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1.
Life Sci ; : 119595, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33974931

RESUMO

AIMS: EphA4 is a member of the Eph receptor family, and expressed mainly in central nervous system (CNS), which is involved in CNS development and multiple diseases. Due to the variability in EphA4 expression, we wondered if EphA4 is expressed in other tissues, and what role does EphA4 play? MATERIALS AND METHODS: We generated an EphA4 knockout (KO) rat line with red fluorescent marker protein encoded by the mCherry cassette inserted downstream of the EphA4 promoter as a reporter. Using this system, we observed high expression of EphA4 in the heart atria and in the brain. KEY FINDINGS: EphaA4 KO rats (EphA4-/-) developed obvious atrial hypertrophy with an increased atria-to-heart weight ratio and atrial cardiomyocyte cross-sectional area at six months of age. EphA4-/- rats had reduced atrial end diastolic volume (EDV), atrial ejection fraction (EF) and left ventricular EF. They also exhibited increased amplitude of QRS complexes and QT intervals, with invisible p waves. RNA sequencing revealed that EphA4 KO altered the transcription of multiple genes involved in regulation of transcription and translation, ion binding, metabolism and cell adhesion. Deletion of EphA4 reduced IGF1 mRNA and protein expression, which is involved in cardiac remodeling. SIGNIFICANCE: Our data demonstrated that EphA4 was highly expressed in the atria and that its deletion caused atrial dysfunction. Our findings also suggested that the EphA4 KO rat could be a potential model for studies on atrial remodeling.

2.
J Exp Bot ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929512

RESUMO

Pentatricopeptide repeat (PPR) proteins are involved in the C-to-U RNA editing of organellar transcripts. Maize genome contains over 600 PPR proteins and few have been found to function in the C-to-U RNA editing in chloroplasts. Here, we report the function of ZmPPR26 in the C-to-U RNA editing and chloroplast biogenesis in maize. ZmPPR26 encodes a DYW-type PPR protein targeted to chloroplasts. The zmppr26 mutant exhibits albino seedling-lethal phenotype. Loss-function of ZmPPR26 abolishes the editing at atpA-1148 site, and decreases the editing at ndhF-62, rpl20-308, rpl2-2, rpoC2-2774, petB-668, rps8-182, and ndhA-50 sites. Over-expression of ZmPPR26 in zmppr26 restores the editing efficiency and rescues the albino seedling-lethal phenotype. Abolished editing at atpA-1148 causes a Leu to Ser change at AtpA-383 that leads to a reduction in the abundance of chloroplast ATP synthase in zmppr26. The protein accumulation and content of photosynthetic complexes are also markedly reduced in zmppr26, providing an explanation for the albino seedling-lethal phenotype. These results indicate that ZmPPR26 is required for the editing at atpA-1148 and important for the editing at the other seven sites in maize chloroplast. The editing at atpA-1148 is critical to the AtpA function, assembly of ATP synthase complex, and chloroplast biogenesis in maize.

3.
Nanotechnology ; 32(29)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33827055

RESUMO

Nanostructure modulation is effective to achieve high performance TiO2-based gas sensors. We herein report a wet-chemistry route to precipitate directly branched TiO2nanowire arrays on alumina tubes for gas sensing applications. The optimized branched TiO2nanowire array exhibits a response of 9.2 towards 100 ppm ethanol; whilst those of the pristine TiO2nanowire array and the branched TiO2nanowire powders randomly distributed are 5.1 and 3.1, respectively. The enhanced response is mainly contributed to the unique porous architecture and quasi-aligned nanostructure, which provide more active sites and also favor gas migration. Phase junctions between the backbone and the branch of the branched TiO2nanowire arrays help the resistance modulation as a result of potential barriers. The facile precipitation of quasi-aligned arrays of branched TiO2nanowires, which arein situgrown on ceramic tubes, thus provides a new economical synthetic route to TiO2-based sensors with excellent properties.

