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1.
ACS Biomater Sci Eng ; 10(8): 5168-5180, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39016069

RESUMO

The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.


Assuntos
Glicopeptídeos , Hidrogéis , Lesões por Radiação , Pele , Cicatrização , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Glicopeptídeos/química , Glicopeptídeos/farmacologia , Glicopeptídeos/uso terapêutico , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Pele/patologia , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/prevenção & controle , Cicatrização/efeitos dos fármacos , Camundongos , Humanos , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Masculino
2.
PLoS One ; 19(7): e0307110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38995946

RESUMO

The complex vibration phenomenon occurs in the downhole environment of the gas-liquid hydrocyclone, which affects the flow field in the hydrocyclone. In order to study the influence of vibration on hydrocyclone separation, the characteristics of the flow field in the downhole gas-liquid hydrocyclone were analyzed and studied under the condition of vibration coupling. Based on Computational Fluid Dynamics (CFD), Computational Solid Mechanics Method (CSM) and fluid-solid coupling method, a fluid-solid coupling mechanical model of a gas-liquid cyclone is established. It is found that under the condition of vibration coupling, the velocity components in the three directions of the hydrocyclone flow field change obviously. The peak values of tangential velocity and axial velocity decrease, and the asymmetry of radial velocity increases. The distribution regularity of vorticity and turbulence intensity in the overflow pipe becomes worse. Among them, the vorticity intensity of the overflow pipe is obviously enhanced, and the higher turbulence intensity near the wall occupies more area distribution range. The gas-liquid separation efficiency of the hydrocyclone will decrease with the increase of the rotational speed of the screw pump, and the degree of reduction can reach more than 10%. However, this effect will decrease with the increase of the rotational speed of the screw pump, so the excitation effect caused by the rotational speed has a maximum limit on the flow field.


Assuntos
Gases , Vibração , Gases/química , Hidrodinâmica , Modelos Teóricos , Simulação por Computador
3.
BMC Med Genomics ; 17(1): 154, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840234

RESUMO

BACKGROUND: Anesthetic drugs may alter exosomal microRNA (miRNA) contents and mediate cancer progression and tumor microenvironment remodeling. Our study aims to explore how the anesthetics (sevoflurane and propofol) impact the miRNA makeup within exosomes in hepatocellular carcinoma (HCC), alongside the interconnected signaling pathways linked to the tumor immune microenvironment. METHODS: In this prospective study, we collected plasma exosomes from two groups of HCC patients (n = 5 each) treated with either propofol or sevoflurane, both before anesthesia and after hepatectomy. Exosomal miRNA profiles were assessed using next-generation sequencing (NGS). Furthermore, the expression data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) was used to pinpoint the differentially expressed exosomal miRNAs (DEmiRNAs) attributed to the influence of propofol or sevoflurane in the context of HCC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to dissect the signaling pathways and biological activities associated with the identified DEmiRNAs and their corresponding target genes. RESULTS: A total of 35 distinct DEmiRNAs were exclusively regulated by either propofol (n = 9) or sevoflurane (n = 26). Through TCGA-LIHC database analysis, 8 DEmiRNAs were associated with HCC. These included propofol-triggered miR-452-5p and let-7c-5p, as well as sevoflurane-induced miR-24-1-5p, miR-122-5p, miR-200a-3p, miR-4686, miR-214-3p, and miR-511-5p. Analyses revealed that among these 8 DEmiRNAs, the upregulation of miR-24-1-5p consistently demonstrated a significant association with lower histological grades (p < 0.0001), early-stage tumors (p < 0.05) and higher survival (p = 0.029). Further analyses using GSEA and GSVA indicated that miR-24-1-5p, along with its target genes, were involved in governing the tumor immune microenvironment and potentially inhibiting tumor progression in HCC. CONCLUSIONS: This study provided bioinformatics evidence suggesting that sevoflurane-induced plasma exosomal miRNAs may have a potential impact on the immune microenvironment of HCC. These findings established a foundation for future research into mechanistic outcomes in cancer patients.


