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1.
J Mater Chem B ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503001

RESUMO

Probiotic-based therapy for ulcerative colitis (UC) is a novel and promising approach that has gained much popularity in recent years. However, probiotics may be easily captured and destroyed by the harsh in vivo environment, which limits their application prospects to a large extent. This work introduces a versatile facile approach for decorating individual probiotics with nanozyme coatings, named Pt-Lipid@EcN. A bimolecular lipid coating is deposited on the surface of probiotics used in the oral treatment of UC using simple self-assembly with a liposome under cytocompatible conditions, and it acts as armor to effectively protect the probiotics from strong digestive acids and enzymes. The obtained results indicated that the liposome-coated Escherichia coli Nissle (EcN) 1917 could significantly improve the colonization rate of the microorganisms in the intestinal tract. We also explored the specific mechanism of Pt-Lipid@EcN to improve the behavior of murine UC models, including reduction of inflammatory effects and histological injury, and regulation of epithelial barrier homeostasis in the intestine. The nanozyme-shielded probiotic exhibited enhanced anti-inflammatory ability in vivo, introducing novel strategies for the application of nanozyme biomedicine in the treatment of colonic inflammatory diseases.

2.
Arch Insect Biochem Physiol ; : e21909, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506545

RESUMO

In recent years, as an emerging pollutant, microplastic (MPs) pollution is gradually becoming a research hotspot. MPs are ubiquitous in the entire ecological environment. Organisms can be exposed to MPs via inhalation or ingestion. In view of the widespread of MPs pollution, the impact of MPs on biology should be further investigated. In previous experiments, we have conducted research on the physiology of Drosophila exposed to polyethylene terephthalate microplastics (PET-MPs). However, will the lifespan of Drosophila be affected under long-term PET-MPs exposure? The analysis of variance analysis of our experimental results indicates that there are significant differences between males and females, F(1, 895) = 68.19, p < 0.001, between PET-MPs concentration, F(3, 895) = 8.11, p < 0.001. There are also significant interactions between sex and MP concentration, F(3, 895) = 4.00, p < 0.01. For Cox and log-rank test, 1 g/L of PET-MPs prolongs the lifespan of male flies. The reason for this phenomenon may be the hormesis effect.

3.
Front Med (Lausanne) ; 9: 832376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572973

RESUMO

The concept of neurotrophic factor tyrosine kinase receptor (NTRK) fusion tumor has emerged in recent years. Moreover, NTRK fusion is unusual in common tumors but can often be identified in rare tumors. The NTRK fusion cervical or uterine tumors are mainly recognized through case reports due to their extremely low incidence. In this study, we reported a new case of EML4-NTRK3 fusion cervical sarcoma to enhance its recognition. To the best of our knowledge, this is the first case from a Chinese institution. We also conducted a literature review, in which a total of 19 cases of NTRK fusion cervical tumors and 4 cases of uterine tumors were retrieved. We summarized the clinicopathological features, treatment methods, and prognosis of these cases. Based on available information, we observed that surgery and complete excision, if possible, are still the primary modes of therapy. In addition, an increasing number of studies have shown that tropomyosin receptor kinases (TRK) inhibitors can improve the prognosis of cancer patients with NTRK gene fusion, which gives a silver lining for patients with metastatic lesions. We found that age and mitotic rate may be associated with recurrence or metastasis by univariate survival analysis. To draw more convincing conclusions, there is a need to establish an international database of rare cases and aggregate these sporadic cases.