4.
Medicine (Baltimore) ; 100(15): e25447, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847650

RESUMO

BACKGROUND: High pretreatment level of D-dimer in small cell lung cancer (SCLC) is commonly encountered, but the impact of high pretreatment D-dimer level on the prognosis of SCLC patients remains undetermined. Therefore, we conducted this meta-analysis focusing specifically on the prognostic value of high pretreatment D-dimer level in SCLC patients comprehensively. METHODS: We searched systematically in PubMed, Embase, and Web of Science for relevant studies published before January 28, 2019. Outcomes including 1-year overall survival (OS), progression-free survival (PFS) rates, and hazard ratios (HRs) of OS and PFS from multivariate analysis were extracted and analyzed. RESULTS: A total of 5 cohort studies consisting of 813 SCLC patients (473 patients with high pretreatment level of D-dimer and 340 with normal level of D-dimer) were finally included for meta-analysis. We found that patients with high pretreatment level of D-dimer had significantly shorter 1-year OS (47.6% vs 79.9%; fixed effects: risk ratio [RR] = 2.506; 95% confidence interval [CI] = [1.948, 3.224]; P < .001) and PFS (15.8% vs 34.0%; random effects: RR = 1.294; 95% CI = [1.060, 1.579]; P = .011) rates than those with normal level of D-dimer. Moreover, high pretreatment D-dimer level was further proved to remain as an unfavorable predictor of OS (fixed effects: HR = 1.865; 95% CI = [1.469, 2.367]; P < .001; I2 = 7.6%) and PFS (fixed effects: HR = 1.513; 95% CI = [1.183, 1.936]; P = .001; I2 = 0.0%) in patients with SCLC. CONCLUSION: High pretreatment level of D-dimer was found to be an independent unfavorable prognostic factor in SCLC patients. However, more studies with sufficient adjustment for confounding factors are encouraged to confirm our conclusions.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Carcinoma de Pequenas Células do Pulmão/terapia , Taxa de Sobrevida
5.
Proc Natl Acad Sci U S A ; 118(15)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33833061

RESUMO

Density estimation is one of the fundamental problems in both statistics and machine learning. In this study, we propose Roundtrip, a computational framework for general-purpose density estimation based on deep generative neural networks. Roundtrip retains the generative power of deep generative models, such as generative adversarial networks (GANs) while it also provides estimates of density values, thus supporting both data generation and density estimation. Unlike previous neural density estimators that put stringent conditions on the transformation from the latent space to the data space, Roundtrip enables the use of much more general mappings where target density is modeled by learning a manifold induced from a base density (e.g., Gaussian distribution). Roundtrip provides a statistical framework for GAN models where an explicit evaluation of density values is feasible. In numerical experiments, Roundtrip exceeds state-of-the-art performance in a diverse range of density estimation tasks.

6.
Ir J Med Sci ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864191

RESUMO

BACKGROUND: This study aimed to explore the correlation between circular RNA_0000190 (circ_0000190) and microRNA-767-5p (miR-767-5p), and their correlations with biochemical indices, risk stratification, treatment response, and survival in multiple myeloma (MM) patients. METHODS: Bone marrow (BM) plasma cells of 86 MM patients (during standard diagnostic procedures) and 30 healthy donors (HDs) (examination of the eligibility for BM transplantation) were obtained, among which circ_0000190 and miR-767-5p expressions were detected using reverse transcription quantitative polymerase chain reaction. In MM patients, Durie-Salmon stage and International Staging System (ISS) stage were assessed. Clinical responses (including complete response (CR) and objective response rate (ORR)) were assessed. The progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Circ_0000190 was decreased, but miR-767-5p was increased in MM patients compared with HDs. Circ_0000190 was negatively correlated with miR-767-5p in both HDs and MM patients. In MM patients, circ_0000190 was negatively correlated with ISS stage, serum creatinine, beta-2-microglobulin, and lactate dehydrogenase but was positively correlated with albumin. Whereas an opposite trend in miR-767-5p was observed. Regarding clinical response, circ_0000190 had the value for predicting increased ORR, while miR-767-5p had the value for predicting decreased CR and ORR. Circ_0000190 high expression was correlated with better PFS and OS, while miR-767-5p high expression was correlated with worse PFS and OS. Multivariate Cox's analyses revealed circ_0000190 high expression as an independent factor predicting better OS. CONCLUSION: Circ_0000190 and its target miR-767-5p are dysregulated, and they are related to risk stratification and prognosis in MM patients.

