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1.
Sensors (Basel) ; 20(9)2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32375212

RESUMO

The measurement accuracy of the precision instruments that contain rotation joints is influenced significantly by the rotary encoders that are installed in the rotation joints. Apart from the imperfect manufacturing and installation of the rotary encoder, the variations of ambient temperature could cause the angle measurement error of the rotary encoder. According to the characteristics of the 2π periodicity of the angle measurement at the stationary temperature and the complexity of the effects of ambient temperature changes, the method based on the Fourier expansion-back propagation (BP) neural network optimized by genetic algorithm (FE-GABPNN) is proposed to improve the angle measurement accuracy of the rotary encoder. The proposed method, which innovatively integrates the characteristics of Fourier expansion, the BP neural network and genetic algorithm, has good fitting performance. The rotary encoder that is installed in the rotation joint of the articulated coordinate measuring machine (ACMM) is calibrated by using an autocollimator and a regular optical polygon at ambient temperature ranging from 10 to 40 °C. The contrastive analysis is carried out. The experimental results show that the angle measurement errors decrease remarkably, from 110.2″ to 2.7″ after compensation. The mean root mean square error (RMSE) of the residual errors is 0.85″.

3.
Oral Dis ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144839

RESUMO

OBJECTIVES: We aimed to investigate whether skeletal-specific H-type blood vessels exist in alveolar bone and how they function in alveolar bone remodeling. MATERIALS AND METHODS: H-type vessels with high expression of CD31 and Endomucin (CD31hi Emcnhi ) were immunostained in alveolar bone. Abundance and age-related changes in CD31hi Emcnhi endothelial cells (H-ECs) were detected by flow cytometry. Osteoprogenitors association with H-type vessels and bone mass were detected in tooth extraction model of alveolar bone remodeling by immunohistofluorescence and micro-CT, respectively. Transcription and expression of H-EC feature genes during in vitro Notch inhibition were measured by RT-qPCR and immunocytofluorescence. RESULTS: We verified that H-type vessels existed in alveolar bone, the abundance of which was highest at infancy age, then decreased but maintained a constant level during aging. In tooth extraction model, H-ECs significantly increased with concomitant perivascular accumulation of Runx2+ osteoprogenitors and gradually augmentation of bone mass. Notch inhibition of in vitro cultured H-ECs resulted in decreased expression levels of Emcn and hes1, but not Pecam1 or Kdr genes, with decreased expression levels of H-EC numbers, accordingly. CONCLUSIONS: The present study suggests that H-type vessels promote osteogenesis during alveolar bone remodeling. Notch signaling pathway regulates expression of Emcn and possibly determines fate and functions of alveolar H-ECs.

4.
World J Gastroenterol ; 26(10): 1042-1055, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32205995

RESUMO

BACKGROUND: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the prognostic and predictive factors remain unclear. AIM: To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC. METHODS: Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS. In order to assess the predictive factors of PA-TACE benefit, the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 378 patients (PA-TACE vs surgery alone, 189:189) from three centers were included after a propensity-score 1:1 matching analysis. Compared to the group receiving surgery alone, PA-TACE prolonged the OS rate in patients with resected HCC (P < 0.001). The Barcelona Clinic Liver Cancer system and ferritin-to-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups. Age (P = 0.023) and microscopic vascular invasion (MVI) (P = 0.002) were also identified in the PA-TACE group, while gender (P = 0.027), hepatitis B virus (P = 0.034) and albumin-bilirubin grade (P = 0.027) were also selected in the surgery alone group. In addition, PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone) < 1]. Notably, a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P = 0.038) and without MVI (P = 0.048). CONCLUSION: FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS. Moreover, high FHR and the absence of MVI were important predictive factors, which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.

