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1.
Aging (Albany NY) ; 122020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32209726

RESUMO

Oxaliplatin is a platinum-based chemotherapeutic drug that is effective and commonly used in the treatment of colorectal cancer (CRC). However, long-term use of oxaliplatin usually induces significant drug resistance. It is urgent to develop strategies to reverse the oxaliplatin resistance to CRC cells. In the present study, we established the model of oxaliplatin-resistant CRC cell lines (SW480/R and HT29/R) through continuous treatment of SW480 and HT29 cells with oxaliplatin. Results of qRT-PCR analysis showed that expression of miR-19a was significantly increased in SW480/R and HT29/R compared to their parental SW480 and HT29. However, combination treatment with anti-miR-19a, an antisense oligonucleotide of miR-19a, was found to resensitize SW480/R and HT29/R cells to oxaliplatin treatment. In the mechanism research, we found that anti-miR-19a increased the expression of PTEN and thus inhibited the phosphorylation of PI3K and AKT in SW480/R and HT29/R cells. As a result, mitochondrial apoptosis induced by oxaliplatin was expanded. We demonstrated that PTEN was the target of miR-19a and inhibition of miR-19a partially reversed the resistance of colorectal cancer to oxaliplatin via PTEN/PI3K/AKT pathway.

2.
Sci Adv ; 6(12): eaay9751, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32206718

RESUMO

Rational design of potent antioxidative agent with high biocompatibility is urgently needed to treat ischemic reperfusion-induced ROS-mediated cerebrovascular and neural injury during ischemia strokes. Here, we demonstrate an in situ synthetic strategy of bioactive zeolitic imidazolate framework-8-capped ceria nanoparticles (CeO2@ZIF-8 NPs) to achieve enhanced catalytic and antioxidative activities and improved stroke therapeutic efficacy. This nanosystem exhibits prolonged blood circulation time, reduced clearance rate, improved BBB penetration ability, and enhanced brain accumulation, where it effectively inhibits the lipid peroxidation in brain tissues in middle cerebral artery occlusion mice and reduces the oxidative damage and apoptosis of neurons in brain tissue. CeO2@ZIF-8 also suppresses inflammation- and immune response-induced injury by suppressing the activation of astrocytes and secretion of proinflammatory cytokines, thus achieving satisfactory prevention and treatment in neuroprotective therapy. This study also sheds light on the neuroprotective action mechanisms of ZIF-8-capped nanomedicine against reperfusion-induced injury in ischemic stroke.

3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 112-117, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148243

RESUMO

OBJECTIVE: Autophagy is a dynamic process that degrades intracellular proteins and damaged organelles, and maintains environmental stability within the cell and provides good conditions for cell survival. Hyperoxic acute lung injury (HALI) is one of the serious complications of clinical oxygen therapy. The pathogenesis of HALI is still unclear. There are studies having shown that autophagy is involved in the pathogenesis of HALI. There are many pathway mechanisms that regulate autophagy, including phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway, mitogen-activated protein kinase/extracellular signaling-regulated protein kinase (MAPK/ERK) signaling pathway, adenosine 5'-monophosphate-activated protein kinase/unc-51 like autophagy activating kinase 1 (AMPK/ULK1) signaling pathway, transforming growth factor ß (TGF-ß) and forkhead box O1 (FoxO1) and Ras guanosine triphosphatease superfamily member Rab11a, each of which is referred to as microRNA-21-5p (miR-21-5p) target gene having a role in regulating autophagy activity in many diseases. In this paper, the above-mentioned signaling pathways of miRNA-21-5p target genes regulating autophagy were reviewed in order to find clues about the mechanism of miRNA-21-5p regulating autophagy in HALI and provide a theoretical basis for subsequent basic research.

4.
Drug Deliv ; 27(1): 469-481, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32166985

RESUMO

As an injectable anticancer drug delivery system, the biological safety of nanocarriers is the most important prerequisite for their clinical application. The objective of our study was to synthesize special ultrasound-responsive highly biocompatible chitosan nanodroplets (BCNDs), observe their spatiotemporally control the delivery of doxorubicin (DOX) in vivo. The experimental results showed that the BCNDs were successfully prepared with high biosafety in vivo and great ultrasound imaging ability. DOX-BCNDs promoted the anticancer effects of DOX in vivo and inhibited the development of tumors. They also reduced the side effects to the heart and kidneys. In conclusion, BCNDs are a new type of smart nanocarrier with high biocompatibility and efficacy have great potential to be used in the clinic.

