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1.
Nanotechnology ; 35(36)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38861963

RESUMEN

Optimizing the width of depletion region is a key consideration in designing high performance photovoltaic photodetectors, as the electron-hole pairs generated outside the depletion region cannot be effectively separated, leading to a negligible contribution to the overall photocurrent. However, currently reported photovoltaic mid-infrared photodetectors based on two-dimensional heterostructures usually adopt a single pn junction configuration, where the depletion region width is not maximally optimized. Here, we demonstrate the construction of a high performance broadband mid-infrared photodetector based on a MoS2/b-AsP/MoS2npn van der Waals heterostructure. The npn heterojunction can be equivalently represented as two parallel-stacked pn junctions, effectively increasing the thickness of the depletion region. Consequently, the npn device shows a high detectivity of 1.3 × 1010cmHz1/2W-1at the mid-infrared wavelength, which is significantly improved compared with its single pn junction counterpart. Moreover, it exhibits a fast response speed of 12 µs, and a broadband detection capability ranging from visible to mid-infrared wavelengths.

2.
Nanotechnology ; 32(46)2021 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-34359053

RESUMEN

Two-dimensional van der Waals heterostructures can combine properties of individual materials to enable high-performance photodetection. Here, a novel ReS2/graphene/WSe2heterostructure, prepared by dry transfer, demonstrates air-stable, high-performance, polarization-sensitive, and broadband photodetection. Dark current can be strongly suppressed by the built-in electric field of the heterostructure. The specific detectivities are up to 1010Jones and 109Jones under zero and reverse bias, respectively. Response time is on the order of a millisecond. The polarization-sensitive photodetection has been observed in the heterostructure due to the low lattice symmetry of ReS2. Broadband photoresponse from visible to infrared range has been demonstrated. A high photoresponsivity of 1.02 A W-1is achieved for illumination at the wavelength of 785 nm. This work provides a viable approach toward future high-performance, air-stable, and polarization-sensitive broadband photodetectors.

3.
Pharm Biol ; 54(12): 3189-3196, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27564455

RESUMEN

CONTEXT: Hepatocellular carcinoma (HCC) is a common cancer around the world, with high mortality rate. Currently, there is no effective drug for the therapy of HCC. Ursolic acid (UA) is a natural product which exists in various medicinal herbs and fruits, exhibiting multiple biological effects such as its outstanding anticancer and hepatoprotective activity, which has drawn many pharmacists' attention. OBJECTIVE: This paper summarizes the current status of the hepatoprotective activity of UA analogues and explains the related mechanism, providing a clear direction for the development of novel anti-HCC drugs. METHODS: All of the data resources were derived from PubMed. By comparing the IC50 values and analyzing the structure-activity relationships, we listed compounds with good pharmacological activity from the relevant literature, and summarized their anti-HCC mechanism. RESULTS: From the database, 58 new UA derivatives possessing wonderful anticancer and hepatoprotective effects were listed, and the relevant anti-HCC mechanism were discussed. CONCLUSION: UA's anti-HCC effect is the result of combined action of many mechanisms. These 58 new UA derivatives, particularly compounds 45 and 53, can be used as potential drugs for the treatment of liver cancer.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Triterpenos/uso terapéutico , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Triterpenos/química , Triterpenos/aislamiento & purificación , Ácido Ursólico
4.
ACS Appl Mater Interfaces ; 15(47): 55043-55054, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-37967170

RESUMEN

Two-dimensional (2D) van der Waals heterostructures based on various 2D transition metal dichalcogenides are widely used in photodetection applications. However, their response time and photoresponsivity are limited, posing a challenge for their applications in high-sensitivity photodetection. Surface charge transfer doping (SCTD) has emerged as a novel doping approach for low-dimensional materials with high specific surface area and attracted considerable attention, as it is simple and effective, does not damage the lattice, and considers various types of dopants. Herein, we prepare p-i-n junction-based photodetectors via the SCTD of WSe2/ReS2 heterojunctions using p-type dopant F4-TCNQ molecules, where doped WSe2 serves as a p-type semiconductor, undoped WSe2 acts as an intrinsic layer, and ReS2 functions as an n-type semiconductor. The surface-charge-transfer-doped WSe2/ReS2 heterojunction leads to a reduction in the Schottky barrier and an increase in the built-in electric field compared with the as-fabricated heterojunction. In the photovoltaic mode and under 785 nm laser illumination, the photodiode exhibits an increase in responsivity from 0.08 to 0.29 A/W, specific detectivity from 1.89 × 1012 to 8.02 × 1012 Jones, and the external quantum efficiency from 12.67 to 46.29%. Additionally, the p-i-n structure expands the depletion region width, resulting in a photovoltaic response time of 7.56/6.48 µs and a -3 dB cutoff frequency of over 85 kHz, an order of magnitude faster than the pristine response time. Herein, we derive an effective and simple scheme for designing high-performance, low-power optoelectronic devices based on 2D van der Waals heterostructures.

