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1.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34850961

RESUMO

Cardiovascular ischemia/reperfusion (I/R) injury is primarily caused by oxygen recovery after prolonged hypoxia. Previous studies found that the long non coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) was involved in cardiovascular pathology, and that NOD­like receptor protein 3 (NLRP3) inflammasome activation­dependent pyroptosis played a key role in cardiovascular I/R injury. The present study aimed to explore the molecular mechanism of I/R pathogenesis in order to provide novel insights for potential future therapies. Cell viability and lactate dehydrogenase enzyme activity assays were used to detect cell injury after human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia/reoxygenation (H/R). The expression of the NEAT1/microRNA (miR)­204/BRCA1/BRCA2­containing complex subunit 3 (BRCC3) axis was examined by reverse transcription­quantitative PCR, and the associations among genes were confirmed by luciferase reporter assays. Western blotting and ELISA were used to measure the level of NLRP3 inflammasome activation­dependent pyroptosis. The results demonstrated that NEAT1, BRCC3 expression and NLRP3 inflammasome activation­dependent pyroptosis were significantly increased in H/R­injured HUVECs, whereas silencing BRCC3 or NEAT1 attenuated H/R­induced injury and pyroptosis. NEAT1 positively regulated BRCC3 expression via competitively binding with miR­204. Moreover, NEAT1 overexpression counteracted miR­204 mimic­induced injury, BRCC3 expression and NLRP3 inflammasome activation­dependent pyroptosis. Taken together, these findings demonstrated that inhibition of lncRNA NEAT1 protects HUVECs against H/R­induced NLRP3 inflammasome activation by targeting the miR­204/BRCC3 axis.

2.
ACS Synth Biol ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878784

RESUMO

CRISPR/Cas has recently emerged as the most reliable system for genome engineering in various species. However, concerns about risks associated with the CRISPR/Cas technology are increasing on potential unintended DNA changes that might accidentally arise from CRISPR gene editing. Developing a system that can detect and report the presence of active CRISPR/Cas tools in biological systems is therefore very necessary. Here, we developed four real-time detection systems that can spontaneously indicate the presence of active CRISPR-Cas tools for genome editing and gene regulation including CRISPR/Cas9 nuclease, base editing, prime editing, and CRISPRa in plants. Using the fluorescence-based molecular biosensors, we demonstrated that the activities of CRISPR/Cas9 nuclease, base editing, prime editing, and CRISPRa can be effectively detected in transient expression via protoplast transformation and leaf infiltration (in Arabidopsis, poplar, and tobacco) and stable transformation in Arabidopsis.

3.
Turk Neurosurg ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34859838

RESUMO

AIM: The purpose of this study was to compare percutaneous endoscopic lumbar discectomy (PELD) and the microscopic tubular technique and evaluate the outcomes of surgery. MATERIAL AND METHODS: We collected information through retrospective analysis of patients with far-lateral lumbar disc herniation (FLLDH) from June 2015 to October 2018. Twenty-six patients underwent paraspinal muscle-splitting microscopic-assisted discectomy (MD) and thirty patients underwent PELD surgery by the same surgical team. Data included the duration of the operation, duration of intraoperative radiation exposure, and average duration of hospitalization. Pre- and postoperative pain scores and neurological functions were recorded using the visual analog scale (VAS) score and Oswestry disability index (ODI). RESULTS: Fifty-six patients remained in the study over the 12-24 months period. The mean operating time was 65.83 ± 16.64 min in the PELD group, mean duration of radiation exposure was 154.98 ± 64.26 mGy, and average of hospitalization was 3.43 days. The mean operating time was 44.96 ± 16.87 min in the MD group, duration of radiation exposure was 42.12 ± 17.28 mGy, and duration of hospitalization was 4.12 days. There were two patients with postoperative transient dysesthesia and one underwent reoperation seven months after surgery in the PELD group. One patient had postoperative transient dysesthesia in the MD group. Except low back pain at three months (p 0.05), all patients in both groups showed significant improvement in VAS and ODI scores compared with pre-operation and until final follow-up (p 0.05). CONCLUSION: Both techniques are minimally invasive, effective, and safe for treating FLLDH in selected patients. Compared with the PELD technique, the MD procedure offers a wider field of vision during operation, shorter operation time, fewer postoperative complications, and shorter learning curve.

