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1.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165554, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513833

RESUMO

Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31710581

RESUMO

A Gram-stain-positive, aerobic, coccus-shaped, non-spore-forming actinobacterium, designated strain N5BH11T, was isolated from a surface-sterilized sample of Mentha haplocalyx Briq. collected from Guizhou, PR China and tested by a polyphasic approach to determine its taxonomic position. Strain N5BH11T grew optimally at 30 °C, pH 6.0-7.0. Substrate mycelia and aerial mycelia were not formed, and no diffusible pigments were observed on the media tested. Phylogenetic analysis based on 16S rRNA gene sequence suggested that strain N5BH11T belonged to the genus Nakamurella and had the highest 16S rRNA gene sequence similarity to Nakamurella flavida DS-52T (98.1 %). The DNA G+C content of strain N5BH11T was 71.6 mol%. The average nucleotide identity values between strain N5BH11T and the type strains of Nakamurella panacisegetis, Nakamurella multipartita and Nakamurella lactea were 74.0, 76.5 and 73.6 %, respectively. The estimated DDH values between strain N5BH11T and the type strains of N. panacisegetis, N. multipartita and N. lactea were 20.3%, 21.4 and 20.2 %, respectively. The cell-wall peptidoglycan contained meso-diaminopimelic acid, and MK-8(H4) was the predominant menaquinone. The predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine and unidentified phospholipids. The major fatty acids were iso-C15  :  0, anteiso-C15  :  0, C16  :  0 and C16  :  1ω7c. On the basis of the results of phylogenetic analysis and phenotypic and chemotaxonomic characteristics, strain N5BH11T represents a novel species of the genus Nakamurella, for which the name Nakamurella flava sp. nov. is proposed. The type strain is N5BH11T (=KCTC 49196T=CGMCC 4.7524T).

4.
Adv Healthc Mater ; 8(23): e1900974, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31697035

RESUMO

Endoscopy is a clinical gold standard to exam the interior of a hollow organ or body cavity. For the first of time, this study presents the design and construction of a fluorescent endoscopic system that harnesses the power of the second near-infrared window II (NIR-II) fluorescence imaging. An NIR-II fluorescent molecular probe, indocyanine green (ICG) conjugated bevacizumab (Bev-ICG) that targets vascular endothelial growth factor (VEGF), is successfully synthesized and evaluated along with the NIR-II endoscopy imaging system. Simultaneous NIR-II fluorescence and white-light (WL) imaging of VEGF is validated in an orthotopic rat colorectal cancer model. This NIR-II endoscopy system is a generalizable design, and it is compatible with the most of current clinic endoscopies. Similar hardware upgrades are expected to greatly promote the application of NIR-II fluorescent imaging in the clinic.

5.
J Hazard Mater ; : 121676, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31759761

RESUMO

Organo-functionalized SiO2 nanoparticles are regarded as promising adsorbents for capture of heavy metals. However, actual adsorptivity of a specific functional group onto SiO2 surface is unclear, thus extending a debate on which type of organic group possesses a better affinity toward heavy metals. Herein, surface functionalization of SiO2 with different groups (i.e., -EDTA (ethylenediamine triacetic acid), -COOH, -SO3H, -SH and -NH2) were achieved by a facile silylating reaction. Batch experiments indicated that adsorption capacity of SiO2 was remarkably improved by surface functionalization. Quantitative analysis manifested that one mole of EDTA grafted onto SiO2 surface can adsorb 1.51 mol of Pb(II) ions, which was 7.7, 17.1, 28.4 and 50.2-fold larger than those of COOH-, SO3H-, SH- and NH2-functionalized SiO2, respectively. This is first time to evaluate adsorptivity of functionalized SiO2 on the basis of per effective functional group, which may repair deficiency of conventional assessment method that calculated on the basis of per unit mass. Further, adsorption mechanism of these functionalized SiO2 were identified and uncovered by experimental and theoretical studies. This work not only develops an efficient adsorbent for heavy metal remediation but also provides a valuable insight for evaluation and design of novel SiO2-based materials.

