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1.
Food Chem ; 336: 127707, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32763737

RESUMO

Anthocyanins (ACNs) are naturally derived colorants and antioxidants added to manufactured foods. ACNs were encapsulated in nanocomplexes with chitosan hydrochloride (CHC), carboxymethyl chitosan (CMC) and whey protein isolate (WPI). The ACN-loaded CHC/CMC-WPI nanocomplexes (ACN-CHC/CMC-WPI) showed a preferred particle size (332.20 nm) and zeta potential (+23.65 mV) and a high encapsulation efficiency (60.70%). ACN-CHC/CMC-WPI nanocomplexes exhibited a smooth spherical shape by transmission electron microscopy. Fourier transform infrared (FT-IR) and Raman spectroscopy confirmed interactions between the ACNs and the encapsulation materials (CHC/CMC-WPI). The nanocomplexes or the nanocomplexes incorporated into coffee beverage better protected ACNs at high temperature compared to the unencapsulated ACNs. In simulated gastrointestinal fluids, the ACNs in the ACN-CHC/CMC-WPI were more stable and more slower released over time. The nanocomplexes maintained high DPPH and hydroxyl free radical scavenging activities. This study indicated that CHC/CMC-WPI nanocomplexes can improve the thermal stability and slow the release of ACNs added to food products.

2.
BMC Ophthalmol ; 20(1): 397, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028265

RESUMO

BACKGROUND: To analyse short-term changes in the anterior segment and retina after small incision lenticule extraction (SMILE). METHODS: Patients with myopia scheduled for SMILE were recruited from Ruijin Hospital, Shanghai, China. Basic patient information such as age, sex, and refractive errors was recorded. Ocular measurements were taken before surgery, and 1 day and 1 week after surgery; they included axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white (WTW), pupil diameter (PD), macular thickness (MT), ganglion cell layer thickness (GCL), retinal nerve fiber layer thickness (RNFL), choroidal thickness (CT), macular vessel density, and optic disc vessel density. RESULTS: Sixty-one eyes of 31 patients were selected for this study. AL, CCT, ACD, and postoperative PD were significantly reduced (p < 0.05), while LT was thickened after surgery (p < 0.05). MT at the fovea decreased 1 day and 1 week after surgery (p < 0.05). GCL showed no significant changes after surgery. RNFL was unchanged 1 day after surgery, but the inferior sector was thickened 1 week after surgery. CT was thicker at the fovea 1 day after surgery and 1.0 mm from the fovea in the nasal sector 1 week after surgery. Macular vessel density was significantly decreased 1 day after surgery and most recovered in 1 week. Optic disc vessel density decreased at the peripapillary part 1 day after surgery and recovered after 1 week. ΔACD and ΔLT showed no significant correlation 1 day after surgery. ΔACD was negatively correlated with ΔLT and sphere 1 week after surgery (r = - 0.847, p < 0.000; r = - 0.398, p = 0.002). ΔLT was positively correlated with the sphere 1 week after surgery (r = 0.256, p = 0.048). CONCLUSION: The anterior segment was the most affected, while the retina also underwent changes with regard to MT, RNFL, CT, macular vessel density, and peripapillary vessel density.

3.
Proc Natl Acad Sci U S A ; 117(41): 25628-25633, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-32999068

RESUMO

The realization of the vast potential of digital PCR (dPCR) to provide extremely accurate and sensitive measurements in the clinical setting has thus far been hindered by challenges such as assay robustness and high costs. Here we introduce a lossless and contamination-free dPCR technology, termed CLEAR-dPCR, which addresses these challenges by completing the dPCR sample preparation, PCR, and readout all in one tube. Optical clearing of the droplet dPCR emulsion was combined with emerging light-sheet fluorescence microscopy, to acquire a three-dimensional (3D) image of a half million droplets sealed in a tube in seconds. CLEAR-dPCR provides ultrahigh-throughput readout results in situ and fundamentally eliminates the possibility of either sample loss or contamination. This approach exhibits improved accuracy over existing dPCR platforms and enables a greatly increased dynamic range to be comparable to that of real-time quantitative PCR.

