1.Fexolone inhibits neuronal ferroptosis through the Nrf2/HO-1/GPX4 pathway to alleviates sepsis-associated brain injury.
Rao SUN ; Jinyao ZHOU ; Yang JIAO ; Kaixuan NIU ; Cheng YUAN ; Ximing DENG
Chinese Critical Care Medicine 2025;37(5):452-457
OBJECTIVE:
To observe the protective effect of Fisetin on sepsis-associated brain injury and explore its possible mechanism from the perspective of ferroptosis.
METHODS:
Sprague-Dawley (SD) rats (6-8-week-old male) were randomly divided into three groups: sham operation group (Sham group), colonic ligation and puncture (CLP) induced sepsis model group (CLP group) and Fisetin preprocessing group (CLP+Fisetin group), with 18 rats in each group (12 for observing survival rate and 6 for indicator testing). The CLP+Fisetin group was given Fisetin solution 50 mg×kg-1×d-1 by gavage continuously for 5 days before CLP, with dimethyl sulfoxide (DMSO) as the solute, while Sham group and CLP group were given the same dose of DMSO. The model was established at 2 hours after the last gavage. The general condition of each group of rats were observed, and the 10-day mortality were record. The behavioral testing (new object recognition experiment, elevated cross maze experiment) were performed after 7 days of modeling. After 24 hours of modeling, nerve reflex scoring was performed, and then the rats were euthanized and brain tissue was collected. The pathological changes of brain tissue were observed under a microscope by hematoxylin-eosin (HE) staining, the deposition of iron ion in brain tissue was observed by Prussian blue staining. The content of iron in brain tissue was determined by tissue iron kit, and the content of malondialdehyde (MDA) in brain tissue was determined by colorimetry. The expressions of tumor necrosis factor-α (TNF-α), neuron damage marker S100β, nuclear factor E2-related factor 2 (Nrf2), heme oxygenases-1 (HO-1) and glutathione peroxidase 4 (GPX4) were detected by Western blotting.
RESULTS:
On day 10 post-operation, 12, 3, and 7 animals survived in the Sham group, CLP group, and CLP+Fisetin group, respectively. Compared with the Sham group, rats in the CLP group showed significantly decreased nerve reflex score, new object discrimination index and open arm dwell time. HE staining showed arranged disorderly of neuronal cells, cytoplasm deep staining, nuclear condensation, unclear structures, neuron loss, and significant inflammation in the hippocampus in the hippocampus. Prussian blue staining showed iron ion deposition in the brain tissue. The contents of iron and MDA in brain tissue were elevated, and the expressions of TNF-α and S100β were up-regulated, while the expressions of Nrf2, HO-1, and GPX4 were down-regulated. Compared with the CLP group, the CLP+Fisetin group showed significantly increased neurological reflex score (7.33±1.15 vs. 4.67±1.53), improved new object discrimination index (0.44±0.02 vs. 0.32±0.04), and longer open arm dwell time (minutes: 78.33±9.29 vs. 41.15±9.64). Neuronal cells in the hippocampus were more organized, with less cytoplasmic staining, nuclear condensation, reduced neuronal loss, and fewer inflammatory cells. Iron ion deposition was reduced, and the contents of iron ions and MDA in brain tissue were decreased [iron ion (μg/g): 151.27±14.90 vs. 224.69±17.64, MDA (μmol/g): 470.0±44.3 vs. 709.3±65.4]. The expressions of TNF-α and S100β were significantly decreased (TNF-α/GAPDH: 0.651±0.060 vs. 0.896±0.022, S100β/GAPDH: 0.685±0.032 vs. 0.902±0.014), while the expressions of Nrf2, HO-1, and GPX4 were significantly increased (Nrf2/GAPDH: 0.708±0.108 vs. 0.316±0.112, HO-1/GAPDH: 0.694±0.022 vs. 0.538±0.024, GPX4/GAPDH: 0.620±0.170 vs. 0.317±0.039). All differences were statistically significant (all P < 0.05).
CONCLUSION
Fisetin pretreatment can inhibit ferroptosis and reduce sepsis-associated brain injury by Nrf2/HO-1/GPX4 pathway.
