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1.
Horm Metab Res ; 54(2): 84-93, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35130569

RESUMO

Long-term glycemic fluctuation has been associated with cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). However, the findings are inconsistent. We performed a meta-analysis to summarize the association between parameters of long-term glycemic variability and risk of cardiovascular events in T2DM patients. Medline, Embase, and Web of Science databases were searched for longitudinal follow-up studies comparing the incidence of cardiovascular events in T2DM patients with higher or lower long-term glycemic variability. A random-effect model incorporating the potential heterogeneity among the included studies was used to pool the results. Twelve follow-up studies with 146 653 T2DM patients were included. The mean follow-up duration was 4.9 years. Pooled results showed that compared to those with the lowest glycemic variability, patients with the highest glycemic variability had significantly increased risk of cardiovascular events, as evidenced by the standard deviation of glycated hemoglobin [HbA1c-SD: relative risk (RR)=1.44, 95% confidence interval (CI): 1.23 to 1.69, p<0.001; I2=70%], HbA1c coefficient of variation (HbA1c-CV: RR=1.46, 95% CI: 1.19 to 1.79. p<0.001; I2=83%), standard deviation of fasting plasma glucose (FPG-SD: RR=1.33, 95% CI: 1.07 to 1.65, p=0.009; I2=0%), and FPG coefficient of variation (FPG-CV: RR=1.29, 95% CI: 1.01 to 1.64, p=0.04; I2=47%). In conclusion, increased long-term glycemic variability may be an independent risk factor for cardiovascular events in T2DM patients.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Glicemia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Jejum , Hemoglobina A Glicada/análise , Humanos , Fatores de Risco
2.
Rev. bras. med. esporte ; 28(6): 651-653, Nov.-Dec. 2022. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1376747

RESUMO

ABSTRACT Introduction Core strength training has been extensively used in competitive sports training, achieving remarkable results in the most competitive sports training by maximizing athletes' strength and accuracy. It is believed that a specific protocol for female university tennis players can bring the same results. Objective Verify the effectiveness of core strength training in the performance of female university tennis players. Methods Randomized controlled trial of female university tennis players (n=40) with a specific core strength training protocol versus traditional strength training methods. Changes in tactical skills pre and post-experiment were compared. Descriptive statistical treatment of the collected results was confronted with current literature. Results Compared with traditional strength training, core strength training proved to be more conducive to developing core strength in female college tennis players. Conclusion Core strength training assists in the development of skills and tactics in female college tennis players. Evidence level II; Therapeutic Studies - Investigating the results.


RESUMO Introdução O treino de fortalecimento do core tem sido amplamente utilizado no treinamento esportivo competitivo, alcançando resultados notáveis no treino esportivo mais acirrado ao maximizar a força e precisão dos atletas. Acredita-se que um protocolo específico para as tenistas universitárias possa causar os mesmos resultados. Objetivo Verificar a eficácia do treinamento de força do core no treinamento de tenistas universitárias. Métodos Estudo randomizado controlado de tenistas universitárias (n=40) com protocolo específico de fortalecimento de core para fortalecimento versus métodos tradicionais de treino de força. Foram comparadas as alterações das habilidades táticas pré e pós experimento. O tratamento estatístico descritivo dos resultados coletados foi confrontado com a literatura atual. Resultados Comparado com o treinamento de força tradicional, o treinamento de força do core revelou-se mais propício ao desenvolvimento da força do core em tenistas universitárias. Conclusão O treinamento de força do core auxilia no desenvolvimento da habilidade e tática das tenistas universitárias. Nível de evidência II; Estudos terapêuticos - Investigação de resultados.


RESUMEN Introducción El entrenamiento de la fuerza del core se ha utilizado ampliamente en el entrenamiento deportivo de competición, logrando resultados notables en el entrenamiento deportivo más competitivo al maximizar la fuerza y la precisión de los atletas. Se cree que un protocolo específico para los tenistas universitarios puede provocar los mismos resultados. Objetivo Comprobar la eficacia del entrenamiento de la fuerza del core en el entrenamiento de las tenistas universitarias. Métodos Estudio controlado aleatorio de jugadoras de tenis universitarias (n=40) con un protocolo específico de entrenamiento de la fuerza del core para el fortalecimiento frente a los métodos tradicionales de entrenamiento de la fuerza. Se compararon los cambios en las habilidades tácticas antes y después del experimento. El tratamiento estadístico descriptivo de los resultados recogidos se confrontó con la literatura actual. Resultados En comparación con el entrenamiento de fuerza tradicional, el entrenamiento de fuerza del core demostró ser más propicio para el desarrollo de la fuerza del core en las tenistas universitarias. Conclusión El entrenamiento de la fuerza del core ayuda al desarrollo de la habilidad y la táctica de las tenistas universitarias. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