6.
Mol Cell ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31733991

RESUMO

The COMPASS (complex of proteins associated with Set1) complex represents the prototype of the SET1/MLL family of methyltransferases that controls gene transcription by H3K4 methylation (H3K4me). Although H2B monoubiquitination (H2Bub) is well known as a prerequisite histone mark for COMPASS activity, how H2Bub activates COMPASS remains unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of an extended COMPASS catalytic module (CM) bound to the H2Bub and free nucleosome. The COMPASS CM clamps onto the nucleosome disk-face via an extensive interface to capture the flexible H3 N-terminal tail. The interface also sandwiches a critical Set1 arginine-rich motif (ARM) that autoinhibits COMPASS. Unexpectedly, without enhancing COMPASS-nucleosome interaction, H2Bub activates the enzymatic assembly by packing against Swd1 and alleviating the inhibitory effect of the Set1 ARM upon fastening it to the acidic patch. By delineating the spatial configuration of the COMPASS-H2Bub-nucleosome assembly, our studies establish the structural framework for understanding the long-studied H2Bub-H3K4me histone modification crosstalk.

7.
Medicine (Baltimore) ; 98(46): e17969, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725660

RESUMO

Alanine transaminase (ALT) abnormalities are common in chronic hepatitis B (CHB) carriers during postpartum period. Disturbances in cytokines are considered to be associated with hepatitis Flares. There are limited data on cytokines changes in HBeAg positive patients with ALT abnormalities.This is an observational study. Pregnant patients with hepatitis B e-antigen (HBeAg) positive were enrolled from January 2014 to September 2018. Patients were assigned into three groups based on ALT levels in postpartum 6 to 8 weeks: ALT in normal range, ALT in 1 to 2-fold upper limits of normal (ULN) and ALT >2-fold ULN. Serum cytokines, ratios of regulatory T cells, and the concentration of cortisol were collected and compared among the three groups.Of the 135 mothers enrolled, 80.7% (109/135) completed the postpartum 6-week study. 13.8% (15/109) patients had postpartum ALT higher than 2ULN, 27.5% (30/109) patients had ALT in 1 to 2ULN and 58.7% (64/109) patients had ALT in normal range. Compared to control group, patients with ALT >2ULN had a higher IL-10 level (P < .05). No differences of IL-10 levels were found in the comparison of other inter comparison among three groups. No differences were found in the levels of other collected serum cytokines, cortisol, and regulatory T cells among three groups. On multivariate analysis, abnormal IL-10 level was independent risk factor for postpartum ALT elevating >2ULN. At the same time, the incidence of postpartum ALT elevated >2ULN were higher in patients with abnormal elevation IL-10 level than in patients with normal IL-10 level (14/68 vs 1/41, P = .008).CHB patients with postpartum ALT abnormalities show higher IL-10 level and postpartum ALT abnormalities were mainly occurred in patients with abnormal IL-10 level. IL-10 may be an underlying predictor and treatment target of hepatitis B, and further studies are needed.

8.
Biomater Sci ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31748767

RESUMO

Biofabrication with various hydrogel systems allows the production of tissue or organ constructs in vitro to address various challenges in healthcare and medicine. In particular, photocrosslinkable hydrogels have great advantages such as excellent spatial and temporal selectivity and low processing cost and energy requirements. However, inefficient polymerization kinetics of commercialized photoinitiators upon exposure to UV-A radiation or visible light increase processing time, often compromising cell viability. In this study, we developed a hydrogel crosslinking system which exhibited efficient crosslinking properties and desired mechanical properties with high cell viability, through a dual-photoinitiator approach. Through the co-existence of Irgacure 2959 and VA-086, the overall crosslinking process was completed with a minimal UV dosage during a significantly reduced crosslinking time, producing mechanically robust hydrogel constructs, while most encapsulated cells within the hydrogel constructs remained viable. Moreover, we fabricated a large PEGDA hydrogel construct with a single microchannel as a proof of concept for hydrogels with vasculature to demonstrate the versatility of the system. Our dual-photoinitiator approach allowed the production of this photocrosslinkable hydrogel system with microchannels, significantly improving cell viability and processing efficiency, yet maintaining good mechanical stability. Taken together, we envision the concurrent use of photoinitiators, Irgacure 2959 and VA-086, opening potential avenues for the utilization of various photocrosslinkable hydrogel systems in perfusable large artificial tissue for in vivo and ex vivo applications with improved processing efficiency and cell viability.

