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1.
IEEE Trans Image Process ; 33: 3174-3186, 2024.
Article in English | MEDLINE | ID: mdl-38687649

ABSTRACT

This paper tackles spectral reflectance recovery (SRR) from RGB images. Since capturing ground-truth spectral reflectance and camera spectral sensitivity are challenging and costly, most existing approaches are trained on synthetic images and utilize the same parameters for all unseen testing images, which are suboptimal especially when the trained models are tested on real images because they never exploit the internal information of the testing images. To address this issue, we adopt a self-supervised meta-auxiliary learning (MAXL) strategy that fine-tunes the well-trained network parameters with each testing image to combine external with internal information. To the best of our knowledge, this is the first work that successfully adapts the MAXL strategy to this problem. Instead of relying on naive end-to-end training, we also propose a novel architecture that integrates the physical relationship between the spectral reflectance and the corresponding RGB images into the network based on our mathematical analysis. Besides, since the spectral reflectance of a scene is independent to its illumination while the corresponding RGB images are not, we recover the spectral reflectance of a scene from its RGB images captured under multiple illuminations to further reduce the unknown. Qualitative and quantitative evaluations demonstrate the effectiveness of our proposed network and of the MAXL. Our code and data are available at https://github.com/Dong-Huo/SRR-MAXL.

2.
Biochem Pharmacol ; 223: 116112, 2024 May.
Article in English | MEDLINE | ID: mdl-38458331

ABSTRACT

Glioblastoma (GBM) is the most common malignant glioma among brain tumors with low survival rate and high recurrence rate. Columbianadin (CBN) has pharmacological properties such as anti-inflammatory, analgesic, thrombogenesis-inhibiting and anti-tumor effects. However, it remains unknown that the effect of CBN on GBM cells and its underlying molecular mechanisms. In the present study, we found that CBN inhibited the growth and proliferation of GBM cells in a dose-dependent manner. Subsequently, we found that CBN arrested the cell cycle in G0/G1 phase and induced the apoptosis of GBM cells. In addition, CBN also inhibited the migration and invasion of GBM cells. Mechanistically, we chose network pharmacology approach by screening intersecting genes through targets of CBN in anti-GBM, performing PPI network construction followed by GO analysis and KEGG analysis to screen potential candidate signaling pathway, and found that phosphatidylinositol 3-kinase/Protein Kinase-B (PI3K/Akt) signaling pathway was a potential target signaling pathway of CBN in anti-GBM. As expected, CBN treatment indeed inhibited the PI3K/Akt signaling pathway in GBM cells. Furthermore, YS-49, an agonist of PI3K/Akt signaling, partially restored the anti-GBM effect of CBN. Finally, we found that CBN inhibited GBM growth in an orthotopic mouse model of GBM through inhibiting PI3K/Akt signaling pathway. Together, these results suggest that CBN has an anti-GBM effect by suppressing PI3K/Akt signaling pathway, and is a promising drug for treating GBM effectively.


Subject(s)
Coumarins , Glioblastoma , Proto-Oncogene Proteins c-akt , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , Glioblastoma/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Signal Transduction , Cell Proliferation
3.
Eur J Pharmacol ; 968: 176401, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38331340

ABSTRACT

Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Molecular Docking Simulation , Cell Line, Tumor , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Brain Neoplasms/genetics , Cell Proliferation
4.
Zhen Ci Yan Jiu ; 49(1): 64-70, 2024 Jan 25.
Article in English, Chinese | MEDLINE | ID: mdl-38239140

