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1.
J Transl Med ; 22(1): 243, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443979

RESUMO

BACKGROUND: Peritoneal fibrosis is the prevailing complication induced by prolonged exposure to high glucose in patients undergoing peritoneal dialysis. METHODS: To elucidate the molecular mechanisms underlying this process, we conducted an integrated analysis of the transcriptome and chromatin accessibility profiles of human peritoneal mesothelial cells (HMrSV5) during high-glucose treatment. RESULTS: Our study identified 2775 differentially expressed genes (DEGs) related to high glucose-triggered pathological changes, including 1164 upregulated and 1611 downregulated genes. Genome-wide DEGs and network analysis revealed enrichment in the epithelial-mesenchymal transition (EMT), inflammatory response, hypoxia, and TGF-beta pathways. The enriched genes included VEGFA, HIF-1α, TGF-ß1, EGF, TWIST2, and SNAI2. Using ATAC-seq, we identified 942 hyper (higher ATAC-seq signal in high glucose-treated HMrSV5 cells than in control cells) and 714 hypo (lower ATAC-seq signal in high glucose-treated HMrSV5 cells versus control cells) peaks with differential accessibility in high glucose-treated HMrSV5 cells versus controls. These differentially accessible regions were positively correlated (R = 0.934) with the nearest DEGs. These genes were associated with 566 up- and 398 downregulated genes, including SNAI2, TGF-ß1, HIF-1α, FGF2, VEGFA, and VEGFC, which are involved in critical pathways identified by transcriptome analysis. Integrated ATAC-seq and RNA-seq analysis also revealed key transcription factors (TFs), such as HIF-1α, ARNTL, ELF1, SMAD3 and XBP1. Importantly, we demonstrated that HIF-1α is involved in the regulation of several key genes associated with EMT and the TGF-beta pathway. Notably, we predicted and experimentally validated that HIF-1α can exacerbate the expression of TGF-ß1 in a high glucose-dependent manner, revealing a novel role of HIF-1α in high glucose-induced pathological changes in human peritoneal mesothelial cells (HPMCs). CONCLUSIONS: In summary, our study provides a comprehensive view of the role of transcriptome deregulation and chromosome accessibility alterations in high glucose-induced pathological fibrotic changes in HPMCs. This analysis identified hub genes, signaling pathways, and key transcription factors involved in peritoneal fibrosis and highlighted the novel glucose-dependent regulation of TGF-ß1 by HIF-1α. This integrated approach has offered a deeper understanding of the pathogenesis of peritoneal fibrosis and has indicated potential therapeutic targets for intervention.


Assuntos
Cromatina , Fibrose Peritoneal , Humanos , Cromatina/genética , Fator de Crescimento Transformador beta1/genética , Transcriptoma/genética , Aberrações Cromossômicas , Fator de Crescimento Transformador beta
3.
Biomark Med ; 18(4): 137-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38375795

RESUMO

Aim: To explore the association between the neutrophil-to-platelet ratio (NPR) and futile recanalization (FR) in patients with acute ischemic stroke due to large vascular occlusions after endovascular therapy (EVT). Methods: FR after EVT was defined as a poor 90-day prognosis (modified Rankin scale [mRS] score ≥3) despite successful reperfusion (modified thrombolysis in cerebral infarction grade 2b-3). Patients were divided into high NPR (>35; n = 115) and low NPR (≤35; n = 81) groups. Results: The FR rate was significantly higher in the high NPR group than low NPR group (81.74 vs 55.56%; p = 0.000). NPR was independently associated with FR (odds ratio: 2.107; 95% CI: 1.017-4.364; p = 0.045). Conclusion: High NPR was associated with the risk of FR in patients with acute ischemic stroke due to large vascular occlusions.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicações , AVC Isquêmico/complicações , Neutrófilos , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Isquemia Encefálica/complicações , Estudos Retrospectivos
4.
Clin Appl Thromb Hemost ; 30: 10760296231223192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38166411

