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1.
Cancer Cell Int ; 24(1): 18, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191389

RESUMEN

BACKGROUND: Although non-invasive radiological techniques are widely applied in kidney renal clear cell carcinoma (KIRC) diagnosis, more than 50% of KIRCs are detected incidentally during the diagnostic procedures to identify renal cell carcinoma (RCC). Thus, sensitive and accurate KIRC diagnostic methods are required. Therefore, in this study, we aimed to identify KIRC-associated microRNAs (miRNAs). METHODS: This three-phase study included 224 participants (112 each of patients with KIRC and healthy controls (NCs)). RT-qPCR was used to evaluate miRNA expression in KIRC and NC samples. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to predict the usefulness of serum miRNAs in KIRC diagnosis. In addition, we performed survival and bioinformatics analyses. RESULTS: We found that miR-1-3p, miR-129-5p, miR-146b-5p, miR-187-3p, and miR-200a-3p were significantly differentially expressed in patients with KIRC. A panel consisting of three miRNAs (miR-1-3p, miR-129-5p, and miR-146b-5p) had an AUC of 0.895, ranging from 0.848 to 0.942. In addition, using the GEPIA database, we found that the miRNAs were associated with CREB5. According to the survival analysis, miR-146b-5p overexpression was indicative of a poorer prognosis in patients with KIRC. CONCLUSIONS: The identified three-miRNA panel could serve as a non-invasive indicator for KIRC and CREB5 as a potential target gene for KIRC treatment.

2.
Biomarkers ; 29(5): 276-284, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38767408

RESUMEN

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.


Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.


Asunto(s)
Biomarcadores de Tumor , MicroARNs , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/diagnóstico , MicroARNs/sangre , MicroARNs/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Regulación Neoplásica de la Expresión Génica , Anciano , Perfilación de la Expresión Génica
3.
J Immunol ; 209(6): 1200-1211, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35995508

RESUMEN

Dendritic cells (DCs) are professional APCs equipped with MHC-restricted Ags, costimulations, and cytokines that effectively prime and differentiate naive T cells into distinct functional subsets. The immune signals that DCs carry reflect the route of Ag uptake and the innate stimuli they received. In the mucosal tissues, owing to the great variety of foreign Ags and inflammatory cues, DCs are predominantly activated and migratory. In the small intestine, CD4 Th17 cells are abundant and have been shown to be regulated by DCs and macrophages. Using a mouse commensal bacteria experimental model, we identified that the early priming step of commensal-driven Th17 cells is controlled by bona fide Zbtb46-expressing DCs. CCR7-dependent migration of type 2 DCs (DC2s) from the small intestine to the mesenteric lymph nodes (MLNs) is essential for the activation of naive CD4 T cells. The migratory DC2 population in the MLNs is almost exclusively Esam+ cells. Single-cell RNA sequencing highlighted the abundance of costimulatory markers (CD40 and OX40) and chemokines (Ccl22 and Cxcl16) on MLN migratory DCs. Further resolution of MLN migratory DC2s revealed that the Th17-polarizing cytokine IL-6 colocalizes with DC2s expressing CD40, Ccl17, and Ccl22. Thus, early Th17 cell differentiation is initiated by a small subset of migratory DC2s in the gut-draining lymph nodes.


Asunto(s)
Células Dendríticas , Células Th17 , Bacterias , Quimiocinas , Citocinas , Interleucina-6 , Intestino Delgado , Ganglios Linfáticos , Membrana Mucosa , Receptores CCR7
4.
BMC Public Health ; 24(1): 1314, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750484

