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1.
Front Microbiol ; 14: 1274050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965552

RESUMO

Background: Although studies have shown that wearing masks can affect the skin microbiome, more detailed and comprehensive research on wearing masks needs to be further explored. Objective: This study aimed to characterize the influence of mask wearing on the diversity and structural characteristics of the facial skin microbial community of medical staff during the COVID-19 pandemic by means of metagenomic sequencing (mNGS). Methods: A total of 40 samples were taken by swabbing the cheek in the 2 × 2 cm2 area before and after wearing the masks. DNA was extracted for metagenomic sequencing. Results: A statistically significant decrease was found in the α diversity between BN and AN groups and between B2 h and A2 h groups. BN and AN mean groups before and after 8 h of wearing the medical protective mask (N95), including 10 volunteers, respectively. B2 h and A2 h mean groups before and after 8 h of wearing masks, including 10 volunteers changing mask every 2 h, respectively. The ß diversity was found to be statistically reduced between BS and AS groups (p = 0.025), BN and AN groups (p = 0.009), and B2 h and A2 h group (p = 0.042). The fungal beta diversity was significantly decreased in every group before and after wearing masks. The main bacteria on the face before and after wearing masks were Cutibacterium (68.02 and 71.73%). Among the fungi, Malassezia predominated the facial skin surface before and after wearing masks (35.81 and 39.63%, respectively). Conclusion: Wearing different types of masks and changing masks according to different frequency will have different effects on the facial skin's microbiota.

2.
Bioinformatics ; 39(11)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37930896

RESUMO

MOTIVATION: N-linked glycosylation is a frequently occurring post-translational protein modification that serves critical functions in protein folding, stability, trafficking, and recognition. Its involvement spans across multiple biological processes and alterations to this process can result in various diseases. Therefore, identifying N-linked glycosylation sites is imperative for comprehending the mechanisms and systems underlying glycosylation. Due to the inherent experimental complexities, machine learning and deep learning have become indispensable tools for predicting these sites. RESULTS: In this context, a new approach called EMNGly has been proposed. The EMNGly approach utilizes pretrained protein language model (Evolutionary Scale Modeling) and pretrained protein structure model (Inverse Folding Model) for features extraction and support vector machine for classification. Ten-fold cross-validation and independent tests show that this approach has outperformed existing techniques. And it achieves Matthews Correlation Coefficient, sensitivity, specificity, and accuracy of 0.8282, 0.9343, 0.8934, and 0.9143, respectively on a benchmark independent test set.


Assuntos
Processamento de Proteína Pós-Traducional , Proteínas , Glicosilação , Proteínas/química , Aprendizado de Máquina , Máquina de Vetores de Suporte , Biologia Computacional/métodos
3.
Front Plant Sci ; 14: 1194759, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396647

RESUMO

Background: Drought-resistant varieties are an important way to address the conflict between wheat's high water demand and the scarcity of water resources in the North China Plain (NCP). Drought stress impacts many morphological and physiological indicators in winter wheat. To increase the effectiveness of breeding drought-tolerant varieties, choosing indices that can accurately indicate a variety's drought resistance is advantageous. Results: From 2019 to 2021, 16 representative winter wheat cultivars were cultivated in the field, and 24 traits, including morphological, photosynthetic, physiological, canopy, and yield component traits, were measured to evaluate the drought tolerance of the cultivars. Principal component analysis (PCA) was used to transform 24 conventional traits into 7 independent, comprehensive indices, and 10 drought tolerance indicators were screened out by regression analysis. The 10 drought tolerance indicators were plant height (PH), spike number (SN), spikelet per spike(SP), canopy temperature (CT), leaf water content (LWC), photosynthetic rate (A), intercellular CO2 concentration (Ci), peroxidase activity (POD), malondialdehyde content (MDA), and abscisic acid (ABA). In addition, through membership function and cluster analysis, 16 wheat varieties were divided into 3 categories: drought-resistant, drought weak sensitive, and drought-sensitive. Conclusion: JM418, HM19,SM22, H4399, HG35, and GY2018 exhibited excellent drought tolerance and,therefore, can be used as ideal references to study the drought tolerance mechanism in wheat and breeding drought-tolerant wheat cultivars.