4.
J Alzheimers Dis ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34924383

RESUMO

BACKGROUND: A univariate neurodegeneration biomarker (UNB) based on MRI with strong statistical discrimination power would be highly desirable for studying hippocampal surface morphological changes associated with APOE ɛ4 genetic risk for AD in the cognitively unimpaired (CU) population. However, existing UNB work either fails to model large group variances or does not capture AD induced changes. OBJECTIVE: We proposed a subspace decomposition method capable of exploiting a UNB to represent the hippocampal morphological changes related to the APOE ɛ4 dose effects among the longitudinal APOE ɛ4 homozygotes (HM, N = 30), heterozygotes (HT, N = 49) and non-carriers (NC, N = 61). METHODS: Rank minimization mechanism combined with sparse constraint considering the local continuity of the hippocampal atrophy regions is used to extract group common structures. Based on the group common structures of amyloid-ß (Aß) positive AD patients and Aß negative CU subjects, we identified the regions-of-interest (ROI), which reflect significant morphometry changes caused by the AD development. Then univariate morphometry index (UMI) is constructed from these ROIs. RESULTS: The proposed UMI demonstrates a more substantial statistical discrimination power to distinguish the longitudinal groups with different APOE ɛ4 genotypes than the hippocampal volume measurements. And different APOE ɛ4 allele load affects the shrinkage rate of the hippocampus, i.e., HM genotype will cause the largest atrophy rate, followed by HT, and the smallest is NC. CONCLUSION: The UMIs may capture the APOE ɛ4 risk allele-induced brain morphometry abnormalities and reveal the dose effects of APOE ɛ4 on the hippocampal morphology in cognitively normal individuals.

5.
Front Pediatr ; 9: 721128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796150

RESUMO

Background: Congenital pyriform sinus fistula (CPSF) is a rare branchial cleft deformity. The characteristics and management of CPSF in neonates are different from those in children or adults, and a comprehensive understanding of the imaging features of neonatal CPSF can facilitate its preoperative diagnosis. Thus, the aim of this study was to summarize the ultrasonography (US) and CT imaging findings of CPSF in neonates. Methods: Forty-five full-term neonates with CPSF, confirmed by pathology after surgical resection from January 2012 to October 2020, were included in this retrospective study. All patients underwent preoperative cervical US and contrast-enhanced CT examinations, and the imaging findings were analyzed. Results: Forty-six cervical cystic masses were found in 45 neonates, including one case with bilateral lesions, three cases with lesions on the right side, and 41 cases on the left side. Both US and CT detected neck abnormality among all cases, while the diagnostic accuracy of US (15/46, 32.6%) was lower than that of CT (42/46, 91.3%). Moreover, CT showed significantly higher detection rates of intralesional air bubbles, involvement of the ipsilateral thyroid, deviation of the airway, and expansion into the mediastinal and retropharyngeal space compared with the US. As the age increased, it was more likely to present some features including the absence of air-containing, thick cyst wall, and poorly defined border (ρ <0.05). Conclusion: CPSF in the neonates showed distinctive imaging findings on contrast-enhanced CT scan, which provides important supplementary information for the diagnosis of CPSF after the initial US examination.

6.
J Colloid Interface Sci ; 608(Pt 2): 2050-2057, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34749152

RESUMO

Reformative exploitation for metal organic frameworks (MOFs) has been a topic subject in electrochemical sensing, in which the loading of electroactive species is always introduced to enable them to generate electrochemical signal. However, insulation shielding of MOFs and flimsy combination method interfere with the signal readout of electroactive dyes when they are co-immobilized on electrode surface, indicating that an amelioration is imperatively proposed to solve these issues. Herein, a proton-activated annunciator for responsive release of methylene blue (MB) based on i-motif DNA structure modified UIO-66-NH2 was presented to design electrochemical immunosensor (Squamous cell carcinoma antigen was used as the model analyte). With the catalysis of a ZIF-8 immunoprobe contained glucose oxidase (GOx) to glucose in test tube, protons are produced in ambient solution and then they can be used as the key to unlock the i-motif functionalized UIO-66-NH2, releasing the loaded MB molecules to be readout on an improved electrode. This stimuli-responsive mode not merely eliminates the insulation effect of MOFs but also provides a firm loading method for electroactive dyes. Under the optimal conditions, the proposed immunoassay for SCCA had displayed excellent performance with a wide linear range from 1 µg mL-1 to 1 pg mL-1 and an ultralow detection limit of 1.504 fg mL-1 (S/N = 3) under the optimal conditions.

