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1.
J Cancer Res Ther ; 16(5): 1125-1128, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004758

RESUMO

Objective: The objective was to evaluate the feasibility and safety of computed tomography (CT)-guided percutaneous irreversible electroporation (IRE) in porcine kidneys. Materials and Methods: Under CT guidance, two monopole probes were used to precisely puncture through the renal parenchyma into the renal hilum in nine anesthetized adult Bama miniature pigs. After which, IRE ablation was performed. Biochemical and pathological examinations were carried out 2 h, 2, 7, and 14 days after the procedure. Results: All procedures were performed successfully without any serious complications such as bleeding, infection, or death. All pigs survived until the end of the study. Pathological examinations showed that cells in the ablation area were dead within 2 days after the procedure, whereas the vascular endothelium showed only slight damage. After 2 days, endothelialization ensued and regrowth of smooth muscle cells was observed after 14 days. Hemogram tests indicated a transient increase but gradually returned to baseline levels 14 days after the procedure. Conclusion: IRE was essentially safe, however further studies on tumor ablation using several different animal models are needed.

2.
J Sci Food Agric ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006380

RESUMO

BACKGROUND: Waxy maize (Zea mays L. sinensis Kulesh) is a good material for brewing. Waxy maize wine as a kind of Chinese rice wine is greatly affected by the fermentation starter named Qu. In this study, an innovative mixed Qu (consisting of two yeast and three mold) was produced and the raw-starch brewing method was applied in winemaking. The other three waxy maize wines fermented by three commercial Qu were also analyzed for comparison. RESULTS: Due to superb growth and fermentation characteristics, Saccharomyces cerevisiae CICC1009 and Pichia anomala CICC1851 were chosen to produce yeast Qu. The additive amount of yeast Qu was determined to be 30 g kg-1 . In terms of chemical properties, mixed Qu was more suitable to make maize wine by the raw-starch brewing method compared to the other three. The most influential component for overall aroma profile in maize wines fermented by mixed Qu and Mifeng Qu was ethyl butyrate and ß-damascenone, respectively, while in maize wines fermented by Angel Qu and Like Qu it was ethyl octanoate. Obvious differences were found among four maize wines on bitterness, umami, richness, saltiness and sourness by the electronic tongue. The olfactory characteristics of maize wine fermented by Mifeng Qu were quite different from the other three according to the electronic nose. CONCLUSION: The innovative mixed Qu can be considered as an excellent starter for raw-starch brewing of waxy maize. The chemical indices and volatile flavor compounds of waxy maize wines were greatly affected by different Qu. This article is protected by copyright. All rights reserved.

3.
J Cardiothorac Surg ; 15(1): 289, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004056

RESUMO

BACKGROUND: Diabetes mellitus(DM) is an indicator affects postoperative mortality and morbidity after coronary artery bypass grafting (CABG). Acute kidney injury (AKI) is one of the frequent postoperative complications after CABG. This multi-centre register study designed to investigate the impact of DM on postoperative AKI in primary isolated CABG patients. METHODS: We included all patients (n = 4325) from Jiangsu Province CABG register who underwent primary isolated CABG from September 2017 to August 2019. The patients were divided into 3 groups: No-DM group(n = 3067), DM-oral group (DM with oral hypoglycemic agents, n = 706) and DM-insulin group (DM with insulin treatment, n = 552). The development and severity of AKI were based on Acute Kidney Injury Network (AKIN) criteria. RESULTS: There were totally 338, 108 and 145 patients developed AKI in No-DM, DM-oral and DM-insulin group respectively. Comparing with No-DM group, DM-oral group had a higher rate of AKI(χ2 = 10.071, p = 0.002), DM-insulin group had a higher rate(χ2 = 94.042, p<0.001) and severity of AKI(χ2 = 10.649, p = 0.005). The adjusted odds ratio for AKI was 1.26 (95% CI 1.03-1.57) in DM-oral group and 3.92 (95% CI 3.27-5.16) in DM-insulin group, in comparison with No-DM group. CONCLUSIONS: Independent of baseline renal function or cardiac function, DM was associated with an increased risk of AKI after CABG, especially in patients with insulin treatment, who also had a higher severity of AKI.

