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1.
Ying Yong Sheng Tai Xue Bao ; 32(2): 529-537, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650362

RESUMO

We measured the morphology traits (specific root length, specific root surface area, root tissue density, average root diameter) and architecture traits (root fork, root fork ratio, increase rate of root length, root tip density, root fork density) of fine roots in two mycorrhiza tree species, Castanopsis faberi (ectomycorrhizal) and Schima superba (arbuscular mycorrhizal), in an evergreen broadleaved forest in the middle subtropical zone. Root bags method was used in an in situ nitrogen deposition experiment. The aim of this study was to reveal the differences in the plastic responses of fine root morphology and architecture traits to nitrogen deposition between the different mycorrhizal trees. The plastic responses of specific root length, specific root surface area and root fork to nitrogen addition decreased from the first-order root to the fourth-order root, while root tissue density showed an opposite pattern. Such a result indicated a trade-off between nutrient acquisition and resource maintenance of different fine root orders. Different mycorrhizal tree species adopted diffe-rent adaptation strategies to the variations of soil nitrogen availability. C. faberi adopted an opportuni-stic strategy, which relied on fine root to improve nutrient absorption efficiency, enhanced the capacity of space expansion and in-situ nutrient absorption to focus on rapid nutrient absorption strategy. S. superba did not change fine root morphological traits through the trade-off between nutrient absorption efficiency and root construction cost, but relied more on the complementarity between mycorrhizal fungi and fine root architecture traits for nutrient acquisition. The differences in the cost of maintaining and constructing fine root C between different mycorrhizal trees led to fine root adopting the most suitable nutrient capture strategy.

2.
Inorg Chem ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591740

RESUMO

The quaternary chalcogenide composites Cu2ZnSn1-xAgxSe4 (0 ≤ x ≤ 0.075) have been successfully synthesized by high-temperature melting and annealing followed by hot-pressing. The phase structure of the bulk sample has been analyzed by powder X-ray diffraction and Rietveld refinement combined with Raman spectroscopy to confirm Cu2ZnSnSe4 as the main phase with ZnSe and Cu5Zn8 secondary phases. The thermoelectric properties of all specimens have been investigated in the temperature range of 300-700 K. The replacement of Sn by Ag significantly enhances the electrical transport properties by providing extra charge carriers. The tremendous reduction in electrical resistivity enhances the power factor, and a maximum power factor of 804 µW K-2 m-1 is achieved at 673 K for the specimen with 5% Ag content. Furthermore, increased point defects increase phonon scattering, resulting in reduced thermal conductivity. The combined effect of improved power factor and suppressed thermal conductivity provides a good boost to the dimensionless figure of merit. The maximum figure of merit of zT = 0.25 has been achieved at 673 K for Cu2ZnSn0.95Ag0.05Se4, which is 2.5 times the value of the parent sample.

3.
Talanta ; 225: 122065, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592784

RESUMO

The development of convenient and efficient fluorescence techniques is of great significance for selective detection and precise determination of biotoxic N2H4 in human health and environmental sciences. By the pre-organization-assisted template synthesis, disclosed here is a luminescent Sm(III) macrocycle-based probe Sm-2m bearing dynamic imine bonds as recognition moieties which provides the selective and ratiometric turn-off fluorescence sensing for N2H4 over various amine species based on the N2H4-induced structure transformation. This fluorescent sensing process finished within 20 min shows the low limit of detection (0.18 µM, 7.2 ppb) and wide linear sensing range (0-60.0 µM). Furthermore, probe Sm-2m is also be used to quantitatively determine N2H4 in vapor gas and water samples through fluorescence color changes, which are evaluated by the Sm-2m-impregnated test paper strips and RGB value outputs. Finally, our proposed smartphone-based analytical method gives satisfactory N2H4 detection results. It is thus believed that this work can shed some lights on development of optical probes and detection techniques for N2H4, even other hazardous chemicals.