7.
Anal Chim Acta ; 1187: 339170, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753583

RESUMO

Signal labeling on electrode interface is an important step during the construction of immunosensor and most signal substances are directly affixed on the immunoprobe or substrate so that some problems such as flimsy labeling method and interference of insulating proteins on electrode surface have been existed to affect their readout. In order to solve above problems in electrochemical immunoassay, a lead ions-decodable autocephalous signal integrator based on UIO-66-NH2 was proposed for the detection of prostate specific antigen (PSA). Briefly, a lead ions-dependent DNAzyme functionalized UIO-66-NH2, in which methylene blue was encapsulated, was independently dispersed in solution phase to be closely associated with the lead sulfide labeled sandwich bioconjugates, and internal methylene blue molecules can be sustained released once a cationic exchange reaction was occurred between lead sulfide label and adscititious silver ions. Based on this designing, immunoassay for PSA was effectively connected with the dynamic behavior of methylene blue molecules through the cleavage of DNAzyme on MOFs surface and performed a wide linear range from 1 pg mL-1 to 10 ng mL-1 and a satisfactory detection limit with 0.34 pg mL-1. The proposed strategy was expected to offer more valuable information for the application of MOFs in early and accurate cancer diagnosis.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , Biomarcadores Tumorais , Técnicas Eletroquímicas , Ouro , Humanos , Imunoensaio , Chumbo , Limite de Detecção , Masculino
8.
Nat Commun ; 12(1): 6335, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732747

RESUMO

Single-atom catalysts are becoming increasingly significant to numerous energy conversion reactions. However, their rational design and construction remain quite challenging due to the poorly understood structure-function relationship. Here we demonstrate the dynamic behavior of CuN2C2 site during operando oxygen reduction reaction, revealing a substrate-strain tuned geometry distortion of active sites and its correlation with the activity. Our best CuN2C2 site, on carbon nanotube with 8 nm diameter, delivers a sixfold activity promotion relative to graphene. Density functional theory and X-ray absorption spectroscopy reveal that reasonable substrate strain allows the optimized distortion, where Cu bonds strongly with the oxygen species while maintaining intimate coordination with C/N atoms. The optimized distortion facilitates the electron transfer from Cu to the adsorbed O, greatly boosting the oxygen reduction activity. This work uncovers the structure-function relationship of single-atom catalysts in terms of carbon substrate, and provides guidance to their future design and activity promotion.

9.
Natl Sci Rev ; 8(3): nwaa090, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34691584

RESUMO

The oxygenation of Earth's atmosphere is widely regarded to have played an important role in early-life evolution. Chromium (Cr) isotopes recorded in sedimentary rocks have been used to constrain the atmospheric oxygen level (AOL) over geological times based on the fact that a positive Cr isotopic signature is linked to the presence of Cr(VI) as a result of oxidative continental weathering. However, there is no direct evidence of the presence of Cr(VI) in sedimentary rocks yet. Carbonates are most widely distributed over geological times and were thought to have incorporated Cr(VI) directly from seawater. Here, we present results of Cr valence states in carbonates which show Cr(III) is the dominant species in all samples spanning a wide range of geological times. These findings indicate that Cr(VI) in seawater was reduced either before or after carbonate precipitation, which might have caused Cr isotopic fractionation between seawater and carbonates, or marine carbonates preferentially uptake Cr(III) from seawater. As Cr(III) can come from non-redox Cr cycling, which also can cause isotopic fractionation, we suggest that positively fractionated Cr isotopic values do not necessarily correspond to the rise in AOL.

10.
Nat Commun ; 12(1): 6186, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702816

RESUMO

Although the hollow icosahedral M12 kernel has been extensively observed in metal nanoclusters, its origin remains a mystery. Here we report a reasonable avenue for the generation of the hollow icosahedron: the kernel collapse from several small nano-building blocks to an integrated hollow icosahedron. On the basis of the Au alloying processes from Ag28Cu12(SR)24 to the template-maintained AuxAg28-xCu12(SR)24 and then to the template-transformed Au12CuyAg32-y(SR)30, the kernel evolution/collapse from "tetrahedral Ag4 + 4∗Ag3" to "tetrahedral Au4 + 4∗M3 (M = Au/Ag)" and then to "hollow icosahedral Au12" is mapped out. Significantly, the "kernel collapse" from small-sized nano-building blocks to large-sized nanostructures not only unveils the formation of hollow icosahedral M12 in this work, but also might be a very common approach in constructing metallic kernels of nanoclusters and nanoparticles (not limited to the M12 structure).

