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1.
Food Chem ; 367: 130754, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34384983

RESUMO

N-acetylneuraminic acid (Neu5Ac) is widely spread in many biologically significant glycans of mammals, commonly as a terminal α-glycoside. It is of great significance to develop analytical techniques for detection of Neu5Ac. Herein, a high-sensitive fluorescent biosensor for Neu5Ac has been developed based on FRET between CdSe/ZnS quantum dots (QDs) and BHQ2, as well as exonuclease III (Exo III)-assisted recycling amplification strategy. Employing the specially designed three-level FRET systems and fluorescent signal recovery mechanism, together with five-step recycling signal amplification chain reactions, an ultralow detection limit of 24 fM was achieved. Meanwhile, good linear response ranges within 0.2-12.5 pM and 12.5-1000 pM were founded. The assay has excellent performance in real sample detection, and thus offers great potential for detection of sialic acids modified glycans/lipids in the fields of medical diagnosis and food testing.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Compostos de Selênio , Animais , DNA , Exodesoxirribonucleases , Transferência Ressonante de Energia de Fluorescência , Limite de Detecção , Ácidos Siálicos , Sulfetos , Compostos de Zinco
2.
J Colloid Interface Sci ; 606(Pt 2): 961-970, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34487943

RESUMO

The usage of single-use face masks (SFMs) has increased since the outbreak of the coronavirus pandemic. However, non-degradability and mismanagement of SFMs have raised serious environmental concerns. Moreover, both melt-blown and nanofiber-based mask filters inevitably suffer from poor filtration performance, like a continuous decrease in the removal efficiency for particulate matter (PM) and weak breathability. Herein, we report a new method to create biodegradable and reusable fibrous mask filters. The filter consists of a true nanoscale bio-based poly(lactic acid) (PLA) fiber (an average size of 37 ± 4 nm) that is fabricated via electrospinning of an extremely dilute solution. Furthermore, we designed a multiscale structure with integrated features, such as low basis weight (0.91 g m-2), small pore size (0.73 µm), and high porosity (91.72%), formed by electrospinning deposition of true nanoscale fibers on large pore of 3D scaffold nanofiber membranes. The resultant mask filter exhibited a high filtration efficiency (PM0.3-99.996%) and low pressure drop (104 Pa) superior to the commercial N95 filter. Importantly, this filter has a durable filtering efficiency for PM and natural biodegradability based on PLA. Therefore, this study offers an innovative strategy for the preparation of PLA nanofibers and provides a new design for high-performance nanofiber filters.


Assuntos
Nanofibras , Filtração , Material Particulado , Poliésteres
3.
J Exp Bot ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727176

RESUMO

Vegetable oils are indispensable nutritional components of human diet as well as important raw materials for a variety of industrial applications such as pharmaceuticals, cosmetics, oleochemicals and biofuels. The oil plant genomes are highly diverse, and the genetic variation leads to the diversity in oil biosynthesis and accumulation along with agronomic traits. This review discusses the plant oil biosynthetic pathways, the current state of genome assembly, the polyploidy and asymmetric evolution genomes of oil plants and their wild relatives, and the research progress of pan-genomics in oil plants. The availability of complete high-resolution genomes and pangenomes has enabled the identification of structural variations in the genomes that are associated with the diversity of agronomic and environment fitness traits. These and more future genomes also provide powerful tools to understand crop evolution and to harvest the rich natural variations to improve oil crops for enhanced productivity, oil quality, and adaptability to changing environments.

4.
Chemosphere ; : 132714, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34743871

RESUMO

The level of environmental microplastics in the biosphere is constantly increasing. These environmental microplastics can enter the human body with food, be absorbed through the gut, and have negative effects on the organism health after its digestion. Four sizes (0.1, 0.5, 1, 5 µm) polystyrene microspheres (PS-MPs) and nanospheres (PS-NPs) were selected for this study. The effects of different sizes of polystyrene particles on human colonic epithelial cell CCD841CoN and small intestinal epithelial cell HIEC-6 within 24 h were explored. The uptake of PS-NPs was found to has more potential to enter cells than micro-sized polystyrene PS-MPs that was confirmed by fluorescence microscope, and the intake amount was proportional to the exposure time. PS-MPs had no significant effect on cell viability and apoptosis, but the group treated with high concentration showed low toxicity to oxidative stress level and mitochondrial membrane potential. In addition, the membrane damage caused by PS-MPs was significantly higher than that of PS-NPs. This may be due to the large amount of polystyrene adhering to interstitial, which have a significant negative effect on the cell membrane functions. For the first time human intestinal normal cell lines were used to study the effect of microplastic pollution, which can provide some references for the influence of microplastics on human health in the future.

