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1.
Biomed Res Int ; 2020: 5425741, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32462001

RESUMO

With the popularization of rehabilitation robots, it is necessary to develop quantitative motor function assessment methods for patients with a stroke. To make the assessment equipment easier to use in clinics and combine the assessment methods with the rehabilitation training process, this paper proposes an anthropomorphic rehabilitation robot based on the basic movement patterns of the upper limb, point-to-point reaching and circle drawing movement. This paper analyzes patients' movement characteristics in aspects of movement range, movement accuracy, and movement smoothness and the output force characteristics by involving 8 patients. Besides, a quantitative assessment method is also proposed based on multivariate fitting methods. It can be concluded that the area of the real trajectory and movement accuracy during circle drawing movement as well as the ratio of force along the sagittal axis in backward point-to-point movement are the unique parameters that are different remarkably between stroke patients and healthy subjects. The fitting function has a high goodness of fit with the Fugl-Meyer scores for the upper limb (R 2 = 0.91, p = 0.015), which demonstrates that the fitting function can be used to assess patients' upper limb movement function. The indicators are recorded during training movement, and the fitting function can calculate the scores immediately, which makes the functional assessment quantitative and timely. Combining the training process and assessment, the quantitative assessment method will farther expand the application of rehabilitation robots.

2.
Cancer Lett ; 485: 38-44, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32437725

RESUMO

Bladder cancer is the tenth most common cancer worldwide and has been associated with high mortality and morbidity. Although the treatment of bladder cancer is based on well-defined tumor classifications and gradings, patients still experience different clinical response. The heterogeneity of this disease calls for substantial research with more in-depth molecular characterization, with the hope of identifying new diagnostic and treatment options. In recent years, non-coding RNAs (ncRNAs), particularly, microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circRNAs) were found to be associated with bladder cancer occurrence and development. This review highlights the recent findings concerning ncRNAs and their relevance to the pathogenesis of bladder cancer. This may provide a foundation for developing highly specific diagnostic tools and more robust therapeutic strategies in the future.

3.
Front Immunol ; 11: 638, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411127

RESUMO

Hemophilia A is a genetic disorder that results in the deficiency of functional factor VIII protein, which plays a key role in blood coagulation. Currently, the majority of hemophilia A patients are treated with repeated infusions of factor VIII protein. Approximately 30% of severe hemophilia A patients develop neutralizing antibodies to factor VIII (known as factor VIII inhibitors) due to treatment, rendering factor VIII protein infusions ineffective. Previously, mice receiving murine IL-2 complexed with α-murine IL-2 mAbs (JES6-1A12) showed a lack of factor VIII inhibitor formation after factor VIII treatment, which was associated with the proliferation and the activation of factor VIII-specific regulatory T cells (Tregs). In this paper, we evaluated if an Fc-fused mutated protein analog of mouse IL-2, named Fc.Mut24, engineered to selectively promote the expansion of Tregs in vivo can modulate factor VIII-specific immune responses. The mice received one intraperitoneal injection of Fc.Mut24. When the regulatory T cell population reached its highest frequency and peak activation, the mice received a hydrodynamic injection of factor VIII plasmid (day 4) followed by a second Fc.Mut24 dose (day 7). Peripheral blood was collected weekly. Flow cytometry was used to characterize the peripheral blood cell populations, while ELISA and Bethesda assays were used to assess the inhibitor concentrations and the functional titers in plasma. The activated partial thromboplastin time assay was used to assess the functional activities of factor VIII in blood. The mice receiving Fc.Mut24 showed a dramatic and transient increase in the population of activated Tregs after Fc.Mut24 injection. Factor VIII gene therapy via hydrodynamic injection resulted in high anti-factor VIII inhibitor concentrations in control PBS-injected mice, whereas the mice treated with Fc.Mut24 produced no inhibitors. Most significantly, there were no inhibitors generated after a second hydrodynamic injection of factor VIII plasmid administered at 19 weeks after the first injection in Fc.Mut24-treated mice. The mice receiving Fc.Mut24 maintained high levels of factor VIII activity throughout the experiment, while the control mice had the factor VIII activity dropped to undetectable levels a few weeks after the first factor VIII plasmid injection. Our data show that human therapies analogous to Fc.Mut24 could potentially provide a method to prevent inhibitor formation and induce long-term immune tolerance to factor VIII in hemophilia patients.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32423197