5.
Adv Mater ; : e2004481, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015905

RESUMO

Simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT) can reduce the risks of drug leakage, body burden, and preparation complexity in traditional combination PDT/PTT. Here, a versatile nanoporphyrin (Pp18-lipos) self-assembled from lipid-purpurin 18 conjugates (Pp18-lipids) and pure lipids is presented. The as-prepared Pp18-lipos with 2 mol% Pp18-lipids can perform effective PDT and fluorescence imaging. The Pp18-lipos with 65 mol% Pp18 can perform potent PTT and photoacoustic imaging. The chelation of Mn2+ endows the Pp18-lipids-Mn2+ a high T1 -weighted magnetic resonance imaging contrast. Notably, pretreatment of low-dose PDT facilitates the endocytosis and tumor accumulation of Pp18-lipos, thus achieving synergistic PDT/PTT. Upon exposure to a single 705 nm-laser, the combination of PDT/PTT achieves a significantly higher tumor growth inhibition rate than PDT or PTT alone. In addition, it is found that the synergistic PDT/PTT triggers more potent anti-tumor immune response including tumor infiltration of immune cells and release of related cytokines.

6.
Front Immunol ; 11: 2112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013889

RESUMO

Adult-onset Still's disease (AOSD) is a systemic, multigenic autoinflammatory disease, and the diagnosis of AOSD must rule out neoplasms, infections, and other autoimmune diseases. Development of a rapid and efficient but non-invasive diagnosis method is urgently needed for improving AOSD therapy. In this study, we first performed a urinary proteomic study using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis in patients with AOSD and healthy control (HC) subjects. The urinary proteins were enriched in pathways of the innate immune system and neutrophil degranulation, and we identified that the α-1-acid glycoprotein 1 (LRG1), orosomucoid 1 (ORM1), and ORM2 proteins were highly expressed in patients with AOSD. The elevated urine levels of LRG1, ORM1, and ORM2 were further validated by enzyme-linked immunosorbent assay in active patients with AOSD, disease controls, and HC subjects. Receiver operating characteristic curves showed that the areas under the curve of LRG1, ORM1, and ORM2 were 0.700, 0.837, and 0.736, respectively (all p < 0.05). Furthermore, we found that the urine levels of LRG1, ORM1, and ORM2 were positively correlated with the systemic score and erythrocyte sedimentation rate and that the urine levels of LRG1 were positively correlated with interleukin 1ß (IL-1ß), IL-6, and IL-18 levels, whereas the urine levels of ORM1 were positively correlated with the IL-1ß level. Together, our study identified novel urinary markers for non-invasive and simple screening of AOSD.

7.
Int J Biol Sci ; 16(15): 2761-2774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061794

RESUMO

Phosphoinositides are membrane lipids generated by phosphorylation on the inositol head group of phosphatidylinositol. By specifically distributed to distinct subcellular membrane locations, different phosphoinositide species play diverse roles in modulating membrane trafficking. Among the seven known phosphoinositide species, phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is the one species most abundant at the plasma membrane. Thus, the PI4,5P2 function in membrane trafficking is first identified in controlling plasma membrane dynamic-related events including endocytosis and exocytosis. However, recent studies indicate that PI4,5P2 is also critical in many other membrane trafficking events such as endosomal trafficking, hydrolases sorting to lysosomes, autophagy initiation, and autophagic lysosome reformation. These findings suggest that the role of PI4,5P2 in membrane trafficking is far beyond just plasma membrane. This review will provide a concise synopsis of how PI4,5P2 functions in multiple membrane trafficking events. PI4,5P2, the enzymes responsible for PI4,5P2 production at specific subcellular locations, and distinct PI4,5P2 effector proteins compose a regulation network to control the specific membrane trafficking events.

8.
Biomed Microdevices ; 22(4): 75, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079273

RESUMO

Being easy, safe and reliable, non-invasive prenatal diagnosis (NIPD) has been greatly pursued in recent years. Holding the complete genetic information of the fetus, fetal nucleated red blood cells (fNRBCs) are viewed as a suitable target for NIPD application. However, effective separating fNRBCs from maternal peripheral blood for clinic use still faces great challenges, given that fNRBCs are extremely rare in maternal blood circulation. Here, by combining the high-throughput inertial microfluidic chip with multifunctional microspheres as size amplification, we develop a novel method to isolate fNRBCs with high performance. To enlarge the size difference between fNRBCs and normal blood cells, we use the gelatin coated microspheres to capture fNRBCs with anti-CD147 as specific recognizer at first. The size difference between fNRBCs captured by the microspheres and normal blood cells makes it easy to purify the captured fNRBCs through the spiral microfluidic chip. Finally, the purified fNRBCs are mildly released from the microspheres by enzymatically degrading the gelatin coating. Cell capture efficiency about 81%, high purity of 83%, as well as cell release viability over 80% were achieved using spiked samples by this approach. Additionally, fNRBCs were successfully detected from peripheral blood of pregnant women with an average of 24 fNRBCs per mL, suggesting the great potential of this method for clinical non-invasive prenatal diagnosis.