ABSTRACT

OBJECTIVES: To explore the effects of the combination of he-sea and front-mu points on the feeding compliance rate, the intra-abdominal pressure, the enteral nutrition tolerance score, the score of acute physiological and chronic health evaluation (APACHE)-Ⅱ and gastrointestinal function impairment grade in the patients with enteral nutrition feeding intolerance (ENFI) of critical illness and evaluate clinical effect on ENFI after acupuncture at the he-sea and front-mu points. METHODS: Seventy patients of ENFI were randomized into a control group and an observation group, 35 cases in each one. In the control group, the patients were treated with routine regimen combined with intestinal nutrition support. In the observation group, on the basis of the treatment as the control group, acupuncture was applied to Shangwan (CV13), Zhongwan (CV12), Xiawan (CV10), Qihai (CV6) and Guanyuan (CV4), as well as bila-teral Neiguan (PC6), Zusanli (ST36), Xiajuxu (ST39), Shangjuxu (ST37), Tianshu (ST25) and Daheng (SP15). Of those acupoints, ST25 and SP15 on the same side were attached to one pair of electrodes (20 Hz/100 Hz). Acupuncture was delivered once daily, 30 min each time and for consecutive 7 days. During treatment, the numbers of the cases up to the feeding standard were observed everyday to calculate the feeding compliance rate. The score of enteral nutrition tolerance, the intra-abdominal pressure, the score of APACHE-Ⅱ and the level of acute gastriointestinal injury(AGI) grading were recorded. RESULTS: After treatment, the enteral feeding compliance rate was increased in comparison with that before treatment in the two groups, and the rate in the observation group was higher than that of the control group (P<0.05) except that on the 2nd day. The score of the enteral nutrition tolerance, the intra-abdominal pressure, the score of APACHE-Ⅱ and the level of AGI were all reduced (P<0.05, P<0.01) when compared with those before treatment in the two groups, and these indicators in the observation group were lower (P<0.05) than those of the control group. CONCLUSIONS: Acupuncture at the he-sea and front-mu points relieves the conditions of ENFI, improves the feeding and the recovery of gastrointestinal function, and benefits the prognosis through increasing the amount of enteral nutrition in ENFI patients.


Subject(s)
Acupuncture Therapy , Enteral Nutrition , Humans , Critical Illness/therapy , Intestines , Acupuncture Points
5.
Molecules ; 29(2)2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38257306

ABSTRACT

Hepatocellular carcinoma (HCC), one of the most common malignant cancers with a low 5-year survival rate, is the third leading cause of cancer-related deaths worldwide. The finding of novel agents and strategies for the treatment of HCC is an urgent need. Sesquiterpene lactones (SLs) have attracted extensive attention because of their potent antitumor activity. In this study, a new series of SL derivatives (3-18) were synthesized using epimers 1 and 2 as parent molecules, isolated from Sphagneticola trilobata, and evaluated for their anti-HCC activity. Furthermore, the structures of 4, 6, and 14 were confirmed by X-ray single-crystal diffraction analyses. The cytotoxic activities of 3-18 on two HCC cell lines, including HepG2 and Huh7, were evaluated using the CCK-8 assay. Among them, compound 10 exhibited the best activity against the HepG2 and Huh7 cell lines. Further studies showed that 10 induced cell apoptosis, arrested the cell cycle at the S phase, and induced the inhibition of cell proliferation and migration in HepG2 and Huh7. In addition, absorption, distribution, metabolism, and excretion (ADME) properties prediction showed that 10 may possess the properties to be a drug candidate. Thus, 10 may be a promising lead compound for the treatment of HCC.


Subject(s)
Butyrates , Carcinoma, Hepatocellular , Furans , Liver Neoplasms , Sesquiterpenes , Humans , Carcinoma, Hepatocellular/drug therapy , Isobutyrates , Liver Neoplasms/drug therapy , Sesquiterpenes/pharmacology , Lactones/pharmacology
6.
Biomed Pharmacother ; 170: 115867, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38101281

ABSTRACT

Glioblastoma (GBM) is the most aggressive and lethal type of tumor in the central nervous system, characterized by a high incidence and poor prognosis. Thiotert, as a novel dual targeting agent, has potential inhibitory effects on various tumors. Here, we found that Thiotert effectively inhibited the proliferation of GBM cells by inducing G2/M cell cycle arrest and suppressed the migratory ability in vitro. Furthermore, Thiotert disrupted the thioredoxin (Trx) system while causing cellular DNA damage, which in turn caused endoplasmic reticulum (ER) stress-dependent autophagy. Knockdown of ER stress-related protein ATF4 in U251 cells inhibited ER stress-dependent autophagy caused by Thiotert to some extent. Orthotopic transplantation experiments further showed that Thiotert had the same anti-GBM activity and mechanism as in vitro. Conclusively, these results suggest that Thiotert induces ER stress-dependent autophagy in GBM cells by disrupting redox homeostasis and causing DNA damage, which provides new insight for the treatment of GBM.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/metabolism , Cell Line, Tumor , Endoplasmic Reticulum Stress , Autophagy , G2 Phase Cell Cycle Checkpoints , Brain Neoplasms/genetics , Apoptosis
7.
Nat Commun ; 14(1): 6757, 2023 10 24.
Article in English | MEDLINE | ID: mdl-37875484

