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1.
Am J Physiol Renal Physiol ; 321(4): F517-F526, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34486400

RESUMO

Increasing evidence shows that long noncoding RNAs (lncRNAs) play an important role in kidney disease. In this study, we investigated the role of the lncRNA growth arrest-specific 5 (GAS5) in the pathogenesis of renal fibrosis. We found that GAS5 was markedly decreased in the fibrotic kidney of a unilateral ureteral obstructive nephropathy mouse model. In addition, GAS5 was expressed in mouse tubular epithelial cells (mTECs) and interstitial fibroblasts in normal renal tissue and was especially highly expressed in the cytoplasm. In vitro experiments showed that GAS5 was downregulated by transforming growth factor-ß1 (TGF-ß1) in a dose- and time-dependent manner. Overexpression of GAS5 blocked TGF-ß1-induced collagen type I and fibronectin expression and vice versa. Mechanistic experiments revealed that Smad3 but not Smad2 drove the regulation of GAS5. More importantly, GAS5 interacted with miR-142-5p and was involved in the renoprotective effect by participating in the competing endogenous RNA network. Finally, we also found that knockdown of GAS5 promoted TGF-ß1-induced mouse tubular epithelial cell apoptosis via the Smad3 pathway. Taken together, our results uncovered a lncRNA/miRNA competing endogenous RNA network-based mechanism that modulates extracellular matrix formation and cell apoptosis via the Smad3 pathway.NEW & NOTEWORTHY In this work, we mainly discuss long noncoding RNA growth arrest-specific 5 (GAS5), acting in a renoprotective role via the Smad3/miRNA-142-5p axis, that modulates extracellular matrix formation and cell apoptosis. Overexpression of GAS5 effectively blocked renal fibrosis in vitro. This study reveals that GAS5 may represent as a novel and precision therapeutic target for alleviating renal fibrosis.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 590-594, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494531

RESUMO

Objective To investigate the oral health status and awareness of urban children in Lhasa,aiming to provide a data basis for the prevention and treatment of children's caries and the promotion of oral health education. Methods A total of 504 Tibetan students were selected by cluster sampling from 2 primary schools in Chengguan District of Lhasa.All the participants were required to take oral health examination and complete a questionnaire about oral health awareness and behavior. Results The caries prevalence rate and mean decayed-missing-filled tooth(DMFT)of permanent teeth were 75.00% and 2.18±1.91,respectively.The rates of pit and fissure sealant and filling of permanent teeth were 3.77% and 6.81%,respectively.The caries prevalence rate of first permanent molars was 47.62%.The mean DMFT of permanent teeth and caries prevalence rate of first permanent molar were significantly higher in female group(P=0.001 and P=0.007,respectively).The prevalence rate of dental fluorosis was 61.51%,and the detection rate of dental calculus was 71.83%.Multivariate logistic regression analysis showed that prevalence of caries was influenced by many independent factors including gender,oral health awareness,intention of dental intervention,and dental experience. Conclusion High caries prevalence rate,low filling rate,and poor oral hygiene and health awareness were found among the primary school students in Lhasa,which require continuous dentistry investment and oral health education for the local students and their parents.


Assuntos
Cárie Dentária , Saúde Bucal , Criança , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Higiene Bucal , Prevalência , Instituições Acadêmicas , Estudantes , Inquéritos e Questionários
3.
Int J Nanomedicine ; 16: 5755-5776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471351

RESUMO

Background: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration. Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly. Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and -15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect. Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.