4.
Nat Cell Biol ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020597

RESUMO

PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N6-methyladenosine (m6A) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates cardiac hypertrophy and restores heart function, while administration of a CHAPIR mimic enhances the pathological hypertrophic response in pressure-overloaded mice. Mechanistically, CHAPIR-PIWIL4 complexes directly interact with METTL3 and block the m6A methylation of Parp10 mRNA transcripts, which upregulates PARP10 expression. The CHAPIR-dependent increase in PARP10 promotes the mono-ADP-ribosylation of GSK3ß and inhibits its kinase activity, which results in the accumulation of nuclear NFATC4 and the progression of pathological hypertrophy. Hence, our findings reveal that a piRNA-mediated RNA epigenetic mechanism is involved in the regulation of cardiac hypertrophy and that the CHAPIR-METTL3-PARP10-NFATC4 signalling axis could be therapeutically targeted for treating pathological hypertrophy and maladaptive cardiac remodelling.

5.
Chem Commun (Camb) ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016292

RESUMO

Postsynthetic treatment is an attractive method to enhance photoelectrochemical water splitting. The facile Cl- modification approach developed in this work remarkably promotes the photocurrent density of BiVO4 up to 2.7 mA cm-2 by facilitating carrier transfer in addition to a charge carrier separation efficiency enhancement.

6.
Acta Pharmacol Sin ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037406

RESUMO

Rodent diabetic models, used to understand the pathophysiology of diabetic cardiomyopathy (DCM), remain several limitations. Engineered cardiac tissues (ECTs) have emerged as robust 3D in vitro models to investigate structure-function relationships as well as cardiac injury and repair. Advanced glycation end-products (AGEs), produced through glycation of proteins or lipids in response to hyperglycemia, are important pathogenic factor for the development of DCM. In the current study, we developed a murine-based ECT model to investigate cardiac injury produced by AGEs. We treated ECTs composed of neonatal murine cardiac cells with AGEs and observed AGE-related functional, cellular, and molecular alterations: (1) AGEs (150 µg/mL) did not cause acute cytotoxicity, which displayed as necrosis detected by medium LDH release or apoptosis detected by cleaved caspase 3 and TUNEL staining, but negatively impacted ECT function on treatment day 9; (2) AGEs treatment significantly increased the markers of fibrosis (TGF-ß, α-SMA, Ctgf, Collagen I-α1, Collagen III-α1, and Fn1) and hypertrophy (Nppa and Myh7); (3) AGEs treatment significantly increased ECT oxidative stress markers (3-NT, 4-HNE, HO-1, CAT, and SOD2) and inflammation response markers (PAI-1, TNF-α, NF-κB, and ICAM-1); and (4) AGE-induced pathogenic responses were all attenuated by pre-application of AGE receptor antagonist FPS-ZM1 (20 µM) or the antioxidant glutathione precursor N-acetylcysteine (5 mM). Therefore, AGEs-treated murine ECTs recapitulate the key features of DCM's functional, cellular and molecular pathogenesis, and may serve as a robust in vitro model to investigate cellular structure-function relationships, signaling pathways relevant to DCM and pharmaceutical intervention strategies.

7.
Sci Adv ; 6(40)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32998896

RESUMO

CD4+Foxp3+ regulatory T cells (Tregs) are pivotal for the inhibition of autoimmune inflammatory responses. One way to therapeutically harness the immunosuppressive actions of Tregs is to stimulate the proliferative expansion of TNFR2-expressing CD4+Foxp3+ Tregs via transmembrane TNF (tmTNF). Here, we report that two-pore channel (TPC) inhibitors markedly enhance tmTNF expression on antigen-presenting cells. Furthermore, injection of TPC inhibitors including tetrandrine, or TPC-specific siRNAs in mice, increases the number of Tregs in a tmTNF/TNFR2-dependent manner. In a mouse colitis model, inhibition of TPCs by tetrandrine markedly attenuates colon inflammation by expansion of Tregs Mechanistically, we show that TPC inhibitors enhance tmTNF levels by disrupting surface expression of TNF-α-converting enzyme by regulating vesicle trafficking. These results suggest that the therapeutic potential of TPC inhibitors is mediated by expansion of TNFR2-expressing Tregs and elucidate the basis of clinical use in the treatment of autoimmune and other inflammatory diseases.

8.
Biomed Res Int ; 2020: 9258649, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029531

RESUMO

Methylation of the O6-methylguanine methyltransferase (MGMT) gene promoter is correlated with the effectiveness of the current standard of care in glioblastoma patients. In this study, a deep learning pipeline is designed for automatic prediction of MGMT status in 87 glioblastoma patients with contrast-enhanced T1W images and 66 with fluid-attenuated inversion recovery(FLAIR) images. The end-to-end pipeline completes both tumor segmentation and status classification. The better tumor segmentation performance comes from FLAIR images (Dice score, 0.897 ± 0.007) compared to contrast-enhanced T1WI (Dice score, 0.828 ± 0.108), and the better status prediction is also from the FLAIR images (accuracy, 0.827 ± 0.056; recall, 0.852 ± 0.080; precision, 0.821 ± 0.022; and F 1 score, 0.836 ± 0.072). This proposed pipeline not only saves the time in tumor annotation and avoids interrater variability in glioma segmentation but also achieves good prediction of MGMT methylation status. It would help find molecular biomarkers from routine medical images and further facilitate treatment planning.

