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1.
Aging (Albany NY) ; 122020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474457

RESUMO

OBJECTIVE: This study aimed to evaluate the efficacy of the improved nanoscaled delivery system for doxorubicin (Dox) based on angiopep (ANG)-2 modified graphene oxide (GO), the so-called ANG-Dox-GO, in suppressing the growth and and metastasis of glioma cells. RESULTS: Modification of GO by angiopep-2 significantly increased the cellular uptake of Dox. In addition, ANG-Dox-GO treatment of U87 MG cells significantly inhibited cell viability, decreased clone number, cell migration and invasion andinduced cell apoptosis, with superior efficiency over that of Dox-GO and free Dox. Similar results were observed in in vivo experiments-tumor size and weight of glioma xenograft mice were obviously decreased after treatments with ANG-Dox-GO, Dox-GO and Dox, respectively, as compared with control group, and the efficiency was the highest in ANG-Dox-GO, followed by Dox-Go and Dox. CONCLUSIONS: ANG-Dox-GO exhibited superior anti-glioma effects over Dox-GO both in vitro and in vivo experiments. METHODS: The morphology of ANG-Dox-GO was analyzed by UV visible absorption spectroscopy and atomic force microscopy and its in vitro cellular uptake was measured using confocal imaging analysis. The antitumor effects of GO, unbound Dox, Dox-GO and ANG-Dox-GO were evaluated by MTT assay, colony-forming assay, cell apoptosis assay and Transwell assay in U87 malignant glioma (MG) cells.

2.
Biol Pharm Bull ; 43(6): 985-993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32475920

RESUMO

Acute biliary pancreatitis (ABP) with a high mortality rate is an incurable digestive system disease induced by abnormal bile acid regurgitation due to the biliary obstruction. Dehydrocholic acid (DA) alleviates the severity of cholestatic hepatitis related to biliary inflammation, suggesting DA is potential to develop for the incurable ABP management. Here we identified DA potency and explored the underlying mechanism in ABP. Our data showed that DA administration not only reduced typically clinicopathological parameters including serum levels of amylase and lipase but also suppressed pancreatic tissue edema, necrosis and trypsin activation in ABP mice. We also found that DA significantly reduced the necrosis of pancreatic acinar cells induced by sodium taurocholate (NaT). Further experimental data showed the significant inhibitions of DA on mitochondrial membrane potential depolarization, ATP exhaustion, calcium overload and reactive oxygen species (ROS) erupted in acinar cells induced by NaT, indicating DA could avert acinar cell death through protecting the mitochondrial function, scavenging excessive oxidative stress and balancing calcium. The comprehensive study found DA elevated the expression of transcription factor EB (TFEB) in vitro thus to increase the functional lysosome content. Indeed, DA decreased the Microtubule-associated protein light chain 3 (LC3) II/I ratio as well as ubiquitin-binding protein p62 and Parkin expressions in vivo and in vitro, revealing autophagy restoration maybe through the improvement of TFEB-mediated lysosome biogenesis. These data indicate that DA improves ABP through the mitochondrial protection, antioxidant ability enhancement and autophagy recovery. In conclusion, our study proposes a potential therapy strategy for the incurable ABP.

3.
Bioinformatics ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32407523

RESUMO

SUMMARY: Diverse traits have evolved through cis-regulatory changes in genome sequence that influence the magnitude, timing, and cell type-specificity of gene expression. Advances in high-throughput sequencing and regulatory genomics have led to the identification of regulatory elements in individual species, but these genomic regions remain difficult to align across orders due to their lack of sequence conservation relative to protein coding genes. The groundwork for tracing the evolution of regulatory elements is provided by the recent assembly of hundreds of genomes, the generation of reference-free Cactus multiple sequence alignments of these genomes, and the development of the halLiftover tool for mapping regions across these alignments. We present halLiftover Postprocessing for the Evolution of Regulatory Elements (HALPER), a tool for constructing contiguous regulatory element orthologs from the outputs of halLiftover. We anticipate that this tool will enable users to efficiently identify orthologs of regulatory elements across hundreds of species, providing novel insights into the evolution of traits that have evolved through gene expression. AVAILABILITY AND IMPLEMENTATION: HALPER is implemented in python and available on github: https://github.com/pfenninglab/halLiftover-postprocessing.

