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Pure SnO2 and 1 at.% PdO-SnO2 materials were prepared using a simple hydrothermal method. The micromorphology and element valence state of the material were characterized using XRD, SEM, TEM, and XPS methods. The SEM results showed that the prepared material had a two-dimensional nanosheet morphology, and the formation of PdO and SnO2 heterostructures was validated through TEM. Due to the influence of the heterojunction, in the XPS test, the energy spectrum peaks of Sn and O in PdO-SnO2 were shifted by 0.2 eV compared with SnO2. The PdO-SnO2 sensor showed improved ethanol sensing performance compared to the pure SnO2 sensor, since it benefited from the large specific surface area of the nanosheet structure, the modulation effect of the PdO-SnO2 heterojunction on resistance, and the catalyst effect of PdO on the adsorption of oxygen. A DFT calculation study of the ethanol adsorption characteristics of the PdO-SnO2 surface was conducted to provide a detailed explanation of the gas-sensing mechanism. PdO was found to improve the reducibility of ethanol, enhance the adsorption of ethanol's methyl group, and increase the number of adsorption sites. A synergistic effect based on the continuous adsorption sites was also deduced.
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Background: There are no standard guidelines regarding the number and size of chest tubes that should be selected after thoracic surgery. This study aimed to evaluate the effects of adopting a drainage strategy with bi-pigtail catheters (BPCs) on patients undergoing lobectomy by uniportal video-assisted thoracic surgery (VATS). Methods: A retrospective study was performed of patients undergoing uniportal lobectomy at the Department of Thoracic Surgery of the Cancer Hospital of Dalian University of Technology between August 2021 and August 2022. The patients were divided into the following two groups according to the drainage strategy adopted: (I) a traditional chest tube (TCT) group; and (II) a BPC group. The outcomes measured included postoperative complications, as measured by the Clavien-Dindo method, and the visual analogue scale (VAS) pain scores of the patients after surgery. Results: In total, 868 patients underwent lung resection during the study period, after exclusion, the data of 470 patients who underwent uniport lobectomy were reviewed (235 in the TCT group, and 235 in the BPC group). There were no statistically significant differences between the two groups in terms of baseline data (P>0.05). The incidence of postoperative complications (7.7% vs. 19.1%) and postoperative VAS pain scores at 7-24 hours (3.3±1.0 vs. 3.7±1.5) and 25-48 hours (3.1±0.8 vs. 3.6±1.5) were significantly lower in the BPC group than the TCT group (all P<0.001). Additionally, the postoperative length of stay (4.6±1.5 vs. 5.4±4.5 days) and the collapse rate of the residual lung (19.2%±9.1% vs. 20.9%±9.6%) of the BPC group were better than those of the TCT group (P<0.05). The results of univariable and multivariable analyses showed that a drainage strategy with a TCT was an independent risk factor for decreased postoperative complications, and reduced moderate or severe pain scores at 7-24 and 25-48 hours after surgery. Conclusions: Our drainage strategy with BPCs decreased the incidence of postoperative complications and alleviated the postoperative pain of patients undergoing lobectomy by uniportal VATS and is safe and feasible.
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Currently, the most effective way to improve the anti-fouling performance of water treatment separation membrane is to enhance the hydrophilicity of the membrane surface, but it can still cause contamination, leading to the occurrence of flux reduction. The construction of a strong hydration layer to resist wastewater contamination is still a challenging task. In this study, a defect-free hydration layer barrier was achieved by grafting chitosan polysaccharide derivatives (CS-SDAEM) on the membrane, which achieved in effective fouling prevention and low flux decline rate. A layer of tannic acid-coated carbon nanotubes (TA@CNTs) has been uniformly deposited on the commercial PVDF membrane so that the surface was rich in -COOH groups, providing sufficient reaction sites. These reactive groups facilitate the grafting of amphiphilic polymers onto the membrane. This modification strategy achieved in enhancing the antifouling performance. The modified membrane achieved low contamination rate with DR of 16.9 % for wastewater filtration, and the flux recovery rate was above 95 % with PWF of 1100 (L·m-2·h-1). The membrane had excellent anti-fouling performance, which provided a new route for the future development of water treatment membrane.
