Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 526
Filtrar
1.
BMC Cancer ; 20(1): 998, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054738

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC), in part because of the high metastasis rate, is one of the most prevalent causes of malignancy-related mortality globally. Ubiquitin specific peptidase 6 N-terminal like (USP6NL) has been unmasked to be implicated in some human cancers. However, the precise biological function of USP6NL in TNBC has not been defined. METHODS: RNA expression was examined by real-time quantitative PCR (RT-qPCR), while USP6NL protein level was tested through western blot. Besides, cell proliferation was assessed by using colony formation assay, whereas cell apoptosis estimated by flow cytometry analysis, JC-1 assay and TUNEL assay. Transwell assays were adopted to detect the migration and invasion of indicated TNBC cells. Immunofluorescence (IF) assay evaluated epithelial-mesenchymal transitions (EMT) progress in TNBC. Further, RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays were implemented for measuring the mutual interplay among USP6NL, miR-142-3p and long intergenic non-protein coding RNA 689 (LINC00689). RESULTS: Elevated USP6NL level was uncovered in TNBC cells. RNA interference-mediated knockdown of USP6NL inhibited TNBC cell growth, motility and EMT. Further, USP6NL was proved as the target of a tumor-inhibitor miR-142-3p, and LINC00689 augmented USP6NL expression by absorbing miR-142-3p. Importantly, miR-142-3p deficiency or USP6NL overexpression fully abolished the inhibitory effect of LINC00689 silence on TNBC cellular behaviors. CONCLUSION: All data revealed the important role of USP6NL/LINC00689/miR-142-3p signaling in TNBC. The findings might provide a new and promising therapeutic biomarker for treating patients with TNBC.

2.
Phytomedicine ; 78: 153314, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32882582

RESUMO

BACKGROUND: Sarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known. PURPOSE: This study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN. METHODS: Streptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar. RESULTS: Sar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs. CONCLUSION: Sar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.

3.
ESC Heart Fail ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945150

RESUMO

AIMS: Elevated heart rate (HR) in heart failure (HF) is associated with worse outcomes, particularly in acute HF (AHF). HR reduction with ivabradine reduces cardiovascular events in HF patients with reduced ejection fraction. The present trial aimed to test the hypothesis that the early HR reduction using ivabradine improves clinical outcomes in patients with AHF. METHODS AND RESULTS: SHIFT-AHF is a prospective, multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of ivabradine when adding to standard therapy in AHF patients (SHIFT-AHF). The trial will include 674 AHF patients with left ventricular ejection fraction < 45% and New York Heart Association functional classes III-IV. Participants were enrolled from March 2020 and will be followed up until December 2022. Patients are randomized to treatment with ivabradine or placebo (randomization 1:1). After allocation, the dose of ivabradine is titrated according to HR. Six months' follow-up and three control visits (7, 90, and 180 days after enrolment) are required for every participant. Assessment involves clinical examination, laboratory tests, echocardiography, electrocardiography, heart rhythm, cardiac function, and quality of life. The primary endpoint is a composite of all-cause mortality or re-admission due to worsening HF. Secondary endpoints include the assessments of cardiac remodelling, cardiac functional capacity, and quality of life. CONCLUSIONS: The SHIFT-AHF trial will shed further light on the role of early HR reduction using ivabradine in patients with AHF.

4.
J Control Release ; 328: 127-140, 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32871205

RESUMO

Imaging-guiding and targeted drug delivery to tumors are essential for precision cancer therapy, which is a challenging goal to achieve extraordinary therapeutic efficacy. Functional live cells-based delivery systems are expected to play an important role in imaging-guiding and targeted drug delivery. Herein, we fabricated a delivery system mediated by IR-820 conjugated macrophages for tumor targeted combination therapy under fluorescence imaging guidance. The functional macrophages by nature could cross the barriers and recruit into tumors, and serve as host cells to targeted deliver drugs to tumors. The pH-sensitive doxorubicin nanoparticles were engulfed by the macrophages to enhance the drug loading and decrease the damage on host cells. IR-820 was anchored into macrophages cytoplasm to achieve the dual function of photothermal therapy and fluorescence imaging guidance. With Balb/C mice bearing murine breast tumor (4 T1) as models, the functional macrophages for their innate tumor tropism could targeted transport these therapeutic drugs into tumor site to exert efficient chemo-photothermal combination therapy. Moreover, fluorescence imaging-guided drug delivery was employed as the visible strategy to provide the optimized therapeutic window based on the fluorescence of IR-820. The multi-functional macrophages-mediated delivery system would provide a potential for precise and targeted delivery of combination therapy.