3.
Front Pharmacol ; 13: 931282, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071835

RESUMO

Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. This study explored the core genes and pathways associated with DKD to identify potential diagnostic and therapeutic targets. Methods: We downloaded microarray datasets GSE96804 and GSE104948 from the Gene Expression Omnibus (GEO) database. The dataset includes a total of 53 DKD samples and 41 normal samples. Differentially expressed genes (DEGs) were identified using the R package "limma". The Metascape database was subjected to Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to identify the pathway and functional annotations of DEGs. A WGCAN network was constructed, the hub genes in the turquoise module were screened, and the core genes were selected using LASSO regression to construct a diagnostic model that was then validated in an independent dataset. The core genes were verified by in vitro and in vivo experiments. Results: A total of 430 DEGs were identified in the GSE96804 dataset, including 285 upregulated and 145 downregulated DEGs. WGCNA screened out 128 modeled candidate gene sets. A total of eight genes characteristic of DKD were identified by LASSO regression to build a prediction model. The results showed accuracies of 99.15% in the training set (GSE96804) and 94.44% and 100%, respectively, in the test (GSE104948-GPL22945 and GSE104948-GPL24120). Three core genes (OAS1, SECTM1, and SNW1) with high connectivity were selected among the modeled genes. In vitro and in vivo experiments confirmed the upregulation of these genes. Conclusion: Bioinformatics analysis combined with experimental validation identified three novel DKD-specific genes. These findings may advance our understanding of the molecular basis of DKD and provide potential therapeutic targets for its clinical management.

4.
J Anal Methods Chem ; 2022: 3415938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072919

RESUMO

The HPTLC method is widely used in the field of quality evaluation and component analysis of traditional Chinese medicine (TCM). This work developed an HPTLC method to determine the five effective components of osthole, columbianadin, isoimperatorin, oxypeucedanin, and imperatorin in Angelicae Pubescentis Radix (APR) from twelve different origins, and the quality difference was analyzed by comprehensive factor analysis and cluster analysis. The results showed that the calibration curves of five components exhibited good linearity within the linear ranges (0.8-4.0 µg). The RSD of precision was 1.06%-1.21%, and the repeatability and stability tests were good. The results of cluster analysis showed that the APR from 12 different areas was divided into two categories, and at the same time, it was found that the quality of Dazhou in Sichuan and Huating in Gansu was better than in other areas. In this study, a simple, rapid, and efficient method for quality evaluation of TCM was established by the HPTLC method.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36056284

RESUMO

The Tibetan Plateau (TP) is known as the water tower of Asia, and the water quality has long been a focus of public concern, especially in the Yarlung Tsangpo River Basin (YTRB), a unique area that is climate-sensitive, geologically complex, eco-fragile, and densely populated. Thallium (Tl) is a typical metal that is more toxic than Pb, Cd, and As and often occurs in sulfide minerals. Although large-scale polymetallic sulfide mineralization developed in the YTRB, the geochemical dispersion and potential risk of Tl in aquatic environments of the YTRB remain poorly understood. In this study, the concentration, distribution, source, and health risk of Tl and associated metal(loid)s in the hot springs and surface water in the YTRB were systematically analyzed. The results showed that the trace elements (Cd, Cr, Zn, Cu, Al, Sr, Ni, Co, Mn, Pb) in water environments are within the recommended limits, except for Tl and As. Principal component analysis (PCA) and correlation analysis (CA) showed that the elements of Tl and As were positively related to each other in either both hot spring water and surface water, indicating their common origin. Spatial variations suggested that high levels of Tl and As observed in the north YTRB, which may be relevant to the reduction-dissolution of Tl (As)-bearing minerals and the magmatic hydrothermal system formed in the shallow part of the northern YTRB. Furthermore, source apportionment identified natural sources of Cu, Ni, Cr, Co, Mn, Zn, and Cd and anthropogenic inputs of Al and Pb. Exposure assessment studies have found that ingestion is the primary route of As and Tl exposure to local population, and balneological and bathing purposes do not constitute a human health concern. This study offers valuable insights into the risk of naturally occurring Tl enrichment being hidden in As-rich hydrosphere in the YTRB and other regions with similar geoenvironmental contexts.