Animals
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Ferroptosis/drug effects*
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Rats, Sprague-Dawley
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NF-E2-Related Factor 2/metabolism*
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Sepsis/complications*
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Male
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Rats
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Phospholipid Hydroperoxide Glutathione Peroxidase
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Neurons/drug effects*
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Signal Transduction
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Brain Injuries/metabolism*
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Flavonols
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Flavonoids/pharmacology*
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Heme Oxygenase-1/metabolism*
;
Heme Oxygenase (Decyclizing)
2.Study on Self-management Level of Elderly Diabetic Mellitus Patients in Dongcheng District of Beijing and Its Influencing Factors
Yuqing YANG ; Quan CHEN ; Qile HE ; Jinyao ZHANG ; Zhuocun WU ; Yanli WAN
Journal of Medical Informatics 2024;45(1):59-63,88
Purpose/Significance To investigate the status quo and influencing factors of self-management level of elderly diabetic mellitus patients in Dongcheng District of Beijing,and to provide references for further development of community diabetes health educa-tion and health management.Method/Process The survey is conducted on 1 962 cases of elderly patients with type 2 diabetes mellitus who are randomly selected from community-level health service institutions in Dongcheng District of Beijing and are investigated by self-made questionnaires and the summary of diabetes self-care activities.Multiple stepwise regression and logistic regression are used to analyze the influencing factors of patients'self-management level.Result/Conclusion The self-management level of elderly diabetic mellitus patients is affected by many factors,among which the awareness of disease-related knowledge,the form of medical security and the use of health-related software to manage chronic diseases are the main influencing factors(P<0.05).Local management depart-ments can take targeted health interventions to further improve the self-management ability of elderly diabetic mellitus patients.
3.Research Progress of the Infectious Disease Prediction Models Based on Internet Data
Qile HE ; Jinyao ZHANG ; Zhuocun WU ; Yuqing YANG ; Wei ZHAO ; Hongpu HU
Journal of Medical Informatics 2024;45(2):32-37
Purpose/Significance The paper systematically reviews relevant research on infectious disease prediction models based on internet data,helps to realize the advancement of infectious disease surveillance,and provides references for the construction of intelli-gent three-dimensional prevention and treatment system of infectious diseases.Method/Process The development history and research direction of infectious disease surveillance and early warning based on internet data collected in the core database of Web of Science and CNKI in the past 20 years are reviewed,major existing problems and challenges are analyzed,and common prediction models and their optimization directions are summarized.Result/Conclusion The study on internet infectious disease surveillance shows the trend of diver-sification of monitoring diseases,refinement and specialization of data sources.Due to the complexity and uncertainty of internet data,most of the existing models are only suitable for short-term or real-time prediction.By constructing a combination model,strengthening multi-source data fusion,improving the selection of keywords and influencing factors,the model can be further optimized and the fitting effect and prediction capacity can be strengthened.
4.Immune enhancement of 30% ethanol elution fraction of Artemisia absinthium ethanol extract with macroporous resin
Zihang MA ; Jinyao LI ; Xinglong YANG ; Jingwen JIANG ; Qiuyan CHEN ; Lijie XIA
International Journal of Biomedical Engineering 2023;46(1):10-17
Objective:To investigate the effects of 30% ethanol elution fraction of Artemisia absinthium extract with macroporous resin (AAEM-30%) on the dendritic cell (DC) and immunity of mice. Methods:AAEM-30% was obtained from the alcoholic extracts of A. absinthium by AB-8 macroporous resin, and its polysaccharide, flavonoid, and terpenoid contents were determined. The expressions of AAEM-30% on DC surface molecular cluster of differentiation (CD) 40, CD80 and CD86 were detected in vitro by flow cytometry, and the expressions of DC cytokines IL-6 and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The effect of AAEM-30% on the immune function of ICR mice was measured in vivo with different doses (50 and 100 mg/kg) and different administration methods (subcutaneous injection, intraperitoneal injection, and gavage). Results:The contents of polysaccharides, flavonoids, and terpenoids in AAEM-30% were 24.30%, 22.50% and 28.19%, respectively. AAEM-30% significantly enhanced the expression of CD40, and CD86 and the secretion of IL-6 and TNF-α (all P<0.001). Compared with the control group, no statistically significant differences were found in the body mass of mice compared with the three administration methods (all P>0.05). The thymus index in the 50 and 100 mg/kg AAEM-30% intraperitoneal injection groups and the spleen index in the 50 mg/kg AAEM-30% gavage group were increased (all P<0.05). CD19 + cells increased in the 100 mg/kg AAEM-30% intraperitoneal injection group ( P<0.01) and in the 50 mg/kg AAEM-30% gavage group ( P<0.05). The CD11b + and CD11c + counts increased in the 100 mg/kg AAEM-30% gavage group ( P<0.05). The number of CD4 + and CD8 + T lymphocytes was increased by both gavage and intraperitoneal administration (all P<0.05). Conclusions:AAEM-30% can promote the maturation of DC and enhanced the immunity of mice without obvious side effects.