4.
Int J Mol Sci ; 24(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37175676

RESUMO

Abscisic acid receptors (ABR) play crucial roles in transducing the ABA signaling initiated by osmotic stresses, which has a significant impact on plant acclimation to drought by modulating stress-related defensive physiological processes. We characterized TaPYL5, a member of the ABR family in wheat (Triticum aestivum), as a mediator of drought stress adaptation in plants. The signals derived from the fusion of TaPYL5-GFP suggest that the TaPYL5 protein was directed to various subcellular locations, namely stomata, plasma membrane, and nucleus. Drought stress significantly upregulated the TaPYL5 transcripts in roots and leaves. The biological roles of ABA and drought responsive cis-elements, specifically ABRE and recognition sites MYB, in mediating gene transcription under drought conditions were confirmed by histochemical GUS staining analysis for plants harbouring a truncated TaPYL5 promoter. Yeast two-hybrid and BiFC assays indicated that TaPYL5 interacted with TaPP2C53, a clade A member of phosphatase (PP2C), and the latter with TaSnRK2.1, a kinase member of the SnRK2 family, implying the formation of an ABA core signaling module TaPYL5/TaPP2C53/TaSnRK2.1. TaABI1, an ABA responsive transcription factor, proved to be a component of the ABA signaling pathway, as evidenced by its interaction with TaSnRK2.1. Transgene analysis of TaPYL5 and its module partners, as well as TaABI1, revealed that they have an effect on plant drought responses. TaPYL5 and TaSnRK2.1 positively regulated plant drought acclimation, whereas TaPP2C53 and TaABI1 negatively regulated it. This coincided with the osmotic stress-related physiology shown in their transgenic lines, such as stomata movement, osmolytes biosynthesis, and antioxidant enzyme function. TaPYL5 significantly altered the transcription of numerous genes involved in biological processes related to drought defense. Our findings suggest that TaPYL5 is one of the most important regulators in plant drought tolerance and a valuable target for engineering drought-tolerant cultivars in wheat.


Assuntos
Secas , Triticum , Triticum/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Transdução de Sinais , Ácido Abscísico/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Plantas Geneticamente Modificadas/metabolismo
5.
Nanotechnology ; 34(33)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37192605

RESUMO

The temperature-dependent external quantum efficiency (EQE) droops of 265 nm, 275 nm, 280 nm, and 285 nm AlGaN-based ultraviolet-c light-emitting diodes (UVC-LEDs) differed in Al contents have been comprehensively investigated. The modifiedABCmodel (R = An+Bn2+Cn3) with the current-leakage related term,f(n)= Dn4, has been employed to analyze the recombination mechanisms in these UVC-LED samples. Experimental results reveal that, at relatively low electrical-current levels, the contribution of Shockley-Read-Hall (SRH) recombination exceeds those of the Auger recombination and carrier leakage. At relatively high electrical-current levels, the Auger recombination and carrier leakage jointly dominate the EQE droop phenomenon. Moreover, the inactivation efficiencies of 222 nm excimer lamp, 254 nm portable Mercury lamp, 265 nm, 280 nm, and 285 nm UVC-LED arrays in the inactivation ofEscherichia colihave been experimentally investigated, which could provide a technical reference for fighting against the new COVID-19.