11.
Front Plant Sci ; 12: 704697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484267

RESUMO

The phenylpropanoid pathway serves as a rich source of metabolites in plants and provides precursors for lignin biosynthesis. Lignin first appeared in tracheophytes and has been hypothesized to have played pivotal roles in land plant colonization. In this review, we summarize recent progress in defining the lignin biosynthetic pathway in lycophytes, monilophytes, gymnosperms, and angiosperms. In particular, we review the key structural genes involved in p-hydroxyphenyl-, guaiacyl-, and syringyl-lignin biosynthesis across plant taxa and consider and integrate new insights on major transcription factors, such as NACs and MYBs. We also review insight regarding a new transcriptional regulator, 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, canonically identified as a key enzyme in the shikimate pathway. We use several case studies, including EPSP synthase, to illustrate the evolution processes of gene duplication and neo-functionalization in lignin biosynthesis. This review provides new insights into the genetic engineering of the lignin biosynthetic pathway to overcome biomass recalcitrance in bioenergy crops.

12.
Nanomicro Lett ; 13(1): 189, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34490543

RESUMO

Surface chemistry modification represents a promising strategy to tailor the adsorption and activation of reaction intermediates for enhancing activity. Herein, we designed a surface oxygen-injection strategy to tune the electronic structure of SnS2 nanosheets, which showed effectively enhanced electrocatalytic activity and selectivity of CO2 reduction to formate and syngas (CO and H2). The oxygen-injection SnS2 nanosheets exhibit a remarkable Faradaic efficiency of 91.6% for carbonaceous products with a current density of 24.1 mA cm-2 at -0.9 V vs RHE, including 83.2% for formate production and 16.5% for syngas with the CO/H2 ratio of 1:1. By operando X-ray absorption spectroscopy, we unravel the in situ surface oxygen doping into the matrix during reaction, thereby optimizing the Sn local electronic states. Operando synchrotron radiation infrared spectroscopy along with theoretical calculations further reveals that the surface oxygen doping facilitated the CO2 activation and enhanced the affinity for HCOO* species. This result demonstrates the potential strategy of surface oxygen injection for the rational design of advanced catalysts for CO2 electroreduction.

13.
J Phys Chem Lett ; 12(33): 8016-8023, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34433277

RESUMO

Exploring high-efficiency catalysts for the electrochemical hydrogen evolution reaction (HER) in alkaline environments is attractive but remains challenging. Here we report a coordination regulation strategy to tune the atomic structure of Ru cluster catalysts supported on Ti3C2Tx MXene (Ru-Ti3C2Tx) for the HER. We identify that the coordination number (CN) of Ru-Ru could be slightly regulated from 2.1 to 2.8 by adjusting the synthesized temperature so as to achieve an optimal catalytic configuration. The Ru-Ti3C2Tx with a CNRu-Ru of 2.8 exhibits the best catalytic activity with a low overpotential of 96 mV at 10 mA cm-2 and a mass activity about 11.5 times greater than the commercial Pt/C catalyst. Density functional theory calculations demonstrated that the small Ru clusters have a stronger covalent interaction with Ti3C2Tx support leading to an optimal ΔGH* value. This work opens up a general avenue to modulate the coordination environment of catalysts for the HER.

14.
Mol Cell Biol ; 41(10): e0033221, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34309413

RESUMO

Evidence exists reporting that saikosaponin-d (Sa) can prevent experimental sepsis, and this study aims to illustrate the molecular events underlying its renoprotective effects on lipopolysaccharide (LPS)-induced renal inflammation simulating sepsis. Through network pharmacology analysis and bioinformatics analysis, we identified that Sa may influence sepsis development by mediating TCF7. Dual luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays were used to explore the interactions between TCF7, FOSL1, and matrix metalloproteinase 9 (MMP9). The experimental data suggest that Sa attenuated LPS-induced renal injury, as evidenced by the reduced production of proinflammatory cytokines as well as cell apoptosis in the renal tissues of LPS-induced mice. Mechanically, Sa inhibited FOSL1 by inhibiting TCF7, which reduced the expression of inflammatory factors in renal cells. TCF7 activated the FOSL1 expression and consequently promoted the expression of MMP9. Also, Sa reduced cell apoptosis and the expression of inflammatory factors by inhibiting the TCF7/FOSL1/MMP9 axis in vivo. In conclusion, Sa suppresses FOSL1 transcription by downregulating TCF7, thereby inhibiting MMP9 expression and ultimately reducing the renal inflammation and cell apoptosis induced by sepsis.


