Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Anal Biochem ; 601: 113767, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32454029

RESUMO

Long noncoding RNAs (lncRNAs) play critical roles in many pathological and biological processes, such as post-transcription, cell differentiation and gene regulation. Increasingly more studies have shown that lncRNAs function through mainly interactions with specific RNA binding proteins (RBPs). However, experimental identification of potential lncRNA-protein interactions is costly and time-consuming. In this work, we propose a novel convolutional neural network-based method with the copy-padding trick (named LPI-CNNCP) to predict lncRNA-protein interactions. The copy-padding trick of the LPI-CNNCP convert the protein/RNA sequences with variable-length into the fixed-length sequences, thus enabling the construction of the CNN model. A high-order one-hot encoding is also applied to transform the protein/RNA sequences into image-like inputs for capturing the dependencies among amino acids (or nucleotides). In the end, these encoded protein/RNA sequences are feed into a CNN to predict the lncRNA-protein interactions. Compared with other state-of-the-art methods in 10-fold cross-validation (10CV) test, LPI-CNNCP shows the best performance. Results in the independent test demonstrate that our LPI-CNNCP can effectively predict the potential lncRNA-protein interactions. We also compared the copy-padding trick with two other existing tricks (i.e., zero-padding and cropping), and the results show that our copy-padding rick outperforms the zero-padding and cropping tricks on predicting lncRNA-protein interactions. The source code of LPI-CNNCP and the datasets used in this work are available at https://github.com/NWPU-903PR/LPI-CNNCP for academic users.


Assuntos
Redes Neurais de Computação , RNA Longo não Codificante/química , Proteínas de Ligação a RNA/química , Sequência de Aminoácidos , Humanos
2.
Appl Microbiol Biotechnol ; 104(9): 3807-3823, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32125478

RESUMO

Panax ginseng is a traditional Chinese medicine with significant pharmaceutical effects and broad application. Rare ginsenosides with high antitumor activities can be generated via oriented modification of their glycosyl moiety. For this purpose, suitable microorganisms and their enzymatic systems can be used. In this review, we address several issues associated with these systems. Under aerobic conditions, fungus biotransformation provides an efficient and inexpensive biotransformation process that can be easily scaled up. Considering the profound use of probiotics, wild strains generally recognized as safe have shown a potential through classical fermentation in food manufacturers of deglycosylated ginsenosides. Commonly applied recombinant enzymes from E. coli, especially recombinant hyperthermophilic enzymes, showed efficient conversion in biomedical or pharmaceutical industries. In this review, key genes dedicated to the production of ginsenosides (especially in Saccharomyces cerevisiae) are highlighted in relation to the large-scale production of ginsenosides. We also evaluate biocatalytic strategies that are aimed to improve product specificity and biocatalytic efficiency with industrial applications. Perspectives of protein engineering and solvent engineering in the development and large-scale preparation of ginsenosides in anticancer drugs, food and health care products are explored. KEY POINTS : • Modification of ginsenosides with food/engineered microorganisms is summarized. • Optimization of cell factories by protein engineering remains challenging. • Solvent engineering offers an attractive potential alternative.


Assuntos
Biocatálise , Ginsenosídeos/biossíntese , Glicosídeo Hidrolases/metabolismo , Engenharia de Proteínas/métodos , Biotransformação , Escherichia coli/metabolismo , Fermentação , Medicina Tradicional Chinesa , Panax
3.
Opt Express ; 26(25): 32532-32553, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30645419

RESUMO

We propose simultaneous measurement and reconstruction tailoring (SMaRT) for quantitative phase imaging; it is a joint optimization approach to inverse problems wherein minimizing the expected end-to-end error yields optimal design parameters for both the measurement and reconstruction processes. Using simulated and experimentally-collected data for a specific scenario, we demonstrate that optimizing the design of the two processes together reduces phase reconstruction error over past techniques that consider these two design problems separately. Our results suggest at times surprising design principles, and our approach can potentially inspire improved solution methods for other inverse problems in optics as well as the natural sciences.