4.
Pulm Pharmacol Ther ; : 102000, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33601000

RESUMO

BACKGROUND: Although myricetin exerts anti-inflammation, anti-cancer, and anti-oxidation effects, the relationship between myricetin and tumor necrosis factor alpha (TNF-α) -stimulated inflammation in A549 cells remains unclear. This study sought to assess whether myricetin has an anti-inflammatory effect on TNF-α-induced A549 cells and clarify the potential mechanisms. METHODS: Cell viability was examined with a Cell Counting Kit-8, and cytokine levels were determined by enzyme-linked immunosorbent assay and reverse transcription-quantitative PCR. Potential mechanisms were further explored by western blotting, immunofluorescence, and SIRT1 activity assays. RESULTS: In A549 cells, TNF-α stimulation upregulated the production of interleukin-6 (IL-6) and interleukin-8 (IL-8). Moreover, TNF-α activated the nuclear factor-κB (NF-κB) pathway, as confirmed by IκB-α degradation, and phosphorylation and nuclear migration of NF-κB p65. However, pretreatment with myricetin significantly attenuated the observed responses triggered by TNF-α. Mechanistically, myricetin strongly increased the deacetylase activity through decreasing phosphorylation, but not expression, of sirtuin-1 (SIRT1) in TNF-α-stimulated A549 cells. Myricetin-mediated SIRT1 activation was further evidenced by the decreased acetylation of NF-κB p65 and p53. Subsequently, all of these concurrent changes were reversed by the addition of salermide (SIRT1 inhibitor), illustrating the critical role of SIRT1 in mediation of anti-inflammatory processes by myricetin. CONCLUSIONS: Myricetin, an enhancer of SIRT1, inhibited TNF-α-induced NF-κB activation in A549 cells, therefore, reducing their inflammatory response. Our findings provide insight for novel therapies for inflammation-related diseases, such as asthma and chronic obstructive pulmonary disease.

5.
Carbohydr Polym ; 257: 117667, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33541670

RESUMO

While gut bacteria have different abilities to utilize dietary fibers, the degree of fiber structural alignment to bacteria species is not well understood. Corn bran arabinoxylan (CAX) was used to investigate how minor polymer fine structural differences at the genotype × environment level influences the human gut microbiota. CAXs were extracted from 4 corn genotypes × 3 growing years and used in in vitro fecal fermentations. CAXs from different genotypes had varied contents of arabinose/xylose ratio (0.46-0.54), galactose (58-101 mg/g), glucuronic acid (18-32 mg/g). There was genotype- but not environment-specific differences in fine structures. After 24 h fermentation, CAX showed different acetate (71-86 mM), propionate (35-44 mM), butyrate (7-10 mM), and total short chain fatty acid (SCFA) (117-137 mM) production. SCFA profiles and gut microbiota both shifted in a genotype-specific way. In conclusion, the study reveals a very high specificity of fiber structure to gut bacteria use and SCFA production.

6.
J Clin Lab Anal ; : e23722, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33543801

RESUMO

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease mediated by acetylcholine receptor antibodies. Exosomes were shown to be involved in the immune modulation and autoimmune diseases. However, the expression and function of exosomal long noncoding RNAs (lncRNAs) in MG are still unclear. METHODS: We conducted high-throughput sequencing to detect the lncRNA profiles of serum exosomes in 6 MG patients (2 grade I, 2 grade IIa, and 2 grade IIb) and 6 healthy controls (HC). Then, differentially expressed (DE) lncRNAs with the greatest difference between the MG and HC groups were selected for further quantitative real-time polymerase chain reaction (qRT-PCR) validation in additional 30 MG patients and 10 HC. The DE lncRNAs were used to construct the coding/noncoding network and perform enrichment analysis. RESULTS: We identified 378 significantly upregulated and 348 significantly downregulated lncRNAs in MG patients compared with HC. The top 5 lncRNAs (NR_104677.1, ENST00000583253.1, NR_046098.1, NR_022008.1, and ENST00000581362.1) were validated and shown to be significantly increased in the serum exosome of MG, and the expression level of NR_046098.1 significantly increased with the MG grading. Enrichment analysis showed that DE genes mainly participated in the basic biological regulation of MG and immune-related pathways, such as autoimmune thyroid disease pathway and T-cell receptor signaling pathway. A specific lncRNA-miRNA-mRNA regulatory network associated with the 5 lncRNAs, 14 MG-related miRNAs and 30 mRNAs was constructed. CONCLUSIONS: We conducted a comprehensive analysis of exosomal lncRNAs to reveal potential biomarkers for the MG diagnosis and severity assessment.

