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1.
Comput Math Methods Med ; 2020: 7980249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062042

RESUMO

In the field of brain-computer interfaces, it is very common to use EEG signals for disease diagnosis. In this study, a style regularized least squares support vector machine based on multikernel learning is proposed and applied to the recognition of epilepsy abnormal signals. The algorithm uses the style conversion matrix to represent the style information contained in the sample, regularizes it in the objective function, optimizes the objective function through the commonly used alternative optimization method, and simultaneously updates the style conversion matrix and classifier during the iteration process parameter. In order to use the learned style information in the prediction process, two new rules are added to the traditional prediction method, and the style conversion matrix is used to standardize the sample style before classification.

2.
Dalton Trans ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33094765

RESUMO

The eCO2RR activity is correlated to the internal structural character of the catalyst. We employed two types of structural models of porphyrin-based MOFs of PCN-222(Cu) and PCN-224(Cu) into heterogeneous catalysis to illustrate the effect of structural factors on the eCO2RR performance. The composite catalyst PCN-222(Cu)/C displays better activity and selectivity (η = 450 mV, FEHCOOH = 44.3%, j = 3.2 mA cm-2) than PCN-224(Cu)/C (η = 450 mV, FEHCOOH = 34.1%, j = 2.4 mA cm-2) for the CO2 reduction to HCOOH in the range of -0.7--0.9 V (vs. RHE) due to its higher BET surface area, CO2 uptake, and a larger pore diameter. It is interesting that PCN-224(Cu)/C displays better performance in the range of -0.4--0.6 V (vs. RHE) due to its greater heat of adsorption, Qst and a higher affinity for CO2 molecule, which could promote the capture of CO2 onto the exposed active sites. As a result, PCN-224(Cu)/C exhibits better stability for the long-term electrolysis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32996777

RESUMO

Background: Sevoflurane (Sev), a volatile anesthetic agent, is widely used in neurosurgery for anesthesia maintenance, accompanied with antitumor activity postanesthesia in multiple human cancers, including glioma. However, the molecular mechanism hidden in Sev in glioma is largely unclear, including associated informative noncoding RNAs, such as long noncoding RNAs (lncRNA) and microRNAs (miRNAs). Methods: Expression of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), miRNA (miR)-146b-5p, and stanniocalcin-1 (STC1) was measured by real-time quantitative polymerase chain reaction and western blotting. Cell proliferation, apoptosis, migration, and invasion in vitro were examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, fluorescence-activated cell sorting method, and transwell assays, respectively. Tumor growth in vivo was determined by xenograft models. The direct interaction between genes was confirmed by dual-luciferase reporter assay. Results: Sev enhanced apoptotic rate, but inhibited cell viability, migration, and invasion abilities of human glioma A172 and U251 cells in vitro, as well as tumor growth inhibition in vivo. The tumor-suppressive role of Sev in glioma was accompanied with downregulated KCNQ1OT1 and STC1, and upregulated miR-146b-5p. Overexpression of KCNQ1OT1 through transfection reversed, while KCNQ1OT1 silencing aggravated the antitumor role of Sev in A172 and U251 cells. Moreover, KCNQ1OT1-mediated tumor-promoting activity in A172 and U251 cells under Sev treatment was abrogated by miR-146b-5p restoration or STC1 deletion. Essentially, KCNQ1OT1 could positively regulate STC1 by acting as miR-146b-5p decoy. Conclusion: KCNQ1OT1 knockdown mediated the role of Sev in glioma cell proliferation, apoptosis, migration, and invasion both in vitro and in vivo through miR-146b-5p/STC1 pathway.

5.
Curr Pharm Des ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940173

RESUMO

Edema is a gradually accumulation of fluid in the interstitial tissues or luminal cavities, which is regulated by ion transport pathways and reflects a dysfunction of fluid and salt homeostasis. Increasing evidence suggests that some herbal monomers significantly reduce organ/tissue edema. In this review, we briefly summarized the electrolyte permeability involved in pathomechanisms of organ edema, and the benefits of herbal monomers on ionic transport machinery, including Na+ -K+ -ATPase, Na+ and Clchannels, Na+ -K+ -2Clco-transporter, etc. The pharmaceutical relevance is implicated for developing advanced strategies to mitigate edematous disorders. In conclusion, the natural herbal monomers regulate electrolyte permeability in many edematous disorders, and further basic and clinical studies are needed.

