Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 214
Filter
1.
Quant Imaging Med Surg ; 14(6): 3901-3913, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38846285

ABSTRACT

Background: Previous studies have confirmed that malignant transformation of dysplastic nodule (DN) into hepatocellular carcinoma (HCC) is accompanied by reduction of iron content in nodules. This pathological abnormality can serve as the basis for magnetic resonance imaging (MRI). This study was designed to identify the feasibility of iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantitative (IDEAL-IQ) measurement to distinguish early hepatocellular carcinoma (eHCC) from DN. Methods: We reviewed MRI studies of 35 eHCC and 23 DN lesions (46 participants with 58 lesions total, 37 males, 9 females, 31-80 years old). The exams include IDEAL-IQ sequence and 3.0T MR conventional scan [including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and Gadopentic acid (Gd-GDPA)-enhanced]. Then, 3 readers independently diagnosed eHCC, DN, or were unable to distinguish eHCC from DN using conventional MRI (CMRI), and then assessed R2* value of nodules [R2* value represents the nodule iron content (NIC)] and R2* value of liver background [R2* value represents the liver background iron content (LBIC)] with IDEAL-IQ. Statistical analysis was conducted using the t-test for comparison of means, the Mann-Whitney test for comparison of medians, the chi-square test for comparison of frequencies, and diagnostic efficacy was evaluated by using receiver operating characteristic (ROC) curve. Results: This study evaluated 35 eHCC participants (17 males, 6 females, 34-81 years old, nodule size: 10.5-27.6 mm, median 18.0 mm) and 23 DN participants (20 males, 3 females, 31-76 years old, nodule size: 16.30±4.095 mm). The NIC and ratio of NIC to LIBC (NIC/LBIC) of the eHCC group (35.926±12.806 sec-1, 0.327±0.107) was lower than that of the DN group (176.635±87.686 sec-1, 1.799±0.629) (P<0.001). Using NIC and NIC/LBIC to distinguish eHCC from DN, the true positive/false positive rates were 91.3%/94.3% and 87.0%/97.1%, respectively. The rates of CMRI, NIC and NIC/LBIC in diagnosis of eHCC were 77.1%, and 94.3%, 97.1%, respectively, and those of DN were 65.2%, 91.3%, and 87.0%, respectively. The diagnosis rate of eHCC and DN by CMRI was lower than that of NIC and NIC/LBIC (eHCC: P=0.03, 0.04, DN: P=0.02, 0.04). Conclusions: Using IDEAL-IQ measurement can distinguish DN from eHCC.

2.
iScience ; 27(5): 109793, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38736547

ABSTRACT

Vesicular fusion plays a pivotal role in cellular processes, involving stages like vesicle trafficking, fusion pore formation, content release, and membrane integration or separation. This dynamic process is regulated by a complex interplay of protein assemblies, osmotic forces, and membrane tension, which together maintain a mechanical equilibrium within the cell. Changes in cellular mechanics or external pressures prompt adjustments in this equilibrium, highlighting the system's adaptability. This review delves into the synergy between intracellular proteins, structural components, and external forces in facilitating vesicular fusion and release. It also explores how cells respond to mechanical stress, maintaining equilibrium and offering insights into vesicle fusion mechanisms and the development of neurological disorders.

3.
J Intensive Care Soc ; 25(2): 140-146, 2024 May.
Article in English | MEDLINE | ID: mdl-38737310

ABSTRACT

Background: Venous thromboembolism (VTE) in critically ill patients has been well-studied in Western countries. Many studies have developed risk assessments and established pharmacological protocols to prevent deep venous thrombosis (DVT). However, the DVT rate and need for pharmacologic VTE prophylaxis in critically ill Taiwanese patients are limited. This study aimed to prospectively determine the DVT incidence, risk factors, and outcomes in critically ill Taiwanese patients who do not receive pharmacologic VTE prophylaxis. Methods: We conducted a prospective study in a surgical intensive care unit (SICU) of a tertiary academic medical center in Taiwan. Adult patients admitted to SICU from March 2021 to June 2022 received proximal lower extremities DVT surveillance with venous duplex ultrasound. No patient received pharmacologic VTE prophylaxis. The outcomes were the incidence and risk factors of DVT. Results: Among 501 enrolled SICU patients, 21 patients (4.2%) were diagnosed with proximal lower extremities DVT. In a multivariate regression analysis, hypoalbuminemia (odd ratio (OR) = 6.061, 95% confidence interval (CI): 1.067-34.421), femoral central venous catheter (OR = 4.515, 95% CI: 1.547-13.174), ICU stays more than 10 days (OR = 4.017, 95% CI: 1.270-12.707), and swollen leg (OR = 3.427, 95% CI: 1.075-10.930) were independent risk factors for DVT. In addition, patients with proximal lower extremities DVT have more extended ventilator days (p = 0.045) and ICU stays (p = 0.044). Conclusion: Our findings indicate critically ill Taiwanese patients have a higher incidence of DVT than results from prior retrospective studies in the Asian population. Physicians who care for this population should consider the specific risk factors for DVT and prescribe pharmacologic prophylaxis in high-risk groups.