5.
J Orthop Surg Res ; 15(1): 422, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943096

RESUMO

BACKGROUND: This study aimed to analyze and compare the clinical and functional outcomes of distal tibia fractures treated with intramedullary nailing (IMN) using the suprapatellar (SP) and infrapatellar (IP) surgical approaches. METHODS: A retrospective analysis was performed in 63 patients with distal fractures that were treated with IMN between August 2014 and August 2018. A total of 27 and 36 patients underwent IMN using the SP and IP techniques, respectively. The surgical time, blood loss, closed reduction rate, rate of adjuvant reduction technique, fracture healing time, and complications were reviewed in this study. Anterior knee pain was assessed using the visual analog scale. The Lysholm Knee Scoring Scale and American Orthopaedic Foot and Ankle Society (AOFAS) scale were used as clinical measurements. RESULTS: A total of 63 patients, with a minimum follow-up of 12 months, were evaluated. The average surgical time, blood loss, rate of adjuvant reduction technique, closed reduction rate, fracture healing time, and Lysholm Knee Scoring Scale score were insignificantly different (P > 0.05) between the two groups. However, the SP approach was superior to the IP approach in terms of pain score, AOFAS score, and fracture deformity rate (P < 0.05). CONCLUSIONS: In the treatment of distal tibia fractures, the SP IMN technique is associated with a significantly higher functional outcome, lower knee pain, and lower rate of fracture deformity than the IP IMN technique.

6.
J Orthop Surg Res ; 15(1): 341, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32819408

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

7.
Sensors (Basel) ; 20(17)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825318

RESUMO

Localization is an indispensable technology for underwater wireless sensor networks (UWSNs). In what concerns UWSNs, the accurate location information is not only the requirement of the marine field applications but also the basis of the other corresponding research, for instance, network routing and topology control. Recently, an astonishing surge of interest has been drawn in the received signal strength (RSS)-based scheme due to cost-effectiveness and synchronization-free compared with others. However, unlike the terrestrial wireless sensor networks (WSNs), the acoustic signal may suffer the absorption loss in the underwater environment besides the path loss, which degrades the localization accuracy and limits the capability of the RSS-based technology in UWSNs. In this context, a robust localization method with an absorption mitigation technique (AMT) is developed. First, an RSS-based analytically tractable measurement model is conducted, where the maximum likelihood estimator (MLE) is derived. Nevertheless, it is quite challenging to solve the problem using MLE under a non-convex expression. Therefore, by exploiting certain approximations, the considered localization problem is converted into an optimization expression with a maximum absorption loss involved. A min-max strategy is then presented, with which the problem is turned to minimize the worst situation of the absorption loss. After a simple manipulation, the problem is further investigated as a generalized trust region sub-problem (GTRS) framework. Although the GTRS is a non-convex scheme, the solution can be obtained through an iteration method by introducing a multiplier. In addition, the closed-form expression of the Cramer-Rao lower bound (CRLB) of the analytically tractable measurement model is derived. Numerical simulations demonstrate the effectiveness of the proposed method compared with the state-of-the-art approaches in different scenarios.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32746191

RESUMO

Endoscopic ultrasound (EUS), an interventional imaging technology, utilizes a circular array to delineate the cross-sectional morphology of internal organs through the gastrointestinal (GI) track. However, the performance of conventional EUS transducers has scope for improvement because of the ordinary piezoelectric parameters of Pb(Zr,Ti)O3 (PZT) bulk ceramic as well as its inferior mechanical flexibility which can cause material cracks during the circular shaping process. To achieve both prominent imaging capabilities and high device reliability, a 128-element 6.8-MHz circular array transducer is developed using a Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) 1-3 composite with a high electromechanical coupling coefficient (kt ~ 0.78) and good mechanical flexibility. The characterization results exhibit a large average bandwidth of 58%, a high average sensitivity of 100 mVpp, and a crosstalk of less than -37 dB near the center frequency. Imaging performance of the PMN-PT composite-based array transducer is evaluated by a wire phantom, an anechoic cyst phantom, and an ex vivo swine intestine. This work demonstrates the superior performance of the crucial ultrasonic device based on an advanced PMN-PT composite material and may lead to the development of next generation biomedical ultrasonic devices for clinical diagnosis and treatment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32794110