5.
Drug Deliv ; 29(1): 128-137, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34967270

RESUMEN

Chemotherapy is one of the main ways to treat breast cancer clinically. However, the multidrug resistance to anti-tumor drugs limits their clinical use. To overcome these drawbacks, development of drug delivery systems (DDSs) has attracted more and more attention in cancer therapy. At present, the preparation and purification process are complicated for many reported DDSs, while clinic calls for new DDSs that are more convenient for preparation. Here, a new pH-responsive supramolecular organic framework drug delivery complex loading doxorubicin (DOX) is fabricated. Anti-tumor activity of the system in vitro was investigated by cell cytotoxicity, uptake assay, and cell apoptosis analysis. The anti-tumor activity in vivo was investigated by inspecting nude mice body weight, tumor volume, and weight, also a preliminary mechanism probe was conducted by HE and TUNEL staining. The DOX@SOF displayed high stability, good biocompatibility, and pH regulated drug release. At acid condition, the hydrazone bonds would be broken, which result in the dissociation of SOF, and then the drugs would be released from the system. Furthermore, DOX@SOF enhanced cellular internalization. Both in vitro and in vivo experiments reflected that DOX@SOF could enhance the anti-tumor activity of DOX for the MCF-7/ADR tumor cells and tumors. This study provides a highly efficient strategy to prepare stimulus-responsive supramolecular drug delivery complex for treatment of drug-resistant cancer, the results presented inspiring scientific interests in exploring new drug delivery strategy and reversing multi-drug resistance for clinical chemotherapy.


Asunto(s)
Portadores de Fármacos/química , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Doxorrubicina/administración & dosificación , Liberación de Fármacos , Resistencia a Antineoplásicos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Aleatoria , Propiedades de Superficie , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Drug Deliv ; 29(1): 1-9, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34949133

RESUMEN

Chemotherapy is one of the main ways to treat breast cancer clinically. However, the multidrug resistance to anti-tumor drugs limits their clinical use. To overcome these drawbacks, the development of drug delivery systems (DDSs) has attracted more and more attention in cancer therapy. At present, the preparation and purification process are complicated for many reported DDSs, while the clinic calls for new DDSs that are more convenient for preparation. Here a new pH-responsive supramolecular organic framework drug delivery complex loading doxorubicin (DOX) is fabricated. Anti-tumor activity of the system in vitro was investigated by cell cytotoxicity, uptake assay, and cell apoptosis analysis. The anti-tumor activity in vivo was investigated by inspecting nude mice body weight, tumor volume and weight, also a preliminary mechanism probe was conducted by HE and TUNEL staining. The DOX@SOF displayed high stability, good biocompatibility and pH-regulated drug release. At acid condition, the hydrazone bonds would be broken, which result in the dissociation of SOF, and then the drugs would be released from the system. Furthermore, DOX@SOF enhanced cellular internalization. Both in vitro and in vivo experiments reflected that DOX@SOF could enhance the anti-tumor activity of DOX. for the MCF-7/ADR tumor cells and tumors. This study provides a highly efficient strategy to prepare a stimulus-responsive supramolecular drug delivery complex for the treatment of drug-resistant cancer, the results presented inspiring scientific interests in exploring new drug delivery strategies and reversing multi-drug resistance for clinical chemotherapy.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Doxorrubicina/farmacología , Portadores de Fármacos/farmacología , Animales , Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular , Doxorrubicina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Liberación de Fármacos , Resistencia a Antineoplásicos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Ratones Endogámicos BALB C , Ratones Desnudos , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
7.
ACS Nano ; 16(6): 9329-9338, 2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35687375