RESUMEN

BACKGROUND: Medical students are known to be at a greater risk of psychological disorders compared to the general population. However, their rate of help-seeking behavior is low. The purpose of this study was to explore the influencing factors of attitudes towards psychological help-seeking among Chinese medical students and to examine its gender differences. METHODS: A total of 3,453 medical students from three medical colleges in Hainan Province, China, completed anonymous questionnaires that included socio-demographic attributes, the Family APGAR Index, the General Health Questionnaire (GHQ-20), and the Attitudes Towards Seeking Professional Psychological Help Short Form (ATSPPH-SF). Associations between predictor variables and attitudes towards help-seeking were explored using multivariate linear regression, and regression models with interaction terms were employed to test gender difference. RESULTS: The mean score on ATSPPH-SF Scale was 15.04 ± 3.45, with males scoring significantly lower than females (14.34 vs. 15.64, P < 0.0001). For both male and female groups, psych knowledge, mental health status, family function and help-seeking utility perception significantly influenced attitudes toward psychological help-seeking. Furthermore, having more than once psycho-help experiences was positively correlated with women's attitudes. Significant interactions were found between gender and mental health status. CONCLUSION: Attitude towards seeking psychological help was relatively negative among Chinese medical students. The implementation of interventions should take into account the at-risk population, especially the males and individuals with poor mental health.


Asunto(s)
Estudiantes de Medicina , Humanos , Femenino , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Masculino , China , Factores Sexuales , Adulto Joven , Encuestas y Cuestionarios , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Adulto , Conducta de Búsqueda de Ayuda , Trastornos Mentales/psicología , Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Pueblos del Este de Asia
5.
Int J Cosmet Sci ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38818630

RESUMEN

OBJECTIVE: We conducted a study on women with sensitive skin of various skin tones to analyse their skin characteristics and preferences for foundation shades. METHODS: Volunteers were categorized based on their individual typological angle, and their preferences were assessed using self-perception and software-based mass aesthetic assessment. The Baumann Questionnaire is a valuable tool for identifying patients with sensitive skin and gaining a comprehensive understanding of their skin sensitivity. The skin characteristics of two groups were compared using a more suitable classification method. RESULTS: Individuals diagnosed with sensitive skin typically have skin tones classified as Types I, II and III, with Type I being the most common in sensitive skin cases. The sensitive group exhibited higher levels of transepidermal water loss, lighter skin tone, lower yellowness, increased glossiness, higher haemoglobin content, more acne, fewer blackheads, and fewer pores. Among them, Type I skin is characterized by lower elasticity, increased oiliness, higher hydration levels and fewer visible pores. Type II skin is characterized by lower hydration levels, higher oiliness and increased redness. Type III exhibits more pores, decreased oiliness and enhanced elasticity. Foundations No. 2 and No. 3 are fairer than foundations No. 1 and No. 4. In the self-assessment, Type I and Type II subjects preferred No. 3, while Type III subjects preferred No. 1 and No. 4 because they matched their skin tone. The results of the software evaluation showed that popular aesthetics preferred Type I and Type II to use No. 2, and Type III to use No. 2 and No. 3, as they resulted in a fairer complexion. CONCLUSION: Sensitive skin of different skin tone types confronts different skin problems. The findings also highlight the public's inclination towards lighter foundation shades, despite the common practice of selecting shades that harmonize with one's inherent skin tone.


