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1.
Brain Res Bull ; 158: 1-8, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32092434

RESUMO

The inflammatory response induced by traumatic spinal cord injury (SCI) involves the activation of NLRP3 inflammasomes, which are closely related to the activation of microglia. Microglial polarization between M1/M2 phenotypes is a pivotal regulatory factor in neuroinflammatory responses to traumatic SCI-induced secondary injuries, and altering this polarization could be beneficial. Glycyrrhizin is a neuroprotective agent with a potent anti-inflammatory property in different neurological disorders and could potentially be useful in SCI. In this study, we investigated the potency of oral treatment with glycyrrhizin to reduce inflammation and improve functional recovery after traumatic SCI by inhibiting NLRP3 inflammasome activation and promoting microglial M2 polarization. After inducing traumatic SCI by dropping a 10 g impactor on the T9 and T10 spinal segments of male Sprague-Dawley rats, the animals were given glycyrrhizin orally immediately after injury and every 12 h for the next 3 d. Behavioral scores improved in glycyrrhizin-treated animals compared to the SCI group. The functional improvement in glycyrrhizin-treated rats paralleled the decreased expression of NLRP3 inflammasome components, such as ASC, NLRP3, and cleaved caspase-1, as well as IL-1ß and IL-18. At the histopathological level, oral treatment with glycyrrhizin diminished the SCI-enhanced production of Iba-1+CD86+ cells (M1 microglia) but improved the release of Iba-1+CD206+ cells (M2 microglia). Likewise, oral therapy with glycyrrhizin significantly enriched the protein expression levels of M2 microglia-related markers (CD206 and Arg-1) but reduced those of M1 microglia-related markers (CD86 and iNOS) in the injured spinal cord. These findings support and extend the knowledge on post-traumatic SCI glycyrrhizin-mediated neuroprotection. Glycyrrhizin's regulation of NLRP3 inflammasome activation and microglial polarization might be a new approach to understanding the anti-inflammatory potency of glycyrrhizin.

2.
Eur Spine J ; 29(3): 616-627, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31894401

RESUMO

PURPOSE: To determine the safe range of shortening the spinal column at middle thoracic spine and to observe the changes in blood-spinal cord barrier (BSCB), microglia/macrophage activation and inducible nitric oxide synthase (iNOS) activity after shortening-induced spinal cord injury. METHODS: Dogs were allocated to four groups. Group A (control) underwent laminectomy of T7 without shortening the spinal column. Groups B, C and D had 1/3, 1/2, and 2/3 of T7 resected, respectively, followed by spinal shortening. Somatosensory evoked potential (SSEP) and hind-limb function were recorded periodically for 14 days after operation. Spinal cord blood flow (SCBF) and BSCB were detected at the acute phase of shortening. Microglia/macrophage reactions and iNOS activity were observed by immunohistochemistry. RESULTS: Shortening of 1/3 of a vertebral height caused no significant changes in SSEP and hind-limb function after operation, whereas shortening of 1/2 of the height caused SSEP abnormality and paraparesis, and severe neurologic deficit of hind-limb was observed when the shortening reached 2/3 of the height. SCBF increased temporarily and showed a trend of recovery when the shortening was within 1/2 of a vertebral segment height. When it reached 1/2 or 2/3 of the height, SCBF at 6 h post-operation was 86.33% or 74.95% of the baseline, and an increasing BSCB permeability was observed. In the subsequent 7 days, obvious activation of macrophage and increased number of iNOS-positive cells were observed. CONCLUSION: It is safe to shorten the spinal cord within 1/3 of a vertebral height in middle thoracic spine under two-segment laminectomy in canine. The BSCB disruption, macrophage activation, and increased iNOS activity were observed in the acute phase of the injury. These slides can be retrieved under Electronic Supplementary Material.