5.
Int Ophthalmol ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313929

RESUMO

OBJECTIVE: To investigate the role of miR-93-5p in rats with type 2 diabetic retinopathy (DR) through targeting Sirt1. METHODS: The targeting correlation between miR-93-5p and Sirt1 was validated by dual-luciferase reporter gene assay. Type 2 diabetes mellitus (T2DM) rat models were received intravitreal injection of antagomir NC (negative control), miR-93-5p antagomir, miR-93-5p agomir and/or recombinant Sirt1, followed by observation of pathological changes in retina via HE staining. Besides, retinal vascular permeability was determined by fluorescein isothiocyanate-bovine serum albumin (FITC-BSA), while the retinal vasculature was observed through retinal trypsin digestion. Expression of miR-93-5p and Sirt1 was measured by qRT-PCR and Western blotting, while the levels of VEGF, proinflammatory cytokines and anti-oxidative indicators were determined using corresponding kits. RESULTS: MiR-93-5p could target Sirt1 as analyzed by the luciferase reporter gene assay. Rats in the T2DM group presented the up-regulation of miR-93-5p and down-regulation of Sirt1 in the retina, and miR-93-5p inhibition could up-regulate Sirt1 expression in the T2DM rats. Recombinant Sirt1 decreased retinal vascular permeability and acellular capillaries with improved pathological changes in retina from T2DM rats, which was abolished by miR-93-5p agomir. Moreover, miR-93-5p inhibition or Sirt1 overexpression decreased the levels of VEGF and proinflammatory cytokines while enhancing the activity of anti-oxidative indicators. However, indicators above had no significant differences between T2DM group and T2DM + agomir + Sirt1 group. CONCLUSION: MiR-93-5p, via targeting Sirt1, could affect the vascular permeability and acellular capillaries and mitigate the inflammation and oxidative stress in the retinas, which may play a critical role in DR.

6.
J Neurol ; 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34218292

RESUMO

PURPOSE: We aimed to investigate the ability of MRI radiomics features-based machine learning (ML) models to classify the time since stroke onset (TSS), which could aid in stroke assessment and treatment options. METHODS: This study involved 84 patients with acute ischemic stroke due to anterior circulation artery occlusion (51 in the training cohort and 33 in the independent test cohort). Region of infarct segmentation was manually outlined by 3D-slicer software. Image processing including registration, normalization and radiomics features calculation were done in R (version 3.6.1). A total of 4312 radiomic features from each image sequence were captured and used in six ML models to estimate stroke onset time for binary classification (≤ 4.5 h). Receiver-operating characteristic curve (ROC) and other parameters were calculated to evaluate the performance of the models in both training and test cohorts. RESULTS: Twelve radiomics and six clinic features were selected to construct the ML models for TSS classification. The deep learning model-based DWI/ADC radiomic features performed the best for binary TSS classification in the independent test cohort, with an AUC of 0.754, accuracy of 0.788, sensitivity of 0.952, specificity of 0.500, positive predictive value of 0.769, and negative predictive value of 0.857, respectively. Furthermore, adding clinical information did not improve the performance of the DWI/ADC-based deep learning model. The TSS prediction models can be visited at: http://123.57.65.199:3838/deeptss/ . CONCLUSIONS: A unique deep learning model based on DWI/ADC radiomic features was constructed for TSS classification, which could aid in decision making for thrombolysis in patients with unknown stroke onset.

7.
J Cancer Res Ther ; 17(3): 695-701, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269301

RESUMO

Objectives: The aim of the study was to compare the relative diagnostic utility of low-dose computed tomography (LDCT) and standard-dose computed tomography (SDCT)-guided lung biopsy approaches. Materials and Methods: The PubMed, Embase, and Cochrane Library databases were searched for relevant studies published through August 2020. Data pertaining to endpoints including technical success, diagnostic performance, operative time, radiation dose, and complications, were extracted, and meta-analysis was performed using RevMan v5.3. Results: Three retrospective analyses and three randomized controlled trials, were included. The studies included 1977 lung lesions across 1927 patients who underwent LDCT-guided lung biopsy, and 887 lung lesions across 879 patients who underwent SDCT-guided lung biopsy. No significant differences were observed between these LDCT and SDCT groups with respect to the rates of technical success (99.0% vs. 99.5%, odds ratio [OR]: 1.82, P = 0.35,), diagnostic yield (79.6% vs. 76.2%, OR: 0.93, P = 0.47), diagnostic accuracy (96.1% vs. 96.1%, OR: 0.93, P = 0.69), operative time (mean difference [MD]: 1.04, P = 0.30), pneumothorax (19.9% vs. 21.3%, OR: 0.92, P = 0.43) or hemoptysis (4.6% vs. 5.8%, OR: 1.14, P = 0.54). Patients in the LDCT group received a significantly lower radiation dose (MD: ‒209.87, P < 0.00001) than patients in the SDCT group. Significant heterogeneity was observed with respect to the operative duration and radiation dose endpoints (I2 = 84% and 100%, respectively). Conclusions: Relative to SDCT-guided lung biopsy, an LDCT-guided approach is equally safe and can achieve comparable diagnostic efficacy while exposing patients to lower doses of radiation.