ABSTRACT

Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We establish an uncertainty-inspired open set (UIOS) model, which is trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculates an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieves an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicts high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.


Subject(s)
Eye Abnormalities , Retinal Diseases , Humans , Artificial Intelligence , Algorithms , Uncertainty , Retina/diagnostic imaging , Fundus Oculi , Retinal Diseases/diagnostic imaging
8.
Percept Mot Skills ; 130(4): 1687-1713, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37284745

ABSTRACT

Based on the role of the high temporal sensitivity of the auditory modality and the advantage of audio-visual integration in motion perception and anticipation, we investigated the effect of audio-visual information on landing perception in badminton through two experiments; and we explored the regulatory role of attention load. In this study, experienced badminton players were asked to predict the landing position of the shuttle under the conditions of video (visual) or audio-video (audio-visual) presentation. We manipulated flight information or attention load. The results of Experiment 1 showed that, whether the visual information was rich or not, that is, whether or not it contained the early flight trajectory, the addition of auditory information played a promoting role. The results of Experiment 2 showed that attention load regulated the facilitation of multi-modal integration on landing perception. The facilitation of audio-visual information was impaired under high load, meaning that audio-visual integration tended to be guided by attention from top to bottom. The results support the superiority effect of multi-modal integration, suggesting that adding auditory perception training to sports training could significantly improve athletes' performance.


Subject(s)
Motion Perception , Racquet Sports , Humans , Visual Perception/physiology , Motion Perception/physiology , Auditory Perception/physiology , Acoustic Stimulation
9.
Front Plant Sci ; 14: 1189926, 2023.
Article in English | MEDLINE | ID: mdl-37342136

ABSTRACT

Lesion-mimic mutants (LMM) spontaneously produce necrotic spots, a process not affected by environmental stress or pathogen infection. In this study, we identified a LMM, lesion mimic mutant 8 (lmm8) in rice (Oryza sativa). The lmm8 mutant produces brown and off-white lesions on its leaves during the second- and third-leaf stages. The lesion mimic phenotype of the lmm8 mutant was enhanced by light. At the mature stage, lmm8 mutant are shorter and exhibit inferior agronomic traits than the wild type. Contents of photosynthetic pigments and chloroplast fluorescence were significantly reduced in lmm8 leaves, along with increased production of reactive oxygen species and programmed cell death compared to the wild type. The mutated gene was identified as LMM8 (LOC_Os01g18320) by map-based cloning. A point mutation occurred in LMM8, causing a Leu to Arg mutation of the 146th amino acid of LMM8. It is an allele of SPRL1, encoding a protoporphyrinogen IX oxidase (PPOX) located in chloroplasts and involved in the biosynthesis of tetrapyrrole in chloroplasts. The lmm8 mutant showed enhanced resistance and broad-spectrum resistance. Together, our results demonstrate the importance of rice LMM8 protein in defense responses and plant growth in rice, and provides theoretical support for resistance breeding to improve rice yield.

