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1.
J Ethnopharmacol ; 331: 118273, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38703874

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq.ex Havil. was a classical medicinal plant exhibiting the properties of extinguishing wind, arresting convulsions, clearing heat and pacifying the liver. Clinically, it could be utilized for the treatment of central nervous system-related diseases, such as Alzheimer's disease. U. rhynchophylla (UR) and its major ingredient alkaloid compounds (URA) have been proved to exert significant neuroprotective effects. However, the potential mechanism aren't fully understood. AIM OF THE STUDY: This study systematically examined the therapeutic effects of URA on AD pathology in APP-PS1 mice, and revealed the potential mechanism of action. MATERIALS AND METHODS: The cognitive ability was evaluated by morris water maze test in APP-PS1 mice. The H&E staining was used to observe the tissue pathological changes. The ELISA kits were used to detect the level of inflammatory factors. The flow cytometry was used to analyze the percentage of CD4+ effector T cells (Teffs) in spleen. The immunofluorescent staining was performed to count the Teffs and microglia in brain. The protein expression was analyzed by western blot. In vitro, the lymphocyte proliferation induced by ConA was performed by CCK-8 kits. The IFN-γ, IL-17, and TNF-α production were detected by ELISA kits. The effects of URA on glycolysis and the involvement of PI3K/Akt/mTOR signaling pathway was analyzed by Lactic Acid assay kit and western blot in ConA-induced naive T cell. RESULTS: URA treatment improved AD pathology effectively as demonstrated by enhanced cognitive ability, decreased Aß deposit and Tau phosphorylation, as well as reduced neuron apoptosis. Also, the neuroinflammation was significantly alleviated as evidenced by decreased IFN-γ, IL-17 and increased IL-10, TGF-ß. Notably, URA treatment down-regulated the percentage of Teffs (Th1 and Th17) in spleen, and reduced the infiltration of Teffs and microglia in brain. Meanwhile, the Treg cell was up-regulated both in spleen and brain. In vitro, URA was capable of attenuating the spleen lymphocyte proliferation and release of inflammatory factors provoked by ConA. Interestingly, glycolysis was inhibited by URA treatment as evidenced by the decrease in Lactic Acid production and expression of HK2 and GLUT1 via regulating PI3K/Akt/mTOR signaling pathway in ConA-induced naive T cell. CONCLUSION: This study proved that URA could improve AD pathology which was possibly attributable to the restraints of CD4+ T cell mediated neuroinflammation via inhibiting glycolysis.

2.
J Colloid Interface Sci ; 666: 244-258, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38598997

RESUMO

Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic cancer cell environment, causing Ca2+ overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO3 decomposition, promoting the Ca2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.


Assuntos
Carbonato de Cálcio , Glucose Oxidase , Compostos de Manganês , Óxidos , Glucose Oxidase/metabolismo , Glucose Oxidase/química , Glucose Oxidase/farmacologia , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Óxidos/química , Óxidos/farmacologia , Humanos , Animais , Carbonato de Cálcio/química , Carbonato de Cálcio/farmacologia , Carbonato de Cálcio/metabolismo , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas/química , Povidona/química , Povidona/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula , Linhagem Celular Tumoral , Peróxido de Hidrogênio/metabolismo , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Propriedades de Superfície , Camundongos Endogâmicos BALB C
3.
Int J Biol Macromol ; 267(Pt 1): 131292, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580015

RESUMO

To enhance the water-resistance and antibacterial properties of KGM films, mandarin oil (MO), was directly emulsified by pectin and then dispersed to the KGM matrix. The effect of MO concentration (0, 0.5, 1.0, 1.5, and 2 wt%) on the performance of the film-forming emulsions as well as the emulsion films was investigated. The results revealed that pectin could encapsulate and protect MO, and KGM as film matrix could further contributed to the high stability of the film-forming emulsions. The FT-IR, XRD, and SEM suggested that MO stabilized by pectin was uniformly distributed in the KGM matrix. The compatibility and good interaction between KGM and pectin contributed to highly dense and compact structure. Furthermore, increasing the concentration of MO effectively improved water-resistance, oxygen barrier, and antimicrobial activity of the KGM based films. The 1.5 wt% MO loaded KGM film had the highest tensile strength (72.22 MPa) and water contact angle (θ = 95.73°), reduced the WVP and oxygen permeability by about 25.8 % and 32.8 times, respectively, prolonged the shelf life of strawberries for 8 days. As demonstrated, the 1.5 wt% MO-loaded KGM film has considerable potential for high-performance natural biodegradable active films to ensure food safety and reduce environmental impacts.


