elucidated. In addition, the fluorescence intensity of probe 1b with red emission enhanced by 5.4-fold and 5.3-fold after DNA and RNA added, and the fluorescence quantum yield increased from 3% to 17% and 14%, respectively, but the neutral molecule 1a had no response to nucleic acid. Furthermore, confocal microscopy imaging of probes 1a-b showed that 1a targeted lipid droplets while the methylated probe 1b to nucleus in living HeLa cells. The results indicated that the subcellular targeting zone could be changed by alkylation of nitrogen atom on chromenoquinoline-based conveniently, which provided a new idea for designing and synthesizing new subcellular labeled probes.


Assuntos
Corantes Fluorescentes , Ácidos Nucleicos , Humanos , Células HeLa , Corantes Fluorescentes/química , Diagnóstico por Imagem , Fluorescência
6.
Cell Mol Life Sci ; 79(12): 611, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36449080

RESUMO

Deficiency of decidual NK (dNK) cell number and function has been widely regarded as an important cause of spontaneous abortion. However, the metabolic mechanism underlying the crosstalk between dNK cells and embryonic trophoblasts during early pregnancy remains largely unknown. Here, we observed that enriched glutamine and activated glutaminolysis in dNK cells contribute to trophoblast invasion and embryo growth by insulin-like growth factor-1 (IGF-1) and growth differentiation factor-15 (GDF-15) secretion. Mechanistically, these processes are dependent on the downregulation of EGLN1-HIF-1α mediated by α-ketoglutarate (α-KG). Blocking glutaminolysis with the GLS inhibitor BPTES or the glutamate dehydrogenase inhibitor EGCG leads to early embryo implantation failure, spontaneous abortion and/or fetal growth restriction in pregnant mice with impaired trophoblast invasion. Additionally, α-KG supplementation significantly alleviated pregnancy loss mediated by defective glutaminolysis in vivo, suggesting that inactivated glutamine/α-ketoglutarate metabolism in dNK cells impaired trophoblast invasion and induced pregnancy loss.


Assuntos
Aborto Espontâneo , Animais , Feminino , Camundongos , Gravidez , Diferenciação Celular , Glutamina/farmacologia , Fator 15 de Diferenciação de Crescimento , Fator de Crescimento Insulin-Like I , Ácidos Cetoglutáricos/farmacologia
7.
J Sep Sci ; 46(8): e2200984, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36795010

RESUMO

Phorbol is a tetracyclic diterpenoid found in Euphorbia tirucalli, Croton tiglium, and Rehmannia glutinosa, and is nuclear of various phorbol esters. The rapid obtaining of phorbol with high purity highly contributes to its application, such as synthesizing phorbol esters with designable side chains and particular therapeutic efficacy. This study introduced a biphasic alcoholysis method for obtaining phorbol from croton oil by using polarity imparity organic solvents in both phases and established a high-speed countercurrent chromatography method for simultaneous separation and purification of phorbol. The optimized operation conditions of biphasic alcoholysis were a reaction time of 91 min, a temperature of 14°C, and a croton oil-methanol ratio of 1:30 (g:ml). The phorbol during the biphasic alcoholysis was 3.2-fold higher in content than that obtained in conventional monophasic alcoholysis. The optimized high-speed countercurrent chromatography method was using the ethyl acetate/n-butyl alcohol/water at 4.7:0.3:5 (v:v:v) with Na2 SO4 at 0.36 g/10 ml as the solvent system, using the mobile phase flow rate of 2 ml/min, the revolution of 800 r/min, under which the retention of the stationary phase was achieved at 72.83%. The crystallized phorbol following high-speed countercurrent chromatography was obtained as high purity of 94%.