OBJECTIF: Nous avons mené une étude sur des femmes à la peau sensible de différentes carnations afin d'analyser les caractéristiques de leur peau et leurs préférences en matière de teintes de fond de teint. MÉTHODES: Les volontaires ont été classées en fonction de leur angle typologique individuel et leurs préférences ont été évaluées à l'aide d'une auto­perception et d'une évaluation esthétique de masse basée sur un logiciel. Le questionnaire de Baumann est un outil précieux pour identifier les patients à la peau sensible et obtenir une compréhension globale de leur sensibilité cutanée. Les caractéristiques cutanées de deux groupes ont été comparées à l'aide d'une méthode de classification plus appropriée. RÉSULTATS: Les personnes chez qui l'on a diagnostiqué une peau sensible ont généralement des teintes de peau classées en types I, II et III, le type I étant le plus courant dans les cas de peau sensible. Le groupe sensible présente des niveaux plus élevés de perte d'eau transépidermique, un teint plus clair, une couleur moins jaune, une brillance accrue, une teneur en hémoglobine plus élevée, plus d'acné, moins de points noirs et moins de pores. Parmi eux, la peau de type I se caractérise par une élasticité plus faible, un taux de sébum plus élevé, des niveaux d'hydratation plus élevés et moins de pores visibles. La peau de type II se caractérise par des niveaux d'hydratation plus faibles, un taux de sébum plus élevé et des rougeurs plus importantes. Le type III présente plus de pores, une diminution de l'aspect gras et une meilleure élasticité. Les fonds de teint n° 2 et n° 3 sont plus clairs que les fonds de teint n° 1 et n° 4. Lors de l'auto­évaluation, les sujets des types I et II ont préféré le fond de teint n° 3, tandis que les sujets du type III ont préféré le fond de teint n° 1 et le fond de teint n° 4 parce qu'ils correspondaient à leur carnation. Les résultats de l'évaluation du logiciel ont montré que l'esthétique populaire préférait que les sujets de type I et de type II utilisent le n° 2, et que les sujets de type III utilisent le n° 2 et le n° 3, car ils donnaient un teint plus clair. CONCLUSION: Les peaux sensibles de différents types de carnation sont confrontées à des problèmes cutanés différents. Les résultats mettent également en évidence le penchant du public pour les teintes de fond de teint plus claires, malgré la pratique courante consistant à choisir des teintes qui s'harmonisent avec le teint inhérent à la peau.

6.
Angew Chem Int Ed Engl ; : e202409255, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984684

RESUMEN

With the large-scale application of lithium-ion batteries (LIBs), a huge amount of spent LIBs will be generated each year and how to realize their recycling and reuse in a clean and effective way poses a challenge to the society. In this work, using the electrolyte of spent LIBs as solvent, we in-situ fluorinate the conductive three-dimensional porous copper foam by a facile solvent-thermal method and then coating it with a cross-linked sodium alginate (SA) layer. Benefiting from the solid-electrolyte interphase (SEI) that accommodating the volume change of internal CuF2 core and SA layer that inhibiting the dissolution of CuF2, the synthesized CuF2@void@SEI@SA cathode with a pomegranate-like structure (yolk-shell) exhibits a large reversible capacity of ~535 mAh g-1 at 0.05 A g-1 and superb cycling stability. This work conforms to the development concept of green environmental protection and comprehensively realizes the unity of environmental, social and economic benefits.

7.
Chemistry ; 29(11): e202203419, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36396601

RESUMEN

To realize the direct and full use of the widely distributed solar energy, developing novel materials with superb photothermal conversion capability is essential. Although heteropoly blue has intrinsic outstanding solar absorption and photothermal conversion properties, its spectral absorption in the infrared region is weak. Here, composites of heteropoly blue and carbon nanotubes (HPB/CNTs) are synthesized depending on electrostatic interactions by facile microwave sonication and freeze-drying. The doped CNTs can dramatically improve the spectral absorption performance of HPB ontology in the infrared region. As a result, the light absorption of the optimized HPB/CNTs (20 %) reaches more than 95 % in the range of 200-2400 nm, showing promising prospects as high-performance photothermal conversion material in the applications of solar desalination and wastewater treatment.

8.
Virus Genes ; 59(2): 188-194, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36229721

RESUMEN

me53, a highly conserved immediate early gene in all Lepidoptera baculoviruses, has been of great interest in recent years. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is in the family Baculoviridae, genus Alphabaculovirus. The me53 gene of AcMNPV has been sequenced, and it was transcribed late after infection. The structure of ME53 protein and its roles in the infection of host cells were summarized and discussed, including that (1) the production of Budding Virus (BV); (2) nucleocapsid formation in the host nuclei; (3) ME53 forms a lesion on the cell membrane of AcMNPV-infected cells and co-locates with GP64 and the primary capsid protein VP39; (4) the nuclear translocation signal sequence of ME53 is essential for optimal baculovirus production. In this review, we focus on the emerging roles of ME53 by discussing novel mechanisms identified to mediate or interact by ME53, which provides an important reference for the effective transformation, utilization and improvement of the anti-insect activity of AcMNPV.


