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1.
J Agric Food Chem ; 72(25): 14241-14254, 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38864682

RÉSUMÉ

Nattokinase is a nutrient in healthy food natto that has the function of preventing and treating blood thrombus. However, its low thermostability and fibrinolytic activity limit its application in food and pharmaceuticals. In this study, we used bioinformatics analysis to identify two loops (loop10 and loop12) in the flexible region of nattokinase rAprY. Using this basis, we screened the G131S-S161T variant, which showed a 2.38-fold increase in half-life at 55 °C, and the M3 variant, which showed a 2.01-fold increase in activity, by using a thermostability prediction algorithm. Bioinformatics analysis revealed that the enhanced thermostability of the G131S-S161T variant was due to the increased rigidity and structural shrinkage of the overall structure. Additionally, the increased rigidity of the local region surrounding the active center and its mutated sites helps maintain its normal conformation in high-temperature environments. The increased catalytic activity of the M3 variant may be due to its more efficient substrate binding mechanism. We investigated strategies to improve the thermostability and fibrinolytic activity of nattokinase, and the resulting variants show promise for industrial production and application.


Sujet(s)
Stabilité enzymatique , Température élevée , Subtilisines , Subtilisines/composition chimique , Subtilisines/génétique , Subtilisines/métabolisme , Cinétique , Bacillus subtilis/enzymologie , Bacillus subtilis/génétique , Bacillus subtilis/composition chimique , Biologie informatique , Protéines bactériennes/composition chimique , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Domaine catalytique
2.
Int J Mol Sci ; 25(11)2024 May 22.
Article de Anglais | MEDLINE | ID: mdl-38891819

RÉSUMÉ

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.


Sujet(s)
Nanoparticules métalliques , Tumeurs , Thérapie photothermique , Humains , Thérapie photothermique/méthodes , Tumeurs/thérapie , Nanoparticules métalliques/composition chimique , Nanoparticules métalliques/usage thérapeutique , Animaux , Photosensibilisants/composition chimique , Photosensibilisants/usage thérapeutique
3.
Pharmaceutics ; 16(5)2024 Apr 29.
Article de Anglais | MEDLINE | ID: mdl-38794265

RÉSUMÉ

Sonodynamic therapy (SDT) has attracted significant attention in recent years as it is an innovative approach to tumor treatment. It involves the utilization of sound waves or ultrasound (US) to activate acoustic sensitizers, enabling targeted drug release for precise tumor treatment. This review aims to provide a comprehensive overview of SDT, encompassing its underlying principles and therapeutic mechanisms, the applications of nanomaterials, and potential synergies with combination therapies. The review begins by introducing the fundamental principle of SDT and delving into the intricate mechanisms through which it facilitates tumor treatment. A detailed analysis is presented, outlining how SDT effectively destroys tumor cells by modulating drug release mechanisms. Subsequently, this review explores the diverse range of nanomaterials utilized in SDT applications and highlights their specific contributions to enhancing treatment outcomes. Furthermore, the potential to combine SDT with other therapeutic modalities such as photothermal therapy (PTT) and chemotherapy is discussed. These combined approaches aim to synergistically improve therapeutic efficacy while mitigating side effects. In conclusion, SDT emerges as a promising frontier in tumor treatment that offers personalized and effective treatment options with the potential to revolutionize patient care. As research progresses, SDT is poised to play a pivotal role in shaping the future landscape of oncology by providing patients with a broader spectrum of efficacious and tailored treatment options.

4.
J Agric Food Chem ; 72(21): 11854-11870, 2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38743017

RÉSUMÉ

The critical role of oxidative stress in Alzheimer's disease (AD) has been recognized by researchers recently, and natural antioxidants have been demonstrated to have anti-AD activity in animal models, such as Ginkgo biloba extract, soy isoflavones, lycopene, and so on. This paper summarized these natural antioxidants and points out that natural antioxidants always have multiple advantages which are help to deal with AD, such as clearing free radicals, regulating signal transduction, protecting mitochondrial function, and synaptic plasticity. Based on the available data, we have created a relatively complete pathway map of reactive oxygen species (ROS) and AD-related targets and concluded that oxidative stress caused by ROS is the core of AD pathogenesis. In the prospect, we introduced the concept of a combined therapeutic strategy, termed "Antioxidant-Promoting Synaptic Remodeling," highlighting the integration of antioxidant interventions with synaptic remodeling approaches as a novel avenue for therapeutic exploration.


