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1.
Sleep Breath ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919715

RESUMO

OBJECTIVE: A new index, approximate entropy (ApEn) of oxygen saturation, was used to assess the severity of hypoxemia in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), determine the correlation with other parameters, and explore its clinical value. METHODS: A retrospective analysis was performed on 1200 patients with OSAHS and snorers (normal control). All subjects underwent sleep apnea monitoring for 6 h. Subjects were divided into four subgroups by apnea-hypopnea index (AHI): normal control (AHI < 5), mild OSAHS (5 ≤ AHI < 15), moderate OSAHS (15 ≤ AHI < 30), and severe OSAHS 104 (AHI ≥ 30). ApEn was initially compared among the subgroups. Then a correlation analysis of AHI with ApEn and a correlation analysis of ApEn with oxygen desaturation index (ODI), lowest oxygen saturation (LO2), and T < 90% were performed. (2) The AHI was used as the gold standard, and an attempt was performed to determine the value of ApEn to assess the severity of hypoxemia in OSAHS. RESULTS: Among the 1200 subjects, 822 subjects were men (72%) and mean age was 53.2 ± 15.2 years (range 24-95 years). The ApEn in each group was significantly different (P <0.001), and the ApEn synchronously increased with AHI. Furthermore, a significant difference in ApEn was found among the groups (P <0.001). In addition, ApEn had a good correlation with ODI, LO2, and T <90%. According to the ROC analysis results, the boundary value of ApEn to judge OSAHS patients with mild, moderate, and severe hypoxia was 16.72, 17.84, and 20.06, respectively. CONCLUSION: ApEn synchronously increased with the AHI and had a good correlation with AHI, ODI, LO2, and T <90%. These findings suggest that ApEn may have clinical value for assessing hypoxia severity in OSAHS patients.

2.
World J Surg Oncol ; 18(1): 2, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898548

RESUMO

BACKGROUND: The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients. METHODS: This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram. RESULTS: Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively. CONCLUSIONS: Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.

3.
Inorg Chem ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913025

RESUMO

Treatment of [Ir(PPh3)3Cl] with 2-[5-(pyridin-2-yl)-1H-pyrrol-2-yl]pyridine (Hdpp) in refluxing toluene affords an unexpected pyrrole-metalated iridium(III) hydride complex, [Ir(K2C,N-dpp)(H)(Cl)(PPh3)2] (1), via Cpyrrole-H activation, while the presence of the base KOtBu as the deprotonation reagent produces a pyridine-metalated iridium(III) hydride complex, [Ir(K3C,N,N-dpp)(H)(PPh3)2] (2), via Cpyridine-H activation. Treatment of [Ir(PPh3)3Cl] prepared by a convenient method with Hdpp in the presence of KOtBu under the refluxing mixture solvent toluene/methanol (2:1, v/v) generates the N,N-chelating complex [Ir(K2N,N-dpp)(H)(Cl)(PPh3)2] (3) together with 1 and the N,N-chelating dihydride complex [Ir(K2N,N-dpp)(H)2(PPh3)2] (4). Complex 4 is also readily produced by the reaction of [Ir(PPh3)3Cl] and Hdpp in the presence of KOtBu under refluxing methanol or by the reaction of IrCl3 and PPh3 in refluxing 2-ethoxyethanol. Complexes 1-4 are fully characterized by NMR, IR, and UV-vis spectroscopy and X-ray diffraction analysis. The dpp-/dpp2- ligand shows rich coordination capability, of which pyridine- and pyrrole-cyclometalated coordination modes are first reported. The formation of structural isomers 1 and 3 involved the selective activation of the C-H and N-H bonds of Hdpp is rationalized by theoretical calculations.