Assuntos
Distribuição Contracorrente , Forbóis , Distribuição Contracorrente/métodos , Óleo de Cróton , Solventes/química , Extratos Vegetais/química , Ésteres de Forbol , Cromatografia Líquida de Alta Pressão
8.
Lung ; 201(1): 9-15, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36746813

RESUMO

PURPOSE: There are limited studies on the use of bronchodilators for the treatment of bronchiectasis. This study investigated the efficacy of tiotropium in patients with bronchiectasis and airflow limitation. METHODS: This study was a prospective cohort study, including 169 patients with bronchiectasis and airflow limitation from 2015 to 2019. The clinical outcomes observed in our study were the effect of tiotropium on the frequency of moderate exacerbations, the time to the first severe exacerbation, and the annual decline in FEV1. RESULTS: After 12 months, the annual decline in the FEV1 after bronchodilator use was 27.08 ml or 42.9 ml per year in the group with or without tiotropium, respectively. Treatment with tiotropium was associated with a decreased risk of moderate exacerbation of bronchiectasis (Adjusted RR 0.618 95% CI 0.493-0.774; P < 0.005). The time to the first severe acute exacerbation of bronchiectasis in the tiotropium group was longer than the non-tiotropium group (Adjusted HR 0.333 95% CI 0.219-0.506; P < 0.001). CONCLUSION: In conclusion, prospective cohort study showed that tiotropium effectively ameliorated the annual decline in the FEV1, with a lower-risk rate of moderate exacerbations and prolonging the time to the first-time severe exacerbation in patients with bronchiectasis and airflow limitation.


Assuntos
Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Humanos , Brometo de Tiotrópio/uso terapêutico , Estudos Prospectivos , Derivados da Escopolamina/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Broncodilatadores/uso terapêutico , Resultado do Tratamento
9.
Analyst ; 147(22): 5231-5238, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36278807

RESUMO

Polarity and viscosity, as important microenvironment parameters, play an essential role in cell metabolism. Therefore, 9-acridine carboxaldehyde reacted with cyano compounds to obtain polarity-sensitive probes 1a-b and viscosity-sensitive probes 1c-d. Among them, with the increase in solvent polarity, the maximum emission wavelength of acridine-dicyanoisophorone-based probe 1a red-shifted from 553 nm to 594 nm, the fluorescence quantum yield increased from 0.5% to 35.6%, and the fluorescence intensity enhanced 38 fold. The acridine-cyanofuranone based probe 1b also has a polarity response similar to 1a. Nevertheless, when the solution viscosity increased from 0.89 cP (100% water) to 856 cP (1% water), the fluorescence intensity of the acridine-tricyanodihydrofuran based probe 1c at 430 nm enhanced 5.6 times. The acridine-cyanobenzothiazole based probe 1d also had a viscosity response similar to 1c. In addition, probes 1a-b were used for further HeLa cell imaging experiments due to their good photostability and the results suggested that probe 1a could locate lipid droplets and probes 1b-c could stain lysosomes. Moreover, probes 1a-b could dynamically monitor the changes in intracellular polarity.


Assuntos
Polaridade Celular , Corantes Fluorescentes , Humanos , Espectrometria de Fluorescência , Células HeLa , Substâncias Intercalantes , Água , Viscosidade , Acridinas
10.
Analyst ; 147(12): 2655-2661, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35579071

RESUMO

Aberrant DNA methylation plays a pivotal role in tumor development and metastasis, and is regarded as a valuable non-invasive cancer biomarker. However, the sensitive and accurate quantification of DNA methylation from clinical samples remains a challenge. Herein, we propose an easy-to-operate Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system Assisted Methylation (CAM) approach for the sensitive detection of DNA methylation through the integration of rolling circle amplification and CRISPR-Cas12a-assisted cascade amplification. Briefly, bisulfite was employed to prepare the clinical samples so that the methylated DNA sequences trigger the subsequent triple signal amplifications, whilst the normal counterparts do not. The triple signal amplification procedure consists of methylated DNA sequence-based rolling circle amplification for a preliminary signal enhancement, a nicking enzyme-initiated target cleavage for a secondary amplification, and CRISPR-Cas12a enzyme-mediated trans-cleavage for a tertiary signal enhancement. This proposed approach reveals high sensitivity, which can even distinguish as low as 0.01% methylation levels from mixtures, paving the way towards the acceleration of methylation-based cancer diagnostics and management.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , Técnicas Biossensoriais/métodos , Sistemas CRISPR-Cas/genética , Metilação de DNA , Técnicas de Amplificação de Ácido Nucleico/métodos
11.
Org Biomol Chem ; 20(28): 5558-5565, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35791887