6.
Polymers (Basel) ; 15(9)2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37177323

RESUMO

Glucuronan is a polysaccharide composed of ß-(1,4)-linked d-glucuronic acids having intrinsic properties and biological activities recoverable in many fields of application. Currently, the description of Sinorhyzobium meliloti M5N1CS mutant bacterial strain as the sole source of glucuronan makes it relevant to the exploration of new microorganisms producing glucuronan. In this study, the Peteryoungia rosettifformans strain (Rhizobia), was identified as a wild producer of an exopolysaccharide (RhrBR46) related to glucuronan. Structural and biochemical features, using colorimetric assays, Fourier infrared spectroscopy, nuclear magnetic resonance, high pressure size exclusion chromatography coupled to multi-angle light laser scattering, and enzymatic assays allowed the characterization of a polyglucuronic acid, having a molecular mass (Mw¯) of 1.85 × 105 Da, and being partially O-acetylated at C-2 and/or C-3 positions. The concentration of Mg2+ ions in the cultivation medium has been shown to impact the structure of RhrBR46, by reducing drastically its Mw¯ (73%) and increasing its DA (10%). Comparative structural analyses between RhrBR46 and the glucuronan from Sinorhyzobium meliloti M5N1CS strain revealed differences in terms of molecular weight, degree of acetylation (DA), and the distribution of acetylation pattern. These structural divergences of RhrBR46 might contribute to singular properties or biological activities of RhrBR46, offering new perspectives of application.

7.
Sci Rep ; 12(1): 14257, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35995920

RESUMO

Water scarcity is a key constraint to crop production in North China Plain (NCP), which produces the majority of the country's winter wheat (Triticum aestivum L.). The objective of this three-year field study was to see whether and when irrigation one-time in spring improved grain productivity and water use efficiency. Four sets of irrigation were established at the 3-leaf visible stage (L3) and the L4, L5, and L6 stages. When irrigation time was postponed, the spike number, 1000-grain weight, and water consumption increased progressively, whereas grain yield, grain number, dry matter, harvest, and WUE grew, then dropped, and peaked at L4. The increased grain number can be attributed to the L4's higher daily water consumption and water consumption percentage throughout the jointing-anthesis stages compared to the L3, L5, and L6. The cumulative (37 days), whereas it was longer in L3, L5, and L6(40, 42, and 43 days, respectively). Furthermore, flag leaf senescence was postponed in L4 with a higher post-anthesis leaf area index, photosynthetic rate, chlorophyll content, higher superoxide dismutase activity, and lower malondialdehyde concentration. As a result, single irrigation at the 4-leaf visible stage optimized water deficit and consumption before and after anthesis, resulting in higher yield and WUE in the NCP.


Assuntos
Triticum , Água , Irrigação Agrícola/métodos , Biomassa , Ingestão de Líquidos , Grão Comestível
8.
Front Plant Sci ; 13: 823846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35283926

RESUMO

Water deficit and rehydration frequently occur during wheat cultivation. Previous investigations focused on the water deficit and many drought-responsive genes have been identified in winter wheat. However, the hormone-related metabolic responses and de-peroxidative activities associated with rehydration are largely unknown. In this study, leaves of two winter wheat cultivars, "Hengguan35" (HG, drought-tolerant cultivar) and "Shinong086" (SN, drought-sensitive cultivar), were used to investigate water deficit and the post-rehydration process. Rehydration significantly promoted wheat growth and postponed spike development. Quantifications of antioxidant enzymes, osmotic stress-related substances, and phytohormones revealed that rehydration alleviated the peroxidation and osmotic stress caused by water deficit in both cultivars. The wheat cultivar HG showed a better rehydration-compensation phenotype than SN. Phytohormones, including abscisic acid, gibberellin (GA), jasmonic acid (JA), and salicylic acid (SA), were detected using high-performance liquid chromatography and shown to be responsible for the rehydration process. A transcriptome analysis showed that differentially expressed genes related to rehydration were enriched in hormone metabolism- and de-peroxidative stress-related pathways. Suppression of genes associated with abscisic acid signaling transduction were much stronger in HG than in SN upon rehydration treatment. HG also kept a more balanced expression of genes involved in reactive oxygen species pathway than SN. In conclusion, we clarified the hormonal changes and transcriptional profiles of drought-resistant and -sensitive winter wheat cultivars in response to drought and rehydration, and we provided insights into the molecular processes involved in rehydration compensation.