10.
IEEE Trans Image Process ; 32: 3226-3237, 2023.
Article in English | MEDLINE | ID: mdl-37256801

ABSTRACT

Transformer-based architectures start to emerge in single image super resolution (SISR) and have achieved promising performance. However, most existing vision Transformer-based SISR methods still have two shortcomings: (1) they divide images into the same number of patches with a fixed size, which may not be optimal for restoring patches with different levels of texture richness; and (2) their position encodings treat all input tokens equally and hence, neglect the dependencies among them. This paper presents a HIPA, which stands for a novel Transformer architecture that progressively recovers the high resolution image using a hierarchical patch partition. Specifically, we build a cascaded model that processes an input image in multiple stages, where we start with tokens with small patch sizes and gradually merge them to form the full resolution. Such a hierarchical patch mechanism not only explicitly enables feature aggregation at multiple resolutions but also adaptively learns patch-aware features for different image regions, e.g., using a smaller patch for areas with fine details and a larger patch for textureless regions. Meanwhile, a new attention-based position encoding scheme for Transformer is proposed to let the network focus on which tokens should be paid more attention by assigning different weights to different tokens, which is the first time to our best knowledge. Furthermore, we also propose a multi-receptive field attention module to enlarge the convolution receptive field from different branches. The experimental results on several public datasets demonstrate the superior performance of the proposed HIPA over previous methods quantitatively and qualitatively. We will share our code and models when the paper is accepted.

11.
Article in English | MEDLINE | ID: mdl-37030759

ABSTRACT

This paper proposes a new glass segmentation method utilizing paired RGB and thermal images. Due to the large difference between the transmission property of visible light and that of the thermal energy through the glass where most glass is transparent to the visible light but opaque to thermal energy, glass regions of a scene are made more distinguishable with a pair of RGB and thermal images than solely with an RGB image. To exploit such a unique property, we propose a neural network architecture that effectively combines an RGB-thermal image pair with a new multi-modal fusion module based on attention, and integrate CNN and transformer to extract local features and non-local dependencies, respectively. As well, we have collected a new dataset containing 5551 RGB-thermal image pairs with ground-truth segmentation annotations. The qualitative and quantitative evaluations demonstrate the effectiveness of the proposed approach on fusing RGB and thermal data for glass segmentation. Our code and data are available at https://github.com/Dong-Huo/RGB-T-Glass-Segmentation.

12.
Biomed Pharmacother ; 161: 114462, 2023 May.
Article in English | MEDLINE | ID: mdl-36933380

ABSTRACT

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of ß-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM.


Subject(s)
Brain Neoplasms , Furocoumarins , Glioblastoma , Animals , Mice , Humans , Glioblastoma/pathology , Mice, Nude , Cell Proliferation , Mice, Inbred C57BL , Signal Transduction , Furocoumarins/pharmacology , Furocoumarins/therapeutic use , Cell Line, Tumor , Brain Neoplasms/pathology , Xenograft Model Antitumor Assays
13.
Nat Mach Intell ; 5(7): 799-810, 2023 Jul.
Article in English | MEDLINE | ID: mdl-38706981

ABSTRACT

Medical artificial intelligence (AI) has tremendous potential to advance healthcare by supporting and contributing to the evidence-based practice of medicine, personalizing patient treatment, reducing costs, and improving both healthcare provider and patient experience. Unlocking this potential requires systematic, quantitative evaluation of the performance of medical AI models on large-scale, heterogeneous data capturing diverse patient populations. Here, to meet this need, we introduce MedPerf, an open platform for benchmarking AI models in the medical domain. MedPerf focuses on enabling federated evaluation of AI models, by securely distributing them to different facilities, such as healthcare organizations. This process of bringing the model to the data empowers each facility to assess and verify the performance of AI models in an efficient and human-supervised process, while prioritizing privacy. We describe the current challenges healthcare and AI communities face, the need for an open platform, the design philosophy of MedPerf, its current implementation status and real-world deployment, our roadmap and, importantly, the use of MedPerf with multiple international institutions within cloud-based technology and on-premises scenarios. Finally, we welcome new contributions by researchers and organizations to further strengthen MedPerf as an open benchmarking platform.

14.
Sci Rep ; 12(1): 17623, 2022 10 21.
Article in English | MEDLINE | ID: mdl-36271276

ABSTRACT

Sex differences in a variety of psychological characteristics are well-documented, with substantial research focused on factors that affect their magnitude and causes. Particular attention has focused on mental rotation, a measure of spatial cognition, and on activity interests. We studied whether sex differences in visual perception-luminance contrast thresholds and motion duration thresholds-contribute to sex differences in mental rotation and interest in male-typed activities. We confirmed sex differences in vision, mental rotation, and activity interests in a sample of 132 college students. In novel findings, we showed that vision correlated with mental rotation performance in women, that vision was a better predictor of individual differences in mental rotation than sex, and that contrast thresholds correlated with women's interest in male-typed activities. These results suggest that sex differences in spatial cognition and activity interests may have their roots in basic perceptual processes.