3.
Vaccine ; 38(8): 2034-2044, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31982260

RESUMO

Enterovirus type 71 (EV71) and coxsackievirus A 16 (CA16) are recognized as the major pathogens responsible for human hand-foot-mouth disease. To develop a bivalent EV71-CA16 vaccine, rhesus macaques immunized with two doses of this vaccine via the intradermal route were challenged with EV71 or CA16, and their clinical symptoms, viral shedding, neutralizing antibodies, IFN-γ-specific ELISpots, and tissue viral load were examined longitudinally. Specific immunity against EV71 and CA16 was observed in the macaques, which exhibited controlled proliferation of the EV71 and CA16 viruses and upregulated expression of immune-related genes compared with the controls. Furthermore, broad protection against EV71 and CA16 challenge without immunopathological effects was observed in all the immunized macaques. These studies suggest that the bivalent EV71-CA16 inactivated vaccine was effective against wild-type EV71 or CA16 viral challenge in rhesus macaques.

4.
Biomater Sci ; 8(4): 1117-1126, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31724666

RESUMO

Surgical resection currently remains the mainstay of treatment for patients with gliomas of any grade. The maximum extent of surgical resection is associated with a long-term disease control; however, maximal resection of the brain tumor possibly results in additional neurological deficits. Therefore, improving the precision in brain tumor surgery by visual identification and screening of tumor cells can help to tackle this devastating disease. In the present study, BV2 microglial cells were engineered by iron oxide-nanoparticle stimulation as intraoperative optical imaging agent vehicles and loaded with near-infrared fluorescent dye DiD (DiDBV2-Fe) potentially for fluorescence-guided brain tumor surgery. Activation of BV2 microglial cells by citrate-stabilized iron oxide nanoparticles at a concentration of 62.5 µg mL-1 significantly inhibited M2 markers (arginase-1 and CD206), which is able to minimize risks of the immunosuppressive effects caused by the M2-like phenotype of microglial cells. Meanwhile, activated BV2 microglial cells showed up-regulation of arylsulfatase A, apolipoprotein E, transferrin, and ferritin heavy chain-1 gene expression that tends to promote microglia transport across the blood-brain barrier (BBB). Compared to DiDBV2 without iron oxide activation, DiDBV2-Fe indicated strong tumor tropism in response to monocyte chemoattractant protein-1 (CCL2) secreted by U87MG tumor cells. In vivo experiments proved that DiDBV2-Fe efficiently crossed the BBB and more than 90% fluorescence intensity generated by activated microglial cells was detected in the brain when administered through the carotid artery in an orthotopic glioblastoma mouse model. Notably, DiDBV2-Fe produced clear tumor border demarcation on near-infrared imaging and exhibited a superior tumor-to-brain fluorescence ratio to commercial 5-aminolevulinic acid. Accumulated DiDBV2-Fe induced a strong fluorescence signal in brain tumor tissue for a prolonged period (4-24 h), which is beneficial to perform complex and time-consuming brain operations. Overall, our study suggests that this newly engineered microglial cell has promise for enabling more accurate brain tumor imaging for fluorescence-guided resections.

5.
Arch Insect Biochem Physiol ; 103(3): e21616, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31502703

RESUMO

Recent years have shown a large increase in studies of infection of the silkworm (Bombyx mori) with Cypovirus 1 (previously designated as B. mori cytoplasmic polyhedrosis virus), that causes serious damage in sericulture. Cypovirus 1 has a single-layered capsid that encapsulates a segmented double-strand RNA (dsRNA) genome which are attractive features for the establishment of a biotechnological platform for the production of specialized gene silencing agents, either as recombinant viruses or as viral-like particles with nonreplicative dsRNA cargo. For both combatting viral disease and application of Cypovirus-based pest control, however, a better understanding is needed of the innate immune response caused by Cypovirus infection of the midgut of lepidopteran larvae. Studies of deep sequencing of viral small RNAs have indicated the importance of the RNA interference pathway in the control of Cypovirus infection although many functional aspects still need to be elucidated and conclusive evidence is lacking. A considerable number of transcriptome studies were carried out that revealed a complex response that hitherto remains uncharacterized because of a dearth in functional studies. Also, the uptake mechanism of Cypovirus by the midgut cells remains unclarified because of contrasting mechanisms revealed by electron microscopy and functional studies. The field will benefit from an increase in functional studies that will depend on transgenic silkworm technology and reverse genetics systems for Cypovirus 1.