9.
Aging (Albany NY) ; 122020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033230

RESUMO

Radiotherapy resistance is one of the main causes for treatment failure in colorectal cancer (CRC), and it is associated with the deregulation of certain microRNAs. In this study, we constructed the microRNA-mRNA network consisting of 2275 microRNAs and 7045 target genes, collected the known microRNAs related to CRC-radiosensitivity (CRCR) (n=18) as the seed nodes, and applied the algorithm of random walk with restart (RWR) to the network to identify novel CRCR-related microRNAs (n=263). In functional analysis, 263 novel microRNAs shared a high proportion of the same biological processes and pathways with the known microRNAs. In topological analysis of the sub-network of the 263 microRNAs and their targets, hsa-mir-506-3p and hsa-mir-140-5p were identified as network hub nodes. In plasma, radiosensitive patients had a higher expression level of hsa-mir-506-3p and hsa-mir-140-5p than radioresistant patients. In experimental validation, both hsa-mir-506-3p and hsa-mir-140-5p over-expression could obviously decrease the cell proliferation, survival rate and colonality in CRC cells after radiation. In conclusion, this study combined the novel network-based method with experimental validation, and identified two novel radiosensitive biomarkers of hsa-mir-506-3p and hsa-mir-140-5p in CRC.

10.
Surg Endosc ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030588

RESUMO

BACKGROUND: Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area. METHODS: The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups. RESULTS: Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28-44.74 vs. 29, IQR 29-39.5, p = 0.002) and no. 9 station nodes (2, IQR 1-5 vs. 2, IQR 1-3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20-80 ml vs. 80, IQR 50-80 ml, p < 0.001) and a longer surgical duration (262.5 min, IQR 220-303.25 min vs. 232, IQR 220-255 min, p < 0.001) in the CML group than in the OG group. The incidence of postoperative complications (19.8% vs. 16.0%, p = 0.591) and postoperative hospital stay (8, IQR 7-9 days vs. 8, IQR 7-9 days, p = 0.452) were comparable between the CML and OG groups. CONCLUSION: Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events.

11.
Shanghai Kou Qiang Yi Xue ; 29(3): 250-256, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33043340

RESUMO

PURPOSE: To compare the mechanical properties of 3D-printed titanium meshes and pre-shaped titanium meshes, and to evaluate the effects of 3D-printed titanium meshes on cell proliferation and differentiation. METHODS: 3D- printed titanium meshes were produced and prepared with laser printing machine. The mechanical properties were analyzed by static tension and compression load test. Bone marrow mesenchymal stem cells (BMSCs) were extracted from 4-week-old male SD rats. BMSCs were co-cultured with 3D-printed titanium meshes of different apertures. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Alkaline phosphatase (ALP) activity assay was used to test ALP activity. The expression of related osteogenic genes was tested by real-time PCR. The adhesion and growth of BMSCs were investigated by scanning electron microscopy (SEM) and living / dead cell staining. SPSS 22.0 software package was used for statistical analysis of the results. RESULTS: The results of 3D-printing Ti-meshes tension and compression loading experiment were excellent. The 3D-printing Ti-meshes showed no inhibitory effects on cell proliferation, survival and adhesion, but had a positive effect on osteogenesis of BMSCs. CONCLUSIONS: The mechanical properties of 3D-printed Ti-meshes are excellent. The 3D-printed Ti-meshes have good biocompatibility.


Assuntos
Implantes Dentários , Titânio , Animais , Masculino , Impressão Tridimensional , Ratos , Ratos Sprague-Dawley , Telas Cirúrgicas
12.
Artigo em Inglês | MEDLINE | ID: mdl-33048720

RESUMO

We present an integrated approach for creating and assigning color palettes to different visualizations such as multi-class scatterplots, line, and bar charts. While other methods separate the creation of colors from their assignment, our approach takes data characteristics into account to produce color palettes, which are then assigned in a way that fosters better visual discrimination of classes. To do so, we use a customized optimization based on simulated annealing to maximize the combination of three carefully designed color scoring functions: point distinctness, name difference, and color discrimination. We compare our approach to state-of the-art palettes with a controlled user study for scatterplots and line charts, furthermore we performed a case study. Our results show that Palettailor, as a fully-automated approach, generates color palettes with a higher discrimination quality than existing approaches. The efficiency of our optimization allows us also to incorporate user modifications into the color selection process.