RESUMEN

van der Waals heterostructures (vdWHs) overcoming the lattice and processing limitations of conventional heterostructures provide an opportunity to develop high-performance 2D vdWH solar cells and photodiodes. However, it is challenging to improve the sensitivity and response speed of 2D vdWH photovoltaic devices due to the low light absorption efficiency and electron/hole traps in heterointerfaces. Here, we design a PbS/MoS2/WSe2 heterostructure photodiode in which a light-sensitive PbS quantum dot (QD) layer combined with a MoS2/WSe2 heterostructure significantly enhances the photovoltaic response. The electron current in the heterostructure is increased by the effective collection of photogenerated electrons induced by PbS QDs. The device exhibits a broadband photovoltaic response from 405 to 1064 nm with a maximum responsivity of 0.76 A/W and a specific detectivity of 5.15 × 1011 Jones. In particular, the response speed is not limited by multiple electron traps in the PbS QDs/2D material heterointerface, and a fast rising/decaying time of 43/48 µs and a -3 dB cutoff frequency of over 10 kHz are achieved. The negative differential capacitance and frequency dependence of capacitance demonstrate the presence of interface states in the MoS2/WSe2 heterointerface that hamper the improvement of the response speed. The scheme to enhance photovoltaic performance without sacrificing response speed provides opportunities for the development of high-performance 2D vdWH optoelectronic devices.

8.
Hum Vaccin Immunother ; 18(1): 1-9, 2022 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-34473607

RESUMEN

To control seasonal influenza epidemics in elders, a quadrivalent, inactivated, split-virion influenza vaccine (IIV4) comprising A and B lineages is produced for young individuals and adults aged ≥60 years. In this phase III, randomized, double-blind, active-controlled trial, we compared safety and immunogenicity of IIV4 with a licensed quadrivalent inactivated vaccine (IIV4-HL) produced by Hualan Biological Engineering during the 2019 influenza season. Participants were randomly assigned to receive IIV4 (n = 959) or IIV4-HL (n = 959). Compared to IIV4-HL, geometric mean titers (GMT) of hemagglutination inhibition (HAI) titers and seroconversion rate (SCR) of IIV4 demonstrated better antibody responses in A lineages (H1N1 and H3N2) (P < .01) and equivalent antibody responses in B lineages (B/Yamagata and B/Victoria) (P > .01) in both age groups. After immunization, IIV4 provided a satisfactory SCR and seroprotection rate (SPR) in elders. No discernible variation in immunogenicity was observed between the two age cohorts. In both age groups, IIV4 and IIV4-HL recipients experienced similar levels of solicited and unsolicited adverse events (AEs), and the incidence of AEs was low in both vaccine groups. Most AEs were of mild-to-moderate severity and no grade 3 AEs in IIV4 group, but AEs in adults aged 60-65 were little higher than in adults over 65 years in IIV4 and IIV4-HL groups (IIV4: 14.66% vs. 10.36%; IIV4-HL:14.67% vs. 11.43%). Totally, IIV4 was generally well tolerated and induced high antibody titers against all four influenza strains in elderly, making it a compelling alternative for the elderly aged ≥60 years.Trial registration: Clinical Trials.gov: 2015L00649-2.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Adulto , Anciano , Anticuerpos Antivirales , Pruebas de Inhibición de Hemaglutinación , Humanos , Inmunogenicidad Vacunal , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana/prevención & control , Vacunas Combinadas , Vacunas de Productos Inactivados
9.
Aging (Albany NY) ; 13(7): 9801-9819, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33744852

RESUMEN

Clinical data showed sex variability in the immune response to influenza vaccination, this study aimed to investigate differentially expressed genes (DEGs) that contribute to sex-bias immunity to quadrivalent inactivated influenza vaccines (QIVs) in the elderly. 60 healthy adults aged 60-80 yrs were vaccinated with QIVs, and gene expression was analyzed before and after vaccination. The humoral immunity was analyzed by HAI assay, and the correlation of gene expression patterns of two sex groups with humoral immunity was analyzed. The DEGs involved in type I interferon signaling pathway and complement activation of classical pathway were upregulated within 3 days in females. At Day 28, the immune response showed a male-bias pattern associated with the regulation of protein processing and complement activation of classical pathway. A list of DEGs associated with variant responses to influenza vaccination between females and males were identified by biology-driven clustering. Old females have a greater immune response to QIVs but a rapid antibody decline, while old males have the advantages to sustain a durable response. In addition, we identified genes that may contribute to the sex variations toward influenza vaccination in the aged. Our findings highlight the importance of developing personalized seasonal influenza vaccines.