Asunto(s)
Nucleopoliedrovirus , Animales , Nucleopoliedrovirus/genética , Spodoptera/metabolismo , Línea Celular , Proteínas de la Cápside/metabolismo
9.
Methods ; 202: 70-77, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33992772

RESUMEN

With the advance of deep learning technology, convolutional neural network (CNN) has been wildly used and achieved the state-of-the-art performances in the area of medical image classification. However, most existing medical image classification methods conduct their experiments on only one public dataset. When applying a well-trained model to a different dataset selected from different sources, the model usually shows large performance degradation and needs to be fine-tuned before it can be applied to the new dataset. The goal of this work is trying to solve the cross-domain image classification problem without using data from target domain. In this work, we designed a self-supervised plug-and-play feature-standardization-block (FSB) which consisting of image normalization (INB), contrast enhancement (CEB) and boundary detection blocks (BDB), to extract cross-domain robust feature maps for deep learning framework, and applied the network for chest x-ray-based lung diseases classification. Three classic deep networks, i.e. VGG, Xception and DenseNet and four chest x-ray lung diseases datasets were employed for evaluating the performance. The experimental result showed that when employing feature-standardization-block, all three networks showed better domain adaption performance. The image normalization, contrast enhancement and boundary detection blocks achieved in average 2%, 2% and 5% accuracy improvement, respectively. By combining all three blocks, feature-standardization-block achieved in average 6% accuracy improvement.


Asunto(s)
Aprendizaje Profundo , Enfermedades Pulmonares , Humanos , Pulmón , Enfermedades Pulmonares/diagnóstico por imagen , Redes Neurales de la Computación , Estándares de Referencia
10.
Angew Chem Int Ed Engl ; 62(45): e202312020, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37728941

RESUMEN

Single-ion conductive electrolytes can largely eliminate electrode polarization, reduce the proportion of anion migration and inhibit side reactions in batteries. However, they usually suffer from insufficient ion conductivity due to the strong interaction between cations and cationic receptors. Here we report an ultrafast light-responsive covalent organic frameworks (COF) with sulfonic acid groups modification as the acrylamide polymerization initiator. Benefiting from the reduced electrostatic interaction between Zn2+ and sulfonic acid groups through solvation effects, the as-prepared COF-based hydrogel electrolyte (TCOF-S-Gel) receives an ion conductivity of up to 27.2 mS/cm and Zn2+ transference number of up to 0.89. In addition, sufficient hydrogen bonds endow the single-ion conductive TCOF-S-Gel electrolyte to have good water retention and superb mechanical properties. The assembled Zn||TCOF-S-Gel||MnO2 full zinc-ion battery exhibits high discharge capacity (248 mAh/g at 1C), excellent rate capability (90 mAh/g at 10C) and superior cycling performance. These enviable results enlist the instantaneously photocured TCOF-S-Gel electrolyte to be qualified to large-scaled flexible high-performance quasi-solid-state zinc-ion batteries.

11.
Angew Chem Int Ed Engl ; 62(30): e202306193, 2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37269225

RESUMEN

Polyoxometalates (POMs) are considered as promising catalysts with unique redox activity at the molecular level for energy storage. However, eco-friendly iron-oxo clusters with special metal coordination structures have rarely been reported for Li-ion storage. Herein, three novel redox-active tetranuclear iron-oxo clusters have been synthesized using the solvothermal method with different ratios of Fe3+ and SO4 2- . Further, they can serve as anode materials for Li-ion batteries. Among them, cluster H6 [Fe4 O2 (H2 O)2 (SO4 )7 ]⋅H2 O, the stable structure extended by SO4 2- with a unique 1D pore, displays a specific discharge capacity of 1784 mAh g-1 at 0.2 C and good cycle performance (at 0.2 C and 4 C). This is the first instance of inorganic iron-oxo clusters being used for Li-ion storage. Our findings present a new molecular model system with a well-defined structure and offer new design concepts for the practical application of studying the multi-electron redox activity of iron-oxo clusters.

