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1.
Talanta ; 236: 122899, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635272

RESUMO

A real-time quartz crystal microbalance (QCM) cytosensor was first developed for dynamical and noninvasive monitoring of cell viscoelasticity for evaluation of apoptosis degree. In this work, human breast cancer cells MCF-7 and MDA-MB-231 were employed as cell model and respectively captured on the surface of QCM electrode modified with mercaptosuccinic acid and poly-l-lysine. Cell viscoelasticity was measured dynamically by real-time monitoring energy dissipation with QCM, and the dynamic diagram of the energy dissipation of MDA-MB-231 cells treated with curcumin was first obtained. The results displayed that the changes of energy dissipation in MDA-MB-231 cells and MCF-7 cells were 8.81 × 10-6 and 5.29 × 10-6, particularly due to the difference in cell viscoelasticity. Furthermore, curcumin was used to induce cell apoptosis and suppress energy dissipation of MDA-MB-231 cells. Combining apoptosis assay with QCM measurement, the results revealed good linear relationship between cell viscoelasticity inhibition and apoptosis rate with correlation coefficient R = 0.9908. The QCM cytosensor could rapidly, accurately, dynamically, and noninvasively monitor the changes of cell viscoelasticity for evaluation of apoptosis degree in MDA-MB-231 cells. The study established a new model for cell apoptosis assessment, facilitating understanding of the mechanisms of cell apoptosis on the aspect of mechanical properties.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Curcumina , Apoptose , Neoplasias da Mama/tratamento farmacológico , Curcumina/farmacologia , Feminino , Humanos , Viscosidade
2.
J Colloid Interface Sci ; 605: 263-273, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34332405

RESUMO

Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH2). After loading with 5-fluorouracil (5Fu), this system performed synergistic cancer chemotherapy. In this study, the 5Fu/CaPO-NH2 particles could be efficiently uptaken by cancer cells, and then decompose into Ca2+ and release 5Fu drug in the cytoplasm; therefore calcium overload and reactive oxygen species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial apoptosis. In the PSN1 pancreatic cancer xenograft model, the 5Fu/CaPO-NH2 system performed high tumor inhibition via chemotherapy and calcium overload induced apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH2 drug delivery platform for enhanced 5Fu chemotherapeutic effect.


Assuntos
Fluoruracila , Neoplasias Pancreáticas , Apoptose , Fosfatos de Cálcio , Linhagem Celular Tumoral , Portadores de Fármacos , Fluoruracila/farmacologia , Humanos , Neoplasias Pancreáticas/tratamento farmacológico
3.
Commun Biol ; 4(1): 1237, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725466

RESUMO

The Hippo pathway is frequently dysregulated in cancer, leading to the unrestrained activity of its downstream targets, YAP/TAZ, and aberrant tumor growth. However, the precise mechanisms leading to YAP/TAZ activation in most cancers is still poorly understood. Analysis of large tissue collections revealed YAP activation in most head and neck squamous cell carcinoma (HNSCC), but only 29.8% of HNSCC cases present genetic alterations in the FAT1 tumor suppressor gene that may underlie persistent YAP signaling. EGFR is overexpressed in HNSCC and many other cancers, but whether EGFR controls YAP activation is still poorly understood. Here, we discover that EGFR activates YAP/TAZ in HNSCC cells, but independently of its typical signaling targets, including PI3K. Mechanistically, we find that EGFR promotes the phosphorylation of MOB1, a core Hippo pathway component, and the inactivation of LATS1/2 independently of MST1/2. Transcriptomic analysis reveals that erlotinib, a clinical EGFR inhibitor, inactivates YAP/TAZ. Remarkably, loss of LATS1/2, resulting in aberrant YAP/TAZ activity, confers erlotinib resistance on HNSCC and lung cancer cells. Our findings suggest that EGFR-YAP/TAZ signaling plays a growth-promoting role in cancers harboring EGFR alterations, and that inhibition of YAP/TAZ in combination with EGFR might be beneficial to prevent treatment resistance and cancer recurrence.

