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  1. Article ; Online: Linarin ameliorates ischemia-reperfusion injury by the inhibition of endoplasmic reticulum stress targeting AKR1B1.

    Zhang, Yuqian / Gao, Shenghan / Xia, Shengnan / Yang, Haiyan / Bao, Xinyu / Zhang, Qingxiu / Xu, Yun

    Brain research bulletin

    2024  Volume 207, Page(s) 110868

    Abstract: Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological ... ...

    Abstract Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological mechanisms in ischemic stroke. Linarin has been reported to have anti-inflammation, antioxidant, and anti-apoptotic effects in myocardial ischemia, osteoarthritis, and kidney disease. Whether it exerts neuroprotective functions in ischemic stroke has not been investigated. The results showed that linarin could reduce the infarct volume in cerebral ischemia animal models, improve the neurological function scores and suppress the expression of inflammatory factors mediating the NF-κB. Meanwhile, it could protect the neurons from OGD/R-induced-apoptosis, which was related to the PERK-eIF2α pathway. Our results suggested linarin could inhibit neuronal inflammation and apoptosis induced by endoplasmic reticulum stress. Furthermore, the neuroprotective effect of linarin may be related to the inhibition of AKR1B1. Our study offers new insight into protecting against ischemia-reperfusion injury by linarin treatment in stroke.
    MeSH term(s) Animals ; Signal Transduction ; Reperfusion Injury/metabolism ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Ischemic Stroke/drug therapy ; Endoplasmic Reticulum Stress ; Apoptosis ; Infarction, Middle Cerebral Artery/metabolism ; Glycosides
    Chemical Substances linarin (HBH2I685IU) ; Neuroprotective Agents ; Glycosides
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 197620-5
    ISSN 1873-2747 ; 0361-9230
    ISSN (online) 1873-2747
    ISSN 0361-9230
    DOI 10.1016/j.brainresbull.2024.110868
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    Zs.A 1243: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Arterial transit artifact as a short-term prognostic indicator in acute ischemic stroke.

    Shan, Min / Liu, Kaili / Ma, Yi / Zhang, Qingxiu / Yun, Wenwei / Zhang, Min

    BMC neurology

    2024  Volume 24, Issue 1, Page(s) 58

    Abstract: Background: Arterial transit artifact (ATA) observed on arterial spin labeling (ASL) was recently suggested to be associated with improved functional outcomes following acute ischemic stroke (AIS). AIS is a heterogeneous disease with diverse pathogenic ... ...

    Abstract Background: Arterial transit artifact (ATA) observed on arterial spin labeling (ASL) was recently suggested to be associated with improved functional outcomes following acute ischemic stroke (AIS). AIS is a heterogeneous disease with diverse pathogenic mechanisms depending on the stroke subtype. This study aimed to investigate the association between ATA and 3-month functional outcomes in AIS patients according to etiology subtypes.
    Methods: Consecutive patients with AIS were included. All patients underwent ASL MRI with postlabeling delay (PLD) of 1.5 and 2.5 s. ATA was assessed from the ASL images of both PLDs. Stroke etiologic subtypes were determined according to the modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Short-term functional outcomes were evaluated using the 3-month modified Rankin scale (mRS). Log-binomial regression was applied to analyze the association between ATA and functional outcomes at 3 months after stroke.
    Results: Ninety-eight AIS patients (62.73 ± 13.05 years; 68 men) were finally included. ATA was detected in forty-six patients and most frequently seen in the large-artery atherosclerosis (LAA) subtype (35/46). The ATA group exhibited a lower percentage of patients with mRS > 2 compared to the group without ATA (36.5% vs. 19.6%; P < 0.001). ATA was independently associated with better 3-month clinical outcomes (adjusted risk ratio, 0.35[95% CI, 0.16-0.74]) in the multivariate log-binomial regression model. After stratification by TOAST subtypes, a significant association was found between ATA and better outcomes in the LAA subtype (adjusted risk ratio, 0.20[ 95% CI, 0.05-0.72]) but not in cardioembolism and small artery occlusion (SVO) subtype.
    Conclusion: ATA is associated with better outcomes at 3 months in patients with AIS, especially in the LAA subtype, but this association attenuated in the cardioembolism and SVO subtypes.
    MeSH term(s) Male ; Humans ; Brain Ischemia/complications ; Ischemic Stroke/diagnostic imaging ; Ischemic Stroke/complications ; Prognosis ; Artifacts ; Stroke/complications ; Atherosclerosis/complications ; Arteries
    Language English
    Publishing date 2024-02-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041347-6
    ISSN 1471-2377 ; 1471-2377
    ISSN (online) 1471-2377
    ISSN 1471-2377
    DOI 10.1186/s12883-024-03560-z
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  3. Article ; Online: Correlation between Carotid Blood Flow Velocity and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients with Recent Small Subcortical Infarcts.