8.
Neural Netw ; 142: 351-362, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34116448

RESUMO

Saliency detection is an important and challenging research topic due to the variety and complexity of the background and saliency regions. In this paper, we present a novel unsupervised saliency detection approach by exploiting the grouping and compactness characteristics of the high-level semantic features. First, for the high-level semantic feature, the elastic net based hypergraph model is adopted to discover the group structure relationships of salient regional points, and the calculation of the spatial distribution is constructed to detect the compactness of the saliency regions. Next, the grouping-based and compactness-based saliency maps are improved by a propagation algorithm. The propagation process uses an enhanced similarity matrix, which fuses the low-level deep feature and the high-level semantic feature through cross diffusion. Results on four benchmark datasets with pixel-wise accurate labeling demonstrate the effectiveness of the proposed method. Particularly, the proposed unsupervised method achieves competitive performance with deep learning-based methods.

9.
J Insect Physiol ; 131: 104238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33839141

RESUMO

The ability to detect and remove dead adult bees is an essential part of honeybee colony fitness that prevents the spread of pathogens. Fatty acid olfactory cues stimulate undertaking behavior among different social species within Hymenoptera, but the chemicals responsible for the death cue in Apis cerana have not yet been identified. We explored the Nasonov gland as a potential source of these chemicals in A. cerana. Gas chromatography indicated that unlike A. mellifera, the A. cerana Nasonov gland does not contain any volatile terpenes, only fatty acids. As a bioassay, dead honeybees were rinsed free of their individual cuticular hydrocarbons via dichloromethane and two concentrations of oleic acid and a synthetic blend of the Nasonov pheromone in A. cerana were applied to the dummies. Results showed that oleic acid did not stimulate corpse removal in A. cerana. However, the synthetic pheromone blend of A. cerana Nasonov did stimulate removal.


Assuntos
Abelhas/química , Morte , Feromônios/química , Animais , Comportamento Animal , Sinais (Psicologia)
10.
Neuroreport ; 32(5): 378-385, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33661805

RESUMO

The myeloid differentiation factor 88 (MyD88) adaptor mediates signaling by Toll-like receptors and some interleukins (ILs) in neural and non-neuronal cells. Recently, MyD88 protein was found to express in primary sensory neurons and be involved in the maintenance of persistent pain induced by complete Freund's adjuvant, chronic constriction injury and chemotherapy treatment in rodents. However, whether MyD88 in nociceptive neurons contributes to persistent pain induced by intraplantar injection of formalin remains elusive. Here, using conditional knockout (CKO) mice, we found that selective deletion of Myd88 in Nav1.8-expressing primary nociceptive neurons led to reduced pain response in the recovery phase of 1% formalin-induced mechanical pain and impaired the persistent thermal pain. Moreover, CKO mice exhibited reduced phase II pain response in 1%, but not 5%, formalin-induced acute inflammatory pain. Finally, nociceptor MyD88 deletion resulted in less neuronal c-Fos activation in spinal dorsal horns following 1% formalin stimulation. These data suggest that MyD88 in nociceptive neurons is not only involved in persistent mechanical pain but also promotes the transition from acute inflammatory pain to persistent thermal hyperalgesia induced by low-dose formalin stimulation.