4.
IEEE Trans Cybern ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32396121

RESUMO

Neural networks (NNs) have been deeply studied due to their wide applicability. Since time delays are unavoidable in reality, it is basic and crucial for all applications based on NNs to guarantee system stability under the influence of mixed time delays. To better exploit the variation information of time delay, we introduce the switching idea and approaches into mixed time-delay NNs to solve the stability problem. First, the considered mixed time-delay NNs are modeled as the switched NNs by dividing the two classes of time delays, discrete and distributed time delays, into some variable intervals and combining these intervals as new switching modes. With the help of mode-dependent average dwell-time switching, Lyapunov theory, and mathematical techniques, several exponential stability criteria on the modeled switched systems containing different modes are obtained. Moreover, via introducing the mathematical condition of the unstable subsystem in the switching system, a less conservativeness condition on the exponential stability of the modeled NNs is proposed. We perform three examples for testifying the validity of the proposed methods over existing ones.

5.
Transl Psychiatry ; 10(1): 145, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398686

RESUMO

Prospective studies have shown that abnormally circulating cholesterol is associated with the risk of dementia. However, whether the association is causal or not remains unclear. We attempt to infer the causal association in a MR meta-analysis by using ApoE gene polymorphisms as instrument variables. Studies with dementia risk (27 studies) or circulating lipid levels (7 studies) were included, with totally 3136 dementia patients and 3103 healthy controls. The analyses showed that carriers of ε2 allele significantly were of decreased risk of AD (OR = 0.70; 95% CI: 0.58-0.84; P < 0.01), whereas carriers of ε4 allele were of increased risk of AD (OR = 3.62; 95% CI: 3.03-4.32; P < 0.05), compared to these of ε3 allele. Circulating TC was significantly reduced in carriers of ε2 allele (WMD = - 0.29 mmol/L; 95% CI: -0.54 to -0.03; P < 0.05) and increased in carriers of ε4 allele (WMD = 0.42 mmol/l; 95% CI: 0.001-0.84; P < 0.05). In addition, carriers of ε4 allele had reduction in circulating HDL-C (WMD = - 0.04 mmol/L; 95% CI: - 0.07 to -0.001; P < 0.05). In comparing allele ε2 with ε3, the predicted OR of having AD for 1 mg/dL increment in circulating TC was 0.97 (95% CI: 0.86-0.98; P < 0.05). Comparing allele ε4 with ε3, the predicted OR for a 1 mg/dL increment in TC was 1.08 (95% CI: 1.05-17.58; P < 0.05), and reduction in HDL-C was 2.30 (95% CI: 1.51-43.99; P < 0.05). Our findings demonstrate that high circulating TC and reduced HDL-C levels might be potential risk factors of the development of AD.

6.
Front Immunol ; 11: 701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411135

RESUMO

Follicular helper T (Tfh) cells regulate high-affinity antibody production. Some findings have indicated that Tfh cells could be differentiated into memory cells. Here we have investigated the effects of IFN-α, as an adjuvant, on the generation of memory Tfh cell and memory B cell responses. The data showed that adenoviral vectors expressing: (i) foot-and-mouth disease virus (FMDV) VP1 proteins and porcine IFN-α, or (ii) porcine IFN-α alone, potently enhanced the generation of memory Tfh cells, especially the CCR7 l o memory Tfh subset. Upon rechallenge with FMD recombinant adenoviral vaccines, IFN-α enhances Tfh cells activity, rapidly upregulating their signature Bcl-6, CXCR5, and IL-21 markers. The results suggest that IFN-α enhances the levels of the transcription factor Bcl-6 within Tfh cells, potentially by regulating STAT1. Additionally, IFN-α substantially increased the number of IgG1+ and CD86+ memory B cells, which are responsible for inducing the rapid effector functions of memory Tfh cells after vaccine reactivation, establishing the close relationship between memory B cell and memory Tfh cell subsets. In brief, IFN-α enhances the potency of FMD recombinant adenoviral vaccines to induce memory Tfh and memory B cell responses, thus elevating serum antibody titers. IFN-α administration therefore represents an attractive strategy for enhancing responses to vaccination.