Assuntos
Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Sepse/tratamento farmacológico , Injúria Renal Aguda/genética , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Nefrite/tratamento farmacológico , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Saponinas/metabolismo , Sepse/fisiopatologia
15.
Front Plant Sci ; 12: 704905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305991

RESUMO

A continuous increase in ambient temperature caused by global warming has been considered a worldwide threat. As sessile organisms, plants have evolved sophisticated heat shock response (HSR) to respond to elevated temperatures and other abiotic stresses, thereby minimizing damage and ensuring the protection of cellular homeostasis. In particular, for perennial trees, HSR is crucial for their long life cycle and development. HSR is a cell stress response that increases the number of chaperones including heat shock proteins (HSPs) to counter the negative effects on proteins caused by heat and other stresses. There are a large number of HSPs in plants, and their expression is directly regulated by a series of heat shock transcription factors (HSFs). Therefore, understanding the detailed molecular mechanisms of woody plants in response to extreme temperature is critical for exploring how woody species will be affected by climate changes. In this review article, we summarize the latest findings of the role of HSFs and HSPs in the HSR of woody species and discuss their regulatory networks and cross talk in HSR. In addition, strategies and programs for future research studies on the functions of HSFs and HSPs in the HSR of woody species are also proposed.

16.
J Am Chem Soc ; 143(30): 11317-11324, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34293258

RESUMO

The development of atomically precise dinuclear heterogeneous catalysts is promising to achieve efficient catalytic performance and is also helpful to the atomic-level understanding on the synergy mechanism under reaction conditions. Here, we report a Ni2(dppm)2Cl3 dinuclear-cluster-derived strategy to a uniform atomically precise Ni2 site, consisting of two Ni1-N4 moieties shared with two nitrogen atoms, anchored on a N-doped carbon. By using operando synchrotron X-ray absorption spectroscopy, we identify the dynamically catalytic dinuclear Ni2 structure under electrochemical CO2 reduction reaction, revealing an oxygen-bridge adsorption on the Ni2-N6 site to form an O-Ni2-N6 structure with enhanced Ni-Ni interaction. Theoretical simulations demonstrate that the key O-Ni2-N6 structure can significantly lower the energy barrier for CO2 activation. As a result, the dinuclear Ni2 catalyst exhibits >94% Faradaic efficiency for efficient carbon monoxide production. This work provides bottom-up target synthesis approaches and evidences the identity of dinuclear sites active toward catalytic reactions.

17.
Dalton Trans ; 50(18): 6076-6082, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33890959

RESUMO

ZrO2 is one of the most stable metal oxides which is applicable to various chemical reactions in harsh environments. However, the photocatalytic performance of ZrO2 is relatively poor due to the negligible use of the solar spectrum caused by the wide bandgap (Eg = 5.3 eV). Here, we report plasmon enhanced Au nanoparticles decorated onto ZrO2 through a facile tannic acid-reduction method. The Au/ZrO2 heterojunctions exhibited efficient and stable photocatalytic activity of reducing CO2 into main CO and CH4, at the rates of 25.6 µmol g-1 h-1 and 5.1 µmol g-1 h-1 at most, respectively, approximately 6-fold enhanced compared to the pristine ZrO2, under simulated solar light. The reduction rates could also be improved over 10-fold under visible light when Au nanoparticles were loaded onto ZrO2. UV-Vis diffuse reflectance spectra confirmed the enhanced visible-light absorption of Au/ZrO2 caused by localized surface plasmon resonance (LSPR). Electrochemical impedance spectra (EIS) and photocurrent tests proved the more efficient charge transport and electron-hole separation of Au/ZrO2 heterojunctions. This study demonstrates an effective strategy of LSPR effects to improve the photocatalytic performances of semiconductors.