4.
Opt Express ; 29(24): 40205-40213, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809367

RESUMO

Terahertz wave has been used to obtain the internal information of materials due to its penetrability to optically opaque materials. In this paper, we propose a full-field stress measuring method using terahertz time-domain spectroscopy. The theoretical model of the method was established based on the stress-optical law, and the method was then validated experimentally. A four-point bending experiment was conducted to determine the stress-optical coefficient of the specimen material, after which the proposed method was used to measure the stress distribution of a diametrically loaded disk. The experimental results present a reasonable agreement with the theoretical solution.

5.
Comput Biol Med ; 139: 104989, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34739969

RESUMO

Insomnia is one of the most common sleep disorders which can dramatically impair life quality and negatively affect an individual's physical and mental health. Recently, various deep learning based methods have been proposed for automatic and objective insomnia detection, owing to the great success of deep learning techniques. However, due to the scarcity of public insomnia data, a deep learning model trained on a dataset with a small number of insomnia subjects may compromise the generalization capacity of the model and eventually limit the performance of insomnia detection. Meanwhile, there have been a number of public EEG datasets collected from a large number of healthy subjects for various sleep research tasks such as sleep staging. Therefore, to utilize such abundant EEG datasets for addressing the data scarcity issue in insomnia detection, in this paper we propose a domain adaptation based model to better extract insomnia related features of the target domain by leveraging stage annotations from the source domain. For each domain, two pairs of common encoder and private encoder are firstly trained to extract sleep related features and sleep irrelevant features, respectively. In order to further discriminate source domain and target domain, a domain classifier is introduced. Then, the common encoder of the target domain will be used together with the Long Short Term Memory (LSTM) network for insomnia detection. To the best of our knowledge, this is the first deep learning based domain adaptation model using single channel raw EEG signals to detect insomnia at subject level. We use the Montreal Archive of Sleep Studies (MASS) dataset which contains only healthy subjects as source domain and two datasets which contain both healthy and insomnia subjects as target domain to validate our model's generalizability. Experimental results on the two target domain datasets (a public one and an in-house one) demonstrate that our model generalizes well on two target domain datasets with different sampling rates. In particular, our proposed method is able to improve insomnia detection performance from 50.0% to 90.9% and 66.7%-79.2% in terms of accuracy on the two target domain datasets, respectively.

6.
Theor Appl Genet ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34766198

RESUMO

KEY MESSAGE: Map-based cloning was used to identify the BrWAX2 gene, which was involved in the cuticular wax biosynthesis. The malfunction of BrWAX2 together with other reduced expression of genes in alkane-forming pathway caused the glossy phenotype. Cuticular wax covering the outer plant surface plays various roles in protecting against biotic and abiotic stresses. Wax-less mutant shows glossy in stem and leaf surface and plays important roles in enriching Chinese cabbage germplasm resources for breeding brilliant green varieties. However, genes responsible for the glossy trait in Chinese cabbage are rarely reported. In this study, we identified a glossy Chinese cabbage line Y1211-1. Genetic analysis indicated that the glossy trait in Y1211-1 was controlled by a single recessive locus, BrWAX2 (Brassica rapa WAX 2). Using bulked segregant sequencing (BSA-Seq) and kompetitive allele-specific PCR (KASP) assays, BrWAX2 was fine-mapped to an interval of 100.78 kb. Functional annotation analysis, expression analysis, and sequence variation analysis revealed that Bra032670, homologous to CER1 in Arabidopsis, was the most likely candidate gene for BrWAX2. The gene Bra032670 was absent in glossy mutant. Cuticular wax composition analysis and RNA-Seq analysis suggested that the absence of BrWAX2 together with the decreased expression of other genes in alkane-forming pathway reduced the wax amount and caused the glossy phenotype. Furthermore, we developed and validated the functional marker BrWAX2-sp for BrWAX2. Overall, these results provide insight into the molecular mechanism underlying cuticular wax biosynthesis and reveal valuable information for marker-assisted selection (MAS) breeding in Chinese cabbage.

7.
Analyst ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783798

RESUMO

In this study, a novel method that combines electrochemiluminescence (ECL) analysis and digital image processing was developed for the detection of sulfonamides. This method is based on the ECL system of ruthenium terpyridine, with 1 mM tripropylamine as a co-reactant to enhance the performance. Under the optimal conditions comprising a solution of pH 7 and a scanning rate of 0.08 V s-1, the Pt electrode has an excellent linear detection range from 5 µM to 5 mM, with a detection limit of 0.85 µM (S/N = 3). A wireless camera is used to record the light-emitting process. The recordings are processed, and the digital images are extracted using image-processing algorithms implemented in Python to calculate the brightness value of the image, which has a linear relationship with the logarithm of the sulfonamide concentration. Image analysis simplifies and improves the stability of the ECL analysis process, while also increasing the speed of analysis. The results indicate that the method can successfully detect a sulfonamide concentration of 5 µM. Thus, the analysis method of ECL combined with image processing is feasible for the detection of sulfonamides, thereby displaying its potential applicability as a novel method in drug and food safety, for instance, for sulfonamide detection in antibiotics.

8.
Circ J ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759131

RESUMO

BACKGROUND: Application of drug-coated balloons (DCBs) is popular for the treatment of percutaneous coronary intervention (PCI). A new DCB has been designed as ultrasound-controlled paclitaxel releasing. This study was conducted to determine whether a DCB-only strategy has a similar safety profile and equal angiographic and clinical outcomes to DES implantation in primary ST-elevation myocardial infarction (STEMI) patients, as well as determine the efficiency and safety of this new DCB.Methods and Results:Overall, 184 pretreated STEMI patients were randomized into DCB and DES groups with a 1:1 allocation. The main study end-point was late lumen loss (LLL) during the 9 months after PCI. Late lumen loss was reported to be 0.24±0.39 mm in the DCB group and 0.31±0.38 mm in the DES group (P=0.215). Diameter stenosis was 28.27±15.35% in the DCB group and 25.73±15.41% in the DES group (P=0.312). Major adverse cardiovascular events (MACEs) were reported in 3 patients (3.4%) in the DCB group and 4 patients (4.7%) in the DES group (P=0.718). TLR and TVR in the DCB group was 2.3%, 3.4% and 2.4%, 3.5% in the DES group (P=1.000), respectively. No cardiac death and stent thrombosis (ST) was found in the DCB group at 12 months clinical follow up. CONCLUSIONS: The DCB-only strategy showed good angiographic and clinical outcomes in the 9- and 12-month follow-up periods, respectively. The VasoguardTM DCB is safe and feasible to treat STEMI patients.

9.
Apoptosis ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762220

RESUMO

Nucleophosmin (NPM), a nucleolar-based protein chaperone, promotes Bax-mediated mitochondrial injury and regulates cell death during acute kidney injury. However, the steps that transform NPM from an essential to a toxic protein during stress are unknown. To localize NPM-mediated events causing regulated cell death during ischemia, wild type (WT) and Hsp70 mutant proteins with characterized intracellular trafficking defects that restrict movement to either the nucleolar region (M45) or cytosol (985A) were expressed in primary murine proximal tubule epithelial cells (PTEC) harvested from Hsp70 null mice. After ischemia in vitro, PTEC survival was significantly improved and apoptosis reduced in rank order by selectively overexpressing WT > M45 > 985A Hsp70 proteins. Only Hsp70 with nuclear access (WT and M45) inhibited T95 NPM phosphorylation responsible for NPM translocation and also reduced cytosolic NPM accumulation. In contrast, WT or 985A > M45 significantly improved survival in Hsp70 null PTEC that expressed a cytosol-restricted NPM mutant, more effectively bound NPM, and also reduced NPM-Bax complex formation required for mitochondrial injury and cell death. Hsp70 knockout prevented the cytoprotective effect of suppressing NPM in ischemic PTEC and also increased cytosolic NPM accumulation after acute renal ischemia in vivo, emphasizing the inhibitory effect of Hsp70 on NPM-mediated toxicity. Distinct cytoprotective mechanisms by wild type and mutant Hsp70 proteins identify dual nuclear and cytosolic events that mediate NPM toxicity during stress-induced apoptosis and are rational targets for therapeutic AKI interventions. Antagonizing these early events in regulated cell death promotes renal cell survival during experimental AKI.