9.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692055

RESUMO

BAX is an important proapoptotic protein of the BCL-2 family, and its stability is essential for the regulation of the mitochondrial apoptotic pathway. A previous study revealed that BAX could undergo degradation through the ubiquitin-proteasome pathway. In this study, we identified two lysine sites, K21 and K123, that were critical ubiquitin-binding sites in BAX. Mutation of these two sites prolonged the half-life of BAX and also affected its proapoptotic ability. Intriguingly, we found that ABT-737, a BCL-2 inhibitor, significantly enhanced TRAIL-induced BAX degradation in HCT116 cells and increased TRAIL-induced apoptosis in the HCT116 only with the BAX K21R/K123R mutant, not other BAX mutants. In addition, overexpression of PARKIN, an E3 ubiquitin ligase targeting BAX, dramatically decreased BAX protein level when only treated with ABT-737 in HCT116 cells. Therefore, we speculated that BAX activation is essential for its ubiquitin-dependent degradation.

10.
Medicine (Baltimore) ; 98(44): e17854, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689877

RESUMO

Breast cancer is the most common diagnosed malignancy in women. This study genotyped blood samples from 236 Han Chinese women with breast cancer and 128 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, and rs62514004, to determine whether these WNT1-inducible signaling pathway protein 1 (WISP-1) genetic polymorphisms increase the risk of developing breast cancer. Compared with wild-type (AA) carriers, those carrying the WISP1 rs62514004 AG or AG + GG genetic variants had a greater risk of developing breast cancer. In an evaluation of the association between clinicopathological aspects and the WISP1 SNP rs62514004 in the breast cancer cohort, patients with the GG genotype were less likely than those with the AA genotype to develop stage III/IV disease. Patients carrying the WISP1 rs2929973 GG + TT variant were almost twice as likely as those carrying the GT genotype to have estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors, while those with the WISP1 rs62514004 AG + GG genetic variants were around twice as likely as those with the AA genotype to have HER2-positive tumors. This study details risk associations between WISP1 SNPs and breast cancer susceptibility in women of Han Chinese ethnicity.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Proteínas de Sinalização Intercelular CCN/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Fatores de Risco , Transdução de Sinais
11.
Artigo em Inglês | MEDLINE | ID: mdl-31680365

RESUMO

Research studies have revealed that people with hoarding typically collect and keep items due to their aesthetic appeal, utility and strong emotional attachment to the items resulting in clutter and limiting living spaces. This study aims to explore the experiences of individuals with hoarding disorder to understand and describe-the patterns and reasons for hoarding, experiences with decluttering and the impact of hoarding disorder on significant others and society in the context of a multi-ethnic urban Asian country. A total of 12 participants with hoarding disorder were recruited and interviewed using a simple semi-structured interview guide designed for the study. The resulting transcribed interviews were analysed using thematic analysis. The mean age of the participants was 56.7 years (SD = 14.5). Nine super-ordinate and discrete but interconnecting themes emerged from the qualitative interviews: types of hoarded items, sources of hoarded items, ways of storing/arranging hoarded items, help-seeking/treatment contact, reasons for hoarding, experiences with decluttering, impact upon family, community and self, restricting hoarding behaviours and insight. Key themes identified in the study are consistent with the literature on studies on hoarding which have been done in other populations. Hoarding in the community has serious consequences for individuals with hoarding disorder and others living in the community, which is compounded by the lack of insight among these individuals. There is a pressing need to increase public awareness and recognition of hoarding behaviours to aid efforts in bringing timely and appropriate services to the affected individuals.