18.
J Neurosci Methods ; 357: 109157, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33781789

RESUMO

BACKGROUND: Brain MRI is a promising technique for Parkinson's disease (PD) biomarker development. Its analysis, however, is hindered by the high-dimensional nature of the data, particularly when the sample size is relatively small. NEW METHOD: This study introduces a folded concave penalized machine learning scheme with spatial coupling fused penalty (fused FCP) to build biomarkers for PD directly from whole-brain voxel-wise MRI data. The penalized maximum likelihood estimation problem of the model is solved by local linear approximation. RESULTS: The proposed approach is evaluated on synthetic and Parkinson's Progression Marker Initiative (PPMI) data. It achieves good AUC scores, accuracy in classification, and biomarker identification with a relatively small sample size, and the results are robust for different tuning parameter choices. On the PPMI data, the proposed method discovers over 80 % of large regions of interest (ROIs) identified by the voxel-wise method, as well as potential new ROIs. COMPARISON WITH EXISTING METHODS: The fused FCP approach is compared with L1, fused-L1, and FCP method using three popular machine learning algorithms, logistic regression, support vector machine, and linear discriminant analysis, as well as the voxel-wise method, on both synthetic and PPMI datasets. The fused FCP method demonstrated better accuracy in separating PD from controls than L1 and fused-L1 methods, and similar performance when compared with FCP method. In addition, the fused FCP method showed better ROI identification. CONCLUSIONS: The fused FCP method can be an effective approach for MRI biomarker discovery in PD and other studies using high dimensionality data/low sample sizes.


Assuntos
Doença de Parkinson , Algoritmos , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Máquina de Vetores de Suporte
19.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537822

RESUMO

MicroRNA­199a­3p (miR­199a­3p) is aberrantly expressed in various types of cancer where it exhibits a tumor suppressive role. However, the biological role of miR­199a­3p in ovarian cancer (OC) remains unclear. The present study aimed to investigate whether miR­199a­3p was a tumor suppressor in OC and to identify the possible mechanisms. It was found that miR­199a­3p expression was significantly downregulated in the tumor tissues and blood samples of patients with OC, as well as in three OC cell lines. In addition, its low expression was closely associated with International Federation of Gynecology and Obstetrics disease stage, histological grade and lymph node metastasis. It was demonstrated that overexpression of miR­199a­3p inhibited the viability and promoted apoptosis of OV90 and SKOV­3 cells. In addition, Yes­associated protein 1 (YAP1), a well­known oncogene, was identified as a direct target of miR­199a­3p in OC cells. Additionally, it was observed that YAP1 was significantly increased and inversely correlated with miR­199a­3p expression in OC tissues. Notably, YAP1 overexpression abrogated the tumor suppressive effects of miR­199a­3p in vitro. Collectively, the present results indicated that miR­199a­3p suppressed viability in OC cells, at least partly via inhibiting the YAP1 oncogene, suggesting that miR­199a­3p may act as a biomarker and therapeutic target for patients with OC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose , Biomarcadores Tumorais/metabolismo , MicroRNAs/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Neoplásico/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas/genética , RNA Neoplásico/genética , Fatores de Transcrição/genética
20.
J Cell Mol Med ; 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33484504

RESUMO

Recent studies indicate that circular RNAs are involved in dysregulation of kidney injury. Nevertheless, the underlying mechanisms remain largely unclear. Therefore, this study sought to investigate the role of circ-USP1 in the pathogenesis of early renal allografts. Thirty-two male C57BL/6J mice aged between 6 and 8 weeks were divided into the sham and allograft groups. Thereafter, the association between miR-194-5p, circ-USP1 and DNMT3A was confirmed using a combination of bioinformatics and the luciferase reporter gene assay. Additionally, the expression of circ-USP1, miR-194-5p and DNMT3A mRNA was detected through qPCR. Afterwards, the Western blot assay was performed to examine the expression of DNMT3A protein. Finally, the TUNEL assay was conducted to determine the rate of apoptosis in DNMT3A cells. The expression of circ-USP1 increased, while that of miR-194-5p decreased in renal allografts. Additionally, silencing circ-USP1 reduced kidney injuries caused by renal allografts in mice. Moreover, miR-194-5p was a target for circ-USP1, and DNMT3A was a target of miR-194-5p. Finally, it was shown that silencing circ-USP1 reduced DNMT3A expression in the kidney of mice that received renal allografts. Circ-USP1 functions as a competing endogenous RNA for miR-194-5p. This occurs in order to regulate DNMT3A expression in kidney injury induced by hypoxia in acute renal allografts.

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