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1.
Biomater Sci ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31524211

RESUMO

Doxorubicin (DOX) liposome is a widely used nano-medicine for colorectal cancer treatment. However, doxorubicin therapy increases the level of reactive oxygen species (ROS) in tumor cells, such as hydrogen peroxide (H2O2), which can stabilize hypoxia-inducible-factor-1α (HIF-1α). In a tumor hypoxic microenvironment, HIF-1 can up-regulate tumor-resistance related proteins, including P-glycoprotein (P-gp), glucose transporter 1 (GLUT-1), and matrix metalloproteinase 9 (MMP-9), leading to tumor tolerance to chemotherapy. The functional inhibition of HIF-1 can overcome this resistance and enhance the efficacy of tumor therapy. Here, we encapsulated one of the most effective HIF-1 inhibitors, acriflavine (ACF), and DOX in liposomes (DOX-ACF@Lipo) to construct bifunctional liposomes. ACF and DOX, released from DOX-ACF@Lipo, could effectively suppress the function of HIF-1 and the process of DNA replication, respectively. Consequently, the bifunctional liposome has great potential to be applied in clinics to overcome chemotherapy resistance induced by hypoxia.

2.
Aging Clin Exp Res ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489598

RESUMO

BACKGROUND: There is very limited guidance in regard to how biological age should be estimated and how different comorbidity conditions influence the benefit-risk ration of interventions. Frailty is an important health-related problem in patients, especially in older adults. It is a reflection of biologic rather than chronologic age; frailty may explain why there remains substantial heterogeneity in clinical outcomes within the older patients' population. AIMS: We aimed to review the prognostic value of frailty for adverse outcomes in older patients with acute coronary syndrome (ACS). METHODS: Studies published until December 31, 2018, identified by systematic Medline, Embase, and Cochrane Controlled Register of Trials (CENTRAL) searches were reviewed for the association between frailty and mortality in older patients with ACS. We used the Newcastle-Ottawa Quality Assessment Scale to assess the quality of the included studies. We extracted the information of hazard ratios (HR) and odds ratios (OR) with accompanying 95% confidence intervals (CI), and P values of multivariable analysis. Heterogeneity across studies was determined using the Cochran Q value by Review Manager 5.3. RESULTS: A total of 11 articles involving 7212 patients were included in this meta-analysis. Two studies (Sujino, Y 2015 and Alonso, S.GL 2016; n = 264) reported that frailty was significantly associated with in-hospital mortality in patients with ACS (range of reported OR between 6.38 and 12.0). We performed a subgroup analysis of the other nine studies based on differences in the follow-up time. Pooled meta-analysis demonstrates that frailty was associated with short-term, medium-term, and long-term mortality (HR = 3.67, 4.09, 1.66). There was no association between frailty and bleeding in older patients with ACS. CONCLUSIONS: Frailty measured by Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS), the Edmonton Frail Scale (EFS), Fried score, Green scores, frailty instrument from the Survey of Health, Ageing and Retirement in Europe (SHARE-FI) index, and FRAIL (Fatigue, Resistance, Ambulation, Illnesses, Loss of weight) scale, leads to significantly higher mortality rates in older patients with ACS.

3.
Opt Express ; 27(15): 21843-21855, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510254

RESUMO

We study the controllable optical response in a three-mode optomechanical system comprised of two indirectly coupled cavity modes and an intermediate mechanical mode. The two cavity modes are assumed to have different frequencies and driven by two control fields on the red and blue sidebands, respectively. When the system is perturbed by two probe fields satisfying the specific matching condition, a series of intriguing phenomena can be observed by adjusting phases and amplitudes of the control fields, such as absorption-amplification switching, ultra-narrow response windows, frequency-independent perfect reflection, and ultralong optical group delay. We also compare our system with conventional optomechanical systems to highlight its distinct features. Our results may have potential applications in optical communication and quantum information processing.