7.
Front Immunol ; 11: 626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32373117

RESUMO

Pathogen-initiated chronic inflammation or autoimmune diseases accelerate proliferation and promote differentiation of hematopoietic stem cells (HSCs) but simultaneously reduce reconstitution capacity. Nevertheless, the effect of acute infection and inflammation on functional HSCs is still largely unknown. Here we found that acute infection elicited by heat-inactivated Escherichia coli (HIEC) expanded bone marrow lineage-negative (Lin)- stem-cell antigen 1 (Sca-1)+cKit+ (LSK) cell population, leading to reduced frequency of functional HSCs in LSK population. However, the total number of BM phenotypic HSCs (Flk2-CD48-CD150+ LSK cells) was not altered in HIEC-challenged mice. Additionally, the reconstitution capacity of the total BM between infected and uninfected mice was similar by both the competitive repopulation assay and measurement of functional HSCs by limiting dilution. Thus, occasionally occurring acute inflammation, which is critical for host defenses, is unlikely to affect HSC self-renewal and maintenance of long-term reconstitution capacity. During acute bacterial infection and inflammation, the hematopoietic system can replenish hematopoietic cells consumed in the innate inflammatory response by accelerating hematopoietic stem and progenitor cell proliferation, but preserving functional HSCs in the BM.

8.
J Cell Physiol ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32385917

RESUMO

miRNAs, a kind of noncoding small RNA, play a significant role in adipose differentiation. In this study, we explored the effect of miR-324-5p in adipose differentiation, and found that miR-324-5p could promote adipocytes differentiation and increase body weight in mice. We overexpressed miR-324-5p during adipocytes differentiation, by oil red O and bodipy staining found that lipid accumulation was increased, and the expression level of adipogenic related genes were significantly increased. And the opposite experimental results were obtained after inhibiting miR-324-5p. In vivo, we injected miR-324-5p agomiR in obese mice and found that body weight, adipocyte area, and adipogenic-related gene expression level were significantly increased but lipolytic genes were decreased. To further explore the mechanism of miR-324-5p regulation in lipid accumulation, we constructed Krueppel-like factor 3 (KLF3) 3'-untranslated region luciferase reporter vector and KLF3 pcDNA 3.1 overexpression vector, and found that miR-324-5p was able to directly target KLF3. Overall, in this study we found that miR-324-5p could promote mice preadipoytes differentiation and increase mice fat accumulation by targeting KLF3.

9.
Plant Biotechnol J ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32452105

RESUMO

Effective evaluation of millions of crop genetic stocks is an essential component of exploiting genetic diversity to achieve global food security. By leveraging genomics and data analytics, genomic prediction is a promising strategy to efficiently explore the potential of these gene banks by starting with phenotyping a small designed subset. Reliable genomic predictions have enhanced selection of many macroscopic phenotypes in plants and animals. However, the use of genome prediction strategies for analysis of microscopic phenotypes is limited. Here, we exploited the power of genomic prediction for eight maize traits related to the shoot apical meristem (SAM), the microscopic stem cell niche that generates all the above-ground organs of the plant. With 435,713 genome-wide single nucleotide polymorphisms (SNPs), we predicted SAM morphology traits for 2,687 diverse maize inbreds based on a model trained from 369 inbreds. An empirical validation experiment with 488 inbreds obtained a prediction accuracy of 0.37~0.57 across eight traits. In addition, we show that a significantly higher prediction accuracy was achieved by leveraging the U value (upper bound for reliability) that quantifies the genomic relationships of the validation set with the training set. Our findings suggest that double selection considering both prediction and reliability can be implemented in choosing selection candidates for phenotyping when exploring new diversity is desired. In this case, individuals with less extreme predicted values and moderate reliability values can be considered. Our study expands the turbocharging gene banks via genomic prediction from the macro-phenotypes into the micro-phenotypic space.