10.
Front Genet ; 12: 736423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630526

RESUMO

Recent evidence suggests that splicing factors (SFs) and alternative splicing (AS) play important roles in cancer progression. We constructed four SF-risk-models using 12 survival-related SFs. In Luminal-A, Luminal-B, Her-2, and Basal-Like BRCA, SF-risk-models for three genes (PAXBP1, NKAP, and NCBP2), four genes (RBM15B, PNN, ACIN1, and SRSF8), three genes (LSM3, SNRNP200, and SNU13), and three genes (SRPK3, PUF60, and PNN) were constructed. These models have a promising prognosis-predicting power. The co-expression and protein-protein interaction analysis suggest that the 12 SFs are highly functional-connected. Pathway analysis and gene set enrichment analysis suggests that the functional role of the selected 12 SFs is highly context-dependent among different BRCA subtypes. We further constructed four AS-risk-models with good prognosis predicting ability in four BRCA subtypes by integrating the four SF-risk-models and 21 survival-related AS-events. This study proposed that SFs and ASs were potential multidimensional biomarkers for the diagnosis, prognosis, and treatment of BRCA.

11.
Front Cell Dev Biol ; 9: 719209, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650973

RESUMO

ATP-binding cassette (ABC) transporter family are major contributors to the drug resistance establishment of breast cancer cells. Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. However, recent studies suggest that the biological function of BCRP is not limited in its drug pump activity. Herein, the role of BCRP in the proliferation and survival of drug-resistant breast cancer cells was investigated. We found that BCRP is not the major drug pump to efflux epirubicin in the resistant cells that express multiple ABC transporters. Silencing of BCRP significantly impairs cell proliferation and induces apoptosis of the resistant cells in vitro and in vivo. RNA-sequencing and high-throughput proteomics suggest that BCRP is an inhibitory factor of oxidative phosphorylation (OXPHOS). Further research suggests that BCRP is localized in the mitochondria of the resistant cells. Knockdown of BCRP elevated the intracellular reactive oxygen species level and eventually promotes the cell to undergo apoptosis. This study demonstrated that BCRP exerts important onco-promoting functions in the drug-resistant breast cancer cells independent of its well-recognized drug efflux activity, which shed new light on understanding the complex functional role of ABC transporters in drug-resistant cells.

12.
Adv Mater ; : e2106073, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613639

RESUMO

Electrochromic devices (ECDs) have emerged as a unique class of optoelectronic devices for the development of smart windows. However, current ECDs typically suffer from low coloration efficiency (CE) and high energy consumption, which have thus hindered their practical applications, especially as components in solar-powered EC windows. Here, the high-performance ECDs with a fully crystalline viologen-immobilized 2D polymer (V2DP) thin film as the color-switching layer is demonstrated. The high density of vertically oriented pore channels (pore size ≈ 4.5 nm; pore density ≈ 5.8 × 1016 m-2 ) in the synthetic V2DP film enables high utilization of redox-active viologen moieties and benefits for Li+ ion diffusion/transport. As a result, the as-fabricated ECDs achieve a rapid switching speed (coloration, 2.8 s; bleaching, 1.2 s), and a high CE (989 cm2 C-1 ), and low energy consumption (21.1 µW cm-2 ). Moreover, it is managed to fabricate transmission-tunable, self-sustainable EC window prototypes by vertically integrating the V2DP ECDs with transparent solar cells. This work sheds light on designing electroactive 2D polymers with molecular precision for optoelectronics and paves a practical route toward developing self-powered EC windows to offset the electricity consumption of buildings.

13.
J Fish Biol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553785

RESUMO

Sox genes encode transcription factors with a high-mobility group (HMG) box, playing critical roles in the initiation and maintenance of a variety of developmental processes, such as sex determination and differentiation. In the present study, we identified 26 Sox genes in the genome of spinyhead croaker Collichthys lucidus (Richardson, 1844) with homology-based analysis of the HMG box. The transcriptome-based expression profiles revealed that the expression of the Sox gene in gonads began to differ between sexes when the body length was 2.74 ± 0.24 cm. At that time, three Sox genes (Sox11b, Sox8a and Sox19) were significantly upregulated, accompanied by the downregulation of 12 Sox genes in the ovary, and six Sox genes were temporarily significantly upregulated in the testis. Afterwards, the expression profile of Sox genes changed only with a small amplitude in both the ovary and testis. For adult tissues, huge differences were observed in the expression profiles of Sox genes between ovaries and testes, as well as small differences in somatic tissues between sexes. These results provide clues to further decipher the role of Sox genes in the processes of sex determination and differentiation in spinyhead croaker and other teleosts.