Sujet(s)
Maladie d'Alzheimer , Antioxydants , Ginkgo biloba , Stress oxydatif , Extraits de plantes , Maladie d'Alzheimer/traitement médicamenteux , Maladie d'Alzheimer/métabolisme , Antioxydants/pharmacologie , Humains , Animaux , Stress oxydatif/effets des médicaments et des substances chimiques , Ginkgo biloba/composition chimique , Extraits de plantes/composition chimique , Extraits de plantes/pharmacologie , Espèces réactives de l'oxygène/métabolisme
5.
Langmuir ; 40(12): 6295-6303, 2024 Mar 26.
Article de Anglais | MEDLINE | ID: mdl-38484330

RÉSUMÉ

In this study, the heterostructure cathode material LiCoO2@Co3O4@Li6.4La3Zr1.4Ta0.6O12 was prepared by coating Li6.4La3Zr1.4Ta0.6O12 on the surface of LiCoO2 through a one-step solid-phase synthesis. The morphology, structure, electrical state, and elemental contents of both pristine and modified materials were assessed through a range of characterization techniques. Theoretical calculations revealed that the LCO@LLZTO material possessed a reduced diffusion barrier compared to LiCoO2, thereby facilitating the movement of Li ions. Electrochemical tests indicated that the capacity retention rate of the modified cathode composites stood at 70.43% following 300 cycles at a 2C rate. This high rate occurred because the Li6.4La3Zr1.4Ta0.6O12 film on the surface enhanced the migration of Li+, and the spinel phase of Co3O4 had better interfacial stability to alleviate the generation of microcracks by inhibiting the phase change from the layered phase to the rock-salt phase, which considerably improved the electrochemical properties.

6.
Front Oncol ; 14: 1352028, 2024.
Article de Anglais | MEDLINE | ID: mdl-38529369

RÉSUMÉ

Rationale and objectives: To construct a predictive model for benign and malignant peripheral pulmonary lesions (PPLs) using a random forest algorithm based on grayscale ultrasound and ultrasound contrast, and to evaluate its diagnostic value. Materials and methods: We selected 254 patients with PPLs detected using chest lung computed tomography between October 2021 and July 2023, including 161 malignant and 93 benign lesions. Relevant variables for judging benign and malignant PPLs were screened using logistic regression analysis. A model was constructed using the random forest algorithm, and the test set was verified. Correlations between these relevant variables and the diagnosis of benign and malignant PPLs were evaluated. Results: Age, lesion shape, size, angle between the lesion border and chest wall, boundary clarity, edge regularity, air bronchogram, vascular signs, enhancement patterns, enhancement intensity, homogeneity of enhancement, number of non-enhancing regions, non-enhancing region type, arrival time (AT) of the lesion, lesion-lung AT difference, AT difference ratio, and time to peak were the relevant variables for judging benign and malignant PPLs. Consequently, a model and receiver operating characteristic curve were constructed with an AUC of 0.92 and an accuracy of 88.2%. The test set results showed that the model had good predictive ability. The index with the highest correlation for judging benign and malignant PPLs was the AT difference ratio. Other important factors were lesion size, patient age, and lesion morphology. Conclusion: The random forest algorithm model constructed based on clinical data and ultrasound imaging features has clinical application value for predicting benign and malignant PPLs.

7.
Nutrients ; 16(6)2024 Mar 11.
Article de Anglais | MEDLINE | ID: mdl-38542707

RÉSUMÉ

As one of the malignant diseases globally, cancer seriously endangers human physical and mental health because of its high morbidity and mortality. Conventional cancer treatment strategies, such as surgical resection and chemoradiotherapy, are effective at the early stage of cancer but have limited efficacy for advanced cancer. Along with cancer progress and treatment, resistance develops gradually within the population of tumor cells. As a consequence, drug resistance become the major cause that leads to disease progression and poor clinical prognosis in some patients. The mechanisms of cancer drug resistance are quite complex and involve various molecular and cellular mechanisms. Therefore, exploring the mechanisms and finding specific targets are becoming imperative to overcome drug resistance. In recent years, plant-derived natural products have been evaluated as potential therapeutic candidates against cancer with drug resistance due to low side effects and high anticancer efficacy. A growing number of studies have shown that natural products can achieve superior antitumor effects through multiple signaling pathways. The mechanisms include regulation of multiple drug resistance (MDR)-related genes, inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, induction of autophagy, and blockade of the cell cycle. This paper reviews the molecular and cellular mechanisms of cancer drug resistance, as well as the therapeutic effects and mechanisms of plant-derived natural products against cancer drug resistance. It provides references for developing therapeutic medication for drug-resistant cancer treatment with high efficacy and low side effects.