    Lv, Yi-Jun / Zhang, Min / Yun, Wen-Wei / Zhang, Qing-Xiu / Li, Jing-Wei

    Current neurovascular research

    2023  

    Abstract: Background: The common and internal carotid arteries are the upstream vessels of the small cerebral vessels. The relationship between hemodynamic changes in the significant cervical vessels and cerebral small vessel disease (CSVD) remains uncertain. ... ...

    Abstract Background: The common and internal carotid arteries are the upstream vessels of the small cerebral vessels. The relationship between hemodynamic changes in the significant cervical vessels and cerebral small vessel disease (CSVD) remains uncertain. This research sought to analyze the correlation between carotid blood flow velocity and the total magnetic resonance imaging (MRI) burden of CSVD in patients with recent small subcortical infarcts (RSSIs).
    Methods: Data were gathered from individuals diagnosed with RSSIs admitted to Changzhou Second People's Hospital between January 2022 and June 2023. Brain MRI was performed on every patient to determine the overall MRI burden of CSVD, along with carotid duplex ultrasound to evaluate carotid blood flow velocity and pulsatility index (PI) of the common carotid (CCA) and internal carotid (ICA) arteries. The association between carotid blood flow velocity and the total MRI load of CSVD was examined using univariate and multivariate analyses.
    Results: For our investigation, 272 individuals with RSSIs were screened. 82 individuals had a moderate to severe load of CSVD, while 190 participants showed a mild burden. Patients with moderate to severe burden of CSVD had lower end-diastolic velocity (EDV) and higher PI in CCA and ICA than those with mild load (P < 0.001). After adjusting for variables like age, hypertension, systolic blood pressure, and blood homocysteine levels, multivariate logistic regression analysis showed that EDV in CCA (OR, 0.894; P = 0.011), PI in CCA (OR, 5.869; P = 0.017), EDV in ICA (OR, 0.909; P = 0.008), and PI in ICA (OR, 5.324; P = 0.041) were independently related to moderate to severe CSVD burden. Spearman correlation analysis showed that EDV in CCA and ICA was negatively related to the total MRI load of CSVD in patients with RSSIs (P < 0.001). PI in CCA and ICA was positively associated with the whole MRI load of CSVD (P < 0.001).
    Conclusion: Low carotid blood flow velocity and high carotid pulsatility index are independently associated with moderate to severe burden of CSVD.
    Language English
    Publishing date 2023-12-01
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2296350-9
    ISSN 1875-5739 ; 1567-2026
    ISSN (online) 1875-5739
    ISSN 1567-2026
    DOI 10.2174/0115672026285373231120054627
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    Zs.A 6646: Show issues Location:
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  4. Article ; Online: Stattic alleviates pulmonary fibrosis in a mouse model of rheumatoid arthritis-relevant interstitial lung disease.

    Xie, Lihu / Li, Youyou / Tang, Wenting / Zhang, Qingxiu / Luo, Cong / Long, Xiaoping

    Experimental biology and medicine (Maywood, N.J.)

    2023  Volume 248, Issue 8, Page(s) 712–721

    Abstract: Approximately 20% of rheumatoid arthritis (RA) patients have RA-related interstitial lung disease (RA-ILD). Stattic, an STAT3 inhibitor, has been confirmed to be relevant to both RA and ILD. Therefore, this study explored the effect of Stattic on the ... ...