4.
Opt Express ; 27(17): 24393-24402, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510328

RESUMO

Output entanglement is a key element in quantum information processing. Here, we show how to obtain optimal entanglement between two filtered output fields in a three-mode optomechanical system. First, we obtain the key analytical expression of optimal time delay between the two filtered output fields, from which we can obtain the optimal coupling for output entanglement without time delay. In this case, our linearized analysis predicts that the entanglement saturates to an optimal value as the optomechanical coupling is increased. Furthermore, we obtain the optimal output entanglement with time delay. These results should be very helpful in conceiving new optomechanical schemes of quantum information processing with their efficiency depending critically on the degree of output entanglement.

5.
BMC Geriatr ; 19(1): 222, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416442

RESUMO

BACKGROUND: Frailty is common and associated with poorer outcomes in the elderly, but its prognostic value in acute coronary syndromes (ACS) requires clarification. We thus undertook a systematic review and meta-analysis to evaluate the relationship between frailty and poor prognosis in patients with ACS. METHODS: We systematically searched PubMed, Embase to find literatures which studied the prognostic value of frailty in elderly patients with ACS. Our main endpoints were the all-cause mortality, cardiovascular disease (CVD), major bleeding and readmissions. We pooled studies using random-effect generic inverse variance method, and conducted three pre-specified subgroup analyses. RESULTS: Of 1216 identified studies, 15 studies were included in our analysis. Compared with the normal group, frailty (HR = 2.65; 95%CI: 1.81-3.89, I2 = 60.2%) and pre-frailty (HR = 1.41; 95%CI: 1.19-1.66, I2 = 0%) were characterized by a higher risk of mortality after adjustment. Frailty also was associated with increased risk of any-type CVD, major bleeding and hospital readmissions in elderly patients with ACS. The pooled effect sizes in frail patients were 1.54 (95%CI: 1.32-1.79), 1.51 (95%CI: 1.14-1.99) and 1.51 (95%CI: 1.09-2.10). CONCLUSIONS: Frailty provides quantifiable and significant prognostic value for mortality and adverse events in elderly ACS patients, helping doctors to appraise the comprehensive prognosis risk and to applicate appropriate management strategies.

6.
Ital J Pediatr ; 45(1): 87, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331363

RESUMO

BACKGROUND: The purpose of this study was to analyze the growth status and to identify the risk factors that influence the catch-up growth of preterm infants after discharge and to provide evidence for feeding strategies and the need for further research. METHODS: A descriptive correlational analysis was applied. The sample consisted of 309 preterm infants and their caregivers selected from June to August 2017 from five women's and children's hospitals. Self-designed questionnaires based on knowledge, attitude and practice and the Health Belief Model (HBM) were used to measure the catch-up growth status of preterm infants after discharge. Logistic regression was used to determine the risk factors for the catch-up growth of preterm infants. RESULTS: The results showed that of 309 preterm infants, only 14 (4.5%) were underweight, and 52 (17.4%) did not meet the criteria for catch-up growth at 12 months of actual age. The logistic regression analysis showed that gestational age, regular health care, caregivers' educational background, mothers' daily contact with the baby, monthly average family income, the addition of a breast milk supplement, and daily milk volume were risk factors that affected the catch-up growth of preterm infants after discharge. CONCLUSIONS: The rate of catch-up growth of preterm infants is still not high. We should pay much more attention to preterm infants of small gestational age and guide their child care on a regular basis to detect and correct risk factors in a timely fashion, especially those involving lower daily milk volume, lower degree of culture and family economic difficulties. Second, we suggest that the government publish relevant policy that appropriately increases the length of maternity leave for preterm mothers. Future studies should have larger sample sizes and explore other important factors influencing the catch-up growth of preterm infants.