5.
Theranostics ; 10(8): 3779-3792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206122

RESUMO

Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabetic and burn wound healing were evaluated by analyzing the rates of wound closure, re-epithelialization, scar formation, collagen deposition, skin cell proliferation and neovascularization using histological analyses and immunostaining. In vitro functional assays were conducted to assess fasting and refeeding on the angiogenic activities of endothelial cells. Transcriptome sequencing was employed to identify the differentially expressed genes in endothelial cells after fasting treatment and the role of the candidate genes in the fasting-induced promotion of angiogenesis was demonstrated. Results: Two times of 24-h fasting in a week after but especially before wound injury efficiently induced faster wound closure, better epidermal and dermal regeneration, less scar formation and higher level of angiogenesis in mice with diabetic or burn wounds. In vitro, fasting alone by serum deprivation did not increase, but rather reduced the abilities of endothelial cell to proliferate, migrate and form vessel-like tubes. However, subsequent refeeding did not merely rescue, but further augmented the angiogenic activities of endothelial cells. Transcriptome sequencing revealed that fasting itself, but not the following refeeding, induced a prominent upregulation of a variety of pro-angiogenic genes, including SMOC1 (SPARC related modular calcium binding 1) and SCG2 (secretogranin II). Immunofluorescent staining confirmed the increase of SMOC1 and SCG2 expression in both diabetic and burn wounds after fasting treatment. When the expression of SMOC1 or SCG2 was down-regulated, the fasting/refeeding-induced pro-angiogenic effects were markedly attenuated. Conclusion: This study suggests that fasting combined with refeeding, but not fasting solely, enhance endothelial angiogenesis through the activation of SMOC1 and SCG2, thus facilitating neovascularization and rapid wound healing.

6.
Int J Nanomedicine ; 15: 1373-1385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184592

RESUMO

Background: Photothermal therapy (PTT) has great potential application in the treatment of tumors. However, due to the low penetration of near-infrared light (NIR) and the low concentration of nanomaterials in the tumor site, the application of PTT has been limited. Purpose: The objective of this study was to investigate the therapeutic effect of transcatheter intra-arterial infusion of lecithin-modified Bi nanoparticles (Bi-Ln NPs) combined with interventional PTT (IPTT) on hepatocellular carcinoma. Methods: Bi-Ln NPs were prepared by emulsifying the hydrophobic Bi nanoparticles and lecithin, and the photothermal conversion and cytotoxicity of Bi-Ln NPs were then measured by infrared imaging and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, respectively. Twenty-four VX2 hepatic carcinoma rabbits were randomly divided into four groups. Rabbits in group A received Bi-Ln NPs by intra-arterial infusion and NIR laser treatment (IA Bi-Ln NPs + Laser), group B received Bi-Ln NPs by intravenous infusion and NIR laser treatment (IV Bi-Ln NPs + Laser), group C received PBS (phosphate buffer saline) via intra-arterial infusion with NIR laser treatment (IA PBS + Laser), group D received PBS via intra-arterial infusion (IA PBS). Transcatheter intra-arterial infusion was conducted by superselective intubation under digital subtraction angiography (DSA) guidance. IPTT was performed by introducing an NIR optical fiber access to the rabbit VX2 hepatic carcinoma under real-time ultrasound guidance. Magnetic resonance imaging (MRI) was performed to evaluate the tumor size. Hematoxylin and eosin (H&E) stain and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were conducted 7 days after treatment to evaluate the necrosis rate and viability of tumor, respectively. Results: The Bi-Ln NPs have the advantages of good biological compatibility and high photothermal conversion efficiency. Minimally invasive transcatheter intra-arterial infusion can markedly increase the concentration of Bi-Ln NPs in tumor tissues. IPTT can contribute to the significant improvement in the photothermal efficiency of Bi-Ln NPs. Compared to other groups, the group of IA Bi-Ln NPs + Laser showed a significantly higher tumor inhibition rate (TIR) of 93.38 ± 19.57%, a higher tumor necrosis rate of 83.12 ± 8.02%, and a higher apoptosis rate of (43.26 ± 10.65%) after treatment. Conclusion: Transcatheter intra-arterial infusion combined with interventional PTT (IPTT) is safe and effective in eradicating tumor cells and inhibiting tumor growth and may provide a novel and valuable choice for the treatment of hepatocellular carcinoma in the future.