Sujet(s)
Produits biologiques , Tumeurs , Humains , Phosphatidylinositol 3-kinases/métabolisme , Produits biologiques/pharmacologie , Produits biologiques/usage thérapeutique , Tumeurs/traitement médicamenteux , Tumeurs/anatomopathologie , Protéines proto-oncogènes c-akt/métabolisme , Résistance aux médicaments antinéoplasiques , Transduction du signal , Lignée cellulaire tumorale
8.
Int J Biol Macromol ; 265(Pt 2): 130824, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38492708

RÉSUMÉ

Polysaccharide-functionalized gold nanoparticles (Polysaccharide-Au NPs) with high stability were successfully prepared by a straightforward method. Notably, the Au (III) ion acts as a strong Lewis acid to facilitate glycosidic bond breaking. Subsequently, the polysaccharide conformation was transformed to an open-chain form, exposing highly reduced aldehyde or ketone groups that reduce Au (III) to Au (0) crystal species, further growing into Au NPs. As-prepared Au NPs displayed excellent stability over a longer storage period (more than 70 days), a wide range of temperatures (25-60 °C), and pH range (3-11), varying concentrations (0-200 mM) and types of salt ions (Na+, K+, Ca2+, Mg2+), and glutathione solutions (5 mM). More interestingly, polysaccharide-Au NPs retained the antioxidant activity of polysaccharides and reduced oxidative damage at the cellular level through decreased reactive oxygen species (ROS) production. The intracellular levels of ROS pretreated with polysaccharide and polysaccharide-Au NPs were decreased 53.12-75.85 % compared to the H2O2 group, respectively. Therefore, the green synthesized Au NPs from natural active polysaccharides exhibit potential applications in biomedical fields.


Sujet(s)
Antioxydants , Nanoparticules métalliques , Antioxydants/pharmacologie , Espèces réactives de l'oxygène , Peroxyde d'hydrogène , Or/composition chimique , Nanoparticules métalliques/composition chimique , Polyosides/pharmacologie
9.
Pharmaceutics ; 16(1)2024 Jan 09.
Article de Anglais | MEDLINE | ID: mdl-38258099

RÉSUMÉ

Clinical drug administration aims to deliver drugs efficiently and safely to target tissues, organs, and cells, with the objective of enabling their therapeutic effects. Currently, the main approach to enhance a drug's effectiveness is ensuring its efficient delivery to the intended site. Due to the fact that there are still various drawbacks of traditional drug delivery methods, such as high toxicity and side effects, insufficient drug specificity, poor targeting, and poor pharmacokinetic performance, nanocarriers have emerged as a promising alternative. Nanocarriers possess significant advantages in drug delivery due to their size tunability and surface modifiability. Moreover, nano-drug delivery systems have demonstrated strong potential in terms of prolonging drug circulation time, improving bioavailability, increasing drug retention at the tumor site, decreasing drug resistance, as well as reducing the undesirable side effects of anticancer drugs. Numerous studies have focused on utilizing polysaccharides as nanodelivery carriers, developing delivery systems based on polysaccharides, or exploiting polysaccharides as tumor-targeting ligands to enhance the precision of nanoparticle delivery. These types of investigations have become commonplace in the academic literature. This review aims to elucidate the preparation methods and principles of polysaccharide gold nanocarriers. It also provides an overview of the factors that affect the loading of polysaccharide gold nanocarriers with different kinds of drugs. Additionally, it outlines the strategies employed by polysaccharide gold nanocarriers to improve the delivery efficiency of various drugs. The objective is to provide a reference for further development of research on polysaccharide gold nanodelivery systems.