6.
Ann Med Surg (Lond) ; 80: 104130, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36045770

RESUMO

Introduction: With the increasingly common operation of mechanical thrombectomy (MT) in acute cerebral infarction cases, iatrogenic CCFs were occasionally reported. All of cases reported type A CCFs, and patients were presented with either asymptom from generation of fistula to duration of postoperative follow-up or distinct presentations at once after MT. Case presentation: A 48-year-old postmenopausal female, without history of systemic hypertension and diabetes mellitus, underwent an operation of MT outside our institution about half a year ago. An intraoperative DSA showed an iatrogenic low-flow fistula between meningohypophyseal trunk and ICA. After 4 mouths' postoperative conservative observation, patient's presentation progressed from asymptom to serious optic signs. The patient underwent trans-arterial interventional occlusion. On postoperative day one, visual presentations of patient relieved significantly. Discussion: We discuss the reason for possibility of iatrogenic injury to meningohypophyseal trunk and clinical progressive presentation. A sudden swerve just beyond derivation of meningohypophyseal trunk is prone to being damaged by a misguided guide wire. The progression of clinical presentation, as a focal point in our case, is not reported in iatrogenic before, but some studys still find that spontaneous dural CCFs are inclined to occur in middle-aged or elderly women, especially in postmenopausal women, so age and sex are regarded as background factors of progressing. In addition, the change of drainage route is an immediate cause of progressive presentations. Conclusion: We expect that when a manipulation of MT is conducted leading an iatrogenic CCF, our neurointerventionist should maintain appropriate vigilance on sex, age, menstrual history and medical history, then take an earlier and timely interventional measure.

7.
J Integr Plant Biol ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053143

RESUMO

Brassinosteroids (BRs) and abscisic acid (ABA) are essential regulators of plant growth and stress tolerance. Although the antagonistic interaction of BRs and ABA is proposed to ensure the balance between growth and defense in model plants, the crosstalk between BRs and ABA in response to chilling in tomato (Solanum lycopersicum), a warm-climate horticultural crop, is unclear. Here, we determined that overexpression of the BR biosynthesis gene DWARF (DWF) or the key BR signaling gene BRASSINAZOLE-RESISTANT1 (BZR1) increases ABA levels in response to chilling stress via positively regulating the expression of the ABA biosynthesis gene 9-CIS-EPOXYCAROTENOID DIOXYGENASE1 (NCED1). BR-induced chilling tolerance was mostly dependent on ABA biosynthesis. Chilling stress or high BR levels decreased the abundance of BRASSINOSTEROID-INSENSITIVE2 (BIN2), a negative regulator of BR signaling. Moreover, we observed that chilling stress increases BR levels and results in the accumulation of BZR1. BIN2 negatively regulated both the accumulation of BZR1 protein and chilling tolerance by suppressing ABA biosynthesis. Our results demonstrate that BR signaling positively regulates chilling tolerance via ABA biosynthesis in tomato. The study has implications in production of warm-climate crops in horticulture. This article is protected by copyright. All rights reserved.