Assuntos
Bismuto/química , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas Experimentais/terapia , Nanopartículas Metálicas/administração & dosagem , Fototerapia , Ultrassonografia/métodos , Animais , Apoptose , Carcinoma Hepatocelular/patologia , Terapia Combinada , Feminino , Artéria Hepática , Raios Infravermelhos , Infusões Intra-Arteriais , Lecitinas/química , Neoplasias Hepáticas Experimentais/patologia , Masculino , Nanopartículas Metálicas/química , Necrose , Coelhos
7.
ACS Appl Mater Interfaces ; 12(9): 10107-10117, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32046483

RESUMO

Natural compound eyes provide the inspiration for developing artificial optical devices that feature a large field of view (FOV). However, the imaging ability of artificial compound eyes is generally based on the large number of ommatidia. The lack of a tunable imaging mechanism significantly limits the practical applications of artificial compound eyes, for instance, distinguishing targets at different distances. Herein, we reported zoom compound eyes that enable variable-focus imaging by integrating a deformable poly(dimethylsiloxane) (PDMS) microlens array (MLA) with a microfluidic chamber. The thin and soft PDMS MLA was fabricated by soft lithography using a hard template prepared by a combined technology of femtosecond laser processing and wet etching. As compared with other mechanical machining strategies, our combined technology features high flexibility, efficiency, and uniformity, as well as designable processing capability, since the size, distribution, and arrangement of the ommatidia can be well controlled during femtosecond laser processing. By tuning the volume of water injected into the chamber, the PDMS MLA can deform from a planar structure to a hemispherical shape, evolving into a tunable compound eye of variable FOV up to 180°. More importantly, the tunable chamber can functionalize as the main zoom lens for tunable imaging, which endows the compound eye with the additional capability of distinguishing targets at different distances. Its focal length can be turned from 3.03 mm to infinity with an angular resolution of 3.86 × 10-4 rad. This zoom compound eye combines the advantages of monocular eyes and compound eyes together, holding great promise for developing advanced micro-optical devices that enable large FOV and variable-focus imaging.

8.
Theranostics ; 10(5): 2293-2308, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089743

RESUMO

Osteoporosis and osteoporotic fractures severely compromise quality of life in elderly people and lead to early death. Human umbilical cord mesenchymal stromal cell (MSC)-derived extracellular vesicles (hucMSC-EVs) possess considerable therapeutic effects in tissue repair and regeneration. Thus, in the present study, we investigated the effects of hucMSC-EVs on primary and secondary osteoporosis and explored the underlying mechanisms. Methods: hucMSCs were isolated and cultured. EVs were obtained from the conditioned medium of hucMSCs and determined by using transmission electron microscopy, dynamic light scattering and Western Blot analyses. The effects of hucMSC-EVs on ovariectomy-induced postmenopausal osteoporosis and tail suspension-induced hindlimb disuse osteoporosis in mouse models were assessed by using microcomputed tomography, biomechanical, histochemical and immunohistochemical, as well as histomorphometric analyses. Proteomic analysis was applied between hucMSC-EVs and hucMSCs to screen the candidate proteins that mediate hucMSC-EVs function. The effects of hucMSC-EVs on osteogenic and adipogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs), and osteoclastogenesis of the macrophage cell line RAW264.7 in vitro were determined by using cytochemical staining and quantitative real-time PCR analysis. Subsequently, the roles of the key protein in hucMSC-EVs-induced regulation on BMSCs and RAW264.7 cells were evaluated. Results: hucMSCs were able to differentiate into osteoblasts, adipocytes or chondrocytes and positively expressed CD29, CD44, CD73 and CD90, but negatively expressed CD34 and CD45. The morphological assessment revealed the typical cup- or sphere-shaped morphology of hucMSC-EVs with diameters predominantly ranging from 60 nm to 150 nm and expressed CD9, CD63, CD81 and TSG101. The systemic administration of hucMSC-EVs prevented bone loss and maintained bone strength in osteoporotic mice by enhancing bone formation, reducing marrow fat accumulation and decreasing bone resorption. Proteomic analysis showed that the potently pro-osteogenic protein, CLEC11A (C-type lectin domain family 11, member A) was very highly enriched in hucMSC-EVs. In addition, hucMSC-EVs enhanced the shift from adipogenic to osteogenic differentiation of BMSCs via delivering CLEC11A in vitro. Moreover, CLEC11A was required for the inhibitory effects of hucMSC-EVs on osteoclast formation. Conclusion: Our results suggest that hucMSC-EVs serve as a critical regulator of bone metabolism by transferring CLEC11A and may represent a potential agent for prevention and treatment of osteoporosis.