Assuntos
Carcinoma Hepatocelular , Biologia Computacional , Progressão da Doença , Exossomos , Neoplasias Hepáticas , MicroRNAs , Propofol , Sevoflurano , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , MicroRNAs/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Exossomos/metabolismo , Exossomos/genética , Sevoflurano/farmacologia , Propofol/farmacologia , Masculino , Anestésicos/farmacologia , Anestésicos/efeitos adversos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Microambiente Tumoral
4.
J Nanobiotechnology ; 22(1): 250, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750519

RESUMO

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.


Assuntos
Regeneração Óssea , Fosfatos de Cálcio , Osteogênese , Osteossarcoma , Alicerces Teciduais , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Animais , Regeneração Óssea/efeitos dos fármacos , Alicerces Teciduais/química , Coelhos , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Osteogênese/efeitos dos fármacos , Poliésteres/química , Humanos , Diferenciação Celular/efeitos dos fármacos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Células de Schwann/efeitos dos fármacos , Nanofibras/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Selênio/química , Selênio/farmacologia
5.
Adv Healthc Mater ; 13(20): e2400406, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38683036

RESUMO

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy.


Assuntos
Senescência Celular , Hidrogéis , Óxido Nítrico , Cicatrização , Cicatrização/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Senescência Celular/efeitos da radiação , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Humanos , Óxido Nítrico/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Terapia Neoadjuvante , Camundongos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Desoxiadenosinas/química , Desoxiadenosinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação
6.
J Clin Invest ; 134(6)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38488012

RESUMO

As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocalization of genomic DNA, which acted as a powerful driver of cGAS/STING axis-dependent inflammatory phenotype acquisition during NP cell senescence. Mechanistically, disassembly of the ATR-tripartite motif-containing 56 (ATR-TRIM56) complex with the enzymatic liberation of ubiquitin-specific peptidase 5 (USP5) and TRIM25 drove changes in ATR ubiquitination, with ATR switching from K63- to K48-linked modification, c thereby promoting ubiquitin-proteasome-dependent dynamic instability of ATR protein during NP cell senescence progression. Importantly, an engineered extracellular vesicle-based strategy for delivering ATR-overexpressing plasmid cargo efficiently diminished DNA damage-associated NP cell senescence and substantially mitigated IVDD progression, indicating promising targets and effective approaches to ameliorate the chronic pain and disabling effects of IVDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Idoso , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Envelhecimento , Senescência Celular , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Disco Intervertebral/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/farmacologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
8.
Comput Biol Med ; 173: 108327, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552279

RESUMO

Endometrial cancer (EC) is one of the most common malignant tumors in women, and the increasing incidence and mortality pose a serious threat to the public health. Early diagnosis of EC could prolong the survival period and optimize the survivorship, greatly alleviating patients' suffering and social medical pressure. In this study, we collected urine and serum samples from the recruited patients, analyzed the samples using LC-MS approach, and identified the differential metabolites through metabolomic analysis. Then, the differentially expressed genes were identified through the systematic transcriptomic analysis of EC-related dataset from Gene Expression Omnibus (GEO), followed by network profiling of metabolic-reaction-enzyme-gene. In this experiment, a total of 83 differential metabolites and 19 hub genes were discovered, of which 10 different metabolites and 3 hub genes were further evaluated as more potential biomarkers based on network analysis. According to the KEGG enrichment analysis, the potential biomarkers and gene-encoded proteins were found to be involved in the arginine and proline metabolism, histidine metabolism, and pyrimidine metabolism, which was of significance for the early diagnosis of EC. In particular, the combination of metabolites (histamine, 1-methylhistamine, and methylimidazole acetaldehyde) as well as the combination of RRM2, TYMS and TK1 exerted more accurate discrimination abilities between EC and healthy groups, providing more criteria for the early diagnosis of EC.