7.
Nat Commun ; 12(1): 2177, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846355

RESUMO

The recent advancements in single-cell technologies, including single-cell chromatin accessibility sequencing (scCAS), have enabled profiling the epigenetic landscapes for thousands of individual cells. However, the characteristics of scCAS data, including high dimensionality, high degree of sparsity and high technical variation, make the computational analysis challenging. Reference-guided approaches, which utilize the information in existing datasets, may facilitate the analysis of scCAS data. Here, we present RA3 (Reference-guided Approach for the Analysis of single-cell chromatin Accessibility data), which utilizes the information in massive existing bulk chromatin accessibility and annotated scCAS data. RA3 simultaneously models (1) the shared biological variation among scCAS data and the reference data, and (2) the unique biological variation in scCAS data that identifies distinct subpopulations. We show that RA3 achieves superior performance when used on several scCAS datasets, and on references constructed using various approaches. Altogether, these analyses demonstrate the wide applicability of RA3 in analyzing scCAS data.


Assuntos
Epigênese Genética , Análise de Célula Única , Análise por Conglomerados , Células HEK293 , Humanos , Padrões de Referência
8.
BMC Ophthalmol ; 21(1): 135, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33714272

RESUMO

BACKGROUND: To report the structure and visual outcomes of pars plana vitrectomy (PPV) for laser-induced full-thickness macular holes (MHs). METHODS: This retrospective study enrolled 10 patients who underwent vitrectomy for MHs caused by laser injury. Best corrected visual acuity (BCVA), macular spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA) were used for assessment. RESULTS: Four patients were injured by unexpected expose of an yttrium aluminum garnet (YAG) laser, and six patients were accidentally injured by a handheld laser. The MH minimum diameters (MDs) ranged from 55 to 966 µm (mean = 548.00 ± 286.10 µm), and BCVA ranged from 20/400 to 20/50 (mean = logMAR 0.87 ± 0.29) preoperatively. All 10 eyes underwent PPV, internal limiting membrane (ILM) peeling, and gas tamponade. All eyes demonstrated closure of the MH with different degrees of discontinuity of the outer layer of the retina, and four eyes exhibited serious retinal pigment epithelium (RPE) destruction. Postoperative BCVA values were significantly improved (mean = logMAR 0.55 ± 0.33; P = 0.032, t = 2.234). The mean BCVA of the destroyed RPE group was significantly worse than that of the non-destroyed RPE group both before and after surgery (P = 0.019; Wilcoxon signed rank test). Further, OCTA indicated choroidal ischemia in the laser-induced MHs. CONCLUSION: Vitrectomy can be successful in closing laser-induced full-thickness MHs and improving visual acuity. However, If RPE/choroid is involved in laser damage in addition to the outer retinal layer, this may indicate poor visual prognosis.

9.
World Neurosurg ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33746099

RESUMO

BACKGROUND: Gliomas, particularly high-grade gliomas, are the most common primary brain tumors. From the Chinese Glioma Genome Atlas (CGGA) database, the relationships between the altered molecular pathways and gliomas could be easily observed. A close connection in the occurrence of the pathogenesis exists between the microenvironment, the glioma, and the associated genes. METHODS: Validation of the role of ZNF311 oncogene was confirmed by data from the CGGA dataset on glioblastoma and low-grade glioma. Furthermore, we used CIBERSORT to analyze the correlation between ZNF311 and cancer immune infiltrates. RESULTS: According to our analysis, ZNF311 was expressed higher in patients with grade-depended glioma with poor prognosis. In addition, we obtained valuable prognostic results between isocitrate dehydrogenase 1 (IDH1) and ZNF311 through the analysis of integrated correlations. Similarly, we simultaneously revealed the prognostic results between 1p/19q and ZNF311. In addition, we found that ZNF311 is correlated with a large number of tumor-infiltrating immune cells. CONCLUSIONS: Based on the study findings, we conclude that ZNF311 is potentially a novel biomarker for assessing prognosis and immune infiltration in glioblastoma and diffuse glioma cases.