RESUMO

Lacustrine groundwater discharge (LGD) can play an important role in water and contaminant mass balance of lakes. Dongting Lake is the second largest fresh lake in China which is connected to Yangtze River and has quite prominent ecological status and function within Yangtze River basin. However, the effect of groundwater discharge on the balance of water and contaminant in Dongting Lake has long been overlooked. This study estimated the groundwater discharge and associated contaminants input into Dongting Lake during the dry season using multiple tracers (222Rn, 18O, Cl-). After sensitivity analysis of different models, it is found that the result of 222Rn mass balance model is the most reliable. Based on the 222Rn mass balance model, the groundwater discharge rate is estimated to be 73.94 mm/d and the contribution of LGD to water balance is 10.94%. As the main nutrient components, NH3-N, P and Si from groundwater input account for 23.65%, 5.12% and 30.15%  % of the total input, respectively. As the main heavy metal components, Fe, Mn and As from groundwater input all account for more than 50% of the total input. Although the LGD rate is relatively small, the contaminant input from LGD is significant enough, which may be a potential threat to the ecological stability of Dongting Lake. In this study, the mass balance models of multiple tracers were integrated to understand the role of groundwater in maintaining the water balance and pollution status of Dongting Lake, which has certain reference significance for the LGD study in plain lakes or reservoirs with complex water systems in humid regions.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32839956

RESUMO

The clayey aquitard has the potential to release geogenic poisonous chemicals such as arsenic (As) to the adjacent aquifer owing to complex hydrologic or biogeochemical processes. However, it remains unclear whether the aquitard has effect on As enrichment in the underlying aquifer in regions without extensive groundwater pumping, and the related processes have been poorly known. Based on piezometer water chemistry, stable water isotopes, sediment chemistry and reactive-transport model, this study aims to reveal the impact process of the aquitard to As accumulation of underlying aquifer from central Yangtze River Basin, a As-affected area without extensive groundwater pumping. On the whole, As migrated from top to bottom of the aquitard (especially the depth over 10 m) and significantly influenced the As accumulation in the underlying aquifer. Nonetheless, the results of three topical boreholes showed two different hydrogeological conditions affected As release in the aquitard and enrichment in the underlying aquifer. Different hydrogeological conditions could result in the input of different species organic carbon and then impact As concentrations in the aquifer. When the aquitard was near surface water bodies, the reductive dissolution of iron oxides was the main driver for As release and the aquitard had a significant influence on the enrichment of arsenic in the aquifer. At areas without surface water bodies nearby, the desorption of As(V) from minerals was the main source of As and the concentrations of As in pore water were quite low; this pattern had little effect on the enrichment of arsenic in the aquifer.

11.
Appl Opt ; 59(22): 6729-6736, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32749378

RESUMO

Development of a lightweight, low-cost, easy-to-use and low-maintenance lidar technique has been of great interest for atmospheric aerosol remote sensing in recent years and remains a great challenge. In this work, an 808 nm mini-Scheimpflug lidar (SLidar) system with about 450 mm separation between the transmitter and the receiver has been developed by employing a 114 mm aperture Newtonian telescope (F4). System performances, such as the beam characteristic, the range resolution, and the signal-to-noise ratio of the lidar signal, have been carefully investigated. Despite employing a small receiving aperture, all-day measurements were still feasible with about a one-minute signal averaging for both the horizontal urban area monitoring and the slant atmospheric sounding in the boundary layer. The lidar signal in the region of 29-50 m with a scattering angle less than 179.5° could be slightly underestimated due to the variation of the phase function. The extinction coefficient evaluated in the region between 29 and 2000 m according to the Klett method agreed well with the concentrations of particulate matters for both horizontal and slant measurements. The promising result demonstrated in this work has shown great potential to employ the robust mini-SLidar system for atmospheric monitoring in the boundary layer.