Assuntos
Emulsões , Frutas , Mananas , Pectinas , Pectinas/química , Emulsões/química , Frutas/química , Mananas/química , Permeabilidade , Embalagem de Alimentos/métodos , Conservação de Alimentos/métodos , Resistência à Tração , Antibacterianos/química , Antibacterianos/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Água/química
4.
Int J Biol Macromol ; 265(Pt 1): 130895, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492692

RESUMO

Fruit is prone to rot and deterioration due to oxidative browning and microbial infection during storage, which can cause serious economic losses and food safety problems. It is urgent to develop a multifunctional composite coating to extend the shelf life of fruits. In this work, multifunctional quaternized chitosan nanoparticles (QCs/TA NPs) with excellent antibacterial and antioxidant properties were prepared based on electrostatic interaction using tannic acid instead of conventional cross-linking agents. Meanwhile, konjac glucomannan (KGM) with high viscosity, edible and biodegradable properties was used as a dispersant to disperse and stabilize the nanoparticles, and as a film-forming agent to form a multifunctional composite coating. The composite coating exhibited excellent oxygen and water vapor barrier properties, antioxidant, antibacterial, mechanical properties, hydrophobicity, and UV shielding properties. Surprisingly, the oxygen permeability of the K-NPs-15 composite film was as low as 1.93 × 10-13 (cm3·cm)/(cm2·s·Pa). The banana spray preservation experiments proved that the K-NPs-15 composite coating could effectively prolong the shelf life of bananas. Therefore, this study provides a new idea for designing multifunctional freshness preservation coatings, which has a broad application prospect.


Assuntos
Anti-Infecciosos , Mananas , Musa , Nanocompostos , Polifenóis , Antioxidantes/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos , Oxigênio
5.
Talanta ; 272: 125766, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38340392

RESUMO

As one of the major public health problems, cancers seriously threaten the human health. Among them, lung cancer is considered to be one of the most life-threatening malignancies. Therefore, developing early diagnosis technology and timely treatment for lung cancer is urgent. Recent research has witnessed that measuring changes of biomarkers expressed in lung cancer has practical significance. Meanwhile, we note that bioimaging with organic fluorescent probes plays an important role for its high sensitivity, real-time analysis and simplicity of operation. In the past years, kinds of organic fluorescent probes targeting lung cancer related biomarker have been developed. Herein, we summarize the research progress of organic fluorescent probes for the detection of lung cancer related biomarkers in this review, along with their design principle, luminescence mechanism and bioimaging application. Additionally, we put forward some challenges and future prospects from our perspective.


Assuntos
Corantes Fluorescentes , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Biomarcadores Tumorais , Luminescência
6.
Int J Biol Macromol ; 263(Pt 1): 130337, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395285

RESUMO

In cold storage, fruits and vegetables still keep a low respiratory rate. Although cold storage is beneficial to maintain the quality of some fruits and vegetables, several factors (temperature and humidity fluctuations, heat inflow, air velocity, light, etc.) will accelerate moisture loss. Biopolymer films have attracted great attention for fruits and vegetables preservation because of their biodegradable and barrier properties. However, there is still a certain amount of water transfer occurring between storage environment/biopolymer films/fruits and vegetables (EFF). The effect of biopolymer films to inhibit moisture loss of fruits and vegetables and the water transfer mechanism in EFF system need to be studied systematically. Therefore, the moisture loss of fruits and vegetables, crucial properties, major components, fabrication methods, and formation mechanisms of biopolymer films were reviewed. Further, this study highlights the EFF system, responses of fruits and vegetables, and water transfer in EFF. This work aims to clarify the characteristics of EFF members, their influence on each other, and water transfer, which is conducive to improving the preservation efficiency of fruits and vegetables purposefully in future studies. In addition, the prospects of studies in EFF systems are shown.