10.
Cancer Lett ; 508: 1-12, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33713738

RESUMO

Interleukin (IL)-17 is a prominent cytokine that promotes pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) and is associated with the oncogenic pathways in tumor progression. However, the mechanism and therapeutic value of the IL-17 axis remain unclear. In this study, we verified the activation of the IL-17 and Notch pathways in PanIN/PDAC via complementary approaches and validated their pro-tumor effects on tumor progression. Additionally, we found a positive correlation between IL-17 and Notch; the IL-17 axis can upregulate Notch activity via the canonical NF-κB pathway in vitro, thus synergistically promoting PanIN/PDAC. Furthermore, we observed that the co-inhibition of IL-17 and the Notch pathway can enhance the therapeutic effect by restricting tumor growth in vivo. Our study highlights the synergistic effect of the IL-17 axis and Notch pathway in promoting PanIN/PDAC and further suggests that IL-17-Notch co-inhibition is a novel therapeutic strategy with superior potential in treating PDAC.

11.
Eur J Pharmacol ; 900: 174046, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33745958

RESUMO

This study is designed to investigate the role of novel protein kinases C (nPKC) in mediating pulmonary artery smooth muscle cells (PASMCs) proliferation in pulmonary hypertension (PH) and the underlying mechanisms. Mouse PASMCs was isolated using magnetic separation technology. The PASMCs were divided into 24 h group, 48 h group and 72 h group according to different hypoxia treatment time, then detected cell proliferation rate and nPKC expression level in each group. We treated PASMCs with agonists or inhibitors of PKCdelta (PKCδ) and PKCepsilon (PKCε) and exposed them to hypoxia or normoxia for 72 h, then measured the proliferation of PASMCs. We also constructed a lentiviral vector containing siRNA fragments for inhibiting PKCδ and PKCε to transfected PASMCs, then examined their proliferation. PASMCs isolated successfully by magnetic separation method and were in good condition. Hypoxia promoted the proliferation of PASMCs, and the treatment for 72 h had the most significant effect. Hypoxia upregulated the expression of PKCδ and PKCε in mouse PASMCs, leading to PASMCs proliferation. Moreover, Our study demonstrated that hypoxia induced upregulation of PKCδ and PKCε expression resulting to the proliferation of PASMCs via up-regulating the phosphorylation of AKT and ERK. Our study provides clear evidence that increased nPKC expression contributes to PASMCs proliferation and uncovers the correlation between AKT and ERK pathways and nPKC-mediated proliferation of PASMCs. These findings may provide novel targets for molecular therapy of pulmonary hypertension.

12.
Water Res ; 196: 117014, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33751971

RESUMO

Freshwater lakes are threatened by harmful cyanobacterial blooms, whose basic unit is Cyanobacterial Aggregate (CA). CA-attached bacteria play a significant role through different blooming stages with substantial variation of their taxonomic structure. However, little is known about their functional variations and functional links with cyanobacteria due to the lack of reference genomes. In this longitudinal study, we collected 16 CA samples from Lake Taihu, one of China's largest freshwater lakes, from April 2015 to February 2016, and sequenced their V4 region of 16S rRNA genes, full metagenomes (MG), and metatranscriptomes (MT). The analysis of these data revealed the dynamics of microbial taxonomic and functional structure in CAs, influenced by both external environmental factors and internal metabolism. 55 OTUs, 456 genes, and 37 transcripts showed significantly differential abundance across the early, middle, and late blooming stages (ANOVA test, P < 0.05). Total nitrogen and total phosphorus were proved to be the most important environmental drivers of microbial taxonomic and functional variations in CAs (Mantel's r > 0.25, P < 0.05). We constructed 161 high-quality metagenome-assembled genomes (MAGs), out of which 22 were cyanobacterial strains with diverse energy pathways, transporters and prokaryotic defense systems. Based on these MAGs, we constructed a cyanobacteria-bacteria co-nitrogen-pathway and a cyanobacteria-bacteria co-phosphorus-pathway, by which we demonstrated how nitrogen and phosphorus influence the dynamics of the microbial structure to a certain extent by affecting these co-pathways. Overall, these results characterized the taxonomic, functional, and transcriptional variations of microbes in CAs through different blooming stages. Genome assembly and metabolic analysis of cyanobacteria and their attached bacteria suggested that the material exchange and signal transduction do, indeed, exist among them. Our understanding of the underlying molecular pathways for cyanobacterial blooms could lead to the control of blooms by interventional strategies to disrupt critical microbes' expression.