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Quitosana , Emulsões , Membranas Artificiais , Nanotubos de Carbono , Polivinil , Purificação da Água , Purificação da Água/métodos , Quitosana/química , Polivinil/química , Nanotubos de Carbono/química , Taninos/química , Polissacarídeos/química , Água/química , Águas Residuárias/química , Óleos/química , Interações Hidrofóbicas e Hidrofílicas , Filtração/métodos , Polímeros de FluorcarbonetoRESUMO
The triphenylamine Schiff-base (TPASB) with dual proton transfer sites (N1 H1-O1 [R1] and N2 H2-O2 [R2]), which is crucial in the field of optoelectronic materials. Herein, a novel molecular design strategy for preparing of TPASB-1 and TPASB-2 via the selective methylation of the hydroxyl group at the R2 or R1 position was proposed. The analysis of electronic structures and potential energy surfaces revealed that a single excited state intramolecular proton transfer (ESIPT) process of TPASB occurs only at R1. Nevertheless, the ESIPT process of TPASB-2 was successfully turned on at R2. More noteworthy is that compared to TPASB, the methylation of hydroxyl group at the R2 position triggers the TICT process of TPASB-1, effectively reducing the potential barrier of ESIPT at the R1 position. This theoretical study explains the role of the substituent effect in regulating ESIPT behaviour, and provides valuable guidance for synthesising efficacious ESIPT-active compounds.
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Background: The most effective method and length of time for administering adjuvant immunotherapy after surgery for non-small cell lung cancer (NSCLC) are still unknown. Various clinical trials have utilized diverse strategies for adjuvant treatment. In this case, we explore the potential benefits of neoadjuvant immunotherapy combined with chemotherapy in managing locally advanced lung squamous carcinoma, which often poses challenges for treatment. This multimodal approach aims to downstage tumors and optimize surgical outcomes. Case Description: Following a diagnosis of stage IIIB lung cancer, the patient underwent three cycles of neoadjuvant therapy using sintilimab, Abraxane, and Lobaplatin, resulting in a significant 45% reduction in tumor size. Subsequently, a right lower lobe lobectomy and systematic lymphadenectomy were performed using a uniportal video-assisted thoracic surgery (VATS) approach. Postoperative analysis revealed negative lymph nodes, with only a 5-mm residual tumor in the tumor bed, downstaging the cancer to IA1. Remarkably, the patient experienced a smooth recovery without any postoperative complications. One cycle of adjuvant therapy was administered following the operation to further support the patient's recovery and minimize the risk of disease recurrence. This comprehensive treatment approach underscores the importance of neoadjuvant therapy in optimizing surgical outcomes and improving long-term prognosis for patients with locally advanced lung cancer. Conclusions: For patients with stage III locally advanced lung squamous carcinoma, the combination of Sintilimab and Platinum-based drugs can be used as a neoadjuvant therapy which can reduce the difficulty of the operation.