Subject(s)
Sex Characteristics , Space Perception , Female , Male , Humans , Cognition , Visual Perception , Attention , Sex Factors
15.
Front Psychol ; 13: 730820, 2022.
Article in English | MEDLINE | ID: mdl-35832905

ABSTRACT

Previous researchers have found that head-down bed rest (HDBR) will affect the emotional state of individuals, and negative emotions such as anxiety are closely related to attention bias. The present study adopted the dot-probe task to evaluate the effects of 15-days of -6° HDBR on the attention bias of threatening stimulus in 17 young men, which was completed before (Pre-HDBR), during (HDBR-1, HDBR-8, HDBR-15), after (Post-HDBR) the bed rest. In addition, self-report inventories (State Anxiety Inventory, SAI; Positive Affect and Negative Affect Scale, PANAS) were conducted to record emotional changes. The results showed that the participants' negative affect scores on HDBR-8 were significantly lower than the HDBR-1 in PANAS while there was no significant difference on positive affect scores and anxiety scores in SAI. And the results showed that at the Pre-HDBR, HDBT-1, HDBR-15, Post-HDBR, the response speed to threatening stimulus was faster than neutral stimulus, but no statistical significance. However, reaction time of threatening stimulus is significantly longer than neutral stimulus in the HDBR-8, indicating that HDBR may have an effect on the participants' attention bias, and this effect is manifested as attention avoidance.

17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(2): 113-120, 2022 Feb.
Article in Chinese | MEDLINE | ID: mdl-35387714

ABSTRACT

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.


Subject(s)
Gastrointestinal Diseases , Sepsis , China , Consensus , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/therapy , Humans , Medicine, Chinese Traditional , Sepsis/complications , Sepsis/therapy
18.
Allergol Immunopathol (Madr) ; 50(2): 7-15, 2022.
Article in English | MEDLINE | ID: mdl-35257540

ABSTRACT

BACKGROUND: As a systemic inflammatory reaction, sepsis is associated with various organ dysfunctions. The capillary leakage and the imbalance between T helper 17 and regulatory T (Th17/Treg) cells are associated with sepsis-induced lung injury. Taxifolin (TXL) has been found to play a vital role in regulating this diverse disease. However, the detailed functioning and mechanism of TXL in regulating sepsis-induced lung capillary leak remain elusive. METHODS: Balb/c mice were used to establish sepsis-induced lung injury model through administration of lipopolysaccharide (LPS). The structure of lung tissues was observed by using hematoxylin & eosin staining. Protein level and total cells in bronchoalveolar lavage fluid (BALF) were measured by bicinchoninic acid (BCA) protein assay kit and hematimetry assay, respectively. Quantitative real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were employed to detect the level of inflammatory cytokines. The content of Th17 and Treg cells were measured by flow cytometry analysis. Western blot assay was used to determine the protein level of retinoid-related orphan receptor-γt (RORγt), Forkhead box P3 (Foxp3), Janus kinase 2 (JAK2), phospho(p)-JAK2, signal transducer and activator of transcription 3 (STAT3), and phospho(p)-STAT3. RESULTS: Taxifolin effectively prolonged the survival period of sepsis mice and alleviated LPS-induced lung injury in a dose-dependent manner. Moreover, TXL reduced LPS-induced increase in protein levels and T cell content in BALF, and effectively restored the wet:dry ratio of lung tissue and tissue permeability. Treating with TXL notably inhibited the production of pro-inflammatory cytokines induced by sepsis and influenced the balance between Th17 and Treg cells. Furthermore, TXL treatment suppressed the activation of JAK/STAT3 signaling pathway in a dose-dependent manner. CONCLUSION: Our findings revealed that TXL alleviated sepsis-induced capillary leak in the lungs of mice by regulating JAK/STAT3 signaling pathway.