9.
Onco Targets Ther ; 14: 1317-1329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658797

RESUMO

PURPOSE: A near-infrared (NIR)-triggered trans-activating transcriptional activator (TAT)-based targeted drug delivery system for the combined chemo/photothermal therapy of melanoma, namely, TAT-TSL-TMZ (temozolomide)/IR820, was developed for the first time. METHODS: TAT-TSL-TMZ/IR820 liposomes were synthesized via thin-film dispersion and sonication. IR820 and TMZ were encased in the inner layer and lipid bilayer of the liposomes, respectively. RESULTS: Dynamic light scattering results showed that the liposomes had an average hydrodynamic size of 166.9 nm and a zeta potential of -2.55 mV. The encapsulation rates of TMZ and IR820 were 35.4% and 28.6%, respectively. The heating curve obtained under near-infrared (NIR) laser irradiation showed that TAT-TSL-TMZ/IR820 liposomes had good photothermal conversion efficiency. The in vitro drug release curve revealed that NIR laser irradiation could accelerate drug release from TAT-TSL-TMZ/IR820 liposomes. The results of inverted fluorescence microscopy and flow cytometry proved that the uptake of TAT-TSL-TMZ/IR820 liposomes by human melanoma cells (MV3 cells) was concentration-dependent and that the liposomes modified with membrane peptides were more likely to be ingested by cells than unmodified liposomes. Confocal laser scanning microscopy indicated that TAT-TSL-TMZ/IR820 liposomes entered MV3 cells via endocytosis and was stored in lysosomes. In addition, TAT-TSL-TMZ/IR820 liposomes exposed to NIR laser showed 89.73% reduction in cell viability. CONCLUSION: This study investigated the photothermal conversion, cell uptake, colocation and chemo/photothermal effect of TAT-TSL-TMZ/IR820 liposomes.

10.
Nanomedicine (Lond) ; 16(3): 221-235, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33533660

RESUMO

Background: The hypoxia of the tumor microenvironment (TME), low transfer efficiency of photosensitizers and limited diffusion distance of reactive oxygen species restrict the application of photodynamic therapy (PDT). Aim: To produce TME-responsive and effective nanoparticles for sensitizing PDT. Materials & methods: CD44 and mitochondria grade-targeted hyaluronic acid (HA)-triphenylphosphine (TPP)-aminolevulinic acid (ALA)-catalase (CAT) nanoparticles (HTACNPs) were synthesized via a modified double-emulsion method. In vitro and in vivo experiments were performed to investigate the antitumor efficacy of HTACNP-mediated PDT. Results: HTACNPs specifically targeted MV3 cells and the mitochondria and produced O2 to relieve TME hypoxia. HTACNP-mediated PDT produced reactive oxygen species to induce irreversible cell apoptosis. HTACNP-PDT inhibited melanoma growth effectively in vivo. Conclusion: HTACNP-mediated PDT improved TME hypoxia and effectively enhanced PDT for cancer.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Hipóxia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos
11.
Cardiol Res Pract ; 2021: 8841736, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33489357