4.
Int J Biol Sci ; 18(7): 2882-2897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541895

RESUMO

Cold-inducible RNA-binding protein (CIRBP) is documented to be required for maintaining cardiac function, however, its role in chemotherapy-induced cardiotoxicity remains obscured. Herein, we report that CIRBP decreases cardiomyocyte apoptosis and attenuates cardiotoxicity through disrupting OGF-OGFR signal. CIRBP deficiency is involved in diverse chemotherapeutic agents induced cardiomyocyte apoptosis. Delivery of exogenous CIRBP to the mouse myocardium significantly mitigated doxorubicin-induced cardiac apoptosis and dysfunction. Specifically, OGFR was identified as a downstream core effector responsible for chemotherapy-induced cardiomyocyte apoptosis. CIRBP was shown to interact with OGFR mRNA and to repress OGFR expression by reducing mRNA stability. CIRBP-mediated cytoprotection against doxorubicin-induced cardiac apoptosis was demonstrated to largely involve OGFR repression by CIRBP. NTX as a potent antagonist of OGFR successfully rescued CIRBP ablation-rendered susceptibility to cardiac dyshomeostasis upon exposure to doxorubicin, whereas another antagonist ALV acting only on opioid receptors did not. Taken together, our results demonstrate that CIRBP confers myocardium resistance to chemotherapy-induced cardiac apoptosis and dysfunction by dampening OGF/OGFR axis, shedding new light on the mechanisms of chemo-induced cardiotoxicity and providing insights into the development of an efficacious cardioprotective strategy for cancer patients.

5.
Molecules ; 27(9)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35566376

RESUMO

Laminaria japonica is widely consumed as a key food and medicine. Polysaccharides are one of the most plentiful constituents of this marine plant. In this study, several polysaccharide fractions with different charge numbers were obtained. Their physicochemical properties and anticoagulant activities were determined by chemical and instrumental methods. The chemical analysis showed that Laminaria japonica polysaccharides (LJPs) and the purified fractions LJP0, LJP04, LJP06, and LJP08 mainly consisted of mannose, glucuronic acid, galactose, and fucose in different mole ratios. LJP04 and LJP06 also contained minor amounts of xylose. The polysaccharide fractions eluted by higher concentration of NaCl solutions showed higher contents of uronic acid and sulfate group. Biological activity assays showed that LJPs LJP06 and LJP08 could obviously prolong the activated partial thromboplastin time (APTT), indicating that they had strong anticoagulant activity. Furthermore, we found that LJP06 exerted this activity by inhibiting intrinsic factor Xase with higher selectivity than other fractions, which may have negligible bleeding risk. The sulfate group may play an important role in the anticoagulant activity. In addition, the carboxyl group and surface morphology of these fractions may affect their anticoagulant activities. The results provide information for applications of L. japonica polysaccharides, especially LJP06 as anticoagulants in functional foods and therapeutic agents.

6.
Hum Vaccin Immunother ; : 1-8, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507867

RESUMO

Over 2 years into the COVID-19 pandemic, information on the safety and efficacy of COVID-19 vaccination, particularly for people in high-risk populations, has become a popular topic of discussion. The purpose of this study was to analyze the content and characteristics of YouTube videos related to COVID-19 vaccination and pregnancy. The 50 most viewed English language videos on pregnancy and COVID-19 vaccination were included in this study. The 50 YouTube videos were viewed 4,589,613 times, with 6% uploaded by consumers, 40% by medical professionals, and 44% by television or internet-based news. Videos from consumer sources more often mentioned a human trial of the COVID-19 vaccine (75% of consumer videos vs. 65% of medical professional videos and 31.8% of television or internet-based news videos, P = .036) and more often mentioned anti-vaccination sentiment, fear, or distrust of the vaccines (37.5% of consumer videos vs 5.0% of medical professional videos and 4.5% of television or internet-based news videos, P = .018). Videos uploaded by medical professionals more often mentioned emergency use of the COVID-19 vaccines (P = .016), passive immunity in general (P = .011), and that the COVID-19 vaccine is either unlikely to or will not cause harm in breastfeeding more often than did videos from consumer or television-based news sources (P = .034). New information regarding COVID-19 vaccination and pregnancy is continuing to emerge, and this study highlights that the information found in the most viewed YouTube videos on this topic can quickly become outdated.