7.
Food Funct ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599218

RESUMO

Neonatal hypoxic-ischemic (HI) brain injury can lead to mortality and severe long-term disabilities including cerebral palsy and brain injury. However, the treatment options for neonatal hypoxic-ischemic (HI) brain injury are limited. Apigenin is abundantly present in vegetables, celery, and chamomile tea with diverse biological functions, such as anti-inflammatory, anti-apoptotic, antioxidant, and anticancer effects. However, it has not yet been reported whether apigenin exerts a neuroprotective effect against neonatal hypoxic-ischemic (HI) brain injury. In this study, we investigated whether apigenin could ameliorate HI brain injury and explored the associated mechanism using in vivo experiments. We found that apigenin remarkably reduced the infarct volume and ameliorated cerebral edema, decreased inflammatory response, inhibited apoptosis, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. Mechanistically, we found that apigenin exerted a neuroprotective effect against HI brain injury by activating the PI3K/Akt/Nrf2 pathway. In summary, all these results demonstrate that apigenin could be a potential therapeutic approach for neonatal hypoxic-ischemic (HI) brain injury.

8.
ACS Appl Mater Interfaces ; 13(7): 8015-8025, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33561348

RESUMO

Deoxyribozyme (DNAzyme) is regarded as a promising gene therapy drug. However, poor cellular uptake efficacy and low biological stability limit the utilization of DNAzyme in gene therapy. Here, we report a well-known programmable DNAzyme-based nanotweezer (DZNT) that provides a new strategy for the detection of TK1 mRNA and survivin mRNA-targeted gene silencing therapy. At the end of the DZNT arm, there are two functionalized single-stranded DNA and each consists of two parts: the segment complementary to TK1 mRNA and the split-DNAzyme segment. The hybridization with intracellular TK1 mRNA enables the imaging of TK1 mRNA. Meanwhile, the hybridization draws the split-DNAzyme close to each other and activates DNAzyme to cleave the survivin mRNA to realize gene silencing therapy. The results demonstrate that the DZNT nanocarrier has excellent cell penetration, good biocompatibility, and noncytotoxicity. DZNT can image intracellular biomolecule TK1 mRNA with a high contrast. Furthermore, the split-DNAzyme can efficiently cleave the survivin mRNA with the aid of TK1 mRNA commonly present in cancer cells, accordingly can selectively kill cancer cells, and has no harm to normal cells. Taken together, the multifunctional programmable DZNT provides a promising platform for the early diagnosis of tumors and gene therapy.

9.
Cancer Biol Med ; 18(1): 227-244, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33628597

RESUMO

Objective: Natural extracts, including nobiletin, have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs. However, whether and how nobiletin affects tumor growth and progression in renal cell carcinoma (RCC) are still unclear. Methods: Cell proliferation, cell cycle and apoptosis analyses, colony-formation assays, immunoblotting analysis, and qRT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro. The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib. Results: Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells. Mechanistically, nobiletin decreased SKP2 protein expression by reducing its transcriptional level. The downregulated SKP2 caused accumulation of its substrates, p27 and p21, which further inhibited the activity of the G1 phase-related protein, CDK2, leading to inhibition of cell proliferation and tumor formation. A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor, palbociclib. A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model. Conclusions: Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor, palbociclib, on RCC, which indicates a potential new therapeutic strategy.

10.
Pituitary ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33502672

RESUMO

PURPOSE: To develop an index for the differential diagnosis of corticotropin-dependent Cushing syndrome (CS). METHODS: The development cohort included 112 consecutive patients with clinicopathologically confirmed corticotropin-dependent CS at the Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, from December 2004 to May 2020, and data of 126 patients from studies published from 2016 to August 2020, identified through search in PubMed, Embase and the Cochrane Library, was extracted for external validation. The index was calculated as the product of plasma adrenocorticotropic hormone (ACTH, pmol/L) and urinary free cortisol (UFC, nmol/24 h) divided by 10,000. The discriminative ability was tested using receiver operating characteristics (ROC) curve analysis. RESULTS: In development cohort, area under curve of ROC analysis of the ACTH-UFC index in identifying Cushing disease (CD) was 0.977. The diagnostic accuracy of ACTH-UFC index ≤ 11 was comparable to that of 48 h 8 mg/d high-dose dexamethasone test (HDDST) in identifying CD, with sensitivity, specificity, positive and negative likelihood ratios of 96.6%, 87.5%, 7.73, and 0.04, respectively. The sensitivity of ACTH-UFC index ≤ 11 in parallel combination with pituitary magnetic resonance imaging (MRI) was 100% for identifying CD. The performance of the ACTH-UFC index in parallel or serial combination with pituitary MRI was similar in the validation cohort. CONCLUSIONS: ACTH-UFC index provides a rapid, convenient and non-invasive adjunctive approach for the differential diagnosis of corticotropin-dependent CS, with no risk of aggravating metabolic disturbances. Investigations for ectopic causes of corticotropin-dependent CS should be performed with ACTH-UFC index > 11 and negative contrasted pituitary MRI.