RESUMO

INTRODUCTION: The relationship between ventricular pre-excitation and left ventricular dysfunction has been described in the absence of sustained supraventricular tachycardia in a series of case reports. However, there have been no systematic studies about the effect of ventricular pre-excitation on cardiac function in adult patients with different accessory pathway locations. METHODS AND RESULTS: Patients were divided into four groups based on the type and location of their accessory pathway: septal, right free wall, left free wall, and concealed. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, electrocardiogram recordings, electrophysiological properties, and transthoracic echocardiographic data (septal-to-posterior wall motion delay (SPWMD) and interventricular mechanical delay (IVMD) indicating intraventricular and interventricular dyssynchrony) were compared before and after successful ablation. Before radiofrequency catheter ablation, left ventricular ejection fraction (LVEF) was significantly lower in patients with septal and right free wall accessory pathways. Within three months after radiofrequency catheter ablation, NT-proBNP levels decreased, left ventricular function improved, and intraventricular left ventricular dyssynchrony disappeared. There was a negative correlation between initial LVEF with initial QRS duration and initial SPWMD. Notably, SPWMD had a stronger correlation with LVEF than initial QRS duration. CONCLUSIONS: Anterograde conduction with a septal or right free wall accessory pathway may cause left ventricular dyssynchrony and impair left ventricular function. Intraventricular left ventricular dyssynchrony seems to be responsible for the pathogenesis of left ventricular dysfunction. Radiofrequency catheter ablation results in decreased NT-proBNP levels, normalized QRS duration, mechanical resynchronization, and improved left ventricular function.

12.
Int J Nanomedicine ; 15: 10401-10416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376328

RESUMO

OBJECTIVE: Nanotechnology-based photodynamic therapy (PDT) is a relatively new anti-tumor strategy. However, its efficacy is limited by the hypoxic state in the tumor microenvironment. In the present study, a poly(lactic-co-glycolic acid) (PLGA) nanoparticle that encapsulated both IR820 and catalase (CAT) was developed to enhance anti-tumor therapy. MATERIALS AND METHODS: HA-PLGA-CAT-IR820 nanoparticles (HCINPs) were fabricated via a double emulsion solvent evaporation method. Dynamic light scattering (DLS), transmission electron microscopy (TEM), laser scanning confocal microscopy, and an ultraviolet spectrophotometer were used to identify and characterize the nanoparticles. The stability of the nanoparticle was investigated by DLS via monitoring the sizes and polydispersity indexes (PDIs) in water, PBS, DMEM, and DMEM+10%FBS. Oxygen generation measurement was carried out via visualizing the oxygen bubbles with ultrasound imaging system and an optical microscope. Inverted fluorescence microscopy and flow cytometry were used to measure the uptake and targeting effect of the fluorescent-labeled nanoparticles. The live-dead method and tumor-bearing mouse models were applied to study the HCINP-induced enhanced PDT effect. RESULTS: The results showed that the HCINPs could selectively target melanoma cells with high expression of CD44, and generated oxygen by catalyzing H2O2, which increased the amount of singlet oxygen, ultimately inhibiting tumor growth significantly. CONCLUSION: The present study presents a novel nanoplatform for melanoma treatment.


Assuntos
Receptores de Hialuronatos/metabolismo , Melanoma/tratamento farmacológico , Nanopartículas/química , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Animais , Catalase/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Receptores de Hialuronatos/genética , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/análogos & derivados , Verde de Indocianina/química , Melanoma/metabolismo , Melanoma/patologia , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Oxigênio Singlete/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Oncol Rep ; 42(6): 2512-2520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545500