RESUMO

Photoswitchable fluorescent diarylethenes are promisingly widely applied in the fields of optical memory, all-optical transistors, bioimaging and super-resolution imaging, etc. However, they are facing the problems of fluorescence quenching at aggregated/solid state, inadequate fluorescence ON/OFF switching ratio and the necessity of UV-light irradiation. Herein, we report a novel kind of high-performance diarylethenes with aggregated-induced emission (AIE) by conjugating two diarylethene groups on one AIE-gen, i.e., TPE-2DTE (blue-green fluorescent) and OTPE-2DTE (orange fluorescence). Their open forms show enhanced fluorescence in aggregated state and solid state. The closed form of TPE-2DTE/OTPE-2DTE was effectively generated upon a short-wavelength visible-light (400 nm-450 nm) irradiation, whose fluoresence was dramatically quenched by intramolecular energy transfer.Remarkably, 405 nm purple irradiation gives the fluorescence ON/OFF ratios of 1196: 1 and 1983: 1 for TPE-2DTE and OTPE-2DTE, respectively. The reverse process can be accomplished after another longer wavelength irradiation such as 621 nm and shows considerable fatigue resistance. Taking advantage of superior photoswitching properties under visible-light irradiations, TPE-2DTE and OTPE-2DTE were used for super-resolution imaging with a high resolution of sub-50 nm. This work offers a guidance to design bright-emission and high-performance all-visible light controlled diarylethene photoswitches for practical applications.

6.
Emerg Microbes Infect ; 9(1): 976-987, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32321380

RESUMO

Interferon-induced transmembrane protein 3 (IFITM3) as an antiviral factor can inhibit replication of several viruses including influenza virus. A single-nucleotide polymorphism rs12252-C of IFITM3 results in a truncated IFITM3 protein lacking its first 21 amino acids, which is much higher in the Han Chinese population and associated with severe illness in adults infected with pandemic influenza H1N1/09 virus. To investigate if IFITM3 or IFITM3 rs12252-C could affect the antibody response after influenza vaccination, we detected the haemagglutination inhibition (HI) of 171 healthy young adult volunteers (IFITM3 rs12252-C/C, C/T, T/T carriers) and in an IFITM3-deletion mouse model (Ifitm3-/-) after trivalent inactivated vaccine (TIV) immunization. Seroconversion rates for H1N1, H3N2 and B viruses in IFITM3 rs12252-C/C genotype carriers was lower compared with C/T and T/T donors. Significantly lower levels of specific antibodies to H1N1, H3N2 and B viruses and total IgG were observed in Ifitm3-/- mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, TIV-specific IgG+ antibody secreting cells and T follicular helper cells in Ifitm3-/- mice were lower compared with wild type mice. However, the number of memory B cells was higher in Ifitm3-/- mice at day 7 after booster. The HI level of Ifitm3-/- mice remained lower than WT mice after third vaccination. Moreover, the transcriptional network regulating GC B cell and plasma cell differentiation was abnormal in Ifitm3-/- mice. Our results indicate that IFITM3 deletion attenuated the antibody response. The mechanism of influenza-IFITM3 interactions affecting the antibody response requires further investigation.

7.
Nat Commun ; 11(1): 1813, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286279

RESUMO

The oocyte cytoplasm can reprogram the somatic cell nucleus into a totipotent state, but with low efficiency. The spatiotemporal chromatin organization of somatic cell nuclear transfer (SCNT) embryos remains elusive. Here, we examine higher order chromatin structures of mouse SCNT embryos using a low-input Hi-C method. We find that donor cell chromatin transforms to the metaphase state rapidly after SCNT along with the dissolution of typical 3D chromatin structure. Intriguingly, the genome undergoes a mitotic metaphase-like to meiosis metaphase II-like transition following activation. Subsequently, weak chromatin compartments and topologically associating domains (TADs) emerge following metaphase exit. TADs are further removed until the 2-cell stage before being progressively reestablished. Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. These defects are partially caused by inherited H3K9me3, and can be rescued by Kdm4d overexpression. These observations provide insight into chromatin architecture reorganization during SCNT embryo development.

