CELL BIOLOGY AND TOXICOLOGY
·
2024
·Vol. 40
·期 1
·1-28
·
IF 5.3
Liu Yuhan,Qin Yanling,Zhang Yanning
Uremic encephalopathy (UE) poses a significant challenge in neurology, leading to the need to investigate the involvement of non-coding RNA (ncRNA) in its development. This study employed ncRNA-seq and RNA-seq approaches to identify fundamental ncRNAs, specifically circRNA and miRNA, in the pathogenesis of UE using a mouse model. In vitro and in vivo experiments were conducted to explore the circRNA-PTPN4/miR-301a-3p/FOXO3 axis and its effects on blood–brain barrier (BBB) function and cognitive abilities. The research revealed that circRNA-PTPN4 binds to and inhibits miR-301a-3p, leading to an increase in FOXO3 expression. This upregulation results in alterations in the transcriptional regulation of ZO-1, affecting the permeability of human brain microvascular endothelial cells (HBMECs). The axis also influences the growth, proliferation, and migration of HBMECs. Mice with UE exhibited cognitive deficits, which were reversed by overexpression of circRNA-PTPN4, whereas silencing FOXO3 exacerbated these deficits. Furthermore, the uremic mice showed neuronal loss, inflammation, and dysfunction in the BBB, with the expression of circRNA-PTPN4 demonstrating therapeutic effects. In conclusion, circRNA-PTPN4 plays a role in promoting FOXO3 expression by sequestering miR-301a-3p, ultimately leading to the upregulation of ZO-1 expression and restoration of BBB function in mice with UE. This process contributes to the restoration of cognitive abilities. Graphical Abstract 1. The circRNA-PTPN4/miR-301a-3p/FOXO3 axis is identified as a key regulator of blood–brain barrier integrity and cognitive function in uremic encephalopathy. 2. circRNA-PTPN4 sequestration of miR-301a-3p enhances FOXO3 expression, leading to upregulation of ZO-1 and improved endothelial permeability. 3. Overexpression of circRNA-PTPN4 in uremic mice restores cognitive abilities and reduces neuronal loss and inflammatory infiltration.
研究领域:
神经学
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分子生物学
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非编码RNA
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认知科学
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病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2024
·Vol. 21
·期 15
·3018
·
IF 3.2
Qi Zhang,Chao Hu,Baoqing Qu,Cuiping Zhang,Longtao He
This work aimed to demonstrate the therapeutic effects of tumor microenvironment-responsive nanotherapeutic drugs targeting PSD95/Discs-large/ZO-1 domain (PDZ)-binding-kinase (PBK) in medulloblastoma Daoy and ONS-76 cells. The objective was to provide critical theoretical and practical foundations for the clinical adoption of tumor microenvironment-responsive nanotherapeutic drugs targeting PBK. The rabies virus glycoprotein (RVG) was utilized as a specific targeting molecule to form a tumor microenvironment-responsive nanocomplex, HPAA/RVG/PBK-siRNA, which incorporated glutathione (GSH) as a microenvironment stimulus factor within a hyperbranched polymer polyamide amine (HPAA). This nanocomplex also carried PBK-small interfering RNA (siRNA) for targeted PBK therapy. Characterization of HPAA, maleimide-polyethylene glycol-N-succinyl ester (MAL-PEG-NHS), HPAA-PEG, RVG, HPAA-RVG, and HPAA/RVG/PBK-siRNA was conducted using nuclear magnetic resonance spectroscopy, high-performance liquid chromatography (HPLC), dynamic light scattering, and transmission electron microscopy (TEM). Flow cytometry was employed to assess endocytosis and cell transfection of HPAA-RVG and HPAA/RVG/PBK-siRNA in Daoy and ONS-76 cells. The two cell lines were treated with HPAA/RVG/PBK-siRNA (HPAA/siRNA group), methoxy-PEG polyethylenimine (PEI-25k)/PBK-siRNA (PEI group), HPAA/RVG nanocarriers without PBK-siRNA (HPAA/RVG group), Dharmacon™ non-targeting siRNA (shNTC group), PBK-siRNA (Control group 1), AChR inhibitor (Control