12.
J Orthop Surg Res ; 14(1): 366, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727100

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) can be used for bone regeneration in the specified condition. Osteogenic differentiation of BMMSCs is controlled by microRNAs (miRNAs) and other factors. This study was aimed to identify the role and mechanism of miR-889 in regulating the osteogenic differentiation of BMMSCs. METHODS: Osteoporosis patients and normal control bone tissues were collected and used PCR techniques to identify the change of miR-889 and WNT7A. Moreover, the dynamic change of miR-889 and WNT7A during osteogenic differentiation of BMMSCs was also measured. Bioinformatic analysis was performed to identify the target genes and potential pathways of miR-889. Then, we constructed miR-889 mimic and inhibitor, ALP staining, ARS, osteoblastic-related protein, and Wnt ß-catenin signaling pathway-related protein were also measured. WNT7A siRNA was also used to verify the function of miR-889. RESULTS: In the present study, we showed that miR-889 expression was upregulated in osteoporosis patients than healthy control. However, the miR-889 expression was downregulated during osteogenic differentiation. Bioinformatics analysis found that miR-889 targets 666 genes and mainly through Wnt ß-catenin signaling pathway. Administrated miR-889 mimic, the ALP activity, and calcium deposition were decreased than the control group, while miR-889 inhibitor shown the opposite trend. And miR-889 could bind the 3'UTR of WNT7A. We further used WNT7A siRNA to explore the function of miR-889, and the results revealed that co-cultured with miR-889 inhibitor and WNT7A siRNA was associated with a reduction of ALP activity and calcium deposition and osteoblastic-related proteins than miR-889 inhibitor alone. CONCLUSION: Our results revealed that miR-889 plays a negative role in inducing osteogenic differentiation of BMSCs through Wnt ß-catenin signaling pathway.

13.
Cell Mol Life Sci ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659415

RESUMO

In recent years, a large number of circRNAs have been identified in mammalian cells with high-throughput sequencing technologies and bioinformatics. The aberrant expression of circRNAs has been reported in many human diseases including gastric cancer (GC). The number of GC-related circRNAs with validated biological functions and mechanisms of action is growing. CircRNAs are critically involved in GC cell proliferation, apoptosis, migration, and invasion. CircRNAs have been shown to function as regulators of parental gene transcription and alternative splicing and miRNA sponges. Moreover, circRNAs have been suggested to interact with proteins to regulate their expression level and activities. Several circRNAs have been identified to encode functional proteins. Due to their great abundance, high stability, tissue- and developmental-stage-specific expression patterns, and wide distribution in various body fluids and exosomes, circRNAs exhibit a great potential to be utilized as biomarkers for GC. Herein, we briefly summarize their biogenesis, properties and biological functions and discuss about the current research progress of circRNAs in GC with a focus on the potential application for GC diagnosis and therapy.

14.
Immunity ; 51(5): 930-948.e6, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31604687

RESUMO

Generation of the first T lymphocytes in the human embryo involves the emergence, migration, and thymus seeding of lymphoid progenitors together with concomitant thymus organogenesis, which is the initial step to establish the entire adaptive immune system. However, the cellular and molecular programs regulating this process remain unclear. We constructed a single-cell transcriptional landscape of human early T lymphopoiesis by using cells from multiple hemogenic and hematopoietic sites spanning embryonic and fetal stages. Among heterogenous early thymic progenitors, one subtype shared common features with a subset of lymphoid progenitors in fetal liver that are known as thymus-seeding progenitors. Unbiased bioinformatics analysis identified a distinct type of pre-thymic lymphoid progenitors in the aorta-gonad-mesonephros (AGM) region. In parallel, we investigated thymic epithelial cell development and potential cell-cell interactions during thymus organogenesis. Together, our data provide insights into human early T lymphopoiesis that prospectively direct T lymphocyte regeneration, which might lead to development of clinical applications.

15.
Clin Exp Rheumatol ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31573475

RESUMO

OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

16.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477831

RESUMO

The inflammatory response plays an important role in carcinogenesis. However, the functional role and mechanism of the UCHL3-associated inflammatory response in ovarian cancer remain to be characterized. Here, we report that increased expression of UCHL3 facilitates tumourigenesis by targeting TRAF2 protein, thereby enhancing the inflammatory response. The expression of UCHL3 is elevated in ovarian cancer patients and is associated with an unfavourable prognosis. Genetic ablation of UCHL3 was found to markedly block ovarian cancer cell proliferation, viability and migration both in vitro and in vivo. Mechanistically, luciferase pathway screening results show that NF-κB signalling is clearly activated compared with other pathways. UCHL3 was found to activate NF-κB signalling by deubiquitinating and stabilizing TRAF2, leading to tumourigenesis. Our results indicate that highly expressed UCHL3 enhances inflammation by stabilizing TRAF2, which in turn facilitates tumourigenesis in ovarian cancer, and that UCHL3 is a potential target for ovarian cancer patients with increased inflammation.