    Abstract Approximately 20% of rheumatoid arthritis (RA) patients have RA-related interstitial lung disease (RA-ILD). Stattic, an STAT3 inhibitor, has been confirmed to be relevant to both RA and ILD. Therefore, this study explored the effect of Stattic on the progression of joint disease and pulmonary fibrosis in zymosan-treated female SKG mice, an established model for autoimmune arthritis. The experimental mice developed pulmonary interstitial pneumonia, which is similar to human cellular and fibrotic nonspecific interstitial pneumonia. Oral gavage of Stattic (60 mg/kg/d) was initiated 10 weeks after zymosan injection. Arthritis and lung fibrosis outcome scores decreased significantly following Stattic treatment. An obvious decrease in lung collagen levels, measured using hydroxyproline level determination and collagen staining, was detected after 6 weeks in Stattic-exposed mice with established disease. Stattic also dramatically restricted arthritis progression, based on joint evaluation. Transforming growth factor beta 1 (TGF-β1) is a pivotal fibrosis-causing cytokine, used here to treat myofibroblasts, thereby establishing a lung fibrosis cell model. Stattic treatment can mitigate the TGF-β1-triggered inflammatory response, myofibroblast activation, oxidative stress, and hyperproliferation by modulating the JAK1/STAT3 pathway. Our observations support a direct role of Stattic-inhibited STAT3 activation in lung fibrosis, which may be particularly relevant in the RA-ILD context.
    MeSH term(s) Female ; Animals ; Mice ; Cyclic S-Oxides/pharmacology ; Cyclic S-Oxides/therapeutic use ; Disease Models, Animal ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/etiology ; Idiopathic Pulmonary Fibrosis/pathology ; Arthritis, Rheumatoid/complications ; Bone Density/drug effects ; Cell Proliferation/drug effects ; Apoptosis/drug effects ; Transforming Growth Factor beta1/pharmacology
    Chemical Substances stattic ; Cyclic S-Oxides ; Transforming Growth Factor beta1
    Language English
    Publishing date 2023-03-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 4015-0
    ISSN 1535-3699 ; 1525-1373 ; 0037-9727
    ISSN (online) 1535-3699 ; 1525-1373
    ISSN 0037-9727
    DOI 10.1177/15353702231157934
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    Ua VI Zs.111: Show issues Location:
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  5. Article ; Online: Bone marrow mesenchymal stem cell-derived exosomes alleviate skin fibrosis in systemic sclerosis by inhibiting the IL-33/ST2 axis via the delivery of microRNA-214.

    Xie, Lihu / Long, Xiaoping / Mo, Meili / Jiang, Jinmei / Zhang, Qingxiu / Long, Mei / Li, Mei

    Molecular immunology

    2023  Volume 157, Page(s) 146–157

    Abstract: Interleukin (IL)- 33 is a tissue-derive proinflammatory cytokine that promotes fibrosis in systemic sclerosis (SSc). microRNA (miR)- 214 expression has been elaborated to be downregulated in SSc patients and exert anti-fibrotic and anti-inflammatory ... ...