11.
Pain Ther ; 10(1): 165-179, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33575953

RESUMO

INTRODUCTION: Opioid-induced constipation (OIC) is a distressing side effect during opioid analgesia and is mainly mediated by gastrointestinal µ-opioid receptors. Methylnaltrexone, a peripheral µ-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may alleviate OIC without reversing analgesia. We performed a meta-analysis to assess the efficacy and safety of methylnaltrexone for the treatment of OIC. METHODS: This meta-analysis was registered in PROSPERO (CRD42020187290). We searched PubMed, Embase, and Cochrane Library for randomized controlled trials that compared methylnaltrexone with placebo for the treatment of OIC. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effects model. We used the GRADE approach to assess the certainty of the evidence. RESULTS: Eight trials with 2034 participants were included. Compared with placebo, methylnaltrexone significantly increased rescue-free bowel movement (RFBM) within 4 h after the first dose (eight trials; 1833 participants; RR 3.74, 95% CI 3.02-4.62; high-certainty evidence), RFBM within 24 h after the first dose (two trials; 614 participants; RR 1.98, 95% CI 1.52-2.58; moderate-certainty evidence), and RFBM ≥ 3 times per week (three trials; 1,396 participants; RR 1.33, 95% CI 1.17-1.52; moderate-certainty evidence) and decreased need to take rescue laxatives (three trials; 807 participants; RR 0.73, 95% CI 0.63-0.85; moderate-certainty evidence). For safety outcomes, there was no difference in any adverse events between the two groups (eight trials; 2034 participants; RR 1.11, 95% CI 0.99-1.23; moderate-certainty evidence), including diarrhea, nausea, vomiting, and flatulence; but for the most commonly reported adverse events, the abdominal pain was higher in methylnaltrexone group than that in placebo group (six trials; 1813 participants; RR 2.30, 95% CI 1.29-4.08; moderate-certainty evidence). CONCLUSION: Methylnaltrexone is an effective and safe drug for the treatment of OIC, but the safety of abdominal pain should be considered.

12.
Chem Commun (Camb) ; 57(24): 3010-3013, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33623947

RESUMO

Two fascinating triply interlocked [2]catenanes and one simple triangular prism metallacage were constructed by tuning the widths of the organometallic dinuclear building blocks. Notably, the interlocked architectures were disassembled in the presence of large aromatic molecules to form their corresponding monomeric host-guest complexes.

13.
Invest Ophthalmol Vis Sci ; 62(2): 33, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33616621

RESUMO

Purpose: Meibomian glands play a vital role in maintaining ocular surface stability. This study aimed to investigate whether Hedgehog signaling is involved in the regulation of meibomian gland epithelial cells. Methods: Rat meibomian glands epithelial cells (RMGECs) were isolated from ducts and ductules, and then were cultivated to passage two on Matrigel coated wells in meibomian gland epithelial cells medium (MGECM). Cells were switched from MGECM to differentiation medium (DM) or DM added 10 µg/mL azithromycin (DM + AZM) when reached 50% to 60% confluence. The effects of the Smoothened (Smo) agonist (Smo agonist [SAG]) and antagonist (by cyclopamine) on RMGECs were analyzed using quantitative RT-PCR, cell proliferation analysis, immunofluorescence staining, and Nile red staining. Results: The Hedgehog receptor, Smo, and its downstream molecules, Glis, were expressed both in vivo and in vitro. Smo and Gli1 both decreased with the increase of differentiation in vitro. Smo antagonist, cyclopamine, reduced cell numbers, and the expression of Ki67 in MGECM, and promoted the expression of SREBP1 and lipid production in DM + AZM. Smo agonist, SAG, inhibited the expression of SREBP1 and lipid accumulation in DM + AZM but showed no significant effects on raising cell numbers and the expression of Ki67 in MGECM. Conclusions: The Hedgehog signaling pathway appears to play important roles in RMGECs proliferation and differentiation. This may provide a potential therapeutic way to treat meibomian gland dysfunction (MGD).