12.
J Med Internet Res ; 24(6): e36809, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35763324

RESUMEN

BACKGROUND: Emerging studies have shown the effectiveness of mobile health (mHealth) interventions in reducing depressive symptoms among people living with HIV. Most of these studies included only short-term follow-up, with limited data on long-term effects. OBJECTIVE: The purpose of this study is to assess the long-term effects of a randomized controlled trial called Run4Love on depressive symptoms among people living with HIV at 1-year and 3-year follow-ups. METHODS: A total of 300 people living with HIV with depressive symptoms were recruited and randomized to an intervention or a control group in Guangzhou, China, from September 2017 to January 2018. The intervention group received a 3-month Run4Love program, including adapted evidence-based cognitive behavioral stress management courses and exercise promotion via WeChat (Tencent), a popular social media app. The control group received usual care and a brochure on nutrition. The primary outcome was reduction in depressive symptoms, measured using the Center for Epidemiological Studies-Depression (CES-D) scale. Data used in this study were collected at baseline and at the 1-year and 3-year follow-ups. Generalized estimating equations were used to examine the group differences at 1-year and 3-year follow-ups. RESULTS: Approximately half of the participants completed the assessment at 1-year (149/300, 49.7%) and 3-year (177/300, 59%) follow-ups. At 1-year follow-up, participants in the intervention group reported significant reduction in depressive symptoms compared with the control group (CES-D: from 23.9 to 18.1 in the intervention group vs from 24.3 to 23.3 in the control group; mean -4.79, SD 13.56; 95% CI -7.78 to -1.81; P=.002). At 3-year follow-up, between-group difference in CES-D remained statistically significant (from 23.9 to 20.5 in the intervention group vs from 24.3 to 24.4 in the control group; mean -3.63, SD 13.35; 95% CI -6.71 to -0.54; P=.02). No adverse events were reported during the 3-year follow-up period. CONCLUSIONS: The mHealth intervention, Run4Love, significantly reduced depressive symptoms among people living with HIV, and the intervention effects were sustained at 1-year and 3-year follow-ups. Further research is needed to explore the mechanisms of the long-term effects of mHealth interventions such as Run4Love and to implement these effective interventions among people living with HIV. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-IPR-17012606. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/10274.


Asunto(s)
Infecciones por VIH , Medios de Comunicación Sociales , Telemedicina , Depresión/psicología , Depresión/terapia , Estudios de Seguimiento , Infecciones por VIH/complicaciones , Infecciones por VIH/psicología , Infecciones por VIH/terapia , Humanos
13.
Sensors (Basel) ; 22(23)2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36502143

RESUMEN

Odonate is a new, intelligent three-dimensional gait analysis system based on binocular depth cameras and neural networks, but its accuracy has not been validated. Twenty-six healthy subjects and sixteen patients with post-stroke were recruited to investigate the validity and reliability of Odonate for gait analysis and examine its ability to discriminate abnormal gait patterns. The repeatability tests of different raters and different days showed great consistency. Compared with the results measured by Vicon, gait velocity, cadence, step length, cycle time, and sagittal hip and knee joint angles measured by Odonate showed high consistency, while the consistency of the gait phase division and the sagittal ankle joint angle was slightly lower. In addition, the stages with statistical differences between healthy subjects and patients during a gait cycle measured by the two systems were consistent. In conclusion, Odonate has excellent inter/intra-rater reliability, and has strong validity in measuring some spatiotemporal parameters and the sagittal joint angles, except the gait phase division and the ankle joint angle. Odonate is comparable to Vicon in its ability to identify abnormal gait patterns in patients with post-stroke. Therefore, Odonate has the potential to provide accessible and objective measurements for clinical gait assessment.