Asunto(s)
Inmunidad Humoral , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Transcriptoma , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Vacunación
10.
Emerg Microbes Infect ; 10(1): 1589-1597, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34197281

RESUMEN

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase I clinical trials in humans. A Randomized, double-blind, placebo-controlled Phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive the vaccine (10, 25, and 50 µg) or placebo (V-01: Placebo = 4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed a promising safety profile with approximately 25% vaccine-related overall adverse events (AEs) within 30 days and no grade 3 or worse AEs. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10 µg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in Phase II/III clinical trials.


Asunto(s)
Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal , Interferones/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , China , Método Doble Ciego , Femenino , Humanos , Inmunoglobulina G/sangre , Interferones/administración & dosificación , Interferones/genética , Masculino , Persona de Mediana Edad , Placebos , Vacunación/efectos adversos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología , Adulto Joven
11.
Chin Med J (Engl) ; 134(16): 1967-1976, 2021 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-34310400

RESUMEN

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).


Asunto(s)
COVID-19 , Anciano , Anticuerpos Antivirales , COVID-19/terapia , Vacunas contra la COVID-19 , Método Doble Ciego , Humanos , Inmunización Pasiva , Proteínas Recombinantes de Fusión , SARS-CoV-2 , Sueroterapia para COVID-19
12.
Front Immunol ; 11: 603337, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33343577

RESUMEN

Insights into the potential candidate hub genes may facilitate the generation of safe and effective immunity against seasonal influenza as well as the development of personalized influenza vaccines for the elderly at high risk of influenza virus infection. This study aimed to identify the potential hub genes related to the immune induction process of the 2018/19 seasonal quadrivalent inactivated influenza vaccines (QIVs) in the elderly ≥60 years by using weighted gene co-expression network analysis (WGCNA). From 63 whole blood samples from16 elderly individuals, a total of 13,345 genes were obtained and divided into eight co-expression modules, with two modules being significantly correlated with vaccine-induced immune responses. After functional enrichment analysis, genes under GO terms of vaccine-associated immunity were used to construct the sub-network for identification and functional validation of hub genes. MCEMP1 and SPARC were confirmed as the hub genes with an obvious effect on QIVs-induced immunity. The MCEMP1 expression was shown to be negatively correlated with the QIVs-associated reactogenicity within 7 days after vaccination, which could be suppressed by the CXCL 8/IL-8 and exacerbated by the Granzyme-B cytotoxic mediator. Meanwhile, the SPARC expression was found to increase the immune responses to the QIVs and contribute to the persistence of protective humoral antibody titers. These two genes can be used to predict QIVs-induced adverse reaction, the intensity of immune responses, and the persistence of humoral antibody against influenza. This work has shed light on further research on the development of personalized QIVs with appropriate immune responses and long-lasting immunity against the forthcoming seasonal influenza.


Asunto(s)
Redes Reguladoras de Genes , Inmunidad Humoral/genética , Inmunogenicidad Vacunal/genética , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Transcriptoma , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Biomarcadores/sangre , China , Citocinas/sangre , Método Doble Ciego , Femenino , Regulación de la Expresión Génica , Humanos , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/genética , Gripe Humana/inmunología , Gripe Humana/virología , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Osteonectina/genética , Factores de Tiempo , Vacunación
13.
Colloids Surf B Biointerfaces ; 194: 111144, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32535244

RESUMEN

Histonedeacetylase inhibitor (HDACi) has great potential in targeted antitumor therapy by inhibiting tumor migration, invasion, and metastasis. As one of the typical HDACis, vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) was approved as a therapeutic agent for cancer therapy, however, challenges remain due to their poor solubility, short half-life and low efficiency in cellular penetration. Considering the disadvantages of usual drug carriers, folate and vorinostat bound BSA nanogel (FVBN)was fabricated to implement higher solubility, stability, cellular uptake, and lipase-responsive release. With good dispersion and stability, FVBN significantly increased the cellular uptake of vorinostat through folate-mediated endocytosis. FVBN exhibited comparable cytotoxicity with free SAHA, and the growth of tumor cells was blocked in G1/G0 phase just like SAHA performed in cell cycle arrest tests. Moreover, FVBN not only effectively inhibited the growth of melanoma but also observably prevented pulmonary metastasis of melanoma. In the experiment against nude mice bearing solid ovarian cancer, FVBN showed excellent antitumor effect without liver damage, demonstrating the superiority of gelated and inner-lysosome triggered release strategies to the free SAHA, and it is promising to expand the scope of application of HDACi in clinical cancer therapy.


