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1.
Sci Rep ; 14(1): 21491, 2024 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277616

RESUMO

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Despite of a steadily increasing in morbidity and mortality, there is still no effective therapy. Gut microbial dysbiosis and its derived-metabolites disorder have been shown to play an important role in the development of AP, however, little is known regarding the crosstalk between gut microbiota and metabolites. In this study, we assessed the alterations in gut microbiota and metabolites by constructing three AP mouse models by means of metagenomic and metabolomic sequencing, and further clarified their relationship by correlation analysis. The results revealed that each model exhibited unique flora and metabolite profiles. KEGG analysis showed that the differential flora and metabolite-enriched pathway functions were correlated with lipid metabolism and amino acid metabolism. Moreover, two core differential bacterial species on Burkholderiales bacterium YL45 and Bifidobacterium pseudolongum along with eleven differential metabolites appeared to exert certain effects during the course of AP. In conclusion, further exploration of the crosstalk between microbiota and derived metabolites may provide novel insights and strategies into the diagnosis and treatment of AP.


Assuntos
Microbioma Gastrointestinal , Metabolômica , Metagenômica , Pancreatite , Pancreatite/microbiologia , Pancreatite/metabolismo , Animais , Metabolômica/métodos , Metagenômica/métodos , Camundongos , Metaboloma , Modelos Animais de Doenças , Disbiose/microbiologia , Disbiose/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Doença Aguda
2.
Neuroscience ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39343160

RESUMO

Vitamin D is well known for its role in regulating the absorption and utilization of calcium and phosphorus as well as bone formation, and a growing number of studies have shown that vitamin D also has important roles in the nervous system, such as maintaining neurological homeostasis and protecting normal brain function, and that neurons and glial cells may be the targets of these effects. Most reviews of vitamin D's effects on the nervous system have focused on its overall effects, without distinguishing the contributors to these effects. In this review, we mainly focus on the cells of the central nervous system, summarizing the effects of vitamin D on them and the related pathways. With this review, we hope to elucidate the role of vitamin D in the nervous system at the cellular level and provide new insights into the prevention and treatment of neurodegenerative diseases in the direction of neuroprotection, myelin regeneration, and so on.

3.
Chemistry ; : e202402747, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39305137

RESUMO

Two-dimensional conductive MOF thin films have attracted attention due to their rich pore structure and unique electrical properties, and their applications in many fields, including batteries, sensing, supercapacitors, electrocatalysis, etc. This paper discusses several preparation methods for 2D conductive MOF thin films. And the applications of 2D conductive MOF thin films are summarized. In addition, the current challenges in the preparation of 2D conductive MOF thin films and the great potential in practical applications are discussed.

4.
Entropy (Basel) ; 26(8)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39202145

RESUMO

To tackle the issue of the traditional intelligent diagnostic algorithm's insufficient utilization of correlation characteristics within the time series of fault signals and to meet the challenges of accuracy and computational complexity in rotating machinery fault diagnosis, a novel approach based on a recurrence binary plot (RBP) and a lightweight, deep, separable, dilated convolutional neural network (DSD-CNN) is proposed. Firstly, a recursive encoding method is used to convert the fault vibration signals of rotating machinery into two-dimensional texture images, extracting feature information from the internal structure of the fault signals as the input for the model. Subsequently, leveraging the excellent feature extraction capabilities of a lightweight convolutional neural network embedded with attention modules, the fault diagnosis of rotating machinery is carried out. The experimental results using different datasets demonstrate that the proposed model achieves excellent diagnostic accuracy and computational efficiency. Additionally, compared with other representative fault diagnosis methods, this model shows better anti-noise performance under different noise test data, and it provides a reliable and efficient reference solution for rotating machinery fault-classification tasks.

5.
PLoS One ; 19(8): e0302291, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39186727

RESUMO

PURPOSE: Sarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Twenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015). CONCLUSION: The current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.