6.
Curr Pharm Des ; 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32867648

RESUMO

MicroRNA (miRNA/miR) is a class of small evolutionarily conserved non-coding RNA, which can inhibit the target gene expression at post-transcriptional level and serve as significant roles in cell differentiation, proliferation, migration and apoptosis. Of note, the aberrant miR-21 has been involved in the generation and development of multiple lung diseases, and identified as a candidate of biomarker, therapeutic target, or indicator of prognosis. MiR-21 relieves acute lung injury via depressing the PTEN/Foxo1-TLR4/NF-κB signaling cascade,where as promotes lung cancer cell growth, metastasis, and chemo/radio-resistance by decreasing the expression of PTEN and PDCD4 and promoting the PI3K/AKT transduction.The purpose of this review is to elucidate the potential mechanisms of miR-21 associated lung diseases, with an emphasis on its dual regulating effects, which will trigger novel paradigms in the molecular therapy.

7.
Ann Noninvasive Electrocardiol ; : e12797, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32896950

RESUMO

In patients with preserved ejection fraction or right bundle branch block (RBBB) pattern requiring a high percentage of ventricular pacing, His-bundle pacing (HBP) might be an alternative to biventricular pacing, although the high threshold occasionally occurs. We provided a case of the intrinsic RBBB correction by capturing intra-Hisian left bundle branch (LBB) or distal His-bundle with different output settings. LBB pacing had the advantage of a much lower threshold while remained most synchrony as HBP. LBB pacing might be a promisingly safe and effective procedure for patients with high-grade atrioventricular (AV) block and RBBB pattern.

8.
Brain Res Bull ; 164: 249-256, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32896587

RESUMO

BACKGROUND: Increased permeability of blood-brain barrier (BBB) is a major pathophysiological mechanism of postoperative cognitive dysfunction (POCD) in the elderly. The reduced beneficial gut microbiome due to aging results in a decline in the production of sodium butyrate (NaB), which might enhance the BBB permeability. The present study investigated whether gut microbiome or NaB could improve the postoperative cognitive function in aged and gut dysbiosis mouse model. METHODS: A total of 210 male C57BL/6 J mice were randomly and equally divided into 7 groups (young control, young anesthesia/surgery, young anesthesia/surgery + antibiotic, aged control, aged anesthesia/surgery, aged anesthesia/surgery + Lactobacillus, aged anesthesia/surgery + NaB). Lactobacillus mix and antibiotic mix were administered by oral gavage to establish the gut dysbiosis and microbiome restoration model. Splenectomy was performed under sevoflurane anesthesia. Spatial memory learning ability was measured by Y maze. BBB permeability was detected by FITC-dextran imaging and brain tissue dextran spectrum. Tight junction (TJ) protein of hippocampus brain tissue was quantitated by Western blot. RESULT: Aging and antibiotic mix decreased the expression of the TJ, increased the BBB permeability and induced POCD, which could be reversed by the application of Lactobacillus and NaB. CONCLUSION: Lactobacillus and NaB increased the expression of TJ protein between endothelial cells (ECs), reduced the BBB permeability, and consequently protected the postoperative cognitive functions of the aged and gut dysbiosis mice.

9.
Curr Drug Targets ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32988351

RESUMO

Pulmonary fibrosis (PF) is the most common chronic, progressive interstitial lung disease, mainly occurring in the elderly, with a median survival of 2-4 years after diagnosis. Its high mortality rate attributes to the delay in diagnosis due to its generic symptoms, and more importantly, to the lack of effective treatments. MicroRNAs (miRNAs) are a class of small non-coding RNAs that involve in many essential cellular processes, including extracellular matrix remodeling, alveolar epithelial cell apoptosis, epithelial-mesenchymal transition, etc. We summarized the dysregulated miRNAs in TGF-ß signaling pathway-mediated PF in recent years with dual effects, such as anti-fibrotic let-7 family and pro-fibrotic miR-21 members. Therefore, this review will set out the latest application of miRNAs to provide a new direction for PF treatment.