5.
J Hazard Mater ; : 127785, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34801309

RESUMO

Research on electrokinetics-permeable reactive barrier (EK-PRB) remediation to date has mainly focused on homogeneous soils or soils with micro-scale heterogeneities. The potential impact of macro-scale physical heterogeneities, such as stratified layers or lenses, on EK-PRB remediation has not received much attention. This study investigates the effect of a low permeability stratum on EK-PRB remediation of hexavalent chromium (Cr(VI)). Sandbox experiments were conducted to treat Cr(VI)-contaminated kaolinite/sand media, consisting of vertically-layered high permeability (HPZ) and low permeability zones (LPZ), where distance between LPZ and anode (DLA) was 3, 9, or 15 cm. Parameters including current, moisture content (MC), pH, and removal of Cr(VI) were evaluated. With 72 h of EK-PRB treatment, tests with larger DLA (15 cm) had greater Cr(VI) migration from contaminated area to modified-zeolite PRB. Cr(VI), Cr(III), and Cr(Total) removal and energy utilization efficiency followed the trend as: DLA-15 > DLA-9 > DLA-3. MC generally decreased from anode towards cathode and pH was alkaline in all the zones for DLA-3 and DLA-15. In DLA-9 (LPZ in the middle), MC increased and pH was alkaline in HPZs near cathode whereas HPZs near anode were very dry (MC < 1%) and acidic (pH < 5.5). Our results show that the location of LPZ relative to electrode locations has a significant influence on Cr(VI) removal efficiency and macro-scale physical heterogeneity is an important factor to be considered during EK-PRB remediation.

6.
Food Chem ; 373(Pt B): 131448, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34731806

RESUMO

Due to the highly cost-effective and maneuverable property, Maillard reaction-based time-temperature indicators (TTIs) are considered ideal devices for temperature track and quality indication. The objective of this study was to develop a cold-sensitive TTI based on the Maillard reaction reflecting the freshness of chilled seafood. Firstly, the color evolution trends of a series of Maillard reaction-based TTIs were investigated and the xylose-lysine group represented obvious color change. Fourier transform infrared (FTIR) spectroscopy revealed the color change was associated with the formation of CN bond in melanoidin. Simultaneously, the relationships of the color change of TTI with time and temperature were established. The activation energy value (Ea) of TTI was close to that of mackerel. There existed a good relevance (R2 = 0.98) between the color change of TTI and the total volatile basic nitrogen content of mackerel, suggesting this novel TTI might have the potential to monitor the freshness of mackerel.

7.
J Ovarian Res ; 14(1): 152, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34758863

RESUMO

Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial membrane potential is a universal selective indicator of mitochondrial function. In this study, mitochondrial swelling and membrane defect mitochondria in granulosa cells were observed from PCOS patients and DHT-induced PCOS-like mice, and the cytochrome C level in the cytoplasm and the expression of BAX (BCL2-associated X protein) in mitochondria were significantly increased in GCs, with p-Akt decreased, showing mitochondrial membrane was damaged in GCs of PCOS. Melatonin treatment decreased mitochondrial permeability transition pore (mPTP) opening and increased the JC-1 (5,5',6,6'-tetrachloro1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide) aggregate/monomer ratio in the live KGN cells treated with DHT, indicating melatonin mediates mPTP to increase mitochondrial membrane potential. Furthermore, we found melatonin decreased the levels of cytochrome C and BAX in DHT-induced PCOS mice. PDK1/Akt played an essential role in improving the mitochondrial membrane function, and melatonin treatment increased p-PDK 1 and p-Akt in vivo and in vitro. The SIRT1 was also increased with melatonin treatment, while knocking down SIRT1 mRNA inhibiting the protective effect of melatonin to activate PDK1/Akt. In conclusion, melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS.