7.
Comput Math Methods Med ; 2022: 4756728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450204

RESUMO

The flow of aqueous humor (AH) in the human eye plays a key role in the process of transporting nutrients to the intraocular tissues and maintaining normal intraocular pressure. The pathogenesis of many ophthalmic diseases is also closely related to the flow of AH. Therefore, it is of great significance to study the mechanism of AH dynamics in the human eye. In this paper, we used image processing technology to denoise and segment the anterior segment optical coherence tomography (AS-OCT) images and established a geometric model based on the human eye. At the same time, a model of AH dynamics in the human eye based on the lattice Boltzmann (LB) method was proposed. Then, we simulated the AH flow in the human eye with different morphological structures and different physical properties and analyzed the factors that affect the AH flow, including the shape of anterior chamber (AC), the crypts of iris, the indentation of cornea, the permeability of trabecular meshwork (TM), the secretion rate of AH, and the viscosity of AH. The results showed that the changes in eye tissue morphological structures and physical properties would affect the flow of AH. For example, the maximum velocity of AH flow decreases with the increases in cornea deformation. When the distance of cornea indentation changes from 0.3 mm to 0.5 mm, the maximum velocity of AH reduces by 17%. In the asymmetrical AC, the AH will form two different vortices. In the crypts of the iris, we found that the AH flow forms small vortices, a phenomenon that has not been reported in other papers. In addition, we found that the intraocular pressure (IOP) decreases with the increase of the TM permeability and increases with the increase of the AH secretion rate, and it is not sensitive to changes in the viscosity of AH.


Assuntos
Humor Aquoso , Hidrodinâmica , Câmara Anterior/diagnóstico por imagem , Humanos , Pressão Intraocular , Malha Trabecular/diagnóstico por imagem
8.
Artigo em Inglês | MEDLINE | ID: mdl-35404820

RESUMO

In this study, a multi-scale high-density convolutional neural network (MHCNN) classification method for spatial cognitive ability assessment was proposed, aiming at achieving the binary classification of task-state EEG signals before and after spatial cognitive training. Besides, the multi-dimensional conditional mutual information method was used to extract the frequency band features of the EEG data. And the coupling features under the combination of multi-frequency bands were transformed into multi-spectral images. At the same time, the idea of Densenet was introduced to improve the multi-scale convolutional neural network. Firstly, according to the discreteness of multispectral EEG image features, two-scale convolution kernels were used to calculate and learn useful channel and frequency band feature information in multispectral image data. Secondly, to enhance feature propagation and reduce the number of parameters, the dense network was connected after the multi-scale convolutional network, and the learning rate change function of the stochastic gradient descent algorithm was optimized to objectively evaluate the training effect. The experimental results showed that compared with the classical convolution neural network (CNN) and multi-scale convolution neural network, the proposed MHCNN had better classification performance in the six frequency band combinations with the highest accuracy of 98%: Theta-Alpha2-Gamma, Alpha2-Beta2-Gamma, Beta1-Beta2-Gamma, Theta-Beta2-Gamma, Theta- Alpha1-Gamma, and Alpha1-Alpha2-Gamma. By comparing the classification results of six frequency band combinations, it was found that the combination of the Theta-Beta2-Gamma band had the best classification effect. The MHCNN classification method proposed in this research could be used as an effective biological indicator of spatial cognitive training effect and could be extended to other brain function evaluations.


Assuntos
Eletroencefalografia , Redes Neurais de Computação , Algoritmos , Cognição , Eletroencefalografia/métodos , Humanos
9.
Protein Sci ; 31(5): e4286, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35481641