group 2), and GSH inhibitor (Control group 3), and compared with the control group (medium without any substances). Western blot analysis validated PBK expression levels (ELs) in various cell groups. Additionally, cell viability and proliferation were evaluated using methyl tetrazolium (MTT) assays and 5-Bromo-2'-deoxyuridine (BrdU) incorporation assays. The results revealed proton absorption peaks for HPAA at 2.78 ppm, 3.21 ppm, and 3.49 ppm, while RVG and HPAA-RVG exhibited characteristic absorption peaks at 23.653 min and 23.584 min, respectively, with peak areas of 4,856.6 and 6,927.3 for RVG. The nanoparticle sizes were 50-100 nm for HPAA-RVG and 100 nm for HPAA/RVG/PBK-siRNA, displaying spherical morphology and uniform size distribution. The average potential of HPAA-PEG was lower than that of HPAA ( P <0.05), and HPAA-RVG showed dramatically lower potential than HPAA ( P <0.001). At 8 hours, Daoy cells displayed higher endocytosis rates versus ONS-76 cells ( P <0.05). The transfection rates of HPAA-RVG in both ONS-76 and Daoy cells were higher than those of HPAA, with Daoy cells showing higher transfection rates than HPAA ( P <0.05). Under HPAA-RVG treatment, AChR levels in ONS-76 cells were significantly lower than those in Daoy cells ( P < 0.05). Compared to the control group, the PBK protein expression levels, cell survival rates, and the number of cells in the proliferative phase were significantly reduced in Control group 1, the PEI group, and the HPAA/siRNA group in both ONS-76 and Daoy cells, with the ONS-76 cells in the HPAA/siRNA group showing the lowest values among these groups ( P < 0.05). In summary, the findings indicated that the tumor microenvironment-responsive nanocomposite HPAA/RVG/PBK-siRNA selectively inhibited PBK expression in Daoy medulloblastoma cells, showcasing potential applicability in medulloblastoma therapy.
研究领域:
肿瘤学
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药学
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分子生物学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2019
·Vol. 47
·期 9
·1182-1197
·
IF 3.411
Chaoyang Zhang,Hai Xie,Qian Yang,Yiting Yang,Weiye Li,Haibin Tian,Lixia Lu,Fang Wang,Jing-Ying Xu,Furong Gao,Juan Wang,Caixia Jin,Guoxu Xu,Guo-Tong Xu,Jingfa Zhang
Purpose To explore the mechanisms of erythropoietin (EPO) in maintaining outer blood-retinal barrier (BRB) in diabetic rats. Methods Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin, and then followed by intravitreal injection of EPO. Two and four weeks later, the permeability of outer BRB was examined with FITC-dextran leakage assay, following a method to demarcate the inner and outer retina based on retinal blood supply. The glyoxal-treated ARPE-19 cells, incubated with EPO, soluble EPO receptor (sEPOR), Gö6976, or digoxin, were studied for cell viability and barrier function. The expressions of ZO-1, occludin, VEGFR2, HIF-1α, MAPKs, and AKT were examined with Western blot and immunofluorescence. Results The major Leakage of FITC-dextran was detected in the outer nuclear layer in both 2- and 4-week diabetic rats. The leakage was largely ameliorated in EPO-treated diabetic rats. The protein expressions of ZO-1 and occludin in the RPE-Bruch's membrane choriocapillaris complex were significantly decreased, whereas HIF-1α and JNK pathways were activated, in 4-week diabetic rats. These changes were prevented by EPO treatment. The in vitro study with ARPE-19 cells confirmed these changes, and the protective effect of EPO was abolished by sEPOR. Gö6976 and digoxin rescued the tight junction and barrier function in glyoxal-treated ARPE-19 cells. Conclusions In early diabetic rats, the outer BRB might be more severely damaged and its breakdown is the major factor for retinal oedema. EPO maintains the outer BRB integrity through down-regulation of HIF-1α and JNK signallings, and thus up-regulating ZO-1 and occludin expressions in RPE cells.