4.
Zhonghua Nan Ke Xue ; 24(11): 999-1004, 2018 Nov.
Artigo em Zh | MEDLINE | ID: mdl-32212474

RESUMO

OBJECTIVE: To explore the correlation of Mycoplasma genitalium (MG) infection with male infertility. METHODS: Totally, 27 314 males with infertility and 200 fertile sperm donors underwent MG and routine seminal examinations. The infertile men were divided into azoospermia, oligozoospermia, asthenozoospermia, oligoasthenospermia, and normal semen quality groups based on the results of seminal examination, the 27 286 of them with age data into eight age groups (<21, 21-25, 26-30, 31-35, 36-40, 41-45, 46-50 and ≥51 years old), and the 9 058 with definite diagnosis into primary and secondary infertility groups. Fifty-six cases of MG infection among the infertile males were treated with antibiotics for 2 weeks and examined for changes of the semen parameters. RESULTS: Compared with the normal controls, the oligozoospermia patients showed a significantly higher rate of MG infection (0.50% vs 3.62%, P = 0.024), the highest in the ≥51 yr group (3.68%, P = 0.021), followed by the 21-25 yr group (3.00%, P = 0.048), and so did the infertile males (3.64%, P = 0.011), the men with primary infertility (3.73%, P = 0.010) and those with secondary infertility (3.57%, P = 0.015). MG infection was found to be associated with oligozoospermia (OR = 7.471, 95% CI: 1.001-55.784), primary infertility (OR = 7.704, 95% CI: 1.073-55.309) and secondary infertility (OR = 7.362, 95% CI: 1.026-52.837) but not with the age of the patients. Both sperm concentration and sperm count were significantly lower in the infected men before treatment than in the non-infection group after treatment (P < 0.05). CONCLUSIONS: MG infection is related to male infertility and reduces the semen volume and sperm concentration, but does not affect sperm motility.


Assuntos
Infertilidade Masculina , Infecções por Mycoplasma , Mycoplasma genitalium , Adulto , Humanos , Infertilidade Masculina/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycoplasma/complicações , Mycoplasma genitalium/patogenicidade , Sêmen , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Adulto Jovem
5.
Appl Opt ; 56(22): 6214-6221, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29047816

RESUMO

We propose a multiple-3D-object decryption scheme based on one interference using two beams that are from two different phase-only functions. It takes advantage of off-axis digital holography to extract the optical fields of multiple 3D objects, and respectively utilize single different decryption keys to decrypt multiple 3D objects in the decryption procedure. The advantages of the proposed scheme include the following: each 3D object can be decrypted discretionarily without decrypting a series of other objects earlier; no iterative algorithm is involved; and the decrypted image of each object can be successfully clearly distinguished. The feasibility of the proposed scheme is verified by the optical holograms of real 3D objects.

6.
Hepatology ; 61(1): 303-14, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25145286

RESUMO

UNLABELLED: Macrophages play multidimensional roles in hepatic fibrosis, but their control has not been fully understood. The Notch pathway mediated by recombination signal binding protein Jκ (RBP-J), the transcription factor transactivated by signals from four mammalian Notch receptors, is implicated in macrophage activation and plasticity. In this study, by using mouse hepatic fibrosis models, we show that myeloid-specific disruption of RBP-J resulted in attenuated fibrosis. The activation of hepatic stellate cells and production of profibrotic factors including platelet-derived growth factor (PDGF)-B and transforming growth factor beta1 (TGF-ß1) reduced significantly in myeloid-specific RBP-J deficient mice. The infiltration of inflammatory cells and production of proinflammatory factors were reduced in liver of myeloid-specific RBP-J-deficient mice during fibrosis. In RBP-J-deficient macrophages, the nuclear factor kappa B (NF-κB) activation was remarkably attenuated as compared with the control. This could be attributed to the up-regulation of cylindromatosis (CYLD), a negative regulator of NF-κB, in Notch signal-compromised macrophages, because the knockdown of CYLD in RBP-J-deficient macrophages or overexpression of p65 in RBP-J knockdown cells both restored NF-κB activation and the production of proinflammatory and/or profibrotic factors by macrophages. In human hepatic fibrosis biopsies, stronger Notch activation is correlated with more severe fibrosis, which is accompanied by a lower level of CYLD but irrespective of etiological reasons. CONCLUSION: RBP-J-mediated Notch signaling is required for macrophages to promote hepatic fibrosis by up-regulation of NF-κB activation through CYLD.