9.
World J Microbiol Biotechnol ; 36(2): 33, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060755

RESUMO

Microbiota from herbivore rumen is of great interest for mining glycoside hydrolases for lignocellulosic biomass biorefinement. We previously isolated a highly active but poorly thermostable xylanase (LXY) from a rumen fluid fosmid library of Hu sheep, a local high-reproductive species in China. In this study, we used a universal enzyme-engineering strategy called SpyTag/SpyCatcher molecular cyclization to improve LXY stability via isopeptide-bond-mediated ligation. Both linear and cyclized LXY (L- and C-LXY, respectively) shared similar patterns of optimal pH and temperature, pH stability, and kinetic constants (km and Vmax). However, the C-LXY showed enhanced thermostability, ion stability, and resilience to aggregation and freeze-thaw treatment than L-LXY, without compromise of its catalytic efficiency. Circular dichroism and intrinsic and 8-anilino-1-naphthalenesulfonic acid-binding fluorescence analysis indicated that the cyclized enzyme was more capable of maintaining its secondary and tertiary structures than the linear enzyme. Taken together, these results promote the cyclized enzyme for potential applications in the feed, food, paper pulp, and bioenergy industries.

10.
FASEB J ; 34(3): 3805-3819, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31975555

RESUMO

High-density lipoprotein (HDL), a well-known atheroprotective factor, can be converted to proatherogenic particles in chronic inflammation. HDL-targeted therapeutic strategy for atherosclerotic cardiovascular disease (CVD) is currently under development. This study aims to assess the role of methionine sulfoxide reductase A (MsrA) in abnormal HDL and its related disorders in scavenger receptor class B type I deficient (SR-BI-/- ) mice. First, we demonstrated that MsrA overexpression attenuated ROS level and inflammation in HepG2 cells. For the in vivo study, SR-BI-/- mice were intravenously injected with lentivirus to achieve hepatic MsrA overexpression. High-level hepatic MsrA significantly reduced the plasma free cholesterol contents, improved HDL functional proteins apolipoprotein A-I (apoAI), apoE, paraoxonase1 (PON1), and lecithin:cholesterol acyltransferase (LCAT), while decreased the pro-inflammatory property of dysfunctional HDL, contributing to reduced atherosclerosis and hepatic steatosis in Western diet-fed mice. Furthermore, the study revealed that hepatic MsrA altered the expression of several genes controlling HDL biogenesis, cholesterol esterification, cholesterol uptake mediated by low-density lipoprotein receptor (LDLR) and biliary excretion, as well as suppressed nuclear factor κB (NF-κB) signaling pathway, which largely relied on liver X receptor alpha (LXRα)-upregulation. These results provide original evidence that MsrA may be a promising target for the therapy of dysfunctional HDL-related CVD.

11.
AAPS PharmSciTech ; 21(2): 57, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912318

RESUMO

The aim of this study was to examine the effectiveness of alanine-proline-arginine-proline-glycine (APRPG) peptide-conjugated PEGylated cationic liposomes-encapsulated zoledronic acid (ZOL) (APRPG-PEG-ZOL-CLPs) in achieving vascular normalization. Cisplatin (diamminedichloroplatinum, DDP) was used to improve anticancer efficacy. The present study showed that APRPG-PEG-ZOL-CLPs increased anticancer efficacy, which was regarded as vascular normalization. Our results demonstrated that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evidently repressed by APRPG-PEG-ZOL-CLPs. Moreover, APRPG-PEG-ZOL-CLPs could decrease vessel density, as well as hypoxia-inducible factor 1α (HIF-1α), and increase thrombospondin 1 (TSP-1) expression of tumors. Therefore, the anticancer efficacy of APRPG-PEG-ZOL-CLPs combined with DDP was superior to that of PEG-ZOL-CLP or ZOL treatment combined with DDP schemes, as demonstrated by the obviously evident reduction in tumor volume. These results indicated that APRPG-PEG-ZOL-CLPs were most effective in normalizing tumor vasculature to elevate the therapeutic effect of antitumor drugs.