10.
J Med Virol ; 96(1): e29388, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-38235845

RÉSUMÉ

The use of precise epitope peptides as antigens is essential for accurate serological diagnosis of viral-infected individuals, but now it remains an unsolvable problem for mapping precise B cell epitopes (BCEs) recognized by human serum. To address this challenge, we propose a novel epitope delimitation (ED) method to uncover BCEs in the delineated human IgG-reactive (HR) antigenic peptides (APs). Specifically, the method based on the rationale of similarities in humoral immune responses between mammalian species consists of a pair of elements: experimentally delineated HR-AP and rabbit-recognized (RR) BCE motif and corresponding pair of sequence alignment analysis. As a result of using the ED approach, after decoding four RR-epitomes of human papillomavirus types 16/18-E6 and E7 proteins utilizing rabbit serum against each recombinant protein and sequence alignment analysis of HR-APs and RR-BCEs, 19 fine BCEs in 17 of 22 known HR-APs were defined based on each corresponding RR-BCE motifs, including the type-specificity of each delimited BCE in homologous proteins. The test with 22 known 16/20mer HR-APs demonstrated that the ED method is effective and efficient, indicating that it can be used as an alternative method to the conventional identification of fine BCEs using overlapping 8mer peptides.


Sujet(s)
Protéines des oncogènes viraux , Peptides , Animaux , Humains , Lapins , Séquence d'acides aminés , Peptides/génétique , Déterminants antigéniques des lymphocytes B , Alignement de séquences , Immunoglobuline G , Cartographie épitopique/méthodes , Mammifères
11.
Chem Biol Interact ; 387: 110795, 2024 Jan 05.
Article de Anglais | MEDLINE | ID: mdl-37956922

RÉSUMÉ

In order to search for novel antitumor drugs with high efficiency and low toxicity, the anti-lung cancer activity of phytosphingosine was studied. Phytosphingosine is widely distributed in fungi, plants, animals, and has several biological activities, including anti-inflammation and anti-tumor. However, its anti-lung cancer activity needs to be further investigated. The effects and pharmacological mechanisms of phytosphingosine on lung cancer treatment were investigated both in vitro and in vivo. The results showed that phytosphingosine inhibited the growth of lung cancer cell lines. Phytosphingosine induced apoptosis through a mitochondria-mediated pathway, phytosphingosine arrested the cell cycle at the G2/M phase and induced apoptosis in a dose-dependent manner by increasing Bax/Bcl-2 ratio, which caused the decrease of mitochondrial membrane potential to promote the release of cytochrome C, caspase 9 and 3, and degrade PARP in A549 cells. The results showed that phytosphingosine could damage the mitochondrial functions, increase ROS levels, and arrest the cell cycle at the G2/M stages. Finally, phytosphingosine also inhibited the growth of tumor in mice. Taken together, phytosphingosine suppressed the growth of lung cancer cells both in vitro and in vivo and had potential application in the research and development of antitumor drugs. The aim of the present study was to explain the theoretical basis of phytosphingosine therapy for lung cancer and providing new possibilities for lung cancer treatment.


Sujet(s)
Adénocarcinome pulmonaire , Antinéoplasiques , Tumeurs du poumon , Animaux , Souris , Apoptose , Mort cellulaire , Mitochondries , Adénocarcinome pulmonaire/anatomopathologie , Tumeurs du poumon/anatomopathologie , Mitose , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Antinéoplasiques/métabolisme , Espèces réactives de l'oxygène/métabolisme , Lignée cellulaire tumorale
12.
Acad Radiol ; 31(4): 1528-1537, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-37777427