研究领域:
眼科学
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糖尿病
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Mengmeng Yang,Yuxuan Lu,Shufan Jin,Wanqiu Liu,Miaoshi Yao,Zhiwei Jiang,Yachun Shu
Aim of the study This study investigated the mechanism by which the Postoperative Tongqi Formula (PTQF) treats postoperative ileus (POI) through regulation of the p38 MAPK signaling pathway, Zona occludens 1 (ZO-1) protein, and metabolism. Methods The primary components of PTQF were characterized using UHPLC-Q-TOF-MS/MS. The identified compounds subsequently employed network pharmacology to predict the signaling pathways associated with the inflammatory phase of POI. The anti-inflammatory effects of PTQF were evaluated in vitro using RAW264.7 cells. A rat model of POI was used to assess efficacy based on the spleen index and charcoal powder propulsion rat in the small intestine. Furthermore, pathological damage to the small intestine was analyzed using hematoxylin and eosin (HE) staining as well as immunofluorescence to evaluate ZO-1 protein expression. Inflammatory cytokine levels were quantified using enzyme-linked immunosorbent assay (ELISA). Subsequently, Western blot analysis was performed to examine the p38 MAPK signaling pathway. Finally, a metabolomics approach was employed to analyze serum samples to identify potential metabolic pathways. Results A total of 130 chemical constituents were identified in PTQF. Following the network pharmacology analysis of these compounds, the p38 MAPK signaling pathway was chosen for further investigation. In vitro , PTQF effectively inhibited inflammatory responses in RAW264.7 cells. Results from the spleen index and charcoal powder propulsion rate indicated that PTQF alleviated the inflammatory phase of POI in rats by mitigating systemic and intestinal inflammation. This was supported by reduced levels of inflammatory factors, modulation of ZO-1 protein expression, and a decrease in p38 MAPK phosphorylation levels. Furthermore, serum metabolomics revealed nine differential metabolites linked to intestinal inflammation. Conclusion PTQF mitigates inflammation and intestinal damage in POI rats by modulating inflammatory factors, ZO-1 protein expression, the p38 MAPK signaling pathway, and metabolic disturbances.
研究领域:
药理学
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分子生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Neurology
·
2022
·
IF 4.086
Ren Siying,Han Shanshan,Wang Likun,Huang Yuanxin,Wu Jing,Wu Guofeng
Objective: To investigate the role of minimally invasive surgery (MIS) in intracerebral hemorrhage (ICH) evacuation combined with deferoxamine (DFX) treatment on perihematomal tight junction protein (claudin-5 and ZO-1) expression levels and blood-brain barrier (BBB) permeability in rabbits.Methods: We randomly assigned 65 male rabbits (weight: 1.9–2.6 kg) to a normal control group (NC group, 13 rabbits), hemorrhage model group (HM group, 13), DFX treatment group (DFX group, 13 rabbits), MIS group (MIS group, 13 rabbits), or MIS combined with DFX treatment group (MIS + DFX group, 13 rabbits). ICH was established in all of the groups except the NC group. MIS was performed to evacuate the hematoma 6 h after the ICH model was created in the MIS and MIS + DFX groups. The DFX and MIS + DFX groups were treated with DFX (100 mg/kg, dissolved in 2 mL of 0.9% saline solution, administered intramuscularly) at 2 h, and then every 12 h for 7 d. The same dose of 0.9% saline solution was administered to the NC, HM, and MIS groups at the same time points. Sixty-five rabbits were divided into 5 groups, and 13 rabbits in each group. Neurological deficit (i.e., Purdy's score) was recorded in all rabbits before euthanasia (N total = 65). In each group, 2 rabbits were used for iron concentration measurement (N total = 10), 2 rabbits were used for brain water content measurement (N total = 10), 3 rabbits were used for BBB permeability measurement (N total = 15), 3 rabbits were used for claudin-5, ZO-1 expression detection by Western Blotting (N total = 15), and 3 rabbits were used for claudin-5, ZO-1 mRNA detection by real-time PCR (N total = 15). On day 7, the rabbits were sacrificed and the perihematomal brain tissue was harvested to test the iron concentration, brain water content (BWC), tight junction proteins (claudin-5 and ZO-1) expression, and BBB permeability.Results: Purdy's score, iron concentration, and BWC were lower in the MIS and MIS + DFX groups compared to the HM and DFX groups. The MIS + DFX group showed a significant decrease in these indicators. The use of MIS to evacuate the hematoma led to increased expression levels of claudin-5 and ZO-1, as well as decreased BBB permeability. The MIS + DFX group exhibited a remarkable increase in claudin-5 and ZO-1 expression levels and a significant decrease in BBB permeability.Conclusions: MIS combined with DFX treatment could increase the expression levels of perihematomal tight junction proteins (claudin-5 and ZO-1) expression, reduce BBB permeability, and improve the neurological function. MIS combined with DFX treatment may also prevent secondary brain damage following ICH.