RESUMO

A novel core­shell type thermo­nanoparticle (CSTNP) co­loaded with temozolomide (TMZ) and the fluorescein new indocyanine green dye IR820 (termed IT­CSTNPs) was designed and combined with a near­infrared (NIR) laser to realize its photothermal conversion. The IT­CSTNPs were prepared using a two­step synthesis method and comprised a thermosensitive shell and a biodegradable core. IR820 and TMZ were entrapped in the shell and the core, respectively. Dynamic light scattering results demonstrated that the average hydrodynamic size of the IT­CSTNPs was 196.4±3.1 nm with a ζ potential of ­24.9±1.3 mV. The encapsulation efficiencies of TMZ and IR820 were 6.1 and 16.6%, respectively. Temperature increase curves under NIR laser irradiation indicated that the IT­CSTNPs exhibited the desired photothermal conversion efficiency. The in vitro drug release curves revealed a suitable release capability of IT­CSTNP under physiological conditions, whereas NIR laser irradiation accelerated the drug release. Inverted fluorescence microscopy and flow cytometry results revealed that the uptake of IT­CSTNPs by A375 melanoma cells occurred in a concentration­dependent manner. Confocal laser scanning microscopy results indicated that IT­CSTNPs entered tumour cells via endocytosis and were located in intercellular lysosomes. In summary, the present study explored the photothermal conversion capability, cellular uptake, and intracellular localization of IT­CSTNPs.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Portadores de Fármacos/química , Hipertermia Induzida/métodos , Melanoma/terapia , Neoplasias Cutâneas/terapia , Temozolomida/administração & dosagem , Antineoplásicos Alquilantes/farmacocinética , Linhagem Celular Tumoral , Terapia Combinada/métodos , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos/efeitos da radiação , Difusão Dinâmica da Luz , Endocitose/efeitos da radiação , Humanos , Hipertermia Induzida/instrumentação , Verde de Indocianina/administração & dosagem , Verde de Indocianina/análogos & derivados , Lasers , Melanoma/patologia , Nanopartículas/química , Nanopartículas/efeitos da radiação , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Neoplasias Cutâneas/patologia , Temozolomida/farmacocinética
14.
Exp Ther Med ; 18(3): 2353, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31410184

RESUMO

[This retracts the article DOI: 10.3892/etm.2017.4355.].

15.
Sci Rep ; 9(1): 2595, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30796322

RESUMO

Ultraviolet (UV) irradiation, particularly ultraviolet A (UVA), stimulates reactive oxygen species (ROS) production in the epidermis and dermis, which plays a major part in the photoageing of human skin. Several studies have demonstrated that cerium oxide nanoparticles (CeO2 NP) can exhibit an antioxidant effect and free radical scavenging activity. However, the protective role of CeO2 NP in skin photoageing and the underlying mechanisms are unclear. In this study, we investigated the effects of CeO2 NP on UVA-irradiated human skin fibroblasts (HSFs) and explored the potential signalling pathway. CeO2 NP had no apparent cytotoxicity, and could reduce the production of proinflammatory cytokines, intracellular ROS, senescence-associated ß-galactosidase activity, and downregulate phosphorylation of c-Jun N-terminal kinases (JNKs) after exposure to UVA radiation. Based on our findings, CeO2 NPs have great potential against UVA radiation-induced photoageing in HSFs via regulating the JNK signal-transduction pathway to inhibit oxidative stress and DNA damage.


Assuntos
Senescência Celular/efeitos dos fármacos , Cério/farmacologia , Fibroblastos , Envelhecimento da Pele/efeitos dos fármacos , Pele , Raios Ultravioleta/efeitos adversos , Linhagem Celular , Citocinas/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/patologia
17.
Int J Cancer ; 143(12): 3050-3060, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29981170

RESUMO

Nanoparticle-based phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit strong efficacy, minimal invasion and negligible side effects in tumor treatment. These phototherapies have received considerable attention and been extensively studied in recent years. In addition to directly killing tumor cells through heat and reactive oxygen species, PTT and PDT can also induce various antitumor effects. In particular, the resultant massive tumor cell death after PTT and PDT triggers immune responses, including the redistribution and activation of immune effector cells, the expression and secretion of cytokines and the transformation of memory T lymphocytes. The antitumor effects can be enhanced by immune checkpoint blockage therapy. This article reviewed the recent advances of nanoparticle-based PTT and PDT, summarized the studies on nanoparticle-based photothermal and photodynamic immunotherapies in vitro and in vivo, and discussed challenges and future research directions.