5.
Horm Metab Res ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772392

ABSTRACT

The aim of the study was to assess the association between lipoprotein(a) [Lp(a)] concentration and incident type 2 diabetes. A meta-analysis of qualified studies on the relationship of low levels of Lp(a) concentration with incident type 2 diabetes was conducted. PubMed and Cochrane libraries were searched for randomized controlled trials containing data on events. Seven randomized trials with 227178 subjects were included in this analysis. We found an inverse association of the levels of Lp(a) concentration with risk of type 2 diabetes with approximately 37% lower relative risk in the group with the highest concentration compared with group with the lowest concentration. The current available evidence from prospective studies suggests that there is an inverse association between the levels of Lp(a) concentration and risk of type 2 diabetes, with a higher risk of type 2 diabetes at low levels of Lp(a) concentration. Therefore, we believe that the low levels of Lp(a) concentration is an independent predictor of incident type 2 diabetes.

6.
Elife ; 132024 May 03.
Article in English | MEDLINE | ID: mdl-38700136

ABSTRACT

Cholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout of Cck gene (Cck-/-) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation upon high-frequency stimulation in the motor cortex of Cck-/- mice, indicating a possible association between motor learning deficiency and neuroplasticity in the motor cortex. In vivo calcium imaging demonstrated that the deficiency of CCK signaling disrupted the refinement of population neuronal activity in the motor cortex during motor skill training. Anatomical tracing revealed direct projections from CCK-expressing neurons in the rhinal cortex to the motor cortex. Inactivation of the CCK neurons in the rhinal cortex that project to the motor cortex bilaterally using chemogenetic methods significantly suppressed motor learning, and intraperitoneal application of CCK4, a tetrapeptide CCK agonist, rescued the motor learning deficits of Cck-/- mice. In summary, our results suggest that CCK, which could be provided from the rhinal cortex, may surpport motor skill learning by modulating neuroplasticity in the motor cortex.


Subject(s)
Cholecystokinin , Learning , Mice, Knockout , Motor Cortex , Motor Skills , Neuronal Plasticity , Animals , Male , Mice , Cholecystokinin/metabolism , Learning/physiology , Motor Cortex/physiology , Motor Cortex/metabolism , Motor Cortex/drug effects , Motor Skills/physiology , Neuronal Plasticity/physiology , Neuronal Plasticity/drug effects
7.
Nat Commun ; 15(1): 4598, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816394

ABSTRACT

Fluorescence microscopy has undergone rapid advancements, offering unprecedented visualization of biological events and shedding light on the intricate mechanisms governing living organisms. However, the exploration of rapid biological dynamics still poses a significant challenge due to the limitations of current digital camera architectures and the inherent compromise between imaging speed and other capabilities. Here, we introduce sHAPR, a high-speed acquisition technique that leverages the operating principles of sCMOS cameras to capture fast cellular and subcellular processes. sHAPR harnesses custom fiber optics to convert microscopy images into one-dimensional recordings, enabling acquisition at the maximum camera readout rate, typically between 25 and 250 kHz. We have demonstrated the utility of sHAPR with a variety of phantom and dynamic systems, including high-throughput flow cytometry, cardiomyocyte contraction, and neuronal calcium waves, using a standard epi-fluorescence microscope. sHAPR is highly adaptable and can be integrated into existing microscopy systems without requiring extensive platform modifications. This method pushes the boundaries of current fluorescence imaging capabilities, opening up new avenues for investigating high-speed biological phenomena.