10.
Life Sci ; 259: 118199, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781064

RESUMO

Cellular senescence, a process whereby cells enter a state of permanent growth arrest, appears to regulate cardiac pathological remodeling and dysfunction in response to various stresses including myocardial infarction (MI). However, the precise role as well as the underlying regulatory mechanism of cardiac cellular senescence in the ischemic heart disease remain to be further determined. Herein we report an inhibitory role of Nrf2, a key transcription factor of cellular defense, in regulating cardiac senescence in infarcted hearts as well as a therapeutic potential of targeting Nrf2-mediated suppression of cardiac senescence in the treatment of MI-induced cardiac dysfunction. MI was induced by left coronary artery ligation for 28 days in mice. Heart tissues from the infarct border zone were used for the analyses. The MI-induced cardiac dysfunction was associated with increased myocardial cell senescence, oxidative stress and apoptosis in adult wild type (WT) mice. In addition, a downregulated Nrf2 activity was associated with upregulated Keap1 levels and increased phosphorylation of JAK and FYN in the infarcted border zone heart tissues. Nrf2 Knockout (Nrf2-/-) enhanced the MI-induced myocardial, cardiac dysfunction and senescence. Qiliqiangxin (QLQX), a herbal medicine which could reverse the MI-induced suppression of Nrf2 activity, significantly inhibited the MI-induced cardiac senescence, apoptosis, and cardiac dysfunction in WT mice but not in Nrf2-/- mice. These results indicate that MI downregulates Nrf2 activity thus promoting oxidative stress to accelerate cellular senescence in the infarcted heart towards cardiac dysfunction and Nrf2 may be a drug target for suppressing the cellular senescence-associated pathologies in infarcted hearts.


Assuntos
Cardiomiopatias/genética , Cardiomiopatias/patologia , Senescência Celular/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/genética , Animais , Cardiomiopatias/diagnóstico por imagem , Ecocardiografia , Inativação Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/diagnóstico por imagem , Miócitos Cardíacos/metabolismo , RNA Interferente Pequeno/farmacologia , Remodelação Ventricular/fisiologia
11.
J Chromatogr A ; 1629: 461499, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-32836104

RESUMO

Efficient and economical separation and enrichment of high-content class compounds from complex natural plants are of great importance. This study describes a novel continuous chromatography system (CCS) with multi-zone and multi-column dynamic tandem techniques for the efficient and economical separation and enrichment of high-content class compounds from natural products. The CCS was split into eight zones (each zone covered 2 or 3 columns connected dynamically in a series) via a multi-channel logic control valve to continuously and automatically separate and enrich class compounds from complex natural plants. CCS separation conditions were optimized by static and dynamic adsorption and desorption experiments. With the CCS system, 120.82 kg of Panax notoginseng saponins (PNS) was isolated from 1.0 t of P. notoginseng. Importantly, the total contents of five main saponins (R1, Rg1, Re, Rb1, and Rd) in PNS exceeded 90%, and the recovery rate exceeded 85%. In addition, this separation system enhanced the separation efficiency and decreased the mobile phase used. Thus, CCS with multi-zone and multi-column dynamic tandem techniques is an efficient and economical method for the large-scale preparation of high-content total saponins from P. notoginseng and will have wide application prospects, especially in the large-scale preparation of high-content class compounds from natural plants.

12.
Cancer Manag Res ; 12: 6019-6031, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765101

RESUMO

Purpose: To predict multiple prognostic factors of HCC including histopathologic grade, the expression of Ki67 as well as capsule formation with intravoxel incoherent motions imaging by extracting the histogram metrics. Patients and Methods: A total of 52 patients with HCC were recruited with the MR examinations undertaken at a 3T scanner. Histogram metrics were extracted from IVIM-derived parametric maps. Independent student t-test was performed to explore the differences in metrics across different subtypes of prognostic factors. Spearman correlation test was utilized to evaluate the correlations between the IVIM metrics and prognostic factors. ROC analysis was applied to evaluate the diagnostic performance. Results: According to the independent student t-test, there were 18, 4, and 8 IVIM-derived histogram metrics showing the capability for differentiating the subtypes of histopathologic grade, Ki67, and capsule formation, respectively, with P-values of less than 0.05. Besides, there existed a lot of significant correlations between IVIM metrics and prognostic factors. Finally, by integrating different histogram metrics showing significant differences between various subgroups together via establishing logistic regression based diagnostic models, greatest diagnostic power was obtained for grading HCC (AUC=0.917), diagnosing patients with highly expressed Ki67 (AUC=0.861) and diagnosing patients with capsule formation (AUC=0.839). Conclusion: Multiple prognostic factors including histopathologic grade, Ki67 expression status, and capsule formation can be accurately predicted with assistance of histogram metrics sourced from a single IVIM scan.