Assuntos
Complicações Pós-Operatórias , Sarcopenia , Coluna Vertebral , Humanos , Sarcopenia/complicações , Sarcopenia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Coluna Vertebral/cirurgia , Incidência
6.
Chem Commun (Camb) ; 60(74): 10180-10183, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39190479

RESUMO

We present generalizing statistical surrogate models to select an optimized photosensitizer, TPP, which is subsequently loaded into autologous exosomes by ultrasonic mixing to achieve tumor targeting with enhanced therapeutic efficacy by photodynamic therapy (PDT). This work contributes to the exploration of PDT enhancement strategies, and provides new prospects for using autologous exosomes as a delivery system.


Assuntos
Exossomos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Exossomos/química , Exossomos/metabolismo , Humanos , Animais , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Porfirinas/química , Porfirinas/farmacologia
7.
Angew Chem Int Ed Engl ; : e202411579, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39086196

RESUMO

Prussian blue analogues (PBAs) have been widely studied in aqueous zinc-ion batteries (AZIBs) due to the characteristics of large specific surface area, open aperture, and straightforward synthesis. In this work, vanadium-based PBA nanocubes were firstly prepared using a mild in-situ conversion strategy at room temperature without the protection of noble gas. Benefiting from the multiple-redox active sites of V3+/V4+, V4+/V5+ and Fe2+/Fe3+, the cathode exhibited an excellent discharge specific capacity of 200 mA h g-1 in AZIBs, which is much higher than those of other metal-based PBAs nanocubes. To further improve the long-term cycling stability of the V-PBA cathode, a high concentration water-in-salt electrolyte (4.5 M ZnSO4 + 3 M Zn(OTf)2), and a water-based eutectic electrolyte (5.55 M glucose + 3 M Zn(OTf)2) were designed to successfully inhibit the dissolution of vanadium and improve the deposition of Zn2+ onto the zinc anode. More importantly, the assembled AZIBs maintained 55% of their highest discharge specific capacity even after 10000 cycles at 10 A g-1 with superior rate capability. This study provides a new strategy for the preparation of pure PBA nanostructures and a new direction for enhancing the long-term cycling stability of PBA-based AZIBs at high current densities for industrialization prospects.

8.
Adv Sci (Weinh) ; : e2403802, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140249

RESUMO

Exploring new carbon-based electrode materials is quite necessary for enhancing capacitive deionization (CDI). Here, hollow mesoporous carbon spheres (HMCSs)/metal-organic frameworks (MOFs) derived carbon materials (NC(M)/HMCSs and NC(M)@HMCSs) are successfully prepared by interface-coating and space-encapsulating design, respectively. The obtained NC(M)/HMCSs and NC(M)@HMCSs possess a hierarchical hollow nanoarchitecture with abundant nitrogen doping, high specific surface area, and abundant meso-/microporous pores. These merits are conducive to rapid ion diffusion and charge transfer during the adsorption process. Compared to NC(M)/HMCSs, NC(M)@HMCSs exhibit superior electrochemical performance due to their better utilization of the internal space of hollow carbon, forming an interconnected 3D framework. In addition, the introduction of Ni ions is more conducive to the synergistic effect between ZIF(M)-derived carbon and N-doped carbon shell compared with other ions (Mn, Co, Cu ions). The resultant Ni-1-800-based CDI device exhibits excellent salt adsorption capacity (SAC, 37.82 mg g-1) and good recyclability. This will provide a new direction for the MOF nanoparticle-driven assembly strategy and the application of hierarchical hollow carbon nanoarchitecture to CDI.

9.
Inorg Chem ; 63(34): 16103-16113, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39149799

RESUMO

The construction of doped molecular clusters is an intriguing way to perform bimetallic doping for electrocatalysts. However, efficiently harnessing the benefits of a doping strategy and alloy engineering to create a nanostructure for electrocatalytic application at the molecular level has consistently posed a challenge. Here we propose an in situ reconstruction strategy aimed at producing an alloy nanostructure through a pyrolysis process, originating from bowknot-like heterometallic clusters. The Schiff base, denoted as ligand L1 (o-vanillin ethylenediamine), was introduced as a precursor to coordinate Fe and Co metals, thereby yielding a heteronuclear metal cluster [(FeCo)(L1)2O]CH3CN. Subsequently, a comprehensive investigation of the in situ reconstruction process [(FeCo)(L1)2O](CH3CN) → [(FeCo)(L1)2O] → [M-O-M/M-O] [CH3+/CH3O+/H2C═N/C2H5+/C4H4+] → [FeCo/Fe3O4/Fe2O3/Co3O4][carbon layer] led to the formation of MOx/CoFe@NC-700 during the pyrolysis. This process reveals that the metals Fe and Co in the clusters undergo partly in situ evolution into FeCo alloys, resulting in the successful preparation of MOx/CoFe@NC (M = Fe, Co) nanomaterials that leverage the advantages of both doping strategies and alloy engineering. The synergistic interaction between alloy particles and metal oxides establishes active sites that contribute to the excellent oxygen evolution (OER) and hydrogen evolution (HER) catalytic behaviors. Notably, these materials exhibit outstanding OER and HER properties under alkaline conditions, with overpotentials of 191 and 88 mV for OER and HER, respectively, at 10 mA cm-2. Investigation of the in situ conversion of Schiff base bimetal clusters into alloy materials through pyrolysis offers a novel strategy for advancing electrocatalytic applications.

10.
Adv Sci (Weinh) ; 11(35): e2400817, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39031527

RESUMO

Although power conversion efficiency (PCE) of solar cells (SCs) continues to improve, they are still far from practical application because of their complex synthesis process, high cost and inferior operational stability. Carbon quantum dots with high material stability and remarkable photoluminescence are successfully used in light-emitting diodes. A good light emitter should also be an efficient SC according to the photon balance in Shockley-Quieisser formulation, in which all excitons are ultimately separated. However, the finite quantum-sized sp2 domain leads to tight exciton bonding, and highly delocalized electron clouds in irregular molecular stacks form disordered charge transfer, resulting in severe energy loss. Herein, an axially growing carbon quantum ribbon (AG-CQR) with a wide optical absorption range of 440-850 nm is reported. Structural and computational studies reveal that AG-CQRs (aspect ratio ≈2:1) with carbonyl groups at both ends regulate energy level and efficiently separate excitons. The stacking-controlled two-dimensional AG-CQR film further directionally transfers electrons and holes, particularly in AB stacking mode. Using this film as active layer alone, the SCs yield a maximum PCE of 1.22%, impressive long-term operational stability of 380 h, and repeatability. This study opens the door for the development of new-generation carbon-nanomaterial-based SCs for practical applications.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38857669

RESUMO

Xanthatin (XAN), a xanthanolide sesquiterpene lactone, isolated from Chinese herb, Xanthium strumarium L, has various pharmacological activities, such as antitumor activity and anti-inflammatory. However, little is known about its potential toxicity and the mechanism. Here, zebrafish model was used to study the developmental toxicity in vivo. Our results indicated that xanthatin increased the mortality and led to the morphological abnormalities including pericardial edema, yolk sac edema, curved body shape and hatching delay. Furthermore, xanthatin damaged the normal structure and/or function of heart, liver, immune and nervous system. ROS elevation and much more apoptosis cells were observed after xanthatin exposure. Gene expression results showed that oxidative stress-related genes nrf2 was inhibited, while oxidative stress-related genes (keap1 and nqo1) and apoptotic genes (caspase3, caspase9 and p53) were increased after xanthatin exposure. Mitophagy related genes pink1 and parkin, and wnt pathway (ß-catenin, wnt8a and wnt11) were significantly increased after xanthatin exposure. Taken together, our finding indicated that xanthatin induced developmental toxicity, and the ROS elevation, apoptosis activation, dysregulation of mitophagy and wnt pathways were involved in the toxicity caused by xanthatin.


Assuntos
Apoptose , Embrião não Mamífero , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Embrião não Mamífero/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Furanos
12.
Int J Oral Sci ; 16(1): 48, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38897993

RESUMO

Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-ß receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-ß pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-ß fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.


Assuntos
Arecolina , Células Epiteliais , Exossomos , Fibroblastos , MicroRNAs , Fibrose Oral Submucosa , Receptor do Fator de Crescimento Transformador beta Tipo I , MicroRNAs/metabolismo , Fibrose Oral Submucosa/metabolismo , Fibrose Oral Submucosa/patologia , Humanos , Fibroblastos/metabolismo , Arecolina/farmacologia , Células Epiteliais/metabolismo , Exossomos/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Proteína Smad7/metabolismo , Diferenciação Celular , Transdução de Sinais , Movimento Celular , Ubiquitina-Proteína Ligases/metabolismo , Areca/efeitos adversos
13.
Sci Total Environ ; 946: 174082, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38906305

RESUMO

This research compared Portland cement and Phosphogypsum-Steel Slag-Based (PSSB) cement in terms of their capabilities to stabilize heavy metals (specifically lead and nickel) in Oil-Based Drill Cuttings (OBDC). In the experimental section, the qualitative analysis of heavy metal constituents in OBDC was captured by X-ray Photoelectron Spectroscopy (XPS). Additionally, an acetic acid leaching test was implemented for the heavy metal leaching concentration to evaluate the ceramsite stabilization effect on OBDC. In the simulation phase, cement models, heavy metal ion models, and stabilization models were constructed to explore the stabilization mechanism of heavy metals. Results demonstrated that PSSB cement exhibits superior stabilization effects on OBDC compared to Portland cement. Flame Atomic Absorption Spectrophotometry (FAAS) tests showed that PSSB cement reduced Ni and Pb leaching by 21.87 % and 47.32 %, respectively, compared to Portland cement. In PSSB cement, the diffusion coefficients for Ni and Pb ions were observed to decrease by 42.92 % and 79.63 %, respectively, as revealed through Mean Square Displacement (MSD) analysis. The cohesive energy of PSSB cement was 76.73 % lower than that of Portland cement, and its interaction energies for stabilizing Ni and Pb ions were 59.43 % and 76.22 % lower, respectively, demonstrating greater stability and efficiency in metal stabilization. PSSB cement exhibited lower heavy metal concentration and better structural stability than Portland cement.

14.
J Colloid Interface Sci ; 673: 807-816, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38906002

RESUMO

PBA frameworks have stood out among metal-organic frameworks because of their easy preparation, excellent stability, porous structures, and rich redox properties. Unfortunately, their non-ideal conductivity and significant volume expansion during cycling prevent more widespread application in alkali-metal-ion (Li+, Na+, and K+) batteries. By changing the type and molar ratio of metal ions, Rubik's PBA frameworks with infinite structural variations were obtained in this study, just like the Rubik's cube undergoes infinite changes during the rotation. X-ray adsorption fine structure measurements have documented the existence and determined the coordination environment of the metal ions in the Rubik's PBA framework. Benefiting from the more stable Rubik's cube structures with diverse composition, enhanced conductivity, and greater adsorption capacity, the obtained Rubik's cubes CoM-PBA anodes, especially CoZn-PBA deliver the enhanced cycling and rate performance in all the alkali-metal-ion batteries. The findings are supported by density functional theory calculations. Ex-situ X-ray photoelectron spectroscopy, and in-situ X-ray diffraction measurements were undertaken to explore the storage mechanism of CoZn-PBA anodes. Our results further demonstrate that the Rubik's cube PBA framework-based materials could be widely applied in the field of alkali-metal-ion batteries.

15.
Cell Death Dis ; 15(6): 462, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942784

RESUMO

S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in a variety of inflammatory diseases. Although S100a8/a9 has been reported to trigger endothelial cell apoptosis, the mechanisms of S100a8/a9-induced endothelial dysfunction during sepsis require in-depth research. We demonstrate that high expression levels of S100a8/a9 suppress Ndufa3 expression in mitochondrial complex I via downregulation of Nrf1 expression. Mitochondrial complex I deficiency contributes to NAD+-dependent Sirt1 suppression, which induces mitochondrial disorders, including excessive fission and blocked mitophagy, and mtDNA released from damaged mitochondria ultimately activates ZBP1-mediated PANoptosis in endothelial cells. Moreover, based on comprehensive scRNA-seq and bulk RNA-seq analyses, S100A8/A9hi neutrophils are closely associated with the circulating endothelial cell count (a useful marker of endothelial damage), and S100A8 is an independent risk factor for poor prognosis in sepsis patients.


Assuntos
Calgranulina A , Calgranulina B , Mitocôndrias , Neutrófilos , Sepse , Calgranulina A/metabolismo , Calgranulina A/genética , Neutrófilos/metabolismo , Sepse/patologia , Sepse/metabolismo , Sepse/genética , Humanos , Calgranulina B/metabolismo , Calgranulina B/genética , Mitocôndrias/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/deficiência , Complexo I de Transporte de Elétrons/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Animais , Camundongos , Masculino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Mitofagia , Camundongos Endogâmicos C57BL , Apoptose
16.
JCI Insight ; 9(14)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888975

RESUMO

The excessive formation and release of neutrophil extracellular traps (NETs) in sepsis may represent a substantial mechanism contributing to multiorgan damage, which is associated with a poor prognosis. However, the precise role of NETs in mediating the transition from innate immunity to adaptive immunity during the progression of inflammation and sepsis remains incompletely elucidated. In this study, we provide evidence that, despite a reduction in the number of CD4+ T cells in the late stage of sepsis, there is a notable upregulation in the proportion of Tregs. Mechanistically, we have identified that NETs can induce metabolic reprogramming of naive CD4+ T cells through the Akt/mTOR/SREBP2 pathway, resulting in enhanced cholesterol metabolism, thereby promoting their conversion into Tregs and augmenting their functional capacity. Collectively, our findings highlight the potential therapeutic strategy of targeting intracellular cholesterol normalization for the management of immunosuppressed patients with sepsis.


Assuntos
Armadilhas Extracelulares , Sepse , Linfócitos T Reguladores , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Sepse/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Humanos , Camundongos , Animais , Neutrófilos/imunologia , Neutrófilos/metabolismo , Masculino , Serina-Treonina Quinases TOR/metabolismo , Colesterol/metabolismo , Tolerância Imunológica/imunologia , Feminino , Camundongos Endogâmicos C57BL
17.
Int J Oral Sci ; 16(1): 35, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719825

RESUMO

The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.


Assuntos
Autofagia , Carcinoma de Células Escamosas , Proliferação de Células , Estresse do Retículo Endoplasmático , Neoplasias Bucais , Fenformin , Fatores de Transcrição , Fenformin/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Neoplasias Bucais/tratamento farmacológico , Autofagia/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Fatores de Transcrição/metabolismo , Fatores de Transcrição/efeitos dos fármacos , Camundongos , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting
18.
J Clin Nurs ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764243