12.
IEEE Trans Med Imaging ; PP2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32833632

RESUMO

The phased-array radio frequency (RF) coil plays a vital role in magnetic resonance-guided focused ultrasound (MRgFUS) neuromodulation studies, where accurate brain functional stimulations and neural circuit observations are required. Although various designs of phased-array coils have been reported, few are suitable for ultrasound stimulations. In this study, an MRgFUS neuromodulation system comprised of a whole brain coverage non-human primate (NHP) RF coil and an MRI-compatible ultrasound device was developed. When compared to a single loop coil, the NHP coil provided up to a 50% increase in the signal-to-noise ratio (SNR) in the brain and acquired better anatomical image-quality. The NHP coil also demonstrated the ability to achieve higher spatial resolution and reduce distortion in echo-planer imaging (EPI). Ultrasound beam characteristics and transcranial magnetic resonance acoustic radiation force (MR-ARF) were measured for simulated positions, and calculated B0 maps were employed to establish MRI-compatibility. The differences between focused off and on ultrasound techniques were measured using SNR, g-factors, and temporal SNR (tSNR) analyses and all deviations were under 2.3%. The EPI images quality and stable tSNR demonstrated the suitability of the MRgFUS neuromodulation system to conduct functional MRI studies. Last, the time course of the blood oxygen level dependent (BOLD) signal of posterior cingulate cortex in a focused ultrasound neuromodulation study was detected and repeated with MR thermometry.

13.
Adv Healthc Mater ; 9(18): e2000387, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32815646

RESUMO

It is of great significance to develop multifunctional biomaterials to effectively deliver anticancer drug to tumor cells for cancer therapy. Here, inspired by the specific tumor microenvironment (TME) cues, a unique multistage pH/redox-responsive polyprodrug composed of amphiphilic pH-sensitive diblock copolymer poly(ethylene glycol) methyl ether-b-poly(ß-amino esters) conjugated with doxorubicin (DOX) via redox-sensitive disulfide bonds (mPEG-b-PAE-ss-DOX) is designed and developed. This polyprodrug can self-assemble into micelles (DOX-ss@PMs) at low concentration with high serum stability, indicating that DOX-ss@PMs have prolonged circulation time. The dual pH/redox-responsiveness of the multistage platform is thoroughly evaluated. In vitro results demonstrate that DOX-ss@PMs can highly accumulate at tumor site, followed by responding to the acidity for disassembly and effectively penetrating into the tumor cells. DOX is released from the platform due to the cleavage of disulfide bonds induced by high glutathione (GSH) concentration, thereby inducing the apoptosis of tumor cells. In vivo studies further reveal that multistage DOX-ss@PMs can more efficiently inhibit the growth of tumors and improve the survival of tumor-bearing mice in comparison to the free drug and control. These results imply that multistage delivery system might be a potential and effective strategy for drug delivery and DOX-ss@PMs could be a promising nanomedicine for cancer chemotherapy.

14.
Gut Microbes ; 12(1): 1794266, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32744162

RESUMO

The early-life gut microbiota is associated with potential development of diseases in adulthood. The sterile womb paradigm has been challenged by recent reports that revealed the presence of the meconium, amniotic fluid, and placenta microbiome. This study aimed to explore the maternal origin of the microbiota of neonate meconium by using the PacBio single-molecule real-time circular consensus sequencing technology. Such technology could produce high fidelity reads of full-length 16S rRNA genes, improving the sensitivity and specificity of taxonomic profiling. It also reduced the risk of false positives. This study analyzed the full-length 16S rRNA-based microbiota of maternal samples (amniotic fluid, feces, vaginal fluid, saliva) and first-pass meconium of 39 maternal-neonate pairs. Alpha- and beta-diversity analyses revealed sample type-specific microbiota features. Most sample types were dominated by sequences representing different genera (Lactobacillus and Curvibacter in the amniotic fluid and vaginal fluid microbiota; Bacillus and Escherichia/Shigella in the meconium microbiota; Bacteroides and Faecalibacterium in the maternal fecal microbiota; Streptococcus and Prevotella in the maternal saliva microbiota). Moreover, specific operational taxonomic units (OTUs) were identified in all sample types. Dyad analysis revealed common OTUs between the meconium microbiota and microbiota of multiple maternal samples. The meconium microbiota shared more features with the amniotic fluid microbiota than the maternal fecal and vaginal microbiota. Our results strongly suggested that the meconium microbiota was seeded from multiple maternal body sites, and the amniotic fluid microbiota contributed most to the seeding of the meconium microbiota among the investigated maternal body sites.

15.
Theranostics ; 10(20): 8957-8973, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802174

RESUMO

Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo. The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro, enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.