Subject(s)
STAT3 Transcription Factor , Sepsis , Animals , Disease Models, Animal , Humans , Lung/metabolism , Mice , Quercetin/analogs & derivatives , Sepsis/complications , Sepsis/drug therapy , Th17 Cells
19.
Neurotox Res ; 40(1): 267-275, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34981455

ABSTRACT

Disruption of the blood-brain barrier (BBB) is an important hallmark of sepsis-associated encephalopathy (SAE). Selegiline, a selective and irreversible inhibitor of monoamine oxidase type B, has been applied for the treatment of nervous disorders. In this study, we aimed to investigate whether selegiline has a protective capacity in the impairment of the BBB in both in vivo and in vitro experiments. In a sepsis mouse model, administration of selegiline ameliorated lipopolysaccharide (LPS)-induced impairment of BBB integrity. Additionally, treatment with selegiline increased the expression of the tight junction protein junctional adhesion molecule A (JAM-A) against LPS. Also, we found that selegiline inhibited the production of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. In an in vitro experimental model, bEnd.3 brain endothelial cells were exposed to LPS. Results indicate that stimulation with LPS significantly increased the permeability of bEnd.3 cells and reduced the expression of JAM-A, both of which were rescued by treatment with selegiline. Additionally, selegiline prevented the activation of the NF-κB/MLCK/p-MLC signaling pathway in LPS-challenged bEnd.3 cells. These results indicate that selegiline exerted a protective effect on BBB dysfunction, which might be attributed to the inhibition of the NF-κB/MLCK/p-MLC signaling pathway. These findings provide a basis for further research into the neuroprotective mechanism of selegiline.


Subject(s)
Lipopolysaccharides , NF-kappa B , Animals , Blood-Brain Barrier , Endothelial Cells , Lipopolysaccharides/toxicity , Mice , NF-kappa B/metabolism , Selegiline/metabolism , Selegiline/pharmacology , Signal Transduction
20.
Bioengineered ; 13(2): 3680-3693, 2022 02.
Article in English | MEDLINE | ID: mdl-35081868

ABSTRACT

Sepsis is mainly characterized by severe inflammation triggered by infection, and sepsis-associated encephalopathy (SAE) is defined as brain damage caused by sepsis. Disruption of the blood-brain barrier (BBB) triggered by injured brain microvascular endothelial cells (BMECs) and damaged tight junction (TJ) structure is closely associated with the pathogenesis of SAE. The present research proposed to evaluate the potential therapeutic effects of Mirtazapine, a central presynaptic α2 receptor antagonist, on LPS-induced BBB disruption. The mice were administered with normal saline and 10 mg/kg Mirtazapine for 8 consecutive days, and from day 6, the experiment group of mice received LPS for 2 days to induce SAE. We found that the increased BBB permeability, elevated concentrations of inflammatory factors in brain tissues, and downregulated zonula occludens -1 (ZO-1) were observed in LPS-stimulated mice, all of which were reversed by 10 mg/kg Mirtazapine. In the in vitro assay, bEnd.3 brain endothelial cells were treated with 1 µM LPS in the absence or presence of Mirtazapine (25, 50 µM). We found that LPS-treated cells had significantly declined transendothelial electrical resistance (TEER), increased monolayer permeability, elevated production of inflammatory factors, and downregulated ZO-1. However, 25 and 50 µM Mirtazapine ameliorated all these LPS- induced aberrations. Mirtazapine also mitigated the decreased level of NF-E2-related factor 2 (Nrf2) in LPS-challenged endothelial cells. The protective effect of Mirtazapine on endothelial permeability against LPS was significantly abolished by the knockdown of Nrf2. Collectively, we concluded that Mirtazapine exerted protective effects on LPS-induced endothelial cells hyperpermeability by upregulating Nrf2.


Subject(s)
Blood-Brain Barrier/metabolism , Capillary Permeability/drug effects , Lipopolysaccharides/toxicity , Mirtazapine/pharmacology , Sepsis-Associated Encephalopathy , Tight Junctions/metabolism , Animals , Male , Mice , Sepsis-Associated Encephalopathy/chemically induced , Sepsis-Associated Encephalopathy/drug therapy , Sepsis-Associated Encephalopathy/metabolism
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