12.
Endocr Relat Cancer ; 27(2): X1-X2, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31995343

RESUMO

The authors and journal apologize for errors in the above paper, which appeared in volume 26 part 3, pages 303­319. The errors relate to the legend of Fig. 1A on page 307 and the artwork of Fig. 8D on page 316:

13.
Environ Int ; 136: 105483, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31999972

RESUMO

BACKGROUND: Current available evidence regarding the detrimental effects of low-level ambient air pollution on conventional semen parameters is inconclusive. In nonreproductive systems, air pollutant exposure has been demonstrated to induce oxidative stress (OS), which is a crucial mechanism that mediates sperm damage and male infertility. Thus, it may be essential to investigate the effects of air pollution on sperm quality in terms of the perspectives of OS and relative molecular damage. OBJECTIVES: We assessed the associations of major air pollutant exposure to oxidative stress-mediated alterations in semen, including seminal plasma malondialdehyde (MDA), sperm mtDNA copy number, and integrity. METHODS: The present study used data gathered from 516 young men participating in the Male Reproductive Health in Chongqing College student (MARCHS) cohort study during the follow-up stage in 2014 (n = 427 on the old campus, which is located in an urban area and has worse air quality, and n = 89 on the new campus, which is not urban and has better air quality). Data regarding major air pollutant exposure during 0-90, 0-9, 10-14 and 70-90 days before each semen examination (corresponding to the entire and three key periods of sperm development, respectively) were collected. The Mann-Whitney U nonparametric test was employed to compare distributions of major air pollutants and to explore differences in MDA, mtDNA copy number, and mtDNA integrity between the two campuses. A linear regression model was used as multivariable analysis to investigate associations of major air pollutant exposure with these biomarkers of oxidative damage to sperm and to adjust for potential confounders. RESULTS: During all four key periods of sperm development, compared with college students on the new campus, college students on the old campus were exposed to higher levels of PM10, PM2.5, NO2, and CO, and had higher air quality index (AQI) values, indicating that these participants suffered from worse air quality. The levels of seminal plasma MDA in college students on the old campus were higher than those for the new campus (2.0 nmol/ml; 0.7, 3.6 vs. 1.6 nmol/ml; 0.4, 3.4, p < 0.001) (medians with 5th and 95th percentiles). There were no significant differences in sperm mtDNA copy number and mtDNA integrity between the two campuses. Furthermore, daily average PM10 exposure during 0-90 days before semen ejaculation was found to be significantly and positively associated with seminal plasma MDA level (10.4; 95% CI, 4.4, 16.4) (percentage change per 10-unit increase in air pollutant concentration; same meanings for the results below); daily average SO2 exposure for 70-90 days and NO2 exposure for 0-9 days prior to sampling were also positively associated with MDA level (74.7; 95% CI, 32.1, 119 and 11.9; 95% CI, 4.8, 19.0, respectively). AQI for 0-90 days and 70-90 days prior to sampling positively correlated with seminal plasma MDA concentrations (11.4; 95% CI, 4.7, 18.1 and 12.2; 95% CI, 5.3, 19.1, respectively). Additionally, daily average SO2 exposures for 10-14 and 0-9 days prior to sampling were negatively associated with sperm mtDNA copy number and mtDNA integrity, respectively (-9.0; 95% CI, -16.4, -1.6 and -38.3; 95% CI, -64.1, -11.8, respectively). However, only the correlations between SO2 exposure and AQI value for 70-90 days prior to sampling and MDA levels remained significant after multiplicity adjustment. CONCLUSIONS: The results indicate that bad air quality, especially SO2 exposure during certain periods of sperm development, might be correlated with oxidative damage to sperm. These findings can deepen the understanding of the potential impacts of air pollution on sperm quality.