5.
Sensors (Basel) ; 20(5)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143487

RESUMO

As unmanned aerial vehicles and other small, low-flying, and low-speed aircrafts are being extensively used, studies on their detection are being extensively conducted in radar application research. However, weak echoes, low Doppler frequencies, and target echoes mixed with ground clutter can considerably degrade the detection performance. Therefore, specific methods for the detection of such targets should be devised. We propose herein a phase compensation and coherent accumulation algorithm based on the fractional Fourier transform (FRFT) for detection and speed estimation of this type of target. First, the energy of the target echo is converged using the FRFT. Next, the phase between the peaks of the target echo is analyzed. Phase compensation and coherent accumulation determined from the expected target speed in the fractional domain eliminate ground clutter and further improve the signal-to-interference-plus-noise ratio. Finally, constant false alarm rate detection is used to identify the target, for which radial speed can be estimated directly according to the peak coordinates. The validity of the algorithm is verified via data simulation and application to real data.

6.
Int J Neurosci ; : 1-7, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32083968

RESUMO

Objective: Recent studies have found that selenium (Se) levels were associated with the risk of Parkinson's disease (PD), but the results were contradictory. Therefore, this meta-analysis was conducted to investigate the correlation between Se levels and PD.Methods: PubMed, Embase and Web of Science were searched published up to 28 October 2019. The differences between groups were analyzed by forest plots and results were pooled and assessed using a random-effect model. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to assess the association between Se levels and the risk of PD. Subgroup analysis, meta-regression, and sensitivity analysis were also conducted. Publication bias was estimated using Begg's regression asymmetry test.Results: Finally, 12 articles involving 601 PD patients and 749 controls were included in this meta-analysis. The meta-analysis revealed a significantly higher cerebrospinal fluid (CSF) Se level in PD patients than those in controls (SMD = 1.22; 95%CI [0.05, 2.39]; p = 0.000). No publication bias was found.Conclusion: The meta-analysis indicated that CSF Se levels in PD patients were significantly higher than those in controls.

7.
Int J Nanomedicine ; 15: 151-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021171

RESUMO

Purpose: Combination therapy for tumors is an important and promising strategy to improve therapeutic efficiency. This study aims at combining tumor targeting, chemo-, and photodynamic therapies to improve the anti-tumor performance. Patients and Methods: Human serum albumin (HSA), as a nontoxic and biodegradable drug carrier, was used to load hydrophobic photosensitizers (mono-substituted ß-4-pyridyloxy phthalocyanine zinc, mPPZ) by a dilution-incubation-purification (DIP) strategy to form molecular complex HSA:mPPZ. This complex was cross-linked as nanoparticles, and then chemotherapy drug doxorubicin (DOX) was adsorbed into the nanoparticles to achieve combined photodynamic therapy and chemotherapy. Next, the surface of the obtained composite was modified by a tumor surface receptor (urokinase receptor) targeting agent (ATF-HSA) using a noncovalent method to obtain the final product (ATF-HSA@HSA:mPPZ:DOX nanoparticles, AHmDN). Results: AHmDN exhibited strong stability, remarkable cytotoxicity and higher uptake to tumor cells. Cell imaging analysis indicated that DOX was separated from AHmDN and uniformly distributed in cell nucleus while mPPZ localized in cytoplasm. The PDT activity of all the samples had been confirmed by the detection of intracellular ROS. In animal experiments, AHmDN was demonstrated to have a prominent tumor-targeting effect using a 3D imaging system. In addition, the enhanced antitumor effect of AHmDN in tumor-bearing mice was also been observed. Importantly, the tumor-targeting effect of such nanoparticles lasted for about 14 days after one injection. Conclusion: These albumin nanoparticles with combined functions of tumor targeting, chemotherapy and photodynamic therapy can highly enhance the anti-tumor effect. This drug delivery system can be applied to package other hydrophobic photosensitizers and chemotherapy drugs for improving therapeutic efficacy to tumors.