Assuntos
Células Epiteliais/metabolismo , Proteínas Hedgehog/genética , Disfunção da Glândula Tarsal/genética , Glândulas Tarsais/metabolismo , Animais , Contagem de Células , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/patologia , Proteínas Hedgehog/metabolismo , Masculino , Disfunção da Glândula Tarsal/metabolismo , Disfunção da Glândula Tarsal/patologia , Glândulas Tarsais/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
14.
Trials ; 22(1): 85, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482853

RESUMO

BACKGROUND: Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease and a leading cause of death worldwide. The clinical utility of commonly used lipid-lowering drugs such as statins and fibrates is sometimes limited by the occurrence of various adverse reactions. Recently, berberine (BBR) has received increasing attention as a safer and more cost-effective option to manage dyslipidemia. Thus, a high-quality randomized controlled trial to evaluate the efficacy and safety of BBR in the treatment of dyslipidemia is deemed necessary. METHODS/DESIGN: This is a randomized, double-blind, and placebo-controlled clinical trial. A total of 118 patients with dyslipidemia will be enrolled in this study and randomized into two groups at a ratio of 1:1. BBR or placebo will be taken orally for 12 weeks. The primary outcome is the percentage of low-density lipoprotein cholesterol reduction at week 12. Other outcome measures include changes in other lipid profiles, high sensitivity C-reactive protein, blood pressure, body weight, Bristol Stool Chart, traditional Chinese medicine symptom form, adipokine profiles, and metagenomics of intestinal microbiota. Safety assessment includes general physical examination, blood and urine routine test, liver and kidney function test, and adverse events. DISCUSSION: This trial may provide high-quality evidence on the efficacy and safety of BBR for dyslipidemia. Importantly, the findings of this trial will help to identify patient and disease characteristics that may predict favorable outcomes of treatment with BBR and optimize its indication for clinical use. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021361 . Registered on 17 February 2019.


Assuntos
Berberina , Medicamentos de Ervas Chinesas , Dislipidemias , Berberina/efeitos adversos , Gerenciamento de Dados , Método Duplo-Cego , Dislipidemias/diagnóstico , Dislipidemias/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Mol Ther ; 29(1): 365-375, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-32956626

RESUMO

Diabetic nephropathy (DN) is a major cause of end-stage renal disease, but treatment remains ineffective. C-reactive protein (CRP) is pathogenic in DN, which significantly correlated with dipeptidyl peptidase-4 (DPP4) expression in diabetic patients with unknown reason. Here, using our unique CRPtg-db/db mice, we observed human CRP markedly induced renal DPP4 associated with enhanced kidney injury compared with db/db mice. Interestingly, linagliptin, a US Food and Drug Administration (FDA)-approved specific DPP4 inhibitor, effectively blocked this CRP-driven DN in the CRPtg-db/db mice. Mechanistically, CRP evoked DPP4 in cultured renal tubular epithelial cells, where CD32b/nuclear factor κB (NF-κB) signaling markedly enriched p65 binding on the DPP4 promoter region to increase its transcription. Unexpectedly, we further discovered that CRP triggers dimerization of DPP4 with CD32b at protein level, forming a novel DPP4/CD32b/NF-κB signaling circuit for promoting CRP-mediated DN. More importantly, linagliptin effectively blocked the circuit, thereby inhibiting the CRP/CD32b/NF-κB-driven renal inflammation and fibrosis. Thus, DPP4 may represent a precise druggable target for CRP-driven DN.

16.
Nat Prod Res ; 35(4): 637-640, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30856004

RESUMO

Vibsane-type diterpenes, the characteristic compounds of Viburnum odoratissimum, exhibited significant cytotoxicity in many cancer cells. To search for the potential target of vibsane-type diterpenes on lung cancer, we combined methods of network pharmacology prediction and experimental verification. 80 active ingredients, 23 potential targets and 39 related pathways were analyzed through constructing the compound-target network and target-pathway network, and the potential target (EGFR) and key pathway (PI3K/Akt) were identified. Vibsanol C, an isolated vibsane-type diterpene with excellent cytotoxicity against lung cancer cells was chosen for further confirmation. Molecular docking study and drug affinity responsive target stability (DARTS) approach further indicated that EGFR is a direct target of Vibsanol C. Moreover, mechanistic studies revealed Vibsanol C might affect PI3K/Akt pathway by Western blot analysis. In conclusion, this study successfully predicted and confirmed the potential target of Vibsane-type diterpenes on lung cancer.