Assuntos
Bombyx/virologia , Reoviridae/fisiologia , Animais , Bombyx/imunologia , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/imunologia , RNA/genética , RNA/metabolismo
6.
World Neurosurg ; 133: e26-e30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31398523

RESUMO

OBJECTIVE: This study aims to report the clinical outcome of stand-alone lateral lumbar interbody fusion (LLIF) on recurrent disk herniation and to compare the outcome of stand-alone LLIF to that of conventional transforaminal lumbar interbody fusion (TLIF). METHODS: A retrospective study of 47 patients with recurrent disk herniation was included from January 2008 to October 2016. The inclusion criteria were 1) with recurrent disk herniation that needs revision surgery, 2) with only 1 previous percutaneous endoscopic lumbar diskectomy surgery, 3) underwent 1-level stand-alone LLIF or 1-level TLIF surgery, and 4) with follow-up more than 1 year. Patients were asked to complete the following questionnaires for outcome evaluation: visual analog scales (VAS) for both low back pain and leg pain, the Oswestry Disability Index (ODI), and the 12-item Short-Form Health Survey. RESULTS: Eighteen patients underwent stand-alone LLIF, and 29 patients underwent TLIF surgery. Radiographic analysis revealed a similar baseline and postoperative lumbar lordosis in both the LLIF and TLIF groups. Two weeks after surgery, the ODI and VAS scores showed a significant decrease in both groups. The TLIF group showed significantly larger postoperative VAS back pain after surgery (P = 0.03). For both VAS leg pain and ODI score during follow-up, no significance difference was found between the LLIF and TLIF groups. CONCLUSIONS: Stand-alone LLIF is a safe and effective approach with low morbidity and acceptable complication rates for patients with recurrent disk herniation after a previous percutaneous endoscopic lumbar diskectomy surgery. Compared with the TLIF procedure, LLIF could achieve a similar improvement of patient-reported outcome with a better VAS back pain score.


Assuntos
Discotomia Percutânea/métodos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Neuroendoscopia/métodos , Reoperação/métodos , Idoso , Avaliação da Deficiência , Feminino , Humanos , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Complicações Pós-Operatórias/etiologia , Recidiva , Estudos Retrospectivos , Ciática/etiologia , Fusão Vertebral/métodos , Resultado do Tratamento
7.
Mol Immunol ; 118: 19-29, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31837507

RESUMO

The role of naturally occurring regulatory T cells (Treg) in the control of the immune tolerance of ANCA-associated vasculitis (AAV) has not been well defined. Therefore, we separate the phenotypically heterogeneous Treg cells into different subsets based on the expression of FOXP3 and CD45RA during AAV pathogenesis. Fifty-four AAV patients (38 patients with renal involvement) and 19 healthy controls (HCs) were enrolled in this study. Levels of CD4+T cell subsets and cytokines were detected by flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The diagnostic value for Treg subsets was evaluated by the areas under the receiver operating characteristic curves (AUC). Patients with AAV had lower percentages and numbers of activated Treg cells (aTreg, P = 0.044, P = 0.002), while higher levels of total Treg cells (P = 0.001, P = 0.026) with diminished immunosuppression capacity. The proportions of effector memory T-cell subpopulation (P < 0.001) were increased in AAV patients. Interestingly, the AUC of the aTreg improved significantly the diagnostic potential of AAV. Furthermore, the ratio of Th17/aTreg was significantly increased in active and renal vasculitis patient and positive correlation between Th17/Treg subset ratio and creatinine or BUN. In addition, we found that cytokine IL-2 and IL-4 exhibited a downward while IL-6, IL-10, TNF-α, IFN-γ and IL-17A trend upward in AAV patients. Increase in total Treg levels, along with functional deficiency, and decrease in aTreg cells constitute potential novel biomarkers for AAV. And the ratio of Th17/aTreg might serve as an important tool to recognize and monitor AAV patients with renal involvement and disease remission.