7.
Biosci Rep ; 39(7)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31292167

RESUMO

As a major cause of blindness, diabetic retinopathy (DR) is often found in the developed countries. Our previous study identified a down-regulated miRNA: miR-144-3p in response to hyperglycemia. The present study aims to investigate the role of miR-144-3p in proliferation of microvascular epithelial cells. Endothelial cells were treated with different concentrations of glucose, after which miR-144-3p were detected with real-time PCR assay. MiR-144-3p mimics or inhibitors were used to increase or knockdown the level of this miRNA. Western blotting assay and ELISA assay were used to measure the expression and concentration of VEGF protein. 5-Bromo-2-deoxyUridine (BrdU) labeled cell cycle assay was used to detect cells in S phase. MiRNA targets were predicted by using a TargetScan tool, and were further verified by luciferase reporter assay. In the present study, we focussed on a significantly down-regulated miRNA, miR-144-3p, and investigated its role in high glucose (HG) induced cell proliferation. Our data showed that miR-144-3p mimics significantly inhibited HG induced cell proliferation and reduced the percentage of cells in S phase. HG induced up-regulation of VEGF was also prohibited by miR-144-3p mimics. Through wound-healing assay, we found that miR-144-3p suppressed cell migration after HG treatments. Moreover, we predicted and proved that fibroblast growth factor (FGF)16 is a direct target of miR-144-3p. Finally, miR-144-3p attenuated HG induced MAPK activation. In conclusion, we demonstrated that miR-144-3p inhibited high glucose-induced cell proliferation through suppressing FGF16 and MAPK signaling pathway, suggesting a possible role of miR-144-FGF16 in the development of DR.

8.
Proc Natl Acad Sci U S A ; 116(24): 11972-11977, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31142648

RESUMO

Cancer immunotherapy can stimulate and enhance the ability of the immune system to recognize, arrest, and eliminate tumor cells. Immune checkpoint therapies (e.g., PD-1/PD-L1) have shown an unprecedented and durable clinical response rate in patients among various cancer types. However, a large fraction of patients still does not respond to these checkpoint inhibitors. The main cause of this phenomenon is the limited T-cell infiltration in tumors. Therefore, additional strategies to enhance T-cell trafficking into tumors are urgently needed to improve patients' immune responses. In this study, we screened an array of perfluorocarbon compounds, reporting that albumin-based perfluorotributylamine nanoparticles (PFTBA@Alb) can effectively increase the permeability of tumor blood vessels, and no distinct side effects were found on normal blood vessels. After i.v. administration of PFTBA@Alb, the number of tumor-infiltrating CD8+ and CD4+ T cells showed an obvious rising trend. More important, a striking tumor inhibition rate, reaching nearly 90%, was observed when combining PFTBA@Alb with anti-PD-L1 antibody. These findings suggest that PFTBA@Alb can be regarded as an enhancer for anti-PD-L1 immunotherapy.

9.
Stem Cells Dev ; 28(12): 791-798, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30950325

RESUMO

Aberrant microRNA expression correlates with age-related osteoporosis, which impairs bone formation by regulating osteoblastic activity, thus leading to age-related bone loss. In this study, we observed that miR-384-5p was significantly upregulated in bone marrow mesenchymal stem cells (BMSCs) from aged rats compared with BMSCs from young rats. In vitro functional assays revealed that overexpression of miR-384-5p in young BMSCs inhibited osteogenic differentiation and accelerated senescence, whereas knockdown of miR-384-5p in aged BMSCs had the opposite effects. Furthermore, we demonstrated that miR-384-5p inhibited the expression of Gli2 at both the mRNA and protein levels by directly binding to the 3' untranslated region of Gli2 mRNA. The osteogenic capacity of Gli2-knockdown BMSCs was rejuvenated by miR-384-5p inhibition. Finally, in vivo assays showed that the inhibition of miR-384-5p prevented bone loss and increased the osteogenic capacity in aged rats. Overall, our study suggests that miR-384-5p functions as a negative regulator of osteogenesis, indicating that the inhibition of miR-384-5p may be a therapeutic strategy against age-related bone loss.

10.
Nat Commun ; 10(1): 1580, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952842

RESUMO

Hypoxia-based agents (HBAs), such as anaerobic bacteria and bioreductive prodrugs, require both a permeable and hypoxic intratumoural environment to be fully effective. To solve this problem, herein, we report that perfluorocarbon nanoparticles (PNPs) can be used to create a long-lasting, penetrable and hypoxic tumour microenvironment for ensuring both the delivery and activation of subsequently administered HBAs. In addition to the increased permeability and enhanced hypoxia caused by the PNPs, the PNPs can be retained to further achieve the long-term inhibition of intratumoural O2 reperfusion while enhancing HBA accumulation for over 24 h. Therefore, perfluorocarbon materials may have great potential for reigniting clinical research on hypoxia-based drugs.