Assuntos
Cisteína Endopeptidases/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Cirrose Hepática/imunologia , Macrófagos/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Células Cultivadas , Enzima Desubiquitinante CYLD , Células Estreladas do Fígado/fisiologia , Hepatite/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Regulação para Cima
7.
Tumour Biol ; 37(7): 9423-31, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26781874

RESUMO

The purpose of this study was to determine the expression of growth differentiation factor 15 (GDF15) and explore its clinical significance in epithelial ovarian cancer (EOC) patients. The expression of GDF15 in EOC tissues and serum samples was evaluated using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. The association of GDF15 expression with clinicopathologic parameters was analyzed. Survival time was assessed using the Kaplan-Meier technique and Cox regression model. Both in EOC tissues and serum, high GDF15 levels were obviously related with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, ascites, and chemoresistance. Kaplan-Meier analysis indicated that EOC patients with high GDF15 expression showed poorer progression-free survival (PFS) and overall survival (OS). Multivariate analysis demonstrated that GDF15 expression was an independent predictor of PFS in EOC patients. Our study shows that elevated GDF15 expression was associated with poor prognosis in EOC patients. We suggest that GDF15 is a novel biomarker for the early detection of EOC, prediction of the response to chemotherapy, and screening for recurrence in EOC patients.


Assuntos
Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Fator 15 de Diferenciação de Crescimento/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia , Prognóstico , Taxa de Sobrevida
8.
Appl Opt ; 55(15): 4052-9, 2016 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-27411131

RESUMO

We propose a multiple-3D-object secure information system for encrypting multiple three-dimensional (3D) objects based on the three-step phase shifting method. During the decryption procedure, five phase functions (PFs) are decreased to three PFs, in comparison with our previous method, which implies that one cross beam splitter is utilized to implement the single decryption interference. Moreover, the advantages of the proposed scheme also include: each 3D object can be decrypted discretionarily without decrypting a series of other objects earlier; the quality of the decrypted slice image of each object is high according to the correlation coefficient values, none of which is lower than 0.95; no iterative algorithm is involved. The feasibility of the proposed scheme is demonstrated by computer simulation results.

9.
Appl Opt ; 54(11): 3273-9, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25967313

RESUMO

We propose a multiple-image encryption (MIE) scheme based on triple interferences for flexibly decrypting high-quality images. Each image is discretionarily deciphered without decrypting a series of other images earlier. Since it does not involve any cascaded encryption orders, the image can be decrypted flexibly by using the novel method. Computer simulation demonstrated that the proposed method's running time is less than approximately 1/4 that of the previous similar MIE method. Moreover, the decrypted image is perfectly correlated with the original image, and due to many phase functions serving as decryption keys, this method is more secure and robust.

10.
J Huazhong Univ Sci Technolog Med Sci ; 34(3): 348-353, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24939297

RESUMO

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.


Assuntos
Doença Hepática Terminal/virologia , Hepatite Viral Animal/virologia , Falência Hepática Aguda/virologia , Vírus da Hepatite Murina/fisiologia , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Adulto , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Western Blotting , Doença Hepática Terminal/genética , Doença Hepática Terminal/patologia , Feminino , Expressão Gênica , Hepatite Viral Animal/genética , Hepatite Viral Animal/patologia , Interações Hospedeiro-Patógeno , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Falência Hepática Aguda/genética , Falência Hepática Aguda/patologia , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/sangue , Proteínas Supressoras da Sinalização de Citocina/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
11.
Asian J Androl ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831691