8.
J Am Chem Soc ; 142(16): 7497-7505, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32223234

RESUMO

A water-soluble probe, TPA-1OH, with aggregation-induced emission activity is synthesized and used for expedient real-time fluorescence in situ visualization of latent fingerprints (LFPs). A TPA-1OH aqueous solution exhibits nonfluorescence in pure water while strong fluorescence upon molecular aggregation induced by addition of poor solvent. Fluorescence images of LFPs on a variety of substrates, including rough surfaces such as walls, bricks, and paper, are developed under 405 nm light, by soaking in or spraying with a TPA-1OH aqueous solution (30 µM) without any necessity of organic cosolvents and post-treatment steps. The probe is noncytotoxic at a concentration lower than 50 µM. The development process of LFPs is demonstrated by real-time fluorescence in situ imaging. The exponential relationship between the relative fluorescence intensity and time is deduced from the fitting curve. The LFP images developed by TPA-1OH are evident and intact enough to allow that the level 1-3 details are displayed and analyzed. Noteworthily, the level 3 details of LFPs such as the fingerprint ridge width and the characteristics of the sweat pores are evidently visible under fluorescence microscopy. Even the nanoscopic details exceeding level 3 are visualized under super-resolution microscopy with sub-50 nm optical resolution.

9.
Elife ; 92020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32250733

RESUMO

Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD+ synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD+ metabolism and Tau homeostasis in aging and neurodegeneration.

10.
J Vasc Surg ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32273224

RESUMO

OBJECTIVE: An analysis was conducted of early and midterm outcomes of a large series of patients treated with in situ laser fenestration (ISLF) during thoracic endovascular aortic repair (TEVAR) of acute and subacute complex aortic arch diseases, such as Stanford type A aortic dissection (TAAD), type B aortic dissection (TBAD) requiring proximal sealing at zone 2 or more proximal, thoracic aortic aneurysm or pseudoaneurysm, and penetrating aortic ulcer. We present the perioperative and follow-up outcomes and discuss the rate of complications. METHODS: This is a retrospective review of prospectively collected data from January 2017 to March 2019 of patients treated with TEVAR and ISLF of aortic arch branches at a large tertiary academic institution in an urban city in China. Preoperative, intraoperative, and follow-up clinical and radiographic data are analyzed and discussed. RESULTS: A total of 148 patients presented with symptomatic and acute or subacute TAAD, TBAD, thoracic aortic aneurysm, or penetrating aortic ulcer for a total of 183 arch vessels. There were 105 men and 43 women, 21 to 79 years of age (mean, 54.9 ± 12.9 years). Time from symptom onset to time of surgery was an average of 7 ± 3 days. Survivor follow-up duration ranged from 5 to 24 months (mean, 15 ± 5 months). Single-vessel fenestration was carried out in 124 cases, two-vessel fenestration in 13 cases, and three-vessel fenestration in 11 cases. There were four cases with technical failure to laser fenestration, with a technical success rate of 97.3%. Postoperatively, there were seven cases of endoleak (4.7%; one type IB distal from the left subclavian artery branch stent graft, three type IIIC at the fenestration site, and three type II), three retrograde dissections (2.0%), and five strokes (3.4%); death occurred in three patients with 30-day mortality of 2.9%, and two deaths occurred during follow-up for 3.4% mortality at an average 15 months of follow-up. There was no branch stent graft occlusion or spinal ischemia postoperatively or during follow-up. The distribution of arch diseases varied significantly according to the number of vessels that were laser fenestrated; TAAD was more likely to receive multivessel laser fenestrations, and TBAD was more likely to receive single-vessel fenestration (P < .001). The rate of complications was distributed differently between the three ISLF groups, with more complications occurring in multivessel fenestrations. However, a statistical weakening was observed when frequency of complications between the three groups was stratified by type of arch disease. The complication rate varied significantly between the different arch diseases, higher in TAAD than in TBAD (P = .008). CONCLUSIONS: ISLF during TEVAR for treatment of acute and subacute complex aortic arch diseases in the proximal aortic arch is safe and effective on the basis of these early to midterm follow-up data of a large cohort. However, care should be taken in intervening on TAAD using TEVAR with adjunctive multivessel laser fenestration. Continued investigation of TEVAR and adjunctive ISLF is needed to elucidate the long-term outcomes of this minimally invasive treatment for complex aortic arch disease in an urgent setting.