13.
Theranostics ; 10(25): 11794-11819, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052247

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease manifested by cognitive impairment. As a unique approach to open the blood-brain barrier (BBB) noninvasively and temporarily, a growing number of studies showed that low-intensity focused ultrasound in combination with microbubbles (FUS/MB), in the absence of therapeutic agents, is capable of ameliorating amyloid or tau pathology, concurrent with improving memory deficits of AD animal models. However, the effects of FUS/MB on both the two pathologies simultaneously, as well as the memory behaviors, have not been reported so far. Methods: In this study, female triple transgenic AD (3×Tg-AD) mice at eight months of age with both amyloid-ß (Aß) deposits and tau phosphorylation were treated by repeated FUS/MB in the unilateral hippocampus twice per week for six weeks. The memory behaviors were investigated by the Y maze, the Morris water maze and the step-down passive avoidance test following repeated FUS/MB treatments. Afterwards, the involvement of Aß and tau pathology were assessed by immunohistochemical analysis. Neuronal health and phagocytosis of Aß deposits by microglia in the hippocampus were examined by confocal microscopy. Further, hippocampal proteomic alterations were analyzed by employing two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with mass spectrometry. Results: The three independent memory tasks were indicative of evident learning and memory impairments in eight-month-old 3×Tg-AD mice, which developed intraneuronal Aß, extracellular diffuse Aß deposits and phosphorylated tau in the hippocampus and amygdala. Following repeated FUS/MB treatments, significant improvement in learning and memory ability of the 3×Tg-AD mice was achieved. Amelioration in both Aß deposits and phosphorylated tau in the sonicated hemisphere was induced in FUS/MB-treated 3×Tg-AD mice. Albeit without increase in neuron density, enhancement in axonal neurofilaments emerged from the FUS/MB treatment. Confocal microscopy revealed activated microglia engulfing Aß deposits in the FUS/MB-treated hippocampus. Further, proteomic analysis revealed 20 differentially expressed proteins, associated with glycolysis, neuron projection, mitochondrial pathways, metabolic process and ubiquitin binding etc., in the hippocampus between FUS/MB-treated and sham-treated 3×Tg-AD mice. Conclusions: Our findings reinforce the positive therapeutic effects on AD models with both Aß and tau pathology induced by FUS/MB-mediated BBB opening, further supporting the potential of this treatment regime for clinical applications.

14.
Cell Death Dis ; 11(10): 858, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33056982

RESUMO

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, has greatly affected clinical outcomes in non-small cell lung cancer (NSCLC) patients. The long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to NSCLC gefitinib resistance remain poorly understood. In this study, by analyzing the differentially expressed lncRNAs in gefitinib-resistant cells and gefitinib-sensitive cells in the National Institute of Health GEO dataset, we found that lncRNA CASC9 expression was upregulated, and this was also verified in resistant tissues. Gain and loss of function studies showed that CASC9 inhibition restored gefitinib sensitivity both in vitro and in vivo, whereas CASC9 overexpression promoted gefitinib resistance. Mechanistically, CASC9 repressed the tumor suppressor DUSP1 by recruiting histone methyltransferase EZH2, thereby increasing the resistance to gefitinib. Furthermore, ectopic expression of DUSP1 increased gefitinib sensitivity by inactivating the ERK pathway. Our results highlight the essential role of CASC9 in gefitinib resistance, suggesting that the CASC9/EZH2/DUSP1 axis might be a novel target for overcoming EGFR-TKI resistance in NSCLC.

15.
Mol Psychiatry ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051604

RESUMO

Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.

16.
Biol Direct ; 15(1): 20, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076954

RESUMO

BACKGROUND: The nematode worm, Caenorhabditis elegans, is a saprophytic species that has been emerging as a standard model organism since the early 1960s. This species is useful in numerous fields, including developmental biology, neurobiology, and ageing. A high-quality comprehensive molecular interaction network is needed to facilitate molecular mechanism studies in C. elegans. RESULTS: We present the predicted functional interactome of Caenorhabditis elegans (FIC), which integrates functional association data from 10 public databases to infer functional gene interactions on diverse functional perspectives. In this work, FIC includes 108,550 putative functional associations with balanced sensitivity and specificity, which are expected to cover 21.42% of all C. elegans protein interactions, and 29.25% of these associations may represent protein interactions. Based on FIC, we developed a gene set linkage analysis (GSLA) web tool to interpret potential functional impacts from a set of differentially expressed genes observed in transcriptome analyses. CONCLUSION: We present the predicted C. elegans interactome database FIC, which is a high-quality database of predicted functional interactions among genes. The functional interactions in FIC serve as a good reference interactome for GSLA to annotate differentially expressed genes for their potential functional impacts. In a case study, the FIC/GSLA system shows more comprehensive and concise annotations compared to other widely used gene set annotation tools, including PANTHER and DAVID. FIC and its associated GSLA are available at the website http://worm.biomedtzc.cn .