4.
Plant Mol Biol ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894456

RESUMO

KEY MESSAGE: This study revealed that the Arabidopsis UGT75B1 plays an important role in modulating ABA activity by glycosylation when confronting stress environments. The cellular ABA content and activity can be tightly controlled in several ways, one of which is glycosylation by family 1 UDP-glycosyltransferases (UGTs). Previous analysis has shown UGT75B1 activity towards ABA in vitro. However, the biological role of UGT75B1 remains to be elucidated. Here, we characterized the function of UGT75B1 in abiotic stress responses via ABA glycosylation. GUS assay and qRT-PCR indicated that UGT75B1 is significantly upregulated by adverse conditions, such as osmotic stress, salinity and ABA. Overexpression of UGT75B1 in Arabidopsis leads to higher seed germination rates and seedling greening rates upon exposure to salt and osmotic stresses. In contrast, the big UGT75B1 overexpression plants are more sensitive under salt and osmotic stresses. Additionally, the UGT75B1 overexpression plants showed larger stomatal aperture and more water loss under drought condition, which can be explained by lower ABA levels examined in UGT75B1 OE plants in response to water deficit conditions. Consistently, UGT75B1 ectopic expression leads to downregulation of many ABA-responsive genes under stress conditions, including ABI3, ABI5 newly germinated seedlings and RD29A, KIN1, AIL1 in big plants. In summary, our results revealed that the Arabidopsis UGT75B1 plays an important role in coping with abiotic stresses via glycosylation of ABA.

5.
Chem Commun (Camb) ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895373

RESUMO

To monitor delicate changes of biological HOCl in vivo, a new probe (OH-substituted coumarin-hemicyanine, probe 2) was synthesized for NIR and ratiometric HOCl detection. Selectivity studies indicated that the electron-donating group (OH) substituted on the indolium moiety enhanced the selectivity to detect HOCl. With HOCl, the probe showed a ratiometric fluorescence (I500/I650) with a low detection limit (49.1 nM) and a rapid response (within 2 min). In addition, probe 2 was successfully applied to visualize exogenous and endogenous HOCl in living cells and animals and exhibited a perfect mitochondria target ability. This probe has been further studied as a potential and powerful tool to probe HOCl in arthritis models.

6.
Virulence ; 11(1): 39-48, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31851866

RESUMO

Metformin, as the first-line oral drug for type 2 diabetes, has proven benefits against aging, cancer and cardiovascular diseases. But the influence of metformin to the immune response and its molecular mechanisms remain obscure. Metformin increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Meanwhile, metformin protects the animals from the infection by enhancing the tolerance to the pathogen infection rather than by reducing the bacterial burden. Through the screening of classical immune pathways in C. elegans, we find metformin enhances innate immunity through p38 MAPK pathway. Furthermore, activated p38/PMK-1 by metformin acts on the intestine for innate immune response. In addition, metformin-treated mice have increased resistance to P. aeruginosa PA14 infection and significantly increased the levels of active PMK-1. Therefore, promoted p38/PMK-1-mediated innate immunity by metformin is conserved from worms to mammals. Our work provides a conserved mechanism by which metformin enhances immune response and boosts its therapeutic application in the treatment of pathogen infection.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31834438

RESUMO

A microbial floc consisting of a community of microbes embedded in extracellular polymeric substances matrix can provide microbial resistances to toxic chemicals and harsh environments. Phenol is a toxic environmental pollutant and a typical lignin-derived phenolic inhibitor. In this study, we genetically engineered Escherichia coli cells by expressions of diguanylate cyclases (DGCs) to promote proteinaceous and aliphatic biofloc formation. Compared with the planktonic E. coli cells, the biofloc-forming cells improved phenol removal rate by up to 2.2-folds, due to their substantially improved tolerance (up to 149%) to phenol and slightly enhanced cellular activity (20%) of phenol hydroxylase (PheH). The engineered bioflocs also improved E. coli tolerance to other toxic compounds such as furfural, 5-hydroxymethylfurfural, and guaiacol. Additionally, the strategy of the engineered biofloc formation was applicable to Pseudomonas putida and enhanced its tolerance to phenol. This study highlights a strategy to form engineered bioflocs for improved cell tolerance and removal of toxic compounds, enabling their universality of use in bioproduction and bioremediation.