RÉSUMÉ

RATIONALE AND OBJECTIVES: The purpose of this study is to conduct a comparison between the newly introduced Angio PLanewave UltraSensitive (AngioPLUS) method and the power Doppler ultrasound (PDUS) technique, evaluating the efficacy of these two methods in detecting synovial blood flow in wrist and finger joints of rheumatoid arthritis (RA) patients. Furthermore, the study aimed to investigate the potential associations between the observed blood flow patterns and various symptoms and indicators associated with RA. MATERIALS AND METHODS: A cohort of 101 patients diagnosed with RA was included and subsequently categorized into two groups: 20 male participants (19.80%) and 81 female participants (80.20%). Their grayscale ultrasound, PDUS, and AngioPLUS were utilized to acquire data, and subsequent scoring was conducted. Serological tests of the patients were also performed, and DAS28 scores were calculated. The McNemar and Wilcoxon tests were used to compare the blood flow display rate and grading of PDUS as well as AngioPLUS, respectively. RESULTS: AngioPLUS blood was significantly improved compared to PDUS. In all joints, the proportion of slight and significant improvement in wrist joints was the highest (14.11% and 1.98%, respectively). AngioPLUS was moderately correlated with C-reactive Protein (CRP), Disease Activity Score that includes 28-joint counts, and swollen joint counts and weakly correlated with platelet, hemoglobin, tender joint counts, and CRP before and after treatment. CONCLUSION: Compared to PDUS, AngioPLUS has a better auxiliary diagnostic role in evaluating disease activity and can provide a reference to improve the management of RA further.


Sujet(s)
Polyarthrite rhumatoïde , Articulation du doigt , Humains , Mâle , Femelle , Poignet , Échographie-doppler/méthodes , Polyarthrite rhumatoïde/imagerie diagnostique , Articulation du poignet/imagerie diagnostique , Protéine C-réactive , Indice de gravité de la maladie , Articulations/imagerie diagnostique
13.
Int J Mol Sci ; 24(23)2023 Nov 29.
Article de Anglais | MEDLINE | ID: mdl-38069279

RÉSUMÉ

Tumors are a major public health issue of concern to humans, seriously threatening the safety of people's lives and property. With the increasing demand for early and accurate diagnosis and efficient treatment of tumors, noninvasive optical imaging (including fluorescence imaging and photoacoustic imaging) and tumor synergistic therapies (phototherapy synergistic with chemotherapy, phototherapy synergistic with immunotherapy, etc.) have received increasing attention. In particular, light in the near-infrared second region (NIR-II) has triggered great research interest due to its penetration depth, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Nanomaterials with many advantages, such as high brightness, great photostability, tunable photophysical properties, and excellent biosafety offer unlimited possibilities and are being investigated for NIR-II tumor imaging-guided synergistic oncotherapy. In recent years, many researchers have tried various approaches to investigate nanomaterials, including gold nanomaterials, two-dimensional materials, metal sulfide oxides, polymers, carbon nanomaterials, NIR-II dyes, and other nanomaterials for tumor diagnostic and therapeutic integrated nanoplatform construction. In this paper, the application of multifunctional nanomaterials in tumor NIR-II imaging and collaborative therapy in the past three years is briefly reviewed, and the current research status is summarized and prospected, with a view to contributing to future tumor therapy.


Sujet(s)
Nanoparticules , Nanostructures , Tumeurs , Humains , Photothérapie/méthodes , Polymères/usage thérapeutique , Nanostructures/usage thérapeutique , Tumeurs/thérapie , Tumeurs/traitement médicamenteux , Imagerie optique , Nanomédecine théranostique/méthodes
14.
Nanomaterials (Basel) ; 13(24)2023 Dec 12.
Article de Anglais | MEDLINE | ID: mdl-38133019

RÉSUMÉ

Coal-based Carbon Dots (C-CDs) have gradually become a research focus due to the abundant raw materials and low preparation cost. Still, before coal-based carbon dots are widely used, a systematic biological toxicity study is the basis for the safe utilization of C-CDs. However, the level of toxicity and the mechanism of toxicity of C-CDs for organisms are still unclear. To ensure the safe utilization of C-CDs, the present study investigated C-CD nanomaterials as stressors to probe their biotoxic effects on plant, bacterial, and animal cells as well as the photocatalytic oxidative properties of C-CDs. The results showed that low concentrations of C-CDs could promote various growth indicators of wheat, and high concentrations of C-CDs had significant inhibitory effects on wheat growth; C-CDs had significant toxic effects on (S. aureus) at specific concentrations and were light-related; meanwhile, at concentrations of 1-5000 µg/mL, C-CDs were almost not toxic to HeLa cells; however, when irradiated at 365 nm, even low concentrations of C-CDs were toxic to cells by the mechanism that C-CDs could generate singlet oxygen (1O2) by photocatalytic oxidation under 365 nm excitation light, resulting in enhanced toxicity of C-CDs to cells.