RESUMO

In this paper, two cationic probes 1a and 1b and a neutral dye 1c were successfully designed and synthesized according to the Knoevenagel condensation reaction, which combines the good optical properties of hemocyanine and the biocompatibility of nitrogen-containing heterocyclic rings based on a quinoxaline skeleton. Probes 1a and 1b showed an OFF-ON fluorescence response to nucleic acids with excellent selectivity. Specifically, the fluorescence intensity of probe 1a was enhanced by 18 and 133 times, respectively, along with the increase of DNA or RNA concentrations (0-600 µg mL-1). Furthermore, a good linear correlation between the fluorescence intensity of probes 1a and 1b and the concentrations of DNA or RNA (0-350 µg mL-1) was obtained. In particular, the maximum emission wavelengths of probes 1a and 1b reached the near-infrared region (660-664 nm) when DNA or RNA was detected, which might reduce the light damage to cells and facilitate cell experiments. Fluorescence imaging revealed that all three dyes could be localized in the mitochondria of HeLa cells. The difference was that probes 1a and 1b could stain the nucleic acid in the mitochondria, while dye 1c was only a neutral mitochondrial biomarker. The results indicated that probes 1a and 1b are promising in the development of low toxicity mitochondrial nucleic acid probes and are expected to be used in monitoring the normal state of mitochondrial nucleic acids for living cells, which will help improve the situation in that currently reported studies of fluorescent probes are mainly focused on the nucleic acids in the nucleus, but less so on DNA in the mitochondria.


Assuntos
Corantes Fluorescentes , Ácidos Nucleicos , Células HeLa , Humanos , Mitocôndrias , Quinoxalinas , RNA , Esqueleto
12.
BMC Nephrol ; 23(1): 195, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610615

RESUMO

BACKGROUND AND AIMS: To explore the biological variation (BV) of kidney injury markers in serum and urine of healthy subjects within 24 hours to assist with interpretation of future studies using these biomarkers in the context of known BV. MATERIALS AND METHODS: Serum and urine samples were collected every 4 hours (0, 4, 8, 12, 16 and 20 hours) from 31 healthy subjects within 24 hours and serum creatinine (s-Crea), serum ß2-microglobin (s-ß2MG), serum cystatin C (s-CYSC), serum neutrophil gelatinase-associated lipoprotein (s-NGAL), urine creatinine (u-Crea), urine ß2-microglobin (u-ß2MG), urine cystatin C (u-CYSC), urine neutrophil gelatinase-associated lipoprotein (u-NGAL) were measured. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA analysis on trend-corrected data (if relevant), and analytical (CVA), within-subject (CVI), and between-subject (CVG) biological variation were calculated. RESULTS: The concentration of kidney injury markers in male was higher than that in female, except for u-CYSC and u-NGAL. There were no significant difference in serum and urine kidney injury markers concentration at different time points. Serum CVI was lower than urine CVI, serum CVG was higher than CVI, and urine CVG was lower than CVI. The individual index (II) of serum kidney injury markers was less than 0.6, while the II of urinary kidney injury markers was more than 1.0. CONCLUSIONS: This study provides new short-term BV data for kidney injury markers in healthy subjects within 24 hours, which are of great significance in explaining other AKI / CKD studies.


Assuntos
Injúria Renal Aguda , Cistatina C , Biomarcadores , Creatinina , Feminino , Gelatinases , Humanos , Rim , Lipocalina-2/urina , Masculino
13.
Molecules ; 27(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36364136

RESUMO

In order to improve the mechanical strength and imprinting efficiency, a novel bovine serum albumin (BSA) molecularly imprinted poly(ionic liquid)/calcium alginate composite cryogel membrane (MICM) was prepared. The results of the tensile test indicated that the MICM had excellent mechanical strength which could reach up to 90.00 KPa, 30.30 times higher than the poly (ionic liquid) membrane without calcium alginate; the elongation of it could reach up to 93.70%, 8.28 times higher than the poly (ionic liquid) membrane without calcium alginate. The MICM had a very high welling ratio of 1026.56% and macropore porosity of 62.29%, which can provide effective mass transport of proteins. More remarkably, it had a very high adsorption capacity of 485.87 mg g-1 at 20 °C and 0.66 mg mL-1 of the initial concentration of BSA. Moreover, MICM also had good selective and competitive recognition toward BSA, exhibiting potential utility in protein separation. This work can provide a potential method to prepare the protein-imprinted cryogel membrane with both high mechanical strength and imprinting efficiency.