5.Progress in microRNA/lncRNA regulating dendritic cell differentiation, maturation and function
Shanshan CAI ; Jinyao LI ; Lin YANG ; Aipire ADILA·
Chinese Journal of Microbiology and Immunology 2022;42(7):570-576
Dendritic cells (DC) as professional antigen-presenting cells can activate na?ve T cells and play an important role in bridging innate immunity and acquired immunity. Therefore, the differentiation and maturation of DC and the mechanism in its function regulatory have attracted much attention. With the rapid development of high-throughput sequencing, noncoding RNAs (ncRNAs) have been gradually known. In recent years, increasing studies have reported that ncRNAs play an importantly role in regulating the differentiation and maturation of DC. In this paper, the regulatory effects of microRNAs and long ncRNAs on the differentiation, maturation and function of DC were reviewed.
6.Advances in Molecular Biomarker for Pulmonary Large Cell Neuroendocrine Carcinoma.
Jinyao ZHANG ; Lin YANG ; Junling LI
Chinese Journal of Lung Cancer 2020;23(11):983-988
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a pathological subtype of lung neuroendocrine cancer, which accounts for 2.4%-3.1% in surgical specimens of lung cancer. It is characterized by high invasiveness and poor prognosis, and highly correlated with smoking. There are few relevant studies due to the low incidence and small sample size. Therefore, it is relatively difficult to diagnosis and treatment in clinical practice. In this review, we described molecular subtype, diagnostic and prognostic-related markers about large cell neuroendocrine carcinoma of lung based on the recent progress in genomic sequencing and molecular markers, to find the direction for the next research.
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7.Curvelet denoising algorithm for medical ultrasound image based on adaptive threshold.
Zhemin ZHUANG ; Weike YAO ; Jinyao YANG ; FenLan LI ; Ye YUAN
Chinese Journal of Medical Instrumentation 2014;38(6):398-401
The traditional denoising algorithm for ultrasound images would lost a lot of details and weak edge information when suppressing speckle noise. A new denoising algorithm of adaptive threshold based on curvelet transform is proposed in this paper. The algorithm utilizes differences of coefficients' local variance between texture and smooth region in each layer of ultrasound image to define fuzzy regions and membership functions. In the end, using the adaptive threshold that determine by the membership function to denoise the ultrasound image. The experimental text shows that the algorithm can reduce the speckle noise effectively and retain the detail information of original image at the same time, thus it can greatly enhance the performance of B ultrasound instrument.
Algorithms
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Diagnostic Imaging
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Image Processing, Computer-Assisted
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Ultrasonics
8.The protective effect of atorvastatin on myocardium in patients with percutaneous coronary intervention
Feng XU ; Haitao XU ; Xuecheng YANG ; Lu CHENG ; Jinyao LIU
Chinese Journal of Postgraduates of Medicine 2012;(34):8-11
Objective To investigate the effect of atorvastatin on the expressions of solubility P-selectin(sP-selectin) and high sensitive C reactive protein(hs-CRP) in patients with percutaneous coronary intervention (PCI),and to explore the protective effect of atorvastatin on myocardium.Methods A total of 100 acute coronary syndrome patients having underwent successful PCI were enrolled in this study.All patients were divided into 3 groups by random digits table method:standard treatment group (group A,30 patients,atorvastatin 20 mg),low-dose atorvastatin pretreatment group (group B,35 patients,preoperative 12 h and 2 h atorvastatin 40 mg and 20 mg,respectively) and high-dose atorvastatin pretreatment group (group C,35 patients,preoperative 12 h and 2 h atorvastatin 80 mg and 40 mg,respectively).The level of sP-selectin was measured with ELISA.The level of hs-CRP was measured with latex enhanced