14.
Plant J ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31908046

RESUMO

Phytohormone brassinosteroids (BRs) are essential for plant growth and development, but the mechanisms of BR-mediated pollen development remain largely unknown. In this study, we show that pollen viability, pollen germination and seed number decreased in the BR-deficient mutant d^im , which has a lesion in the BR biosynthetic gene DWARF (DWF), and in the bzr1 mutant, which is deficient in BR signaling regulator BRASSINAZOLE RESISTANT 1 (BZR1), compared with those in wild-type plants, whereas plants overexpressing DWF or BZR1 exhibited the opposite effects. Loss or gain of function in the DWF or BZR1 genes altered the timing of reactive oxygen species (ROS) production and programmed cell death (PCD) in tapetal cells, resulting in delayed or premature tapetal degeneration, respectively. Further analysis revealed that BZR1 could directly bind to the promoter of RESPIRATORY BURST OXIDASE HOMOLOG 1 (RBOH1), and that RBOH1-mediated ROS promote pollen and seed development by triggering PCD and tapetal cell degradation. In contrast, the suppression of RBOH1 compromised BR signaling-mediated ROS production and pollen development. These findings provide strong evidence that BZR1-dependent ROS production plays a critical role in the BR-mediated regulation of tapetal cell degeneration and pollen development in Solanum lycopersicum (tomato) plants.

15.
Drug Deliv Transl Res ; 10(1): 93-107, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31418132

RESUMO

The metronomic administration of a low-dose cytotoxic agent with no prolonged drug-free breaks is an anti-angiogenic cancer treatment method. The use of nano-formulations in this manner enhances anti-tumor efficacy and reduces toxicity by inhibiting angiogenic activity, reduces adverse effects, and changes the biodistribution of TP in the body, steering TP away from potentially endangering healthy tissues. The present study uses liposomes and Asn-Gly-Arg (NGR) peptide conjugated aminopeptidase N(APN)-targeted liposomes for triptolide (TP), as a model for the investigation of targeted metronomic administration and subsequent effects on the toxicity profile and efficacy of the chemotherapeutic agent. Metronomic NGR-PEG-TP-LPs have been found to have enhanced anti-tumor activity, a phenomenon that is attributed to an increase in angiogenic inhibition properties. In vitro experiments demonstrate that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) are obviously suppressed in comparison with that of other treatment groups. In vivo experiments also demonstrate that the anti-tumor efficacy of targeted metronomic administration is superior to that of liposome-administered treatments given at maximum tolerated dose (MTD) schemes, as is evidenced by markedly decreased tumor volume, vessel density, and the volume of circulating endothelial progenitor cells (CEPCs) in serum. Moreover, we observed that the metronomic administration of NGR-PEG-TP-LPs could elevate thrombospondin-1 (TSP-1) expression in tumors, a finding that is consistent with the promotion of TSP-1 secretion specifically from HUVECs. Additionally, metronomic NGR-PEG-TP-LPs have minimal drug-associated toxicity (weight loss, hepatotoxicity and nephrotoxicity in mice). Our research demonstrates the significance of targeted metronomic administration using liposomes for anti-angiogenic cancer therapy.

16.
Gut ; 69(2): 343-354, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30926653

RESUMO

OBJECTIVE: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. METHODS: A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically. RESULTS: Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. CONCLUSIONS: The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.


Assuntos
Epitopos de Linfócito B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/imunologia , Adjuvantes Imunológicos , Animais , Antivirais/uso terapêutico , Terapia Combinada , DNA Viral/sangue , Relação Dose-Resposta Imunológica , Feminino , Anticorpos Anti-Hepatite B/biossíntese , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/terapia , Hepatite B Crônica/virologia , Imunidade Humoral/imunologia , Imunoterapia/métodos , Macaca fascicularis , Masculino , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Coelhos
17.
J Hazard Mater ; 384: 121311, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31585278