11.
Fish Shellfish Immunol ; 100: 238-245, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32135341

RESUMO

Licorice is a widely used herbal medicine for the treatment of various diseases in southern Europe and parts of Asia. It has been reported that the isoliquiritin (ISL) from Glycyrrhiza root has the activity of promoting angiogenesis. The purpose of this study was to investigate the effect of ISL on the wound healing activity of zebrafish and its mechanism. 6-month-old zebrafish were injured in the skin (2 mm in diameter) and then treated with ISL. By measuring wound size and by histological examination, we found that ISL improved wound healing. In addition, 4-day-old zebrafish embryos of double transgenic line [Tg(fli-1:EGFP)]/[Tg(mpeg:mCherry)] were suffered from tissue traumas and then treated with ISL. Through fluorescent microscopy, we found that ISL promoted macrophage recruitment and angiogenesis in the wound area. Through qPCR analysis, we found that ISL up-regulated the expression of genes related to inflammation and angiogenesis in zebrafish embryos. These results showed that ISL could promote inflammatory response and angiogenesis, which played key roles in promoting wound healing. Therefore, ISL can be used as a promising candidate to promote wound healing.

12.
Cancer Lett ; 483: 66-74, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32142917

RESUMO

Endometrial cancer, a type of primary epithelial malignant tumor in the endometrium, is one of the three most common malignant tumors of the female reproductive system. While the incidence of endometrial cancer has been recently rising, its etiology remains unclear. In this study we found that EM2D9, an independently developed monoclonal antibody, specifically recognized endometrial cancer cells; we further determined that EM2D9 target protein was α5ß1. In vitro and in vivo experiments showed that EM2D9 inhibited the migration of endometrial cancer cells. Real-time quantitative PCR results showed that the expression of CD151 mRNA in endometrial carcinoma cells significantly decreased after EM2D9 treatment. We also found that EM2D9 affected the FAK signaling pathway. Collectively, these results shed light on a new mechanism for the development of endometrial carcinoma.

13.
Sci Total Environ ; 723: 138079, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32222506

RESUMO

There are a large number of abandoned mining areas in China, where external-soil spray seeding is a common technique used to assist with the restoration of these areas. However, the soil component of external-soil spray seeding is deficient, and they are prone to collapse, which complicates ecological restoration. In this study, we added a mineral-solubilizing microbial strain to an external-soil spray seeding substrate in Robinia pseudoacacia and Lespedeza bicolor pots, which were monitored from December 2018 to November 2019. We investigated their root growth and root tensile properties, as well as root-reinforced soil shear strength. The results revealed that the addition of the microbial strain in the substrate improved root growth of Robinia pseudoacacia. The root-reinforced soil shear strength, tensile force and strength were also strengthened by the added microbial strain. Although the growth rate of Robinia pseudoacacia was faster than that of Lespedeza bicolor, the shear strength of the root-reinforced Robinia pseudoacacia soil was lower than that of the Lespedeza bicolor root-reinforced soil of the same diameter. Finally, compared with the cohesion, the change in the friction angle is relatively small, and differences in cohesion resulted in shear strength changes under the same treatment. Our results suggested that the addition of a mineral-solubilizing microbial strain to the external-soil spray seeding substrate could help plants strengthen the soil and positively enhance its effects. These results might also enrich the existing data on the effects of mineral-solubilizing microbial strains on plant roots, while guiding further studies toward improving the efficacy of external-soil spray seeding technologies.

14.
Exp Hematol ; 82: 53-65, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32007477

RESUMO

The histone lysine demethylase KDM5 family is implicated in normal development and stem cell maintenance by epigenetic modulation of histone methylation status. Deregulation of the KDM5 family has been reported in various types of cancers, including hematological malignancies. However, their transcriptional regulatory roles in the context of leukemia remain unclear. Here, we find that KDM5B is strongly expressed in normal CD34+ hematopoietic stem/progenitor cells and chronic myeloid leukemia (CML) cells. Knockdown of KDM5B in K562 CML cells reduced leukemia colony-forming potential. Transcriptome profiling of KDM5B knockdown K562 cells revealed the deregulation of genes involved in myeloid differentiation and Toll-like receptor signaling. Through the integration of transcriptome and ChIP-seq profiling data, we show that KDM5B is enriched at the binding sites of the GATA and AP-1 transcription factor families, suggesting their collaborations in the regulation of transcription. Even though the binding of KDM5B substantially overlapped with H3K4me1 or H3K4me3 mark at gene promoters, only a small subset of the KDM5B targets showed differential expression in association with the histone demethylation activity. By characterizing the interacting proteins in K562 cells, we discovered that KDM5B recruits protein complexes involved in the mRNA processing machinery, implying an alternative epigenetic action mediated by KDM5B in gene regulation. Our study highlights the oncogenic functions of KDM5B in CML cells and suggests that KDM5B is vital to the transcriptional regulation via multiple epigenetic mechanisms.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 232: 118174, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32106034