研究领域:
神经科学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Cong Zhang,Qingrong Li,Jianghao Xing,Yan Yang,Mengmei Zhu,Liting Lin,Yue Yu,Xiaojun Cai,Xianwen Wang
Colon mucosal overexpression of reactive oxygen and nitrogen species (RONS) accelerates the development of inflammatory bowel disease (IBD) and destroys the mucosa and its barrier. IBD can be alleviated by removing RONS from the inflamed colon. The preparation of strong and efficient nanoantioxidants remains a challenge despite the development of numerous nanoantioxidants. In this paper, Zn-TA nanoparticles with fine hollow microstructure (HZn-TA) were successfully prepared and could be effectively used to treat IBD. In the first step, ZIF-8 nanoparticles were synthesized by a one-pot method. On this basis, HZn-TA nanoparticles were etched by TA, and a multifunctional nanase was developed for the treatment of IBD. RONS, including reactive oxygen species (ROS) and nitric oxide (NO), can be eliminated to increase cell survival following Hydrogen peroxide (H 2 O 2) stimulation, including reactive oxygen species (ROS) and nitric oxide (NO with hydrogen peroxide (H 2 O 2 ). In a model for preventing and delaying acute colitis, clearance of RONS has been shown to reduce intestinal inflammation in mice by reducing colon damage, proinflammatory cytokine levels, the spleen index, and body weight. Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate zonula occludens protein 1 (ZO-1) and claudin-1 expression. Based on the results of this study, HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS. Therefore, we pioneered the application of HZn-TA nanoparticles for the treatment of IBD, which are capable of clearing RONS without significant adverse effects. Statement of significance ➢ HZn-TA nanoparticles were successfully prepared and could be effectively used to treat IBD. ➢ Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate ZO-1 and claudin-1 expression. ➢ HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS.
研究领域:
医学
·
生物化学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Stroke & Cerebrovascular Diseases
·
2021
·
IF 2.136
Yue Shu,Juan Huang,Meng Gao,Shengwei Gan,Shujuan Zhu,Shiye Xu,Zhengyu Yang,Yuhui Liao,Weitian Lu
Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis , neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema , and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment .
研究领域:
神经科学
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药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Chronic Obstructive Pulmonary Disease
·
2024
·
IF 2.7
Liguo Lu,Chengdong Zhu,Jian Xu,Yulan Hu,Juxiang Dai,Sheng Wang,Tao Wei
Introduction The Lifei Decoction (LD) is a commonly utilized Chinese medicine for the treatment of sepsis and bronchial inflammation. However, its therapeutic potential in chronic obstructive pulmonary disease (COPD) remains unknown. Therefore, the objective of this study was to investigate the therapeutic efficacy and underlying mechanism of LD in a mouse model of COPD induced by cigarette smoke (CS) combined with lipopolysaccharide (LPS).Methods Hematoxylin-eosin (H&E) staining was employed to observe the pathological alterations in lung tissue, while ELISA was utilized for the detection of levels of inflammatory factors in both lung tissue and bronchoalveolar lavage fluid (BALF). Additionally, Western blot analysis was conducted to assess the expression of p-NF-κB, GDF11, ZO-1, and Occludin-1 proteins. The changes in intestinal flora were evaluated using the viable bacteria count method.Results The administration of LD demonstrates significant efficacy in mitigating pulmonary tissue damage in a murine model, while concurrently inhibiting the activation of the inflammatory pathway NF-κB to attenuate the levels of pro-inflammatory factors. Moreover, LD exhibits the capacity to enhance the expression of intestinal functional proteins ZO-1 and Occludin-1, thereby rectifying dysbiosis within the gut microbiota.Conclusion The LD shows great promise as a potential treatment for COPD.