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The majority of the immune cell population in the tumor microenvironment (TME) consists of tumor-associated macrophages (TAM), which are the main players in coordinating tumor-associated inflammation. TAM has a high plasticity and is divided into two main phenotypes, pro-inflammatory M1 type and anti-inflammatory M2 type, with tumor-suppressive and tumor-promoting functions, respectively. Considering the beneficial effects of M1 macrophages for anti-tumor and the high plasticity of macrophages, the conversion of M2 TAM to M1 TAM is feasible and positive for tumor treatment. This study sought to evaluate whether the glycopeptide derived from simulated digested Codonopsis pilosula extracts could regulate the polarization of M2-like TAM toward the M1 phenotype and the potential regulatory mechanisms. The results showed that after glycopeptide dCP1 treatment, the mRNA relative expression levels of some M2 phenotype marker genes in M2-like TAM in simulated TME were reduced, and the relative expression levels of M1 phenotype marker genes and inflammatory factor genes were increased. Analysis of RNA-Seq of M2-like TAM after glycopeptide dCP1 intervention showed that the gene sets such as glycolysis, which is associated with macrophage polarization in the M1 phenotype, were significantly up-regulated, whereas those of gene sets such as IL-6-JAK-STAT3 pathway, which is associated with polarization in the M2 phenotype, were significantly down-regulated. Moreover, PCA analysis and Pearson's correlation also indicated that M2-like TAM polarized toward the M1 phenotype at the transcriptional level after treatment with the glycopeptide dCP1. Lipid metabolomics was used to further explore the efficacy of the glycopeptide dCP1 in regulating the polarization of M2-like TAM to the M1 phenotype. It was found that the lipid metabolite profiles in dCP1-treated M2-like TAM showed M1 phenotype macrophage lipid metabolism profiles compared with blank M2-like TAM. Analysis of the key differential lipid metabolites revealed that the interconversion between phosphatidylcholine (PC) and diacylglycerol (DG) metabolites may be the central reaction of the glycopeptide dCP1 in regulating the conversion of M2-like TAM to the M1 phenotype. The above results suggest that the glycopeptide dCP1 has the efficacy to regulate the polarization of M2-like TAM to M1 phenotype in simulated TME.
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Codonopsis , Fenótipo , Macrófagos Associados a Tumor , Animais , Humanos , Camundongos , Glicopeptídeos/metabolismo , Glicopeptídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/imunologia , Microambiente Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacosRESUMO
In this study, the dual strategy of 1-butyl-3-vinylimidazolium bromide ionic liquid (IL) grafting and carbon nanotubes (CNTs) nanocomposition was applied to modify poly(vinylidene fluoride) (PVDF)-based membranes. The highly hydrophilic/oleophobic and fouling-resistant PVDF-g-IL/CNTs membranes with excellent separation efficiency were obtained by the nonsolvent-induced phase separation method with ethanol-water mixed solution as the coagulation bath. The grafted IL not only generated hydrophilic groups on PVDF chains but also acted together with the CNTs to induce the formation of hydrophilic ß-crystalline phase of PVDF, which significantly improved the hydrophilicity and pore structure of the modified PVDF membranes. As a result, the pure water flux of the optimal membrane increased up to 294.2 L m-2 h-1, which was 5.2 times greater than that of the pure PVDF membrane. Simultaneously, the electrostatic interaction of the positive IL and the integration of CNTs enhanced adsorption sites of the membranes, producing exceptional retention and adsorption of dye wastewater and oil-water emulsion. This study presents a straightforward and efficient approach for fabricating PVDF separation membranes, which have potential applications in the purification of various polluted wastewater.
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Although chemical methods for the selective derivatization of amino acid (AA) side chains in peptides and proteins are available, selective N-terminal labeling is challenging, especially for glycine, which has no side chain at the α-carbon position. We report here a double activation at glycine's α-methylene group that allows this AA to be differentiated from the other 19 AAs. A condensation reaction of dibenzoylmethane with glycine results in the formation of an imine, and subsequent tautomerization is followed by intramolecular cyclization, leading to the formation of a fluorescent pyrrole ring. Additionally, the approach exhibits compatibility with AAs possessing reactive side chains. Further, the method allows for selective pull-down assays of N-terminal glycine peptides from mixtures without prior knowledge of the N-terminal peptide distribution.