Assuntos
Biomarcadores Tumorais , Neoplasias do Endométrio , Humanos , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Biomarcadores , Metabolômica , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Perfilação da Expressão Gênica
9.
Anal Bioanal Chem ; 416(10): 2439-2452, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38400939

RESUMO

Nucleic acid modifications have attracted increasing attention in recent years since they have been found to be related to a number of diseases including cancer. Previous studies have shown that the early development of endometrial cancer (EC) is often accompanied by changes in methylation levels of related genes, and the expression of related proteins that regulate reactive oxygen species (ROS) shows significant differences in EC cells and tissues. However, it has not been reported whether nucleic acid modifications related to methylation or ROS can serve as biomarkers for EC. Accurate quantification of these nucleic acid modifications still has challenges because their amounts in urine are very low and the interferences in urine are complicated. In this study, a novel dispersive solid-phase extraction (DSPE) method based on chitosan-carbon nanotube-Al2O3 (CS-CNT-Al2O3) has been established for the analysis of 5-hydroxymethyluracil (5 mU), 5-methyl-2'-deoxycytidine (5-mdC), 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), 5-formyl-2'-deoxycytidine (5-fdC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in EC patient urine samples coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV. Firstly, the synthesis of the CS-CNT-Al2O3 nanocomposite was conducted by a sono-coprecipitation method and was characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and Fourier transform infrared (FTIR). Under the optimal extraction conditions of DSPE, we successfully quantified 5 mU, 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in urine samples from 37 EC patients and 39 healthy controls. The results showed that there were significant differences in the levels of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in EC patients compared to the healthy control group. The receiver operator characteristic (ROC) curve analysis was carried out to evaluate the potential of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG to distinguish EC patients from healthy volunteers. The area under the curve (AUC) for 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG was 0.7412, 0.667, 0.8438, and 0.7981, respectively. It indicated that 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG had certain potential in distinguishing between EC patients and healthy volunteers and they could act as potential non-invasive biomarkers for early diagnosis of EC. Moreover, the present study would stimulate investigations of the effects of nucleic acid modifications on the initiation and progression of EC.


Assuntos
Neoplasias do Endométrio , Ácidos Nucleicos , Humanos , Feminino , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Espécies Reativas de Oxigênio , 8-Hidroxi-2'-Desoxiguanosina , Neoplasias do Endométrio/diagnóstico , Extração em Fase Sólida , Biomarcadores
10.
Heliyon ; 10(1): e23548, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38187245

RESUMO

Background: Postoperative analgesia is an essential component of enhanced recovery after surgery following abdominal surgery. Studies comparing the effectiveness of epidural analgesia with that of other analgesic modalities after liver surgery have reported inconsistent results. Consequently, the use of epidural analgesia for open hepatectomy is controversial. Objective: The present single-center retrospective study aimed to compare the efficacy and safety of patient-controlled epidural analgesia (PCEA) and patient-controlled intravenous analgesia (PCIA) in adults undergoing open hepatectomy. Methods: Patients who underwent open hepatectomy between January 2018 to December 2019 at Zhongshan Hospital, Fudan University were retrospectively analyzed. Propensity score matching was used to adjust baseline information between the PCEA and PCIA groups. The primary outcome measure was scores of the numeric rating scales (NRSs) for resting, exercise, and nocturnal pain at postoperative 24 h (postoperative day 1 [POD1]) and 48 h (POD2). The secondary outcome indicators included postoperative nausea and vomiting (PONV), hypotension, pruritus, respiratory depression, functional activity score (FAS), effective analgesic pump compression ratio, analgesic relief rate, discontinuation of the analgesic pump, reasons for discontinuation of the analgesic pump, and patient satisfaction with postoperative analgesia. Results: The NRS scores of the PCEA group on POD1 were significantly lower than those of the PCIA group (P < 0.05). On POD2, the difference between the two groups was significant only for motion NRS scores (P < 0.05). The PCIA group had significantly more patients with lower FAS functional class than the PCEA group (P < 0.001). The effective analgesic pump compression ratio and the analgesic relief rate at 2 days after the surgery were lower in the PCEA group than in the PCIA group (P < 0.001). The incidence of pump discontinuation was higher in the PCEA group than in the PCIA group on POD2 (P = 0.044). Moreover, on POD1 and POD2, the PCEA group showed a higher incidence of pruritus and hypotension than the PCIA group (P < 0.001). Both groups showed no significant difference in PONV incidence. Conclusion: In patients undergoing open hepatectomy, PCEA was more effective than PCIA in relieving moderate to severe pain on POD1. However, improving the safety and effectiveness of PCEA remains a challenge.