Assuntos
Líquidos Iônicos , Impressão Molecular , Criogéis , Soroalbumina Bovina , Alginatos , Impressão Molecular/métodos , Adsorção
14.
Reproduction ; 163(1): 57-68, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34866594

RESUMO

Endometriosis (EMS) is a chronic benign inflammatory disease characterized by the growth of endometrial-like tissue in aberrant locations outside of the uterine cavity. Angiogenesis and abnormal immune responses are the fundamental requirements of endometriotic lesion survival in the peritoneal cavity. Follistatin-like I (FSTL1) is a secreted glycoprotein that exhibits varied expression levels in cardiovascular disease, cancer and arthritis. However, the role of FSTL1 in the development of EMS remains to be fully elucidated. Results of the present study demonstrated that the expression of FSTL1 was significantly increased in ectopic endometrial stromal cells (ESCs) and peritoneal fluid from patients with EMS, compared to the control group. Both conditions of hypoxia and estrogen treatment induced human ESCs to produce increased levels of FSTL1 and disco-interacting protein 2 homolog A (DIP2A). Furthermore, the expression levels of DIP2A, IL8 and IL1ß were increased in FSTL1 overexpressed HESCs. Additionally, FSTL1 treatment increased the proliferation of HUVECs in a dose-dependent manner in vitro and markedly increased the tube formation of HUVECs. Moreover, treatment with FSTL1 facilitated M1 polarization of macrophages, increased the secretion of proinflammatory factors and inhibited the expression of scavenger receptor CD36. Results of the present study suggested that the elevated expression of FSTL1 may play a key role in accelerating the development of EMS via enhancing the secretion of proinflammatory factors and promoting angiogenesis.


Assuntos
Endometriose , Proteínas Relacionadas à Folistatina , Endometriose/patologia , Endométrio/patologia , Feminino , Folistatina , Proteínas Relacionadas à Folistatina/genética , Proteínas Relacionadas à Folistatina/metabolismo , Proteínas Relacionadas à Folistatina/farmacologia , Humanos , Neovascularização Patológica/patologia
15.
Lipids Health Dis ; 20(1): 25, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722242

RESUMO

BACKGROUND: To investigate the correlation between the thickness of epicardial adipose tissue (EAT), C-reactive protein (CRP), interleukin (IL) -6, visfatin, juxtaposed with another zinc finger protein 1 (JAZF1) and type 2 diabetic mellitus (T2DM) macroangiopathy. METHODS: The study enrolled 82 patients with T2DM with macroangiopathy (the Complication Group), and 85 patients with T2DM (the Diabetes Group) who were admitted to Shandong Provincial Third Hospital from February 2018 to February 2020. In addition, 90 healthy people who underwent physical examination at the same hospital during the same period were enrolled (the Healthy Control Group). Age, gender, height, weight, waist circumference (WC), hip circumference (HC), diabetic course and therapeutic drugs, waist hip ratio (WHR), and body mass index (BMI) were recorded and calculated. RESULTS: The baseline characteristics of the three groups were comparable, and the diabetic course of the Complication Group and the Diabetes Group was not significantly different (P > 0.05). The WHR of the Complication Group was higher than that of the Diabetes Group and the Healthy Control Group, with statistical significance (P < 0.05). The FPG, 2hPG, HbA1C, CRP, IL-6, Visfatin, JAZF1, HOMA-IR, EAT thickness, and baPWV of the Complication Group were all higher than those of the Diabetes Group and the Healthy Control Group (P < 0.05, respectively). The JAZF1 and FIns of the Complication Group and Diabetes Group were lower than those of the Healthy Control Group, and JAZF1 of the Complication Group was lower than the Diabetes Group with statistical significance (P<0.05, respectively). Pearson correlation analysis showed that the EAT thickness was positively correlated with CRP, IL-6, visfatin, and JAZF1 (r = 0.387, 0.451, 0.283, 0.301, respectively, all P<0.001). Pearson correlation analysis showed that baPWV was positively correlated with EAT thickness, CRP, IL-6, visfatin, and JAZF1 (r = 0.293, 0.382, 0.473, 0.286, respectively, all P < 0.001). Multivariate stepwise regression analysis showed that FPG, 2hPG, HbA1C, CRP, IL-6, visfatin, JAZF1, and EAT thickness were independent risk factors that affected T2DM macroangiopathy. CONCLUSIONS: Clinical monitoring and treatment of T2DM macroangiopathy can use CRP, IL-6, Visfatin, JAZF1, and EAT thickness as new targets to delay the progression of the disease. Further research on the relationship between the above factors and the pathogenesis of T2DM macroangiopathy may be helpful provide new treatment strategies.