Assuntos
Antineoplásicos/farmacologia , Diterpenos/farmacologia , Viburnum/química , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Dalton Trans ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33325957

RESUMO

Three new NiII/CoII-metal organic frameworks were self-assembled by the reaction of C3 symmetric 1,3,5-tribenzoic acid (H3BTC) and 2,4,6-tris(4-pyridyl)-1,3,5-triazine (4-TPT) ligands and NiII/CoII salts under solvothermal conditions. Isomorphous MOF1 and MOF2 exhibit a 3D pillar-layer framework based on binuclear M2(OH)(COO)2 units connected by tritopic BTC3- and 4-TPT ligands with a novel (3,5)-connected topology net. MOF3 displays a 3-fold interpenetrated 3D network exhibiting a (3,4)-connected topology net. The porous MOF3 can reversibly take up I2. The activated MOFs contain both Lewis acid (NiII center) and basic (uncoordinated pyridyl or carboxylic groups) sites, and act as bifunctional acid-base catalysts. The catalytic measurements demonstrate that the activated MOF3 exhibits good activities for benzyl alcohol oxidation and the Knoevenagel reaction and can be recycled and reused for at least four cycles without losing its structural integrity and high catalytic activity. Thus, the catalytic properties for the oxidation-Knoevenagel cascade reaction have also been studied.

18.
Biomed Res Int ; 2020: 4854390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381555

RESUMO

Introduction: DNA methylation plays a vital role in prognosis prediction of cancers. In this study, we aimed to identify novel DNA methylation site biomarkers and create an efficient methylated site model for predicting survival in kidney renal papillary cell carcinoma (KIRP). Methods: DNA methylation and gene expression profile data were downloaded from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Differential methylated genes (DMGs) and differential expression genes (DEGs) were identified and then searched for the hub genes. Cox proportional hazards regression was applied to identify DNA methylated site biomarkers from the hub genes. Kaplan-Meier survival and ROC analyses were used to validate the effective prognostic ability of the methylation gene site biomarker. The biomarker sites were validated in the GEO cohorts. The GO and KEGG annotation was done to explore the biological function of DNA methylated site signature. Results: Nine DMGs with opposite expression patterns containing 47 methylated sites were identified. Finally, four methylated sites were identified using the hazard regression model (cg04448376, cg24387542, cg08548498, and cg14621323) located in UTY, LGALS9B, SLPI, and PFN3, respectively. These sites classified patients into high- and low-risk groups in the training cohort. The 5-year survival rates for patients with low-risk and high-risk scores were 97.5% and 75.9% (P < 0.001). The prognostic accuracy and signature methylation sites were validated in the test (TCGA, n = 87) and GEO cohorts (n = 14). Multivariate regression analysis showed that the signature was an independent prediction prognostic factor for KIRP. Based on this analysis, we developed methylated site signature nomogram that predicts an individual's risk of survival. Functional analysis suggested that these signature genes are involved in the biological processes of protein binding. Conclusions: Our study demonstrated that the methylated gene site signature might be a powerful prognostic tool for evaluating survival rate and guiding tailored therapy for KIRP patients.