8.
Clin Chim Acta ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805270

RESUMO

BACKGROUND: T790M mutation was a primary lead cause in the acquired resistance to EGFR-TKIs confirmed in earlier studies. Since the shortcomings of tumor tissue detection are well known, the liquid biopsy is more appropriate to track T790M status. We assessed the accuracy and clinical significance of the droplet digital PCR (ddPCR) detection of T790M mutation in plasma. METHODS: We retrieved PubMed, Embase, Cochrane, and Web of science with no limitation of language and publication year. Summary sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio of detection of EGFR T790M status were calculated from extracted data from included articles. The summary receiver operating curve (SROC), diagnostic odds ratio (DOR), and the area under the summary receiver operating curve (AUC) was used to assess the overall diagnostic accuracy. I2 and meta-regression were used to evaluate heterogeneity and the source of heterogeneity, respectively. RESULT: We identified 15 studies in the total search of 1364 reports, including 427 paired tissue and plasma samples. The pooled sensitivity and the pooled specificity were 0.68 (95% CI 0.61-0.75) and 0.85 (95% CI 0.75-0.91) by the bivariate model, respectively. The AUC and the pooled DOR were 0.78 (95% CI 0.74-0.81) and 12 (95% CI 7-22), respectively. None of the cofactors could account for the heterogeneity. CONCLUSION: The plasma analysis is of a promising performance to screen EGFR-T790M mutation status by ddPCR.

9.
Mol Imaging Biol ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792839

RESUMO

PURPOSE: Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC. PROCEDURES: Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models. RESULTS: Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)4 generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA)4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection. CONCLUSION: These findings potentiate the use of RWY-dL-(Gd-DOTA)4 for the MRI of HCC to improve the diagnosis of HCC.

10.
Bioorg Chem ; : 103413, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31791679

RESUMO

A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced ß-amyloid (Aß) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7 nM for hAChE and 0.66 µM for hBuChE) and the good Aß aggregation inhibition (49.2% at 20 µM), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Aß-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation.

11.
Molecules ; 25(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861927

RESUMO

Anwuligan, a natural 2,3-dibenzylbutane lignan from the nutmeg mace of Myristica fragans, has been proved to possess a broad range of pharmacological effects. A rapid, simple, and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been established and successfully applied to the study of pharmacokinetics and tissue distribution of anwuligan after intravenous or intragastric administration. Sample preparation was carried out through a liquid-liquid extraction method with ethyl acetate as the extraction reagent. Arctigenin was used as the internal standard (IS). A gradient program was employed with a mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile. The mass spectrometer was operated in a positive ionization mode with multiple reaction monitoring. The transitions for quantification were m/z 329.0→205.0 for anwuligan and m/z 373.0→137.0 for IS, respectively. Calibration curves were linear over the ranges of 0.5-2000 ng/mL for both plasma samples and tissue samples (r > 0.996). The absolute bioavailability is 16.2%, which represented the existing of the obvious first-pass effect. An enterohepatic circulation was found after the intragastric administration. Anwuligan could be distributed rapidly and widely in different tissues and maintained a high concentration in the liver. The developed and validated LC-MS/MS method and the pharmacokinetic study of anwuligan would provide reference for the future investigation of the preclinical safety of anwuligan as a candidate drug.

12.
BMC Urol ; 19(1): 135, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870347

RESUMO

BACKGROUND: To investigate the surgical methods and clinical results of robot-assisted laparoscopic antegrade inguinal lymphadenectomy. METHODS: A retrospective study was performed on clinical data from 19 patients with penile cancer admitted from March 2013 to October 2017. Among them, nine patients underwent robot-assisted laparoscopic antegrade inguinal lymphadenectomy (robot-assisted group) and 10 patients underwent open inguinal lymphadenectomy (open group). In the robot-assisted group, preoperative preparation, patient position, robot placement, design of operating channel and establishment of operating space are described. Key surgical procedures and techniques are also summarized. In addition, the number of lymph nodes removed, postoperative complications and follow-up in both groups were statistically analyzed. RESULTS: For the 9 patients in the robot-assisted group, surgery was successfully accomplished at 17 sides without intraoperative conversion to open surgery. The surgery time for each side was 45~90 min using laparoscope with an average of 68.5 ± 13.69 min/side. The intraoperative blood loss was estimated to be < 10 ml/side, and the number of removed lymph nodes was not significantly different from that of the open group (12 ± 4.2/side vs.11 ± 5.8/side, P = 0.84). There were no postoperative complications such as skin necrosis, delayed wound healing and cellulitis in the robot-assisted group. Skin-related complications occurred in 9 (45%) of the 20 sides in the open group. During a median follow-up of 25 months in robot-assisted group and 52.5 mouths in open group, was not significantly different there were no statistical differences in recurrence-free survival between the groups (75% vs 60%, p = 0.536). CONCLUSION: Robot-assisted laparoscopic antegrade inguinal lymphadenectomy achieved the desired surgical outcomes with fewer intraoperative and postoperative complications. The robotic arms of the surgical system were placed between the lower limbs of each patient. There was no need to re-position the robotic arms during bilateral inguinal lymphadenectomy. This simplified the procedure and reduced the use of trocars. If necessary, pelvic lymphadenectomy could be performed simultaneously using the original trocar position.