8.
Lab Invest ; 100(4): 596-605, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31857694

RESUMO

Enterovirus A71 (EV-A71) infection is primarily responsible for fatal hand, foot, and mouth disease (HFMD) cases. Infants and younger children are more likely to suffer central nervous system damage as a result of EV-A71 infection, but this virus mostly does not affect older children and adults. This study investigated the possible mechanism underlying the age-dependent lethal effect of EV-A71 infection by comparing neonatal and adult mouse models of EV-A71 infection. Although viral proliferation is absent in both neonatal and adult mice, we observed that EV-A71, as a stimulus for astrocytes, elevates the levels of cytokines and monoamine neurotransmitters in neonatal mice. Then, we selected IL-6 and adrenaline as targets in a pharmacological approach to further validate the roles of these factors in mediating the mortality of neonatal mice after EV-A71 infection. Intracerebral injection of IL-6 and adrenaline enhanced the severity of EV-A71 infection, while treatment with an anti-IL-6-neutralizing antibody or the adrenergic-antagonist phenoxybenzamine reversed the lethal effect of EV-A71 in neonatal mice. These results suggest that the central nervous system (CNS) damage in neonatal cases of EV-A71 infection might be caused by an activated fetal cerebral immune response to the virus, including the disruption of brainstem function through increased levels of cytokines and neurotransmitters, rather than the typical cytopathic effect (CPE) of viral infection.

10.
Huan Jing Ke Xue ; 40(6): 2631-2638, 2019 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854654

RESUMO

Microplastics (MPs, plastic fibers, debris, or particles that are generally smaller than 5 mm in diameter) can serve as carriers for hazardous substances, which are ingested by organisms in the ocean and can affect their growth and metabolism. Moreover, MPs will spread with ocean currents, and MP pollution has become a global problem. In this study, the MP abundance distribution of four typical beaches near the coast of Qingdao was studied by the combination of ordinary microscope and fluorescence microscope methods. In addition, the distribution of MPs collected from various beaches in different particle size ranges, shapes, and chemical compositions was discussed. Abundances on the sea surface varied between 5.05×103 particles·m-3 and 1.25×104 particles·m-3, and the concentration of MPs in sand varied between 1.91×103 particles·m-2 and 4.35×103 particles·m-2, with no significant differences detected among the four beaches examined. The results show the pervasiveness of MP pollution in coastal environments of Qingdao. The size of particles found in this study ranged from 5 mm to 50 µm, and increases in abundance were detected with the decreasing particle size. Polypropylene (PP), polyethylene (PE), polystyrene (PS), polyethylene terephthalate (PET), polyvinyl chloride (PVC), 96% polystyrene+4% butadiene copolymer (SB), polymethyl acrylate (PMA), and polyamide (PA) were present in seawater in coastal environments of Qingdao, and compared with the seawater samples, no PA or PMA were found in sand. Research results indicated that fiber was dominant in seawater and sand. MPs in the sand were similar to those in seawater in terms of the particle size, shape, and composition, thus indicating that the seawater and sand of the bathing beaches in Qingdao may have the same pollution sources, e. g., the packaging industry, clothing textile industry, and tourism. This paper studies the distribution and sources of MPs in the bathing beaches of Qingdao, and it provides basic data for research and supervision of environmental MP pollution in Chinese coastal zones.

11.
Huan Jing Ke Xue ; 40(9): 4033-4041, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854866

RESUMO

Through the application of multi-isotope tracing, IsoSource model calculation, and microbial detection, the source of nitrate pollution in the lower reaches of the Fenhe River was screened, and the contribution rate of each source was calculated. The results showed that the main forms of nitrogen-containing substances in the lower reaches of the Fenhe River are NO3--N and NH4+-N and that the NO3--N content in 77.8% of the samples exceed the national drinking water standard. The abundance of denitrifying microorganisms in Jishan, Hejin, and the Fenhe River into the Yellow River is high, and many dominant bacteria participate in denitrification, resulting in nitrogen fractionation. The contents of δ15N-NO3- and δ18O-NO3- in the isotopes ranged from 5.30‰ to 12.90‰ and from 1.3‰ to 1.8‰, respectively. Manure and sewage were the main sources of nitrate in the Linfen section, accounting for 68% of the total nitrate source. In the Xiangfen section, the main sources of nitrate in the river were manure and sewage, at 37.5%, and agricultural fertilizer, at 37%. Agrochemicals are the main sources of nitrate in the Hejin section of the river, with a contribution ratio of 49.3%.