10.
Aging (Albany NY) ; 12(9): 8289-8300, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396524

RESUMO

OBJECTIVE: Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aimed to investigated the anti-tumor effect of doxorubicin (Dox)-loaded Pluronic P123 (P123) and PEG2000-DSPE mixed NMs in drug-resistant breast cancer cells. RESULTS: The expression of P-gp and MDR1 gene was highly expressed in MCF-7R but not MCF-7 cells. The cellular uptake of P123-PEG2000-DSPE (Dox) was higher than that of free Dox and PEG2000-DSPE (Dox) in MCF-7R cells. Furthermore, compared with free Dox, both PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell viability, and promoted cell apoptosis in MCF-7R cells. In addition, the P123-modified NMs obviously inhibited the expression of P-gp and MDR1. CONCLUSIONS: P123-PEG2000-DSPE (Dox) had a superior anti-tumor activity than PEG2000-DSPE (Dox) in MCF-7R cells through P-gp-mediated drug excretion and drug resistance mechanisms. METHODS: The PEG2000-DSPE NMs (PEG2000-DSPE), P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE), Dox-loaded PEG2000-DSPE NMs (PEG2000-DSPE (Dox)), and Dox-loaded Pluronic P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE (Dox)) were prepared, and then the morphologies and the size distribution of PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.

11.
Plant Dis ; : PDIS07191469RE, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32441579

RESUMO

Potato common scab is an important soilborne disease worldwide that can significantly reduce the quality and economic values of potato. The disease is caused by multiple species of Streptomyces, which are not well controlled due to lack of effective strategies. Streptomyces galilaeus has been recently identified as a dominant species causing potato common scab in Inner Mongolia, China. This study was focused on screening and characterizing antagonists for biological control against pathogenic S. galilaeus. Bacterial strain PBSH9 was isolated from a potato tuber. PBSH9 was identified as a Streptomyces sp. on the basis of morphological, physiological, and biochemical characteristics, as well as DNA sequence analysis. PBSH9 inhibited S. galilaeus with a diameter of inhibitory zone of 19.8 mm on agar plates. The extracellular filtrate of PBSH9 also inhibited S. galilaeus growth with a diameter of inhibition zone of 10.0 mm. Furthermore, PBSH9 promoted potato sprouting and emergence. Disease control was up to 81.88% in greenhouse trials, and from 47.64 to 73.97% in 3-year field trials. Among the tested inoculation methods, seed treatment was more effective than soil drenching for PBSH9 application. PBSH9 not only effectively controlled potato common scab but also increased potato growth. Thus, it can be a potential candidate for biocontrol agent.

12.
Eur J Med Chem ; 200: 112462, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32464472

RESUMO

Platelet thrombosis is the main pathogeny resulting in the low curability of ischemic stroke, a leading cause of mortality and disability worldwide. Metformin, a biguanide derivative that is the first-line oral medicine for type 2 diabetes, alleviates the severity of ischemic stroke in diabetic patients and suppresses platelet activation in experimental animal model. However, the clinical implementation of commercial biguanide analogs for stroke related to platelet thrombosis remains challenging due to its weak potency, poor pharmacokinetic characteristics and possible hypoglycemia. Here, twenty-three biguanide derivatives were designed and synthesized based on the principles of bioisosteres. These derivatives were evaluated for the activity of antiplatelet thrombosis in vivo. We found that N-trifluoromethanesulfonyl biguanide derivative, compound b10, uniquely prevented cerebral infarction as well as neuronal function injury, and significantly decrease the mortality rate of ischemic stroke in the middle cerebral artery occlusion mice without significant side effects. We verified that b10 directly inhibited platelets thrombus formation and decreased the compactness of stroke thrombi. Particularly, b10 exhibited good potency to inhibit human platelet activation including platelet aggregation, adhesion, pseudopodia formation, integrin GPIIb/IIIa activation, CD62P expression and clot retraction. Meanwhile, the pharmacokinetics assessment showed that b10 had satisfying pharmacological characteristics including a longer duration and a higher oral absorption ratio than its parent compound. In addition, b10 remarkably ameliorated not only stroke related to platelet thrombosis but also carotid artery thrombus formation. It is concluded that the novel potent antiplatelet thrombotic agent derived from biguanide is a promising candidate for stroke treatment.