Assuntos
Hipertermia Induzida , Imunoterapia/métodos , Nanopartículas , Neoplasias/terapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Citocinas/biossíntese , Citocinas/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Memória Imunológica/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia , Fármacos Fotossensibilizantes/administração & dosagem , Linfócitos T/imunologia
18.
Biochem Biophys Res Commun ; 503(3): 1450-1456, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30054042

RESUMO

Vascular disease can manifest as stenotic plaques or ectatic aneurysms. Human abdominal aortic aneurysms (AAA) comprise an inflammatory disease characterized by the predominance of T helper type 2 (Th2) cytokine expression. Leptin has been clearly demonstrated to play an important role in regulating Th0 cell to Th1. So, we hypothesize that leptin has a protective effect on aneurysm formation. In this study, we demonstrated that intraperitoneal injection of leptin attenuated Ang II-induced AAA formation in ApoE-/- mice with no effect on serum lipids and systolic blood pressure. To investigate the mechanisms involved, we found that leptin pretreatment exhibited decreased protein expression of matrix metalloproteinase 2 (MMP-2) and MMP-9 and increased transforming growth factor-ß1 (TGF-ß1). We also examined potential mechanism of leptin as a modulator of the immune response. Our results proved that pretreatment with leptin downregulated protein expression of Th2 cytokine IL-4 and mRNA levels of GATA-3, the key transcription factor for Th2 polarization, and upregulated Th1 cytokine INF-γ and T-bet, the key transcription factor for Th1 polarization. Taken together, leptin, with the effect of regulation of Th1/Th2 cytokines, may have therapeutic potential for the treatment of AAA. Leptin may constitute a novel therapeutic strategy to prevent AAA formation.


Assuntos
Angiotensina II/farmacologia , Aneurisma da Aorta Abdominal/metabolismo , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Leptina/metabolismo , Angiotensina II/administração & dosagem , Animais , Aneurisma da Aorta Abdominal/genética , Inflamação/metabolismo , Injeções Intraperitoneais , Leptina/administração & dosagem , Leptina/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangue , Proteínas Recombinantes/metabolismo , Linfócitos T/metabolismo , Células Th1
19.
Mol Cancer ; 17(1): 91, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769134

RESUMO

Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease. Clinical studies on some neoplasms, such as glioblastoma, ovarian cancer, and cholangiocarcinoma, have achieved desirable outcome. This review describes the history and evolution of CAR-T, generalizes the structure and preparation of CAR-T, and summarizes the latest advances on CAR-T cell therapy in different tumor types. The last section presents the current challenges and prospects of CAR-T application to provide guidance for subsequent research.


Assuntos
Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/transplante , Ensaios Clínicos como Assunto , Engenharia Genética , Humanos , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia , Resultado do Tratamento
20.
Cancer Lett ; 423: 16-26, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29524557

RESUMO

Chemotherapy is an important treatment for malignant tumors; however, its efficacy and clinical application are limited by its side effects and drug resistance properties. Chemotherapy and phototherapy exhibit synergistic anti-tumor effects. In the present study, a carboxylated poly(amido-amine) (PAMAM) with low cytotoxicity was synthesized as a delivery nanocarrier for loading chemotherapeutic drugs, temozolomide (TMZ), and fluorescent dye indocyanine green (ICG). Hyaluronic acid (HA), which targets the CD44-overexpressing cancer cells, was modified on the nanocarrier surface to enhance the selective killing of melanoma cells. Temperature effect and singlet oxygen production experiments showed that the ICG-loaded nanoparticles exhibited good capability to generate heat and singlet oxygen under near-infrared (NIR) light (808 nm) irradiation. In vivo imaging measurement confirmed that the ICG-encapsulated nanoparticle was delivered successfully and effectively accumulated in the tumor site. In vitro and in vivo experiments revealed that the joint application of TMZ- and ICG-loaded nanoparticle can kill melanoma cells and suppress growth after NIR light irradiation. Thus, HA-modified carboxylated PAMAM loaded with TMZ and ICG serves as a promising nanoplatform for melanoma treatment.


Assuntos
Receptores de Hialuronatos/metabolismo , Hipertermia Induzida/métodos , Melanoma/terapia , Poliaminas/química , Temozolomida/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Verde de Indocianina , Melanoma/metabolismo , Camundongos , Nanopartículas , Temozolomida/química , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
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