RESUMO

ABSTARCT: Necrozoospermia is a poorly documented condition with a low incidence, and its definition and clinical significance are unclear. Herein, we provide a reference range for necrozoospermia and discuss its possible etiology and impact on male fertility and assisted reproductive outcomes. We extracted relevant information from 650 Chinese male partners of infertile couples and statistically analyzed sperm vitality. Necrozoospermia was present in 3.4% (22/650) of our study population, and the lower cut-off value for sperm vitality was 75.3%. We compared two methods for assessing sperm vitality (eosin-nigrosin head staining and hypo-osmotic swelling test [HOST]), for which the percentage in the eosin-nigrosin group (mean ± standard deviation [s.d.]: 77.5% ± 10.5%) was significantly higher than that in the HOST group (mean ± s.d.: 58.1% ± 6.7% [5-10 min after incubation] and 55.6% ± 8.2% [25-30 min after incubation]; both P < 0.001). The incidence of necrozoospermia increased with age (odds ratio [OR] = 1.116, 95% confidence interval [CI]: 1.048-1.189, P = 0.001), while the percentage of normal sperm morphology and DNA fragmentation index (DFI) were significantly associated with necrozoospermia, with ORs of 0.691 (95% CI: 0.511-0.935, P = 0.017) and 1.281 (95% CI: 1.180-1.390, P < 0.001), respectively. In the following 6 months, we recruited 166 patients in the nonnecrozoospermia group and 87 patients in the necrozoospermia group to compare intracytoplasmic sperm injection (ICSI) and pregnancy outcomes between the two groups. The necrozoospermia group had a significantly lower normal fertilization rate (74.7% vs 78.2%, P = 0.041; OR = 0.822; 95% CI: 0.682-0.992) than that in the nonnecrozoospermia group. This study presents substantial information on necrozoospermia to establish comprehensive and applicable reference values for sperm vitality for spontaneous conception and artificially assisted reproductive management.

12.
Fitoterapia ; 169: 105600, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37419421

RESUMO

Arrhythmia is one of the commonly heart diseases with observed abnormal heart-beat rhythm that caused by the obstacles of cardiac activity and conduction. The arrhythmic pathogenesis is complex and capricious and related with other cardiovascular diseases that may lead to heart failure and sudden death. In particular, calcium overload is recognized as the main reason causing arrhythmia through inducing apoptosis in cardiomyocytes. Moreover, calcium channel blockers have been widely used as the routine drugs for the treatment of arrhythmia, but the different arrhythmic complications and adverse effects limit their further applications and demand new drug discovery. Natural products have always been the rich minerals for the development of new drugs that could be employed as the versatile player for the discovery of safe and effective anti-arrhythmia drugs with new mechanisms. In this review, we summarized natural products with the activity against calcium signaling and the relevant mechanism of actions. We are expected to provide an inspiration for the pharmaceutical chemists to develop more potent calcium channel blockers for the treatment of arrhythmia.


Assuntos
Produtos Biológicos , Bloqueadores dos Canais de Cálcio , Humanos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Produtos Biológicos/farmacologia , Estrutura Molecular , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/induzido quimicamente , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Cálcio
13.
World J Hepatol ; 15(3): 386-392, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37034232

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD comprises a continuum of liver abnormalities from nonalcoholic fatty liver to nonalcoholic steatohepatitis, and can even lead to cirrhosis and liver cancer. However, a well-established treatment for NAFLD has yet to be identified. Exosomes have become an ideal drug delivery tool because of their high transmissibility, low immunogenicity, easy accessibility and targeting. Exosomes with specific modifications, known as engineered exosomes, have the potential to treat a variety of diseases. Here, we review the treatment of NAFLD with engineered exosomes and the potential use of exosomes as biomarkers and therapeutic targets for NAFLD.