11.
Theranostics ; 11(3): 1232-1248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391532

RESUMO

Rationale: Glial scars present a major obstacle for neuronal regeneration after stroke. Thus, approaches to promote their degradation and inhibit their formation are beneficial for stroke recovery. The interaction of microglia and astrocytes is known to be involved in glial scar formation after stroke; however, how microglia affect glial scar formation remains unclear. Methods: Mice were treated daily with M2 microglial small extracellular vesicles through tail intravenous injections from day 1 to day 7 after middle cerebral artery occlusion. Glial scar, infarct volume, neurological score were detected after ischemia. microRNA and related protein were examined in peri-infarct areas of the brain following ischemia. Results: M2 microglial small extracellular vesicles reduced glial scar formation and promoted recovery after stroke and were enriched in miR-124. Furthermore, M2 microglial small extracellular vesicle treatment decreased the expression of the astrocyte proliferation gene signal transducer and activator of transcription 3, one of the targets of miR-124, and glial fibrillary acidic protein and inhibited astrocyte proliferation both in vitro and in vivo. It also decreased Notch 1 expression and increased Sox2 expression in astrocytes, which suggested that astrocytes had transformed into neuronal progenitor cells. Finally, miR-124 knockdown in M2 microglial small extracellular vesicles blocked their effects on glial scars and stroke recovery. Conclusions: Our results showed, for the first time, that microglia regulate glial scar formation via small extracellular vesicles, indicating that M2 microglial small extracellular vesicles could represent a new therapeutic approach for stroke.

12.
Anal Chim Acta ; 1144: 34-42, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453795

RESUMO

Herein, we report our strategy to develop the efficient chemosensor and real-time monitoring technique for cyanuric chloride (TCT) detection. A luminescent macrocyclic mononuclear Sm(III) complex Sm-2k bearing with two dynamic imine bonds has been constructed via the template synthesis between dialdehyde H2Qk and matched diamine 1,2-bis(2-aminoethoxy)ethane. Sensing experiments reveal that complex Sm-2k exhibits the turn-off fluorescent and colorimetric response for TCT in CH3OH. It is especially encouraging that this optical sensing process is not only rapid within 60 s but also high-efficient in the presence of TCT analogues as well as sensitive with the low limit of detection (LOD, 1.74 µM) and wide linear sensing range. Mechanism studies demonstrate that TCT sensing is mainly based on the imine bond transformation of probe Sm-2k, which is due to the increased acidity induced by TCT. Meanwhile, a smartphone-based analytical method was developed to make complex Sm-2k accessible for the real-time TCT detection by RGB value outputs. It is believed that this work can shed some constructive lights on design of chemosensors and convenient detection technique for highly reactive analytes.

13.
Food Chem ; 343: 128402, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33406572

RESUMO

A new method was investigated to decline the antigenicity of ß-Lactoglobulin (ß-LG) by site specifically conjugating ß-LG at the N-terminus with 5 kDa and 10 kDa monomethoxy polyethylene glycol propyl aldehyde (mPEG-ALD). The optimal reaction conditions were molar ratio of 1:10 (ß-LG:mPEG-ALD), reaction time for 16 h, and pH 5.0, and the content of mono-PEGylated ß-LG was 51.3%. The results showed that mono-PEGylated ß-LG with molecular mass of 23.2 kDa and 28.5 kDa. The peptide fragments of mPEG5kDa-ALD-ß-LG produced the same sequence pattern of ß-LG except for the absence of one peptides f(1-14), indicating that α-amino group at the N-terminal was selectively modified. Furthermore, the conformation of modified ß-LG underwent into slight change. The antigenicity of mPEG5kDa-ALD-ß-LG and mPEG10kDa-ALD-ß-LG decreased from 144.4 µg/mL to 66.7 and 39.0 µg/mL respectively. It was speculated that the steric hindrance effect of PEG was the main reason for the decline of antigenicity of ß-LG.