8.
J Clin Lab Anal ; : e24677, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086857

RESUMO

OBJECTIVE: Clinically, to make a definite diagnosis of aplastic anemia (AA), idiopathic cytopenia of undetermined significance (ICUS) or myelodysplastic syndrome (MDS), they should be distinguished from each other. AA and ICUS have some incidence to transform into MDS. Immunosuppressive therapy (IST) is effective in AA and partial ICUS patients, while other ICUSs are more likely to progress to MDS without response to IST. To date, we neither found a technical method that could easily identify AA from hypoproliferative MDS, nor a simple parameter that could indicate ICUS with a response to IST. Here, we detected the concentration of free immune checkpoints in bone marrow supernatant of AA, ICUS, and MDS patients, analyzed the differences of immune status among these three diseases, to try to find a way to predict the response to IST in ICUSs. METHODS: Seventy-four novel patients were enrolled with newly diagnosed acquired bone marrow failure (including 29 AA patients, 11 ICUS patients, and 34 MDS patients), bone marrow supernatants were collected. Luminex liquid suspension array technology was used to measure the concentrations of 17 immune checkpoints to analyze the differences of immune status among these three diseases. RESULTS: The levels of 17 free immune checkpoints were elevated in MDS and showed a strong correlation with each other, followed by ICUS, and with the weakest in AA. By drawing the ROC curve, we found eight immune checkpoints, including sCD40, sCD86/B7-2, sCTLA-4, sGITR, sHVEM, sPD-1, sTIM-3, and sTLR-2, could easily distinguish AA from hypoproliferative MDS. ICUSs with lower concentrations of these eight free immune checkpoints predicted a better IST response. CONCLUSION: In conclusion, we found that there were notable differences in the immune status of AA, ICUS, and MDS. The concentrations of sCD40, sCD86/B7-2, sCTLA-4, sGITR, sHVEM, sPD-1, sTIM-3, and sTLR-2 could be used to identify AA and hypoproliferative MDS patients, as well as to distinguish ICUS patients who could benefit from IST.

9.
Front Neurol ; 13: 917308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119703

RESUMO

Objective: Turn-amplitude clouds were widely used in automatic electromyography (EMG) interference pattern analysis. Earlier works employed the intercept ± 2SD (standard deviation) of the linear regression equation as the upper and lower boundaries of the clouds. The goal of this study was to employ the linear regression method and percentile method to calculate the reference value of turn-amplitude clouds, identify the determining criteria in accordance with the receiver operator characteristic curve (ROC), and analyze the sensitivity and specificity of the linear regression cloud, percentile cloud, and quantitative assessment of the motor unit potential (QMUP). Methods: First, we explore what factors affect the number of turns per second and the mean amplitude. Then, their logarithms were taken for the normal test. All muscle data were used to calculate the reference values of percentile clouds. However, the reference values of the linear regression clouds were obtained for the muscles with a bivariate normal distribution, homogeneous variances and a linear correlation. We calculated the prediction interval with the standard errors of the intercept and slope of the linear regression equation, which can determine the upper and lower boundaries of the linear regression clouds. Furthermore, we obtained ROCs of these clouds, which were used as the determining criteria to determine the optimum cut-off values. Finally, our study analyzed the sensitivity and specificity of the linear regression cloud, percentile cloud, and QMUP. Results: We here presented the reference values and ROCs of the linear regression clouds and percentile clouds. We suggest the determining criteria be based on ROCs. The areas under the curve (AUC) of both clouds are larger than 0.8, revealing that they have significant diagnostic value. Our results display that the specificities of the linear regression clouds, percentile clouds, and QMUP are almost identical to each other, whereas the sensitivity of percentile cloud is higher than those of QMUP and linear regression clouds. Conclusion: According to ROCs, the researchers determine the determining criteria of the linear regression clouds and percentile clouds. Our findings suggest that the percentile clouds possess a wide application range and significant diagnostic value, therefore it may be the optimum for automatic EMG interference pattern analysis.

10.
Virol J ; 19(1): 150, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115975

RESUMO

BACKGROUND: Integrating CRISPR-Cas12a sensors with isothermal signal amplification can be exploited to develop low-cost, disposable, and ultrasensitive assays for the diagnostics of human pathogens. METHODS: RT-RAA-Cas12a-mediated real-time or end-point fluorescent and lateral flow strip (LFS) assays for direct detection of norovirus (NOV) genotype GII.4 or GII.17 were explored. RESULTS: The results showed that our RT-RAA-Cas12a-mediated fluorescent and LFS assay could detect NOV GII.4 or GII.17 by targeting the viral protein 1 gene. Our RT-RAA-Cas12a-mediated fluorescent and LFS assay can specifically detect NOV GII.4 or GII.17 with no cross-reactivity for other related viruses. The low limit of detection could reach 0.1 copies/µL within approximately 30-40 min, and the results were visualized using an ultraviolet light illuminator or on a LFS without complex equipment. In addition, our RT-RAA-Cas12a-mediated fluorescent and LFS assay provided a visual and faster alternative to real-time RT-PCR assay, with 95.7% and 94.3% positive predictive agreement and 100% negative predictive agreement. CONCLUSIONS: Together, our RT-RAA-Cas12a-mediated approach would have a great potential for point-of-care diagnostics of NOV GII.4 and/or GII.17 in resource-limited settings.