Asunto(s)
Análisis de la Marcha , Accidente Cerebrovascular , Humanos , Fenómenos Biomecánicos , Reproducibilidad de los Resultados , Marcha , Articulación de la Rodilla
14.
Entropy (Basel) ; 24(12)2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36554114

RESUMEN

An echo state network (ESN) is an efficient recurrent neural network (RNN) that is widely used in time series prediction tasks due to its simplicity and low training cost. However, the "black-box" nature of reservoirs hinders the development of ESN. Although a large number of studies have concentrated on reservoir interpretability, the perspective of reservoir modeling is relatively single, and the relationship between reservoir richness and reservoir projection capacity has not been effectively established. To tackle this problem, a novel reservoir interpretability framework based on permutation entropy (PE) theory is proposed in this paper. In structure, this framework consists of reservoir state extraction, PE modeling, and PE analysis. Based on these, the instantaneous reservoir states and neuronal time-varying states are extracted, which are followed by phase space reconstruction, sorting, and entropy calculation. Firstly, the obtained instantaneous state entropy (ISE) and global state entropy (GSE) can measure reservoir richness for interpreting good reservoir projection capacity. On the other hand, the multiscale complexity-entropy analysis of global and neuron-level reservoir states is performed to reveal more detailed dynamics. Finally, the relationships between ESN performance and reservoir dynamic are investigated via Pearson correlation, considering different prediction steps and time scales. Experimental evaluations on several benchmarks and real-world datasets demonstrate the effectiveness and superiority of the proposed reservoir interpretability framework.

15.
J Immunol ; 203(6): 1436-1446, 2019 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-31420466

RESUMEN

Therapeutic manipulation of regulatory T cells (Tregs) has been regarded as a promising approach for the treatment of immune disorders. However, a better understanding of the immunomodulatory mechanisms of Tregs and new safe and effective methods to improve the therapeutic effects of Tregs are highly desired. In this study, we have identified the key roles of a cAMP-adenosine positive feedback loop in the immunomodulatory function of Tregs. Adult male C57BL/6J mice were used for an experimental autoimmune uveitis (EAU) model, Tregs, and uveitogenic T cells (UTs). In established EAU, induced Tregs (iTregs) administration alleviated the inflammatory response. In vitro, iTregs inhibited UTs proliferation and inflammatory cytokine production. Mechanistically, cAMP is partially responsible for iTreg-mediated inhibition on UTs. Importantly, intracellular cAMP regulates CD39 expression and CD39-dependent adenosine production in iTregs, and cAMP directly participates in iTreg-derived adenosine production by a CD39 signaling-independent extracellular cAMP-adenosine pathway. Moreover, extracellular adenosine increases the intracellular cAMP level in Tregs. More importantly, increasing the cAMP level in iTregs before transfer improves their therapeutic efficacy in established EAU. Notably, the cAMP-adenosine loop exists in both iTregs and naturally occurring Tregs. These findings provide new insights into the immunosuppressive mechanisms of Tregs and suggest a new strategy for improving the therapeutic efficacy of Tregs in established autoimmune disease.


Asunto(s)
Adenosina/inmunología , AMP Cíclico/inmunología , Linfocitos T Reguladores/inmunología , Animales , Antígenos CD/inmunología , Apirasa/inmunología , Enfermedades Autoinmunes/inmunología , Femenino , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Uveítis/inmunología
16.
J Hum Genet ; 65(6): 497-511, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32152365

RESUMEN

In the 20th century, our familiar structure of DNA was the double helix. Due to technical limitations, we do not have a good way to understand the finer structure of the genome, let alone its transcriptional regulation. Until the advent of 3C technologies, we were no longer blind to this one. Three-dimensional (3D) genomics is a new subject, which mainly studies the 3D structure and transcriptional regulation of eukaryotic genomes. Now, this field mainly has Hi-C series and CHIA-PET series technologies. Through 3D genomics, we can understand the basic structure of DNA, understand the growth and development of organisms and the occurrence of diseases, so as to promote human medical and health undertakings. The review introduces the main research techniques of 3D genomics and their characteristics, the latest development of 3D genome structure, the relationship between diseases and 3D genome structure, the applications of 3D genome in precision medicine, and the development of the 4D nucleome project.