RESUMO

In Staphylococcus aureus, vancomycin-resistance-associated response regulator (VraR) is a part of the VraSR two-component system, which is responsible for activating a cell wall-stress stimulon in response to an antibiotic that inhibits cell wall formation. Two VraR-binding sites have been identified: R1 and R2 in the vraSR operon control region. However, the binding of VraR to a promoter DNA enhancing downstream gene expression remains unclear. VraR contains a conserved N-terminal receiver domain (VraRN ) connected to a C-terminal DNA binding domain (VraRC ) with a flexible linker. Here, we present the crystal structure of VraRC alone and in complex with R1-DNA in 1.87- and 2.0-Å resolution, respectively. VraRC consisting of four α-helices forms a dimer when interacting with R1-DNA. In the VraRC -DNA complex structure, Mg2+ ion is bound to Asp194. Biolayer interferometry experiments revealed that the addition of Mg2+ to VraRC enhanced its DNA binding affinity by eightfold. In addition, interpretation of NMR titrations between VraRC with R1- and R2-DNA revealed the essential residues that might play a crucial role in interacting with DNA of the vraSR operon. The structural information could help in designing and screening potential therapeutics/inhibitors to deal with antibiotic-resistant S. aureus via targeting VraR.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/química , DNA/metabolismo , Proteínas de Ligação a DNA/química , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/metabolismo , Staphylococcus aureus/química , Staphylococcus aureus/genética , Vancomicina/farmacologia
10.
Genes (Basel) ; 13(4)2022 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-35456447

RESUMO

The subgenus Cerasus and its relatives include many crucial economic drupe fruits and ornamental plants. Repetitive elements make up a large part of complex genomes, and some of them play an important role in gene regulation that can affect phenotypic variation. However, the variation in their genomes remains poorly understood. This work conducted a comprehensive repetitive sequence identification across the draft genomes of eight taxa of the genus Prunus, including four of the Prunus subgenus Cerasus (Prunus&nbsp;pseudocerasus, P. avium, P. yedoensis and P. × yedoensis) as well as congeneric species (Prunus salicina, P. armeniaca, P. dulcis and P. persica). Annotation results showed high proportions of transposable elements in their genomes, ranging from 52.28% (P. armeniaca) to 61.86% (P. pseudocerasus). The most notable differences in the contents of long terminal repeat retrotransposons (LTR-RTs) and tandem repeats (TRs) were confirmed with de novo identification based on the structure of each genome, which significantly contributed to their genome size variation, especially in P. avium and P.salicina. Sequence comparisons showed many similar LTR-RTs closely related to their phylogenetic relationships, and a highly similar monomer unit of the TR sequence was conserved among species. Additionally, the predicted centromere-associated sequence was located in centromeric regions with FISH in the 12 taxa of Prunus. It presented significantly different signal intensities, even within the diverse interindividual phenotypes for Prunus tomentosa. This study provides insight into the LTR-RT and TR variation within Prunus and increases our knowledge about its role in genome evolution.


Assuntos
Prunus avium , Prunus , Centrômero , Elementos de DNA Transponíveis/genética , Genoma de Planta/genética , Filogenia , Prunus/genética , Prunus avium/genética , Retroelementos/genética
11.
Chem Commun (Camb) ; 58(40): 5996-5999, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35485395

RESUMO

Herein, we report a facile synthetic method towards diketopyrrolopyrrole-aza-BODIPY hybrids by a two-step strategy. The three resulting fluorophores (LAB-TH4 ∼ LAB-TH6) showed absorption maxima up to 637 nm with molar extinction coefficients (ε) up to 32 300 M-1 cm-1 and emission maxima at 661 nm with a fluorescence quantum yield of 25.2% in solution. Due to good biocompatibility and strong ROS generation ability, they are useful fluorophores for bioimaging and photodynamic therapy (PDT). In addition, as a useful scaffold, a novel NIR-emissive conjugated polymer can be constructed by further bromination and Suzuki coupling polymerization.

12.
J Comput Assist Tomogr ; 46(3): 327-332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35405712

RESUMO

OBJECTIVE: To predict early tumor response to transarterial chemoembolization (TACE) based on volumetric oil deposition on posttreatment computed tomography (CT) in patients with leiomyosarcoma liver metastases. METHODS: This retrospective lesion-by-lesion based study included 32 lesions. The volumetric percent enhancing tumor on pre-TACE and 1-month post-TACE venous phase magnetic resonance imaging (MRI), and the percent oil deposition on CT 1 day after TACE were calculated. The predicted post-TACE enhanced percentage was computed by subtracting percent oil deposition from baseline percent enhanced. RESULTS: Mean percentage of viable tumor on pre-TACE MRI was 90.6% ± 9.3%. Mean oil deposition was calculated as 51.4% ± 26.2%. Mean percentage of measured residual tumor enhancement 1 month after TACE was 58.3% ± 27%, which correlates with predicted enhancement percentage of 43.9% ± 25.1% (r = 0.72, P < 0.001). A threshold of 35.5% for enhancement reduction was determined to predict tumor response with an accuracy of 78.1%. CONCLUSION: Volumetric oil deposition on CT can predict residual enhancement on post-TACE MRI.