16.
Theranostics ; 10(20): 8974-8995, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802175

RESUMO

Rationale: Peripheral nerves are unique in their remarkable elasticity. Schwann cells (SCs), important components of the peripheral nervous system (PNS), are constantly subjected to physiological and mechanical stresses from dynamic stretching and compression forces during movement. So far, it is not clear if SCs sense and respond to mechanical signals. It is also unknown whether mechanical stimuli can interfere with the intercellular communications between neurons and SCs, and what role extracellular vesicles (EVs) play in this process. The present study aimed to examine the effect of mechanical stimuli on the EV-mediated intercellular communication between neurons and SCs, explore their effect on axonal regeneration, and investigate the underlying mechanism. Methods: Purified SCs were stimulated using a magnetic force-based mechanical stimulation (MS) system and EVs were purified from mechanically stimulated SCs (MS-SCs-EVs) and non-stimulated SCs (SCs-EVs). The effect of MS-SCs-EVs on axonal elongation was examined in vitro and in vivo. High throughput miRNA sequencing was performed to compare the differential miRNA profiles between MS-SCs-EVs and SCs-EVs. The functional role of differentially expressed miRNAs on neurite extension in MS-SCs-EVs was examined. Also, the putative target genes of differentially expressed miRNAs in MS-SCs-EVs were predicted by bioinformatics tools, and the regulatory effect of those miRNAs on putative target genes was validated both in vitro and in vivo. Results: The MS-SCs-EVs showed an average size of 137.52±1.77 nm, and could be internalized by dorsal root ganglion (DRG) neurons. Compared to SCs-EVs, MS-SCs-EVs showed a stronger ability to enhance neurite outgrowth in vitro and nerve regeneration in vivo. High throughput miRNA sequencing identified a number of differentially expressed miRNAs in MS-SCs-EVs. Further analysis of those EV-miRNAs demonstrated that miR-23b-3p played a predominant role in MS-SCs-EVs since its deprivation abolished their enhanced axonal elongation. Furthermore, we identified neuropilin 1 (Nrp1) in neurons as the target gene of miR-23b-3p in MS-SCs-EVs. This observation was supported by the evidence that miR-23b-3p could decrease Nrp1-3'-UTR-WT luciferase activity in vitro and down-regulate Nrp1 expression in neurons. Conclusion: Our findings suggested that mechanical stimuli are capable of modulating the intercellular communication between neurons and SCs by altering miRNA composition in MS-SCs-EVs. Transfer of miR-23b-3p by MS-SCs-EVs from mechanically stimulated SCs to neurons decreased neuronal Nrp1 expression, which was responsible, at least in part, for the beneficial effect of MS-SCs-EVs on axonal regeneration. Our results highlighted the potential therapeutic value of MS-SCs-EVs and miR-23b-3p-enriched EVs in peripheral nerve injury repair.

17.
Drug Deliv ; 27(1): 1156-1164, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32755291

RESUMO

In this work, we prepared a stimuli-responsive system for drug delivery and controlled release by engineering the bovine serum albumin (BSA). The doxorubicin (DOX)-loaded BSA nanoparticles (NPs) were conveniently prepared using desolvation method, followed by crosslinking through Schiff base bonds, leading to pH-sensitive DOX-loaded system (DOXs@BSA NPs). The resulted DOXs@BSA NPs showed high drug loading capacity (21.4%), and the particle size was about 130 nm with narrow polydispersity and high negative surface charge (-20.5 mV). The pH-sensitivity of DOXs@BSA NPs was evidenced by the size changes and charge reversal after incubation at different pH values. The DOXs@BSA NPs showed high serum stability which indicated the prolonged circulation time. The in vitro drug release experiment showed that the release of DOX was obviously accelerated by acidity because of disassembly of NPs induced by cleavage of Schiff base bonds. The drug release mechanism was thoroughly studied using a semi-empirical model, further confirming the pH played an important role in drug controlled release process. The results of cytotoxicity assay revealed that DOXs@BSA NPs exhibited much higher toxic effects for tumor cells in comparison to the free DOX control. Collectively, these results demonstrated that DOXs@BSA NPs might be potential application for drug delivery and controlled release in cancer chemotherapy. Moreover, this work also showed that preparation of stimuli-responsive drug delivery system by engineering the commercial biomaterials could be a promising method to develop multi-functional nanomedicine.