9.
Adv Mater ; : e2004853, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33089578

RESUMO

Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regulatory protein alpha (SIRPα) on macrophages to CD47, a "don't eat me" signal on cancer cells, prevents macrophage phagocytosis of cancer cells. Second, colony stimulating factors, secreted by cancer cells, polarize tumor-associated macrophages (TAMs) to a tumorigenic M2 phenotype. Here, it is reported that genetically engineered cell-membrane-coated magnetic nanoparticles (gCM-MNs) can disable both mechanisms. The gCM shell genetically overexpressing SIRPα variants with remarkable affinity efficiently blocks the CD47-SIRPα pathway while the MN core promotes M2 TAM repolarization, synergistically triggering potent macrophage immune responses. Moreover, the gCM shell protects the MNs from immune clearance; and in turn, the MN core delivers the gCMs into tumor tissues under magnetic navigation, effectively promoting their systemic circulation and tumor accumulation. In melanoma and breast cancer models, it is shown that gCM-MNs significantly prolong overall mouse survival by controlling both local tumor growth and distant tumor metastasis. The combination of cell-membrane-coating nanotechnology and genetic editing technique offers a safe and robust strategy in activating the body's immune responses for cancer immunotherapy.

10.
J Investig Med ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077486

RESUMO

MicroRNA-363-3 p (miR-363-3 p) has been reported to play a crucial role in tumor development and progression, and function as a tumor suppressor in many types of cancer. In our previous studies, we found that miRNA-363-3 p inhibited papillary thyroid carcinoma (PTC) progression by targeting PIK3CA. Meanwhile, we found that NIN1/RPN12 binding protein 1 (NOB1) was significantly upregulated in thyroid carcinoma tissue and downregulation of NOB1 expression significantly inhibited cell proliferation, migration and invasion in PTC. However, the correlation of NOB1 and miR-363-3 p has not been investigated. Here, we performed bioinformatic analysis to explore miRNA targeting NOB1. We found that NOB1 was a target of miR-363-3 p and miR-363-3 p regulated NOB1 expression at the translational and transcriptional levels by targeting its 3' untranslated region (3'-UTR). Further, we showed that miR-363-3 p inhibited tumor progression by targeting NOB1 in vitro and in vivo. We found that overexpression miR-363-3 p or silencing NOB1 significantly increased G0/G1-phase and decreased S-phase in the human papillary thyroid cells, which led to a significant delay in cell proliferation, indicating miR-363-3 p and NOB1 are crucial for human papillary thyroid cancer tumorigenesis. Collectively, our data unveil that miR-363-3 p negatively regulates NOB1 activity by reducing its stability. This study provides a new therapeutic target for regulation of NOB1 stability to modulate human papillary thyroid cancer progression.

11.
Metab Brain Dis ; 35(8): 1431-1432, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33064265

RESUMO

In the original published article: A wrong GFAP immunohistochemistry staining image was inadvertently chosen to present as Control group image (the published Fig.1B).

12.
Sci Rep ; 10(1): 17673, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077778

RESUMO

Nature reserves play an extraordinarily important role in conserving animal populations and their habitats. However, landscape change and unreasonable zoning designations often render these protected areas inadequate. Therefore, regular evaluation of the efficacy of protected lands is critical for maintaining and improving management strategies. Using species distribution models and GAP analysis, we assessed the changes in suitable habitat for the Brown Eared-pheasant (Crossoptilon mantchuricum) in two Chinese nature reserves between 1995 and 2013. Our results showed that the habitat suitability of Brown Eared-pheasant has changed dramatically during this period, and fragmentation analyses showed an increase in concentration area and decrease in patch area. In particular, our findings show that the national nature reserves need to adjust their ranges to ensure the conservation of this flagship species. Our study further provides a new viewpoint for evaluating the efficacy of protected lands, particularly in highly urbanized regions where conservation goals must be balanced with changing landscapes.