RESUMO

Here, Au-doped carbon dots (CDAu) nanosols with good stability were prepared by hydrothermal reaction method. We found that CDAu can efficiently catalyze the nanoreaction of reducing AgNO3 by glucose, and at 420 nm,the reaction products of yellow spherical silver nanosol exhibit an intense surface plasmon resonance (SPR) absorption peak. The nucleic acid aptamers (Apt) can be adsorbed on the surface of carbon dots, so that their catalytic activity was suppressed, the nanosilvers were reduced, the solution color becomes lighter, and the Abs value was weakened. When As3+ was added, it forms a stable conjugate with the Apt, releases free carbon dots, restored its catalytic activity, and the color and Abs signals enhanced linearly. Based on the Apt regulation and the catalytic amplification effect of CDAu on AgNO3-glucose, a new extremely sensitive SPR spectrophotometric method for the determination of arsenic ion content of 0.025-0.75 µg/L was established, and the detection limit of As3+ is 0.01 µg/L.

16.
Aging (Albany NY) ; 12(4): 3354-3370, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065779

RESUMO

Bladder cancer stem cells (BCSCs), exhibiting self-renewal and differentiation capacities, may contribute to the tumor initiation, metastasis, recurrence and drug resistance of bladder cancer. However, the underlying functional mechanisms of BCSCs remain to be clarified. In this study, we describe the differentially-expressed mRNAs, lncRNAs, and circRNAs in BCSCs compared with that in bladder cancer non-stem cells (BCNSCs) through the transcriptome microarray data analysis using bladder cancer patients' specimens. CircRNA_103809, the top one among the highly expressed circRNA identified in BCSCs, promotes the self-renewal, migration and invasion capabilities of bladder cancer by acting as a miR-511 sponge. Additionally, GO and KEGG pathway analysis suggest the differentially expressed genes identified may be involved in the cellular metabolism, differentiation and metastasis regulation of the cancer cells. Co-expression networks of lncRNAs/mRNAs and circRNAs/mRNAs constructed by WGCNA give a picture of the non-coding/coding RNAs regulating patterns in BCSCs. Notably, as core genes in the networks, AHCY, C6orf136 and LRIG1 show high potential to be prognosticators for bladder cancer. Therefore, further studies of non-coding RNA functional mechanisms in BCSCs is valuable for detecting the pathogenic mechanisms and discovering novel biomarkers in bladder cancer.

17.
Injury ; 51(4): 1069-1076, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32061356

RESUMO

INTRODUCTION: This study aimed to investigate the effectiveness and safety of the Chinese Aircraft-shaped Sleeve (CASS) system on the clinical outcomes of tibial intermedullary nailing using a suprapatellar approach for the treatment of tibial fractures in a cohort of adult Chinese patients over a minimum one-year follow-up. METHODS: After institutional review board approval, skeletally mature patients with Orthopaedic Trauma Association (OTA) type 42 tibial shaft fractures were randomized into either a SP approach using CASS group or a conventional SP approach group after informed consent was obtained. The operations were performed by a single senior orthopaedic surgeon according to group assignments. A group of 33 patients were treated using the CASS system and the other group of 34 patients were treated using a conventional SP approach. Both groups fully complied with research requirements and completed 12 months of follow-up. Magnetic resonance images (MRI) were obtained for the evaluation of the patellofemoral joint (PFJ) and residual debris preoperatively, as well as one week and 12 months postoperatively. Radiographs were used to assess alignment and union, visual analog scores (VAS) were used to assess anterior knee pain, and range of motion (ROM) and the Lysholm knee scoring scales were used for evaluating the operated knee at the 12-month follow-up. RESULTS: Differences in cartilage lesion changes observed by MRI between the two groups were statistically significant (P = 0.030 at 1 week postoperatively; P = 0.025 at 12 months postoperatively). No significant differences were evident with respect to debris residue, malalignments, nonunion, VAS, ROM and Lysholm knee scoring scale with the exception of stair climbing (P = 0.02). CONCLUSION: Based on the data of this one-year clinical follow-up study, the SP approach using the CASS system offers the potential to benefit patients suffering from tibial shaft fractures, who will be treated with intramedullary nailing especially for smaller patients.