13.
Sci Rep ; 9(1): 20243, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882881

RESUMO

Staphylococcus aureus is a common pathogen in chronic rhinosinusitis (CRS) patients, the pathogenesis of which involves the ability to form biofilms and produce various virulence factors. Tobacco smoke, another risk factor of CRS, facilitates S. aureus biofilm formation; however, the mechanisms involved are unclear. Here, we studied the effect of nicotine on S. aureus biofilm formation and the expression of virulence-related genes. S. aureus strains isolated from CRS patients and a USA300 strain were treated with nicotine or were untreated (control). Nicotine-treated S. aureus strains showed dose-dependent increases in biofilm formation, lower virulence, enhanced initial attachment, increased extracellular DNA release, and a higher autolysis rate, involving dysregulation of the accessory gene regulator (Agr) quorum-sensing system. Consequently, the expression of autolysis-related genes lytN and atlA, and the percentage of dead cells in biofilms was increased. However, the expression of virulence-related genes, including hla, hlb, pvl, nuc, ssp, spa, sigB, coa, and crtN was downregulated and there was reduced bacterial invasion of A549 human alveolar epithelial cells. The results of this study indicate that nicotine treatment enhances S. aureus biofilm formation by promoting initial attachment and extracellular DNA release but inhibits the virulence of this bacterium.

14.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4405-4411, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872625

RESUMO

The application of chemical fingerprint to evaluate the quality of traditional Chinese medicine has been widely accepted and used in many countries. However,only by analyzing the type and content of its chemical components to evaluate the quality of traditional Chinese medicines,the gold standard of quality evaluation by evaluating pharmacodynamic effects is ignored. The study of Chinese medicinal spectrum-effect relationships combining the chemical composition with the pharmacodynamic activity of traditional Chinese medicine,which can evaluate the quality of traditional Chinese medicine from more comprehensive and different angles,has been applied in many fields of traditional Chinese medicine research. This paper mainly summarizes the research methods of the Chinese medicinal spectrum-effect relationships and its application in the field of traditional Chinese medicine study,and provides reference for the research,development and application of the Chinese medicinal spectrum-effect relationships.

15.
Fish Shellfish Immunol ; 97: 300-312, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31866448

RESUMO

In cultivated European eels, Aeromonas hydrophila, Edwardsiella anguillarum and Vibrio vulnificus are three important bacterial pathogens. In this study, an expressed recombinant Outer membrane proteinⅡ (rOmpⅡ) from A. hydrophila was intraperitoneally injected into European eels (Angullia angullia). All examined eels were equally divided into three groups. One group was injected with PBS only (PBS group), one group was injected with 1:1 mixture of PBS and Freund's incomplete adjuvant (PBS + F, adjuvant group), and the third group was injected with 1:1 mixture of 1 mg mL-1 rOmpⅡ and Freund's incomplete adjuvant (rOmpⅡ+F, OmpⅡ group). The immunogenicity of OmpⅡ was studied by detecting the expression of 4 immune-related genes, stimulation index (SI) of the whole blood cell, serum antibody titer, lysozyme and Superoxide Dismutase (SOD) activity, and relative percent of survival (RPS) rate. The results showed that gene expression of MHC-Ⅱ, LysC, SOD and IgM in the OmpⅡ group significantly increased in liver, spleen, kidney and intestine. At 28 days post the immunization (dpi), the SI of whole blood cells in the OmpⅡ group increased significantly; at 14, 21, 28 and 42 dpi, the serum antibody titers against A. hydrophila and E. anguillarum in the OmpⅡ group were significantly higher than that of the PBS and the adjuvant group; the SOD in the OmpⅡ group was found increased significantly in liver, kidney, mucus and serum. On the 28 dpi, eels were challenged by A. hydrophila, E. anguillarum and V. vulnificus for cross protection study. The results showed that the RPS of the OmpⅡ group were 83.33%, 55.56% and 33.33% respectively. These results showed that the expressed OmpⅡ from A. hydrophila significantly improve the immune function of Europena eels and their resistance to the infection of A. hydrophila and E. anguillarum simultaneously.