immunoturbidimetry.Results Before operation,the levels of sP-selectin in group A,B,C were (2.32 ±0.40),(2.51 ± 0.33),(2.47 ± 0.28) μ g/L.After 6 and 12 h of operation,the levels of sP-selectin in group A,B,C were (4.12 ± 0.75),(3.34 ± 0.42),(3.31 ± 0.46) μ g/L and (5.64 ± 1.07),(4.08 ± 0.74),(3.84 ±0.48) μg/L.The levels of sP-selectin in group A,B,C after operation were significantly higher than that before operation (P < 0.05).At the same time point,the levels of sP-selectin in group B,C after operation were significantly lower than that in group A (P< 0.05).Before operation,the levels of hs-CRP in group A,B,C were (4.32 ±0.51),(4.46 ±0.57),(4.29 ±0.43) mg/L,after 6 and 12 h of operation,the levels of hs-CRP in group A,B,C were (8.91 ± 1.34),(7.44 ± 1.06),(7.28 ±0.95) mg/L and (13.66 ± 1.49),(8.08 ± 1.14),(7.92 ± 1.04) mg/L.The levels of hs-CRP in group A,B,C after operation were significantly higher than that before operation (P< 0.05).At the same time point,the levels of hs-CRP in group B,C after operation were significantly lower than that in group A (P < 0.05).The analysis of Pearson correlation showed,the level of sP-selectin was positively related with hs-CRP (r =0.753,P <0.01).The incidence of perioperative myocardial infarction was 23.3% (7/30),5.7% (2/35) and 2.9% (1/35) in group A,B and C,respectively.The incidence in group A was significantly higher than that in group B and C (P < 0.05).But there was no significant difference between group B and group C (P> 0.05).Conclusion The atorvastatin pretreatment can decrease the levels of sP-selectin and hs-CRP in patients after PCI,which play an important role in myocardium protection.
9.Growth-inhibiting effect of psoralen plus ultraviolet-A light therapy on K562 cells
Dejie ZHANG ; Shilin HUANG ; Nannan CHEN ; Yang XIANG ; Peiman YANG ; Jinyao ZHAO
Journal of Integrative Medicine 2005;3(6):480-3
OBJECTIVE: To observe the effects of psoralen plus ultraviolet-A light (PUVA) on K562 cells and the relative mechanism. METHODS: The effects of psoralen, ultraviolet-A light and PUVA on K562 cells were assayed by monotetrazolium test (MTT). DNA content was analyzed by flow cytometry (FCM). The apoptotic rates of K562 cells treated with 40 and 80 microg/ml psoralen for 24 and 48 hours were assayed by Annexin-V-FITC/PI reagent kit on FCM respectively. The ultrastructures of apoptotic cells were observed by a transmission electron microscope (TEM). RESULTS: Either single psoralen therapy or single ultraviolet-A irradiation had inhibiting effect on K562 cells. The inhibiting effect of PUVA on K562 cells was stronger than that of the single psoralen therapy or single ultraviolet-A light irradiation (P<0.05). Apoptotic peak (AP) was detected by FCM. TEM test showed that K562 cells treated with PUVA were smaller, having condensed cell nucleus, assembled chromatin, disintegrated nucleus body and the majority of the cells appeared to be apoptotic conformation. CONCLUSION: Psoralen has inhibiting effect on K562 cells, and the effect of PUVA is more significant. It is suggested that 10 min irradiation and 40 microg/ml terminal concentration of psoralen be probably the best choice for PUVA. The inhibiting effect of PUVA is due to apoptosis.
10.EXPRESSION OF ABC GENE FAMILY IN MCF-7/ADM CELL LINE AND THE REVERSAL EFFECT OF REALGAR ON THESE GENES
Yuhua WANG ; Changhui GE ; Jinyao ZHAO ; Peiman YANG ;
Acta Anatomica Sinica 2002;0(06):-
Objective To study the expression of ABC gene family of MCF 7/ADM cells as compared to parental cell line MCF 7/S, and its reversion by realgar of the expressed genes. Methods Expression of ABC family genes was examined by RT PCR, and cell growth by MTT test. Results The expression of ABC gene family was positive in MCF 7/ADM cells compared to MCF 7/S cells; Realgar can down regulate the expression ABC gene family in MCF 7/ADM cells; the IC 50 of ADM to MCF 7/ADM cells was decreased.Conclusion ABC gene family was responsible for the induced resistance of MCF 7/ADM cells to ADM; Realgar is able to reverse partly the multidrug resistance of the human breast cancer cell line MCF 7/ADM. [

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