Assuntos
Proteína C-Reativa/genética , Proteínas Correpressoras/genética , Proteínas de Ligação a DNA/genética , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Idoso , Índice de Massa Corporal , Correlação de Dados , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/patologia , Feminino , Humanos , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/genética , Pericárdio/metabolismo , Pericárdio/patologia , Relação Cintura-Quadril
16.
Proc Natl Acad Sci U S A ; 115(17): 4435-4440, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29632184

RESUMO

Cells have developed regulatory mechanisms that underlie flagellar assembly and maintenance, including the transcriptional regulation of flagellar genes, an initial step for making flagella. Although transcriptional regulation of flagellar gene expression is required for flagellar assembly in Chlamydomonas, no transcription factor that regulates the transcription of flagellar genes has been identified. We report that X chromosome-associated protein 5 (XAP5) acts as a transcription factor to regulate flagellar assembly in Chlamydomonas While XAP5 proteins are evolutionarily conserved across diverse organisms and play vital roles in diverse biological processes, nothing is known about the biochemical function of any member of this important protein family. Our data show that loss of XAP5 leads to defects in flagellar assembly. Posttranslational modifications of XAP5 track flagellar length during flagellar assembly, suggesting that cells possess a feedback system that modulates modifications to XAP5. Notably, XAP5 regulates flagellar gene expression via directly binding to a motif containing a CTGGGGTG-core. Furthermore, recruitment of RNA polymerase II (Pol II) machinery for transcriptional activation depends on the activities of XAP5. Our data demonstrate that, through recruitment of Pol II, XAP5 defines a class of transcription factors for transcriptional regulation of ciliary genes. This work provides insights into the biochemical function of the XAP5 family and the fundamental biology of the flagellar assembly, which enhance our understanding of the signaling and functions of flagella.


Assuntos
Chlamydomonas/metabolismo , Flagelos/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas/metabolismo , RNA Polimerase II/metabolismo , Fatores de Transcrição/metabolismo , Chlamydomonas/genética , Flagelos/genética , Proteínas de Plantas/genética , RNA Polimerase II/genética , Fatores de Transcrição/genética , Transcrição Gênica/fisiologia
17.
Genomics ; 112(2): 1128-1138, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31251979

RESUMO

Cold stress imposes a great impact on the growth of nearly all photosynthetic organisms, including Chlamydomonas reinhardtii (C. reinhardtii). Despite prior studies on the mechanism of stress acclimation in plants, little has been done on the early events of cold sensing in C. reinhardtii. Here, we used C. reinhardtii as a model to study early events of cold signal transduction. By analyzing transcriptomic changes of C. reinhardtii exposed to cold, we found that 3471 genes were differentially expressed after 1 h of cold exposure. These genes were associated with a wide range of biological events and processes such as protein synthesis, cell cycle and protein kinase-based phosphorylation. Besides, the promoter of one gene (named as crAP2) which belongs to AP2/EREBP family and was significantly induced by cold was cloned, and functional analysis was conducted using GUS activity analysis through Agrobacterium-mediated transient assay in tobacco leaves.