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Corantes Fluorescentes , Glicina , Peptídeos , Glicina/química , Corantes Fluorescentes/química , Peptídeos/química , Estrutura MolecularRESUMO
BACKGROUND: Traditional Chinese medicine injection for Activating Blood Circulation (TCMi-ABC), which exhibits comparable anticoagulant and antiplatelet effects, is commonly used as an adjuvant treatment for acute myocardial infarction (AMI) in China. OBJECTIVE: The aim of this study was to conduct a meta-analysis to assess the efficacy and safety of TCMi-ABC in combination with conventional western medicine in reducing mortality associated with AMI. METHODS: We conducted a comprehensive search of PubMed, Cochrane Library, EMBASE, Web of Science, CBM, WanFang Data, and CNKI databases. Randomized controlled trials (RCTs) investigating the use of TCMi-ABC (including Danhong injection, sodium tanshinone IIA sulfonate injection, salvia miltiorrhiza ligupyrazine injection, and puerarin injection) for the treatment of AMI were included. The search included studies published from the inception of the databases up to December 2022. Two authors independently screened RCTs, extracted data, and assessed the risk of bias. Meta-analysis was performed using RevMan 5.3 and Stata 17.0. The quality of evidence was evaluated using the GRADE approach. RESULTS: A total of 52 RCTs involving 5363 patients were included in the analysis, none of which described independent testing of the purity or potency of the TCMi-ABC product used. 19/52 reported random sequence generation. All RCTs lack adequate description of allocation concealment. 51/52 failed to assess blinding. The meta-analysis results demonstrated that the combined application of TCMi-ABC, compared with conventional western medicine treatment alone, significantly reduced in-hospital mortality in AMI patients [RR= 0.41, 95% CI (0.29, 0.59), P < 0.05], decreased the incidence of malignant arrhythmia [RR= 0.40, 95% CI (0.26, 0.61), P < 0.05], and increased left ventricular ejection fraction (LVEF) [MD= 5.53, 95% CI (3.81, 7.26), P < 0.05]. There was no significant difference in the incidence of adverse events between the two groups (P > 0.05). The GRADE evidence quality classification indicated that the evidence for in-hospital mortality, malignant arrhythmia, and adverse events was of moderate quality, while the evidence for LVEF was of low quality. CONCLUSION: TCMi-ABC demonstrates additional clinical value in reducing mortality and the risk of malignant arrhythmia in patients with AMI. However, further validation of these findings is warranted through high-quality clinical trials due to methodological weaknesses in randomization, blinding, allocation concealment, and insufficient assessing for the purity/potency of herbs and the gram amount of active constituents. SYSTEMATIC REVIEW REGISTRATION: [INPLASY], identifier [INPLASY202170082].
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Anticoagulantes , Medicamentos de Ervas Chinesas , Infarto do Miocárdio , Inibidores da Agregação Plaquetária , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Anticoagulantes/uso terapêutico , Circulação Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Injeções , Medicina Tradicional Chinesa/métodos , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêuticoRESUMO
Stimuli-responsive nano-assemblies from amphiphilic macromolecules could undergo controlled structural transformations and generate diverse macroscopic phenomenon under stimuli. Due to the controllable responsiveness, they have been applied for broad material and biomedical applications, such as biologics delivery, sensing, imaging, and catalysis. Understanding the mechanisms of the assembly-disassembly processes and structural determinants behind the responsive properties is fundamentally important for designing the next generation of nano-assemblies with programmable responsiveness. In this review, we focus on structural determinants of assemblies from amphiphilic macromolecules and their macromolecular level alterations under stimuli, such as the disruption of hydrophilic-lipophilic balance (HLB), depolymerization, decrosslinking, and changes of molecular packing in assemblies, which eventually lead to a series of macroscopic phenomenon for practical purposes. Applications of stimuli-responsive nano-assemblies in delivery, sensing and imaging were also summarized based on their structural features. We expect this review could provide readers an overview of the structural considerations in the design and applications of nanoassemblies and incentivize more explorations in stimuli-responsive soft matters.
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This study aimed to conduct a visual analysis of the relevant literature on mitochondrial dynamics in heart failure, explore the research progress, frontier topics, and development trends in this field, and provide references for the study concerning mitochondrial dynamics in the prevention and treatment of heart failure. The Web of Science was searched from inception to October 1, 2023 to identify relevant English literature on mitochondrial dynamics in heart failure. Bibliometric methods were utilized to statistically analyze the eligible literature, and CiteSpace 6.2.R5 software was employed to visualize data such as countries of publication, institutions, authors, and keywords. A total of 1755 Science Citation Index articles were included. The global publication volume showed an increasing trend year by year, with China and the United States having the most publications, and the United States displaying the highest centrality in publications. As revealed by keyword and citation analyses, the research hotspots and frontiers in this field mainly included the pathogenesis of heart failure, mitochondrial dynamics markers, mitochondrial quality control, and potential therapeutic targets for heart failure. Research on mitochondrial dynamics in heart failure is under vigorous development. It is a development trend in this research field to explore the differential gene expression and molecular mechanisms of targeted treatment in the mitochondrial dynamics in heart failure, which will contribute to the formulation of new strategies for the prevention and treatment of heart failure.
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Insuficiência Cardíaca , Dinâmica Mitocondrial , Humanos , Insuficiência Cardíaca/terapia , Bibliometria , China , MitocôndriasRESUMO
Electronic cigarettes (e-cigarettes), as alternative nicotine delivery methods, has rapidly increased among youth and adults in recent years. However, cardiovascular safety is an important consideration regarding e-cigarettes usage. e-cigarette emissions, including nicotine, propylene glycol, flavorings, nitrosamine, and metals, might have adverse effects on cardiovascular health. A large body of epidemiological evidence has indicated that e-cigarettes are considered an independent risk factor for increased rates of cardiovascular disease occurrence and death. The incidence and mortality of various types of cardiovascular disease, such as cardiac arrhythmia, hypertension, acute coronary syndromes, and heart failure, have a modest growth in vapers (users of e-cigarettes). Although the underlying biological mechanisms have not been fully understood, studies have validated that oxidative stress, inflammation, endothelial dysfunction, atherosclerosis, hemodynamic effects, and platelet function play important roles in which e-cigarettes work in the human body. This minireview consolidates and discusses the epidemiological and biological links between e-cigarettes and various types of cardiovascular disease.
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Doenças Cardiovasculares , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Vaping/efeitos adversos , Vaping/epidemiologia , Animais , Nicotina/efeitos adversos , Nicotina/administração & dosagemRESUMO
Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Antígeno B7-H1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antineoplásicos/uso terapêuticoRESUMO
Rechargeable hydrogen gas batteries, driven by hydrogen evolution and oxidation reactions (HER/HOR), are emerging grid-scale energy storage technologies owing to their low cost and superb cycle life. However, compared with aqueous electrolytes, the HER/HOR activities in nonaqueous electrolytes have rarely been studied. Here, for the first time, we develop a nonaqueous proton electrolyte (NAPE) for a high-performance hydrogen gas-proton battery for all-climate energy storage applications. The advanced nonaqueous hydrogen gas-proton battery (NAHPB) assembled with a representative V2(PO4)3 cathode and H2 anode in a NAPE exhibits a high discharge capacity of 165 mAh g-1 at 1 C at room temperature. It also efficiently operates under all-climate conditions (from -30 to +70 °C) with an excellent electrochemical performance. Our findings offer a new direction for designing nonaqueous proton batteries in a wide temperature range.
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Eco-friendly and efficient energy production and storage technologies are highly demanded to address the environmental and energy crises. Porous organic polymers (POPs) are a class of lightweight porous network materials covalently linked by organic building blocks, possessing high surface areas, tunable pores, and designable components and structures. Due to their unique structural and compositional advantages, POPs have recently emerged as promising electrode materials for energy storage devices, particularly in the realm of supercapacitors and ion batteries. In this work, a comprehensive overview of recent progress and applications of POPs as electrode materials in energy storage devices, including the structural features and synthesis strategies of various POPs, as well as their applications in supercapacitors, lithium batteries, sodium batteries, and potassium batteries are provided. Finally, insights are provided into the future research directions of POPs in electrochemical energy storage technologies. It is anticipated that this work can provide readers with a comprehensive background on the design of POPs-based electrode materials and ignite more research in the development of next-generation energy storage devices.
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INTRODUCTION: Radical surgery including mediastinal lymph node dissection is the standard treatment for early-stage non-small cell lung cancer (NSCLC). About 50% lung nodules are pure ground glass or part-solid nodules, which are predominantly clinical stage IA NSCLC. Non-solid nodules rarely develop mediastinal lymph node metastasis. METHOD AND ANALYSIS: A phase III study was started in China to evaluate the non-inferiority in overall survival of spared mediastinal lymph node dissection compared with mediastinal lymph node dissection in stage IA NSCLC. A total of 1362 patients will be enrolled from 4 institutions in 2-3 years. The second endpoints are relapse-free survival and perioperative data, including duration of hospitalisation, duration of chest tube placement, operation time, blood loss. ETHICS AND DISSEMINATION: This protocol has been reviewed and approved by the Clinical Research Review Board of Tianjin Medical University Cancer Institute and Hospital. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04631770.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Linfonodos/patologia , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Ensaios Clínicos Fase III como AssuntoRESUMO
Integrins are transmembrane receptors that possess distinct ligand-binding specificities in the extracellular domain and signaling properties in the cytoplasmic domain. While most integrins have a short cytoplasmic tail, integrin ß4 has a long cytoplasmic tail that can indirectly interact with the actin cytoskeleton. Additionally, 'inside-out' signals can induce integrins to adopt a high-affinity extended conformation for their appropriate ligands. These properties enable integrins to transmit bidirectional cellular signals, making it a critical regulator of various biological processes.Integrin expression and function are tightly linked to various aspects of tumor progression, including initiation, angiogenesis, cell motility, invasion, and metastasis. Certain integrins have been shown to drive tumorigenesis or amplify oncogenic signals by interacting with corresponding receptors, while others have marginal or even suppressive effects. Additionally, different α/ß subtypes of integrins can exhibit opposite effects. Integrin-mediated signaling pathways including Ras- and Rho-GTPase, TGFß, Hippo, Wnt, Notch, and sonic hedgehog (Shh) are involved in various stages of tumorigenesis. Therefore, understanding the complex regulatory mechanisms and molecular specificities of integrins are crucial to delaying cancer progression and suppressing tumorigenesis. Furthermore, the development of integrin-based therapeutics for cancer are of great importance.This review provides an overview of integrin-dependent bidirectional signaling mechanisms in cancer that can either support or oppose tumorigenesis by interacting with various signaling pathways. Finally, we focus on the future opportunities for emergent therapeutics based on integrin agonists. Video Abstract.
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Proteínas Hedgehog , Neoplasias , Humanos , Integrinas/metabolismo , Transdução de Sinais , CarcinogêneseRESUMO
Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of monosaccharide found in human body fluids and tissues, primarily functions in protein glycosylation rather than carbohydrate metabolism. Recent research has demonstrated direct anticancer effects of mannose in vitro and in vivo. Simply supplementing cell culture medium or drinking water with mannose achieved these effects. Moreover, mannose enhances the effectiveness of current cancer treatments including chemotherapy, radiotherapy, targeted therapy, and immune therapy. Besides the advancements in basic research on the anticancer effects of mannose, recent studies have reported its application as a biomarker for cancer or in the delivery of anticancer drugs using mannose-modified drug delivery systems. This review discusses the progress made in understanding the regulatory roles of mannose in cancer progression, the mechanisms underlying its anticancer effects, and its current application in cancer diagnosis and treatment.
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Antineoplásicos , Neoplasias , Humanos , Manose/uso terapêutico , Manose/metabolismo , Manose/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Glucose/metabolismo , Sistemas de Liberação de MedicamentosRESUMO
OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION: DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.