12.
Huan Jing Ke Xue ; 40(8): 3596-3603, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854765

RESUMO

In order to assess the waters of the lower reaches of the Fenhe River and the interaction with inorganic nitrogen, Illumina high-throughput sequencing technology was used to analyze samples based on the analysis of water quality indicators of nine rivers. The community structure and diversity of nirS-type denitrifying bacteria was diagnosed and statistical analysis was carried out to analyze the relationship between these communities and inorganic nitrogen content. The results show that the lower reaches of the Fenhe River are seriously polluted with inorganic nitrogen and the overall water quality standard was classified as V. The range of calculated Shannon index values was 3.36-7.54, indicating that the diversity of the denitrifying bacterial community is high in this basin. The relative abundance of the dominant genera represented 89.8% of the total community, which included Rhodobacter, Pseudomonas, and Thauera. The DO, pH, and inorganic nitrogen content were the main factors affecting the denitrifying bacterial community in the lower reaches of the Fenhe River. The dominant genus, Rhodobacter, and the genus Thauera were negatively correlated with NO3--N and NO2--N, and were positively correlated with NH4+-N. Pseudodomomas was the dominant genus in the Jishan and Hejin areas, and in the Fenhe River feeding into the Yellow River, and was negatively correlated with NO3--N and NO2--N but positively correlated with NH4+-N. The dominant genera of nirS-type denitrifying bacteria in the lower reaches of the Fenhe River promote denitrification and play a role in reducing the content of nitrate nitrogen in the water.


Assuntos
Nitrogênio , Rios , Bactérias , Desnitrificação , Nitratos
13.
Int Immunopharmacol ; 77: 105912, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669890

RESUMO

AIM: The study aimed to investigate the changes in peripherallymphocyte and CD4+T subsets and to observe the regulatory effect of low-dose interleukin-2 (ld-IL2) on these cells in polymyositis or dermatomyositis (PM/DM). METHODS: Lymphocyte subsets (CD3+T, CD4+T, CD8+T, B and natural killer (NK) cells), CD4+T subsets (Th1, Th2, Th17 and regulatory T (Treg) cells) and multiple cytokines of 71 patients after admission and treatment were measured by flow cytometry, as well as these indicators in 30 healthy controls (HCs). In DM, 35 cases were administrated with ld-IL2 combined with conventional therapy, the remaining 26 patients received conventional therapy only. RESULTS: The numbers of CD3+T and CD4+T cells in PM/DM were markedly decreased. Meanwhile, the absolute number and percentage of peripheral Treg cells in PM/DM, as well as Th1 cells in DM, were significantly lower than those in HCs (P < 0.05), but Th2 and Th17 cells had no significant difference. The ratio of Th17/Treg in PM (P = 0.031) and in DM (P = 0.003) were obviously higher than that in HCs. The deficiency of Treg cells was associated with the occurrence of interstitial lung disease (ILD) in myositis patients. Meanwhile, reduced production of IL-2 was also observed in PM/DM (P < 0.001). ld-IL2 combination therapy could significantly increase the numbers of CD4+T subsets in DM, especially Treg cells (expanded 2.5 times). CONCLUSIONS: The decline of peripheral Treg cells and serum IL-2 were found in PM/DM. ld-IL2 combination therapy could significantly increase the number of Treg cells.