Assuntos
Infecções por Caliciviridae , Norovirus , Sistemas CRISPR-Cas , Infecções por Caliciviridae/diagnóstico , Genótipo , Humanos , Norovirus/genética , Sensibilidade e Especificidade , Proteínas Virais/genética
11.
Talanta ; 253: 123935, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36122434

RESUMO

In this study, MIL-101(Cr)/cellulose aerogel/melamine sponge composite was fabricated through a simple soaking method. The composite was packed in the syringe barrel and used as the sorbent for microextraction in packed syringe. Coupled to UPLC-MS/MS, the proposed method was employed for the analysis of trace nitroimidazoles in water samples. The parameters affecting the extraction efficiency, including sorbent type, pH value of sample solution, sample solution volume and elution solvent were optimized. Under the optimal conditions, good linearity (r > 0.99 for five analytes), high sensitivity (limit of detection: 8.250-16.33 ng L-1), ideal precision (intra-day precision: 1.1%-5.3%, inter-day precision: 1.8%-6.7%) and satisfactory accuracy (recovery: 70.4%-96.7%) were achieved. The proposed method was proved to be efficient, easily operative and environmentally friendly.

13.
Contrast Media Mol Imaging ; 2022: 5473244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101803

RESUMO

In recent years, imaging technology has made rapid progress to improve the sensitivity of tumor diagnostic. With the development of genetic engineering and synthetic biology, various genetically encoded molecular imaging probes have also been extensively developed. As a biomedical imaging method with excellent detectable sensitivity and spatial resolution, genetically encoded molecular imaging has great application potential in the visualization of cellular and molecular functions during tumor development. Compared to chemosynthetic dyes and nanoparticles with an imaging function, genetically encoded molecular imaging probes can more easily label specific cells or proteins of interest in tumor tissues and have higher stability and tissue contrast in vivo. Therefore, genetically encoded molecular imaging probes have attracted increasing attention from researchers in engineering and biomedicine. In this review, we aimed to introduce the genetically encoded molecular imaging probes and further explained their applications in tumor imaging.


Assuntos
Nanopartículas , Neoplasias , Humanos , Imagem Molecular/métodos , Sondas Moleculares , Neoplasias/diagnóstico por imagem , Neoplasias/genética
14.
Int. j. clin. health psychol. (Internet) ; 22(3): 1-8, Sept. - dec. 2022. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-EMG-197

RESUMO

Background/objective: Negative emotional states, such as depression, anxiety, and stress challenge health care due to their long-term consequences for mental disorders. Accumulating evidence indicates that regular physical activity (PA) can positively influence negative emotional states. Among possible candidates, resilience and exercise tolerance in particular have the potential to partly explain the positive effects of PA on negative emotional states. Thus, the aim of this study was to investigate the association between PA and negative emotional states, and further determine the mediating effects of exercise tolerance and resilience in such a relationship.Method: In total, 1117 Chinese college students (50.4% female, Mage=18.90, SD=1.25) completed a psychosocial battery, including the 21-item Depression Anxiety Stress Scale (DASS-21), the Connor-Davidson Resilience Scale (CD-RISC), the Preference for and Tolerance of the Intensity of Exercise Questionnaire (PRETIE-Q), and the International Physical Activity Questionnaire short form (IPAQ-SF). Regression analysis was used to identify the serial multiple mediation, controlling for gender, age and BMI.Results: PA, exercise intensity-tolerance, and resilience were significantly negatively correlated with negative emotional states (Ps<.05). Further, exercise tolerance and resilience partially mediated the relationship between PA and negative emotional states.Conclusions: Resilience and exercise intensity-tolerance can be achieved through regularly engaging in PA, and these newly observed variables play critical roles in prevention of mental illnesses, especially college students who face various challenges. Recommended amount of PA should be incorporated into curriculum or sport clubs within a campus environment. (AU)