    Abstract Interleukin (IL)- 33 is a tissue-derive proinflammatory cytokine that promotes fibrosis in systemic sclerosis (SSc). microRNA (miR)- 214 expression has been elaborated to be downregulated in SSc patients and exert anti-fibrotic and anti-inflammatory effects. This study elucidates the role of bone marrow mesenchymal stem cell-derived exosome (BMSC-Exos)-delivered miR-214 in SSc and the relationship between this miR and IL-33/ST2 axis. SSc clinical samples were obtained to evaluate levels of miR-214, IL-33, and ST2. Primary fibroblasts and BMSC-Exos were extracted, followed by the co-culture of PKH6-labeled BMSC-Exos and fibroblasts. Subsequently, Exos extracted from miR-214 inhibitor-transfected BMSCs were co-cultured with TGF-β1-stimulated fibroblasts, after which the expression of fibrotic markers, miR-214, IL-33, and ST2, as well as fibroblast proliferation and migration, was determined. A skin fibrosis mouse model was induced with bleomycin (BLM) and treated with BMSC-Exos. Collagen fiber accumulation, collagen content, α-SMA expression, and IL-33 and ST2 levels were examined in BLM-treated or IL-33-knockout mice. IL-33 and ST2 were upregulated and miR-214 was downregulated in SSc patients. Mechanistically, miR-214 targeted IL-33 and blocked the IL-33/ST2 axis. BMSC-Exos delivering miR-214 inhibitor augmented proliferation, migration, and fibrotic gene expression in TGF-β1-stimulated fibroblasts. Similarly, IL-33 induced migration, proliferation, and fibrotic gene expression in fibroblasts via ST2. In BLM-treated mice, IL-33 knockout suppressed skin fibrosis, and BMSC-Exos delivered miR-214 to suppress the IL-33/ST2 axis, thus mitigating skin fibrosis. Conclusively, BMSC-Exos alleviate skin fibrosis through the blockade of the IL-33/ST2 axis by delivering miR-214.
    MeSH term(s) Mice ; Animals ; Transforming Growth Factor beta1/metabolism ; Interleukin-1 Receptor-Like 1 Protein/genetics ; Exosomes/genetics ; Interleukin-33 ; Fibrosis ; Mesenchymal Stem Cells/metabolism ; Scleroderma, Systemic/genetics ; Scleroderma, Systemic/therapy ; Scleroderma, Systemic/metabolism ; Collagen/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism
    Chemical Substances Transforming Growth Factor beta1 ; Interleukin-1 Receptor-Like 1 Protein ; Interleukin-33 ; Collagen (9007-34-5) ; MicroRNAs ; Mirn214 microRNA, mouse
    Language English
    Publishing date 2023-04-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2023.03.017
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    Zs.A 166: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  6. Article ; Online: Influence of nimodipine combined with ulinastatin on neurological function and inflammatory reaction in patients with cerebral vasospasm after subarachnoid hemorrhage.

    Chen, Ming / Zhang, Qingxiu / Liu, Haiyan / Zou, Wenwei / Wei, Xiue

    Clinical neurology and neurosurgery

    2021  Volume 210, Page(s) 106981

    Abstract: Objective: This study aimed to discuss the influence of nimodipine+ulinastatin on the neurological function and inflammatory reaction in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH).: Methods: Overall, 90 patients with ... ...

    Abstract Objective: This study aimed to discuss the influence of nimodipine+ulinastatin on the neurological function and inflammatory reaction in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH).
    Methods: Overall, 90 patients with CVS after SAH who were admitted to our hospital were enrolled in this study and randomly divided into research and control groups (n = 45 for both groups). On the basis of conventional therapy, patients in the control group were injected with ulinastatin and those in the research group were injected with ulinastatin+nimodipine through an intravenous drip for 7 days with the others the same as those of the control group.
    Results: Blood flow velocity in all cerebral arteries was lower in the research group than in the control group after treatment (P < 0.05). Calcitonin gene-related peptide and nitric oxide levels were higher in the research group than in the control group after treatment (P < 0.05). Endothelin levels were lower in the research group than in the control group (P < 0.05). The total effective rate was higher in the research group than in the control group (P < 0.05). Glasgow Coma Scale scores were higher in the research group than in the control group (P < 0.05).
    Conclusion: The drug combination of nimodipine and ulinastatin improved blood flow and neurological function in patients with CVS after SAH and enhanced the therapeutic efficacy; the underlying mechanism may be associated with the regulation of vascular endothelial dilatation function and the inhibition of relevant inflammatory factors' expression.
    MeSH term(s) Adult ; Blood Flow Velocity/drug effects ; Cerebral Arteries/drug effects ; Cerebral Arteries/physiopathology ; Drug Therapy, Combination ; Female ; Glycoproteins/administration & dosage ; Glycoproteins/therapeutic use ; Humans ; Male ; Middle Aged ; Nimodipine/administration & dosage ; Nimodipine/therapeutic use ; Subarachnoid Hemorrhage/complications ; Subarachnoid Hemorrhage/physiopathology ; Treatment Outcome ; Trypsin Inhibitors/administration & dosage ; Trypsin Inhibitors/therapeutic use ; Vasodilator Agents/administration & dosage ; Vasodilator Agents/therapeutic use ; Vasospasm, Intracranial/drug therapy ; Vasospasm, Intracranial/etiology ; Vasospasm, Intracranial/physiopathology
    Chemical Substances Glycoproteins ; Trypsin Inhibitors ; Vasodilator Agents ; Nimodipine (57WA9QZ5WH) ; urinastatin (OR3S9IF86U)
    Language English
    Publishing date 2021-10-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 193107-6
    ISSN 1872-6968 ; 0303-8467
    ISSN (online) 1872-6968
    ISSN 0303-8467
    DOI 10.1016/j.clineuro.2021.106981
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    Ui I Zs.53: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Mechanical properties and mechanism of soil treated with nano-aqueous adhesive (NAA).