15.
Surg Endosc ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741159

RESUMO

BACKGROUND: Sarcopenia is a negative predictor for postoperative recovery. This study was performed to evaluate the short-term outcomes of laparoscopic surgery in colorectal cancer patients with sarcopenia. METHODS: We conducted a study of patients who underwent curative surgeries for colorectal cancer in two centers from July 2014 to July 2018. In order to reduce selection bias, we conducted a propensity score matching analysis. Preoperative characteristics including age, gender, anemia, body mass index, hypoalbuminemia, America society of anesthesiology scores, epidural anesthesia, operative procedure, stoma, tumor location, and combined resection were incorporated in the model, and produced 58 matched pairs. The third lumbar skeletal muscle mass, handgrip strength, and 6 m usual gait speed were measured to define sarcopenia. Short-term outcomes were compared between the two groups. RESULTS: In a total of 1136 patients, 272 had sarcopenia diagnosed, and 227 were further analyzed in this study. Among them, 108 patients underwent laparoscopic colorectal surgery and 119 underwent open colorectal surgery. In the matched cohort, the clinical characteristics of the two groups were well matched. The laparoscopic group had significantly reduced overall complications (15.5% vs. 36.2%, P = 0.016) and shorter postoperative hospital stays (10.5 vs. 14, P = 0.027). Subgroup analysis of postoperative complications showed that the incidence of surgical complications (P = 0.032) was lower in the laparoscopic group. Hospitalization costs (P = 0.071) and 30-day readmissions (P = 0.215) were similar between the two groups. CONCLUSION: Laparoscopic surgery for colorectal cancer is a safe and feasible option with better short-term outcomes in patients with sarcopenia.

16.
Mol Med Rep ; 20(6): 5239-5248, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638220

RESUMO

The two­edged effect of matrix metalloproteinase­9 (MMP9) makes it difficult to understand its role in liver fibrogenesis and fibrosis resolution. The present study aimed to investigate the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. MMP9­/­ mice were used to induce liver fibrosis by thioacetamide. The degrees of liver fibrogenesis and fibrosis resolution were designated by the levels of collagen I, III and IV, which were determined via western blotting. Liver injury and the transcriptional levels of MMPs and tissue inhibitor of metalloproteinases (TIMPs) were also determined. It was revealed that, in the absence of MMP9, acute liver injury was attenuated and the expression of collagen was alleviated at the early stage of liver fibrosis, particularly in the first 3 weeks. However, their levels increased to levels as high as those in the control group by week 8. During liver fibrosis resolution, in the absence of MMP9, the ratio of (MMP9 + MMP13)/TIMP1 and the ratio of (MMP2+ MMP14)/TIMP2 were decreased, and the collagen levels were increased. The present study revealed the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. The information obtained here will improve current understanding of the effect that MMP9 has in liver fibrogenesis and fibrosis resolution.

17.
Theranostics ; 9(23): 6936-6948, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31660078

RESUMO

Objective: Engineered immune cells (e.g., therapeutic T cells) provide a revolutionary approach to combat cancer. Certain activated immune cells can exquisitely sense and respond to the tumor microenvironment. Here, we propose a paradigm based on engineering macrophages to allow selective intercellular drug delivery and augmentation of antitumor activities by hijacking tumor microtube networks. Methods: Macrophages were engineered via anchoring lipopolysaccharides on the plasma membrane (LM). The tumor tropism of LM encapsulating doxorubicin (LM-Dox) was monitored by a real-time cell migration assay and small animal in vivo imaging. Monocyte chemoattractant protein-1 (CCL2) was measured by quantitative PCR and ELISA. Intercellular conduit formation was characterized by confocal laser scanning microscopy and scanning electron microscopy. LM-Dox activation of tumor-associated macrophages to release TNF-α was evaluated by western blot and immunofluorescence assays. The potential therapeutic effects of LM-Dox in a 3D tumor-immune model and a murine orthotopic lung cancer model were tested. Results: LM-Dox exhibited tumor tropism in response to CCL2 produced by A549 lung tumor cells and lung tumor tissues resulting in a remarkably higher amount of tumor accumulation than the case of Lipo-Dox (~ 4-fold). Intriguingly, LM-Dox accumulated at tumor sites hijacked the established tumor microtube networks and even stimulated microtube formation with tumor cells but not with normal cells to enable selective and rapid transport of the drug to tumor cells. Simultaneously, LM-Dox induced secretion of TNF-α in tumor-associated macrophages, which increased the antitumor activity of Dox. Thus, LM-Dox increased the inhibitory effects on tumor growth and metastasis in a mouse orthotopic lung cancer model and minimized the side effects of Dox-induced tumor invasion. Conclusion: Lipopolysaccharide-anchored macrophages that can hijack tumor microtube networks for selective drug transport may serve as versatile bioactive carriers of anticancer drugs. In the clinical context, these engineered microphages represent a personalized medicine approach that can be translated into potential use of patient-derived monocytes/macrophages for drug delivery by means of cell-to-cell communication.