Assuntos
Humanos , Adolescente , Adulto Jovem , Exercício Físico , Resiliência Psicológica , Tolerância ao Exercício , Inquéritos e Questionários , China , Universidades
15.
Front Bioeng Biotechnol ; 10: 943695, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061446

RESUMO

Wound infection and excessive exudate can affect the process of wound healing. However, the disadvantage of the anti-microbial wound dressings is that the biological fluids are ineffectively removed. Inspired by making "Chinese Jianbing", a composite wound nano-dressing was developed consisting of a hydrophilic outer layer (chitosan&polyvinyl alcohol: CTS-PVA) and a hydrophobic inner layer (propolis&polycaprolactone: PRO-PCL) by combining casting and electrospinning methods for effective antibacterial and unidirectional removing excess biofluids. In vitro, the composite wound nano-dressing of PRO-PCL and CTS-PVA (PPCP) could strongly inhibit Pseudomonas aeruginosa. Furthermore, PPCP wound dressing had excellent antioxidant properties and blood coagulation index for effective hemostatic. Importantly, it had a preferable water absorption for removing excess biofluid. In vivo, it had anti-inflammatory properties and promoted collagen Ⅰ preparation, which realized 80% wound healing on day 7. In short, the PPCP wound dressing provides a new direction and option for antibacterial and removes excess biofluid.

16.
Acta Derm Venereol ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36065746

RESUMO

There is a recognized need to better understand chang-es in the epidemiology of psoriasis and psoriatic arthritis (PsA) over time in Asia. Using the Taiwan National Health Insurance claim records this population-based study examined changes in the prevalence, incidence, and mortality rates in patients with psoriasis or psoriatic arthritis in Taiwan over 12 years. Patients with ≥1 diagnosis code for psoriasis or psoriatic arthritis, recorded either by dermatologists or rheumatologists, were identified. Annual age- and sex-standardized prevalence and incidence rates were calculated using the Taiwan general population as reference. To investigate mortality, each patient in the incident cohort was matched to 10 comparators from the general population by sex and age (at diagnosis). The risk of mortality between study cohorts and comparators was analysed by Cox proportional hazard regression. The prevalence of psoriasis (0.18-0.86%) and psoriatic arthritis (0.01-0.08%) increased steadily b-etween 2006 and 2017. The incidence rates, however, remained stable (psoriasis: 62-65 per 100,000 person-years; psoriatic arthritis: 6-5 per 100,000 person-years). The risk of all-cause mortality for patients with psoriasis (hazard ratio 1.16; 95% confidence interval: 1.13-1.19) was higher than the general population, despite a decreasing trend over time in the all-cause mortality rates for both groups. The steady increase in the prevalence of psoriasis despite stable incidence rates suggests that improvements in life expectancy may be the key determinant of this increase.

17.
J Infect ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36057384

RESUMO

OBJECTIVES: RNA therapeutics is an emerging field that widens the range of treatable targets and would improve disease outcome through bypassing the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (M.tb). METHODS: We screened for microRNA with immune-regulatory functions against M.tb by next generation sequencing of peripheral blood mononuclear cells, followed by validation in an independent cohort. RESULTS: Twenty three differentially expressed microRNAs were identified between 12 active pulmonary TB patients and 4 healthy subjects, and 35 microRNAs before and after 6-month anti-TB therapy. Enriched predicted target pathways included proteoglycan, HIF-1 signaling, longevity-regulating, central carbon metabolism, and autophagy. We validated miR-431-3p down-regulation and miR-1303 up-regulation accompanied with corresponding changes in their predicted target genes in an independent validation cohort of 46 active TB patients, 30 latent TB infection subjects, and 24 non-infected healthy subjects. In vitro experiments of transfections with miR-431-3p mimic/miR-1303 short interfering RNA in THP-1 cells under ESAT-6 stimuli showed that miR-431-3p and miR-1303 were capable to augment and suppress autophagy/apoptosis/phagocytosis of macrophage via targeting MDR1/MMP16/RIPOR2 and ATG5, respectively. CONCLUSIONS: This study provides a proof of concept for microRNA-based host-directed immunotherapy for active TB disease. The combined miR-431-3p over-expression and miR-1303 knock-down revealed new vulnerabilities of treatment-refractory TB disease.