RESUMO

AIM AND OBJECTIVES: To investigate the prevalence of dysphagia in patients with COPD, identify the risk factors for dysphagia, develop a visual clinical prediction model and quantitatively predict the probability of developing dysphagia. BACKGROUND: Patients with COPD are at high risk of dysphagia, which is strongly linked to the acute exacerbation of their condition. The use of effective tools to predict its risk may contribute to the early identification and treatment of dysphagia in patients with COPD. DESIGN: A cross-sectional design. METHODS: From July 2021 to April 2023, we enrolled 405 patients with COPD for this study. The clinical prediction model was constructed according to the results of a univariate analysis and a logistic regression analysis, evaluated by discrimination, calibration and decision curve analysis and visualized by a nomogram. This study was reported using the TRIPOD checklist. RESULTS: In total, 405 patients with COPD experienced dysphagia with a prevalence of 59.01%. A visual prediction model was constructed based on age, whether combined with cerebrovascular disease, chronic pulmonary heart disease, acute exacerbation of COPD, home noninvasive positive pressure ventilation, dyspnoea level and xerostomia level. The model exhibited excellent discrimination at an AUC of .879. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. CONCLUSION: The model we devised may be used in clinical settings to predict the occurrence of dysphagia in patients with COPD at an early stage. RELEVANCE TO CLINICAL PRACTICE: The model can help nursing staff to calculate the risk probability of dysphagia in patients with COPD, formulate personalized preventive care measures for high-risk groups as soon as possible to achieve early prevention or delay of dysphagia and its related complications and improve the prognosis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

19.
Biomed Pharmacother ; 174: 116591, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631144

RESUMO

The characteristics of fibrosis include the abnormal accumulation of extracellular matrix proteins and abnormal tissue repair caused by injury, infection, and inflammation, leading to a significant increase in organ failure and mortality. Effective and precise treatments are urgently needed to halt and reverse the progression of fibrotic diseases. Exosomes are tiny vesicles derived from endosomes, spanning from 40 to 160 nanometers in diameter, which are expelled into the extracellular matrix environment by various cell types. They play a crucial role in facilitating cell-to-cell communication by transporting a variety of cargoes, including proteins, RNA, and DNA. Epithelial cells serve as the primary barrier against diverse external stimuli that precipitate fibrotic diseases. Numerous research suggests that exosomes from epithelial cells have a significant impact on several fibrotic diseases. An in-depth comprehension of the cellular and molecular mechanisms of epithelial cell-derived exosomes in fibrosis holds promise for advancing the exploration of novel diagnostic biomarkers and clinical drug targets. In this review, we expand upon the pathogenic mechanisms of epithelium-derived exosomes and highlight their role in the fibrotic process by inducing inflammation and activating fibroblasts. In addition, we are particularly interested in the bioactive molecules carried by epithelial-derived exosomes and their potential value in the diagnosis and treatment of fibrosis and delineate the clinical utility of exosomes as an emerging therapeutic modality, highlighting their potential application in addressing various medical conditions.


Assuntos
Células Epiteliais , Exossomos , Fibrose , Exossomos/metabolismo , Humanos , Animais , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Comunicação Celular , Inflamação/patologia , Inflamação/metabolismo , Biomarcadores/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia
20.
Nat Commun ; 15(1): 3043, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589394

RESUMO

Carbon quantum dots are emerging as promising nanomaterials for next-generation displays. The elaborate structural design is crucial for achieving thermally activated delayed fluorescence, particularly for improving external quantum efficiency of electroluminescent light-emitting diodes. Here, we report the synthesis of onion-like multicolor thermally activated delayed fluorescence carbon quantum dots with quantum yields of 42.3-61.0%. Structural, spectroscopic characterization and computational studies reveal that onion-like structures assembled from monomer carbon quantum dots of different sizes account for the decreased singlet-triplet energy gap, thereby achieving efficient multicolor thermally activated delayed fluorescence. The devices exhibit maximum luminances of 3785-7550 cd m-2 and maximum external quantum efficiency of 6.0-9.9%. Importantly, owing to the weak van der Waals interactions and adequate solution processability, flexible devices with a maximum luminance of 2554 cd m-2 are realized. These findings facilitate the development of high-performance carbon quantum dots-based electroluminescent light-emitting diodes that are promising for practical applications.

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