Assuntos
Chlamydomonas reinhardtii/genética , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas , Chlamydomonas reinhardtii/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
18.
RNA Biol ; 17(1): 87-97, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532701

RESUMO

Formed by back splicing or back fusion of linear RNAs, circular RNAs (circRNAs) constitute a new class of non-coding RNAs of eukaryotes. Recent studies reveal a spliceosome-dependent biogenesis of circRNAs where circRNAs arise at the intron-exon junctions of mRNAs. In this study, using a novel de novo identification method, we show that circRNAs can originate from the interior regions of exons, introns, and intergenic transcripts in human, mouse and rice, which were referred to as interior circRNAs (i-circRNAs). Many i-circRNAs have some remarkable characteristics: multiple i-circRNAs may arise from the same genomic locus; their back fusion points may not be associated with the AG/GT splicing sites, but rather a new pair of motif AC/CT, their back fusion points are adjacent to complementary sequences; and they may circulate on short homologous sequences. We validated several i-circRNAs in HeLa cells by Polymerase Chain Reaction followed by Sanger sequencing. Our results combined showed that i-circRNAs are bona fide circRNAs, indicated novel biogenesis pathways independent of the splicing apparatus, and expanded our understanding of the origin, diversity, and complexity of circRNAs.


Assuntos
Eucariotos/genética , RNA Circular , Processamento Alternativo , Animais , Sequência de Bases , Linhagem Celular , Loci Gênicos , Humanos , Sítios de Splice de RNA , Splicing de RNA
19.
BMC Genomics ; 20(1): 444, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159719

RESUMO

BACKGROUND: Host genetic backgrounds affect gene functions. The genetic backgrounds of genetically engineered organisms must be identified to confirm their genetic backgrounds identity with those of recipients. Marker-assisted backcrossing (MAB), transgenesis and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) editing are three commonly used genetic engineering techniques. However, methods for genetic background screening between genetically engineered organisms and corresponding recipients suffer from low efficiency, low accuracy or high cost. RESULTS: Here, we improved our previously reported AmpSeq-SSR method, an amplicon sequencing-based simple sequence repeat (SSR) genotyping method, by selecting SSR loci with high polymorphism among varieties. Ultimately, a set of 396 SSRs was generated and applied to evaluate the genetic backgrounds identity between rice lines developed through MAB, transgenesis, and CRISPR/Cas9 editing and the respective recipient rice. We discovered that the percentage of different SSRs between the MAB-developed rice line and its recipient was as high as 23.5%. In contrast, only 0.8% of SSRs were different between the CRISPR/Cas9-system-mediated rice line and its recipient, while no SSRs showed different genotypes between the transgenic rice line and its recipient. Furthermore, most differential SSRs induced by MAB technology were located in non-coding regions (62.9%), followed by untranslated regions (21.0%) and coding regions (16.1%). Trinucleotide repeats were the most prevalent type of altered SSR. Most importantly, all altered SSRs located in coding regions were trinucleotide repeats. CONCLUSIONS: This method is not only useful for the background evaluation of genetic resources but also expands our understanding of the unintended effects of different genetic engineering techniques. While the work we present focused on rice, this method can be readily extended to other organisms.


Assuntos
Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Repetições de Microssatélites , Oryza/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Proteínas Serina-Treonina Quinases/genética , Sistemas CRISPR-Cas , Edição de Genes , Técnicas de Transferência de Genes , Engenharia Genética , Proteínas de Plantas/antagonistas & inibidores , Polimorfismo Genético , Proteínas Serina-Treonina Quinases/antagonistas & inibidores
20.
J Chem Phys ; 150(20): 204507, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31153173

RESUMO

Glassy materials are nonequilibrium and their energy states have crucial influences on properties. Recent studies have shown that oscillating deformations (vibrations) can cause either accelerated aging (lowering energy) or rejuvenation (elevating energy); however, the underlying atomic mechanisms remain elusive. Using metallic glasses (MGs) as model systems, we show that the vibration-induced accelerated aging is correlated with the strain field of the stringlike atomic motions stemming from the Johari-Goldstein (ß) relaxation, whereas the rejuvenation is associated with nonlinear response and the formation of nanoscale shear bands attributing to the activation of α relaxation. Both processes are affected by thermal fluctuations, which result in an optimal temperature for accelerated aging. These results suggest intrinsic correlations among relaxation dynamics, mechanical properties, and the vibration induced structural rearrangements in MGs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA