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1.
Mol Med Rep ; 22(1): 145-154, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377728

RESUMO

Long-term and high-dose glucocorticoid treatment is recognized as an important influencing factor for osteoporosis and osteonecrosis. Nicotinamide mononucleotide (NMN) is an intermediate of NAD+ biosynthesis, and is widely used to replenish the levels of NAD+. However, the potential role of NMN in glucocorticoid­induced osteogenic inhibition remains to be demonstrated. In the present study, the protective effects of NMN on dexamethasone (Dex)­induced osteogenic inhibition, and its underlying mechanisms, were investigated. Bone mesenchymal stem cells were treated with Dex, which decreased the levels of the osteogenic markers alkaline phosphatase, Runt­related transcription factor 2 and osteocalcin. NMN treatment attenuated Dex­induced osteogenic inhibition and promoted the expression of sirtuin 1 (SIRT1) and peroxisome proliferator­activated receptor gamma coactivator (PGC)­1α. SIRT1 knockdown reversed the protective effects of NMN and reduced the expression levels of PGC­1α. Collectively, the results of the present study reveal that NMN may be a potential therapeutic target for glucocorticoid­induced osteoporosis.

2.
Med Hypotheses ; 142: 109810, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32413701
3.
Dalton Trans ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32421135

RESUMO

Hofmann-type spin-crossover (SCO) frameworks attract much attention due to their predictable structures and diverse SCO behaviours. In this paper, we report two isostructural two-dimensional (2D) Hofmann-type SCO frameworks [FeII(ppe)2MII(CN)4]·3H2O (ppe = 1-(2-pyridyl)-2-(4-pyridyl)ethylene and M = Pd for 1 and Pt for 2). X-ray crystallographic studies, magnetic measurements and Mössbauer spectra jointly reveal that both compounds undergo complete hysteretic two-step SCO, i.e. HS1.0 ⇌ HS0.6-0.5LS0.4-0.5 ⇌ LS1.0 conversion with thermal hysteresis loops of 14 K and 28 K wide for 1 and 13 K and 26 K wide for 2. The dehydrated samples, 1-dehydrated and 2-dehydrated, display different SCO behaviours, unveiling that the SCO behaviours are affected by guest water molecules.

4.
Biomed Mater ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32422624

RESUMO

Full-thickness skin injury is a serious and intractable clinical problem. Wound dressing is urgently needed to treat serious skin defects or induce skin reconstruction. For the first time, we demonstrated a borosilicate bioglass (BBG) incorporated sodium alginate (SA) wound dressing by a simple and effective technique for accelerated wound healing. The physical and chemical properties, in vitro and in vivo properties of SA-BBG composite wound dressing have been investigated. The results show that the SA-BBG composite dressing possess good water absorption performance. Boron ions and silicon ions in borosilicate bioglass can maintain stable and sustained release. Most importantly, SA-BBG composite wound dressing shows outstanding wound healing ability in full-thickness skin defects in rats. The wounds were treated with SA-BBG composite dressing groups had almost closed at day 15. When the ratio of sodium alginate to bioglass in the sponge is 3:1, the wound healing effect is the best. In conclusion, SA-BBG composite dressing shows great potential application in skin wound healing and SA3BBG works best.

5.
Biomater Sci ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400782

RESUMO

Herein, we successfully constructed a combination therapeutic nanoplatform with high tumor targeting for cancer treatment by integrating gold nanorods with disulfiram (denoted Au-DSF). The Au-DSF integrates possess a uniform length (70 nm), excellent photothermal conversion ability and a high DSF loading content (23.2%), and the loaded DSFs show glutathione-, acid-, and laser-responsive release properties. The Au-DSF integrates show significantly enhanced cellular uptake efficiency in breast cancer cells due to the ability of DSF to chelate to the intracellular copper (Cu) which is present at high concentrations. Furthermore, the Au-DSF exhibits improved circulation time (mean residence time = 28.4 h) and increased tumor accumulation (12.0%), due to the targeting of DSF to the abundant Cu ions at the tumor site. Moreover, the DSF/Cu complexes potently elevate reactive oxygen species, which effectively induce cancer cell apoptosis. In vivo experiments show that the Au-DSF integrates dramatically decrease tumor size via photothermal therapy and chemotherapy. Hematoxylin-eosin and TUNEL staining show that the Au-DSF integrates induce necrosis and apoptosis in cancer cells. The high therapeutic efficiency of the Au-DSF integrates for breast cancer is further demonstrated by the reduced elasticity seen in ultrasound elastography, and the absence of perfusion of the contrast agent in contrast-enhanced ultrasound imaging in tumors.

6.
Ann Epidemiol ; 44: 1-7.e2, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32279914

RESUMO

PURPOSE: Preexposure prophylaxis (PrEP) in the form of daily emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) is effective for preventing HIV infection. Implementation has been limited by an inability to systematically evaluate uptake and use. All-Payer Claims Databases (APCDs) provide an opportunity to evaluate population-level PrEP implementation. METHODS: We used 2012-2017 data from Rhode Island's APCD and developed an algorithm to identify individuals prescribed FTC/TDF for PrEP. We describe PrEP implementation by patient demographics and provider type and mapped PrEP implementation across ZIP codes. We compared APCD data to electronic medical record data and comprehensive pharmaceutical claims data (AIDSVu.org). RESULTS: The Rhode Island APCD represented approximately 87% of the state's population. PrEP use increased 31-fold from 2012 to 2017. Users were predominantly privately insured, male, and concentrated in Providence County (76.6%). Infectious diseases providers had 3.2 times the odds of being a PrEP prescriber compared to primary care providers. Compared to other pharmaceutical and electronic medical record data, the APCD underestimated the number of PrEP users in Rhode Island but improved in capturing users over time. CONCLUSIONS: APCDs are a useful data source for characterizing PrEP use across a state. There is a need to increase PrEP prescribing among primary care providers, especially in areas with underserved populations.

7.
Plant Signal Behav ; 15(5): 1746034, 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32264754

RESUMO

Herbaceous peony (Paeonia lactiflora Pall.) is known as the flower phase. This phase is somewhat resistant to drought, but long-term drought and severe water shortage will affect its normal growth and development. In this study, physiological indices and the transcriptome of P. lactiflora were determined to clarify its physiological responses and gene expression changes under drought stress. The results showed that under drought stress, soluble sugar content, peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) activities, and chlorophyll, carotenoid and flavonoid contents were significantly increased, and soluble protein content, superoxide dismutase (SOD), glutathione reductase (GR), dehydroascorbate reductase (DHAR), monodehydroascorbate reductase (MDHAR), ascorbic acid (AsA) and glutathione (GSH) activity first increased and then decreased after day 14. Moreover, drought stress also significantly reduced chlorophyll content, photosynthesis and chlorophyll fluorescence parameters. Transcriptomic analysis revealed that compared with the Control, 10,747 differentially expressed genes (DEGs) were upregulated and 11,835 downregulated under drought stress. These DEGs were classified into three categories and 46 functional groups by GO function classification. The 3,179 DEGs were enriched into 128 pathways by KEGG pathway enrichment. The ROS system, chlorophyll degradation and photosynthetic capacity, as well as secondary pathways of biosynthesis and sugar metabolism were included. Additionally, relevant genes expressed in some metabolic pathways were discovered. These results provide a theoretical basis for understanding the responses of P. lactiflora to drought stress.

8.
Clin Interv Aging ; 15: 441-449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256059

RESUMO

Background and Aim: The presence of malnutrition in hospitalized geriatric patients is associated with an increased risk of mortality. This study aimed to examine the performance of Nutritional Risk Screening 2002 (NRS2002) and Mini Nutritional Assessment Short Form (MNA-SF) in predicting mortality for hospitalized geriatric patients in China. Methods: A prospective analysis was performed in 536 hospitalized geriatric patients aged ≥65 years. Nutrition status was assessed using the MNA-SF and NRS2002 scales within 24 hrs of admission. Anthropometric measures and biochemical parameters were carried out for each patient. Patients were follow-up for up to 2.5 years. Results: At baseline, 161 (30.04%) patients had malnutrition/nutritional risk according to NRS2002 assessment. According to MNA-SF, 284 (52.99%) patients had malnutrition/nutritional risk. Malnutrition/nutritional risk patients had lower anthropometric and biochemical parameters (P<0.05). NRS2002 and MNA-SF had a strong correlation with classical nutritional markers (P<0.05). NRS2002 versus MNA-SF showed moderate agreement (kappa=0.493, P<0.001). During a median follow-up time of 795 days (range 10-947 days), 118 (22%) participants died. The Kaplan-Meier curve demonstrated that malnutrition/nutritional risk patients according to NRS2002 or MNA-SF assessment had a higher risk of mortality than the normal nutrition patients (χ 2=17.67, P<0.001; χ 2=28.999, P<0.001, respectively). From the components of the Cox regression multivariate models, only the NRS2002 score was an independent risk factor influencing the mortality. Conclusion: Both NRS2002 and MNA-SF scores could predict mortality in Chinese hospitalized geriatric patients. But only NRS2002 score was the independent predictor for mortality.

9.
Biotechnol Lett ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32318881

RESUMO

OBJECTIVE: To obtain a novel pullulanase with synthetic ability from a microorganism and characterize its substrates specificity. RESULTS: A novel pullulanase, PulY103A, from Bacillus megaterium Y103 was purified, characterized and expressed in Escherichia coli. PulY103A contained the signature sequences of type I pullulanases and showed 94.7% identity with a type I pullulanase (BmPul) from B. megaterium WW1210, showing similar molecular weight (110.8 kDa) and optimal pH (6.5). However, PulY103A had an optimal temperature of of 45 °C and exhibited relatively higher activity toward amylose (48.3%) compared with pullulan (100%), soluble starch (67.5%), and amylopectin (23.1%). The thin-layer chromatography results showed that the major pullulan hydrolysis products were maltotriose and maltohexaose, which differed from those reported in other pullulanases. On the basis of enzyme specificity, PulY103A was an amylopullulanase, which presented transglycosylation activity by forming α-1,4-glucosidic linkages. CONCLUSIONS: A novel amylopullulanase with transglycosylation activity was characterized. The features of this enzyme suggested its potential to produce maltohexaose.

10.
Eur J Clin Nutr ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32273572

RESUMO

OBJECTIVE: This study aimed to examine the efficacy of Nutritional Risk Screening 2002 (NRS2002) and Mini Nutritional Assessment Short Form (MNA-SF) in recognizing sarcopenia and predicting its mortality in Chinese geriatric hospitalized patients. METHODS: A prospective analysis was performed in 430 hospitalized geriatric patients. Nutrition status was assessed using the NRS2002 and MNA-SF scales. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the revised consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Patients were follow-up for up to 26 months. RESULTS: The overall prevalence of sarcopenia was 35.3% in this population. In the sarcopenic patients, 53 (34.9%) were malnutrition/nutritional risk according to NRS2002 assessment and 101 (66.4%) patients were malnutrition/nutritional risk according to MNA-SF assessment. NRS2002 vs MNA-SF showed moderate agreement (κ = 0.460, P < 0.001). Receiver operating characteristic analysis showed that the area under the curve of MNA-SF was larger than NRS2002 in recognizing sarcopenia (0.763 vs 0.649, P = 0.001). During a median follow-up time of 20.22 months, 48 (31.6%) sarcopenic patients died. The Kaplan-Meier curve demonstrated that malnutrition/nutritional risk patients according to whether NRS2002 or MNA-SF assessment had a higher risk of death than the normal nutrition patients (χ2 = 15.728, P < 0.001; χ2 = 7.039, P = 0.008, respectively). Age, serum albumin levels, and NRS2002 score were independent factors influencing the mortality. CONCLUSION: MNA-SF score may be better than the NRS2002 score to recognize sarcopenia in Chinese geriatric population. Both NRS2002 and MNA-SF scores could predict mortality, but NRS2002 score was the independent predict factor.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32297434

RESUMO

Immunotherapy has made great strides in improving clinical outcomes in cancer treatment. However, few patients exhibit adequate response rates for key outcome measures and desired long-term responses, and they often suffer systemic side effects due to the dynamic nature of the immune system. This has motivated a search for alternative strategies to improve unsatisfactory immunotherapeutic outcomes. In recent years, biomaterial-assisted immunotherapy has shown promise in cancer treatment with improved therapeutic efficacy and reduced side effects. These biomaterials have illuminated fundamental mechanisms underlying the immunoediting process, while greatly improving the efficacy of chimeric antigen receptor (CAR) T-cell therapy, cancer vaccine therapy, and immune checkpoint blockade therapy. This minireview discusses recent advances in engineered biomaterials that address limitations associated with conventional cancer immunotherapies.

12.
Chemistry ; 26(30): 6778-6783, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32129523

RESUMO

Manipulating the collective molecular movements to implement macroscopic mechanical response of bulk material is attractive and challenging. Here, an organic-inorganic hybrid single crystal is synthesized, which exhibits a giant macroscopic shape transformation with a remarkable thermal hysteretic feature. The colossal anisotropic shape change, which manifests as an abrupt elongation of ca. 9 % along the crystallographic c-axis and a concomitant contraction of ca. 9 % in a perpendicular direction, is induced by a significant reorientation of imidazolium, accompanied with a substantial configurational variation in CuBr4 2- complex anions. The synergistic motions of both the molecular cations and anions engender a remarkable large thermal hysteresis (>30 K) in the shape transformation of the single crystal, implying that this material may play a role in alternating memory media. Furthermore, due to the stable crystal lattice, a single crystal that demonstrates naked-eye detectable large shape transformation was used as a thermal actuator to spontaneously control an electric circuit by temperature variation.

13.
J Colloid Interface Sci ; 570: 197-204, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151829

RESUMO

High-efficiency cancer treatment remains the main challenge at present. In this study, a mesoporous platinum nanoparticle- (mesoPt) based nanoplatform is exported for effective tumor treatment, integrating computed tomography (CT) imaging, photothermal conversion, and chemotherapeutic drug delivery capabilities. Mesoporous platinum nanoparticles are facilely synthesized by using Pluronic F127 as a structure-directing agent without seeds or organic reagents and have a spherical structure and uniform diameter of 94 nm. The surface of the mesoPt is modified with polyethylene glycol (PEG), and the prepared mesoPt-PEG shows excellent biocompatibility. Doxorubicin (Dox)-loaded PEG@Pt (PEG@Pt/Dox) is further prepared by electrostatic adsorption and the drug-loading capacity is as high as 25%. In vitro studies demonstrate that Dox can be controllably released from PEG@Pt/Dox in pH 5.5 phosphate buffered solution (PBS). Confocal imaging verifies that PEG@Pt/Dox can efficiently enter Dox-resistant breast cancer cells (MCF-7/ADR), deliver Dox into the cytoplasm when incubated for 1 h or 12 h, and release Dox into the nucleus when incubation is prolonged to 24 h. Cell transmission electron microscopy and flow cytometry also confirm that PEG@Pt/Dox could be internalized by cells. Upon irradiation by an 808 nm laser, the anticancer effect of PEG@Pt/Dox is significantly improved and kills approximately 84% of cancer cells when the concentration of Dox is 8 µg/mL. The killing efficacy of MCF-7/ADR cells is significantly higher in the combination group than in the monochemotherapy group. Hence, multifunctional nanoplatform PEG@Pt/Dox presents an effective strategy to realize efficient combination of chemotherapy and photothermals for drug-resistant cancer.

14.
Biomater Sci ; 8(8): 2227-2233, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32129325

RESUMO

An enveloped virus with soft and rough shells has strong penetration ability for cells. Inspired by the unique structure of virus, we successfully constructed virus-mimicking mesoporous organosilica nanocapsules (denoted as VMONs) for the first time by decorating small-sized silica nanoparticles on soft mesoporous organosilica hollow spheres. TEM and SEM images reveal that the prepared VMONs display uniform diameters (240 nm), a soft framework, a rough surface, and excellent dispersity. Quantitative nanomechanical mapping further demonstrates that the VMONs possess an extremely low Young's modulus (36 MPa) and a scraggly surface. In view of the successful construction of the virus-mimicking nanocapsules, the VMONs are further modified with human serum albumin (HSA) and Cy5.5-maleimide (Mal-Cy5.5) to investigate their cell penetration ability. Flow cytometry analysis reveals that the internalization of VMONs@HSA-Cy5.5 increases 2.74-fold compared to that of the conventional mesoporous nanosphere. Confocal laser scanning microscopy images show that the VMONs@HSA-Cy5.5 diffuses deeper for multicellular spheroids compared to both hard and soft mesoporous organosilica nanospheres. The penetration ability of the VMONs and SMONs increases 18.49 and 6.13-fold compared to that of MONs at the depth of 60 µm. Thanks to the excellent cellular penetration ability, the virus-mimicking VMONs@HSA-Cy5.5 can effectively deliver the anticancer drug doxorubicin (Dox) into drug-resistant MCF-7/ADR human breast cancer cells and significantly enhance the chemotherapeutic efficacy. Taken together, the constructed virus-mimicking organosilica nanocapsules with a soft framework and a rough surface possess strong cellular internalization and tumor penetration abilities, providing a unique and effective nanoplatform for biomedical applications.

15.
Food Chem ; 319: 126548, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32151902

RESUMO

Paeonia ostii is an emerging woody oil crop and cultivated on a large scale in China. This study attempted to characterize the characteristics of P. ostii seed oil body (OB) and found the key genes related to its morphology. The results showed that P. ostii seed oil contained five dominant fatty acid compositions that were stored in OBs. During the development of seeds, oil yield and fatty acid content were in line with OB accumulation. Moreover, NaCl concentration and pH value could influence P. ostii OB stability. Additionally, oleosins (OLEs) were identified as the most abundant proteins in OBs. Based on the expression levels of OLEs, PoOLE17.5 was isolated, which might be localized in OBs. And overexpression of PoOLE17.5 in tobacco obviously increased seed size and hundred-seed weight, altered OB morphology and increased fatty acid content. These results could provide a theoretical basis for improving oil yield of P. ostii seeds.

16.
Nano Lett ; 20(3): 1791-1799, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32097556

RESUMO

Here, we show that the turn-on voltage for the hydrogen evolution reaction on a graphene surface can be tuned in a semiconductor-insulator-graphene (SIG) device immersed in a solution. Specifically, it is shown that the hydrogen evolution reaction (HER) onset for the graphene can shift by >0.8 V by application of a voltage across a graphene-Al2O3-silicon junction. We show that this shift occurs due to the creation of a hot electron population in graphene due to tunneling from the Si to graphene. Through control experiments, we show that the presence of the graphene is necessary for this behavior. By analyzing the silicon, graphene, and solution current components individually, we find an increase in the silicon current despite a fixed graphene-silicon voltage, corresponding to an increase in the HER current. This additional silicon current appears to directly drive the electrochemical reaction, without modifying the graphene current. We term this current "direct injection current" and hypothesize that this current occurs due to electrons injected from the silicon into graphene that drives the HER before any electron-electron scattering occurs in the graphene. To further determine whether hot electrons injected at different energies could explain the observed total solution current, the nonequilibrium electron dynamics was studied using a 2D ensemble Monte Carlo Boltzmann transport equation (MCBTE) solver. By rigorously considering the key scattering mechanisms, we show that the injected hot electrons can significantly increase the available electron flux at high energies. These results show that semiconductor-insulator-graphene devices are a platform which can tune the electrochemical reaction rate via multiple mechanisms.