研究领域:
药理学
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呼吸病学
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免疫学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2021
·
IF 4.711
Huan Lan,Lu-Ying Zhang,Wen He,Wan-Ying Li,Zhen Zeng,Bo Qian,Chengqiang Wang,Jia-Le Song
The integrity and permeability of the intestinal epithelial barrier are important indicators of intestinal health. Impaired intestinal epithelial barrier function and increased intestinal permeability are closely linked to the onset and progression of various intestinal diseases. Sinapic acid (SA) is a phenolic acid that has anti-inflammatory, antihyperglycemic, and antioxidant activities; meanwhile, it is also effective in the protection of inflammatory bowel disease (IBD), but the specific mechanisms remain unclear. Here, we evaluated the anti-inflammatory of SA and investigated its potential therapeutic activity in LPS-induced intestinal epithelial barrier and tight junction (TJ) protein dysfunction. SA improved cell viability; attenuated epithelial permeability; restored the protein and mRNA expression of claudin-1, ZO-1, and occludin; and reversed the redistribution of the ZO-1 and claudin-1 proteins in LPS-treated Caco-2 cells. Moreover, SA reduced the inflammatory response by downregulating the activation of the TLR4/NF-κB pathway and attenuated LPS-induced intestinal barrier dysfunction by decreasing the activation of the MLCK/MLC pathway. This study demonstrated that SA has strong anti-inflammatory activity and can alleviate the occurrence of high intercellular permeability in Caco-2 cells exposed to LPS.
研究领域:
药理学
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免疫学
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细胞生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
World Journal of Acupuncture-Moxibustion
·
2025
·
IF 1.3
Xiao-lei ZHANG,Meng-ni HU,Ya-nan LI,Yao WANG,Zhen RONG,Jun MA
Objective
To investigate the effects of electroacupuncture (EA) on the blood-brain barrier permeability and the regulation of matrix metalloproteinases (MMPs) in the mice with Parkinson's disease (PD).
Methods
Forty-eight C57BL/6 mice were randomly assigned into the normal control (NC) group, the PD model (PD) group, the EA group and the EA + SB-3CT inhibitor group (EA + SB-3CT), with 12 mice in each group. In this experiment, the PD model was established by intragastric administration (IG) with rotenone for 4 wk in the PD group, EA group and EA+SB-3CT group. In the EA + SB-3CT group, 1 h after IG with rotenone, the mice were intraperitoneally injected with MMP-2/9 inhibitor, SB-3CT (25 mg/kg/d). After successfully modeled, in the EA group and EA + SB-3CT group, EA was conducted at “Fengfu (GV16)” and bilateral “Taichong (LR3)” and “Zusanli (ST36)”, at 1 mA and 2 Hz for 30 min each time, once a day, for consecutive 2 wk. The behavioral changes of the mice were observed in each group using the open field test, the level of tyrosine hydroxylase (TH) in the substantia nigra was determined by immunohistochemistry, the permeability of the blood-brain barrier was detected by Evans blue staining, and the protein expression of ZO-1, ocludin, claudin-1, MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting.
Results
Compared with the NC group, the behavioral scores increased (P < 0.05), while total time of locomotion, total distance and average speed were reduced (P < 0.05) in the PD group. The expression of TH in the substantia nigra decreased (P < 0.05), Evans blue level in the brain tissue increased (P < 0.05), and the protein expression of ZO-1, occludin and claudin-1 was lower (P < 0.05), whereas MMP-2 and MMP-9 expression was higher (P < 0.05) in the PD group. Compared with the PD group, behavioral scores decreased (P < 0.05), while the total time of locomotion, total distance and average speed increased (P < 0.05) in the EA group. Additionally, TH expression in the substantia nigra was elevated (P < 0.05), Evans blue level in the brain tissue was lower (P < 0.05), the protein expression of ZO-1, occludin and claudin-1 was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was down-regulated (P < 0.05) in the EA group. Compared with the EA group, Evans blue level was reduced (P < 0.05), the protein expression of ZO-1 and occludin was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was further down-regulated (P < 0.05) in the EA+SB-3CT group.