13.
Neurol Sci ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32417986

RESUMO

BACKGROUND AND PURPOSE: Previous studies have revealed a relationship between chronic kidney disease (CKD) and white matter hyperintensities (WMH). However, studies on the WMH and CKD in acute stroke patients are rare, and the conclusion is consistent. Our study aimed to investigate the relationship between the severity of WMH and CKD in acute lacunar infarction patients. METHODS: Consecutive acute lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to the severity of periventricular WMH (PVWMH) and deep WMH (DWMH). We dichotomized the severity of WMH (PVWMH and DWMH, separately) into mild group (Fazekas scores 0-1) and moderate-severe group (Fazekas scores 2-3). Estimated glomerular filtration rate (eGFR), proteinuria, vascular risk factors, and clinical features were compared between these two groups. Multivariable logistic regression analysis was used to investigate the association between the severity of WMH and risk factors. RESULTS: A total of 993 acute lacunar infarction patients aged 25-95 years were enrolled. The proportions of participants presenting moderate-severe group PVWMH and DWMH were 46.6% and 38.6%, respectively. Patients with moderate-severe PVWMH had higher age (P < 0.001) and higher incidence of stroke history (P < 0.001) than those in mild group. The level of serum creatinine and the presence of CKD were significantly higher while the eGFR was significantly lower in patients with moderate-severe PVWMH than those with mild PVWMH. Patients with moderate-severe DWMH (n = 383) also had higher age (P < 0.001) and often had a history of stroke (P < 0.001). But the association between the severity of DWMH and eGFR was not found. Multivariable logistic regression analyses showed stage 2 CKD and stage 3 CKD were independently associated with moderate-severe PVWMH, but not DWMH. CONCLUSIONS: Our study demonstrates that CKD was independently associated with moderate-severe PVWMH in patients with acute lacunar infarction, but not DWMH. PVWMH and DWMH may have distinct pathophysiology.

14.
Chem Commun (Camb) ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32406444

RESUMO

The transformations of cyclopropenes have attracted the attention of organic chemists for decades. As readily accessible strained carbocycles, cyclopropenes show a diverse range of reactivities. This feature article focuses on the developments of cyclopropenes from 2016 until the end of 2019, including reactions through vinylmetal carbenes, reactions through metal complex insertion, addition reactions with 1,3-dipole, radical reactions of cyclopropenes, and reactions of highly reactive in situ generated cyclopropenes. In addition, several new synthetic methods and applications of cyclopropenes are also disclosed in this paper.

15.
Chin J Integr Med ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32445018

RESUMO

OBJECTIVE: To describe and analyze the status quo of cardiovascular clinical practice guidelines or expert consensuses including both Chinese medicine (CM) and integrative medicine, through systematic literatures searching and quality assessment. METHODS: Data bases including Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database were searched for published CM or integrative cardiovascular clinical practice guidelines or expert consensuses. The website www. medlive.cn was also retrieved as supplementary. The clinical practice evaluation tool AGREE II was used to assess the quality of included guidelines or consensuses. RESULTS: A total of 31 relevant clinical practice guidelines or expert consensuses were included, covering diagnosis, treatment, Chinese patent and patient fields. Common cardiovascular diseases like coronary heart diseases, heart failure and arrhythmia were also involved. Through analysis it was found that both the quantity and quality of included guidelines have been improved year by year. A total of 4 evidence-based clinical practice guideline has been found, one of which was a guideline project plan. Except that, the remaining 27 reports were all consensus-based guidelines. The scores of each field, from highest to lowest, were clarity of presentation (58%), scope and purpose (54%), stakeholder involvement (28%), rigor of development (21%), applicability (13%) and editorial independence (8%). CONCLUSIONS: Although clinical practice guidelines in cardiovascular domain of Chinese have gained increasing concern, with both quantity and quality improved, there is still huge gap in methodology and reporting standards between CM guidelines and international ones. On the one hand, it is essential to improve and standardize the methodology of developing CM guidelines. On the other hands, the evaluation system of evidence and recommendation with CM characters should be developed urgently.