Assuntos
Lactoglobulinas/química , Polietilenoglicóis/química , Animais , Antígenos/química , Antígenos/imunologia , Bovinos , Ensaio de Imunoadsorção Enzimática , Lactoglobulinas/imunologia , Peso Molecular , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
14.
Acta Biomater ; 123: 335-345, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476826

RESUMO

Multidrug resistance (MDR) induced by the overexpression of P-glycoprotein (P-gp) transporters mainly leads to chemotherapy (CT) failure. Herein, a NIR/pH dual-sensitive charge-reversal polypeptide nanocomposite (PDA-PLC) was developed for co-delivering a nitric oxide (NO) donor and doxorubicin (DOX). Under near-infrared (NIR) irradiation, the released high-concentration of NO gas inhibited the P-gp expression to sensitize the chemotherapeutic medicine DOX and assisted photothermal therapy (PTT) to eradicate cancer cells without skin scarring. Further, the distinctive charge-reversal capacity of PDA-PLC significantly facilitated cellular uptake in the tumor acidic microenvironment (pH 6.8) and enhanced its stability in the physiological environment (pH 7.4). This DOX-loading polypeptide nanocomposite (PDA-PLC/DOX) provides an effective strategy for the PTT-NO-CT triple-combination therapy to overcome MDR STATEMENT OF SIGNIFICANCE: Multidrug resistance (MDR) has been considered to be the paramount factor of chemotherapy (CT) failure in cancer. In this work, an NIR/pH dual-sensitive charge-reversal polypeptide nanomedicine (PDA-PLC/DOX) was developed to overcome MDR through the triple combination therapy of photothermal therapy (PTT), NO gas therapy, and CT. The distinctive charge-reversal capacity of PDA-PLC/DOX significantly facilitated cellular uptake in the tumor acidic microenvironment (pH 6.8) and enhanced its stability in the physiological environment (pH 7.4), while the NIR trigger-released NO gas greatly inhibited the expression of P-gp and synergistically enhanced PTT and CT efficacy. This polypeptide nanocomposite PDA-PLC/DOX provides an effective strategy of using the PTT-NO-CT triple combination therapy with charge-reversal property to completely eradicate the MCF-7/ADR tumor.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33512871

RESUMO

The aim of the study was to explore the clinicopathologic characteristics of sacrococcygeal yolk sac tumor (SYST) associated with relapse and the role of sensitivity to neoadjuvant chemotherapy in predicting outcome. The authors investigated prognostic factors of age, stage, initial tumor size, pathologic response to neoadjuvant chemotherapy, and alfa fetoprotein. A total of 26 patients with SYST were enrolled. Neoadjuvant chemotherapy was administered to 20 cases. Six patients underwent resection as initial therapy. Recurrence occurred in 12 patients. Nine patients with specimens exhibiting no malignant component after chemotherapy did not experience recurrence. By contrast, relapses occurred in 7 out of 11 patients with viable residual tumor after neoadjuvant chemotherapy. All relapsed patients still achieved partial remission or complete remission after salvage therapy. Five-year relapse-free survival and overall survival rates were 55.2% and 100%, respectively (median follow-up, 59.5 mo; range, 16 to 155). Patients with complete necrosis after neoadjuvant chemotherapy had a better outcome compared with children with viable residual tumor. Relapse-free survival of pediatric SYSTs in this cohort were still low and warrants the multidisciplinary effort.

16.
Ecotoxicol Environ Saf ; 211: 111946, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33493718

RESUMO

Increased applications of quantum dots (QDs) in the biomedical field have aroused attention for their potential toxicological effects. Although numerous studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice. The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes in organ index of main organs, and the abnormality of liver and kidney function parameters. Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs.


Assuntos
Pontos Quânticos/toxicidade , Acrossomo , Animais , Compostos de Cádmio/química , Compostos de Cádmio/toxicidade , Epididimo , Feminino , Fertilidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pontos Quânticos/química , Reprodução , Compostos de Selênio/farmacologia , Motilidade Espermática , Espermatozoides , Sulfetos/toxicidade , Testículo , Distribuição Tecidual , Testes de Toxicidade , Compostos de Zinco/toxicidade
17.
J Mater Chem B ; 9(6): 1698-1706, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33495772

RESUMO

The overexpression of P-glycoprotein (P-gp) in multidrug resistance (MDR) cancer cells increases the efflux of anticancer drugs thereby causing the failure of clinical chemotherapy. To address this obstacle, in this study, we rationally designed a near-infrared (NIR) light-responsive nitric oxide (NO) delivery nanoplatform for targeting the MDR tumors based on core-shell structured nanocomposites. The mesoporous silica shell provided abundant sites for modification of the NO donor, N-diazeniumdiolate, and tumor-targeting molecule, folic acid (FA), and enabled high encapsulation capacity for doxorubicin (DOX) loading. Under NIR light irradiation, the generation of NO gas can efficiently augment chemotherapeutic effects via the inhibition of P-gp expression. Simultaneously, the photothermal conversion agents of the Cu2-xSe core produce a large amount of heat for photothermal therapy (PTT). Finally, this combinational gas/chemo/PTT not only displays a superior and synergistic effect for overcoming MDR cancer, but also provides an efficient strategy to construct a multifunctional nano-drug delivery system with diversified therapeutic modalities.