Assuntos
Carcinoma de Células Renais , Metilação de DNA/genética , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Transcriptoma/genética
19.
Am J Nephrol ; 51(11): 907-918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152735

RESUMO

BACKGROUND: Kidney fibrosis is the ultimate consequence of advanced stages of chronic kidney disease (CKD); however, there are currently no reliable biomarkers or noninvasive diagnostic tests available for the detection of kidney fibrosis. Lysyl oxidase (LOX) promotes collagen cross-linking, and serum LOX levels have been shown to be elevated in patients with fibrosis of the heart, lungs, and liver. However, serum LOX levels have not been reported in patients with kidney fibrosis. We explored whether serum LOX levels are associated with kidney fibrosis. METHOD: Overall, 202 patients with kidney disease underwent renal biopsy, scoring of kidney fibrosis, and determination of the area of kidney fibrosis. LOX levels were measured in serum and in kidney tissues. We analyzed the association of circulating LOX and tissue LOX levels with the scores and areas of kidney fibrosis. LOX expression was also investigated with in vitro and in vivo kidney fibrosis models. RESULTS: Serum LOX levels were higher in patients with kidney fibrosis than in those without kidney fibrosis (p < 0.001) and higher in patients with moderate-severe kidney fibrosis than in patients with mild kidney fibrosis (p < 0.001). Both serum LOX and renal tissue LOX levels correlated with the area of kidney fibrosis (r = 0.748, p < 0.001; r = 0.899, p < 0.001, respectively). Receiver operating characteristic curve analysis of serum LOX levels showed an area under the curve of 0.80 (95% CI: 0.74-0.86). The optimal serum LOX level cutoff point was 253.34 pg/mL for the prediction of kidney fibrosis and 306.56 pg/mL for the prediction of moderate-severe kidney fibrosis. LOX expression levels were significantly upregulated (2.3-2.6 and 6-fold, respectively) in in vitro and in vivo interstitial fibrosis models. CONCLUSIONS: Both serum LOX and tissue LOX levels correlated with the presence and degree of kidney fibrosis in patients with CKD. These results suggest that serum LOX levels could potentially serve as a noninvasive diagnostic biomarker for kidney fibrosis and may further potentially serve as a stratified biomarker for the identification of mild and moderate-severe kidney fibrosis.

20.
J Stroke Cerebrovasc Dis ; 29(9): 105041, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807453

RESUMO

BACKGROUND AND PURPOSE: Ischemia-reperfusion injuries (IRIs) can aggravate the condition of some patients with acute occlusion of major intracranial artery (AOMIA) who received endovascular thrombectomy. Here, we provided data confirming the association of Repressor Element-1 Silencing Transcription factor (REST) with the long-term neuroprotective effect of the middle cerebral artery occlusion (MCAO) rats underwent Gradual Flow Restoration (GFR). METHODS: Long term neuroprotective effects of GFR intervention were evaluated on MCAO rats model after 3d and 7d reperfusion. The neurological deficit score and TTC staining were performed to evaluate the degree of brain damage in GFR and other interventions at different time. Differentially expressed genes related to cerebral ischemia reperfusion injury (CIRI) were initially screened and identified using GSE32529 microarray analysis. REST protein expression in rat brain cortex infarction was detected by Western blot analysis. RESULTS: MCAO rats intervened with GFR exhibited reduced neurological deficit (P < 0.05) and alleviated brain infarction volume (P < 0.01). The REST gene with up-regulated expression and its downstream genes with down-regulated expression were screened by Microarray analysis. The brain cortex infarction in MCAO rats produced high levels of REST expression. The GFR intervention inhibited REST expression, and alleviated brain injury on MCAO rats. CONCLUSION: Our results demonstrated that GFR intervention plays a long-term neuroprotective role and reduces brain edema and damage at reperfusion, possibly by inhibiting REST expression.


Assuntos
Edema Encefálico/prevenção & controle , Córtex Cerebral/metabolismo , Circulação Cerebrovascular , Infarto da Artéria Cerebral Média/terapia , Traumatismo por Reperfusão/prevenção & controle , Reperfusão/métodos , Proteínas Repressoras/metabolismo , Animais , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Edema Encefálico/fisiopatologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Ratos Sprague-Dawley , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Proteínas Repressoras/genética , Transdução de Sinais , Fatores de Tempo , Regulação para Cima
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