18.
PLoS Pathog ; 18(9): e1010759, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36084159

RESUMO

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and SLAM was identified as the primary receptor for PPRV and other Morbilliviruses. Many viruses have been demonstrated to engage extracellular vesicles (EVs) to facilitate their replication and pathogenesis. Here, we provide evidence that PPRV infection significantly induced the secretion levels of EVs from goat PBMC, and that PPRV-H protein carried in EVs can enhance SLAM receptor expression in the recipient cells via suppressing miR-218, a negative miRNA directly targeting SLAM gene. Importantly, EVs-mediated increased SLAM expression enhances PPRV infectivity as well as the expression of various cytokines related to SLAM signaling pathway in the recipient cells. Moreover, our data reveal that PPRV associate EVs rapidly entry into the recipient cells mainly through macropinocytosis pathway and cooperated with caveolin- and clathrin-mediated endocytosis. Taken together, our findings identify a new strategy by PPRV to enhance virus infection and escape innate immunity by engaging EVs pathway.

19.
Sci Total Environ ; 853: 158557, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36084780

RESUMO

Hypoxia caused by global climate change and anthropogenic pollution has exposed marine species to increasing stress. Oxygen sensing mediated by prolyl hydroxylase (PHD) is regarded as the first line of defense under hypoxia exposure; however, the function of PHD in marine molluscan species remains unclear. In this study, we identified two PHD2 gene in the oyster Crassostrea gigas using phylogenetic tree analysis with 36 species, namely, CgPHD2A/B. Under hypoxia, the mRNA and protein expression of CgPHD2A displayed a time-dependent pattern, revealing a critical role in the response to hypoxia-induced stress. Observation of interactions between CgPHD2 and CgHIF-1α proteins under normoxia using co-immunoprecipitation and GST-pull down experiments showed that the ß2ß3 loop in CgPHD2A hydroxylates CgHIF-1α to promote its ubiquitination with CgVHL. With the protein recombination and site-directed mutagenesis, the hydroxylation domain and two target proline loci (P404A and 504A) in CgPHDs and CgHIF-1α were identified respectively. Moreover, the electrophoretic mobility-shift assay (EMSA) and luciferase double reporter gene assay revelaed that CgHIF-1α could regulate CgPHD2A expression through binding with the hypoxia-responsive element in the promoter region (320 bp upstream), forming a feedback loop. However, protein structure analysis indicated that six extra amino acids formed an α-helix in the ß2ß3 loop of CgPHD2B, inhibiting its activity. Overall, this study revealed that two CgPHD2 proteins have evolved, which encode enzymes with different activities in oyster, potentially representing a specific hypoxia-sensing mechanism in mollusks. Illustrating the functional diversity of CgPHDs could help to assess the physiological status of oyster and guide their aquaculture.

20.
Eur J Pharmacol ; 933: 175256, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36088983

RESUMO

Many studies have indicated that the risk of cognitive impairment is higher in patients with rheumatoid arthritis (RA). Additionally, patients with RA may have a lower incidence of cognitive impairment with long-term use of ibuprofen. This study was aimed at investigating the impacts of RA on memory function and the mechanisms that ibuprofen may exhibit to improve memory function in rats with collagen-induced arthritis (CIA). Ibuprofen (30 mg/kg) was given twice daily to CIA rats for two weeks starting from Day 18 following the first immunization. Memory function was measured by the Morris water maze (MWM) test and long-term potentiation (LTP). The proinflammatory cytokine levels and downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), were examined. Furthermore, the glutamatergic system, including glutamate transporters/receptors and brain extracellular levels of glutamate, was investigated. The results showed that the impaired learning memory in CIA rats, examined by the MWM test and LTP, can be ameliorated by ibuprofen treatment. Along with the improvement in memory deficits, ibuprofen attenuated both neuroinflammation and the associated elevated levels of phosphorylated p38, JNK, and p65 in the hippocampus of CIA rats. In addition, the decreased excitatory amino acid transporter 2 level, the increased extracellular glutamate, and the upregulated hippocampal NMDA receptor 2B of CIA rats were all normalized by ibuprofen treatment. These findings suggest that the effect of ibuprofen on the memory improvement in CIA rats is associated with the normalization of the activated MAPK and NF-κB pathways and the aberrant glutamatergic system.

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