18.
Toxins (Basel) ; 13(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477467

RESUMO

Staphylococcus aureus is a Gram-positive opportunistic pathogen which causes infections in a variety of vertebrates. Virulence factors are the main pathogenesis of S. aureus as a pathogen, which induce the host's innate and adaptive immune responses. Toxic shock syndrome toxin 1 (TSST-1) is one of the most important virulence factors of S. aureus. However, the role of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) in TSST-1-induced innate immune response is still unclear. Here, purified recombinant TSST-1 (rTSST-1) was prepared and used to stimulate mouse peritoneal macrophages. The results showed that under the action of adenosine-triphosphate (ATP), rTSST-1 significantly induced interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) production in mouse macrophages and the production was dose-dependent. In addition, rTSST-1+ATP-stimulated cytokine production in macrophage depends on the activation of toll like receptor 4 (TLR4), but not TLR2 on the cells. Furthermore, the macrophages of NLRP3-/- mice stimulated with rTSST-1+ATP showed significantly low levels of IL-1ß production compared to that of wild-type mice. These results demonstrated that TSST-1 can induce the expression of inflammatory cytokines in macrophages via the activation of the TLR4 and NLRP3 signaling pathways. Our study provides new information about the mechanism of the TSST-1-inducing host's innate immune responses.

19.
Int J Psychophysiol ; 162: 34-39, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33497765

RESUMO

BACKGROUND: A number of functional magnetic resonance imaging studies have shown that the dorsolateral prefrontal cortex (dlPFC) is a critical brain region for response inhibition. However, how it exerts this function remains unclear. This study investigated whether stimulating the right dlPFC by transcranial direct current stimulation (tDCS) affects performance on stop signal task. METHODS: A total of 92 healthy subjects were enrolled in the study and randomly divided into three groups. The anode group received anodal stimulation over the right dlPFC and cathodal stimulation over the left supraorbital; the cathode group received cathodal stimulation over the right dlPFC and anodal stimulation over the left supraorbital; and the sham group received sham tDCS. All subjects performed a computer-based stop-signal task before and after tDCS. RESULT: Performance on the response inhibition task after tDCS was improved in groups with both anodal and cathodal stimulation. Specifically, there was a decrease in the stop-signal reaction time in these subjects, whereas no difference was observed in the sham group. Consistent with signal detection theory, discrimination and decision bias was improved by anode tDCS relative to the sham group, while discrimination was also improved in the cathode group. CONCLUSION: Anode and cathode tDCS of the right dlPFC improves response inhibition, with the right dlPFC may playing a key role in this process.

20.
Food Chem ; 339: 128081, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152874

RESUMO

In the present study, three-phase partitioning (TPP) coupled with gradient ethanol precipitation (GEP) was developed for the first time to extract and isolate polysaccharides (GPSs) from raw garlic (Allium sativum L.) bulbs. Four kinds of fructose polymers, namely, GPS35, GPS50, GPS65, and GPS80, were obtained at the final ethanol precipitation concentrations of 35%, 50%, 65%, and 80% (v/v), respectively, and their physicochemical characteristics and in vitro biological activities were investigated. Results indicated that GPS80 had higher carbohydrate (86.68% ± 0.90%) and uronic acid (12.89% ± 0.09%) contents, lower weight-average molecular weight (8.93 × 103 Da), and looser surface morphology than the other three GPSs. Furthermore, among the four GPSs, GPS80 exhibited the strongest antioxidant capacities, inhibitory effects on α-amylase and α-glycosidase, and nitric oxide stimulatory activity on RAW264.7 macrophage cells in vitro. Therefore, this study provides a simple and feasible technological strategy for producing bioactive polysaccharides from raw Allium vegetables.


Assuntos
Precipitação Química , Etanol/química , Alho/química , Caules de Planta/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Fenômenos Químicos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Peso Molecular , Polissacarídeos/isolamento & purificação , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo
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