Assuntos
Antineoplásicos/administração & dosagem , Fluorcarbonetos/farmacologia , Pró-Fármacos/administração & dosagem , Tirapazamina/administração & dosagem , Microambiente Tumoral , Animais , Antineoplásicos/farmacologia , Hipóxia Celular , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Fluorcarbonetos/química , Camundongos , Nanopartículas/química , Pró-Fármacos/farmacologia , Tirapazamina/farmacologia , Hipóxia Tumoral
11.
Fish Shellfish Immunol ; 88: 496-507, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826414

RESUMO

In this study, two experiments were performed to explore the effect of Radix Bupleuri extracts (RBE) on growth, lipid deposition and metabolism and immune response of hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀) using in vitro and in vivo models. In vitro, we used 2 ml/L 20% lipid emulsion (LE)-induced steatosis in hybrid grouper primary hepatocytes, then RBE (200, 400 and 800 µg/ml) was added to the hepatocytes after (post-treatment) the incubation with 20% LE (2 ml/L) in the culture medium. We found that RBE markedly increased cell viability, which were consistent with hepatocytes morphological structure examination and lipid metabolism and immune related genes study. The above result suggested that RBE has a protective effect on this model of hepatocytes damage. In vivo, five graded levels of RBE at 0, 200, 400, 800 and 1600 mg/kg diet were supplemented to a basal diet with 15% lipid levels (high lipid), and fed to a total of 300 hybrid grouper with an average initial weight of 25.58 ±â€¯0.05 g for 8 weeks. Growth performance, liver histology, plasma biochemical parameters, and expression of genes involved in lipid metabolism and immune-related were measured. The study indicated that dietary RBE significantly improved growth performance and feed utilization and reduced hepatosomatic index. Dietary supplementation with 200-800 mg/kg RBE diets effectively decreased serum ALP, ALT, AST and LDH contents in fish. Furthermore, adipogenesis relative mRNA levels of DGAT2, G6PD, ME1 and DGKα in fish fed 200-400 mg/kg RBE diets were lower (P < 0.05) than in those fed RBE0 diets, while dietary supplementation with 200-800 mg/kg RBE diets up-regulated lipolysis-related genes (CPT1, LPL and PPARα) expression in the liver of hybrid grouper. Moreover, dietary RBE down-regulated the expression of apoptosis-related genes (caspase-9), up-regulated the expression of antioxidant genes (CAT) and immune-related genes (MHC2, IKKα and TGF-ß1). Thus, our data suggest that RBE suppressed lipid accumulation and enhanced immune capability in hybrid grouper both in vitro and in vivo. These results offer new insight into RBE as a hepatoprotective in fish.


Assuntos
Bass/imunologia , Suplementos Nutricionais/análise , Fígado Gorduroso/veterinária , Hepatócitos/metabolismo , Metabolismo dos Lipídeos , Extratos Vegetais/administração & dosagem , Ração Animal/análise , Animais , Apoptose , Bass/genética , Bass/crescimento & desenvolvimento , Caspase 9/genética , Sobrevivência Celular , Células Cultivadas , Fígado Gorduroso/tratamento farmacológico , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Hibridização Genética , Lipólise , Fígado/imunologia , Fígado/metabolismo , Masculino , Raízes de Plantas/química , RNA Mensageiro
12.
J Biomed Nanotechnol ; 15(1): 42-61, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30480514