    Huang, Wei / Du, Jiaxin / Lai, Haoqiang / Zhang, Qingxiu / Zhou, Cuiying / Liu, Zhen

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 14711

    Abstract: The loose structure and low mechanical strength of the surface soil make it vulnerable to damage under erosion conditions. Slope ecological protection is one of the effective methods to improve the stability of slope soil. Although it has been proved ... ...

    Abstract The loose structure and low mechanical strength of the surface soil make it vulnerable to damage under erosion conditions. Slope ecological protection is one of the effective methods to improve the stability of slope soil. Although it has been proved that polymer modified materials can effectively improve the soil properties and the environmental protection effect of slope, so far, the improvement mechanism has not been fully understood, especially the chemical mechanism of the material on the enhancement of soil mechanical properties is not clear. In the present study, the effects of nano-aqueous adhesive (NAA) on unconfined compressive strength, shear strength and aggregate characteristics of soil were studied by a series of laboratory experiments. The results show that NAA can increase the strength, aggregate number and stability of the soil, to effectively improve the stability of surface soil. In addition, through infrared spectroscopy and SEM test, it was found that NAA molecules were mainly distributed in the interlayer position of flaky clay minerals, mainly connected with clay minerals through hydrogen bonds, thereby effectively enhancing the cohesion of soil particles.
    MeSH term(s) Adhesives ; Clay ; Conservation of Natural Resources/methods ; Minerals ; Soil/chemistry ; Water
    Chemical Substances Adhesives ; Minerals ; Soil ; Water (059QF0KO0R) ; Clay (T1FAD4SS2M)
    Language English
    Publishing date 2022-08-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-19108-5
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  8. Article: Interpretable Machine Learning Model Predicting Early Neurological Deterioration in Ischemic Stroke Patients Treated with Mechanical Thrombectomy: A Retrospective Study.

    Yang, Tongtong / Hu, Yixing / Pan, Xiding / Lou, Sheng / Zou, Jianjun / Deng, Qiwen / Zhang, Qingxiu / Zhou, Junshan / Zhu, Junrong

    Brain sciences

    2023  Volume 13, Issue 4

    Abstract: Early neurologic deterioration (END) is a common and feared complication for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). This study aimed to develop an interpretable machine learning (ML) model for individualized ... ...

    Abstract Early neurologic deterioration (END) is a common and feared complication for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). This study aimed to develop an interpretable machine learning (ML) model for individualized prediction to predict END in AIS patients treated with MT. The retrospective cohort of AIS patients who underwent MT was from two hospitals. ML methods applied include logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver operating characteristic curve (AUC) was the main evaluation metric used. We also used Shapley Additive Explanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) to interpret the result of the prediction model. A total of 985 patients were enrolled in this study, and the development of END was noted in 157 patients (15.9%). Among the used models, XGBoost had the highest prediction power (AUC = 0.826, 95% CI 0.781-0.871). The Delong test and calibration curve indicated that XGBoost significantly surpassed those of the other models in prediction. In addition, the AUC in the validating set was 0.846, which showed a good performance of the XGBoost. The SHAP method revealed that blood glucose was the most important predictor variable. The constructed interpretable ML model can be used to predict the risk probability of END after MT in AIS patients. It may help clinical decision making in the perioperative period of AIS patients treated with MT.
    Language English
    Publishing date 2023-03-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2651993-8
    ISSN 2076-3425
    ISSN 2076-3425
    DOI 10.3390/brainsci13040557
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  9. Article ; Online: Network pharmacology and transcriptomic profiling elucidate the therapeutic effects of