16.
Exp Lung Res ; 46(6): 174-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362153

RESUMO

Background: Previous studies have revealed the important role of alveolar macrophages (AMs) in the pathogenesis of acute respiratory distress syndrome (ARDS) and potential anti-inflammatory properties of lincRNA-p21. This study aims to study the association between lincRNA-p21 and active AMs to understand the molecular mechanisms of AMs-mediated inflammatory responses in ARDS.Methods: This study was mainly investigated in mice with the intratracheal instillation of lipopolysaccharide (LPS) or LPS-treated AMs. The expression of lincRNA-p21 and classical macrophage markers, IL-12ß and iNOS, was detected by quantitative RT-PCR, while NF-κB p65 translocation was measured by western blotting analysis. And, NF-κB activity was analyzed through luciferase report assays. Gain- and loss-of-function studies were also performed for further investigations.Results: Elevated lincRNA-p21 levels were observed in both LPS-induced ARDS mice and LPS-treated AMs, with upregulated expression of IL-12ß and iNOS, namely M1 activation, and p65 nuclear translocation. Further in vitro studies showed that LPS-induced M1 activation could be counteracted by both lincRNA-p21 inhibition and inhibited NF-κB activation. Moreover, both p65 nuclear translocation and NF-κB activity were promoted by lincRNA-p21 overexpression, while lincRNA-p21 inhibition showed a negative effect on LPS-induced p65 nuclear translocation and increase of NF-κB activity. Additionally, LPS-induced lung injuries could be attenuated by lincRNA-p21 inhibition in vivo.Conclusion: This study revealed elevated lincRNA-p21 levels in LPS-induced ARDS and investigated the potential role of lincRNA-p21 in LPS-induced pro-inflammatory response via NF-κB/p65 mediated pathways, suggesting the potential application of lincRNA-p21 for ADRS therapy.

17.
Infection ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32440918

RESUMO

OBJECTIVES: We aimed to develop a simple algorithm to help early identification of SARS-CoV-2 infection patients with severe progression tendency. METHODS: The univariable and multivariable analysis were computed to identify the independent predictors of COVID-19 progression. The prediction model was established in a retrospective training set of 322 COVID-19 patients and was re-evaluated in a prospective validation set of 317 COVID-19 patients. RESULTS: The multivariable analysis identified age (OR = 1.061, p = 0.028), lactate dehydrogenase (LDH) (OR = 1.006, p = 0.037), and CD4 count (OR = 0.993, p = 0.006) as the independent predictors of COVID-19 progression. Consequently, the age-LDH-CD4 algorithm was derived as (age × LDH)/CD4 count. In the training set, the area under the ROC curve (AUROC) of age-LDH-CD4 model was significantly higher than that of single CD4 count, LDH, or age (0.92, 0.85, 0.80, and 0.75, respectively). In the prospective validation set, the AUROC of age-LDH-CD4 model was also significantly higher than that of single CD4 count, LDH, or age (0.92, 0.75, 0.81, and 0.82, respectively). The age-LDH-CD4 ≥ 82 has high sensitive (81%) and specific (93%) for the early identification of COVID-19 patients with severe progression tendency. CONCLUSIONS: The age-LDH-CD4 model is a simple algorithm for early identifying patients with severe progression tendency following SARS-CoV-2 infection, and warrants further validation.