RESUMO

For the effective inhibition of atherosclerotic plaque rupture, there is an urgent need to develop a carrier which can specifically deliver the therapeutic agents to atherosclerotic lesions. Since the representative hallmark of plaques in advanced atherosclerosis is the large number of macrophages which highly upregulate folate receptor beta (FR-ß), we herein investigated the potential of folate-modified liposomes (FA-P-LP) as the carrier for active targeting of atherosclerotic plaques. In vitro cellular uptake tests, FA-P-LP exhibited an enhanced uptake in activated RAW264.7 macrophages with high expression of FR-ß, whereas this enhanced effect was dramatically diminished when the cells were pretreated with excess amount of free folate, indicating that FA-P-LP were mainly taken up by the receptor-mediated endocytosis. From the in vivo distribution assay, it was confirmly demonstrated that FA-P-LP significantly accumulated in atherosclerotic lesions and were co-localized with macrophages within plaques. Thereafter, we utilized the FA-P-LP to deliver an angiotensin receptor blocker (ARB), telmisartan (Tel), to macrophages in atherosclerotic plaques and evaluated their therapeutic effects on plaque destabilization. After 12 weeks treatment in ApoE-/- mice with established atherosclerosis, FA-P-LP/Tel exerted a marked improvement in key advanced plaque properties without affecting the plasma lipid level and blood pressure. These beneficial effects include the regression of atherosclerotic plaques possibly attributing to the enhanced cellular cholesterol efflux and reduced macrophage infiltration, an increase in the protective collagen layer overlying lesions resulting from suppression of collagenase activity and decrease in matrix 2/9 (MMP 2/9) expression, suppression of oxidative stress, and a reduction in plaque necrosis and calcification. Thus, administration of Tel in a targeted liposome could stabilize the advanced atherosclerotic lesions independent of lipid lowering and blood pressure decrease. In conclusion, FA-P-LP could effectively home to the atherosclerotic lesion through the active targeting mechanism after systemic administration, indicating their high potential as the carrier for atherosclerosis therapy. Together, the FA-P-LP/Tel would be considered as a promising nanotherapeutic approach to prevent plaque rupture, providing an alternative regimen for clinical treatment of advanced atherosclerosis.


Assuntos
Aterosclerose , Animais , Apolipoproteínas E , Ácido Fólico , Lipossomos , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Telmisartan
13.
Chin J Nat Med ; 16(11): 846-855, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30502766

RESUMO

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg-1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.

14.
Theranostics ; 8(18): 4898-4911, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30429876

RESUMO

Tumors are usually hypoxic, which limits the efficacy of current tumor therapies, especially radiotherapy in which oxygen is essential to promote radiation-induced cell damage. Herein, by taking advantage of the ability of perfluorocarbon (PFC) to promote red blood cell penetration, we developed a simple but effective two-stage oxygen delivery strategy to modulate the hypoxic tumor microenvironment using PFC nanoparticles. Methods: We first examined the two-stage oxygen delivery ability of PFC nanoparticles on relieving tumor hypoxia through platelet inhibition. To evaluate the effect of PFC nanoparticles on radiation sensitization, CT26 tumor and SUM49PT tumor model were used. Results: In this study, PFC was encapsulated into albumin and intravenously injected into tumor-bearing mice without hyperoxic breathing. After accumulation in the tumor, PFC nanoparticles rapidly released the oxygen that was physically dissolved in PFC as the first-stage of oxygen delivery. Then, PFC subsequently promoted red blood cell infiltration, which further released O2 as the second-stage of oxygen delivery. Conclusion: The hypoxic tumor microenvironment was rapidly relieved via two-stage oxygen delivery, effectively increasing radiotherapy efficacy. The safety of all substances used in this study has been clinically demonstrated, ensuring that this simple strategy could be rapidly and easily translated into clinical applications to solve the clinical problems associated with tumor hypoxia.