8.
Bioorg Chem ; 119: 105511, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34847428

RESUMO

Euphoesulatin A (Eup A), a new jatrophane diterpenoid isolated from the Euphorbia esula L. (Euphorbiaceae), was reported to inhibit RANKL-induced osteoclastogenesis. However, the underlying mechanism and the effect in osteoporosis mouse model are still unclear. This study is the first to demonstrate that Eup A inhibits osteoclastogenesis in vitro and in vivo. Mechanistic analysis suggested that Eup A (3, 6, 12 µM) dose-dependently inhibited osteoclastogenesis by down-regulating the activation of NFATc1 and NF-κB and MAPKs signal pathways. Moreover, Eup A (10 mg/kg) significantly prevented bone loss in ovariectomized mice. This work provides in vitro and in vivo evidence that Eup A could be a potential candidate for the development of anti-osteoporosis agents.

9.
Accid Anal Prev ; 164: 106471, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34773873

RESUMO

Cyclists are vulnerable road users and face disproportionately high rates of road trauma, especially in low- and middle-income countries. Behaviour of road users is a system outcome, and thus studying cyclist behaviours can identify problems in the whole road transport system and assist in generating long-lasting, cost-effective solutions to promote cyclist safety. This study aims to investigate the similarities and disparities of cycling behaviour among countries with different income levels and cycling prevalence, and the relationships among cyclist demographic characteristics, behaviours and crash involvement. It applies the Cycling Behaviour Questionnaire (CBQ) to measure the behaviour of cyclists in three countries: Australia (high-income, emerging cycling country), China (mid-income, traditional cycling country) and Colombia (low-income, emerging cycling country). A total of 1094 cyclists (Australia 347, China 368, and Colombia 379) with a mean age of 31.8 years completed the online questionnaire. Confirmatory Factor Analysis was used to examine the factorial structure of the CBQ. The results showed that the three-factor CBQ (i.e., Traffic Violations, Errors and Positive Behaviours) had a stable and uniform factorial structure across all three countries. Cyclists reported more frequent positive behaviours than risky behaviours across all three countries. The Australian cyclists reported more positive behaviours and fewer violations than cyclists from the other countries, which is likely to reflect the road environment, policy and enforcement differences. Male cyclists tended to engage in more risky riding than females and reported more crash involvement. Older cyclists reported less risky riding and less involvement in crashes than younger cyclists. Cyclists who rode more often reported more frequent risky riding. The study helps understand the prevalence of risky/positive cyclist behaviours among countries and provides insights for developing systematic countermeasures to improve cycling environment and cyclist safety.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34841872

RESUMO

Rubrene single crystals have received a lot of attention for their great potential in electronic and wearable nanoelectronics due to their high carrier mobility and excellent flexibility. While they exhibited remarkable electrical performances, their intrinsic potential as photon detectors has not been fully exploited. Here, we fabricate a sensitive and ultrafast organic phototransistor based on rubrene single crystals. The device covers the ultraviolet to visible range (275-532 nm), and the responsivity and detectivity can reach up to ∼4000 A W-1 and 1011 jones at 532 nm, respectively. Furthermore, the response times are highly gate-tunable down to sub-90 µs, and the cutoff frequency is ∼4 kHz, which is one of the fastest organic material-based phototransistors reported so far. Equally important is that the fabricated device exhibits stable light detection ability even after 8 months, indicating great long-term stability and excellent environmental robustness. The results suggest that the high-quality rubrene single crystal may be a promising material for future flexible optoelectronics with its intrinsic mechanical flexibility.

11.
Exp Eye Res ; 213: 108823, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34752817

RESUMO

Choroidal neovascularization (CNV), a feature of neovasular age-related macular degeneration (AMD), acts as a leading cause of vision loss in the elderly. Shikonin (SHI), a natural bioactive compound extracted from Chinese herb radix arnebiae, exerts anti-inflammatory and anti-angiogenic roles and also acts as a potential pyruvate kinase M2 (PKM2) inhibitor in macrophages. The major immune cells macrophages infiltrate the CNV lesions, where the production of pro-angiognic cytokines from macrophage facilitates the development of CNV. PKM2 contributes to the neovascular diseases. In this study, we found that SHI oral gavage alleviated the leakage, area and volume of mouse laser-induced CNV lesion and inhibited macrophage infiltration without ocular cytotoxicity. Moreover, SHI inhibited the secretion of pro-angiogenic cytokine, including basic fibroblast growth factor (FGF2), insulin-like growth factor-1 (IGF1), chemokine (C-C motif) ligand 2 (CCL2), placental growth factor and vascular endothelial growth factor (VEGF), from primary human macrophages by down-regulating PKM2/STAT3/CD163 pathway, indicating a novel potential therapy strategy for CNV.

12.
ACS Appl Mater Interfaces ; 13(46): 55339-55348, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34761896

RESUMO

Effective dye separation and desalination are critical for the treatment of highly saline textile wastewater with dye mixtures. In this study, a graphene oxide (GO) membrane with a tunable interlayer distance (d) was fabricated to generate clean water via two-stage filtration, namely, the dye/salt separation and desalination stages. In the first stage, under low pressure (e.g., 0.3 MPa), the membrane with a d value of ca. 7.60 Å was suitable for removing the dye from the saline wastewater. The dye and salt (i.e., Na2SO4) rejection rates of >99% and <6.5% were achieved, respectively, indicating the significant potential to recycle the dyes from the highly saline dye wastewater. In the second stage, under a higher pressure (e.g., 0.8 MPa), the d value was reduced to ca. 7.15 Å, bestowing the membrane with a desalination function. The desalination rate of a single filtration process could reach up to 51.8% from 1.0 g/L saline (i.e., Na2SO4) water. The as-prepared membrane also exhibited excellent practical advantages, including ultrahigh permeability, significant antifouling (against dye) performance, and excellent stability. Furthermore, with the stacking of multistage filtration systems, the proposed membrane technology will be capable of regenerating dye and producing clean water.

13.
Bioresour Technol ; : 126434, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838969

RESUMO

Vanillin is a natural flavoring agent that is widely used in the bioengineering industry. To enable sustainable development, joint consideration of bacterial performance and negative environmental impacts are critical to vanillin biosynthesis. In this study, a cold shock protein (csp) gene was upregulated for maintaining stable growth in Arthrobacter sp. C2 responding to vanillin and cold stress. Furthermore, the recombinant strain C2 was constructed by simultaneously deleting the xylC gene encoding benzaldehyde dehydrase and overexpressing the pchF gene encoding vanillyl alcohol oxidase and achieved a maximum vanillin productivity of 0.85 mg/g DCW/h with alkaline lignin as the substrate. Finally, this process generated an environmental impact value of 25.05, which was the lowest environmental impact achieved according to life cycle assessment (LCA). Improvement strategies included reducing electricity consumption and replacing chemicals. This study achieved the development of an effective strategy, and future studies should focus on precise vanillin biosynthesis methods for large-scale application.

14.
Molecules ; 26(22)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34833882

RESUMO

A stable, earth-abundant, reusable cobalt-based heterogeneous catalyst is developed for the oxidative esterification of alcohols under ambient conditions, featuring broad substrate scope, providing good to excellent product yields. This protocol enables easy recyclability of the catalyst, measured up to five times without significant loss of efficiency. The active sites of Co-N-Si/AC are proposed to be Co-N species.