Assuntos
Conservação de Alimentos , Frutas , Conservação de Alimentos/métodos , Verduras , Biopolímeros , Água
7.
Int J Biol Macromol ; 258(Pt 1): 128836, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104683

RESUMO

The strategy of emulsion coating was used for grape preservation. Camellia oil (CO) was incorporated with KGM/curdlan (KC) to fabricate KC-CO emulsion systems. KC-CO emulsions were analyzed by droplet size distribution and confocal laser scanning microscopy (CLSM), and KC-CO films were investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), mechanical properties, dissolution, gas permeability, water contact angle (WCA). KC-CO coating was used for preservation of 'Kyoho' grapes. The results indicated that the addition of CO had a positive effect on KC system. CO could form a uniform emulsion with KC, and the droplets were evenly dispersed in the KC matrix. KC-CO films displayed a continuous microstructure, and elongation at break (EAB) was improved, while tensile strength decreased. The dissolution, water vapor permeability (WVP), and WCA were significantly enhanced, while the permeability of oxygen and carbon dioxide exhibited no advantage compared with KC film. KC-CO-10 possessed optimal properties and was selected as an emulsion coating for preservation. The results suggested that KC-CO-10 significantly maintained the appearance, total solid and acid content of 'Kyoho' grapes, and delayed the weight loss and firmness decrease. This study contributed to the understanding of polysaccharide-lipid emulsion system and the applications.


Assuntos
Camellia , Vitis , beta-Glucanas , Emulsões , Mananas/química , Permeabilidade , Óleos de Plantas
8.
BMC Mol Cell Biol ; 24(1): 34, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041032

RESUMO

Breast cancer is the most common malignant tumour in women. The early silk-splitting inhibitor protein 1 Emi1 is responsible for mediating ubiquitin protein degradation. The present study investigated the effects of the decreased expression of the Emil gene on the proliferation and invasion of breast cancer cells. The interference efficiency of small interfering ribonucleic acid (siRNA) was quantitatively verified using fluorescence real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, and the effect of Emi1 gene silencing on cell vitality and invasion was determined using MTT and Transwell assays, respectively. The expression of the proliferation genes programmed cell death receptor 4 (PDCD-4), fatty acid synthase ligand (FasL), PTEN and RhoB, along with the invasive genes Maspin, TIMP3 and RECK, was measured using fluorescence RT-qPCR. In breast cancer cells, siRNA successfully reduced the expression of the Emi1 gene, and the expression level of the cell proliferation genes PDCD-4, FasL, PTEN and RhoB, along with invasive genes Maspin, TIMP3 and RECK, decreased significantly (P < 0.05). Furthermore, Emi1 gene silencing reduced the proliferation and invasion abilities of MDA-MB-231 and SUM149PT cells by reducing the expression of proliferative and invasive genes.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Inativação Gênica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proliferação de Células/genética , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo
9.
J Biomater Appl ; 38(1): 109-121, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37285508

RESUMO

Oxidative damage of neurons is one of the key pathological markers of Alzheimer's disease (AD), which eventually leads to neuronal apoptosis and loss. Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of antioxidant response and is considered to be an important therapeutic target for neurodegenerative diseases. In this study, the selenated derivative of antioxidant rutin (Se-Rutin) was synthesized with sodium selenate (Na2SeO3) as raw material by a simple electrostatic-compound in situ selenium reduction method. The effects of Se-Rutin on H2O2 induced oxidative damage in Pheochromocytoma PC12 cells were evaluated by cell viability, apoptosis, reactive oxygen species level and the expression of antioxidant response element (Nrf2). The results showed that H2O2 treatment significantly increased the level of apoptosis and reactive oxygen species, while the level of Nrf2 and HO-1 decreased. However, Se-Rutin significantly reduced H2O2 induced apoptosis and cytotoxicity, and increased the expression of Nrf2 and HO-1, both of which were better than that of pure rutin. Therefore, the activation of Nrf2/HO-1 signaling pathway may be the basis of Se-Rutin's anti-oxidative damage to AD.


Assuntos
Doença de Alzheimer , Nanopartículas , Selênio , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Selênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Peróxido de Hidrogênio , Rutina/farmacologia , Estresse Oxidativo , Transdução de Sinais , Apoptose
10.
Materials (Basel) ; 16(8)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37110002