18.
Nanomedicine (Lond) ; 14(19): 2579-2593, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31609675

RESUMO

Aim: To investigate the role of exosomal miRNAs on gastric cancer (GC) metastasis. Materials & methods: miRNA expression profiles of exosomes with distinct invasion potentials were analyzed using miRNA microarray and validated by quantitative real-time PCR. In vitro and in vivo experiments assessed the role of exosomal miR-196a-1 in GC's metastasis. Results: High expression level of exosomal miR-196a-1 expression was significantly associated with poor survival in GC. Exosomes that contained miR-196a-1 were secreted from high-invasive GC cells. Ectopic miR-196a-1 expression promoted invasion of low-invasive GC cells by targeting SFRP1. Conclusion: miR-196a-1 was delivered from high-invasive GC into low-invasive GC cells via exosomes and promoted metastasis to the liver in vitro and in vivo.

19.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1030-1037, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640957

RESUMO

OBJECTIVE: To investigate the relationship between necroptosis and apoptosis in MCET3-E1 cell death induced by glucocorticoids. METHODS: MC3T3-E1 cells were incubated with 10-6 mol/L dexamethasone followed by treatment with the apoptosis inhibitor z-VAD-fmk (40 µmol/L) or the necroptosis inhibitor necrostatin-1 (40 µmol/L) for 2 h. At 72 h after incubation with dexamethasone, the cells were harvested to determine the cell viability using WST-1 assay and the rate of necrotic cells using annexin V/PI double staining; the percentage of apoptotic cells was determined using Hoechst staining. The mitochondrial membrane potential and the level of ATP in the cells were also evaluated. Transmission electron microscopy was used to observe the microstructural changes of the cells. The expressions of RIP-1 and RIP-3 in the cells were detected by Western blotting. RESULTS: At a concentration of 10-6 mol/L, dexamethasone induced both apoptosis and necroptosis in MC3T3- E1 cells. Annexin V/PI double staining showed that inhibition of cell apoptosis caused an increase in cell necrosis manifested by such changes as mitochondrial swelling and plasma membrane disruption, as shown by electron microscopy; Hoechst staining showed that the percentage of apoptotic cells was significantly reduced. When necroptosis was inhibited by necrostatin-1, MC3T3-E1 cells showed significantly increased apoptosis as shown by both AV/PI and Hoechst staining, and such changes were accompanied by changes in mitochondrial membrane potential and ATP level in the cells. CONCLUSIONS: In the process of dexamethasone-induced cell death, necroptosis and apoptosis can transform reciprocally accompanied by functional changes of the mitochondria.


Assuntos
Apoptose , Morte Celular/efeitos dos fármacos , Dexametasona , Necrose , Células 3T3 , Trifosfato de Adenosina , Animais , Potencial da Membrana Mitocondrial , Camundongos , Microscopia Eletrônica , Mitocôndrias/ultraestrutura
20.
Nanoscale Res Lett ; 14(1): 331, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641875

RESUMO

In this paper, an anomalous spectral data of distributed Bragg reflector (DBR) quantum cascade lasers (QCLs) emitting around 7.6 µm is presented. The two-section DBR lasers, consisting of a gain section and an unpumped Bragg reflector, display an output power above 0.6 W in continuous wave (CW) mode at room temperature. The anomalous spectral data is defined as a longitudinal mode which moves toward shorter wavelengths with increasing temperature or injection current, which is unexpected. Although the longer wavelength modes are expected to start lasing when raising device temperature or injection current, occasional mode hops to a shorter wavelength are seen. These anomalous mode transitions are explained by means of modal analysis. The thermal-induced change of the refractive index implied by an increase in the temperature or injection current yields nearly periodic transitions between cavity modes.

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