8.
Int J Nanomedicine ; 15: 537-552, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021193

RESUMO

Background: Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT. Materials and Methods: The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 µg/mL), (2) NDs (30 µg/mL), (3) PTX-loaded NDs (34 µg/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 µg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy), (7) combination of NDs (30 µg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 µg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT. Results: The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (<300 nm with PDI<0.3 when at pH≧6.0). The NDs exhibited good abilities in pH-dependent charge conversion, biocompatibility and ultrasound contrast echogenicity. The in vitro drug release from PTX-loaded NDs (the highest loading efficiency and encapsulation efficiency were 20.35% and 91.58%) was pH dependent and exhibited an initial burst followed by a sustained drug release. The results of the CCK-8 assay, flow cytometry and migration assay all showed PTX-loaded NDs combined ultrasound and RT significantly enhanced cell responses in CRT. Conclusion: The pH- and ultrasound-responsive PTX-loaded NDs, which exhibited a high echogenicity, drug delivery ability and radiosensitization ability, could be a feasible option for combined imaging and novel enhancing approach in synergistic CRT.

9.
Cell Death Dis ; 11(2): 134, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075957

RESUMO

Psoriasis is a common autoimmune and chronic inflammatory skin disorder globally affecting 0.51-11.43% of adults. Inflammation-associated cell death in keratinocytes plays a key role in the process of integrate inflammatory cascade in psoriasis. Necroptosis is a regulated necrotic cell death mediated by receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL), which participates in many human inflammatory diseases. However, the mechanism and function of programmed necrosis in psoriasis is not well-illustrated. In the current study, we provide evidence for the involvement of necroptosis in psoriasis. RIPK1 and MLKL were significantly upregulated and localized in all layers of the epidermis in human psoriatic lesions, while RIPK3 and phosphorylated MLKL were mainly expressed in keratinocytes, which located in the upper layers. Increased tendency of necroptosis was also found in IMQ-induced psoriasiform skin of mice. Further, we discovered that both the inhibitor of RIPK1 R-7-Cl-O-Necrostatin-1 (Nec-1s) and MLKL-inhibitor necrosulfonamide (NSA) suppressed necroptosis in HaCaT cells and IMQ mouse models, powerfully blocked IMQ-induced inflammatory responses in vivo, and significantly downregulated the production of inflammatory factors like IL-1ß, IL-6, IL-17A, IL-23a, CXCL1, and CCL20. These findings promote the development of new therapies for the treatment of necroptosis-activated pathologies for psoriasis.

10.
J Biotechnol ; 311: 25-34, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057784

RESUMO

Myxococcus xanthus DK1622 is known as a proficient producer of different kinds of secondary metabolites (SM) with various biological activities, including myxovirescin A, myxalamide A, myxochromide A and DKxanthene. Low production of SM in the wild type bacteria makes searching for production optimization methods highly desirable. Identification and induction of endogenous key molecular feature(s) regulating the production level of the metabolites remain promising, while heterologous expression of the biosynthetic genes is not always efficient because of various complicating factors including codon usage bias. This study established proteomic and molecular approaches to elucidate the regulatory roles of the ROK regulatory protein in the modification of secondary metabolite biosynthesis. Interestingly, the results revealed that rok inactivation significantly reduced the production of the SM and also changed the motility in the bacteria. Electrophoretic mobility shift assay using purified ROK protein indicated a direct enhancement of the promoters encoding transcription of the DKxanthene, myxochelin A, and myxalamide A biosynthesis machinery. Comparative proteomic analysis by two-dimensional fluorescence difference in-gel electrophoresis (2D-DIGE) was employed to identify the protein profiles of the wild type and rok mutant strains during early and late logarithmic growth phases of the bacterial culture. Resulting data demonstrated overall 130 differently altered proteins by the effect of the rok gene mutation, including putative proteins suspected to be involved in transcriptional regulation, carbohydrate metabolism, development, spore formation, and motility. Except for a slight induction seen in the production of myxovirescin A in a rok over-expression background, no changes were found in the formation of the other SM. From the outcome of our investigation, it is possible to conclude that ROK acts as a pleiotropic regulator of secondary metabolite formation and development in M. xanthus, while its direct effects still remain speculative. More experiments are required to elucidate in detail the variable regulation effects of the protein and to explore applicable approaches for generating valuable SM in this bacterium.

11.
Biochem Pharmacol ; 174: 113830, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32001235

RESUMO

High glucose-induced endothelial dysfunction is a critical initiating factor in the development of diabetic vascular complications. Omentin-1 has been regarded as a novel biomarker of endothelial function in subjects with type-2 diabetes (T2D); however, it is unclear whether omentin-1 has any direct effect in ameliorating high glucose-induced endothelial dysfunction. In the present study, we analyzed the effect of omentin-1 on high glucose-induced endothelial dysfunction in isolated mouse aortas and mouse aortic endothelial cells (MAECs). Vascular reactivity in aortas was measured using wire myography. The expression levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor δ (PPARδ), Akt, endothelial nitric-oxide synthase (eNOS), and endoplasmic reticulum (ER)-stress markers in MAECs were determined by Western blotting. The production of reactive oxygen species (ROS) and nitric oxide (NO) was assessed by diluted fluoroprobe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM DA), respectively. We found that ex vivo treatment with omentin-1 reversed impaired endothelial-dependent relaxations (EDR) in mouse aortas after high-glucose insult. Elevated ER-stress markers, oxidative stress, and reduction of NO production induced by high glucose in MAECs were reversed by omentin-1 treatment. Omentin-1 also effectively reversed tunicamycin-induced ER stress responses in MAECs, as well as ameliorated impairment of endothelial-dependent relaxation in mouse aortas. Moreover, omentin-1 increased AMPK phosphorylation with a subsequent increase in PPARδ expression, while also restoring the decreased phosphorylation of Akt and eNOS. The effects of omentin-1 were abolished by cotreatment of compound C (AMPK inhibitor) and GSK0660 (PPARδ antagonist). These data indicate that omentin-1 protects against high glucose-induced vascular-endothelial dysfunction through inhibiting ER stress and oxidative stress and increasing NO production via activation of AMPK/PPARδ pathway.

12.
Behav Sleep Med ; : 1-11, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969021

RESUMO

Objectives: The work interval duration between the end of one workday and the start of the following workday is referred to as the daily rest period (DRP). The present study examined whether DRP - a proxy for sleep opportunity between work shifts - is associated with indicators of sleep debt and social jetlag among daytime workers.Methods: We used a web-based survey to gather data on demographics, average DRP in the previous month, time in bed (TIB), bedtime, wake-up time, and sleep timing on workdays and non-workdays. The Japanese daytime workers (n = 3,914) were divided into seven DRP groups (hours) as follows: <11, 11, 12, 13, 14, 15, and ≥16.Results: The two-way analyses of covariance (DRP group x day) for TIB, mid-sleep as sleep timing, bedtime, and wake-up time showed significant interactions (all p < .001). Specifically, TIB was significantly shorter, and mid-sleep and wake-up time were significantly earlier on workdays than on non-workdays, across all DRP groups (all p < .001). Additionally, the different values for TIB (sleep debt), sleep timing (social jetlag), bedtime, and wake-up time were calculated by subtracting workdays from non-workdays. The trend analysis showed that workers with longer DRP (sleep opportunity) had smaller differences in TIB, sleep timing, and wake-up time between workdays and non-workdays (all p < .001).Conclusions: Overall, daytime workers reported significant sleep debt and misalignment between work and free sleep-wake periods. However, workers with shorter DRPs (less sleep opportunity between shifts) reported significantly greater amounts of sleep debt and social jetlag than did workers with longer DRPs.

13.
Biosens Bioelectron ; 153: 112045, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31989940

RESUMO

Ionic liquid composite electrodes have been widely utilized for the fabrication of electrochemical biosensors. However, the biosensing electrode modified with ionic conducting solids remains unexplored. Herein, we prepared a superionic conducting potassium ferrite (K2Fe4O7) under hydrothermal conditions for modifying glassy carbon electrode (GCE). The modified electrode (K2Fe4O7/GCE) showed an excellent electrocatalytic activity towards the oxidation of dopamine (DA). The oxidation peak currents increased linearly with increasing DA concentrations in the range of 1 µM-140 µM, and the detection limit is 0.22 µM (S/N = 3). The developed DA sensor exhibited not only good selectivity for the determination of DA without interfering from ascorbic acid (AA), uric acid (UA), glucose and inorganic ions, but also good reproducibility and stability. Furthermore, the sensor was applied to determine DA concentration in bovine serum and obtained a satisfied result. This study provides a new approach for developing electrochemical biosensors based on ionic conducting solid materials.

14.
Curr Microbiol ; 77(2): 279-285, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31760453

RESUMO

A novel Pseudoalteromonas atlantica phage C7 was isolated from the coastal surface water in the Yellow Sea of China using the agar overlay method. Transmission electron microscopy analysis reveals that it belongs to Siphoviridae with a head of 56 nm in diameter and a tail of 102 nm in length. Microbiological characterization suggests that the phage is stable at a range of temperatures (from - 20 to 65 °C) and the optimal pH range is 6-12. One-step growth curve shows a 45-min latent period and a 105-min rise period. Genomic analysis shows that C7 has a linear, double-stranded 42,261-bp DNA molecule with 40.6% GC content and 76 putative open reading frames (ORFs) with one tRNA. The ORFs are classified into six functional groups as follows: hypothetical protein, phage structure, phage packaging, DNA replication and regulation, transcription, and some additional functions. There are many obviously similarities between C7 and a previously published Pseudoalteromonas phage vB_PspS-H40/1 by genomic comparison. This study provides an important data for further research on the interaction between marine bacteriophages and their hosts.

15.
Int J Mol Med ; 45(1): 93-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746348

RESUMO

Psoriasis is one of the most common immune­mediated inflammatory diseases of the skin. The identification of the pivotal molecular mechanisms responsible for the disease pathogenesis may lead to the development of novel therapeutic options. The present study aimed to identify pivotal differentially expressed genes (DEGs) and methylated DEGs in psoriasis. The raw data from gene microarrays were obtained from the Gene Expression Omnibus database. The data were processed using packages in Bioconductor. In total, 352 upregulated and 137 downregulated DEGs were identified. The upregulated DEGs were primarily enriched in the 'innate immune defense' response and the 'cell cycle'. The downregulated DEGs were primarily enriched in 'cell adhesion' and 'tight junction pathways'. A total of 95 methylated DEGs were identified, which were significantly enriched in the 'interleukin (IL)­17 signaling pathway' and the 'response to interferon'. Based on a comprehensive evaluation of all algorithms in cytoHubba, the key epigenetic­associated hub genes (S100A9, SELL, FCGR3B, MMP9, S100A7, IL7R, IRF7, CCR7, IFI44, CXCL1 and LCN2) were screened out. In order to further validate these genes, the present study constructed a model of imiquimod (IMQ)­induced psoriasiform dermatitis using mice. The levels of these hub genes were increased in the IMQ group. The knockdown of methylation­regulating enzyme ten­eleven translocation (TET) 2 expression in mice attenuated the expression levels of S100A9, SELL, IL7R, MMP9, CXCL1 and LCN2. Furthermore, the hydroxymethylated level of S100A9 was highly expressed in the IMQ group and was significantly decreased by TET2 deficiency in mice. On the whole, using an integrative system bioinformatics approach, the present study identified a series of characteristic enrichment pathways and key genes that may serve as potential biomarkers in psoriasis.

16.
Rev Esp Enferm Dig ; 112(2): 109-117, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830797

RESUMO

BACKGROUND: increasing evidence suggests that marital status is associated with tumor prognosis. The prognostic impact of marital status on colorectal neuroendocrine neoplasms has not been studied adequately. This study explored the relationship between marital status and prognosis of colorectal neuroendocrine neoplasms. METHODS: during 2004-2012, 7,180 colorectal neuroendocrine neoplasm patients were identified from the Surveillance, Epidemiology and End Results database. A primary comparison (married vs unmarried) was performed with a 1:1 propensity matching score. Secondary comparisons were performed individually between three unmarried subgroups (single, divorced/separated, widowed) and the married group. The effect of marital status according to sex and extension of disease was explored. RESULTS: married patients had better survival (overall survival) (p < 0.001) and colorectal neuroendocrine neoplasm cause-specific survival (p = 0.001) rates compared to unmarried patients. Multivariate analysis indicated that marital status was an independent prognostic factor and married patients had a better overall survival (HR = 1.673; 95% CI: 1.446-1.936; p < 0.001) and colorectal neuroendocrine neoplasm cause-specific survival (HR = 1.365; 95% CI: 1.141-1.632; p = 0.001). Subgroup analysis showed that married patients had the best prognosis of cause-specific survival/overall survival and widowed patients had the worst prognosis (log-rank test p < 0.05). Marital status plays a more important role in colorectal neuroendocrine neoplasms patients with localized disease than in those with regional or distant disease. CONCLUSIONS: marital status is an independent prognostic factor for survival in colorectal neuroendocrine neoplasms patients. Married patients have a better prognosis with early stage disease. Single, widowed and male patients are regarded as a high-risk population.

17.
J Control Release ; 318: 197-209, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31672622

RESUMO

With the in-depth research of organelles, the microenvironment characteristics of their own, such as the acid environment of lysosomes and the high temperature environment of mitochondria, could be used as a natural and powerful condition for tumor therapy. Based on this, we constructed a two-step precise targeting nanoplatform which can realize the drug release and drug action triggered by the microenvironment of lysosomes (endosomes) and mitochondria, respectively. To begin with, the mesoporous silica nanoparticles (MSNs) were modified with triphenylphosphonium (TPP) and loaded with 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Then, folic acid (FA) targeted pH-sensitive liposomes containing docetaxel (Lipo/DTX-FA) were prepared by thin-film dispersion method, and the core-shell AIPH/MSN-TPP@Lipo/DTX-FA nanoparticles were constructed by self-assembly during the hydration of the liposomes. When this nanoplatform entered into the tumor cells through FA receptor-mediated endocytosis, the pH-sensitive liposomes were destabilized in the lysosomes, resulting in the release of DTX and AIPH/MSN-TPP nanoparticles. After that, AIPH was delivered to mitochondria by AIPH/MSN-TPP, and the alkyl radicals produced by AIPH under the high temperature environment can cause oxidative damage to mitochondria. Not only that, the DTX could enhance the anti-tumor effect of AIPH by downregulating the expression of anti-apoptotic Bcl-2 protein. The in vitro and in vivo results demonstrate that this delivery system could induce apoptosis based on organelles' s own microenvironment, which provides a new approach for tumor therapy.

18.
Retina ; 40(1): 66-74, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30312258

RESUMO

PURPOSE: To evaluate the effect of internal limiting membrane peeling and air tamponade for idiopathic macular hole, and explore reasons and interventions for persistent holes. METHODS: One hundred and thirty-five eyes with Stage III and IV idiopathic macular hole that underwent 23-gauge vitrectomy, internal limiting membrane peeling, and air tamponade were reviewed. Eyes with persistent holes underwent a second surgery. Outcome-related factors and interventions treating persistent holes were discussed. RESULTS: The initial closure (Type I) rate was 89.63% (121/135). Eyes that underwent the second surgery all obtained final closure (Type I). Diameter of macular hole was significantly smaller (P < 0.001) and duration of symptoms was significantly shorter (P = 0.017) in initially closed cases than in unclosed ones. Binary logistic regression indicated large diameter of macular hole as a risk factor for initial closure (P = 0.004). A cutoff value of 677 µm was provided by receiver operating characteristic curve to predict initial closure (P < 0.001). Best-corrected visual acuity of all individuals improved significantly (P < 0.001) from 20/154 to 20/40 (mean follow-up: 4.5 months). CONCLUSION: Internal limiting membrane peeling and air tamponade for idiopathic macular hole provide satisfactory morphologic and functional outcomes. Large diameter of macular hole and long duration of symptoms are risk factors for initial closure. Proper second surgery can obtain satisfactory outcomes for persistent holes.

19.
Sci Rep ; 9(1): 18321, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797961

RESUMO

The novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.

20.
Phys Chem Chem Phys ; 21(48): 26598-26605, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31793570

RESUMO

The interaction between metallic nanoparticles and fluorescent molecules and its influence on the optical properties of the particles/molecules have been intensively investigated because of their biology and sensing applications. Here, we studied the adsorption and aggregation of a commonly used dye, fluorescein isothiocyanate (FITC), on gold nanoparticles of various diameters. It was observed that the adsorption of FITC on relatively large gold nanoparticles (≥15 nm in diameter) induced quenching in the two-photon fluorescence (TPF) emission from the FITC molecules, while smaller-sized gold nanoparticles (1.6 nm) had no such effect. This difference was interpreted by the fluorescence resonance energy transfer (FRET) between the FITC molecules and the larger gold nanoparticles. At the same time, it was observed that the ratio of TPF quenching was notably higher than the ratio of the FITC molecules chemically adsorbed on the large gold particles. This unexpected observation revealed that the aggregation-induced fluorescence quenching also contributed significantly to the attenuation of the TPF emission. Time-dependent TPF attenuation during the interaction of FITC and the larger gold nanoparticles was recorded and used to confirm this interpretation. With this experimental evidence, a clear picture of the interaction of the FITC molecules on the gold surface was presented: FITC molecules chemically adsorbed on the small gold nanoparticles. However, the relatively larger surface curvature hindered the aggregation of the FITC molecules on the small gold nanoparticles. On the surface of the larger gold nanoparticles, both adsorption and aggregation occured. The influence of the surface curvature on the interfacial structure of the adsorbed molecules on nanoparticles was discussed.

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