RESUMO

Pickering emulsions stabilized by food-grade colloidal particles have attracted increasing attention in recent years due to their "surfactant-free" nature. In this study, the alkali-treated zein (AZ) was prepared via restricted alkali deamidation and then combined with sodium alginate (SA) in different ratios to obtain AZ/SA composite particles (ZS), which were used to stabilize Pickering emulsion. The degree of deamidation (DD) and degree of hydrolysis (DH) of AZ were 12.74% and 6.58% respectively, indicating the deamidation occurred mainly in glutamine on the side chain of the protein. After the treatment with alkali, AZ particle size decreased significantly. Moreover, the particle size of ZS with different ratios was all less than 80 nm. when the AZ/SA ratio was 2:1(Z2S1) and 3:1(Z3S1), the three-phase contact angle (θo/w) were close to 90°, which was favorable for stabilizing the Pickering emulsion. Furthermore, at a high oil phase fraction (75%), Z3S1-stabilized Pickering emulsions showed the best long-term storage stability within 60 days. Confocal laser scanning microscope (CLSM) observations showed that the water-oil interface was wrapped by a dense layer of Z3S1 particles with non-agglomeration between independent oil droplets. At constant particle concentration, the apparent viscosity of the Pickering emulsions stabilized by Z3S1 gradually decreased with increasing oil phase fraction, and the oil-droplet size and the Turbiscan stability index (TSI) also gradually decreased, exhibiting solid-like behavior. This study provides new ideas for the fabrication of food-grade Pickering emulsions and will extend the future applications of zein-based Pickering emulsions as bioactive ingredient delivery systems.

11.
Heliyon ; 9(4): e14766, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37025825

RESUMO

Background: The most common disease caused by biallelic AFG3L2 mutations is spastic ataxia type 5 (SPAX5). Identification of complex phenotypes resulting from biallelic AFG3L2 mutations has been increasing in recent years. Methods: A retrospective analysis was performed on a child with microcephaly and recurrent seizures. The child underwent physical and neurological examinations, laboratory tests, electroencephalography (EEG), and brain magnetic resonance imaging (MRI). Trio-whole-exome sequencing (trio-WES) was performed to identify possible causative mutations. Results: We described a child who exhibited early-onset and intractable epilepsy, developmental regression, microcephaly, and premature death. Neuroimaging revealed global cerebral atrophy (GCA) involving the cerebrum, cerebellum, corpus callosum, brainstem, cerebellar vermis, and basal ganglia. On trio-WES, two novel compound heterozygous mutations, c.1834G > T (p.E612*) and c.2176-6T > A in the AFG3L2 gene, were identified in this patient. Conclusions: Our findings have expanded the mutation spectrum of the AFG3L2 gene and identified a severe neurodegenerative phenotype of global cerebral atrophy caused by biallelic AFG3L2 mutations.

12.
Int J Biol Macromol ; 238: 124088, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36948332

RESUMO

Polydopamine nanoparticles (PDA NPs) are commonly used for photothermal therapy (PTT) of cancer because of their good biocompatibility and photothermal conversion capability. However, it is difficult to achieve a good tumor inhibition effect with a single PTT of PDA. Therefore, in this work, we prepared a combined anticancer nanosystem for enhanced chemodynamic therapy (CDT)/PTT by coating PDAs with an (-)-epigallocatechin gallate (EGCG)/iron (Fe) metal-polyphenol network (MPN). The MPN shell of this nanosystem named EGCG@PDA is degraded by the weakly acidic environment intracellular, releasing EGCG and Fe3+. EGCG inhibits the expression of heat shock proteins (HSPs) in cancer cells, thus eliminating their thermal protection against cancer cells for enhanced PTT. Meanwhile, the reductive EGCG can also reduce Fe3+ to Fe2+, to catalyze the decomposition of overexpressed hydrogen peroxide (H2O2) in cancer cells to generate strong oxidative hydroxyl radicals (OH), i.e., catalyzing the Fenton reaction, for CDT. After the Fenton reaction, the re-oxidized Fe ions can be reduced again by EGCG and reused to catalyze the Fenton reaction, which can achieve enhanced CDT. Both in vitro and in vivo studies have shown that EGCG@PDA has low dark toxicity and good anticancer effects. It is expected to be used for precision cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Polifenóis , Fototerapia , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico , Metais , Linhagem Celular Tumoral
13.
Molecules ; 28(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36838679