14.
Mol Ecol Resour ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010101

RESUMO

The blue king crab, Paralithodes platypus, which belongs to the family Lithodidae, is a commercially and ecologically important species. However, a high-quality reference genome for the king crab has not yet been reported. Here, we assembled the first chromosome-level blue king crab genome, which contains 104 chromosomes and an N50 length of 51.15 Mb. Furthermore, we determined that the large genome size can be attributed to the insertion of long interspersed nuclear elements and long tandem repeats. Genome assembly assessment showed that 96.54% of the assembled transcripts could be aligned to the assembled genome. Phylogenetic analysis showed the blue king crab to have a close relationship with the Eubrachyura crabs, from which it diverged 272.5 million years ago. Population history analyses indicated that the effective population of the blue king crab declined sharply and then gradually increased from the Cretaceous and Neogene periods, respectively. Furthermore, gene families related to developmental pathways, steroid and thyroid hormone synthesis, and inflammatory regulation were expanded in the genome, suggesting that these genes contributed substantially to the environmental adaptation and unique body plan evolution of the blue king crab. The high-quality reference genome reported here provides a solid molecular basis for further study of the blue king crab's development and environmental adaptation.

15.
Med Sci Monit ; 26: e925987, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010148

RESUMO

BACKGROUND Studies have shown that dapagliflozin has antihypertensive effects. However, the effects and mechanisms of dapagliflozin on ambulatory blood pressure (ABP) have not been fully evaluated. In this study, we aimed to evaluate the effects of dapagliflozin treatment on ABP in patients with type 2 diabetes and hypertension. MATERIAL AND METHODS Patients were prospectively enrolled and divided into 2 groups: dapagliflozin treatment group (n=182) and no dapagliflozin treatment group (n=304). Clinical characteristics and measures of treatment, serum uric acid (SUA), 24-h urinary UA (UUA) excretion, and 24-h ABP were collected. The effects and mechanisms of dapagliflozin on 24-h ABP were evaluated. RESULTS After 3 months, the patients without dapagliflozin treatment had higher SUA, lower 24-h UUA excretion, and higher 24-h and daytime systolic blood pressure (SBP) (P<0.05) compared to patients with dapagliflozin treatment. After adjusting for covariates, results showed that dapagliflozin treatment was significantly associated with reduced 24-h SBP (ß=-0.29 and P=0.02) and reduced daytime SBP (ß=-0.33 and P=0.009). After additionally adjusting for SUA and 24-h UUA excretion, there were no significant relationships found between dapagliflozin treatment and 24-h (ß=-012, P=0.10) and daytime SBP (ß=-0.20, P=0.06). CONCLUSIONS In patients with diabetes and hypertension, dapagliflozin treatment was associated with reduced 24-h and daytime SBP, which could be related to the drug's effect of increasing 24-h UUA excretion.

16.
Talanta ; 220: 121368, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32928397

RESUMO

A new method for fishing antitumor ingredients by G-quadruplex recognition from Macleaya cordata seeds extracts was established using a three-phase-laminar-flow-chip (TPL chip). The TPL chip integrated the separation of drugs from the complex ingredients and organic solvent extraction, simplifying pretreatment processes and reducing reagents and time. In addition, the chip method showed a lower false negative result, owing to the gentle membrane-free filtration process based on diffusion separation in microchannel. Four ligands with high content in alkaloids of Macleaya cordata seeds were selected, those are chelerythrine (CHE), sanguinarine (SAN), protopine (PRO), and allocryptopine (ALL), which demonstrated affinity with G-quadruplex and were potential for antitumor.

17.
Eur J Clin Nutr ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994554

RESUMO

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time. SUBJECTS/METHODS: To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD. RESULTS: In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR). CONCLUSIONS: In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD.

18.
J Pharm Sci ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32910947

RESUMO

A localized positive charge on IgG (referred to as a "charge patch") shows an adverse effect on pharmacokinetics (PK), so it would seem to be best practice to avoid charge patches during the discovery stage and closely monitor charge interactions during the development process. In certain circumstances, however, charge patches are required for target binding, in which case completely removing charge patches is not feasible. Therefore, quantitative measurement of a charge patch and its impact on PK is critical to the success of therapeutic antibody development. In this article, we generated mutations of a recombinant human antibody (referred to as mAb1) with disrupted charge patches to investigate how charge patches on IgG antibodies impact both target-binding affinity and PK-related factors. We conclude that it is important to modulate the size of the charge patch in order to balance target-binding affinity and PK.