13.
Sensors (Basel) ; 20(15)2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32759800

RESUMO

Standard convolutional filters usually capture unnecessary overlap of features resulting in a waste of computational cost. In this paper, we aim to solve this problem by proposing a novel Learned Depthwise Separable Convolution (LdsConv) operation that is smart but has a strong capacity for learning. It integrates the pruning technique into the design of convolutional filters, formulated as a generic convolutional unit that can be used as a direct replacement of convolutions without any adjustments of the architecture. To show the effectiveness of the proposed method, experiments are carried out using the state-of-the-art convolutional neural networks (CNNs), including ResNet, DenseNet, SE-ResNet and MobileNet, respectively. The results show that by simply replacing the original convolution with LdsConv in these CNNs, it can achieve a significantly improved accuracy while reducing computational cost. For the case of ResNet50, the FLOPs can be reduced by 40.9%, meanwhile the accuracy on the associated ImageNet increases.

14.
Acta Pharmacol Sin ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814818

RESUMO

Cardiac fibrosis is a typical pathological change in various cardiovascular diseases. Although it has been recognized as a crucial risk factor responsible for heart failure, there is still a lack of effective treatment. Recent evidence shows that microRNAs (miRNAs) play an important role in the development of cardiac fibrosis and represent novel therapeutic targets. In this study we tried to identify the cardiac fibrosis-associated miRNA and elucidate its regulatory mechanisms in mice. Cardiac fibrosis was induced by infusion of angiotensin II (Ang II, 2 mg·kg-1·d-1) for 2 weeks via osmotic pumps. We showed that Ang II infusion induced cardiac disfunction and fibrosis accompanied by markedly increased expression level of miR-99b-3p in heart tissues. Upregulation of miR-99b-3p and fibrotic responses were also observed in cultured rat cardiac fibroblasts (CFs) treated with Ang II (100 nM) in vitro. Transfection with miR-99b-3p mimic resulted in the overproduction of fibronectin, collagen I, vimentin and α-SMA, and facilitated the proliferation and migration of CFs. On the contrary, transfection with specific miR-99b-3p inhibitor attenuated Ang II-induced fibrotic responses. Similarly, intravenous injection of specific miR-99b-3p antagomir could prevent Ang II-infused mice from cardiac dysfunction and fibrosis. We identified glycogen synthase kinase-3 beta (GSK-3ß) as a direct target of miR-99b-3p. In CFs, miR-99b-3p mimic significantly reduced the expression of GSK-3ß, leading to activation of its downstream profibrotic effector Smad3, whereas miR-99b-3p inhibitor caused anti-fibrotic effects. GSK-3ß knockdown ameliorated the anti-fibrotic role of miR-99b-3p inhibitor. These results suggest that miR-99b-3p contributes to Ang II-induced cardiac fibrosis at least partially through GSK-3ß. The modulation of miR-99b-3p may provide a new approach for tackling fibrosis-related cardiomyopathy.

15.
Curr Pharm Des ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32842936

RESUMO

Steady and continuous supply of oxygen is important for humans, since an excess or deficiency in oxygen levels may result in the death of cells, tissue, or the organism. As a mechanical barrier against pathogens, the respiratory epithelium is always exposed to hypoxia in some detrimental external environment and/or pathologic state. The barrier function is accordingly impaired as a result of disrupted cell composition ratio, ion transport, and tight junctions in a hypoxia-inducible factor dependent or independent way. Hypoxia has been identified as an element of the primary or secondary pathogenic factors of many respiratory diseases, but the relationship between hypoxia and epithelial barrier dysfunction is not fully understood. Thus we summarized recent researches on epithelial barrier dysfunction induced by hypoxia in respiratory system, aiming to explore the possible therapeutic targets in hypoxia related respiratory system diseases.