Asunto(s)
Antineoplásicos , Ácidos Hidroxámicos , Vorinostat , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Lisosomas , Ratones , Ratones Desnudos , Vorinostat/farmacología
14.
Int J Nanomedicine ; 14: 5527-5540, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31413561

RESUMEN

Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) grafted folate (FA-PEG-b-PAsp) to obtain the block polymer folate polyethylene glycol-b-poly(asparaginyl-chidamide) (FA-PEG-b-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide-a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-b-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.


Asunto(s)
Aminopiridinas/química , Benzamidas/química , Ácido Fólico/uso terapéutico , Micelas , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Clorofila/análogos & derivados , Clorofila/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Ácido Fólico/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Ratones Endogámicos C57BL , Nanopartículas/química , Nanopartículas/ultraestructura , Fármacos Fotosensibilizantes/farmacología , Polietilenglicoles/química , Especies Reactivas de Oxígeno/metabolismo
15.
Plant Biotechnol J ; 6(2): 176-88, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18021190

RESUMEN

The feasibility of using the FLP/FRT site-specific recombination system in rice for genome engineering was evaluated. Transgenic rice plants expressing the FLP recombinase were crossed with plants harbouring the kanamycin resistance gene (neomycin phosphotransferase II, nptII) flanked by FRT sites, which also served to separate the corn ubiquitin promoter from a promoterless gusA. Hybrid progeny were tested for excision of the nptII gene and the positioning of the ubiquitin promoter proximal to gusA. While the hybrid progeny from various crosses exhibited beta-glucuronidase (GUS) expression, the progeny of selfed parental rice plants did not show detectable GUS activity. Despite the variable GUS expression and incomplete recombination displayed in hybrids from some crosses, uniform GUS staining and complete recombination were observed in hybrids from other crosses. The recombined locus was shown to be stably inherited by the progeny. These data demonstrate the operation of FLP recombinase in catalysing excisional DNA recombination in rice, and confirm that the FLP/FRT recombination system functions effectively in the cereal crop rice. Transgenic rice lines expressing active FLP recombinase generated in this study provide foundational stock material, thus facilitating the future application and development of the FLP/FRT system in rice genetic improvement.


Asunto(s)
ADN Nucleotidiltransferasas/metabolismo , Oryza/genética , Recombinación Genética , ADN de Plantas/genética , Glucuronidasa/metabolismo , Plantas Modificadas Genéticamente
16.
Nucleic Acids Res ; 32(Web Server issue): W649-53, 2004 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-15215469

RESUMEN

We have developed a web server for the life sciences community to use to search for short repeats of DNA sequence of length between 3 and 10,000 bases within multiple species. This search employs a unique and fast hash function approach. Our system also applies information retrieval algorithms to discover knowledge of cross-species conservation of repeat sequences. Furthermore, we have incorporated a part of the Gene Ontology database into our information retrieval algorithms to broaden the coverage of the search. Our web server and tutorial can be found at http://acmes.rnet.missouri.edu.


Asunto(s)
Genómica , Secuencias Repetitivas de Ácidos Nucleicos , Análisis de Secuencia de ADN , Programas Informáticos , Algoritmos , Secuencia Conservada , Genoma , Genoma Bacteriano , Genoma Fúngico , Genoma de Planta , Internet , Factores de Tiempo , Interfaz Usuario-Computador
17.
Plant Dis ; 83(3): 286-292, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30845509

RESUMEN

Isolates of Colletotrichum graminicola from annual blue grass and creeping bent grass were investigated for their morphological characteristics, host specificity, and genetic relatedness. One isolate from maize and one from sorghum (C. sublineolum) were included for comparison. Recently isolated cultures of C. graminicola from annual blue grass were readily distinguished from those isolated from creeping bent grass on the basis of pigmentation. Differences in appressoria size and shape were found only between the turf grass isolates and those from maize and sorghum. Spore length varied significantly between host groups. Differences in host range and virulence were also apparent. In general, isolates from creeping bent grass incited disease on both creeping bent grass and annual blue grass, while those from annual blue grass essentially were limited to host. Random amplified polymorphic DNA (RAPD) marker analysis of C. graminicola isolates from turf grass revealed that a high degree of genetic similarity exists among isolates recovered from the same host, but exceptions were found. Therefore, an absolute distinction between isolates recovered from two turf grass hosts could not be made based on RAPD markers.