19.
Biomater Sci ; 8(20): 5698-5714, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32930254

RESUMO

The combination therapy of cisplatin (CDDP) and metformin (MET) is a clinical strategy to enhance therapeutic outcomes in lung cancer. However, the efficacy of this combination is limited due to the asynchronous pharmacokinetic behavior of CDDP and MET, used as free drugs. Therefore, in this work, hyaluronic acid-cisplatin/polystyrene-polymetformin (HA-CDDP/PMet) dual-prodrug co-assembled nanoparticles were developed, with precise ratiometric co-delivery of CDDP and MET for chemo-immunotherapy against lung cancer. The HA-CDDP/PMet NPs showed a spherical morphology with an average particle size of 166.5 nm and a zeta potential of -17.4 mV at an HA-CDDP and PMet mass ratio of 1/1. The content of CDDP and MET in HA-CDDP/PMet NPs was 3.7% and 15.2%, respectively. In vitro antitumor effects of CDDP and MET resulted in an improved synergistic action on proliferation inhibition and apoptosis induction on Lewis lung cancer cells. Moreover, in vivo by co-delivered HA-CDDP/PMet NPs into tumor cells, with an excellent intracellular CDDP and MET cleavage. These nanoparticles exhibited significantly increased tumor accumulation and tumor growth inhibition and prolonged animal overall survival in Lewis lung cancer bearing mice without nephrotoxicity, excess of free drugs and homo-prodrugs. The synergistic effect of MET and CDDP in HA-CDDP/PMet NPs resulted in up-regulation of the cleaved poly(ADP)-ribose polymerase (PARP) protein to induce tumor cell apoptosis, and down-regulation of the excision repair cross-complementation group 1 (ERCC1) protein level to decrease the resistance to CDDP. The synergistic effect of MET and CDDP in HA-CDDP/PMet NPs also resulted in induction of the adenosine monophosphate (AMP)-activated protein kinase-α (AMPK-α) pathway and inhibition of the mammalian target of rapamycin (mTOR), finally exerting a chemotherapeutic effect and modulating a potent immunotherapeutic function with an increase in CD4+ and CD8+ T cells, a concomitant decrease in regulatory T (Treg) cells, and an increased expression of the cytokines IFN-γ and TNF-α. Therefore, the immunochemotherapy using CDDP and MET mediated by this dual prodrug co-assembled nano-platform might provide a promising treatment strategy against lung cancer.

20.
ACS Appl Mater Interfaces ; 12(41): 45873-45890, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924511

RESUMO

Cancer metastasis is the leading cause of high mortality and disease recurrence in breast cancer. In this study, a novel tumor microenvironment charge reversal polymetformin (PMet)-based nanosystem co-delivering doxorubicin (DOX) and plasmid encoding IL-12 gene (pIL-12) was developed for chemo-gene combination therapy on metastatic breast cancer. Cationic PMet was readily self-assembled into micelles for DOX physical encapsulation and pIL-12 complexation, and a hyaluronidase-sensitive thiolated hyaluronic acid (HA-SH) was then collaboratively assembled to the pIL-12/DOX-PMet micelleplexes, abbreviated as HA/pIL-12/DOX-PMet. DOX/pIL-12 loaded in HA/pIL-12/DOX-PMet micelleplexes presented prolonged circulation in blood, efficient accumulation in tumors, and internalization in tumor cells via CD44 receptor-mediated tumor specific-targeting, and DOX/pIL-12 was co-released in endo/lysosomes tumor microenvironment followed by HAase-triggered HA-SH deshielding from HA/pIL-12/DOX-PMet micelleplexes. Moreover, HA/PMet micelleplexes displayed excellent pIL-12 transfection and IL-12 expression in tumors of 4T1 tumor-bearing mice. Importantly, HA/pIL-12/DOX-PMet micelleplexes synergistically enhanced the NK cells and tumor infiltrated cytotoxic T lymphocytes and modulated the polarization from protumor M2 macrophages to activated antitumor M1 macrophages, with concomitant decreasing of the immunosuppressive regulatory T (Treg) cells, accompanied by an increase in the cytokines expression of IL-12, IFN-γ and TNF-α, consequently showing an improved antitumor and antimetastasis activity in 4T1 breast cancer lung metastasis mice model. In conclusion, the tumor microenvironment charge reversal HA/PMet nanosystem holds great promise for DOX/pIL-12 co-delivery and exploitation in chemo-gene combination therapy on metastatic breast cancer.

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