17.
Biomed Pharmacother ; 120: 109499, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707028

RESUMO

BACKGROUND: Spinal fusion is considered the gold standard procedure for treating spinal degeneration, tumors, and trauma. An inflammatory response is an important part of bone repair. We investigated the polarization change of inflammatory macrophages (M1) and resident macrophages (M2) during low-intensity pulsed ultrasound (LIPUS) treatment. METHODS: Thirty male Sprague Dawley rats (age: 12 weeks; weight: 300 g) were used in the study. A rat spinal fusion model was established by surgical procedures. LIPUS treatment (20 min. d, 5 d/wk) was begun 3 days after surgery. The rats were randomly divided into a control group (5 subgroups, 3 rats in each subgroup) and LIPUS group (5 subgroups, 3 rats in each subgroup), and sacrificed on day 3, 5, 7, 10, and 14 after spinal fusion surgery for further evaluation. Bone volume was measured by micro-CT, fusion region was examined by histological analyses, types of macrophages in the fusion area were examined by immunohistochemical staining. Raw264.7 cells and bone marrow-derived macrophages (BMDM) were used in cell experiments. Cells were divided into a control group and LIPUS group. Flow cytometry was used to examine the rate of resident macrophages, and real-time PCR was used to examine the mRNA expression of anti-inflammation genes. RESULTS: LIPUS promoted spinal fusion and stimulated the transition of F4-80+/Mac-2+ (M1) to F4-80+/Mac-2- (M2), leading to the early appearance of resident macrophages. Cell experiments showed CD206+ macrophages (M2) were significantly increased after LIPUS treatment. M2-related genes and anti-inflammation factors (Arg-1, PPAR-γ, and IL-4) were increased after LIPUS treatment. CONCLUSION: The earlier transition from inflammatory to resident macrophage might be one reason for the positive effect of LIPUS on spinal fusion.

18.
Anal Chem ; 91(23): 15308-15316, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31691562

RESUMO

Exosomes are cell-secreted membrane-coated vesicles with their sizes variable from 30 to 150 nm. So far, there is no simple, fast, and economical way to evaluate the sizes of exosomes in living systems. Here, we put forward a hypothesis in which the sphere sizes (resulting in different curvature) may affect the local mobility/viscosity of exosome membranes. Based on this hypothesis, we propose a novel method to evaluate the exosome sizes by quantifying the membrane viscosity. For this sake, we design a membrane-targeting molecular rotor with its fluorescence lifetime sensitive to viscosity and use it under a fluorescence lifetime imaging microscope (FLIM). Through a multiple-step ultrafiltration technique, we isolate three individual size distributions (10-50, 50-100, and 100-220 nm) with exosomes from HeLa and MCF-7 cell culture media and then perform the FLIM assay on the above two groups. In both cases, we indeed find a regular pattern in which the membrane viscosity reflected by lifetime decreases with exosome sizes. We then perform the assay on exosomes from cancer cells, corresponding normal tissue cells, and serum of breast cancer patients. We find that exosomes from cancer cells have a fluorescence lifetime (larger viscosity) longer than that of normal tissue cells. The average fluorescence lifetime of exosomes from a triple-negative breast cancer patient is longer (or the viscosity is larger) than that of a HER2 positive one. Therefore, our new and simple method may hold application prospects in future cancer diagnosis.

19.
J Pept Sci ; : e3230, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696619

RESUMO

Nonviral vector-based gene therapy is a promising strategy for treating a myriad of diseases. Cell-penetrating peptides are gaining increasing attention as vectors for nucleic acid delivery. However, most studies have focused more on the transfection efficiency of these vectors than on their specificity and toxicity. To obtain ideal vectors with high efficiency and safety, we constructed the vector stearyl-TH by attaching a stearyl moiety to the N-terminus of the acid-activated cell penetrating peptide TH in this study. Under acidic conditions, stearyl-TH could bind to and condense plasmids into nanoparticle complexes, which displayed significantly enhanced cellular uptake and transfection efficiencies. In contrast, stearyl-TH lost the capacities of DNA binding and transfection at physiological pH. More importantly, stearyl-TH and the complexes formed by stearyl-TH and plasmids displayed no obvious toxicity at physiological pH. Consequently, the high transfection efficiency under acidic conditions and low toxicity make stearyl-TH a potential nucleic acid delivery vector for gene therapy.

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