Asunto(s)
Cromatina/genética , ADN/genética , Genoma Humano/genética , Imagenología Tridimensional , Cromatina/ultraestructura , Biología Computacional , ADN/ultraestructura , Genómica , Humanos , Medicina de Precisión
17.
Int Heart J ; 60(2): 400-410, 2019 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-30799380

RESUMEN

Flexible, in vivo maneuverable electrophysiology mapping techniques are not available in rat models. A novel cardiac stereotactic electrophysiology epicardial mapping system (CREAMS) allows for various measurements, including: (1) recording unipolar electrograms at multiple sites; (2) positioning of mapped sites and precision testing (Distance between the two "centers" = 297 ± 54 µm, n = 15); (3) evaluation of electrophysiology in an in vivo Sprague-Dawley rat model with high-frequency stimulation (HFS)-induced Atrial fibrillation (AF) at high right atrium (HRA) sites. We found that of the right atrium dispersion of effective refractory period (P < 0.05) and the window of vulnerability (P < 0.01) were significantly increased (P < 0.05) after HRA HFS. CREAMS has the potential for convenient electrophysiology assessment in a rat AF model through stereo-positioning, and flexible operating manipulation.


Asunto(s)
Fibrilación Atrial , Técnicas Electrofisiológicas Cardíacas/métodos , Atrios Cardíacos/fisiopatología , Sistema de Conducción Cardíaco , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Electrofisiología Cardíaca/métodos , Fenómenos Electrofisiológicos , Femenino , Sistema de Conducción Cardíaco/diagnóstico por imagen , Sistema de Conducción Cardíaco/fisiología , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley
18.
Zhonghua Nan Ke Xue ; 25(3): 248-256, 2019 Mar.
Artículo en Zh | MEDLINE | ID: mdl-32216244

RESUMEN

OBJECTIVE: To compare the differentially expressed proteins in mice with kidney-yang deficiency and those with kidney-yin deficiency induced by hydrocortisone, and explore the similar and different material bases of male infertility caused by the two types of kidney deficiency. METHODS: Thirty Kunming mice were equally randomized into a normal control, a kidney-yang deficiency and a kidney-yin deficiency group. The animals of the normal control group were injected intraperitoneally with normal saline at 0.2 ml qd for 7 days, while those of the latter two groups with hydrocortisone at 25 mg/kg/d for 10 days and 50 mg/kg/d for 7 days, respectively, for establishment of kidney-yang deficiency and kidney-yin deficiency models. Then the pathological changes in the testicular tissue of the mice were observed by HE staining and the differentially expressed proteins were compared among different groups using isobaric tags for relative and absolute quantitation (iTRAQ) and the bioinformatics method. RESULTS: Sod1 was found to be a reproduction-related node protein differentially expressed in the testis tissues of the two types of kidney-deficiency mice, more highly expressed in the kidney-yin than in the kidney-yang deficiency group (P < 0.05). Five reproduction-associated node proteins were co-expressed in the testes of the two groups of kidney-deficiency mice, with significantly up-regulated expression of Rps28 and down-regulated expressions of Rpl11, Rplp2, Svs2 and Svs3a (P < 0.01). CONCLUSIONS: Sod1 may be one of the key material bases for the differentiation of male infertility caused by kidney-yang deficiency from that induced by kidney-yin deficiency, while Rps28, Rpl11, Rplp2, Svs2 and Svs3a may be the common material bases of male infertility caused by the two types of kidney deficiency.