11.
Funct Integr Genomics ; 24(1): 15, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240925

RESUMO

Chronic psoriasis is a kind of immune-mediated skin illness and the underlying molecular mechanisms of pathogenesis remain incompletely understood. Here, we used small RNA microarray assays to scan the differential expressed RNAs in psoriasis patient samples. The downstream miRNAs and its targets were predicted using bioinformatics analysis from online bases and confirmed using fluorescence in situ hybridization and dual­luciferase report gene assay. Cell ability of proliferation and migration were detected using CCK-8 and transwell assays. The results showed that a new snoRNA Snora73 was upregulated in psoriasis patient samples. Overexpression of Snora73 significantly increased psoriasis cells viability and migration, while knockdown of Snora73 got the opposite results. Mechanistically, our results showed that Snora73 acted as a sponge for miR-3074-5p and PBX1 is a direct target of miR-3074-5p in psoriasis cells. Furthermore, miR-3074-5p suppressed psoriasis cell proliferation and migration, while PBX1 promoted cell proliferation and migration in psoriasis. Collectively, these findings reveal a crucial role of Snora73 in progression of psoriasis through miR-3074-5p/PBX1 signaling pathway and suggest a potential therapeutic strategy.


Assuntos
MicroRNAs , Fator de Transcrição 1 de Leucemia de Células Pré-B , Psoríase , RNA Longo não Codificante , RNA Nucleolar Pequeno , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Hibridização in Situ Fluorescente , MicroRNAs/genética , Psoríase/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética
12.
Clin Transl Med ; 13(12): e1494, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38037469

RESUMO

BACKGROUND: Growing evidence has suggested the role of stem cell-derived small extracellular vesicles (sEVs) in intervertebral disc degeneration (IVDD). The cargo sorting of sEVs, particularly miRNAs, may be influenced when the donor cell is subjected to oxidative stress. Here, we discovered that miRNAs containing specific motifs are selectively sorted into intraluminal vesicles within mesenchymal stem cells (MSCs) in response to oxidative stress. METHODS: Analysis of miRNA cargoes in sEVs derived from normal MSCs (C-sEVs) or stressed MSCs (T-sEVs) was conducted using miRNA sequencing. Differential expressed miRNAs in sEVs and the identification of motifs were evaluated through bioinformatics analysis. Protein binding was assessed using immunofluorescent staining and immunoprecipitation analysis. Additionally, RNA pull down and RNA immunoprecipitation (RIP) immunoprecipitation were employed to determine the binding between miRNAs and proteins. The effects of C-sEVs and T-sEVs on IVDD were compared by detecting the expression levels of phenotypic genes in vitro or histological evaluation in vivo. RESULTS: The sorting process of miRNAs is mediated by the nucleocytoplasmic transport of heterogeneous nuclear ribonucleoproteins, which in turn facilitates the phosphorylation of SNAP25 and promotes the transport and secretion of sEVs. Additionally, CHMP1B plays a role in membrane repair and protects against cell ferroptosis upon oxidative stress, concurrently affecting the release of sEVs. Notably, stem cell-derived sEVs associated with ferroptosis impair the therapeutic efficacy for IVDD. However, the application of engineered sEVs containing a specific miRNA inhibitor exhibits the potential to reinstate the therapeutic efficacy for IVDD both in vitro and in vivo. CONCLUSIONS: Taken together, our findings shed light on the mechanism of miRNAs sorting into sEVs and offer new insights for the optimization of sEV-based treatments during intervertebral disc regeneration. regeneration.


Assuntos
Vesículas Extracelulares , Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/terapia , Células-Tronco , MicroRNAs/genética , Vesículas Extracelulares/genética
13.
Biomaterials ; 302: 122295, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37666101

RESUMO

The therapeutic effect of cancer immunotherapy is restrained by limited patient response rate caused by 'cold' tumors with an intrinsically immunosuppressive tumor microenvironment (TME). Activating stimulator of interferon genes (STING) confers promising antitumor immunity even in 'cold' tumors, but the further promotion of STING agonists is hindered by undesirable toxicity, low specificity and lack of controllability. Herein, an ultrasound-controllable cGAS-STING amplifying nanoagonist was constructed by coordinating mitochondria-targeting ligand triphenylphosphonium (TPP) to sonodynamic cobalt organic framework nanosheets (TPP@CoTCPP). The Co ions specifically amplify STING activation only when cytosolic mitochondrial DNA leakage is caused by sonocatalysis-induced ROS production and sensed by cGAS. A series of downstream innate immune proinflammatory responses induced by local cGAS-STING pathway activation under spatiotemporal ultrasound stimulation efficiently prime the antitumor T-cell response against bone metastatic tumor, a typical immunosuppressive tumor. We also found that the coordination of TPP augments the sonodynamic effect of CoTCPP nanosheets by reducing the band gap, improving O2 adsorption and enhancing electron transfer. Overall, our study demonstrates that the targeted and amplified cGAS-STING activation in cancer cell controlled by spatiotemporal ultrasound irradiation boosts high-efficiency sonodynamic-ionicimmunotherapy against immunosuppressive tumor.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Adsorção , Cobalto/farmacologia , Citosol , DNA Mitocondrial , Imunoterapia , Microambiente Tumoral
14.
Front Bioeng Biotechnol ; 11: 1225187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37449087

RESUMO

Introduction: Carbon sequestration by microalgae is an effective approach for achieving carbon neutrality owing to its high carbon capture efficiency and environmental friendliness. To improve microalgae CO2 fixation efficiency, various methods to enhance CO2 transfer at the gas-liquid interface have resulted in high energy consumption. Methods: In this study, a novel aeration device with bubble cutting slices was installed in a photobioreactor for CO2 supply, which could precisely separate bubbles into sizes on the way to rising after departure, achieving CO2 transfer enhancement without extra energy consumption. Subsequently, the bubble cutting dynamic behaviors in the photobioreactor were studied, and the effects of thickness, hydrophilicity, and arrangement of cutting slices on microalgal growth were analyzed. Results: It was found that bubble cutting caused the maximum dry weight and biomass productivity of microalgae to improve by 6.99% and 33.33%, respectively, compared with those of the bioreactor without cutting units, owing to a 27.97% and 46.88% decrease in bubble size and rising velocity, respectively, and an 84.55% prolongation of bubble residence time. Discussion: Parallel cut slices with a thickness and spacing of less than 3 mm successfully cut the bubbles. The hydrophobic slice surface prevented daughter bubble departure and prolonged the bubble residence time, impeding microalgae growth owing to bubble coalescence with subsequent bubbles. The optimal cutting slice parameters and culture conditions for microalgal growth were 1 mm slice thickness, less than 1 mm slice spacing, 5% inlet CO2 concentration, and 70 mL/min gas flow rate.

15.
Chemosphere ; 337: 139411, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37419160

RESUMO

The role of perfluoroalkyl and polyfluoroalkyl substances (PFAS) as thyroid carcinogens is unclear. Therefore, we intended to identify associations between each PFAS congener and their mixture with thyroid cancer risk. This case-control study of thyroid cancer was conducted in Shijiazhuang, Hebei Province, China. Three hundred participants were recruited from January to May 2022 and were matched according to sex and age. Twelve PFAS were assessed using ultra-high-performance liquid chromatography-tandem mass spectrometry. Associations between PFAS congeners and thyroid cancer risk were considered under conditional logistic regression analysis and a restricted cubic spline model. Mixture effects were also assessed with quantile g-computation and a Bayesian kernel machine regression model. Compared to the first tertile, third tertile PFOA, PFNA, PFHxS, PFDA, and PFUnDA concentrations were associated with lower thyroid cancer risk (ORPFOA: 0.32, 95% confidence interval (CI): 0.15-0.69; ORPFNA: 0.18, 95% CI: 0.07-0.46; ORPFHxS: 0.37, 95% CI: 0.15-0.92; ORPFDA: 0.07, 95% CI: 0.02-0.23; ORPFUnDA: 0.12, 95% CI: 0.05-0.30) after adjusting for confounding factors. PFNA, PFDA, and PFUnDA had a negative dose-response relationship with thyroid cancer risk. Mixture analysis also showed that thyroid cancer risk is negatively associated with the overall mixture and carboxylates. In the overall mixture, PFOS and PFDA contributed most to positive and negative changes in thyroid cancer risk, respectively. However, PFOS, PFNA, PFDA, and PFUnDA were of equally high importance. This study is the first to confirm the effects of the PFAS mixture on thyroid cancer, and further large-scale prospective studies are still warranted to test these inverse associations.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Neoplasias da Glândula Tireoide , Humanos , Estudos Prospectivos , Estudos de Casos e Controles , Teorema de Bayes , Fluorocarbonos/toxicidade , China/epidemiologia , Neoplasias da Glândula Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/epidemiologia
16.
Med Sci Monit ; 29: e939277, 2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37301978

RESUMO

BACKGROUND Retinal vein occlusion-induced macular edema (RVO-ME) is a significant global cause of vision loss, with the effectiveness of combined anti-vascular endothelial growth factor (anti-VEGF) drugs and dexamethasone implantation (DEX I) being a relevant, yet not thoroughly explored, area of interest.The aim of this study was to evaluate the 1-year clinical efficacy of combination therapy using anti-vascular endothelial growth factor (VEGF) drugs and dexamethasone implantation (DEX I) in the treatment of macular edema secondary to retinal vein occlusion (RVO-ME). MATERIAL AND METHODS This retrospective study analyzed data from 34 RVO-ME patients treated at the Inner Mongolia Chaoju Eye Hospital between January 2020 and December 2021. All patients underwent initial DEX I treatment, followed by the introduction of anti-VEGF drugs, and were observed for one year. Retinal structural and vascular changes were measured using spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA). The study also evaluated shifts in best corrected visual acuity (BCVA) throughout the observation period. RESULTS Following the combined therapy, patients showed significant improvements in BCVA, intraocular pressure (IOP), central retinal thickness (CRT), and retinal vessel density (VD) (all P<0.05). Upon stratifying the results by RVO type, patients with branch retinal vein occlusion (BRVO)-ME displayed more significant BCVA improvement and CRT reduction at various post-treatment intervals compared to those with central retinal vein occlusion (CRVO)-ME (all P<0.05). CONCLUSIONS The combined use of anti-VEGF drugs and DEX I showed promising one-year efficacy in treating RVO-ME, with greater improvements noted in patients with BRVO-ME compared to those with CRVO-ME. Despite the positive results, close monitoring of IOP elevation, a notable side effect, remains crucial.