14.
World J Gastrointest Oncol ; 15(6): 988-1004, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37389116

RESUMO

BACKGROUND: Glucocorticoid modulatory element-binding protein 1 (GMEB1), which has been identified as a transcription factor, is a protein widely expressed in various tissues. Reportedly, the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers. AIM: To explore GMEB1's biological functions in hepatocellular carcinoma (HCC) and figuring out the molecular mechanism. METHODS: GMEB1 expression in HCC tissues was analyzed employing the StarBase database. Immunohistochemical staining, Western blotting and quantitative real-time PCR were conducted to examine GMEB1 and Yes-associate protein 1 (YAP1) expression in HCC cells and tissues. Cell counting kit-8 assay, Transwell assay and flow cytometry were utilized to examine HCC cell proliferation, migration, invasion and apoptosis, respectively. The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter. Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region. RESULTS: GMEB1 was up-regulated in HCC cells and tissues, and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients. GMEB1 overexpression facilitated HCC cell multiplication, migration, and invasion, and suppressed the apoptosis, whereas GMEB1 knockdown had the opposite effects. GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells. CONCLUSION: GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.

15.
Asian J Androl ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37695214

RESUMO

The clinical applications of acrosin activity are limited. We analyzed 61 578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men; to determine whether correlations exist between acrosin activity and age, sperm concentration, sperm morphology, or sperm motility; and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the clinic. The cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78 µIU per 106 sperm. There was no significant association between acrosin activity and age, sperm concentration, semen volume, total sperm count, progressive motility, or total motile spermatozoa. A weak positive correlation was found between acrosin activity and normal sperm morphology. There was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity (>24.78 µIU per 106 sperm) and the group with low acrosin activity (<24.78 µIU per 106 sperm). The group with a low IVF fertilization rate had a high index of abnormal acrosomal morphology at 21.2%, while the group with a high IVF fertilization rate had a low index of 0.2%. At an acrosin activity of <24.78 µIU per 106 sperm, in one cycle of the same patient, the fertilization rate, normal fertilization rate, and good-quality embryo rate for ICSI were significantly higher than those for IVF. Therefore, the most promising application of acrosin activity could be in the selection of ICSI over IVF for infertile male patients with complete fertilization failure or a low fertilization rate.

16.
Theranostics ; 12(4): 1816-1828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198075

RESUMO

Rationale: Macrophages play multi-dimensional roles in hepatic fibrosis. Studies have implicated Notch signaling mediated by the transcription factor RBP-J in macrophage activation and plasticity. Additionally, we have previously shown that myeloid-specific disruption of RBP-J can ameliorate hepatic fibrosis in mice. Accordingly, we next asked whether blocking Notch signaling in macrophages could serve as a therapeutic strategy to treat hepatic fibrosis. In this study, we used a combination of transcription factor decoy oligodeoxynucleotides (ODNs) and exosomes to test this possibility. Methods: Hairpin-type decoy oligodeoxynucleotides (ODNs) were designed for the transcription factor RBP-J. The effects of RBP-J decoy ODNs on Notch signaling were evaluated by western blot, quantitative RT-PCR, luciferase reporter assays, and electrophoretic mobility shift assays. ODNs were loaded into HEK293T-derived exosomes by electroporation. A hepatic fibrosis mouse model was established by the intraperitoneal injection of carbon tetrachloride or bile duct ligation. Mice with hepatic fibrosis were administered exosomes loaded with RBP-J decoy ODNs via tail vein injection. The in vivo distribution of exosomes was analyzed by fluorescence labeling and imaging. Liver histology was examined using hematoxylin and eosin, Sirius red, and Masson staining, as well as immunohistochemical staining for Col1α1 and αSMA. Results: We found that RBP-J decoy ODNs could be efficiently loaded into exosomes and inhibit the activation of Notch signaling. Furthermore, exosomes administered via the tail vein were found to be primarily taken up by hepatic macrophages in mice with liver fibrosis. Importantly, RBP-J decoy ODNs delivered by exosomes could efficiently inhibit Notch signaling in macrophages and ameliorate hepatic fibrosis in mice. Conclusions: Combined, our data showed that the infusion of exosomes loaded with RBP-J decoy ODNs represents a promising therapeutic strategy for the treatment of hepatic fibrosis.