RESUMO

Metabolic uncouplers are widely used for reducing excess sludge in biological wastewater treatment systems. However, the formation of microbial products, such as extracellular polymeric substances, polyhydroxyalkanoate and soluble microbial products by activated sludge in the presence of metabolic uncouplers remains unrevealed. In this study, the impacts of a metabolic uncoupler o-chlorophenol (oCP) on the reduction of activated sludge yield and formation of microbial products in laboratory-scale sequencing batch reactors (SBRs) were evaluated for a long-term operation. The results show the average reduction of sludge yield in the four reactors was 17.40%, 25.80%, 33.02% and 39.50%, respectively, when dosing 5, 10, 15, and 20 mg/L oCP. The oCP addition slightly reduced the pollutant removal efficiency and decreased the formation of soluble microbial products in the SBRs, but stimulated the productions of extracellular polymeric substances and polyhydroxyalkanoate in activated sludge. Furthermore, the significant reduction of electronic transport system activity occurred after the oCP addition. Microbial community analysis of the activated sludge indicates dosing oCP resulted in a decrease of sludge richness and diversity in the SBRs. Hopefully, this study would provide useful information for reducing sludge yield in biological wastewater treatment systems and behaviors of activated sludge in the presence of uncouplers.

18.
Chemosphere ; 244: 125402, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31809925

RESUMO

Studies in animals suggest an adverse effect of high-level lead exposure on male reproductive outcomes. However, evidence of the effects of low-level lead exposure is inconsistent. The purpose of our study was to explore the relationship between low-level lead exposure from daily environmental contaminants and semen quality in a community population without occupational exposure. We recruited 751 students in the Male Reproductive Health in Chongqing College Students (MARHCS) study and 190 community males from Bishan, Chongqing. Eight urinary metals (Pb, Cd, As, Cu, Zn, Ni, Mn, and Cr), semen quality, and serum sex hormones were detected. Even if the blood lead concentration was below the US lead poisoning standard for children (100 µg/L), a significant dose-response relationship was found between lead exposure and a decrease in semen quality. Multilinear regression showed that urinary Pb was negatively associated with sperm concentration, total sperm count, progressive motility and total sperm motility (regression coefficient: -0.074, -0.103, -0.024, and -0.014, respectively; p: <0.001, <0.001, 0.007, and <0.001, respectively), accompanied by decreased serum follicle-stimulating hormone, serum testosterone and the testosterone/luteinizing hormone ratio (ß coefficient: -0.090, -0.082, and -0.020, respectively; p: 0.002, <0.001, and 0.021, respectively). Logistic regression also indicated that the risk of having abnormal semen quality was higher in the high Pb group (OR: 2.501, 95% CI: 1.411, 4.435, p = 0.002) than in the low Pb group after adjusting for confounders, with a dose-response relationship in the trend test (p = 0.007). Our results revealed an inverse association between Pb exposure at low levels and semen quality.

19.
Ecotoxicol Environ Saf ; 189: 109996, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31785943

RESUMO

A large proportion (60-90%) of ingested tetracyclines are released to slurry, soils, surface waters and ground water, which has raised extensive concerns and may pose a risk to the soil ecosystem. A 56-day experiment was conducted to study the bioremediation by earthworms on soil microbial diversity and partial nitrification processes in oxytetracycline (OTC)-contaminated soil. The results showed that high OTC concentration significantly decreased the activity of soil bacteria, ammonia-oxidizing bacteria (AOB) and archaea (AOA). Earthworms were found to accelerate the degradation efficiency and rate of OTC, and its main metabolites were 4-epi-oxytetracycline (EOTC) and 2-acetyl-2-decarboxamido-oxytetracycline (ADOTC). Earthworms had an important role in the bioremediation of soil microbial diversity by degrading OTC and its metabolite (EOTC), especially in the high OTC condition. Additionally, the results indicated that the effects of earthworms on the degradation of OTC could remediate the abundances of 16S rRNA and AOB amoA genes and the NO3- content in both low and high OTC-contaminated soils. The structural equation model suggested that earthworms could remediate the microbial diversity, the abundances of 16s rRNA and AOB amoA genes by accelerating the degradation of OTC, which contributed to the bioremediation by earthworms on soil microbial diversity and partial nitrification processes in oxytetracycline-contaminated soil.

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