RESUMO

To investigate the predictive role of the neutrophil-platelet ratio (NPR) before intravenous thrombolysis (IVT) on hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). AIS patients treated with IVT without endovascular therapy between June 2019 and February 2023 were included. Patients were divided into high NPR (>35) and low NPR (≤35) groups according to the optimal threshold NPR value for identifying high-risk patients before IVT. The baseline data and the incidence of HT and symptomatic intracranial hemorrhage (sICH) were compared between the two groups. The predictive role of the NPR and other related factors on HT after IVT was analyzed by multivariate logistic regression. A total of 247 patients were included, with an average age of 67.5 ± 12.4 years. Post-thrombolytic HT was observed in 18.6% of the patients, and post-thrombolytic sICH was observed in 1.2% of the patients. There were 69 patients in the high NPR group and 178 patients in the low NPR group. The incidence of HT in the high NPR group was significantly higher than that in the low NPR group (30.4% vs 16.3%, P < .05). The incidence of sICH was significantly higher in the high NPR group than in the low NPR group (14.5% vs 1.7%, P < .001). Multivariate logistic regression analysis showed that NPR > 35 was positively correlated with HT (odds ratio (OR) = 3.236, 95% confidence interval (CI): 1.481-7.068, P = .003) and sICH (OR = 13.644, 95% CI: 2.392-77.833, P = .003). A high NPR (>35) before IVT may be a predictor of HT in AIS patients. This finding may help clinicians make clinical decisions before IVT in AIS patients.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Idoso , Acidente Vascular Cerebral/etiologia , Ativador de Plasminogênio Tecidual/efeitos adversos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , Neutrófilos , Isquemia Encefálica/etiologia , Terapia Trombolítica/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Resultado do Tratamento
5.
Behav Brain Res ; 459: 114782, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38029844

RESUMO

Esketamine is verified as a potential therapeutic drug for the treatment of depression, but it is still unclear the detailed underlying mechanisms by which Esketamine ameliorates depression-related symptoms, which seriously limits the utilization of this drug in clinical practices. In this study, the C57BL6/J mice and mouse primary microglial cells were subjected to lipopolysaccharide (LPS)-induced depressive models in vivo and in vitro, and our results confirmed that LPS-induced neuroinflammation, pyroptotic and apoptotic death contributed to the development of LPS-induced depressive symptoms. Then, the following experiments verified that low-dose Esketamine treatment decreased the expression levels of IL-6, TNF-α and IL-18 to restrain cellular inflammation, downregulated NLRP3, cleaved Caspase-1, IL-1ß and GSDMD-N to hamper pyroptotic cell death, and inhibited cleaved caspase-3 and Bax, but upregulated Bcl-2 to restrict apoptotic cell death in the LPS-treated mice hippocampus tissues and mouse microglial cells, leading to the suppression of depression development. However, high-dose Esketamine did not have those effects. Next, by conducting mechanical experiments, we verified that low-dose Esketamine downregulated GSK-3ß to inactivate NLRP3 inflammasome, and the effects of low-dose Esketamine on cell pyroptosis, neuroinflammation and apoptosis in the LPS-treated microglial cells were all abrogated by overexpressing GSK-3ß and NLRP3. Taken together, low-dose Esketamine ameliorated LPS-induced depressive symptoms in mice through regulating the GSK-3ß/NLRP3 pathway, and our work suggested that appropriate doses of Esketamine were essential for the treatment of depression in clinic.


Assuntos
Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Piroptose , Microglia , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Doenças Neuroinflamatórias , Inflamassomos/metabolismo
6.
Foods ; 12(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38002197

RESUMO

Active functional microbiota for producing volatile flavors is critical to Chinese baijiu fermentation. Microbial communities correlated with the volatile metabolites are generally explored using DNA-based sequencing and metabolic analysis. However, the active functional microbiota related to the volatile flavor compounds is poorly understood. In this study, an integrated metatranscriptomic and metabolomics analysis was employed to unravel the metabolite profiles comprehensively and the contributing active functional microbiota for flavor generation during Niulanshan baijiu fermentation. A total of 395, 83, and 181 compounds were annotated using untargeted metabolomics, including LC-MS, GC-MS, and HS-SPME-GC-MS, respectively. Significant variances were displayed in the composition of compounds among different time-point samples according to the heatmaps and orthogonal partial least-square discriminant analysis. The correlation between the active microbiota and the volatile flavors was analyzed based on the bidirectional orthogonal partial least squares discriminant analysis (O2PLS-DA) model. Six bacterial genera, including Streptococcus, Lactobacillus, Pediococcus, Campylobacter, Yersinia, and Weissella, and five fungal genera of Talaromyces, Aspergillus, Mixia, Rhizophagus, and Gloeophyllum were identified as the active functional microbiota for producing the volatile flavors. In summary, this study revealed the active functional microbial basis of unique flavor formation and provided novel insights into the optimization of Niulanshan baijiu fermentation.

7.
Front Neurosci ; 17: 1270850, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869519

RESUMO

Image caption technology aims to convert visual features of images, extracted by computers, into meaningful semantic information. Therefore, the computers can generate text descriptions that resemble human perception, enabling tasks such as image classification, retrieval, and analysis. In recent years, the performance of image caption has been significantly enhanced with the introduction of encoder-decoder architecture in machine translation and the utilization of deep neural networks. However, several challenges still persist in this domain. Therefore, this paper proposes a novel method to address the issue of visual information loss and non-dynamic adjustment of input images during decoding. We introduce a guided decoding network that establishes a connection between the encoding and decoding parts. Through this connection, encoding information can provide guidance to the decoding process, facilitating automatic adjustment of the decoding information. In addition, Dense Convolutional Network (DenseNet) and Multiple Instance Learning (MIL) are adopted in the image encoder, and Nested Long Short-Term Memory (NLSTM) is utilized as the decoder to enhance the extraction and parsing capability of image information during the encoding and decoding process. In order to further improve the performance of our image caption model, this study incorporates an attention mechanism to focus details and constructs a double-layer decoding structure, which facilitates the enhancement of the model in terms of providing more detailed descriptions and enriched semantic information. Furthermore, the Deep Reinforcement Learning (DRL) method is employed to train the model by directly optimizing the identical set of evaluation indexes, which solves the problem of inconsistent training and evaluation standards. Finally, the model is trained and tested on MS COCO and Flickr 30 k datasets, and the results show that the model has improved compared with commonly used models in the evaluation indicators such as BLEU, METEOR and CIDEr.

8.
Sensors (Basel) ; 23(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37896494

RESUMO

A differential evolution particle swarm optimization (DEPSO) is presented for the design of a high-phase-sensitivity surface plasmon resonance (SPR) gas sensor. The gas sensor is based on a bilayer metal film with a hybrid structure of blue phosphorene (BlueP)/transition metal dichalcogenides (TMDCs) and MXene. Initially, a Ag-BlueP/TMDCs-Ag-MXene heterostructure is designed, and its performance is compared with that of the conventional layer-by-layer method and particle swarm optimization (PSO). The results indicate that optimizing the thickness of the layers in the gas sensor promotes phase sensitivity. Specifically, the phase sensitivity of the DEPSO is significantly higher than that of the PSO and the conventional method, while maintaining a lower reflectivity. The maximum phase sensitivity achieved is 1.866 × 106 deg/RIU with three layers of BlueP/WS2 and a monolayer of MXene. The distribution of the electric field is also illustrated, demonstrating that the optimized configuration allows for better detection of various gases. Due to its highly sensitive characteristics, the proposed design method based on the DEPSO can be applied to SPR gas sensors for environmental monitoring.

9.
Foods ; 12(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685109

RESUMO

Volatile compounds (VOCs) present in the oil extracted from yellow horn seeds were first analyzed using GC-IMS and GC-O-MS at varying roasting temperatures. A total of 97 VOCs were detected using GC-IMS, while 77 were tentatively identified using GC-O-MS. Moreover, both methods allowed the identification of 24 VOCs, of which the type of aldehydes is the most abundant. Combining the results of GC-IMS, GC-O-MS, OAVs, and VIP, it was concluded that hexanal, 2,5-dimethylpyrazine, heptanal, 2-pentylfuran, 1-hexanol, and 1-octen-3-ol were the key aroma compounds. The PLS-DA and OPLS-DA models have demonstrated the ability to discriminate between different oil roasting temperatures with high accuracy. The roasting temperature of 160 °C was found to yield the highest content of main aroma substances, indicating its optimality for yellow horn seed oil production. These findings will prove beneficial for optimizing industrial production and enhancing oil aroma control.

10.
BMC Neurol ; 23(1): 244, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353783

RESUMO

PURPOSE: To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response. RESULTS: A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266-0.927, P = 0.028). CONCLUSION: hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Humanos , Pessoa de Meia-Idade , Isquemia Encefálica/tratamento farmacológico , Proteína C-Reativa , Fibrinolíticos/uso terapêutico , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico
11.
Biomacromolecules ; 24(6): 2790-2803, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37125731

RESUMO

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.


Assuntos
Quitosana , Neoplasias , Humanos , Imunoterapia , Proteínas de Membrana , Neoplasias/tratamento farmacológico , Terapia Fototérmica , Espécies Reativas de Oxigênio , Microambiente Tumoral
12.
Aging (Albany NY) ; 15(5): 1371-1393, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36863715

RESUMO

The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/genética , Metilação , RNA , Redes Reguladoras de Genes , Voluntários Saudáveis
13.
Int J Biol Macromol ; 235: 123833, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36870654

RESUMO

The role of glycosylation in the binding of glycoproteins to carbohydrate substrates has not been well understood. The present study addresses this knowledge gap by elucidating the links between the glycosylation patterns of a model glycoprotein, a Family 1 carbohydrate-binding module (TrCBM1), and the thermodynamic and structural properties of its binding to different carbohydrate substrates using isothermal titration calorimetry and computational simulation. The variations in glycosylation patterns cause a gradual transition of the binding to soluble cellohexaose from an entropy-driven process to an enthalpy-driven one, a trend closely correlated with the glycan-induced shift of the predominant binding force from hydrophobic interactions to hydrogen bonding. However, when binding to a large surface of solid cellulose, glycans on TrCBM1 have a more dispersed distribution and thus have less adverse impact on the hydrophobic interaction forces, leading to overall improved binding. Unexpectedly, our simulation results also suggest an evolutionary role of O-mannosylation in transforming the substrate binding features of TrCBM1 from those of type A CBMs to those of type B CBMs. Taken together, these findings provide new fundamental insights into the molecular basis of the role of glycosylation in protein-carbohydrate interactions and are expected to better facilitate further studies in this area.


Assuntos
Celulose , Polissacarídeos , Glicosilação , Celulose/química , Simulação por Computador , Termodinâmica , Ligação Proteica , Sítios de Ligação
14.
Eur J Pharm Biopharm ; 184: 202-213, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36773724

RESUMO

The formation of hypertrophic scar (HS) involves many pathological processes, such as reduced apoptosis in fibroblasts, excessive collagen deposition by fibroblasts, over-abundant angiogenesis, etc. The therapeutic effects of current treatments targeting one single pathological process are limited. Due to their diverse biological activities, natural products offer a potential solution to this issue. In this study reported herein, we investigated the effects of Protocatechuic aldehyde (PA) on both hypertrophic scar-derived fibroblasts (HSF) and vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs). Microneedles (MN) containing PA and hyaluronic acid (HA) or containing PA, HA, and gelatin were prepared by mixing PA stock solution with HA or HA/gelatin at a ratio of 1:10. The HS prevention and treatment outcomes of these HA-PA-MN and HA/gelatin-PA-MN were tested using a rabbit ear HS model. Our data indicate that PA induces apoptosis and reduces collagen deposition in HSF. In addition, PA attenuates VEGF-stimulated angiogenesis of HUVECs. Furthermore, HA-PA-MN or HA/gelatin-PA-MN are able to effectively penetrate the epidermis of the HS tissues and then quickly dissolve, enabling the fast release of PA directly into the dermis of the HS tissues. HA-PA-MN or HA/Gelatin-PA-MN have also been found to effectively prevent or alleviate HS in a rabbit ear HS model. In conclusion, this study demonstrates that PA can be used to prevent and treat HS by simultaneously regulating HSF and HUVECs, which offers a potential novel reagent for HS management.


Assuntos
Cicatriz Hipertrófica , Animais , Humanos , Coelhos , Cicatriz Hipertrófica/tratamento farmacológico , Gelatina , Ácido Hialurônico/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Fibroblastos
15.
Mol Cell Biochem ; 478(3): 651-663, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36001204

RESUMO

Acute kidney injury (AKI) is one of frequent complications of sepsis with high mortality. Mitochondria is the center of energy metabolism participating in the pathogenesis of sepsis-associated AKI, and SIRT1/PGC1-α signaling pathway plays a crucial role in the modulation of energy metabolism. Erythropoietin (EPO) exerts protective functions on chronic kidney disease. We aimed to assess the effects of EPO on cell damage and energy metabolism in a cell model of septic AKI. Renal tubular epithelial cells HK-2 were treated with LPS and human recombinant erythropoietin (rhEPO). Cell viability was detected by CCK-8 and mitochondrial membrane potential was determined using JC-1 fluorescent probe. Then the content of ATP, ADP and NADPH, as well as lactic acid, were measured for the assessment of energy metabolism. Oxidative stress was evaluated by detecting the levels of ROS, MDA, SOD and GSH. Pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1ß, were measured with ELISA. Moreover, qRT-PCR and western blot were performed to detect mRNA and protein expressions. shSIRT1 was used to knockdown SIRT1, while EX527 and SR-18292 were applied to inhibit SIRT1 and PGC1-α, respectively, to investigate the regulatory mechanism of rhEPO on inflammatory injury and energy metabolism. In LPS-exposed HK-2 cells, rhEPO attenuated cell damage, inflammation and abnormal energy metabolism, as indicated by the elevated cell viability, the inhibited oxidative stress, cell apoptosis and inflammation, as well as the increased mitochondrial membrane potential and energy metabolism. However, these protective effects induced by rhEPO were reversed after SIRT1 or PGC1-α inhibition. EPO activated SIRT1/PGC1-α pathway to alleviate LPS-induced abnormal energy metabolism and cell damage in HK-2 cells. Our study suggested that rhEPO played a renoprotective role through SIRT1/PGC1-α pathway, which supported its therapeutic potential in septic AKI.


Assuntos
Injúria Renal Aguda , Eritropoetina , Sepse , Humanos , Rim/metabolismo , Lipopolissacarídeos/farmacologia , Sirtuína 1/metabolismo , Eritropoetina/metabolismo , Eritropoetina/farmacologia , Eritropoetina/uso terapêutico , Injúria Renal Aguda/patologia , Apoptose , Metabolismo Energético , Sepse/metabolismo , Inflamação/metabolismo
16.
J Environ Manage ; 330: 117167, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36584457

RESUMO

Clinoptilolite based zeolite-geopolymer foams (abbreviated as CFs) were prepared from natural clinoptilolite and calcined clinoptilolite, using H2O2 solution as pore former through a straightforward process. Natural clinoptilolite and CFs are characterized by analytical techniques including optical microscope, XRF, FTIR, XRD, BET, MIP and SEM. The obtained CFs possesses micropores of zeolite and meso/macropores of geopolymer matrix. The porosities range from 66.7 to 69.5%. Clinoptilolite (partially dissolved) and impurity minerals (montmorillonite, illite and albite) contribute to the formation of geopolymer. CFs shows a good static sorption performance for toxic heavy metals at pH = 5 and sorption time of 24 h. Results show that the adsorption amount of CFs for Cr3+, Pb2+, Ni2+, Cu2+ and Cd2+ in the 50 mg/L working solutions are 6.21 mg/g, 6.11-6.13 mg/g, 5.92-6.07 mg/g, 5.53-5.93 mg/g and 5.44-5.79 mg/g, respectively. In addition, CFs could reach a high removal rate (Cr removal rate >80% and Cd > 60%) for different heavy metals after three cycles. The elimination order of toxic metals is Cr3+ > Pb2+ > Ni2+ > Cu2+ > Cd2+. The sequence is in accordance with Hard-Soft-Acid-Base principle, it is also related to the speciation and the ionic radii of the hydrated metal ions. This research provides a feasible approach for preparation of promising foams sorbent based on natural zeolite for wastewater management.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Zeolitas , Humanos , Zeolitas/química , Cádmio/química , Peróxido de Hidrogênio , Chumbo , Metais Pesados/química , Adsorção , Íons , Poluentes Químicos da Água/química
17.
Front Microbiol ; 14: 1330029, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38268702

RESUMO

The global prevalence of Helicobacter pylori (H. pylori) infection remains high, indicating a persistent presence of this pathogenic bacterium capable of infecting humans. This review summarizes the population demographics, transmission routes, as well as conventional and novel therapeutic approaches for H. pylori infection. The prevalence of H. pylori infection exceeds 30% in numerous countries worldwide and can be transmitted through interpersonal and zoonotic routes. Cytotoxin-related gene A (CagA) and vacuolar cytotoxin A (VacA) are the main virulence factors of H. pylori, contributing to its steep global infection rate. Preventative measures should be taken from people's living habits and dietary factors to reduce H. pylori infection. Phytotherapy, probiotics therapies and some emerging therapies have emerged as alternative treatments for H. pylori infection, addressing the issue of elevated antibiotic resistance rates. Plant extracts primarily target urease activity and adhesion activity to treat H. pylori, while probiotics prevent H. pylori infection through both immune and non-immune pathways. In the future, the primary research focus will be on combining multiple treatment methods to effectively eradicate H. pylori infection.

18.
Nat Commun ; 13(1): 7288, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435878

RESUMO

The recent discovery of novel charge density wave (CDW) and pair density wave (PDW) in kagomé lattice superconductors AV3Sb5 (A = K, Rb, Cs) hints at unexpected time-reversal symmetry breaking correlated and topological states whose physical origin and broader implications are not understood. Here, we make conceptual advances toward a mechanism behind the striking observations and new predictions for novel macroscopic phase coherent quantum states. We show that the metallic CDW state with circulating loop currents is a doped orbital Chern insulator near van Hove filling. The emergent Chern Fermi pockets (CFPs) carry concentrated Berry curvature and orbital magnetic moment. We find that the pairing of electrons on the CFPs leads to a superconducting state with an emergent vortex-antivortex lattice and the formation of a complex triple-Q PDW. A plethora of correlated and topological states emerge, including a never-before-encountered chiral topological PDW superconductor, a loop-current pseudogap phase, and vestigial charge-4e and charge-6e superconductivity in staged melting of the vortex-antivortex lattice and hexatic liquid crystal. Our findings reveal previously unknown nature of the superconducting state of a current-carrying Chern metal, with broad implications for correlated and topological materials.

19.
Environ Sci Pollut Res Int ; 29(60): 90984-90994, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35881294

RESUMO

Clay-based materials have attracted attention owing to their dual effects of adsorption and advanced oxidation degradation in removing organic pollutants. In this study, the introduction of humic acid (HA) in the Fe-bearing montmorillonite (Fe-Mt) nano platform enhanced its tetracycline (TC) adsorption and degradation were investigated. The result showed that the adsorption and degradation efficiency of humic acid/poly-hydroxyl-iron/montmorillonite (HA-Fe-Mt) was greater than those of Fe-Mt. The adsorption performance and characterization confirmed that HA-Fe-Mt had more functional groups, stronger hydrophobic character, and higher specific surface area. The introduction of HA onto the Fe-Mt platform enhanced its specific surface area, electrostatic interaction, and hydrophobic character, therefore providing more active sites to interact with the carbonyl and amide groups of TC. Moreover, the catalytic performance and characterization results revealed that HA-Fe-Mt had greater persulfate (PS) activation, the coupled HA would speed up the transmission of electrons between Fe (III) and PS in the Fe (III) / Fe (II) cycle when PS was captured by the HA-Fe-Mt system, and the in situ generated Fe accelerates the generation of reactive oxygen species (ROS) to further degrade TC. Consequently, HA can not only promote the adsorption of TC but also promote the degradation of TC in the Fe-Mt nano platform. HA-Fe-Mt provided a feasible and promising platform with PS activation for TC adsorption and degradation.


Assuntos
Bentonita , Substâncias Húmicas
20.
ACS Appl Mater Interfaces ; 14(27): 30533-30545, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35771755

RESUMO

With the emergence and global spread of bacterial resistance, pathogenic bacterial infections have become a serious threat to human health. Thus, therapeutic strategies with highly antibacterial efficacy and a low tendency to induce drug resistance are strongly desired to combat bacterial infections. Here, an ultra-efficient photodynamic/chemodynamic theranostics platform is developed by intercalating an aggregation-induced emission (AIE) photosensitizer, TPCI, into the nanolayers of iron-bearing montmorillonite (MMT). The formed TPCI/MMT composite can not only perform efficient photodynamic therapy (PDT) through a burst generation of singlet oxygen (1O2) upon white light illumination but also continuously implement chemodynamic therapy (CDT) by converting endogenous hydrogen peroxide into highly toxic hydroxyl radicals (•OH) due to iron release. In addition, the fluorescence of TPCI/MMT can be activated due to the AIE feature of TPCI, which helps guide the location of the antimicrobials. The combination of such powerful bombs (PDT) and unremitting ambushes (CDT) in TPCI/MMT can synergistically and effectively eliminate bacteria and promote faster wound healing in vivo with good biocompatibility and low side effects. The smart and simple design of TPCI/MMT provides a representative paradigm for achieving efficient antimicrobials to combat the coming resistance crisis.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Anti-Infecciosos/uso terapêutico , Bactérias , Humanos , Ferro , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Medicina de Precisão , Nanomedicina Teranóstica , Cicatrização
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