Subject(s)
Microscopy, Fluorescence , Optical Imaging , Microscopy, Fluorescence/methods , Animals , Optical Imaging/methods , Optical Imaging/instrumentation , Humans , Myocytes, Cardiac/cytology , Phantoms, Imaging , Flow Cytometry/methods , Neurons , Image Processing, Computer-Assisted/methods
8.
Materials (Basel) ; 17(10)2024 May 17.
Article in English | MEDLINE | ID: mdl-38793475

ABSTRACT

The hot deformation behavior and mechanism of Ti65 alloy with a bimodal microstructure were investigated by isothermal compression experiments conducted on the Thermecmastor-Z simulator equipment at temperatures ranging from 950 to 1110 °C and strain rates ranging from 0.01 to 10.0 s-1. The Arrhenius constitutive model, based on strain compensation, and Grey Wolf optimization-neural network with back propagation model (GWO-BP), were both established. The differences between the experimental and predicted value of flow stress were compared and analyzed using the two models. The results show that the prediction accuracy of GWO-BP in the two-phase region is higher than that of Arrhenius model. In the single-phase region, both methods demonstrated high prediction accuracy. Compared to the single-phase region, the flow stress of Ti65 alloy shows a higher degree of softening in the two-phase region. During deformation in the two-phase region, the initial lamellar α phase transformed from a kinked and elongated morphology to a globularized topography as the strain rate decreased. Boundary-splitting was the primary mechanism leading to the spheroidization process. The degree of recrystallization increased with the increase in strain rate during the deformation in the single-phase region, while dynamic recovery and strain-induced grain boundary migration were the main deformation mechanisms at a lower strain rate. Discontinuous dynamic recrystallization may be the dominant recrystallization mechanism under a high strain rate of 10 s-1.

9.
Development ; 151(7)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38602507

ABSTRACT

CFAP58 is a testis-enriched gene that plays an important role in the sperm flagellogenesis of humans and mice. However, the effect of CFAP58 on bull semen quality and the underlying molecular mechanisms involved in spermatogenesis remain unknown. Here, we identified two single-nucleotide polymorphisms (rs110610797, A>G and rs133760846, G>T) and one indel (g.-1811_ g.-1810 ins147bp) in the promoter of CFAP58 that were significantly associated with semen quality of bulls, including sperm deformity rate and ejaculate volume. Moreover, by generating gene knockout mice, we found for the first time that the loss of Cfap58 not only causes severe defects in the sperm tail, but also affects the manchette structure, resulting in abnormal sperm head shaping. Cfap58 deficiency causes an increase in spermatozoa apoptosis. Further experiments confirmed that CFAP58 interacts with IFT88 and CCDC42. Moreover, it may be a transported cargo protein that plays a role in stabilizing other cargo proteins, such as CCDC42, in the intra-manchette transport/intra-flagellar transport pathway. Collectively, our findings reveal that CFAP58 is required for spermatogenesis and provide genetic markers for evaluating semen quality in cattle.


Subject(s)
Semen Analysis , Semen , Humans , Cattle , Male , Animals , Mice , Sperm Head , Spermatozoa , Mice, Knockout
10.
Sci Rep ; 14(1): 8619, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38616200

ABSTRACT

The joints are existing throughout the underground rock mass. It is of great significance to investigate the shear performance of the rock mass to maintain the stability of the underground structure. In this study, we conducted orthogonal tests to determine the proportion of rock-like materials, and used JRC curves to make specimen molds and then prepare the specimens. We conducted straight shear tests and uniaxial compression tests to determine the various mechanical parameters of the rock-like materials. Next, we carried out the compression and shear tests to investigate the shear characteristics of the specimens, and study the damage pattern and shear strength of the jointed rock mass under different confining pressures and roughness levels. The mesoscopic displacements in the shear process of joints were analyzed by using ABAQUS. The test results show that the effect of the confining pressure on the shear strength of the joint plane is relatively obvious, and a larger confining pressure indicates a larger shear strength. The effects of different joint plane roughness and shear rated on the shear characteristics of the joint plane are also significant. The mesoscopic displacement difference inside the joint plane with higher roughness is relatively large, and the stress concentration phenomenon is obvious and lasts longer, which leads to the faster destruction of the specimen with higher roughness and the higher destruction degree. Therefore, we suggest that the priority should be given to the reinforcement of jointed rock mass with high roughness during the construction to prevent sudden destabilization and failure.