15.
Ultrason Sonochem ; 101: 106680, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37956509

RÉSUMÉ

In this research, the ultrasound-assisted extraction (UAE) conditions of the water-soluble polysaccharide (FCPS) from Ficus carica fruits were optimized using the response surface methodology. The optimal FCPS yield was 7.97 % achieved by conducting ultrasound-assisted extraction four times at a solid-liquid ratio of 1:20 (g/mL) and an ultrasound temperature of 70 °C. Then, the structure, antioxidant properties, hypoglycemic effects, and immunomodulatory activities of FCPS were evaluated. FCPS was characterized as irregular, rough-surfaced, flaky materials consisting of pyran-type polysaccharides with α- and ß-glycosidic linkages, and composed of multiple monosaccharides and only one homogeneous concentrated polysaccharide component (FCPS1) with a molecular weight of 4.224 × 104 Da. The results suggested FCPS exhibited remarkable antioxidant activity in vitro, as evidenced by improved cell viability and reduced the reactive oxygen species (ROS) levels. Meanwhile, FCPS effectively improved liver-related insulin resistance by promoting glucose consumption in hepatocytes and activated the immune response through activation of murine bone marrow-derived dendritic cells (DCs) and upregulation of interleukin 6 (IL6) and interleukin 12 (IL-12) expression. The findings demonstrate the efficacy of the UAE technique in isolating FCPS with biological functionality and FCPS could potentially serve as a beneficial organic antioxidant source and functional food, carrying important implications for future studies.


Sujet(s)
Antioxydants , Ficus , Animaux , Souris , Antioxydants/composition chimique , Ficus/composition chimique , Hypoglycémiants/pharmacologie , Polyosides/composition chimique , Immunité
16.
Int J Mol Sci ; 24(22)2023 Nov 15.
Article de Anglais | MEDLINE | ID: mdl-38003540

RÉSUMÉ

To overcome the shortcomings of traditional extraction methods, such as long extraction time and low efficiency, and considering the low content and high complexity of total flavonoids in Artemisia absinthium L., in this experiment, we adopted ultrasound-assisted enzymatic hydrolysis to improve the yield of total flavonoids, and combined this with molecular docking and network pharmacology to predict its core constituent targets, so as to evaluate its antitumor activity. The content of total flavonoids in Artemisia absinthium L. reached 3.80 ± 0.13%, and the main components included Astragalin, Cynaroside, Ononin, Rutin, Kaempferol-3-O-rutinoside, Diosmetin, Isorhamnetin, and Luteolin. Cynaroside and Astragalin exert their cervical cancer inhibitory functions by regulating several signaling proteins (e.g., EGFR, STAT3, CCND1, IGFIR, ESR1). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the anticancer activity of both compounds was associated with the ErbB signaling pathway and FoxO signaling pathway. MTT results showed that total flavonoids of Artemisia absinthium L. and its active components (Cynaroside and Astragalin) significantly inhibited the growth of HeLa cells in a concentration-dependent manner with IC50 of 396.0 ± 54.2 µg/mL and 449.0 ± 54.8 µg/mL, respectively. Furthermore, its active components can mediate apoptosis by inducing the accumulation of ROS.


Sujet(s)
Artemisia absinthium , Humains , Cellules HeLa , Simulation de docking moléculaire , Flavonoïdes/pharmacologie , Antioxydants/pharmacologie , Protéines
17.
Molecules ; 28(22)2023 Nov 15.
Article de Anglais | MEDLINE | ID: mdl-38005327

RÉSUMÉ

A novel photochromic heteropolyacid-based composite film consisting of phosphomolybdic acid (PMoA), ZnO, and polyvinylpyrrolidone (PVP) was fabricated by a sol-gel process. The microstructure and photochromic properties of the PMoA/ZnO/PVP were characterized via Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and ultraviolet-visible spectroscopy (UV-Vis). The FTIR spectra showed that the basic structures of ZnO and PVP, and the Keggin structure of PMoA in the PMoA/ZnO/PVP composite film, had not been destroyed during the preparation. The TEM images demonstrated that ZnO presented a rod-like structure, while PMoA was spherical, and many PMoA balls adhered to the surface of the ZnO rods. The XPS spectra of Mo 3d indicated that the valency of Mo atoms in the PMoA/ZnO/PVP was changed by visible light exposure. After visible light irradiation, the PMoA/ZnO/PVP varied from slight yellow to blue, while undergoing an opposite color change upon heating. The discoloration mechanism of the PMoA/ZnO/PVP was consistent with the photoelectron transfer mechanism.