Conclusion
EA can effectively ameliorate the motor dysfunction of PD mice, reduce the damage of dopaminergic neurons, and play a neuroprotective role. EA can effectively improve the blood–brain barrier permeability in PD mice by up-regulating the expression of tight junction proteins, ZO-1 and occludin, and down-regulating the expression of matrix metalloporteinases, MMP-2 and MMP-9. The neuroprotective role of EA may be obtained by improving the blood-brain barrier permeability mediated by MMP-2/9 pathway.
研究领域:
神经科学
·
药理学
·
病理生理学
·
中医
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Physiology
·
2023
·
IF 4
Senyue Liu,Lin Luo,Fengyuan Zuo,Xiaoli Huang,Liang Zhong,Sha Liu,Yi Geng,Yangping Ou,Defang Chen,Wenlong Cai,Yongqiang Deng
Nitrogen from ammonia is one of the most common pollutants toxics to aquatic species in aquatic environment. The intestinal mucosa is one of the key mucosal defenses of aquatic species, and the accumulation of ammonia nitrogen in water environment will cause irreversible damage to intestinal function. In this study, histology, immunohistochemistry, ultrastructural pathology, enzyme activity analysis and qRT-PCR were performed to reveal the toxic effect of ammonia nitrogen stress on the intestine of Pelteobagrus fulvidraco . According to histological findings, ammonia nitrogen stress caused structural damage to the intestine and reduced the number of mucous cells. Enzyme activity analysis revealed that the activity of bactericidal substances (Lysozyme, alkaline phosphatase, and ACP) had decreased. The ultrastructure revealed sparse and shortened microvilli as well as badly degraded tight junctions. Immunohistochemistry for ZO-1 demonstrated an impaired intestinal mucosal barrier. Furthermore, qRT-PCR revealed that tight junction related genes ( ZO-1, Occludin, Claudin-1 ) were downregulated, while the pore-forming protein Claudin-2 was upregulated. Furthermore, as ammonia nitrogen concentration grew, so did the positive signal of Zap-70 (T/NK cell) and the expression of inflammation-related genes ( TNF , IL-1β , IL-8, IL-10) . In light of the above findings, we conclude that ammonia nitrogen stress damages intestinal mucosal barrier of Pelteobagrus fulvidraco and induces intestinal inflammation.
研究领域:
水生毒理学
·
环境科学
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鱼类生理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUTRITION
·
2025
·Vol. 64
·期 6
·1-17
·
IF 4.3
Chen Huihui,Lin Hongzhou,Qian Rengcheng,Tang Guoqi,Ding Yinjuan,Jiang Yalan,Guo Xiaoling,Wang Dexuan
Purpose Nephrotic syndrome (NS) is the main cause of the increasing end-stage renal disease (ESRD) patients worldwide. Podocytes are considered the crucial cells involved in the progression of NS, and their damage can directly lead to proteinuria. The objective of this study was to explore the protective effects of xanthohumol (XN) on podocyte injury. Methods Adriamycin (ADR)-induced podocyte injury in vivo and in vitro models were established to explore the effects of XN on adriamycin nephropathy (AN) by urine and serum biochemical assay, periodic acid-schiff (PAS) staining, immunohistochemistry, immunofluorescence, western blot, and real-time quantitative PCR (RT-qPCR). Results The results showed that XN could upregulate the expressions of podocyte specific marker Wilms’ tumor protein 1 (Wt1), and glomerular filtration related functional proteins such as Nephrin, Synaptopodin, Zonula occludens 1 (ZO-1), and Crumbs2 (Crb2) as well as downregulate the expression of podocyte injury marker Desmin in ADR-treated podocytes to restrain the podocyte actin cytoskeleton disruption. Conclusion Our study showed that XN treatment significantly attenuated ADR-induced podocyte injury, suggesting that XN may be a potential therapy option for patients with NS.
研究领域:
肾脏病学
·
分子生物学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）