18.
Urology ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32283169

RESUMO

OBJECTIVE: To determine the outcomes and mechanisms of delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) in a rat model of irreversible stress urinary incontinence (SUI). MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats were randomly assigned into 3 groups: sham control, vaginal balloon dilation + ß-aminopropionitrile (BAPN; SUI group), and vaginal balloon dilation + BAPN + treatment with Li-ESWT (SUI-Li-ESWT group). An irreversible SUI model was developed by inhibiting the urethral structural recovery with BAPN daily for 5 weeks. Thereafter, in the SUI-Li-ESWT group, Li-ESWT was administered twice per week for 2 weeks. After a 1-week washout, all 24 rats were evaluated with functional and histologic studies at 17 weeks of age. Endogenous progenitor cells were detected via the EdU-labeling method. RESULTS: Functional analysis with leak point pressure testing showed that the SUI-Li-ESWT group had significantly higher leak point pressures compared with untreated rats. Increased urethral and vaginal smooth and striated muscle content and increased thickness of the vaginal wall were noted in the SUI-Li-ESWT group. The SUI group had significantly decreased neuronal nitric oxide /tyrosine hydroxylase positive nerves ratio in the smooth muscle layers of the urethra, while the SUI-Li-ESWT group had neuronal nitric oxide/tyrosine hydroxylase+ nerves ratio similar to that of the control group. The continuality of urothelial cell lining was also improved in the SUI-Li-ESWT group. In addition, there were significantly increased EdU-positive cells in the SUI-Li-ESWT group. CONCLUSION: Li-ESWT appears to increase smooth muscle content in the urethra and the vagina, increase the thickness of urethral wall, improve striated muscle content and neuromuscular junctions, restore the integrity of the urothelium, and increase the number of EdU-retaining progenitor cells in the urethral wall.

19.
J Cell Mol Med ; 24(10): 5438-5445, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32281724

RESUMO

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumour, which has posed a heavy health and financial burden worldwide. Due to limited symptoms at the early stage and the limitation in current biomarkers, HCC patients are usually diagnosed at the advanced stage with a pessimistic overall survival rate. Circular RNAs (circRNAs) are a subclass of single-stranded RNAs characterized by a covalently closed loop structure without 3'- or 5'-end. With advances in high-throughput sequencing technology and bioinformatics, accumulating studies have demonstrated the promotor or suppressor roles of circRNAs in the carcinogenesis, progression, and metastasis of HCC. Moreover, circRNAs are characteristic of higher abundance, stability and conservation compared with linear RNAs. Therefore, circRNAs have emerged as one of the most promising diagnostic and prognostic biomarkers for HCC with reliable accuracy, sensitivity and specificity. In this review, we briefly introduce the characteristics of circRNAs and summarize the roles of circRNAs in the biological procedures of HCC. Furthermore, we provide an overview on the potential diagnostic and prognostic value of circRNAs as biomarkers for patients with HCC. Finally, we discuss future perspectives of circRNAs in cancer research.

20.
Chem Biol Interact ; 324: 109089, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32272095

RESUMO

Ulcerative colitis (UC) is a chronic, idiopathic and inflammatory disease of the rectal and colonic mucosa. Studies have shown that Toll-like receptors (TLR) 4 and Signal Transducer and Activator of Transcription 3 (STAT3)-mediated the decline in immune function and inflammatory infiltration are potential pathomechanism of UC occurrence and development. In this study, the anti-inflammation of Erianin, a natural bibenzyl compound with the antioxidant, antitumor, and anti-inflammatory activities, was investigated in a dextran sodium sulphate-induced UC mouse model. Three-week Erianin administration resulted in the increment on the body weight and colon length, and the reduction on the activity index score of UC mice. Liver, spleen, and renal organ indexes and pathological observations confirmed that Erianin was not cytotoxic and had an effect of improving immune organ function. The haematoxylin and eosin staining sections of colon tissue show Erianin's effect of reversing inflammation in the mucosal laye. Proteomic analysis and enzyme-linked immunosorbent assay indicated that Erianin regulated the levels of inflammatory and oxidative stress-related factors and immunochemokines in serum and colon tissues thereby reducing cell peroxidative damage and reducing immune inflammatory responses. Further data obtained by Western Blotting confirmed that Erianin's anti-UC activity was mediated by inhibiting the TLR4 and STAT3 signaling.


Assuntos
Anti-Inflamatórios/uso terapêutico , Bibenzilas/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/toxicidade , Antioxidantes/uso terapêutico , Bibenzilas/toxicidade , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana , Rim/patologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Baço/patologia
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