Assuntos
Exossomos , Oligodesoxirribonucleotídeos , Animais , Células HEK293 , Humanos , Cirrose Hepática , Camundongos , Oligodesoxirribonucleotídeos/farmacologia , Transdução de Sinais
18.
Infect Dis Immun ; 1(1): 28-35, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38630115

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces. Methods: In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality. Results: The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 109/L, neutrophil count of more than 7 × 109/L, lymphocyte count of less than 0.8 × 109/L, platelet count of less than 100 × 109/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively. Conclusions: We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.

19.
PLoS One ; 15(9): e0238564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32911499

RESUMO

BACKGROUND: The prevalence of human immunodeficiency virus (HIV) varies markedly among different risk groups in China, spreading fromhigh-risk populations to the general population. Indeed, China is in a critical period of HIV/acquired immunodeficiency syndrome (AIDS) prevention and control; however, data regarding HIV testing, infection and coinfection among infertile couples are lacking. This study aimed to estimate the HIV/AIDS prevalence to identify risk factors among infertile couples in Hunan, China. METHODS: A cross-sectional hospital-based study was conducted to evaluate the prevalence of HIV/other infections (hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium (MG) infections) among 338,432 infertile individuals in Hunan, China, from 2012 to 2018. We calculated linear trends in prevalence using bivariate linear regression. RESULTS: The overall prevalence rates of HIV, chlamydia, gonorrhea, MG, syphilis, and HBV and HCV antibody positivity in this study were 0.04%, 1.73%, 0.05%, 2.60%, 2.15%, 12.01% and 0.56%, respectively. The predominant infection was HBV, followed by MG, syphilis, and chlamydia. Only 1.13% of the participants (382/338432) reported sexually transmitted disease (STD) signs and symptoms suggesting genital tract infection. However, from 2012-2018, the variation in HIV prevalence was not significant (ß = 0.000, PTREND = 0.907). The characteristics of the HIV-infected infertile population have not shifted dramatically, with women accounting for 32.56% of HIV cases in China. Overall, 87.60% of HIV-infected individuals have a relatively low education. In total, 37.98% of HIV-positive patients engage in high-risk behaviors. CONCLUSIONS: This study expands upon existing knowledge of HIV prevalence in the infertile Chinese population. However, much work is needed to achieve popularization of prevention knowledge and change concept. Routine HIV screening is urgently needed for all adults with high-risk behaviors.


Assuntos
Infecções por HIV/complicações , Infertilidade/complicações , Adulto , China/epidemiologia , Doenças Transmissíveis/complicações , Doenças Transmissíveis/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Infertilidade/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
20.
Zhonghua Nan Ke Xue ; 15(11): 974-9, 2009 Nov.
Artigo em Zh | MEDLINE | ID: mdl-20218307

RESUMO

OBJECTIVE: To investigate the relationship of the mutation of the spermatogenesis-associated gene KLHL-10 with azoospermia, oligospermia and asthenospermia. METHODS: Genomic DNA was extracted from the peripheral blood samples of 325 patients with idiopathic azoospermia (n = 11), oligozoospermia (n = 196) or asthenospermia (n = 118) and 100 fertile male controls. KLHL-10 mutations were detected for all the DNA specimens by PCR, DHPLC and sequencing techniques. RESULTS: A novel heterozygous mutation (C88 --> A) was identified in exon 1 from 1 oligospermia patient and 3 fertile male controls and another one (C424 --> A) confirmed in exon 2 from 4 fertile controls, 3 oligospermia patients and 1 asthenospermia man. Both of the mutations were synonymous, but neither missense mutation nor microdeletion of the KLHL-10 gene was found. CONCLUSION: The KLHL-10 gene is not a major contributor to azoospermia, oligospermia or asthenospermia in Chinese population. The value of this gene in the diagnosis of male infertility remains to be further investigated.


Assuntos
Astenozoospermia/genética , Azoospermia/genética , Oligospermia/genética , Proteínas/genética , Adulto , Estudos de Casos e Controles , Éxons , Frequência do Gene , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Mutação , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA