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1.
BMC Neurol ; 24(1): 207, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886670

ABSTRACT

OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.


Subject(s)
Endovascular Procedures , Ischemic Stroke , Humans , Male , Female , Ischemic Stroke/surgery , Ischemic Stroke/therapy , Aged , Endovascular Procedures/methods , Middle Aged , Aged, 80 and over , Medical Futility , Thrombectomy/methods , Prospective Studies , Prognosis
2.
Foods ; 13(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38890954

ABSTRACT

Prickly ash peel oleoresin (PPO) is a highly concentrated oil of Prickly ash essential oil and has a stronger aroma. However, its low water solubility, high volatility, difficulty in transport and storage, and decomposition by light, heat, and oxygen limit its wider application. To solve this problem, this study used freeze-drying or spray-drying, with soybean protein isolate (SPI) or gum Arabic (GA), combined with aqueous maltodextrin (MD) as the encapsulating agents to prepare four types of PPO microcapsules (POMs). Spray-dried microcapsules with GA as the encapsulating agent achieved a high encapsulation efficiency (EE) of 92.31 ± 0.31%, improved the thermal stability of the PPO, and had spherical morphology. (Headspace solid-phase microextraction/gas chromatography-mass spectrometry) HS-SPME/GC-MS detected 41 volatile compounds in PPO; of these, linalool, ß-myrcene, sabinene, and D-limonene were identified as key flavor components. Principal component analysis (PCA) effectively distinguished the significant differences in flavor between PPO, spray-dried SPI/MD microcapsules (SS), and spray-dried GA/MD microcapsules (SG). During 15 days of air-exposure, the loss of flavor from SG (54.62 ± 0.54%) was significantly lower than PPO (79.45 ± 1.45%) and SS (57.55 ± 0.36%). During the air-exposure period, SG consistently had the highest antioxidant capacity, making it desirable for PPO packaging, and expanding its potential applications within the food industry.

3.
Sensors (Basel) ; 24(8)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38676267

ABSTRACT

The rapid increase in the number of vehicles has led to increasing traffic congestion, traffic accidents, and motor vehicle crime rates. The management of various parking lots has also become increasingly challenging. Vehicle-type recognition technology can reduce the workload of humans in vehicle management operations. Therefore, the application of image technology for vehicle-type recognition is of great significance for integrated traffic management. In this paper, an improved faster region with convolutional neural network features (Faster R-CNN) model was proposed for vehicle-type recognition. Firstly, the output features of different convolution layers were combined to improve the recognition accuracy. Then, the average precision (AP) of the recognition model was improved through the contextual features of the original image and the object bounding box optimization strategy. Finally, the comparison experiment used the vehicle image dataset of three vehicle types, including cars, sports utility vehicles (SUVs), and vans. The experimental results show that the improved recognition model can effectively identify vehicle types in the images. The AP of the three vehicle types is 83.2%, 79.2%, and 78.4%, respectively, and the mean average precision (mAP) is 1.7% higher than that of the traditional Faster R-CNN model.

4.
J Transl Med ; 22(1): 243, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38443979

ABSTRACT

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.


Subject(s)
Chromatin , Peritoneal Fibrosis , Humans , Chromatin/genetics , Transforming Growth Factor beta1/genetics , Transcriptome/genetics , Chromosome Aberrations , Transforming Growth Factor beta
6.
Biomark Med ; 18(4): 137-143, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38375795

ABSTRACT

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.


Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Humans , Stroke/therapy , Stroke/complications , Ischemic Stroke/complications , Neutrophils , Endovascular Procedures/adverse effects , Treatment Outcome , Brain Ischemia/complications , Retrospective Studies
7.
Clin Appl Thromb Hemost ; 30: 10760296231223192, 2024.
Article in English | MEDLINE | ID: mdl-38166411

ABSTRACT

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.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Middle Aged , Aged , Stroke/etiology , Tissue Plasminogen Activator/adverse effects , Ischemic Stroke/drug therapy , Ischemic Stroke/etiology , Neutrophils , Brain Ischemia/etiology , Thrombolytic Therapy/adverse effects , Fibrinolytic Agents/therapeutic use , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/drug therapy , Treatment Outcome
8.
Behav Brain Res ; 459: 114782, 2024 02 29.
Article in English | MEDLINE | ID: mdl-38029844

ABSTRACT

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.