Assuntos
Cianobactérias , Microbiota , China , Cianobactérias/genética , Eutrofização , Proliferação Nociva de Algas , Lagos , Estudos Longitudinais , RNA Ribossômico 16S/genética
13.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33649814

RESUMO

Muscle atrophy, a side effect from administration of the anti­inflammatory medication dexamethasone (DEX), is preventable by concomitant administration of the major monomeric constituent of Panax ginseng C.A. Meyer, 20(S)­ginsenoside Rg3 (S­Rg3). Putative S­Rg3­associated prevention of DEX­induced muscle atrophy may involve S­Rg3 mitigation of DEX­induced mitochondrial dysfunction. In the present study, MTT assays revealed enhanced cell viability following S­Rg3 treatment of DEX­injured C2C12 myotubes. Subsequent PCR and western blotting results demonstrated S­Rg3­induced reduction of expression of muscle atrophy F­box protein (atrogin­1) and muscle RING­finger protein­1, proteins previously linked to muscle atrophy. Additionally, S­Rg3 treatment of DEX­injured myotubes led to aggregation of Rg3 monomers in cells and dose­dependent increases in cellular mitochondrial basal respiratory oxygen consumption rate and intracellular ATP levels compared with their levels in untreated DEX­injured myotubes. In addition, S­Rg3 treatment significantly reversed DEX­induced reductions of expression of key mitochondrial respiratory electron transport chain subunits of protein complexes II, III and V in DEX­injured myotube cells. Furthermore, S­Rg3 alleviation of mitochondrial dysfunction associated with DEX­induced injury of C2C12 myotubes was linked to S­Rg3­associated decreases in both forkhead box O3 (FoxO3) protein expression and phosphorylation of AMP­activated protein kinase (AMPK). Collectively, these results implicate S­Rg3 modulation of signaling within the AMPK­FoxO3 pathway as a putative mechanism underlying S­Rg3 alleviation of DEX­induced muscle atrophy.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Dexametasona/farmacologia , Proteína Forkhead Box O3/genética , Ginsenosídeos/farmacologia , Mitocôndrias Musculares/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Proteína Forkhead Box O3/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Camundongos , Mitocôndrias Musculares/metabolismo , Modelos Biológicos , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/prevenção & controle , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Transdução de Sinais/genética , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
14.
Andrology ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657666

RESUMO

BACKGROUND: The mechanism of erectile dysfunction (ED) caused by low androgen status is not fully understood. OBJECTIVES: To investigate whether low androgen status inhibits erectile function of rats by inducing pyroptosis in the corpus cavernosum (CC). MATERIALS AND METHODS: Thirty-six eight-weeks-old healthy male Sprague-Dawley rats were equally divided into six groups: sham-operated group (4w sham, 8w sham), castration group (4w cast, 8w cast), and castration + testosterone (T) group (4w cast + T, 8w cast + T). The rats in castration + T groups were injected with testosterone propionate subcutaneously every other day. After 4 and 8 weeks, the ratio of maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP), the level of serum T, the concentration of nitric oxide (NO) and interleukin-1ß (IL-1ß), the expression of NOD-like receptor pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), Caspase-1 p20, gasdermin D-N (GSDMD-N), transforming growth factor ß1 (TGF-ß1), collagen-I, and collagen-III, the ratio of smooth muscle/collagen (SM/C), and the proportion of pyroptotic cells in the CC were analyzed. RESULTS: The ratio of ICPmax/MAP (3/5 V) and SM/C, the level of NO and serum T was significantly decreased in castration groups when compared to other groups (p < 0.01). NLRP3, ASC, Caspase-1, and GSDMD were mainly expressed in the cytoplasm of smooth muscle cells (SMCs) and endothelial cells (ECs) in the CC. The expression of NLRP3, ASC, Caspase-1p20, GSDMD-N, IL-1ß, TGF-ß1, collagen-I, and collagen-III was significantly increased in castration groups when compared with other groups (p < 0.01). The proportion of pyroptotic cells in the CC was increased significantly in castration groups when compared with other groups (p < 0.05). DISCUSSION AND CONCLUSION: Low androgen status inhibits erectile function of rats by promoting CC fibrosis and reducing NO synthesis through pyroptosis of SMCs and ECs in the CC.