14.
Adv Mater ; 33(43): e2104370, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34510593

RESUMO

Neural systems can selectively filter and memorize spatiotemporal information, thus enabling high-efficient information processing. Emulating such an exquisite biological process in electronic devices is of fundamental importance for developing neuromorphic architectures with efficient in situ edge/parallel computing, and probabilistic inference. Here a novel multifunctional memristor is proposed and demonstrated based on metalloporphyrin/oxide hybrid heterojunction, in which the metalloporphyrin layer allows for dual electronic/ionic transport. Benefiting from the coordination-assisted ionic diffusion, the device exhibits smooth, gradual conductive transitions. It is shown that the memristive characteristics of this hybrid system can be modulated by altering the metal center for desired metal-oxygen bonding energy and oxygen ions migration dynamics. The spike voltage-dependent plasticity stemming from the local/extended movement of oxygen ions under low/high voltage is identified, which permits potentiation and depression under unipolar different positive voltages. As a proof-of-concept demonstration, memristive arrays are further built to emulate the signal filtering function of the biological visual system. This work demonstrates the ionic intelligence feature of metalloporphyrin and paves the way for implementing efficient neural-signal analysis in neuromorphic hardware.

15.
Phys Chem Chem Phys ; 23(35): 19195-19201, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524291

RESUMO

Bi is an attractive catalyst towards the electrochemical reduction of CO2 to formate. In this work, nanoporous bismuth was prepared by dealloying Mg3Bi2 with tartaric acid (TA) solution, and the size of the primary Bi nanoparticles was adjusted according to the concentration of TA. When the concentration of TA increased from 2 wt% to 20 wt%, the particle size of Bi increased from about 70 nm to 400 nm. The synthesized nanoporous Bi samples were investigated as electrocatalysts for the reduction of CO2 in KHCO3 electrolyte, and it was found that the smaller the particle size, the higher the catalytic activity. However, nanoporous Bi comprising 70 nm particles suffered from mass transfer difficulty and sintering during the reaction, whereas the 100 nm nanoporous Bi delivered both a high formate formation current and faradaic efficiency (FE) (16 mA cm-2, FE > 90% at -0.88 V vs. RHE) and showed excellent durability.

17.
Biomolecules ; 11(8)2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34439883

RESUMO

Isotopically dimethyl labeling was applied in a quantitative post-translational modification (PTM) proteomic study of phosphoproteomic changes in the drought responses of two contrasting soybean cultivars. A total of 9457 phosphopeptides were identified subsequently, corresponding to 4571 phosphoprotein groups and 3889 leading phosphoproteins, which contained nine kinase families consisting of 279 kinases. These phosphoproteins contained a total of 8087 phosphosites, 6106 of which were newly identified and constituted 54% of the current soybean phosphosite repository. These phosphosites were converted into the highly conserved kinase docking sites by bioinformatics analysis, which predicted six kinase families that matched with those newly found nine kinase families. The overly post-translationally modified proteins (OPP) occupies 2.1% of these leading phosphoproteins. Most of these OPPs are photoreceptors, mRNA-, histone-, and phospholipid-binding proteins, as well as protein kinase/phosphatases. The subgroup population distribution of phosphoproteins over the number of phosphosites of phosphoproteins follows the exponential decay law, Y = 4.13e-0.098X - 0.04. Out of 218 significantly regulated unique phosphopeptide groups, 188 phosphoproteins were regulated by the drought-tolerant cultivar under the water loss condition. These significantly regulated phosphoproteins (SRP) are mainly enriched in the biological functions of water transport and deprivation, methionine metabolic processes, photosynthesis/light reaction, and response to cadmium ion, osmotic stress, and ABA response. Seventeen and 15 SRPs are protein kinases/phosphatases and transcription factors, respectively. Bioinformatics analysis again revealed that three members of the calcium dependent protein kinase family (CAMK family), GmSRK2I, GmCIPK25, and GmAKINß1 kinases, constitute a phosphor-relay-mediated signal transduction network, regulating ion channel activities and many nuclear events in this drought-tolerant cultivar, which presumably contributes to the development of the soybean drought tolerance under water deprivation process.