    Han, Lu / Lin, Guoyuan / Li, Jianchao / Zhang, Qingxiu / Ran, Tao / Huang, Tao / Hu, Ruihan / Feng, Shu / Zou, Gaoliang / Chen, Shaojie / Zhao, Xueke

    Aging

    2024  Volume 16, Issue 5, Page(s) 4759–4777

    Abstract: Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. ...

    Abstract Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of β-sitosterol, a major constituent of
    MeSH term(s) Mice ; Animals ; NF-kappa B/metabolism ; Ranunculus/metabolism ; Network Pharmacology ; Liver Cirrhosis/metabolism ; Gene Expression Profiling ; Liver/metabolism
    Chemical Substances NF-kappa B
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.205629
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  10. Article ; Online: Bile acids induce liver fibrosis through the NLRP3 inflammasome pathway and the mechanism of FXR inhibition of NLRP3 activation.

    Feng, Shu / Xie, Xingming / Li, Jianchao / Xu, Xu / Chen, Chaochun / Zou, Gaoliang / Lin, Guoyuan / Huang, Tao / Hu, Ruihan / Ran, Tao / Han, Lu / Zhang, Qingxiu / Li, Yuanqingxiao / Zhao, Xueke

    Hepatology international

    2024  

    Abstract: Background: Altered patterns of bile acids (BAs) are frequently present in liver fibrosis, and BAs function as signaling molecules to initiate inflammatory responses. Therefore, this study was conducted to uncover the notably altered components of BAs ... ...

    Abstract Background: Altered patterns of bile acids (BAs) are frequently present in liver fibrosis, and BAs function as signaling molecules to initiate inflammatory responses. Therefore, this study was conducted to uncover the notably altered components of BAs and to explore the pathway of altered BA induced inflammation in the development of liver fibrosis.
    Methods: Bile acids were quantified by ultraperformance liquid chromatography coupled to mass spectrometry (UPLC‒MS/MS). Cell Counting Kit-8 assays were used to determine the proliferative capacity of HSCs. Transwell assays and wound healing assays were used to determine the migratory capacity of LX2 cells. Protein expression was evaluated by western blotting.
    Results: Plasma bile acid analysis showed higher levels of GCDCA, TCDCA, GCA and TCA in patients with liver fibrosis than in normal controls. The AUC of GCDCA was the highest. Western blotting showed that GCDCA treatment increased the expression of NLRP3-related proteins and collagen1 in vitro and significantly increased LX2 cells proliferation and migration. Furthermore, knockdown of NLRP3 or overexpression of FXR in LX2 cells decreased the expression of the above proteins, and FXR inhibited NLRP3 (ser 295) phosphorylation in vitro and vivo. In vivo, HE, Masson's trichrome, and Sirius Red staining showed that GCDCA increased collagen fibers in the mouse liver, and the expression of NLRP3-related proteins, collagen 1, and α-SMA in the liver increased significantly. However, the knockout of NLRP3 reversed these patterns.
    Conclusion: (1) Primary conjugated bile acids increased in patients with liver fibrosis; (2) GCDCA induce hepatic fibrosis via the NLRP3 inflammasome pathway; (3) FXR inhibits NLRP3 activity by restraining its phosphorylation; (4) knockdown or knockout of NLRP3 may relieve the onset of hepatic fibrosis.
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2270316-0
    ISSN 1936-0541 ; 1936-0533
    ISSN (online) 1936-0541
    ISSN 1936-0533
    DOI 10.1007/s12072-023-10610-0
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