16.
Acta Pharmacol Sin ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32860005

RESUMO

Forsythin extracted from Forsythiae Fructus is widely used to treat fever caused by the common cold or influenza in China, Japan and Korea. The present study aimed to analyze the pharmacokinetics, metabolism and excretion routes of forsythin in humans and determine the major enzymes and transporters involved in these processes. After a single oral administration, forsythin underwent extensive metabolism via hydrolysis and further sulfation. In total, 3 of the 13 metabolites were confirmed by comparison to reference substances, i.e., aglycone M1, M1 sulfate (M2), and M1 glucuronide (M7). Hydrolysis was the initial and main metabolic pathway of the parent compound, followed by extensive sulfation to form M2 and a reduced level of glucuronidation to form M7. In addition, the plasma exposure of M2 and M7 were 86- and 4.2-fold higher than that of forsythin. Within 48 h, ~75.1% of the administered dose was found in urine, with M2 accounting for 71.6%. Further phenotyping experiments revealed that sulfotransferase 1A1 and UDP-glucuronosyltransferase 1A8 were the most active hepatic enzymes involved in the formation of M2 and M7, respectively. The in vitro kinetic study provided direct evidence that M1 showed a preference for sulfation. Sulfated conjugate M2 was identified as a specific substrate of organic anion transporter 3, which could facilitate the renal excretion of M2. Altogether, our study demonstrated that sulfation dominated the metabolism and pharmacokinetics of forsythin, while the sulfate conjugate was excreted mainly in the urine.

17.
J Neuroinflammation ; 17(1): 250, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859236

RESUMO

BACKGROUND: Mast cells play an important role in early immune reactions in the brain by degranulation and the consequent inflammatory response. Our aim of the study is to investigate the effects of rh-relaxin-2 on mast cells and the underlying mechanisms in a germinal matrix hemorrhage (GMH) rat model. METHODS: One hundred seventy-three P7 rat pups were subjected to GMH by an intraparenchymal injection of bacterial collagenase. Clodronate liposome was administered through intracerebroventricular (i.c.v.) injections 24 h prior to GMH to inhibit microglia. Rh-relaxin-2 was administered intraperitoneally at 1 h and 13 h after GMH. Small interfering RNA of RXFP1 and PI3K inhibitor LY294002 were given by i.c.v. injection. Post-GMH evaluation included neurobehavioral function, Western blot analysis, immunofluorescence, Nissl staining, and toluidine blue staining. RESULTS: Our results demonstrated that endogenous relaxin-2 was downregulated and that RXFP1 level peaked on the first day after GMH. Administration of rh-relaxin-2 improved neurological functions, attenuated degranulation of mast cells and neuroinflammation, and ameliorated post-hemorrhagic hydrocephalus (PHH) after GMH. These effects were associated with RXFP1 activation, increased expression of PI3K, phosphorylated AKT and TNFAIP3, and decreased levels of phosphorylated NF-κB, tryptase, chymase, IL-6, and TNF-α. However, knockdown of RXFP1 and PI3K inhibition abolished the protective effects of rh-relaxin-2. CONCLUSIONS: Our findings showed that rh-relaxin-2 attenuated degranulation of mast cells and neuroinflammation, improved neurological outcomes, and ameliorated hydrocephalus after GMH through RXFP1/PI3K-AKT/TNFAIP3/NF-κB signaling pathway.