Assuntos
Fosfoproteínas/metabolismo , Proteoma/metabolismo , Proteínas de Soja/metabolismo , Soja/metabolismo , Secas , Pressão Osmótica , Fosforilação
18.
J Chem Neuroanat ; 117: 102016, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34454019

RESUMO

The thermogenesis resulting from brown adipose tissue (BAT)-induced energy consumption is an important method of energy regulation. It has been reported that brain-derived neurotrophic factor (BDNF)-positive neurons in the paraventricular nucleus (PVN) can regulate adaptive thermogenesis in interscapular brown adipose tissue (IBAT), but the upstream regulatory mechanism is still unclear. Our previous studies have found that a large number of dopamine (DA) receptors (DRs) are expressed on BDNF-positive neurons in the PVN and that the substantia nigra (SN) can directly project to the PVN (forming the SN-PVN pathway). Therefore, we speculate that DA in the SN can regulate the expression of BDNF via DRs and then affect IBAT thermogenesis. In this study, bilateral SN lesions were induced in rats with 6-hydroxydopamine (6-OHDA), and the altered expression of DRs and BDNF in the PVN and the metabolic changes in IBAT were studied via double immunofluorescence and western blotting. The results showed that BDNF-positive neurons in the PVN expressed DR 1 (D1) and DR 2 (D2) and were surrounded by a large number of tyrosine hydroxylase (TH)-positive nerve fibers. Compared with the control group, the 6-OHDA group exhibited significantly fewer TH-positive neurons and significantly lower TH expression in the SN, but body weight, IBAT weight and food consumption did not differ between the groups. In the PVN, BDNF expression was upregulated in the 6-OHDA group, while D2 and TH expression was downregulated. In IBAT, the expression of uncoupling protein-1 (UCP-1), phosphorylated hormone-sensitive lipase (p-HSL), TH and ß3-adrenergic receptor (ß3-AR) was increased, while the expression of fatty acid synthase (FAS) was decreased. The IBAT cell diameter was also decreased in the 6-OHDA group. The results suggest that the SN-PVN pathway may be an upstream neural pathway that can affect BDNF expression in the PVN and that DRs may mediate its regulatory effects. This study expands our understanding of the relationship between DA and obesity.

20.
J Biochem Mol Toxicol ; 35(10): e22867, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34369042

RESUMO

Accumulated evidence has manifested that long noncoding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to be involved in tumorigenesis. However, SNHG7 expression and its functional effects on PD remain uncharted. Rotenone (Rot) was adopted to construct PD models in Sprague-Dawley (SD) rats and SH-SY5Y cells, respectively. The expression levels of caspase 3, tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba1) in SD rat striatum were measured via immunohistochemistry and western blot. Additionally, the expressions of inflammatory cytokines (interleukin 1ß [IL-1ß], IL-6, tumor necrosis factor α) and oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase) in the brain tissues were examined using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Moreover, the protein levels of tumor necrosis factor receptor-associated factor (TRAF5), I-κB, nuclear factor-κB (NF-κB), HO-1, Nrf2 were detected via western blot. Bioinformatics was applied to predict the targeting relationship between SNHG7, miR-425-5p, and TRAF5. Dual-luciferase activity assay and RNA immunoprecipitation assays were conducted to verify their interactions. In comparison to healthy donors, SNHG7 was found upregulated while miR-425-5p expression was downregulated in PD patients. Functional experiments confirmed that SNHG7 downregulation or miR-425-5p overexpression attenuated neuronal apoptosis in the Rot-mediated PD model, TH-positive cell loss, and microglial activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-425-5p and promoted TRAF5 mediated inflammation and oxidative stress. Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated inflammation and oxidative stress, and similar results were observed in the Rot-mediated rat model of PD.

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