11.
Comput Biol Med ; 174: 108379, 2024 May.
Article in English | MEDLINE | ID: mdl-38631115

ABSTRACT

OBJECTIVE: Blurry medical images affect the accuracy and efficiency of multimodal image registration, whose existing methods require further improvement. METHODS: We propose an edge-based similarity registration method optimised for multimodal medical images, especially bone images, by a balance optimiser. First, we use a GPU (graphics processing unit) rendering simulation to convert computed tomography data into digitally reconstructed radiographs. Second, we introduce the improved cascaded edge network (ICENet), a convolutional neural network that extracts edge information of blurry medical images. Then, the bilateral Gaussian-weighted similarity of pairs of X-ray images and digitally reconstructed radiographs is measured. The a balanced optimiser is iteratively applied to finally estimate the best pose to perform image registration. RESULTS: Experimental results show that, on average, the proposed method with ICENet outperforms other edge detection networks by 20%, 12%, 18.83%, and 11.93% in the overall Dice similarity, overall intersection over union, peak signal-to-noise ratio, and structural similarity index, respectively, with a registration success rate up to 90% and average reduction of 220% in registration time. CONCLUSION: The proposed method with ICENet can achieve a high registration success rate even for blurry medical images, and its efficiency and robustness are higher than those of existing methods. SIGNIFICANCE: Our proposal may be suitable for supporting medical diagnosis, radiation therapy, image-guided surgery, and other clinical applications.


Subject(s)
Bone and Bones , Neural Networks, Computer , Tomography, X-Ray Computed , Humans , Bone and Bones/diagnostic imaging , Tomography, X-Ray Computed/methods , Algorithms , Multimodal Imaging/methods , Image Processing, Computer-Assisted/methods
12.
J Org Chem ; 89(10): 7233-7242, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38666895

ABSTRACT

A self-catalyzed, visible-light-induced, directly selective C3-H aroylation of quinoxalin-2(1H)-ones via energy transfer and hydrogen atom transfer (HAT) catalysis has been developed. The method is highly atom-economical, eco-friendly, and easy to handle. Notably, the reaction proceeded efficiently with ambient air as the sole oxidant at room temperature.

13.
BMC Psychol ; 12(1): 176, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38539260

ABSTRACT

The study aims to investigate the precise processes by which the advancement of physical education and technological progress leads to ecological conservation efforts within China's distinctive socio-cultural and economic framework. Acknowledging the pivotal role that economic advancement plays in a nation's environmental sustainability, this research utilizes cross-sectional quantitative data gathered using a five-point Likert scale survey. The sample size included 503 undergraduate students from Zhengzhou, China, and structural equation modeling was utilized to analyze the data. The study investigates how technology progress influences the relationship between compatibility, environmental sustainability, and the relative benefits of physical education. It fills the gap in the literature by illuminating how technical innovation and advanced physical education development contribute to China's pursuit of a sustainable environment. The findings emphasize the critical significance of higher physical education in fostering environmental sustainability. Furthermore, the research indicates that students participating in more rigorous physical education programs tend to possess a more well-rounded and mature mindset. This mindset is essential for healthy and long-lasting mental development, motivating individuals to critically consider environmental sustainability. The study provides valuable theoretical and practical insights that can be applied to enhance environmental sustainability in the country.


Subject(s)
Inventions , Physical Education and Training , Humans , Cross-Sectional Studies , China
14.
ACS Appl Mater Interfaces ; 16(13): 16309-16316, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38507679

ABSTRACT

Constructing highly active and noble metal-free electrocatalysts is significant for the anodic oxygen evolution reaction (OER). Herein, uniform carbon-coated CoP nanospheres (CoP/C) are developed by a direct impregnation coupling phosphorization approach. Importantly, CoP/C only takes a small overpotential of 230 mV at the current density of 10 mA cm-2 and displays a Tafel slope of 56.87 mV dec-1. Furthermore, the intrinsic activity of CoP/C is 21.44 times better than that of commercial RuO2 under an overpotential of 260 mV. In situ Raman spectroscopy studies revealed that a large number of generated Co-O and Co-OH species could facilitate the *OH adsorption, effectively accelerating the reaction kinetics. Meanwhile, the carbon shell with a large number of mesoporous pores acts as the chainmail of CoP, which could improve the active surface area of the catalyst and prevent the Co sites from oxidative dissolution. This work provides a facile and effective reference for the development of highly active and stable OER catalysts.