Subject(s)
Lipopolysaccharides , NLR Family, Pyrin Domain-Containing 3 Protein , Mice , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Pyroptosis , Microglia , Depression/chemically induced , Depression/drug therapy , Neuroinflammatory Diseases , Inflammasomes/metabolism
10.
Foods ; 12(22)2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38002197

ABSTRACT

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.

11.
Front Neurosci ; 17: 1270850, 2023.
Article in English | MEDLINE | ID: mdl-37869519

ABSTRACT

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.

12.
Sensors (Basel) ; 23(20)2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37896494

ABSTRACT

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.

13.
Foods ; 12(17)2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37685109

ABSTRACT

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.

14.
BMC Neurol ; 23(1): 244, 2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37353783

ABSTRACT

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.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Aged , Humans , Middle Aged , Brain Ischemia/drug therapy , C-Reactive Protein , Fibrinolytic Agents/therapeutic use , Ischemic Stroke/diagnosis , Ischemic Stroke/drug therapy , Retrospective Studies , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Urokinase-Type Plasminogen Activator/therapeutic use
15.
Biomacromolecules ; 24(6): 2790-2803, 2023 06 12.
Article in English | MEDLINE | ID: mdl-37125731

ABSTRACT

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.


Subject(s)
Chitosan , Neoplasms , Humans , Immunotherapy , Membrane Proteins , Neoplasms/drug therapy , Photothermal Therapy , Reactive Oxygen Species , Tumor Microenvironment
16.
Aging (Albany NY) ; 15(5): 1371-1393, 2023 02 20.
Article in English | MEDLINE | ID: mdl-36863715

ABSTRACT

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.


Subject(s)
Atrial Fibrillation , Humans , Atrial Fibrillation/genetics , Methylation , RNA , Gene Regulatory Networks , Healthy Volunteers
17.
Int J Biol Macromol ; 235: 123833, 2023 Apr 30.
Article in English | MEDLINE | ID: mdl-36870654

ABSTRACT

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.


Subject(s)
Cellulose , Polysaccharides , Glycosylation , Cellulose/chemistry , Computer Simulation , Thermodynamics , Protein Binding , Binding Sites
18.
Eur J Pharm Biopharm ; 184: 202-213, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36773724

ABSTRACT

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.


Subject(s)
Cicatrix, Hypertrophic , Animals , Humans , Rabbits , Cicatrix, Hypertrophic/drug therapy , Gelatin , Hyaluronic Acid/metabolism , Vascular Endothelial Growth Factor A/metabolism , Endothelial Cells/metabolism , Fibroblasts
19.
J Environ Manage ; 330: 117167, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36584457

ABSTRACT

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.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Zeolites , Humans , Zeolites/chemistry , Cadmium/chemistry , Hydrogen Peroxide , Lead , Metals, Heavy/chemistry , Adsorption , Ions , Water Pollutants, Chemical/chemistry
20.
Mol Cell Biochem ; 478(3): 651-663, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36001204

ABSTRACT

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.


Subject(s)
Acute Kidney Injury , Erythropoietin , Sepsis , Humans , Kidney/metabolism , Lipopolysaccharides/pharmacology , Sirtuin 1/metabolism , Erythropoietin/metabolism , Erythropoietin/pharmacology , Erythropoietin/therapeutic use , Acute Kidney Injury/pathology , Apoptosis , Energy Metabolism , Sepsis/metabolism , Inflammation/metabolism
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