18.
Life Sci ; 247: 117402, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035930

RESUMO

AIMS: Gastric cancer (GC) is one of the most common malignant tumors in the world. Anti-angiogenic therapy is a useful strategy for the treatment of advanced GC. This study was aimed to systemically compare the anti-angiogenesis, anti-cancer efficacy, as well as the safety of four known anti-angiogenic drugs, namely ramucirumab, apatinib, regorafenib and cabozantinib. MAIN METHODS: Anti-angiogenic effect was evaluated for the intersegmental vessels (ISVs) and subintestinal veins (SIVs) formation in the Tg (fli-1: EGFP) zebrafish embryos. Anti-cancer efficacy was tested for the in vivo cell proliferation in cell line derived tumor xenograft (CDX) model based on Tg (fli-1: EGFP) zebrafish embryos. KEY FINDINGS: All four drugs exhibited anti-angiogenic abilities and tumor inhibition effects in fli-1: EGFP transgenic zebrafish. Using zebrafish xenografted model, we found that effectiveness of ramucirumab in anti-GC-proliferation is better than apatinib, regorafenib and cabozantinib. The combination of anti-angiogenic drugs and cisplatin showed no significant benefit in tumors. Meanwhile, toxicity assay showed that all tested anti-angiogenic drugs could cause cardiovascular-related side effects. The therapeutic index (LD50/ED50) of cabozantinib is higher than apatinib and regorafenib, suggesting a potential as an anti-GC drug. SIGNIFICANCE: The comparison of GC-related anti-angiogenic drugs was first reported. It was found that cabozantinib had a potential as an anti-GC drug. Zebrafish model was an ideal animal model for the research of anti-angiogenic behaviors.


Assuntos
Inibidores da Angiogênese/farmacologia , Anilidas/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Neovascularização Patológica/tratamento farmacológico , Compostos de Fenilureia/farmacologia , Piridinas/farmacologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Feminino , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/tratamento farmacológico , Peixe-Zebra/embriologia
19.
J Cell Physiol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012286

RESUMO

Mesenchymal stem/stromal cells (MSCs) play an important role in bone tissue engineering because MSCs possess multilineage potential of differentiation to mesenchymal tissues. Semaphorin 3A (Sema3A) and hypoxia-inducible factor-1α (HIF1α) are proved as important regulatory factors for osteogenesis and angiogenesis. The aim of this study was to investigate the effects of Sema3A and HIF1α co-overexpression on the osteogenesis and angiogenesis in induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs). Importantly, we assessed the potential osteogenic effectiveness of Sema3A and HIF1α co-overexpressed iPSC-MSCs seeded on hydroxyapatite (HA) scaffold in a mouse calvarial defect model. The overexpression for Sema3A, HIF1α, or Sema3A-HIF1α fusion in iPSC-MSCs was performed by separately infecting with conducted lentiviral vector. We determined the cell proliferation, the expressions of osteogenic, and endothelial markers of iPSC-MSCs cultured in osteogenic or endothelial induction medium in vitro. A mouse model calvarial defect was created and implanted with the Empty implant, HA scaffold alone, HA scaffold combined with iPSC-MSCs that infected with negative control or Sema3A-HIF1α fusion for 8 weeks in vivo. The results showed that Sema3A and HIF1α co-overexpression reversed the reduced cell proliferation that reduced by Sema3A overexpression alone. Importantly, the co-overexpression significantly increased the expressions of osteogenic and angiogenic related-genes compared with negative control after induction. Moreover, the Sema3A-HIF1α co-overexpressed iPSC-MSCs seeded on HA scaffold boosted the new bone and collagen fiber formation and facilitated repair of calvarial defect in a mouse model, which might have the potential application for bone defect reconstruction.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31971108

RESUMO

Icariin (ICA), is one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim, has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and anti-osteoporosis. Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the estrogen receptor (ER) in hFOB1.19 human osteoblast cells. The experimental results show that ICA can stimulate cell proliferation and increase the activity of alkaline phosphatase (ALP), osteocalcin (BGP) and I collagen (Col I) and the amount of calcified nodules. Furthermore the mRNA and protein expression of OPG and RANKL and the OPG/RANKL mRNA and protein expression ratios were upregulated by ICA. The above mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50 ng/mL. Subsequent mechanistic studies comparing 50 ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of upregulated expression is connected with the estrogen receptor. In conclusions, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.

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