18.
Biochem Pharmacol ; 182: 114209, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32860826

RESUMO

Diabetic cardiomyopathy is one of the major cardiovascular complications of diabetes mellitus associated with left ventricular diastolic dysfunction. There are still no specific therapeutic guidelines for the disease. In recent years, glucagon-like peptide 1 receptor agonists were proved to exert cardioprotective effects in comprehensive studies. Therefore, we examined whether a novel oral availably glucagon-like peptide 1 receptor agonist, oral hypoglycemic peptide 2 (OHP2), could protect against diabetic cardiomyopathy in high-fat diets and continuous streptozocin injection induced rat models. After treatment for eight weeks, heart function was evaluated by echocardiography. As expected, OHP2 improved cardiac structure and function beyond glycemic control. Both hyperlipidemia and myocardium lipid accumulation were decreased by OHP2 treatment. In addition, OHP2 reversed oxidative stress and mitochondrial dysfunction in diabetic hearts. In vitro study suggested that OHP2 prevented palmitic acid-induced oxidative stress and mitochondrial dysfunction via suppressing intercellular lipid accumulation. Hence, our present findings pointed out that OHP2 is a promising oral glucagon-like peptide 1 receptor agonist for preventing diabetic cardiomyopathy.

19.
Soft Matter ; 16(32): 7598-7605, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32720671

RESUMO

The bidirectional intelligent regulation of hydrogels is a critical challenge in on-demand functional hydrogels. In this paper, a photo-triggered hydrogel for bidirectional regulation based on IR820-α-cyclodextrin/polyethylene glycol methyl acrylate was developed. This thermosensitive hydrogel can soften from gel to sol under near-infrared irradiation based on the photothermal effect of IR820, while the hydrogel can stiffen based on the photo-crosslinking of polyethylene glycol methyl acrylate under UV laser irradiation. After implanting in vivo, the softness and stiffness of the hydrogel can be regulated in a bidirectional manner by the switching of the irradiation wavelength. Moreover, the location and status of the hydrogel was tracked in vivo by fluorescence imaging due to the fluorescence labeling of IR820. The controlled and visible hydrogel could be potentially applied to different biomedical fields for precise treatment.

20.
Oncol Lett ; 20(2): 1973-1981, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32724443

RESUMO

Effect of CXCL8 gene silencing-mediated JAK-STAT signaling pathway on epithelial-mesenchymal transition (EMT) of human cutaneous melanoma cells was explored. Eighty patients with cutaneous melanoma were enrolled in the study. Cells were transfected accordingly and divided into five groups: The blank group (human cutaneous melanoma cells), NC group (human cutaneous melanoma cells + blank vector plasmid transfection), CXCL8 siRNA group (human cutaneous melanoma cells + CXCL8 silent expression vector plasmid transfection), AG490 group (human cutaneous melanoma cells + JAK-STAT signal pathway inhibitor transfection), CXCL8 siRNA + AG490 group (human cutaneous melanoma cells + JAK-STAT signaling pathway inhibitor + CXCL8 silent expression vector plasmid transfection). The expression levels of CXCL8, JAK2, STAT3, epithelial cadherin (E-cadherin), neurotrophic cadherin (N-cadherin) and vimentin in tissues and cells were detected by RT-qPCR and western blot analysis. CCK-8 and flow cytometry were used to detect cell proliferation and apoptosis. Compared with adjacent normal tissues, the expression of E-cadherin in human cutaneous melanoma tissues was significantly decreased, whereas the expression of CXCL8, JAK2, STAT3, vimentin and N-cadherin was significantly increased (P<0.05). Compared with the blank group, CXCL8 siRNA group and CXCL8 siRNA + AG490 group had significantly lower expression of CXCL8 (P<0.05). Compared with the blank group, the expression levels of JAK2, STAT3, vimentin and N-cadherin in CXCL8 siRNA group, AG490 group and CXCL8 siRNA + AG490 group were decreased, the expression of E-cadherin was increased, the cell proliferation ability was decreased and apoptosis was increased (P<0.05). Compared with CXCL8 siRNA group, the expression of JAK2, STAT3, vimentin and N-cadherin in CXCL8 siRNA + AG490 group were significantly decreased, the expression of E-cadherin was significantly increased, cell proliferation ability was decreased and apoptosis was increased (P<0.05). In conclusion, CXCL8 gene expression silencing may inhibit EMT and cell proliferation while promoting cell apoptosis of human cutaneous melanoma cells by inhibiting the activation of JAK-STAT signaling pathway.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA