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1.
J Nanosci Nanotechnol ; 20(2): 692-700, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383064

RESUMO

Fluorescent bimetallic Au-Ag nanoclusters (Au-AgNCs) were found to exhibit oxidase-like activity and could catalyze the oxidation of 3,3',5,5' tetramethylbenzidine (TMB) to oxTMB. On the basis of this property, we assembled a fluorescent nanoplatform as a turn-on probe for sensing mercury (II) ions (Hg2+) through the inner-filter effect (IFE). Au-AgNCs and oxTMB were chosen as IFE absorber and fluorophore pair for the first time. In the absence of Hg2+, the Au-AgNCs absorption band well. Covered the fluorescence emission band of oxTMB, and as a result, the fluorescence of oxTMB was reduced. In the presence of Hg2+, Hg2+ was reduced to Hg0 by extra BSA in Au-AgNCs probe system and anchored on the surface of Au-AgNCs. The absorption intensity for Au-AgNCs then decreased at 418 nm, resulting in the recovery of fluorescence from oxTMB. The formed Au-Hg thin amalgam layer obviously enhanced the oxidase-like activity of Au-AgNCs as well as hindered the IFE activity between Au-AgNCs and oxTMB. Therefore, based on the Hg2+ stimulating oxidaselike properties of Au-AgNCs, a fluorometric assay for determination of Hg2+ was developed in this study. The proposed sensing strategy showed a linear range from 10 nM to 500 nM, with ultralow LOD of ~0.7 nM for Hg2+. Moreover, the detection probe system was stable over a wide pH range, making it able to be applied in complex sample systems. We have successfully demonstrated the detection of Hg2+ in tap water samples. The fluorescent assay reported here, for sensitive and selective determination of Hg2+, may find great application in multiple areas, such as environmental and pharmaceutical analysis.

2.
J Nanosci Nanotechnol ; 20(1): 433-441, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383190

RESUMO

The production of p-type silicon/intrinsic ultrananocrystalline diamond/n-type nanocrystalline iron disilicide heterojunction devices was conducted via coaxial arc plasma deposition and pulsed laser deposition. The results of current density-voltage (J-V) curves justified a large leakage current along with minimal response under illumination. A recombination process controls the mechanism for carrier portage in the zone of V ≤ 0.16 V, while a space-charge-limited current process governs the carrier portage mechanism in the circumstance of V value beyond 0.16 V. Frequency (f) dependent conductance (G/ω)-V and capacitance (C)-V curves were measured to extract the series resistance (Rs) and density of the interface state (nss). On the basis of extraction in the manner of Nicollian-Brews, the value of Rs rose with f abatement. With zero bias voltage applied, the value of Rs was 189.84 Ω at 2 MHz and rose to 715.10 Ω at 20 kHz. The acquired Rs may be attributable to the occurrence of Rs in the neutral zones as well as Ohmic contact. The values for nss, which were extracted in the manner of Hill-Coleman, were 1.23×1011 eV-1 cm-2 at 2 MHz and 6.51×1012 eV-1 cm-2 at 20 kHz. This result was an indicator of the occurrence of interface states at the zone of the junction interface performing as a source of leakage current and a trap center for the carriers originated by light.

3.
Oncol Rep ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31485666

RESUMO

Osteosarcoma is a serious malignancy in pediatric patients, which comprises 2.4% of fatal cancer in children and achieves 20% of all primary bone cancers. In the present study, we employed three human osteosarcoma cell lines MG­63, HOS and U2OS for susceptibility to cytolytic activity of freshly isolated healthy donor NK cells. Cells were lysed by NK cells in a dose dependent manner. MG­63 cells exhibited less susceptibility to NK cells than HOS and U2OS cells at all cell ratios. The specific mechanism underlying the effects of NK cells on osteosarcoma cells was determined by antibody blockage experiments. The results revealed that granzyme B was the key factor in the NK cell­induced cytotoxicity of human osteosarcoma cells. To the best of our knowledge, the present study is the first to investigate the expression of PD­L1 in MG­63, HOS and U2OS cells. The relative expression of the PD­L1 gene and protein in MG­63 cell was greater than HOS and U2OS cells. The specific lysis of human osteosarcoma cells induced by NK cells was enhanced when PD­L1/PD­1 was blocked by the PD­L1 antibody. The present study proposed that the PD­L1/PD­1 axis serves an important role in NK cell­induced cytotoxicity in osteosarcoma via granzyme B secretion. Our findings may contribute to the development of precise treatments for osteosarcoma based on the expression profile of PD­L1 in patients with this disease.

4.
Qual Life Res ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471814

RESUMO

PURPOSE: To identify the effects of whole body vibration (WBV) on health-related quality of life (HRQOL) in patients with chronic conditions. METHODS: Five databases (the Cochrane Library, PubMed, Medline, EBSCO, and Web of science) were searched (from inception until April 30, 2019) for original articles. All studies were randomized controlled trials reporting the effects of WBV on HRQOL. Two independent reviewers extracted trial data and assessed the risk of bias using the risk of bias tool recommended by the Cochrane Back Review Group. RESULTS: Of the 349 articles that were screened, 17 articles, including 763 participants with various chronic conditions, met the inclusion criteria. Six studies reported significant improvements in HRQOL. No evidence was observed to suggest that WBV was more effective than other types of exercises. The study participants, exercise protocols, HRQOL instruments, study duration, and frequency as well as amplitude of WBV varied across the studies. Meta-analysis was not conducted due to the heterogeneity of study designs and outcome measures. CONCLUSIONS: This study has demonstrated that WBV may improve HRQOL in patients with chronic conditions. However, the evidence was not strong enough to warrant recommendation and thus further high-quality studies with larger sample sizes and longer intervention durations are needed.

5.
Plant Sci ; 287: 110174, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31481216

RESUMO

Asteraceae is the largest family of angiosperms, comprising approximately 24,000 species. Molecular genetic studies of Asteraceae are essential for understanding plant diversity. Chrysanthemum morifolium is the most industrially important ornamental species in Asteraceae. Most cultivars of C. morifolium are autohexaploid and self-incompatible. These properties are major obstacles to the genetic analysis and modern breeding of C. morifolium. Furthermore, high genome heterogeneity complicates molecular biological analyses. In this study, we developed a model strain in the genus Chrysanthemum. C. seticuspe is a diploid species with a similar flowering property and morphology to C. morifolium and can be subjected to Agrobacterium-mediated transformation. We isolated a natural self-compatible mutant of C. seticuspe and established a pure line through repeated selfing and selection. The resultant strain, named Gojo-0, was favorable for genetic analyses, including isolation of natural and induced mutants, and facilitated molecular biological analysis, including whole genome sequencing, owing to the simplicity and homogeneity of its genome. Interspecific hybridization with Chrysanthemum species was possible, enabling molecular genetic analysis of natural interspecific variations. The accumulation of research results and resources using Gojo-0 as a platform is expected to promote molecular genetic studies on the genus Chrysanthemum and the genetic improvement of chrysanthemum cultivars.

6.
Cell Res ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481760

RESUMO

Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified protein C receptor (Procr) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of Procr in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr+ cells are enriched for cancer stem cells (CSCs) in Wnt1 basal-like tumors, but not in Brca1 basal-like tumors or PyVT luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR+ TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31482338

RESUMO

PURPOSE: To develop, validate, and compare early warning models of the 30-day mortality risk for patients with malignant biliary obstruction (MBO) undergoing percutaneous transhepatic biliary stent placement (PTBS). MATERIALS AND METHODS: Between January 2013 and October 2018, this multicenter retrospective study included 299 patients with MBOs who underwent PTBS. The training set consisted of 166 patients from four cohorts, and another two independent cohorts were allocated as external validation sets A and B with 75 patients and 58 patients, respectively. A logistic model and an artificial neural network (ANN) model were developed to predict the risk of 30-day mortality after PTBS. The predictive performance of these two models was validated internally and externally. RESULTS: The ANN model had higher values of area under the curve than the logistic model in the training set (0.819 vs 0.797), especially in the validation sets A (0.802 vs 0.714) and B (0.732 vs 0.568). Both models had high accuracy in the three sets (75.9-83.1%). Along with a high specificity, the ANN model improved the sensitivity. The net reclassification improvement and integrated discrimination improvement also demonstrated that the ANN model led to improvements in predictive ability compared with the logistic model. CONCLUSIONS: Early warning models were proposed to predict the risk of 30-day mortality after PTBS in patients with MBO. The ANN model has higher accuracy and better generalizability than the logistic model.

8.
J Clin Sleep Med ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31482802

RESUMO

STUDY OBJECTIVES: The association between posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) has been reported inconsistently, and the association between antidepressant use and the risk of developing OSA in patients with PTSD has not been previously studied. Therefore, we used the Longitudinal National Health Insurance Database (LHID) to investigate the impact of PTSD and antidepressant use on the risk of OSA development. METHODS: Identified from the LHID, 2,316 individuals aged ≥ 18 years with PTSD, but with no history of OSA, and 23,160 control individuals matched for age, sex, obesity and index date were enrolled between 2000 and 2015 and followed up until the end of 2015 to identify the development of OSA. A two-tailed Bonferroni-corrected P < .00038 (.05/13) was considered statistically significant as we examined 13 antidepressants. RESULTS: Individuals with PTSD had increased risk of developing OSA (adjusted hazard ratio 4.672, 95% confidence interval 2.246-9.787, P < .001) after adjusting for demographic data, medical comorbidities, and medication. Treatment with antidepressants was not significantly associated with an increased risk of developing OSA compared to no antidepressant treatment. CONCLUSIONS: Asian patients with PTSD had increased risk of developing OSA, and treatment with antidepressants did not play a key role in increasing the risk of OSA development. Further studies are required to investigate the underlying mechanisms of PTSD and the roles of antidepressants on the risk of developing OSA.

9.
Arq Bras Cardiol ; 2019 Aug 29.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31482945

RESUMO

BACKGROUND: In clinical observation, patients with acute coronary syndrome complicated with peripheral artery disease have poor prognosis, so the relationship between the diseases and clinical characteristics need to be further explored. OBJECTIVE: This study aims to investigate clinical characteristics and independent risk factors for in-hospital adverse events in acute coronary syndrome patients with a history of peripheral arterial disease (PAD). METHODS: A total of 5,682 patients with acute coronary syndrome were included into this study. These patients were divided into two groups according to the presence or absence of a history of PAD: PAD group (n = 188), and non-PAD (control) group (n = 5,494). Then, the clinical characteristics and incidence of in-hospital adverse events were analyzed; p < 0.05 was considered statistically significant. RESULTS: The age of PAD patients was higher than that in the control group (65.5 ± 10.3 years vs. 58.6 ± 11 years, p < 0.001), and the proportion of PAD patients with diabetes history and stroke history was higher than that in the control group (73 [39%] vs. 1472 [26.8%], p = 0.018; 36 [19.3%] vs. 396 [7.2%], p < 0.001). The multivariate logistic regression analysis between groups based on in-hospital adverse events revealed that a history of PAD (OR = 1.791, p = 0.01), a history of diabetes (OR = 1.223, p = 0.001), and age of > 65 years old (OR = 4.670, p < 0.001) were independent risk factors for in-hospital adverse events. CONCLUSION: A history of PAD, advanced age, and a history of diabetes are independent risk factors for in-hospital adverse events in patients with acute coronary syndrome.

10.
Urol Oncol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31474505

RESUMO

OBJECTIVES: In Taiwan, urothelial cell carcinoma (UCC) is a common malignancy of urinary tract that is associated with genetic and environmental carcinogens. WW domain-containing oxidoreductase (WWOX) has been identified as a tumor suppressor gene that associated with several cancers development and progression. The study aimed to explore the impact of WWOX gene polymorphisms on the clinicopathological status and prognosis of patients with UCC. MATERIALS AND METHODS: A total of 1,293 participants, including 431 patients with UCC and 862 healthy controls, were recruited for this study. Five polymorphisms of the WWOX gene were examined by a real-time PCR assay. RESULTS: We found that individuals carrying TT polymorphism at rs11545028 and at least 1 G allele at rs3764340 associated with more susceptible to UCC. At least 1 A allele at rs12918952 associated with more advance disease and high grade tumor. Patients with T allele at rs11545028 associated with worse relapse free survival in all patients and worse disease specific survival (DSS) in male. Patients with A allele at rs12918952 associated with worse DSS in all patients and worse relapse free survival, DSS and overall survival in male. CONCLUSIONS: This is the first reported correlation between WWOX polymorphisms and UCC risk and clinicopathologic feature. Genetic variants of WWOX contribute to the pathologic staging, grading, and prognosis. The findings regarding these biomarkers provided a potential prediction of UCC progression.

11.
EMBO Mol Med ; : e10168, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475771

RESUMO

Accurate risk stratification for patients with stage II/III colon cancer is pivotal for postoperative treatment decisions. Here, we aimed to identify and validate a circRNA-based signature that could improve postoperative prognostic stratification for these patients. In current retrospective analysis, we included 667 patients with R0 resected stage II/III colon cancer. Using RNA-seq analysis of 20 paired frozen tissues collected postoperation, we profiled differential circRNA expression between patients with and without recurrence, followed by quantitative validation. With clinical information, we generated a four-circRNA-based cirScore to classify patients into high-risk and low-risk groups in the training cohort. The patients with high cirScores in the training cohort had a shorter disease-free survival (DFS) and overall survival (OS) than patients with low cirScores. The prognostic capacity of the classifier was validated in the internal and external cohorts. Loss-of-function assays indicated that the selected circRNAs played functional roles in colon cancer progression. Overall, our four-circRNA-based classifier is a reliable prognostic tool for postoperative disease recurrence in patients with stage II/III colon cancer.

12.
BMC Urol ; 19(1): 81, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477090

RESUMO

BACKGROUND: Metastatic tumors of the penis are uncommon, and fewer than 500 cases have been reported since 1870. Most penile secondary tumors originate in organs of the genitourinary tract, followed by the gastrointestinal tract. Primary tumors of sarcoma origin are extremely rare. Herein, we present a teenager who had recurrent sarcoma of the right femur with penile metastasis. CASE PRESENTATION: The 20-year-old male patient was diagnosed with sarcoma of the right femur when he was 16 days old. He was stable following combination chemotherapy with the VAC regimen (vincristine, adriamycin, and cyclophosphamide) and debulking surgery. In January 2018, five months ago, he presented with right leg pain and swelling, and a recurrent tumor was found. Following excision of the tumor showed recurrent sarcoma. However, 2 months after the operation, right thigh swelling with tenderness occurred. A firm nodule on the glans of the penis was also noted. Penile metastasis was suspected and a biopsy was performed. The final pathology report disclosed pleomorphic sarcoma with penile metastasis. Symptoms including priapism and inguinal lymph node enlargement progressed rapidly within 2 weeks. He also complained of voiding difficulty with urine retention. The patient died 35 days after admission due to pneumonia with septic shock. CONCLUSION: Penile metasitasis largely occurs from organs in the pelvis. To the best of our knowledge, this is the first case of a teenager with a secondary penile tumor, metastasizing from sarcoma of the bone. It presented as a palpable mass, and then progressed into priapism. The patient had a dismal prognosis and the symptoms progressed faster than his physicians anticipated.

13.
J Phys Chem B ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498631

RESUMO

SWEETs and their prokaryotic counterparts SemiSWEETs were recently classified as transporters that translocate sugar across cellular membranes. SemiSWEETs are commonly used as a model system to infer biological properties of SWEETs; however, this presumes that the homologs are comparable to begin with. We evaluate this presumption by comparing their protein dynamics and substrate transport mechanism using 532 µs of simulation data in conjunction with Markov state models (MSM). MSM weighted conformational landscape plots reveal significant differences between SWEETs and SemiSWEETs despite having similar structural topology. The presence of glucose reduces the free energy barrier between the functionally important intermediate states to enhance the transport process while the substrate has no effect on SemiSWEET. The glucose adopts more rotational degrees of freedom in SWEET while its conformation is restricted for SemiSWEET. Our study provides biological insights on the unexplored novelty of difference in the functional mechanism of two close homologous proteins.

14.
J Foot Ankle Surg ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494030

RESUMO

No consensus had been reached about the optimal treatment for syndesmotic fixation. We performed a review of randomized controlled trials (RCTs) to assist in clarifying many of the controversies that were debated for years despite new technology and options. PubMed, Embase, and the Cochrane Library were searched through specific terms and limits. Only RCTs were selected for final inclusion. Study screening and data extraction were performed independently by 2 reviewers. Thirteen RCTs, including 828 cases, met the inclusion criteria and are summarized in this review. Pooled results demonstrated that dynamic fixation had better functional outcomes as well as lower rates of malreduction and complications compared with syndesmotic screw fixation. Both absorbable screw and tricortical screw fixation showed similar results to quadricortical metallic screws. Therefore, dynamic fixation is recommended for the treatment of syndesmosis injuries.

15.
J Clin Pharm Ther ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31497885

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Pharmacists play vital roles in medicines optimization in different care settings. Studies have shown that optimizing patient's pre-existing co-morbidities prior to the surgery leads to better post-operative outcomes. The Enhanced Surgical medicines optimization service (ESMOS) is an innovative surgical pharmacy service introduced at a large teaching hospital in the UK in September 2017 which aimed to reduce the length of stay and post-operative complications in general surgical patients. This purpose of this study is to evaluate the implementation and outcomes of this service at 12 months after it was rolled out. METHODS: This cohort study was undertaken between September 2017 and September 2018. Adult patients undergoing elective major general surgical procedures were included and stratified into four sub-specialties, including hepato-pancreato-biliary (HPB), upper gastrointestinal (GI), lower GI and vascular surgery. Patients undergoing emergency and day case procedures or with missing outcome data were excluded from this study. Patients' demographics, baseline co-morbidities, high-risk medications, American Society of Anaesthesiologists (ASA) physical status classification, surgical procedure, post-operative complications, length of stay and nature of pharmacist interventions were collected and reported by descriptive statistics. Length of stay was compared with the corresponding expected length of stay by the national standard. RESULTS AND DISCUSSION: A total of 246 patients were included in the four general sub-specialties: HPB (n = 82), upper GI (n = 17), lower GI (n = 87) and vascular (n = 60). There was a significant reduction in the median length of stay in three surgical specialties, compared with the national standard: lower GI (median reduction: -2; IQR: -4, 1.8; P = .038), HPB (median reduction: -4.5; IQR: -7, -1; P = .001) and vascular (median reduction: -2; IQR: -4, 0; P = .043). WHAT IS NEW AND CONCLUSION: The ESMOS model is a novel care pathway that allows both early identification of medicines optimization and peri-operative drug management issues in surgical patients, and potentially reduces the overall length of stay.

16.
Org Lett ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490082

RESUMO

Pentalenolactone is a microbial sesquiterpenoid with antibiotic activity. Its biosynthetic pathway was elucidated by a combination of genetic and biochemical characterizations of all genes involved. For the related neopentalenoketolactone biosynthetic gene cluster from Streptomyces avermitilis, an α-ketoglutarate-dependent mononuclear nonheme iron enzyme, PtlD, was proposed to catalyze both desaturation and olefin epoxidation reactions. Yet, these activities remained to be validated by in vitro biochemical evidence. In this report, we demonstrated that PtlD has multiple activities, including hydroxylation, desaturation, and epoxidation, and confirmed the presence of the elusive epoxide intermediate in a neopentalenoketolactone pathway.

17.
Int J Clin Pract ; : e13415, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508877

RESUMO

BACKGROUND: Epidemiological studies have identified an association between thyroid dysfunction (TD) and various kidney diseases. In this study, the prevalence of TD in type 2 diabetic mellitus (T2DM) patients with diabetic kidney disease (DKD) was evaluated to analyze the potential association between TD and DKD in T2DM patients. METHODOLOGY: A total of 2,108 T2DM patients from Anhui Provincial Hospital were recruited in this study. Demographic and clinical characteristics were collected from 834 T2DM patients with DKD and 1,274 T2DM patients without DKD (non-DKD). All patients were stratified into a number of groups based on UACR (urine albumin-to-creatinine ratio) or eGFR (estimated glomerular filtration rate): e (1) A1: normoalbuminuria (<30), A2: microalbuminuria (30-300), and A3: macroalbuminuria (>300); (2) F1: normal filtration (60-139), F2: hyper filtration (≥ 140), and F3: low filtration (< 60). RESULTS: Significant differences were observed between the non-DKD and DKD groups (P < 0.05) in age, sex ratio, duration, systolic blood pressure, total cholesterol, low density lipoprotein cholesterol, serum creatinine, blood urea nitrogen, free triiodothyronine (FT3), free thyroxine (FT4), and sensitive thyrotropin hormone (sTSH). The macro-albuminuira and low filtration groups had the lowest levels of FT3 and FT4 and the highest level of sTSH, compared with all other groups (P < 0.0167). The prevalence of subclinical hypothyroidism in the DKD group was significantly higher than that in the non-DKD group (χ2 =13.92, P < 0.01). Logistic regression analysis showed that hypothyroidism was associated with increased UACR or reduced eGFR in T2DM patients. Compared to controls, T2DM patients with hypothyroidism exhibited a higher UACR and urinary excretion of transferrin, as well as a lower excretion of urinary Tamm-Horsfall protein (THP) (P<0.0167). CONCLUSION: Subclinical hypothyroidism is more prevalent in T2DM patients with DKD than in T2DM patients without DKD. Hypothyroidism is associated with albuminuria and decreased eGFR in T2DM patients. This article is protected by copyright. All rights reserved.

18.
Cell Death Dis ; 10(9): 676, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515484

RESUMO

Autophagy is recently implicated in regulating vascular smooth muscle cell (SMC) homeostasis and in the pathogenesis of vascular remodeling. Transcription factor EB (TFEB) is a master regulator of autophagy signaling pathways. However, the molecular mechanisms and functional roles of TFEB in SMC homeostasis have not been elucidated. Here, we surveyed the ability of TFEB to regulate autophagy pathway in SMCs, and whether pharmacological activation of TFEB favors SMC homeostasis preventing dedifferentiation and pathogenic vascular remodeling. In primary cultured SMCs, TFEB activator trehalose induced nuclear translocation of TFEB and upregulation of TFEB-controlled autophagy genes leading to enhanced autophagy signaling. Moreover, trehalose suppressed serum-induced SMC dedifferentiation to synthetic phenotypes as characterized by inhibited proliferation and migration. These effects of trehalose were mimicked by ectopic upregulation of TFEB and inhibited by TFEB gene silencing. In animal experiments, partial ligation of carotid arteries induced downregulation of TFEB pathway in the media layer of these arteries. Such TFEB suppression was correlated with increased SMC dedifferentiation and aggravated high-fat diet (HFD)-induced neointima formation. Treatment of mice with trehalose reversed this TFEB pathway suppression, and prevented SMC dedifferentiation and HFD-induced neointima formation. In conclusion, our findings have identified TFEB as a novel positive regulator for autophagy pathway and cellular homeostasis in SMCs. Our data suggest that suppression of TFEB may be an initiating mechanism that promotes SMC dedifferentiation leading to accelerated neointima formation in vascular disorders associated with metabolic stress, whereas trehalose reverses these changes. These findings warrant further evaluation of trehalose in the clinical settings.

19.
J Biomed Mater Res A ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515902

RESUMO

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal (TK) conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid responsive metallic coordinated interaction. The structure and acid responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, FT-IR, DLS and TEM. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated towards HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy. This article is protected by copyright. All rights reserved.

20.
J Mater Chem B ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31517375

RESUMO

A detection and degradation platform was developed to optically quantify the 6-enolate, 8-keto-dG, an important tautomer of mitochondrial mutated DNA 8-oxo-dG. We first found that 6-enolate, 8-keto-dG offers particular fluorescence emission under the conditions between pH ∼ 7 and ∼11. Thus, a mitochondria-targeting photosensitizer NV-12P was prepared to offer simultaneously photoinduced electron transfer and fluorescence resonance energy transfer (FRET) with 6-enolate, 8-keto-dG. Furthermore, NV-12P can also generate a reactive oxygen species to degrade 6-enolate, 8-keto-dG under irradiation conditions. This is the first publication about optical characterization, concentration detection and photodegradation of 6-enolate, 8-keto-dG, either in biological or in vitro applications.

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