18.
Int J Pharm ; 570: 118688, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31513870

RESUMO

In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscopy (SEM). H-GCS had minimal in vitro cytotoxicity against L-929 and HCEC cells over a concentration range of 0-0.8 mg/mL. Additionally, the H-GCS hydrogel exhibited good ocular tolerance and biocompatibility after a single instillation. Moreover, H-GCS hydrogel significantly prolonged the precorneal retention of fluorescein sodium compared with its aqueous solution. An in vivo pharmacokinetic study demonstrated that the levofloxacin-loaded H-GCS hydrogel could provide a significantly higher Cmax and AUC0-12h compared with the levofloxacin aqueous solution, thus increasing ocular bioavailability. Overall, the proposed H-GCS hydrogel acts as an in situ gelling system that might represent a promising vehicle for topical ocular drug delivery.

19.
J Cell Mol Med ; 23(11): 7830-7843, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502361

RESUMO

Mitochondrial dynamic disorder is involved in myocardial ischemia/reperfusion (I/R) injury. To explore the effect of mitochondrial calcium uniporter (MCU) on mitochondrial dynamic imbalance under I/R and its related signal pathways, a mouse myocardial I/R model and hypoxia/reoxygenation model of mouse cardiomyocytes were established. The expression of MCU during I/R increased and related to myocardial injury, enhancement of mitochondrial fission, inhibition of mitochondrial fusion and mitophagy. Suppressing MCU functions by Ru360 during I/R could reduce myocardial infarction area and cardiomyocyte apoptosis, alleviate mitochondrial fission and restore mitochondrial fusion and mitophagy. However, spermine administration, which could enhance MCU function, deteriorated the above-mentioned myocardial cell injury and mitochondrial dynamic imbalanced. In addition, up-regulation of MCU promoted the expression and activation of calpain-1/2 and down-regulated the expression of Optic atrophy type 1 (OPA1). Meantime, in transgenic mice (overexpression calpastatin, the endogenous inhibitor of calpain) I/R model and OPA1 knock-down cultured cell. In I/R models of transgenic mice over-expressing calpastatin, which is the endogenous inhibitor of calpain, and in H/R models with siOPA1 transfection, inhibition of calpains could enhance mitochondrial fusion and mitophagy, and inhibit excessive mitochondrion fission and apoptosis through OPA1. Therefore, we conclude that during I/R, MCU up-regulation induces calpain activation, which down-regulates OPA1, consequently leading to mitochondrial dynamic imbalance.

20.
Mar Drugs ; 17(9)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505835

RESUMO

Diverse bioactive substances derived from marine organisms have been attracting growing attention. Besides small molecules and polypeptides, numerous studies have shown that marine proteins also exhibit antitumor activities. Small anticancer proteins can be expressed in vivo by viral vectors to exert local and long-term anticancer effects. Herein, we purified and characterized a novel protein (ASP-3) with unique antitumor activity from Arca subcrenata Lischke. The ASP-3 contains 179 amino acids with a molecular weight of 20.6 kDa. The spectral characterization of ASP-3 was elucidated using Fourier Transform infrared spectroscopy (FTIR) and Circular Dichroism (CD) spectroscopy. Being identified as a sarcoplasmic calcium-binding protein, ASP-3 exhibited strong inhibitory effects on the proliferation of Human hepatocellular carcinoma (HepG2) cells with an IC50 value of 171.18 ± 18.59 µg/mL, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The RNA-seq analysis showed that ASP-3 regulated the vascular endothelial growth factor receptor (VEGFR) signaling pathway in HepG2 cells. Immunofluorescence results indicated that ASP-3 effectively reduced VEGFR2 phosphorylation in HepG2 cells and affected the downstream components of VEGF signaling pathways. The surface plasmon resonance (SPR) analysis further demonstrated that ASP-3 direct interacted with VEGFR2. More importantly, the therapeutic potential of ASP-3 as an anti-angiogenesis agent was further confirmed by an in vitro model using VEGF-induced tube formation assay of human umbilical vein endothelial cells (HUVECs), as well as an in vivo model using transgenic zebrafish model. Taken together, the ASP-3 provides a good framework for the development of even more potent anticancer proteins and provides important weapon for cancer treatment using novel approaches such as gene therapy.

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