15.
PeerJ ; 9: e12116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616607

RESUMO

Background: Cervical cancer is the fourth most common gynecological tumor in terms of both the incidence and mortality of females worldwide. Cervical squamous cell carcinoma (CSCC) accounts for 70-80% of cervical cancers, and endocervical adenocarcinoma (EAC) accounts for 20-25%. Unlike CSCC, EAC has worse clinical outcomes and prognosis. In this study, we explored the relationship between various types of long noncoding RNAs (lncRNAs) and pathological types of cervical cancer. Methods: RNA sequencing (RNA-Seq) and clinical data from The Cancer Genome Atlas (TCGA) were used in this study. A single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE package were used to assess lncRNA activity and immune responses, respectively. RT-qPCR was performed to verify our findings. Results: We explored the relationship between various types of lncRNAs and pathological types of cervical cancer. A series of long intergenic noncoding RNAs (lincRNAs) and antisense RNAs, which are the major types of lncRNAs, were identified to be specifically expressed in EAC and associated with a poor recurrence prognosis in patients with cervical cancer, suggesting that they might serve as independent prognostic markers of recurrence in patients with cervical cancer. RT-qPCR was performed to verify the 10 EAC-specific lncRNAs in cervical cancer samples we collected. Furthermore, the overexpression of these lncRNAs was positively correlated with EAC pathology levels but negatively correlated with immune responses in the microenvironment of cervical cancer. Conclusions: These lncRNAs potentially represent new biomarkers for the prediction of the recurrence prognosis and help obtain deeper insights into potential immunotherapeutic approaches for treating cervical cancer.

16.
Acta Crystallogr F Struct Biol Commun ; 77(Pt 10): 348-355, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605439

RESUMO

Human coronavirus NL63 (HCoV-NL63), which belongs to the genus Alphacoronavirus, mainly infects children and the immunocompromized and is responsible for a series of clinical manifestations, including cough, fever, rhinorrhoea, bronchiolitis and croup. HCoV-NL63, which was first isolated from a seven-month-old child in 2004, has led to infections worldwide and accounts for 10% of all respiratory illnesses caused by etiological agents. However, effective antivirals against HCoV-NL63 infection are currently unavailable. The HCoV-NL63 main protease (Mpro), also called 3C-like protease (3CLpro), plays a vital role in mediating viral replication and transcription by catalyzing the cleavage of replicase polyproteins (pp1a and pp1ab) into functional subunits. Moreover, Mpro is highly conserved among all coronaviruses, thus making it a prominent drug target for antiviral therapy. Here, four crystal structures of HCoV-NL63 Mpro in the apo form at different pH values are reported at resolutions of up to 1.78 Å. Comparison with Mpro from other human betacoronaviruses such as SARS-CoV-2 and SARS-CoV reveals common and distinct structural features in different genera and extends knowledge of the diversity, function and evolution of coronaviruses.


Assuntos
Coronavirus Humano NL63/química , Cristalização/métodos , Cristalografia por Raios X/métodos , Humanos , Concentração de Íons de Hidrogênio , Conformação Proteica
17.
Exp Ther Med ; 22(6): 1368, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34659514

RESUMO

Ding's herbal enema (DHEP) is a traditional Chinese medicinal therapy that has been used to treat ulcerative colitis (UC) in China. The present study determined the molecular mechanism of the effect of DHEP in UC treatment. C57BL/6J mice were treated with 3.5% (w/v) dextran sulfate sodium (DSS) for 7 days to establish an animal model of colitis. The mice were divided into five groups (n=5): Control, vehicle, DHEP, mesalazine and ß-sitosterol. After oral administration for 7 days, the body weight, disease activity index, histopathology and inflammatory factors were analyzed. The fractions of CD4+Foxp3+ regulatory T (Treg) cells and CD4+IL-17A+ T helper (Th) cells were determined by flow cytometry. Gut microbiota composition was analyzed by next-generation sequencing. The results revealed that DHEP and ß-sitosterol could significantly alleviate the symptoms of DSS-induced UC. Furthermore, the levels of IL-6, cyclooxygenase-2, TNF-α and p65 were reduced after administration of DHEP. Additionally, the data indicated that DHEP could increase the abundance of seven operational taxonomic units (OTUs) and decrease the abundance of 12 OTUs in the gut microbiota. The content of short-chain fatty acids in the colon remodeled the balance of Treg/Th17 cells in DSS-induced UC in mice. The present study preliminarily defined the mechanism of action of DHEP in UC that may be associated with the regulation of the gut microbiota composition, and maintenance of the balance between Treg and Th17 cells. Furthermore, ß-sitosterol exhibited the same effects with DHEP and it could be a possible substitute for DHEP in UC treatment.

18.
Antioxidants (Basel) ; 10(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34679729

RESUMO

To investigate the effects of tannins (TA) on porcine oocyte in vitro maturation (IVM), different concentrations of TA (0, 1, 10 and 100 µg/mL) were supplemented with a maturation medium and the COCs and subsequent embryonic development were examined. The results showed that 10 µg/mL TA significantly improved the cumulus expansion index (CEI), cumulus-expansion-related genes (PTGS1, PTGS2, PTX-3, TNFAIP6 and HAS2) expression and blastocyst formation rates after parthenogenetic activation (PA), in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) compared to the control groups, but not oocyte nuclear maturation. Nevertheless, 10 µg/mL TA dramatically enhanced the mRNA expression of oocyte-development-related genes (BMP15, GDF9, CDC2 and CYCLIN B1), GSH, ATP, SOD1, PGC1α, BMP15, GDF9 and CDC2 levels and reduced intracellular ROS level in porcine oocytes. These results indicated that porcine oocyte cytoplasmic maturation was improved by 10 µg/mL TA treatment during IVM. In contrast, a high concentration of TA (100 µg/mL) significantly decreased the CEI and PTGS1, PTGS2, PTX-3 and HAS2 mRNA expressions in cumulus cells, and reduced oocyte nuclear maturation and the total cell numbers/blastocyst. In general, these data showed that 10 µg/mL TA supplementation has beneficial effects on oocyte cytoplasmic maturation and subsequent embryonic development in pigs.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34601618

RESUMO

Polyunsaturated fatty acid (PUFA) synthase is a special and effective enzyme for PUFA synthesis, and dehydratase (DH) domain played a crucial role in it. In this work, we compared four different DH domains from different strains (Schizochytrium sp. HX-308 and Shewanella sp. BR-2) and different gene clusters. First bioinformatics analysis showed that DH1, 2 and DH3 were similar to FabA and PKS-DH, respectively, and all of them got a hot-dog structure. Second, four DH domains were expressed in Escherichia coli that increased biomass. Especially, Schi-DH1,2 presented the highest dry cell weight of 2.3 g/L which was 1.62 times of that of control. Fatty acids profile analysis showed that DH1,2 could enhance the percentage of unsaturated fatty acids, especially DH1,2 from Schizochytrium sp., while DH3 benefited for the saturated fatty acid biosynthesis. Furthermore, five kinds of fatty acids were added to the medium to study the substrate preferences. Results revealed that DH1,2 domain preferred to acting on C16:0, while DH3 domain trended acting on C14:0 and C15:0, which illustrated DH from different clusters do have specific substrate preference. Besides, DH expression could save the cell growth inhibition by mid-chain fatty acids. This study provided more information about the catalysis mechanism of polyunsaturated fatty acid synthase and might promote the modification study based on this enzyme.

20.
Inflammation ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34595678

RESUMO

One type of age-related macular degeneration (AMD), neovascular (nAMD), characterized by choroidal neovascularization (CNV), accounts for the majority of the severe central vision impairment associated with AMD. Endothelial cells (ECs) in direct contact with retinal pigment epithelial (RPE) cells are more prone to the pathological angiogenesis involved in CNV. Herein, we investigated the effect of crosstalk between RPE cells and choroidal endothelial cells (CECs) via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis on the development of choroidal neovascularization (CNV) in vitro and in vivo. ANXA1 expression and secretion from ARPE-19 cells were upregulated by hypoxia. FPR2 expression, especially on the plasma membrane, in HCECs was upregulated under hypoxic conditions. ANXA1 secreted from ARPE-19 cells inhibited NLRP3 inflammasome activation and NLRP3 inflammasome-mediated pyroptosis in HCECs by activating the FPR2/SHP2 axis. Moreover, ANXA1 secreted by ARPE-19 cells promoted behaviors of HCECs, including proliferation, migration, and tube formation, by activating the FPR2/SHP2 axis and inhibiting NLRP3 inflammasome-mediated pyroptosis. Inhibiting the upregulated ANXA1/FPR2/SHP2/NLRP3 inflammasome/pyroptosis axis decreased the volume of CNV. Our data suggest that the crosstalk between RPE cells and CECs via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis promotes CNV. This finding could identify a potential target for the prevention and treatment of CNV.

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