13.
Infect Drug Resist ; 15: 1391-1397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392368

RESUMO

Aim: To reduce the inspection time for urinary tract pathogens and provide a rapid and effective therapeutic plan for clinical anti-infection treatment, this study developed a rapid identification (ID) and antimicrobial sensitivity test (AST) method by DOT-MGA. Methods: We grouped midstream urine samples with single bacteria according to the number of bacteria (≤5/5-15/≥ 15) under per oil microscope after Gram staining. Then we adopted differential centrifugation to process the grouped samples to collect precipitate. MALDI-TOF MS was performed using precipitate directly or after short-term culture. If succeed, we resuspended the precipitate into droplets with or without antibiotics at a MALDI target. Four hours later, mass spectrometer (MS) was used to identify the culture on the target and to analyse AST. Results: Samples (count ≥ 15), which precipitate can be directly identified by MS; otherwise, the precipitate need a short-term cultured for 3-6 h before ID. The consistency of the ID results between conventional culture and the precipitate is 100%. Compared with broth microdilution method, DOT-MGA for predicting AST had a high consistency. EA and CA for IPM, LEV, CAZ, NIT, and FOT were 100%/100%, 98%/90%, 98%/92%, 100%/90%, 98%/94%, respectively. No VME was observed in all tests. Besides, MIC50 for the five antibiotics by DOT-MGA and broth microdilution method were ≤1/≤0.5,>2/2,≤4/≤2,≤32/≤16,≤64/≤32 and MIC90 were ≤1/≤0.5, >2/>4, 16/16, 128/128, 128/64. Conclusion: This study can shorten the ID time (minimum 0.5h) and AST (minimum 4h) of the main pathogens of urinary tract infection to 5-10 hours, which greatly reduce the inspection time and provide substantial help for the rapid diagnosis and treatment of patients with urinary tract infection.

14.
ACS Nano ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35403424

RESUMO

The key challenges facing the commercialization of lithium-sulfur (Li-S) batteries are shortening the lithium polysulfide (LiPS) intermediate existence time while accelerating solid-phase conversion reactions. Herein, inspired by highly efficient natural enzymes with Fe/N active sites for oxygen reduction reactions, we report a periodic expansion catalysis concept, i.e., Ru and P synergic stereoselectivity, for designing sulfur reduction reaction (SRR) catalysts. As a proof of concept, a RuP2-configuration molecular catalyst was exploited to assemble an interlayer in Li-S batteries that adsorbs LiPSs, optimizes Li+ migration paths, and catalyzes SRRs. Comprehensive investigation identified the elimination of steric hindrance and strong electron orbital couplings between metallic d band and nonmetallic p band as the main contributing factors of PEC for the SRRs. As a result, the Li-S battery with ∼0.5 wt % catalyst additive showed enhanced cycling stability even under a high sulfur loading (6.5 mg cm-2) and low electrolyte/sulfur ratio (9 µL mg-1).

15.
Front Immunol ; 13: 833058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464462

RESUMO

The immune system plays a complex role in tumor formation and development. On the one hand, immune surveillance can inhibit the growth of tumors; on the other hand, immune evasion of tumors can create conditions conducive for tumor development and growth. CircRNAs are endogenous non-coding RNAs with a covalently closed loop structure that are abundantly expressed in eukaryotic organisms. They are characterized by stable structure, rich diversity, and high evolutionary conservation. In particular, circRNAs play a vital role in the occurrence, development, and treatment of tumors through their unique functions. Recently, the incidence and mortality of digestive cancers, especially those of gastric cancer, colorectal cancer, and liver cancer, have remained high. However, the functions of circRNAs in digestive cancers immunity are less known. The relationship between circRNAs and digestive tumor immunity is systematically discussed in our paper for the first time. CircRNA can influence the immune microenvironment of gastrointestinal tumors to promote their occurrence and development by acting as a miRNA molecular sponge, interacting with proteins, and regulating selective splicing. The circRNA vaccine even provides a new idea for tumor immunotherapy. Future studies should be focused on the location, transportation, and degradation mechanisms of circRNA in living cells and the relationship between circRNA and tumor immunity. This paper provides a new idea for the diagnosis and treatment of gastrointestinal tumors.


Assuntos
Neoplasias Gastrointestinais , MicroRNAs , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/terapia , Humanos , MicroRNAs/genética , Splicing de RNA , RNA Circular/genética , Microambiente Tumoral
16.
Front Psychiatry ; 13: 874859, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479498

RESUMO

Background: Previous research studies have demonstrated that impaired interoception is involved in emotional information processing in major depressive disorder (MDD). Heartbeat-evoked potential (HEP) amplitudes, an index for interoception, could be manipulated by emotional faces in healthy people. Considering negative emotional bias is the core characteristic in MDD, we hypothesized that interoception dysfunction was associated with the negative emotional bias in MDD. Methods: An electroencephalogram (EEG) study under an emotional faces task was applied to explore the relationship between interoception and emotional bias. HEPs before emotional faces stimuli were used to predict the late positive potential (LPP) amplitudes and it worked as an index of emotional bias. Twenty-seven patients with MDD and 27 healthy controls (HCs) participated in this study. Source analysis gave an auxiliary description for results in sensory level. Results: Major depressive disorders (MDDs) had poor performance in the heartbeat count task (HCT) and attenuate HEP average amplitudes (455-550 ms). Compared with HCs, cluster-based permutation t-tests revealed that MDDs had attenuated LPP amplitudes (300-1,000 ms) over centroparietal regions and enhanced LPP amplitudes over frontocentral regions. Furthermore, abnormal attenuated HEPs could predict aberrant LPPs under sad face stimuli in MDDs, which could be associated with the dysfunction of the anterior cingulate cortex (ACC) and right insula. Conclusion: Mediated by ACC and insula, interoception dysfunction contributes to the negative emotional bias of MDD, highlighting the importance of interoception in the disorder.

17.
Infect Drug Resist ; 15: 685-696, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250283

RESUMO

INTRODUCTION: Carbapenemase-mediated antimicrobial resistance is currently a hot spot of global concern. Carbapenem-resistant organisms are highly prevalent in hospitals associated with difficult-to-treat infections, resulting in poor clinical outcome due to limited treatment options. It is urgently needed to have a rapid, efficient, and convenient molecular assay for identifying such resistant strains. METHODS: For this end, we developed a new laboratory assay targeting Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) based on loop-mediated isothermal amplification, CRISPR-Cas12a, and lateral flow immunochromatographic strip (CRISPR-Cas-LAMP-lateral flow strip). The method was designed to use a guide RNA (gRNA) to recognize the target DNA and guide Cas12a to cleave the target DNA, and simultaneously cleave any single-stranded DNA within the cleavage reaction system. RESULTS: The cleavage products are visible to the naked eye on the lateral flow strip. This method is highly sensitive in direct detection of bacteria in samples containing at least 3×105 CFU/mL without the need for bacterial culture. DISCUSSION: It provides shorter turnaround time and higher specificity than the conventional bacterial culture and susceptibility testing method. This new assay is applicable for extensive use in hospital infection control, as well as identification and treatment of resistant strains due to simple operation and inexpensive apparatuses.

18.
Toxicology ; 470: 153141, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35259468

RESUMO

Deregulation of apoptosis signaling is an important feature of cancer cells and plays an essential role in tumorigenesis. Xanthohumol is an active ingredient in Traditional Chinese Medicines Hops (Humulus lupulus L.). Recently studies have shown the profound anti-tumor activities of Xanthohumol in multiple cancer models. However, its potency in non-small cell lung cancer (NSCLC) and the underlying mechanisms are still elusive. Here, we have investigated the potency of Xanthohumol against NSCLC cells in vitro and xenograft mouse models. Xanthohumol suppressed cell viability, colony formation and induced apoptosis in A549, H520, and H358 cells. Xanthohumol activated mitochondrial apoptosis through upregulation of (p53-upregulated modulator of apoptosis) PUMA expression. After Xanthohumol treatment, the Akt activity was inhibited, which resulted in dephosphorylation of FOXO3a and PUMA induction. Silent PUMA or FOXO3a impaired Xanthohumol-induced apoptosis in NSCLC cells. In nude mice, Xanthohumol administration suppressed NSCLC xenograft tumor growth and increased PUMA expression in tumor tissues. Briefly, our studies revealed a novel mechanism by which Xanthohumol exerted its anti-tumor activity in a PUMA-dependent manner in NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Flavonoides , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Propiofenonas
19.
Acta Neuropathol ; 143(4): 505-521, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35303161

RESUMO

Inhibition of Bruton's Tyrosine Kinase (BTKi) is now viewed as a promising next-generation B-cell-targeting therapy for autoimmune diseases including multiple sclerosis (MS). Surprisingly little is known; however, about how BTKi influences MS disease-implicated functions of B cells. Here, we demonstrate that in addition to its expected impact on B-cell activation, BTKi attenuates B-cell:T-cell interactions via a novel mechanism involving modulation of B-cell metabolic pathways which, in turn, mediates an anti-inflammatory modulation of the B cells. In vitro, BTKi, as well as direct inhibition of B-cell mitochondrial respiration (but not glycolysis), limit the B-cell capacity to serve as APC to T cells. The role of metabolism in the regulation of human B-cell responses is confirmed when examining B cells of rare patients with mitochondrial respiratory chain mutations. We further demonstrate that both BTKi and metabolic modulation ex vivo can abrogate the aberrant activation and costimulatory molecule expression of B cells of untreated MS patients. Finally, as proof-of-principle in a Phase 1 study of healthy volunteers, we confirm that in vivo BTKi treatment reduces circulating B-cell mitochondrial respiration, diminishes their activation-induced expression of costimulatory molecules, and mediates an anti-inflammatory shift in the B-cell responses which is associated with an attenuation of T-cell pro-inflammatory responses. These data collectively elucidate a novel non-depleting mechanism by which BTKi mediates its effects on disease-implicated B-cell responses and reveals that modulating B-cell metabolism may be a viable therapeutic approach to target pro-inflammatory B cells.


Assuntos
Tirosina Quinase da Agamaglobulinemia , Linfócitos B , Esclerose Múltipla , Inibidores de Proteínas Quinases , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Comunicação Celular , Humanos , Esclerose Múltipla/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
20.
Nanoscale ; 14(11): 4234-4243, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35234767

RESUMO

Cracks play an important role in strain sensors. However, a systematic analysis of how cracks influence the strain sensors has not been proposed. In this work, an intelligent and highly sensitive strain sensor based on indium tin oxide (ITO)/polyurethane (PU) micromesh is realized. The micromesh has good skin compatibility, water vapor permeability, and stability. Due to the color of the ITO/PU micromesh, it can be invisible on the skin. Based on the fragility of ITO, the density and resistance of cracks in the micromesh are greatly improved. Therefore, the ITO/PU micromesh strain sensor (IMSS) has an ultrahigh gauge factor (744.3). In addition, a finite element model based on four resistance layers is proposed to explain the performance of the IMSS and show the importance of high-density cracks. Compared with other strain sensors based on low-density cracks, the IMSS based on high-density cracks has larger sensitivity and better linearity. Physiological signals, such as respiration, pulse, and joint motion, can be monitored using the IMSS self-fixed on the skin. Finally, an invisible and artificial throat has been realized by combining the IMSS with a convolutional neural network algorithm. The artificial throat can translate the throat vibrations of the tester automatically with an accuracy of 86.5%. This work has great potential in health care and language function reconstruction.

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