18.
Int J Biol Macromol ; 253(Pt 6): 127373, 2023 Dec 31.
Article de Anglais | MEDLINE | ID: mdl-37839602

RÉSUMÉ

Nattokinase is a promising thrombolytic drug due to its powerful fibrinolytic effect and few side effects. However, the low fibrinolytic activity and stability of nattokinase have limited its industrial production and oral application. In this study, the basic and neutral amino acid residues on the surface of recombinant nattokinase AprY from Bacillus mojavensis LY-06 (rAprY) were mutated to acidic amino acid residues by surface charge engineering strategy, and two variants K12D and N109D with 92.6 % and 8.4 % increased fibrinolytic activity were obtained. The R45E variant with enhanced acid stability and thermostability was also screened, its acid stability at pH 4 and t1/2 at 55 °C were 3.7-fold and 1.8-fold higher than that of wild type rAprY, respectively. Bioinformatics analysis showed that the increased activities of K12D and N109D variants were related to the increased flexibility of the region around their active centers. The increased rigidity of 97-103 amino acid residues around the active center of R45E may be the reason for its enhanced stability and reduced catalytic activity. The multipoint mutation K12D-N109D (M2)'s catalytic activity did not increase cumulatively, but its pH stability did. The nattokinase variants generated in this study have potential for industrial production and application.


Sujet(s)
Bacillus subtilis , Subtilisines , Bacillus subtilis/génétique , Subtilisines/métabolisme , Mutation , Acides , Stabilité enzymatique
19.
Biomed Pharmacother ; 168: 115758, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37866002

RÉSUMÉ

Cross-presentation (XPT) is an adaptation of the cellular process in which dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules for recognition of the cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, resulting in immunity or tolerance. Recent advances in DCs have broadened our understanding of the underlying mechanisms of XPT and strengthened their application in tumor immunotherapy. In this review, we summarized the known mechanisms of XPT, including the receptor-mediated internalization of exogenous antigens, endosome escape, engagement of the other XPT-related proteins, and adjuvants, which significantly enhance the XPT capacity of DCs. Consequently, various strategies to enhance XPT can be adopted and optimized to improve outcomes of DC-based therapy.


Sujet(s)
Cross-priming , Cellules dendritiques , Présentation d'antigène , Antigènes/métabolisme , Antigènes d'histocompatibilité de classe I
20.
Front Immunol ; 14: 1208349, 2023.
Article de Anglais | MEDLINE | ID: mdl-37711617

RÉSUMÉ

Introduction: Lactococcus lactis (L.L) is safe and can be used as vehicle. In this study, the immunoregulatory effect of L.L on dendritic cell (DC) activation and mechanism were investigated. The immune responses and antigen cross-presentation mechanism of DC-based vaccine prepared with OVA recombinant L.L were explored. Methods: Confocal microscopy and flow cytometry were used to analyze the mechanism of L.L promoting DC maturation, phagosome membrane rupture and antigen presentation. The antitumor effect of DC vaccine prepared with L.L-OVA was assessed in the B16-OVA tumor mouse model. Results: L.L significantly promoted DC maturation, which was partially dependent on TLR2 and downstream MAPK and NF-κB signaling pathways. L.L was internalized into DCs by endocytosis and did not co-localized with lysosome. OVA recombinant L.L enhanced antigen cross-presentation of DCs through the phagosome-to-cytosol pathway in a reactive oxygen species (ROS)- and proteasome-dependent manner. In mouse experiments, L.L increased the migration of DCs to draining lymph node and DC vaccine prepared with OVA recombinant L.L induced strong antigen-specific Th1 and cytotoxic T lymphocyte responses, which significantly inhibited B16-OVA tumor growth. Conclusion: This study demonstrated that recombinant L.L as an antigen delivery system prepared DC vaccine can enhance the antigen cross-presentation and antitumor efficacy.


Sujet(s)
Lactococcus lactis , Vaccins , Animaux , Souris , Présentation d'antigène , Cross-priming , Lactococcus lactis/génétique , Espèces réactives de l'oxygène , Lysosomes , Cellules dendritiques
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