18.
Chem Commun (Camb) ; 50(10): 1244-6, 2014 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-24336685

RESUMEN

Methane can be stored in tea clathrates, that is kinetics of methane clathrate formation can be significantly accelerated (90% saturation uptake in 20 min) by ingredients (polyphenols and saponins) in tea infusions with a volumetric capacity of up to 172 v/v.


Asunto(s)
Metano/química , Polifenoles/química , Saponinas/química , Té/química , Cinética
19.
Plant Physiol ; 146(2): 468-77, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18162589

RESUMEN

Phytic acid (PA) contains the major portion of the phosphorus in the soybean (Glycine max) seed and chelates divalent cations. During germination, both minerals and phosphate are released upon phytase-catalyzed degradation of PA. We generated a soybean line (CAPPA) in which an Escherichia coli periplasmic phytase, the product of the appA gene, was expressed in the cytoplasm of developing cotyledons. CAPPA exhibited high levels of phytase expression, >or=90% reduction in seed PA, and concomitant increases in total free phosphate. These traits were stable, and, although resulted in a trend for reduced emergence and a statistically significant reduction in germination rates, had no effect on the number of seeds per plant or seed weight. Because phytate is not digested by monogastric animals, untreated soymeal does not provide monogastrics with sufficient phosphorus and minerals, and PA in the waste stream leads to phosphorus runoff. The expression of a cytoplasmic phytase in the CAPPA line therefore improves phosphorus availability and surpasses gains achieved by other reported transgenic and mutational strategies by combining in seeds both high phytase expression and significant increases in available phosphorus. Thus, in addition to its value as a high-phosphate meal source, soymeal from CAPPA could be used to convert PA of admixed meals, such as cornmeal, directly to utilizable inorganic phosphorus.


Asunto(s)
6-Fitasa/genética , 6-Fitasa/metabolismo , Fosfatasa Ácida/genética , Fosfatasa Ácida/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Glycine max/metabolismo , Fósforo/metabolismo , Ácido Fítico/metabolismo , Semillas/metabolismo , Alimentación Animal/análisis , Expresión Génica , Germinación , Ácido Fítico/química , Plantas Modificadas Genéticamente , Semillas/genética , Glycine max/citología , Glycine max/genética
20.
Transgenic Res ; 17(5): 839-50, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18256901

RESUMEN

RNA interference (RNAi) has been recently employed as an effective experimental tool for both basic and applied biological studies in various organisms including plants. RNAi deploys small RNAs, mainly small interfering RNAs (siRNAs), to mediate the degradation of mRNA for regulating gene expression in plants. Here we report an efficient siRNA-mediated gene silencing of the omega-3 fatty acid desaturase (FAD3) gene family in a complex genome, the soybean (Glycine max). The FAD3 enzyme is responsible for the synthesis of alpha-linolenic acids (18:3) in the polyunsaturated fatty acid pathway. It is this fatty acid that contributes mostly to the instability of soybean and other seed oils. Therefore, a significant reduction of this fatty acid will increase the stability of the seed oil, enhancing the seed agronomical value. A conserved nucleotide sequence, 318-nt in length, common to the three gene family members was used as an inverted repeat for RNA interference. The RNAi expression cassette was driven by a seed-specific promoter. We show that the transgene-produced siRNA caused silencing of FAD3 that was comparable to the fad3 mutant phenotype and, furthermore, that such a silencing is stably inherited in engineered soybean lines. Since the pool size of the alpha-linolenic acids is small relative to the other polyunsaturated fatty acids in soybean, the significant reduction of this fatty acid suggests a role and great potential for the siRNA strategy in silencing gene families in a complex genome.


Asunto(s)
Silenciador del Gen , Genes de Plantas , Glycine max/genética , Mutación , ARN Interferente Pequeño/genética , Ácido alfa-Linolénico/metabolismo , Secuencia de Bases , Datos de Secuencia Molecular , Plantas Modificadas Genéticamente , Homología de Secuencia de Ácido Nucleico , Glycine max/metabolismo
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