RESUMO

Natural polysaccharides with high viscosity, good thermal stability, and biocompatibility can improve the mechanical properties of inorganic silica aerogels and enhance their application safety. However, the effects of the preparation methods of polysaccharide-silica aerogels on their microstructure and application properties have not been systematically studied. To better investigate the effect of the microstructure on the properties of aerogel materials, two aerogels with different structures were prepared using Konjac glucomannan (KGM) and tetraethoxysilane (TEOS) via physical blending (KTB) and co-precursor methods (KTC), respectively. The structural differences between the KTB and KTC aerogels were characterized, and the thermal insulation and fire-retardant properties were further investigated. The compressive strength of the KTC aerogels with a cross-linked interpenetrating network (IPN) structure was three times higher than that of the KTB aerogels, while their thermal conductivity was 1/3 of that of the KTB aerogels. The maximum limiting oxygen index (LOI) of the KTC aerogels was 1.4 times, the low peak heat release rate (PHRR) was reduced by 61.45%, and the lowest total heat release (THR) was reduced by 41.35% compared with the KTB aerogels. The results showed that the KTC aerogels with the IPN have better mechanical properties, thermal insulation, and fire-retardant properties than the simple physically blending KTB aerogels. This may be due to the stronger hydrogen-bonding interactions between KGM and silica molecules in the KTC aerogels under the unique forcing effect of the IPN, thus enhancing their structural stability and achieving complementary properties. This work will provide new ideas for the microstructure design of aerogels and the research of new thermal insulation and fire-retardant aerogels.


Assuntos
Retardadores de Chama , Mananas , Força Compressiva , Dióxido de Silício
14.
Acta Biomater ; 159: 312-323, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36708854

RESUMO

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size Ti3C2Tx MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size Ti3C2Tx MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.


Assuntos
Hipertermia Induzida , Neoplasias , Humanos , Fototerapia/métodos , Terapia Fototérmica , Hipertermia Induzida/métodos , Titânio , Neoplasias/patologia , Anti-Inflamatórios , Proteínas de Choque Térmico , Linhagem Celular Tumoral
15.
J Colloid Interface Sci ; 634: 836-851, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36565625

RESUMO

Chemodynamic therapy (CDT) is a novel cancer therapeutic strategy. However, barriers such as high glutathione (GSH) concentration and low concentration of metal ions intracellular reduce its treatment effect. In this work, a nanosystem named GA-Fe@HMDN-PEI-PEG with a "dynamic protection" property was reported for enhanced cancer CDT. Mesoporous hollow manganese dioxide (MnO2) nanoparticle (HMDN) was prepared to load gallic acid-ferrous (GA-Fe) nanodots fabricated from gallic acid (GA) and ferrous ion (Fe2+). Then the pores of HMDN were blocked by polyethyleneimine (PEI), which was then grafted with methoxy poly(ethylene glycol) (mPEG) through a pH-sensitive benzoic imine bond. mPEG could protect the nanoparticles (NPs) against the nonspecific uptake by normal cells and enhance their accumulation in the tumor. However, in the slightly acidic tumor microenvironment, hydrolysis of benzoic imine led to DePEGylation to reveal PEI for enhanced uptake by cancer cells. The reaction between HMDN and GSH could consume GSH and obtain manganese ion (Mn2+) for the Fenton-like reaction for CDT. GA-Fe nanodots could also offer Fe for the Fenton reaction, and reductive GA could reduce the high-valence ions to low-valence for reusing in Fenton and Fenton-like reactions. These properties allowed GA-Fe@HMDN-PEI-PEG for precise medicine with a high utilization rate and common side effects.


Assuntos
Nanopartículas , Neoplasias , Humanos , Compostos de Manganês/farmacologia , Compostos de Manganês/química , Óxidos/farmacologia , Óxidos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Ácido Gálico , Iminas , Linhagem Celular Tumoral , Peróxido de Hidrogênio , Glutationa/química , Microambiente Tumoral
16.
Comput Intell Neurosci ; 2022: 1552745, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36573070

RESUMO

The knowledge tracing model takes students' learning behaviours data as input to determine their current knowledge status and predict their future answers. The learning behaviours data describes three main types of learning behaviours: learning process, learning end, and learning interval. The classical knowledge tracing models only use the data of the learning end, which contains limited information and the models cannot accurately describe constraint in the same learning behaviour in the time series. Subsequent models add other types of learning behaviours data but do not integrate different types of learning behaviours, and the models cannot accurately describe collaboration in different learning behaviours. To address these issues, knowledge tracing via attention-enhanced encoder-decoder is proposed to synthesize and analyse the three types of learning behaviours mentioned above and firstly adopts the multiheaded attention mechanism to describe constraint in the same learning behaviours; secondly adopts the channel attention mechanism modelling collaboration in the three types of learning behaviours. In the experiments, various comparisons are made with related models on several real data sets, and the results show that our model achieves certain advantages in terms of performance and knowledge state representation. In terms of practical application, an intelligent learning platform based on the model has been implemented, which predicts the future answer of students in the teaching process of two offline courses: computer and English and has achieved better performance than other knowledge tracing models.


