1.Celastrol directly targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression.
Yuyu ZHU ; Lixin ZHAO ; Wei YAN ; Hongyue MA ; Wanjun ZHAO ; Jiao QU ; Wei ZHENG ; Chenyang ZHANG ; Haojie DU ; Meng YU ; Ning WAN ; Hui YE ; Yicheng XIE ; Bowen KE ; Qiang XU ; Haiyan SUN ; Yang SUN ; Zijun OUYANG
Acta Pharmaceutica Sinica B 2025;15(2):876-891
Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.
2.Yiqi Yangyin Huazhuo Tongluo Formula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Kelei GUO ; Yingli LI ; Chenguang XUAN ; Zijun HOU ; Songshan YE ; Linyun LI ; Liping CHEN ; Li HAN ; Hua BIAN
Journal of Southern Medical University 2025;45(1):27-34
OBJECTIVES:
To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism.
METHODS:
Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay.
RESULTS:
MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera.
CONCLUSIONS
YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals
;
MicroRNAs/genetics*
;
Podocytes/pathology*
;
Drugs, Chinese Herbal/pharmacology*
;
Autophagy/drug effects*
;
Rats, Wistar
;
Protein Kinases/metabolism*
;
Rats
;
Forkhead Box Protein O1
;
Mice
;
Mitochondria/drug effects*
;
Ubiquitin-Protein Ligases/metabolism*
;
Glucose
;
Diabetic Nephropathies
;
Male
;
Membrane Proteins/metabolism*
;
Intracellular Signaling Peptides and Proteins
3.Discussion on issues and strategies for the transformation of scientific and technological achievements in specialized hospitals
Zijun TANG ; Wei ZHANG ; Xiaofen MO
Modern Hospital 2024;24(10):1480-1482,1489
Promoting the transformation of scientific and technological achievements in hospitals can significantly enhance the new productivity levels and innovation capabilities in China's biomedicine sector.However,specialized hospitals face several challenges due to their smaller scale and singular discipline layout.These include insufficient interdisciplinary collaboration,in-adequate funding and capacity to attract funds,a lack of awareness and motivation among hospital staff regarding achievement transformation,limited experience in transforming results,and difficulties in industrializing outcomes.To effectively improve the transformation of scientific and technological achievements,specialized hospitals can adopt strategies such as strengthening the in-tegration of industry,academia,research,and healthcare;increasing financial investment;enhancing theoretical training on a-chievement transformation;building a team of transformation professionals;and exploring diverse pathways for achievement trans-formation.
4.Construction and clinical practice of vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics
Xinhua XIA ; Ying WANG ; Pengbo YAN ; Yanling SUN ; Meimei SI ; Lie QIN ; Yuxia WANG ; Yanan LI ; Ling CHEN ; Zijun ZHANG
Chinese Journal of Practical Nursing 2024;40(4):283-288
Objective:To establish an environmental management strategy for the prevention of ventilator-associated pneumonia from the perspective of etiological characteristics and to verify its application effect.Methods:Based on a sampling survey, this study constructed preventive management strategies for ventilator-associated pneumonia by blocking pathogen characteristics from the perspective of both colonization and infection management in patients. From July 2021 to June 2023, a non-synchronous randomized controlled study was conducted, including a control group of 59 cases and an experimental group of 57 cases from ICU of Tianjin Teda Hospital, all of them were mechanically ventilated patients. The effectiveness of the strategy was confirmed.Results:In the control group, there were 35 males and 24 females, with an average age of (46.97 ± 18.84) years. In the experimental group, there were 39 males and 18 females, with an average age of (47.49 ± 13.85) years. During the study period, there were 9 cases of ventilator-associated pneumonia (VAP) in the control group and 2 cases in the experimental group, the difference between the two groups was statistically significant (exact odds ratio=0.031). The duration of mechanical ventilation in the experimental group (122.41 ± 18.36) h, which was shorter than that in the control group (187.62 ± 18.05) h, and the difference was statistically significant ( t=19.28, P<0.05). The length of ICU stay in the experimental group was (8.38 ± 0.79) d, in the control group was (10.99 ± 1.10) d, the difference between them was statistically significant ( t=14.66, P<0.05). On the 7th day, there were 7 cases of positive pathogenic bacteria in sputum culture in the experimental group, which was significantly different from the 29 cases in the control group ( χ2=16.73, P<0.05). Conclusions:The vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics can reduce the incidence of VAP, shorten the duration of mechanical ventilation and ICU stay, and reduce the pathogen load in the sputum of mechanically ventilated patients on the 7th day.