15.
Biomater Sci ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30420976

RESUMO

Abraxane® (Abx), an FDA approved albumin-bound paclitaxel nano-formulation, is one of the most common chemical drugs for the treatment of metastatic triple-negative breast cancer (mTNBC). However, acquired resistance and metastasis are critical factors that limit the treatment of mTNBC by Abx. In particular, both the tumor hypoxic microenvironment and the increase in hydrogen peroxide (H2O2) levels via paclitaxel stimulation primarily mediate the resistance to chemotherapy, where multiple drug resistance proteins such as P-gp and tumor invasion-related cytokines such as VEGF are continuously activated to pump out chemical drugs and aggravate tumor metastasis, respectively. Therefore, it is of great importance to combine tumor oxygenation with commercial chemical drugs for overcoming the acquired resistance and metastasis. In this study, a facile method was developed to deposit manganese dioxide (MnO2) onto the surface of Abraxane® (Abx) to form MnO2-modified Abx (M-Abx). The modification process did not change the critical characteristics of the parent Abx, which might have great potential for application in clinics for the treatment of mTNBC. Tumor oxygenation mediated by M-Abx specifically occurs within the H2O2-overexpressed tumor microenvironment, and significantly downregulates the content of tumor progression-related proteins, such as HIF-1α, P-gp, and VEGF. Ultimately, M-Abx treatment results in about a 2-fold increase in inhibition efficiency of tumor growth in both primary and metastatic tumors compared with traditional Abx therapy. Therefore, oxygen-rich chemotherapy was realized to efficiently sensitize paclitaxel, relieve acquired resistance and inhibit tumor metastasis.

16.
Int J Pharm ; 553(1-2): 21-28, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30316795

RESUMO

The aim of this study is to investigate the potential of D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) modified nanoliposomes as an ophthalmic delivery system of brinzolamide (Brz) for glaucoma treatment. The Brz loaded nanoliposomes containing TPGS (T-LPs/Brz) were firstly developed by a thin-film dispersion method. The average particle size was 96.87 ±â€¯4.43 nm. The entrapment efficiency of the Brz was 95.41 ±â€¯3.03% and the drug loading was 4.00 ±â€¯0.13%. T-LPs/Brz exhibited obvious sustained release of Brz; in stark contrast to the normal liposomes of Brz (LPs/Brz) and the commercial formulation AZOPT® (Brz ophthalmic suspension, Brz-Sus). Enhanced trans-corneal transport of Brz was achieved with T-LPs/Brz. Compared with both Brz-Sus and LPs/Brz, the apparent permeability coefficient (Papp) of T-LPs/Brz was 10.2 folds and 1.38 folds higher, respectively. Moreover, T-LPs/Brz extended the cornea residence of Brz. White New Zealand rabbits treated with T-LPs/Brz had 3.18 folds and 1.57 folds Brz concentration 2 h after treatment than Brz-Sus and LPs/Brz, respectively. Further pharmacodynamic studies showed that T-LPs/Brz maintained an effective intraocular pressure (IOP) reduction from 3 h to 11 h after administration, while Brz-Sus and LPs/Brz presented effective IOP decreases from 3 h to 6 h and 3 h to 8 h respectively. The preliminary safety evaluation demonstrated that T-LPs/Brz had no significant side effects; specifically, no cornea damage and eye irritation. All the results indicated that TPGS modified nanoliposomes were a promising ocular delivery carriers for Brz to treat glaucoma. As such, T-LPs/Brz might be worthy of further translational study.

17.
Small ; 14(45): e1801694, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30307696

RESUMO

Currently, limited tumor drug permeation and poor oxygen perfusion are two major bottlenecks that significantly impair the efficacy of existing antitumor drugs, especially oxygen-sensitive antitumor drugs. One vital cause of these major bottlenecks is the abnormal tumor vessel barrier. To the best knowledge of the authors, platelets play a vital role in the maintenance of an abnormal tumor blood barrier through platelet-tumor interaction. Thus, platelet inhibition may present a new way to enhance drug delivery. In this study, it is originally discovered that perfluorotributylamine-based albumin nanoparticles (PFTBA@HSA) possess excellent platelet inhibiting abilities, which then selectively disrupt the tumor vessel barrier, resulting in a remarkably enhanced intratumoral drug accumulation. Interestingly enough, the tumor hypoxia is also obviously relieved by enhanced oxygen carrier red blood cell distribution and PFTBA@HSA infiltration in the tumors. Finally, the efficacy of oxygen-sensitive antitumor drugs is significantly amplified by PFTBA@HSA owing to enhanced drug permeation and relieved tumor hypoxia. Therefore, for the first time, it is demonstrated that PFTBA@HSA could be used as an effective way to improve the efficacy of existing tumor therapies by disrupting tumor vessel barriers through targeted platelet inhibition.