Assuntos
Dexametasona , Edema Macular , Oclusão da Veia Retiniana , Humanos , Dexametasona/uso terapêutico , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Fatores de Crescimento do Endotélio Vascular , Acuidade Visual
18.
BMC Gastroenterol ; 23(1): 37, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36759769

RESUMO

OBJECTIVES: To explore the prevalence, characteristics, age distribution and etiology changes of chronic atrophic gastritis (CAG) in South China. METHODS: This study included all patients who underwent endoscopy examinations from 2011 to 2020 in our hospital. Patients were divided into groups 1 (2011-2015) and 2 (2016-2020). The prevalence, characteristics, age distribution and etiology changes of CAG were compared between groups. RESULTS: Overall CAG prevalence was 20.92% (24,084/115,110) from 2011 to 2020; prevalence significantly differed between groups (18.78%, 8468/45,087, in group 1 and 22.30%, 15,616/70,023, in group 2). Patients with CAG had significantly younger age (under 45) and more corpus atrophy and more autoimmune atrophic gastritis (AAG) in group 2 than in group 1. AAG prevalence in group 2 was 30.11% (4702/15,616) significantly higher than 13.57% (1149/8468) in group 1. 82 patients with AAG later exhibited gastric cancer without obvious clinical features over the decade. CONCLUSIONS: CAG is increasing and seems starting earlier among people during the study period. We need to focus on diagnosis and treatment of corpus related atrophy and AAG, especially for the young. Laboratory examination, endoscopic biopsy and surveillance are important for CAG.


Assuntos
Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Humanos , Gastrite Atrófica/patologia , Estudos Retrospectivos , Gastrite/patologia , Biópsia , Atrofia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/diagnóstico
19.
Crit Rev Food Sci Nutr ; 63(21): 4942-4965, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34852703

RESUMO

Excessive use of pesticides can cause contamination of the environment and agricultural products that are directly threatening human life and health. Therefore, in the process of food safety supervision, it is crucial to conduct sensitive and rapid detection of pesticide residues. The recognition element is the vital component of sensors and methods for fast testing pesticide residues in food. Improper recognition elements may lead to defects of testing methods, such as poor stability, low sensitivity, high economic costs, and waste of time. We can use the molecular biological technique to address these challenges as a good strategy for recognition element production and modification. Herein, we review the molecular biological methods of five specific recognition elements, including aptamers, genetic engineering antibodies, DNAzymes, genetically engineered enzymes, and whole-cell-based biosensors. In addition, the application of these identification elements combined with biosensor and immunoassay methods in actual detection was also discussed. The purpose of this review was to provide a valuable reference for further development of rapid detection methods for pesticide residues.


Assuntos
Técnicas Biossensoriais , Resíduos de Praguicidas , Praguicidas , Humanos , Praguicidas/análise , Resíduos de Praguicidas/análise , Contaminação de Alimentos/análise , Inocuidade dos Alimentos , Técnicas Biossensoriais/métodos
20.
Medicine (Baltimore) ; 101(47): e31678, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451432

RESUMO

RATIONALE: 5-Fluorouracil (5-FU) and actinomycin D (ActD) are often used in chemotherapy for various cancers. Side effects are more common in bone marrow suppression, liver function impairment, and gastrointestinal responses. Skin effects are rare and easy to be ignored by doctors and patients, which can lead to life-threatening consequence. PATIENT CONCERNS: We reported a 45-year-old woman patient developed skin erythema and fingernail belt in chemotherapy of 5-FU and ActD. DIAGNOSIS: Erythema multiforme drug eruption. INTERVENTIONS: Laboratory tests including blood and urine routine, liver and kidney function, electrolytes and coagulation function and close observation. OUTCOMES: The rash was gone and the nail change returned. LESSONS: Delays in diagnosis or treatment may lead to serious consequence. We should pay attention to the dosage of 5-FU and ActD, monitor adverse reactions strictly, to reduce occurrence of skin malignant events.


Assuntos
Toxidermias , Eritema Multiforme , Mola Hidatiforme Invasiva , Neoplasias Uterinas , Feminino , Gravidez , Humanos , Pessoa de Meia-Idade , Dactinomicina/efeitos adversos , Fluoruracila/efeitos adversos , Eritema Multiforme/induzido quimicamente , Toxidermias/etiologia
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