Asunto(s)
Riñón/fisiopatología , Proteínas de Secreción de la Vesícula Seminal/metabolismo , Testículo/metabolismo , Deficiencia Yang , Deficiencia Yin , Animales , Hidrocortisona , Riñón/metabolismo , Masculino , Medicina Tradicional China , Ratones , Distribución Aleatoria , Reproducción , Superóxido Dismutasa-1 , Testículo/patología
19.
Arch Toxicol ; 92(4): 1407-1419, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29264619

RESUMEN

Lanthanum (La) can impair learning memory and induce behavioral abnormalities in animals. However, the mechanism underlying these adverse effects of La is still elusive. It has been demonstrated that lactate derived from astrocytes is the major energy source for neurons during long-term memory (LTM) formation and the deficiency of lactate supply can result in LTM damage. However, little work has been done with respect to the impact of La on the lactate production in astrocytes and astrocyte-neuron lactate transport (ANLT). Herein, experiments were undertaken to explore if there was such an adverse effect of La. Primary culture rat cortical astrocytes and primary co-culture rat cortical astrocyte-neuron were treated with (0.125, 0.25 and 0.5 mM) lanthanum chloride (LaCl3) for 24 h. The results showed that LaCl3 treatment significantly downregulated the mRNA and protein expression of glucose transporter 1 (GLUT1), glycogen synthase (GS), glycogen phosphorylase (GP), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 1, 2 and 4 (MCT 1 2 and 4); upregulated the mRNA and protein expression of lactate dehydrogenase B (LDHB); and decreased the glycogen level, total LDH and GP activity, GS/p-GS ratio and lactate contents. Moreover, rolipram (20, 40 µM) or forskolin (20, 40 µM) could increase the lactate content by upregulating GP expression and the GS/p-GS ratio, as well as antagonize the effects of La. These results suggested that La-induced learning-memory damage was probably related to its suppression of lactate production in astrocytes and ANLT. This study provides some novel clues for clarifying the mechanism underlying the neurotoxicity of La.


Asunto(s)
Astrocitos/metabolismo , Glucógeno/metabolismo , Ácido Láctico/metabolismo , Lantano/toxicidad , Animales , Transporte Biológico/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Técnicas de Cocultivo , Lantano/administración & dosificación , Memoria a Largo Plazo/efectos de los fármacos , Cultivo Primario de Células , Ratas
20.
BMC Urol ; 18(1): 17, 2018 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-29514670

RESUMEN

BACKGROUND: Due to the lack of strong evidence to identify the relationship between antihypertensive drugs use and the risk of prostate cancer, it was needed to do a systematic review to go into the subject. METHODS: We systematically searched PubMed, Web of Science and Embase to identify studies published, through May 2015. Two evaluators independently reviewed and selected articles involving the subject. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of the studies. All extracted results to evaluate the relationship between antihypertensive drugs usage and prostate cancer risk were pool-analysed using Stata 12.0 software. RESULTS: A total of 12 cohort and 9 case-control studies were ultimately included in our review. Most of the studies were evaluated to be of high quality. There was no significant relationship between angiotensin converting enzyme inhibitors (ACEI) usage and the risk of prostate cancer (RR 1.07, 95% CI 0.96-1.20), according to the total pool-analysed. Use of angiotensin receptor blocker (ARB) was not associated with the risk of prostate cancer (RR 1.09, 95% CI 0.97-1.21), while use of CCB may well increase prostate cancer risk based on the total pool-analysed (RR 1.08, 95% CI 1-1.16). Moreover, subgroup analysis suggested that use of CCB clearly increased prostate cancer risk (RR 1.10, 95% CI 1.04-1.16) in terms of case-control studies. There was also no significant relationship between use of diuretic (RR 1.09, 95% CI 0.95-1.25) or antiadrenergic agents (RR 1.22, 95% CI 0.76-1.96) and prostate cancer risk. CONCLUSIONS: There is no significant relationship between the use of antihypertensive drugs (ACEI, ARB, beta-blockers and diuretics) and prostate cancer risk, but CCB may well increase prostate cancer risk, according to existing observational studies.


Asunto(s)
Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/efectos adversos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Neoplasias de la Próstata/epidemiología , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Estudios de Casos y Controles , Estudios de Cohortes , Humanos , Hipertensión/diagnóstico , Masculino , Estudios Observacionales como Asunto , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/diagnóstico , Factores de Riesgo
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