Assuntos
Aprendizagem , Estudantes , Humanos
17.
Hematology ; 27(1): 1305-1311, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36519257

RESUMO

OBJECTIVES: To explore the application of third-generation sequencing (TGS) for genetic diagnosis and prenatal genetic screening of thalassemia genes. METHODS: Two groups of subjects were enrolled in this study. The first group included 176 subjects with positive hematological phenotypes for thalassemia. Thalassemia-associated genes were detected simultaneously in each sample using both the PacBio TGS platform based on single-molecule real-time (SMRT) technology and the conventional PCR-reverse dot blot (PCR-RDB). Sanger sequencing was used for validation when results were discordant between the two methods. The second group included 53 couples with at least one partner having a positive thalassemia hematological phenotype, and they were screened for homotypic thalassemia variants by TGS, and the risk of pregnancies with babies presenting with severe thalassemia, was assessed. RESULTS: Of the 176 subjects, 175 had concordant genotypes between the two methods, including 63 normal subjects and 112 α- and/or ß-thalassemia gene carriers, with a concordance rate of 99.43%. TGS detected a rare ß-thalassemia gene variant -50 (G > A) that was not detected by conventional PCR-RDB. TGS identified seven of the 53 couples as homotypic thalassemia gene carriers, five of whom were at risk of pregnancies with severe thalassemia. CONCLUSION: TGS could effectively detect common and rare thalassemia variants with high accuracy and efficiency. This approach would be suitable for prenatal thalassemia genetic screening in areas with high incidence of thalassemia.


Assuntos
Talassemia alfa , Talassemia beta , Gravidez , Feminino , Humanos , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/genética , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Testes Genéticos , China/epidemiologia , Diagnóstico Pré-Natal/métodos , Genótipo , Mutação
18.
Front Bioeng Biotechnol ; 10: 952510, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910031

RESUMO

Coronavirus disease 19 (COVID-19) is still a major public health concern in many nations today. COVID-19 transmission is now controlled mostly through early discovery, isolation, and therapy. Because of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the contributing factor to COVID-19, establishing timely, sensitive, accurate, simple, and budget detection technologies for the SARS-CoV-2 is urgent for epidemic prevention. Recently, several electrochemical DNA biosensors have been developed for the rapid monitoring and detection of SARS-CoV-2. This mini-review examines the latest improvements in the detection of SARS-COV-2 utilizing electrochemical DNA biosensors. Meanwhile, this mini-review summarizes the problems faced by the existing assays and puts an outlook on future trends in the development of new assays for SARS-CoV-2, to provide researchers with a borrowing role in the generation of different assays.

19.
Materials (Basel) ; 15(15)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35955225

RESUMO

Coating nanosized anticancer drug delivery systems (DDSs) with poly(ethylene glycol) (PEG), the so-called PEGylation, has been proven an effective method to enhance hydrophilicity, aqueous dispersivity, and stability of DDSs. What is more, as PEG has the lowest level of protein absorption of any known polymer, PEGylation can reduce the clearance of DDSs by the mononuclear phagocyte system (MPS) and prolong their blood circulation time in vivo. However, the "stealthy" characteristic of PEG also diminishes the uptake of DDSs by cancer cells, which may reduce drug utilization. Therefore, dynamic protection strategies have been widely researched in the past years. Coating DDSs with PEG through dynamic covalent or noncovalent bonds that are stable in blood and normal tissues, but can be broken in the tumor microenvironment (TME), can achieve a DePEGylation-based "tumor-triggered" targeting or intracellular drug release, which can effectively improve the utilization of drugs and reduce their side effects. In this review, the stimuli and methods of "tumor-triggered" targeting or intracellular drug release, based on DePEGylation, are summarized. Additionally, the targeting and intracellular controlled release behaviors of the DDSs are briefly introduced.

20.
Front Chem ; 10: 905475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601546

RESUMO

As a new type of "zero-dimensional" fluorescent carbon nanomaterials, carbon dots (CDs) have some unique optical and chemical properties, they are being explored for a variety of applications in bio-related fields, such as bioimaging, biosensors, and therapy. This review mainly summarizes the recent progress of CDs in bioimaging. The overview of this review can be roughly divided into two categories: (1) In vitro bioimaging based on CDs in different cells and important organelles. (2) The distribution, imaging and application of CDs in mice and zebrafish. In addition, this review also points out the potential advantages and future development directions of CDs for bioimaging, which may promote the development of CDs in the field of bioimaging.

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