15.
Chin Med Sci J ; 39(1): 9-18, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38426412

ABSTRACT

Objective Aberrant expression of ATP binding cassette subfamily B member 1 (ABCB1) plays a key role in several cancers. However, influence of G protein coupled receptor family C group 5 type A (GPRC5A)-regulated ABCB1 expression on lung adenocarcinoma proliferation remains unclear. Therefore, this study investigated the effect of GPRC5A regulated ABCB1 expression on the proliferation of lung adenocarcinoma. Methods ABCB1 expressions in lung adenocarcinoma cell lines, human lung adenocarcinoma tissues, and tracheal epithelial cells and lung tissues of GPRC5A knockout mice and wild-type mice were analyzed with RT-PCR, Western blot, or immunohistochemical analysis. Cell counting kit-8 assay was performed to analyze the sensitivity of tracheal epithelial cells from GPRC5A knockout mice to chemotherapeutic agents. Subcutaneous tumor formation assay was performed to confirm whether down-regulation of ABCB1 could inhibit the proliferation of lung adenocarcinoma in vivo. To verify the potential regulatory relationship between GPRC5A and ABCB1, immunofluorescence and immunoprecipitation assays were performed. Results ABCB1 expression was up-regulated in lung adenocarcinoma cell lines and human lung adenocarcinoma tissues. ABCB1 expression in the tracheal epithelial cells and lung tissues of GPRC5Adeficient mice was higher than that in the wild type mice. Tracheal epithelial cells of GPRC5A knockout mice were much more sensitive to tariquidar and doxorubicin than those of GPRC5A wild type mice. Accordingly, 28 days after injection of the transplanted cells, the volume and weight of lung tumor in ABCB1knockout cell-transplanted GPRC5A-/-C57BL/6 mice were significantly smaller than those in wild type cell-transplanted mice (P= 0.0043, P= 0.0060). Furthermore, immunofluorescence and immunoprecipitation assays showed that GPRC5A regulated ABCB1 expression by direct binding.Conclusion GPRC5A reduces lung adenocarcinoma proliferation via inhibiting ABCB1 expression. The pathway by which GPRC5A regulates ABCB1 expression needs to be investigated.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Animals , Humans , Mice , Adenocarcinoma of Lung/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Cell Line, Tumor , Cell Proliferation , Lung Neoplasms/pathology , Mice, Inbred C57BL , Mice, Knockout , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism
16.
Nat Commun ; 15(1): 1975, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38438356

ABSTRACT

Imaging flow cytometry (IFC) combines flow cytometry and fluorescence microscopy to enable high-throughput, multiparametric single-cell analysis with rich spatial details. However, current IFC techniques remain limited in their ability to reveal subcellular information with a high 3D resolution, throughput, sensitivity, and instrumental simplicity. In this study, we introduce a light-field flow cytometer (LFC), an IFC system capable of high-content, single-shot, and multi-color acquisition of up to 5,750 cells per second with a near-diffraction-limited resolution of 400-600 nm in all three dimensions. The LFC system integrates optical, microfluidic, and computational strategies to facilitate the volumetric visualization of various 3D subcellular characteristics through convenient access to commonly used epi-fluorescence platforms. We demonstrate the effectiveness of LFC in assaying, analyzing, and enumerating intricate subcellular morphology, function, and heterogeneity using various phantoms and biological specimens. The advancement offered by the LFC system presents a promising methodological pathway for broad cell biological and translational discoveries, with the potential for widespread adoption in biomedical research.


Subject(s)
Biological Assay , Biomedical Research , Flow Cytometry , Microfluidics , Single-Cell Analysis
17.
JMIR Form Res ; 8: e50561, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38324352

ABSTRACT

BACKGROUND: Tumor immunotherapy is an innovative treatment today, but there are limited data on the quality of immunotherapy information on social networks. Dissemination of misinformation through the internet is a major social issue. OBJECTIVE: Our objective was to characterize the quality of information and presence of misinformation about tumor immunotherapy on internet-based videos commonly used by the Chinese population. METHODS: Using the keyword "tumor immunotherapy" in Chinese, we searched TikTok, Tencent, iQIYI, and BiliBili on March 5, 2022. We reviewed the 118 screened videos using the Patient Education Materials Assessment Tool-a validated instrument to collect consumer health information. DISCERN quality criteria and the JAMA (Journal of the American Medical Association) Benchmark Criteria were used for assessing the quality and reliability of the health information. The videos' content was also evaluated. RESULTS: The 118 videos about tumor immunotherapy were mostly uploaded by channels dedicated to lectures, health-related animations, and interviews; their median length was 5 minutes, and 79% of them were published in and after 2018. The median understandability and actionability of the videos were 71% and 71%, respectively. However, the quality of information was moderate to poor on the validated DISCERN and JAMA assessments. Only 12 videos contained misinformation (score of >1 out of 5). Videos with a doctor (lectures and interviews) not only were significantly less likely to contain misinformation but also had better quality and a greater forwarding number. Moreover, the results showed that more than half of the videos contain little or no content on the risk factors and management of tumor immunotherapy. Overall, over half of the videos had some or more information on the definition, symptoms, evaluation, and outcomes of tumor immunotherapy. CONCLUSIONS: Although the quality of immunotherapy information on internet-based videos commonly used by Chinese people is moderate, these videos have less misinformation and better content. Caution must be exercised when using these videos as a source of tumor immunotherapy-related information.