18.
Front Pharmacol ; 9: 980, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233368

RESUMO

Liposomes (LPs) as commonly used mRNA delivery systems remain to be rationally designed and optimized to ameliorate the antigen expression of mRNA vaccine in dendritic cells (DCs). In this study, we synthesized mannose-cholesterol conjugates (MPn-CHs) by click reaction using different PEG units (PEG100, PEG1000, and PEG2000) as linker molecules. MPn-CHs were fully characterized and subsequently used to prepare DC-targeting liposomes (MPn-LPs) by a thin-film dispersion method. MPn-LPs loaded with mRNA (MPn-LPX) were finally prepared by a simple self-assembly method. MPn-LPX displayed bigger diameter (about 135 nm) and lower zeta potential (about 40 mV) compared to MPn-LPs. The in vitro transfection experiment on DC2.4 cells demonstrated that the PEG length of mannose derivatives had significant effect on the expression of GFP-encoding mRNA. MP1000-LPX containing MP1000-CH can achieve the highest transfection efficiency (52.09 ± 4.85%), which was significantly superior to the commercial transfection reagent Lipo 3K (11.47 ± 2.31%). The optimal DC-targeting MP1000-LPX showed an average size of 132.93 ± 4.93 nm and zeta potential of 37.93 ± 2.95 mV with nearly spherical shape. Moreover, MP1000-LPX can protect mRNA against degradation in serum with high efficacy. The uptake study indicated that MP1000-LPX enhanced mRNA expression mainly through the over-expressing mannose receptor (CD206) on the surface of DCs. In conclusion, mannose modified LPs might be a potential DC-targeting delivery system for mRNA vaccine after rational design and deserve further study on the in vivo delivery profile and anti-tumor efficacy.

19.
J Evid Based Med ; 11(4): 242-245, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30094948

RESUMO

BACKGROUND: Depression is an independent risk factor in coronary artery disease (CAD). Our objective was to evaluate the impact of depression on heart rate variability (HRV) in patients with stable CAD. METHODS: This study included patients with a stable CAD who admitted to our hospital in the geriatric medical center from August 2016 to December 2016. All patients agreed to participate in the study and sign informed consent. The study group included 90 CAD patients with a diagnosis of depression and 99 CAD patients without depression. All study population underwent a 24-hour Holter recording for HRV. The depression was assessed by 5-Item Geriatric Depression. RESULTS: There was a linear correlation between age and HRV. There were no significant differences in heart rate variability between male and female patients, married and unmarried/widowed, smoking and nonsmoking, drinking and nondrinking groups. Multiple linear regression analysis showed that there were correlations between depression and HRV. ß-blockers were associated with SDNN, SDANN, SDNN index, and RMSSD in HRV. CONCLUSION: Depression is an important risk factor for heart rate variability in elderly patients with CAD. Clinicians should pay attention for evaluation of depressive patients with CAD.

20.
Cell Mol Biol (Noisy-le-grand) ; 64(10): 66-72, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30084797

RESUMO

Near-Infrared (NIR) dyes, with improved tissue penetration, minimal invasiveness and high specificity, have gained great interests in diagnosing and treating tumors. However, the poor solubility in aqueous medium and low 1O2 quantum yields of NIR dyes restrict their application in PDT (photodynamic therapy) research. Herein, a novel nanosystem with modifying the NIR dyes and encapsulating perfluorocarbon is reported for improving the PDT effectiveness of NIR dyes. By adding the PEG2000-SH and the C13 carbon chain to a NIR representative dye IR780, the new formed material PEG-IR780-C13 shows good solubility in water. Then PFTBA was encapsulated into PEG-IR780-C13 to form a nanosystem (PFTBA@PEG-IR780-C13). When exposed to laser irradiation, the nanosystem showed enhanced production of 1O2 and significantly increased PDT both in vivo and in vitro. Therefore, this work provides an approach for design and application of NIR dyes.


Assuntos
Antineoplásicos/química , Corantes/química , Fluorcarbonetos/química , Indóis/química , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Corantes/uso terapêutico , Fluorcarbonetos/uso terapêutico , Humanos , Indóis/uso terapêutico , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Polietilenoglicóis/uso terapêutico , Solubilidade
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