15.
J Ocul Pharmacol Ther ; 37(4): 241-247, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33524301

RESUMO

Purpose: This study presents clinical features and prognosis after long-term (12-18 months) antitubercular therapy (ATT) in patients with ocular tuberculosis (OTB) in East China, an endemic area of tuberculosis. Methods: This retrospective study reviewed data from OTB patients treated at the Eye and ENT Hospital of Fudan University from 2008 to 2018. All the patients completed a minimum follow-up of 6 months after the cessation of ATT. Results: Sixty-six patients with OTB were studied. The ocular manifestations included retinal vasculitis (51.6%), choroiditis (24.2%), panuveitis (23.2%), intermediate uveitis (7.4%), scleritis (5.3%), anterior uveitis (2.1%), and optic neuropathy (1%). Except for two patients (ATT for 6 months), all other patients (64/66, 96.97%) received ATT for at least 12 months (6 patients for 12 months, 30 patients for 15 months, and 28 patients for 18 months). Treatment in conjunction with oral corticosteroids was used in 48 patients (72.7%). The average initial best-corrected visual acuity (BCVA) was 0.8 ± 0.64 (LogMAR), which improved to 0.31 ± 0.35 (LogMAR) at the last follow-up (P < 0.05). The final BCVA was significantly associated with the initial BCVA and the duration of clinical symptoms. A complete remission of uveitis was achieved in 97% of the patients. Conclusions: This study observed a favorable prognosis with long-term ATT regimens. Patients with better baseline visual acuity and a shorter duration of clinical symptoms before diagnosis had a better prognosis.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33609806

RESUMO

Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses and is important in controlling a variety of processes in monocytes and macrophages. However, the role of HIF-1α in the teleost immune system remains less known. In this study, we cloned the cDNA sequence of HIF-1α from the ayu (Plecoglossus altivelis, PaHIF-1α). Sequence and phylogenetic tree analysis showed that PaHIF-1α clustered within the fish HIF-1α tree and was closely related to that of Northern pike (Esox lucius). PaHIF-1α was expressed in all tested tissues and expression increased in liver, head kidney, and body kidney upon Vibrio anguillarum infection. PaHIF-1α was found to regulate the expression of cytokines in ayu monocytes/macrophages (MO/MФ). PaHIF-1α mediated hypoxia-induced enhancement of MO/MФ phagocytic and bactericidal activities to enhance host defenses. Compared with the control, intermittent hypoxia further increased the expression of PaHIF-1α mRNA, improved the survival rate, and reduced the bacterial load of V. anguillarum-infected ayu. Therefore, PaHIF-1α may play a predominant role in the modulation of ayu MO/MФ function.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33581335

RESUMO

The establishment of a landscape of enhancers across human cells is crucial to deciphering the mechanism of gene regulation, cell differentiation, and disease development. High-throughput experimental approaches, though having successfully reported enhancers in typical cell lines, are still too costly and time consuming to perform systematic identification of enhancers specific to different cell lines. Existing computational methods, though capable of predicting regulatory elements purely relying on DNA sequences, lack the power of cell line-specific screening. Recent studies have suggested that chromatin accessibility of a DNA segment is closely related to its potential function in regulation, and thus may provide useful information in identifying regulatory elements. Motivated by the above understanding, we integrate DNA sequences and chromatin accessibility data to accurately predict enhancers in a cell line-specific manner. We proposed DeepCAPE, a deep convolutional neural network to predict enhancers via the integration of DNA sequences and DNase-seq data. Benefitting from the well-designed feature extraction mechanism and skip connection strategy, our model not only consistently outperforms existing methods in the imbalanced classification of cell line-specific enhancers against background sequences, but also has the ability to self-adapt to different sizes of datasets. Besides, with the adoption of auto-encoder, our model is capable of making cross cell-line predictions. We further visualize kernels of the first convolutional layer and show the match of identified sequence signatures and known motifs. We finally demonstrate the potential ability of our model to explain functional implications of putative disease-associated genetic variants and discriminate disease-related enhancers.

18.
Cell Death Dis ; 12(2): 142, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33542215

RESUMO

Many novel non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in various physiological and pathological processes. The PI3K/AKT signaling pathway is important for its role in regulating skeletal muscle development. In this study, molecular and biochemical assays were used to confirm the role of miRNA-145 (miR-145) in myoblast proliferation and apoptosis. Based on sequencing data and bioinformatics analysis, we identified a new circRILPL1, which acts as a sponge for miR-145. The interactions between circRILPL1 and miR-145 were examined by bioinformatics, a luciferase assay, and RNA immunoprecipitation. Mechanistically, knockdown or exogenous expression of circRILPL1 in the primary myoblasts was performed to prove the functional significance of circRILPL1. We investigated the inhibitory effect of miR-145 on myoblast proliferation by targeting IGF1R to regulate the PI3K/AKT signaling pathway. A novel circRILPL1 was identified that could sponge miR-145 and is related to AKT activation. In addition, circRILPL1 was positively correlated with muscle proliferation and differentiation in vitro and could inhibit cell apoptosis. The newly identified circRILPL1 functions as a miR-145 sponge to regulate the IGF1R gene and rescue the inhibitory effect of miR-145 on the PI3K/AKT signaling pathway, thereby promoting myoblast growth.

19.
Mini Rev Med Chem ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33596801

RESUMO

In recent years, marine-derived Penicillium fungi have received remarkable interest as a valuable source of novel natural products encompassing diverse chemical structures and bioactive properties. Mangroves, sediments, algae, and sponges are the four main sources of marine-derived Penicillium fungi. As of 2014, more than 390 novel natural products have been isolated from the marine-derived Penicillium fungi, mainly including polyketides, alkaloids, terpenoids, and macrolides. Biological investigations have shown that these compounds possess antimicrobial, anti-inflammatory, cytotoxic, and other activities with potential applications in new drug development. To provide an updated catalog of this field, our mini-review summarized the origins, structures, and bioactivities of 188 secondary metabolites from marine-derived Penicillium fungi based on bioactivities classification published from 2015 to 2020.

20.
Andrology ; 9(1): 342-351, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507631

RESUMO

BACKGROUND: Type 5 phosphodiesterase inhibitor (PDE5I) has become the first-line treatment for erectile dysfunction (ED). However, its effective rate for hypertension ED is only 60%-70%. How to improve the efficacy of ED treatment is the focus of current research. OBJECTIVE: To explore whether icariin can improve the erectile function of spontaneously hypertensive rats (SHR) by affecting post-translational protein-protein interactions to regulate endothelial nitric oxide synthetase (eNOS) activity. METHOD: Twelve-week-old healthy male SHR rats and Wistar-Kyoto rats (WKY) were randomly divided into four groups: SHR control group, SHR + icariin (10 mg/kg·d gavage) treatment group, WKY control group, and WKY + icariin (10 mg/kg·d gavage) treatment group (n = 5). After 4 weeks, the maximum penile intracavernous pressure/mean arterial pressure (ICPmax/MAP), the expression of heat-shock protein 90 (Hsp90), caveolin-1, calmodulin, p-eNOS, and eNOS in penile cavernous tissue and the content of nitric oxide (NO) and cGMP were measured. The interaction between eNOS and Hsp90, caveolin-1, and calmodulin were detected by immunoprecipitation. RESULT: The ICPmax/MAP in the SHR + icariin treatment group (0.08 ± 0.01, 0.23 ± 0.07, 0.40 ± 0.05) was significantly higher than the SHR group (0.03 ± 0.01, 0.13 ± 0.03, 0.21 ± 0.02) under 3V and 5V electrical stimulations (P < .05). Compared with the SHR group, the expression of HSP90, calmodulin, P-eNOS, eNOS, and P-eNOS/eNOS in the penile cavernous tissue of rats in the WKY group and the SHR + icariin treatment group were significantly increased (P < .05), and the expression of caveolin-1 was significantly decreased (P < .05). The NO content (2.16 ± 0.22 µmol/g) and cGMP concentration (3.69 ± 0.12 pmol/mg) in the SHR + icariin treatment group were significantly higher than those in the SHR group (1.01 ± 0.14 µmol/g, 2.31 ± 0.22 pmol/mg) (P < .05). Compared with the SHR group, the interaction between eNOS and HSP90 in the cavernosa of the rats in the SHR + icariin treatment group was significantly increased (P < .05), the interaction between eNOS and caveolin-1 was significantly decreased (P < .01), and the interaction between eNOS and calmodulin did not significantly change. DISCUSSION AND CONCLUSION: Up-regulating the expression of HSP90 and calmodulin and inhibiting caveolin-1 in SHR corpus cavernosum, promoting the interaction between eNOS and HSP90, inhibiting the interaction between eNOS and caveolin-1, increasing p-eNOS/eNOS, may be the mechanism of icariin that improves SHR erectile function.

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