18.
Viruses ; 16(2)2024 01 25.
Article in English | MEDLINE | ID: mdl-38399960

ABSTRACT

Over the last three years, the pandemic of COVID-19 has had a significant impact on people's lives and the global economy. The incessant emergence of variant strains has compounded the challenges associated with the management of COVID-19. As the predominant variant from late 2021 to the present, Omicron and its sublineages, through continuous evolution, have demonstrated iterative viral fitness. The comprehensive elucidation of the biological implications that catalyzed this evolution remains incomplete. In accordance with extant research evidence, we provide a comprehensive review of subvariants of Omicron, delineating alterations in immune evasion, cellular infectivity, and the cross-species transmission potential. This review seeks to clarify the underpinnings of biology within the evolution of SARS-CoV-2, thereby providing a foundation for strategic considerations in the post-pandemic era of COVID-19.


Subject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , Exercise , Immune Evasion , Spike Glycoprotein, Coronavirus
19.
Mol Neurobiol ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38376762

ABSTRACT

Ischemia-reperfusion (I/R) injury is a key influencing factor in the outcome of stroke. Inflammatory response, oxidative stress, and neuronal apoptosis are among the main factors that affect the progression of I/R injury. Farrerol (FAR) is a natural compound that can effectively inhibit the inflammatory response and oxidative stress. However, the role of FAR in cerebral I/R injury remains unknown. In this study, we found that FAR reduced brain injury and neuronal viability after cerebral I/R injury. Meanwhile, administration of FAR also reduced the inflammatory response of microglia after brain injury. Mechanistically, FAR treatment directly reduced neuronal death after oxygen glucose deprivation/re-oxygenation (OGD/R) through enhancing cAMP-response element binding protein (CREB) activation to increase the expression of downstream neurotrophic factors and anti-apoptotic genes. Moreover, FAR decreased the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, inhibited microglia activation, and reduced the production of inflammatory cytokines in microglia after OGD/R treatment or LPS stimulation. The compromised inflammatory response by FAR directly promoted the survival of neurons after OGD/R. In conclusion, FAR exerted a protective effect on cerebral I/R injury by directly decreasing neuronal death through upregulating CREB expression and attenuating neuroinflammation. Therefore, FAR could be a potentially effective drug for the treatment of cerebral I/R injury.

20.
Aging (Albany NY) ; 16(4): 3200-3230, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38349858

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) encompasses a diverse group of disorders characterized by chronic inflammation and fibrosis of the pulmonary interstitium. Three ILDs, namely idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease-associated ILD (CTD-ILD), exhibit similar progressive fibrosis phenotypes, yet possess distinct etiologies, encouraging us to explore their different underlying mechanisms. METHODS: Transcriptome data of fibrotic lung tissues from patients with IPF, fHP, and CTD-ILD were subjected to functional annotation, network, and pathway analyses. Additionally, we employed the xCell deconvolution algorithm to predict immune cell infiltration in patients with fibrotic ILDs and healthy controls. RESULTS: We identified a shared progressive fibrosis-related module in these diseases which was related to extracellular matrix (ECM) degradation and production and potentially regulated by the p53 family transcription factors. In IPF, neuron-related processes emerged as a critical specific mechanism in functional enrichment. In fHP, we observed that B cell signaling and immunoglobulin A (IgA) production may act as predominant processes, which was further verified by B cell infiltration and the central role of CD19 gene. In CTD-ILD, active chemokine processes were enriched, and active dendritic cells (aDCs) were predicted to infiltrate the lung tissues. CONCLUSIONS: This study revealed shared and specific molecular and cellular pathways among IPF, fHP, and CTD-ILD, providing a basis for understanding their pathogenesis and identifying potential therapeutic targets.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Humans , Transcriptome , Lung Diseases, Interstitial/genetics , Idiopathic Pulmonary Fibrosis/genetics , Fibrosis , Gene Expression Profiling
SELECTION OF CITATIONS
SEARCH DETAIL
...