18.
Bone Joint J ; 102-B(8): 981-996, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731832

RESUMO

AIMS: Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition. METHODS: Seven databases were searched for studies of HS and ACDF from inception of the study to 1 September 2019. Both random-effects and fixed-effects models were used to evaluate the overall effect of the C2-C7 range of motion (ROM), ROM of superior/inferior adjacent levels, adjacent segment degeneration (ASD), heterotopic ossification (HO), complications, neck disability index (NDI) score, visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Odom's criteria, blood loss, and operating and hospitalization time. To obtain more credible results contour-enhanced funnel plots, Egger's and Begg's tests, meta-regression, and sensitivity analyses were performed. RESULTS: In total, 17 studies involving 861 patients were included in the analysis. HS was found to be superior to ACDF in maintaining C2-C7 ROM and ROM of superior/inferior adjacent levels, but HS did not reduce the incidence of associated level ASD. Also, HS did not cause a higher rate of HO than ACDF. The frequency of complications was similar between the two techniques. HS failed to achieve more favourable outcomes than ACDF using the NDI, VAS, JOA, and Odom's scores. HS did not show any more advantages in operating or hospitalization time but did show reduction in blood loss. CONCLUSION: Although HS maintained cervical kinetics, it failed to reduce the incidence of ASD. This finding differs from previous reports. Moreover, patients did not show more benefits from HS with respect to symptom improvement, prevention of complications, and clinical outcomes. Cite this article: Bone Joint J 2020;102-B(8):981-996.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia/métodos , Degeneração do Disco Intervertebral/cirurgia , Amplitude de Movimento Articular/fisiologia , Fusão Vertebral/métodos , Substituição Total de Disco/métodos , Adulto , Idoso , Bases de Dados Factuais , Avaliação da Deficiência , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Japão , Masculino , Pessoa de Meia-Idade , Cervicalgia/etiologia , Cervicalgia/fisiopatologia , Cervicalgia/cirurgia , Medição da Dor , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilose/diagnóstico por imagem , Espondilose/cirurgia , Resultado do Tratamento
19.
Chaos ; 30(7): 073118, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32752620

RESUMO

The role of sequence complexity in 23 051 somatic missense mutations including 73 well-known mutation hotspots across 22 major cancers was studied in human TP53 proteins. A role for sequence complexity in TP53 protein mutations is suggested since (i) the mutation rate significantly increases in low amino acid pair bias complexity; (ii) probability distribution complexity increases following single point substitution mutations and strikingly increases after mutation at the mutation hotspots including six detectable hotspot mutations (R175, G245, R248, R249, R273, and R282); and (iii) the degree of increase in distribution complexity is significantly correlated with the frequency of missense mutations (r = -0.5758, P < 0.0001) across 20 major types of solid tumors. These results are consistent with the hypothesis that amino acid pair bias and distribution probability may be used as novel measures for protein sequence complexity, and the degree of complexity is related to its susceptibility to mutation, as such, it may be used as a predictor for modeling protein mutations in human cancers.

20.
Biosci Rep ; 40(8)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32744323

RESUMO

BACKGROUNDS: Rheumatoid arthritis (RA) is a frequent autoimmune disease. Emerging evidence indicated that ZNFX1 antisense RNA1 (ZFAS1) participates in the physiological and pathological processes in RA. However, knowledge of ZFAS1 in RA is limited, the potential work pathway of ZFAS1 needs to be further investigated. METHODS: Levels of ZFAS1, microRNA (miR)-2682-5p, and ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to explore the ability of cell proliferation in fibroblast-like synoviocytes (FLS-RA). Cell apoptosis was measured via flow cytometry. Also, levels of ADAMTS9, apoptosis-related proteins, cleaved-caspase-3 (active large subunit), and autophagy-related proteins were identified adopting Western blot. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the productions of inflammatory cytokines. Beside, the interrelation between miR-2682-5p and ZFAS1 or ADAMTS9 was verified utilizing dual-luciferase reporter assay. RESULTS: High levels of ZFAS1 and ADAMTS9, and a low level of miR-2682-5p were observed in RA synovial tissues and FLS-RA. Knockdown of ZFAS1 led to the curbs of cell proliferation, inflammation, autophagy, and boost apoptosis in FLS-RA, while these effects were abolished via regaining miR-2682-5p inhibition. Additionally, the influence of miR-2682-5p on cell phenotypes and inflammatory response were eliminated by ADAMTS9 up-regulation in FLS-RA. Mechanically, ZFAS1 exerted its role through miR-2682-5p/ADAMTS9 axis in RA. CONCLUSION: ZFAS1/miR-2682-5p/ADAMTS9 axis could modulate the cell behaviors, inflammatory response in FLS-RA, might provide a potential therapeutic target for RA treatment.

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