17.
J Colloid Interface Sci ; 583: 614-625, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33039860

RESUMO

The fabrication of high-performance and stable electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is of importance for sustainable water-splitting technologies. Herein, the cobalt (Co) nanoparticles and molybdenum carbide (Mo2C) heterostructures anchored N-doped carbon (Co/Mo2C@NC-800) was designed as bifunctional electrocatalyst for overall water splitting via a simple pyrolysis approach for metal organic frameworks (MOFs) precursor. This composite shows a remarkable performance for HER and OER with a small overpotential of 121 mV and 311 mV at 10 mA cm-2, respectively. When the optimized electrocatalyst was employed as both anode and cathode for overall water splitting in a two-electrode system, the electrolyzer achieves a low cell voltage of 1.67 V at 10 mA cm-2 in 1 M KOH, as well as a superior and stable long-time operation of 30 h. The promising hybrid material demonstrates excellent electrocatalysis performance due to effective combination of the best of both worlds: Mo2C with remarkable HER performance and Co nanoparticles with excellent OER activity. The Mo2C possesses strong hydrogen binding energy and Co exhibits prominent electrical conductivity, thus the construction of heterostructures achieves more active sites with different functions and significantly boosts HER and OER process. The novel and effective synthesis strategy provides new insights into the design of outstanding non-noble metal bifunctional electrocatalysts for overall water splitting.

18.
Ultrasonics ; 110: 106272, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33065465

RESUMO

Sonodynamic therapy (SDT) is a promising modality for cancer treatment. Sinoporphyrin sodium (DVDMS), purified from Photofrin II, shows great potential in SDT evidenced by growing studies. The purpose of the current study was to investigate the antitumor effect of SDT combined with DVDMS on human glioblastoma (U87 MG) cell line in vitro. The cellular uptake of DVDMS was investigated by confocal microscopy and IVIS spectrum imaging system. In addition, DVDMS toxicity and anti-tumor effect of SDT were assessed by flow cytometry. The generation of intracellular reactive oxygen species (ROS) was determined using DCFH-DA staining. Simultaneously, fluorescence microscopy was performed to access the destabilization of mitochondrial membrane potential (MMP). The results showed that DVDMS could easily enter the cells and accumulated in the cytoplasm, especially the mitochondria. And the intracellular DVDMS increased with incubation time or concentrations. The results also showed remarkable cytotoxicity of DVDMS-mediated SDT (center frequency: 0.970 MHz; peak-rarefactional pressure: 0.52-MPa; acoustic power: 0.32 W; pulse repetition frequency: 1 Hz; duty cycle: 1-30%; duration: 3 min) on U87 MG cells, while DVDMS alone was non-toxic to the cells. In comparison with the control group, the SDT-treated group showed significant generation of intracellular ROS and loss of MMP at 1 h post-treatment. These results indicated that DVDMS-mediated SDT could induce great cytotoxicity in U87 MG cells via the production of ROS and showed potentials in the treatment for glioblastoma.

20.
Vet Microbiol ; 250: 108851, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33002681

RESUMO

Infection by enveloped viruses includes endocytosis and/or membrane fusion at the plasma membrane, where host cell proteases play an essential role. Among them, elastase-mediated infection has been documented for several enveloped viruses. Porcine reproductive and respiratory syndrome virus (PRRSV), an economically critical factor in global swine industry, is previously reported to infect host cells via low pH-dependent clathrin-mediated endocytosis (CME) and undergo membrane fusion in recycling endosomes. In the current study, we identified that elastase was significantly elevated in the lung tissues of highly pathogenic PRRSV (HP-PRRSV)-infected pigs compared to the mock-infected ones. We subsequently demonstrated that elastase contributed to HP-PRRSV infection in both MARC-145 cells and porcine alveolar macrophages (PAMs). Mechanistically, HP-PRRSV entered host cells at the cell surface via elastase-mediated membrane fusion, independent of low pH and CME, and its glycoprotein 5 (GP5) was cleaved by the protease during this process. All these findings deepen our understanding of HP-PRRSV infection, and are beneficial for prevention and control of the disease.

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