17.
ACS Appl Mater Interfaces ; 12(8): 9050-9061, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32024363

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) infections lead to a high mortality rate for cystic fibrosis or immunocompromised patients. The alginate of the biofilm was believed to be the key factor disabling immune therapy and antibiotic treatments. A silver nanocomposite consisting of silver nanoparticles and a mesoporous organosilica layer was created to deliver two pharmaceutical compounds (alginate lyase and ceftazidime) to degrade the alginate and eradicate P. aeruginosa from the lungs. The introduction of thioether-bridged mesoporous organosilica into the nanocomposites greatly benefited the conjunction of foreign functional molecules such as alginate lyase and increased their hemocompatibility and drug-loading capacity. Silver nanocomposites with a uniform diameter (∼39 nm) exhibited a high dispersity, good biocompatibility, and high ceftazidime-loading capacity (380.96 mg/g). Notably, the silver nanocomposites displayed a low pH-dependent drug release and degradation profiles (pH 6.4), guaranteeing the targeted release of the drugs in the acidic niches of the P. aeruginosa biofilm. Indeed, particles loaded with alginate lyase and ceftazidime exhibited high inhibitory and degradation effects on the biofilm of P. aeruginosa PAO1 based on the specific catalytic activity of the enzyme to the alginate and antibacterial function of their loaded ceftazidime and silver ions. It should be noted that the enzyme-decorated nanocomposites succeeded in eradicating P. aeruginosa PAO1 from the mouse lungs and decreasing the lung injuries. No deaths or serious side effects were observed during the experiments. We believe that the silver nanocomposites with high biocompatibility and organic group-incorporated framework have the potential to be used to deliver multiple functional molecules for antibacterial therapy in clinical application.

18.
Chem Commun (Camb) ; 56(14): 2071-2086, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32016228

RESUMO

The development of molecular materials whose physical properties can be switched between different states has attracted significant attention for their potential application in sensing, information processing, spintronics, and smart actuators. Generally speaking, such functional bistability can be induced by the motion of electrons or constituted molecules in response to external stimuli. In this Feature Article, we will introduce how to manipulate the structural variations, including spin crossover, molecular reorientation, and molecular displacement, to tune the magnetic properties, optical properties, dielectric properties, and mechanical response of single-crystal materials, with a highlight of our contributions to this booming field.

19.
J Cell Physiol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012263

RESUMO

Trimethylamine N-oxide (TMAO) is produced from the phosphatidylcholine metabolism of gut flora and acts as a risk factor of cardiovascular disease. However, the underlying mechanisms for its proatherogenic action remain unclear. This study aimed to observe the effect of TMAO on endothelial cell pyroptosis and explore the underlying mechanisms. Our results showed that TMAO promoted the progression of atherosclerotic lesions in apolipoprotein E-deficient (apoE-/- ) mice fed a high-fat diet. Pyroptosis and succinate dehydrogenase complex subunit B (SDHB) upregulation were detected in the vascular endothelial cells of apoE-/- mice and in cultured human umbilical vein endothelial cells (HUVECs) treated with TMAO. Overexpression of SDHB in HUVECs enhanced pyroptosis and impaired mitochondria and high reactive oxygen species (ROS) level. Pyroptosis in the SDHB overexpression of endothelial cells was inhibited by the ROS scavenger NAC. In summary, TMAO promotes vascular endothelial cell pyroptosis via ROS induced through SDHB upregulation, thereby contributing to the progression of atherosclerotic lesions.

20.
DNA Cell Biol ; 39(4): 661-670, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32101022

RESUMO

Fibroblast growth factor 21 (FGF21) is a hormone-like member of the FGF family that is associated with cell death in atherosclerosis. However, its underlying mechanisms remain unclear. In this study, the effect of FGF21 on endothelial cell pyroptosis and its potential mechanisms were investigated. Results showed that FGF21 inhibits oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis and related molecular expression in human umbilical vein endothelial cells (HUVECs). Mitochondrial function was damaged by ox-LDL and restored by FGF21. A mechanism proved that ubiquinol cytochrome c reductase core protein I (UQCRC1) was downregulated by ox-LDL and upregulated by FGF21. Further, the silencing of UQCRC1 aggravated HUVEC pyroptosis and impaired mitochondrial function and reactive oxygen species (ROS) production. Moreover, Tet methylcytosine dioxygenase (TET2) was involved in the regulation of UQCRC1 expression and pyroptosis. In summary, FGF21 inhibited ox-LDL-induced HUVEC pyroptosis through the TET2-UQCRC1-ROS pathway.


Assuntos
Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/metabolismo , Piroptose/fisiologia , Aterosclerose/patologia , Sobrevivência Celular , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/genética , Fatores de Crescimento de Fibroblastos/genética , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
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