5.Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study
Tingting CHEN ; Chenggong ZENG ; Juan WANG ; Feifei SUN ; Junting HUANG ; Jia ZHU ; Suying LU ; Ning LIAO ; Xiaohong ZHANG ; Zaisheng CHEN ; Xiuli YUAN ; Zhen YANG ; Haixia GUO ; Liangchun YANG ; Chuan WEN ; Wenlin ZHANG ; Yang LI ; Xuequn LUO ; Zelin WU ; Lihua YANG ; Riyang LIU ; Mincui ZHENG ; Xiangling HE ; Xiaofei SUN ; Zijun ZHEN
Cancer Research and Treatment 2024;56(4):1252-1261
Purpose:
The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored.
Materials and Methods:
On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL).
Results:
A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse.
Conclusion
This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).
6.Copper Deficiency Myeloneuropathy in a Patient With Wilson’s Disease
Yu WANG ; Zijun WEI ; Jianing MEI ; Xueyi HAN ; Hongping ZHAO ; Yulong ZHU ; Ping JIN ; Yunyun ZHANG
Journal of Movement Disorders 2024;17(1):123-126
7.Literature Survey on Edible Medicinal Plants in Lancang-Mekong Countries
Qingqing LI ; Shuo WANG ; Zijun ZHANG ; Yuanchen ZHAO ; Shihuan TANG ; Zhiyong LI ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(11):179-189
Lancang-Mekong countries refer to the six countries that the Lancang-Mekong River flows through, including China, Laos, Myanmar, Thailand, Cambodia, and Vietnam. These countries are geographically adjacent with similar cultures and have long history of traditional medicine and high plant diversity. Since ancient times, medicinal plants have been introduced into China from the countries along the river, including a variety of medicinal plants with edible and healthcare values, which is an important way for the transnational circulation of medicinal resources. This paper briefly described the history and application of edible medicinal plants in the six Lancang-Mekong countries and summarized more than 150 edible medicinal plants from the other five countries except China. These 150 medicinal plants belong to 66 families such as Labiatae, and 12 species of them are used as edible medicinal plants in all the six countries. Further, we collected the information of these edible medicinal plants, including the origins, efficacy, indications, medicinal edible parts, edible values, and the traditional application of these plants in China. Some valuable edible medicinal plants in the other five countries are considered to have a promising prospect of application in China and may be introduced to China as new medicinal resources. These efforts will be conducive to the cooperation in traditional medicine among Lancang-Mekong countries.
8.Effects of total flavone of oldenlandia diffusa on the proliferation and apoptosis of hepatocellular carcinoma stem cell
Bowen YAO ; Yazhao LI ; Zijun LIAO ; Ye LU ; Xiang ZHANG ; Jiequn MA ; Qian LI ; Yanbing ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):389-395
【Objective】 To investigate the effects of total flavone of oldenlandia diffusa (FOD) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) stem cells sorted from Huh7. 【Methods】 Human HCC cell lines Huh7 was cultured in vitro; CD133 positive (CD133+) stem cells in Huh7 cell line were sorted by flow cytometry, and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting. CD133+-Huh7 was stimulated by different concentrations (0 μg/mL, 50 μg/mL, 100 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h, 72 h and 96 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on CD133+-Huh7 proliferation while Annexin V-PE/7-AAD was used to detect the effect of FOD on CD133+-Huh7 apoptosis. Western blotting was used to detect the protein expressions of protein 53 (P53), factor associated suicide-Fas-associating protein with a novel death domain (Fas-FADD), B-cell lymphoma-2 (Bcl-2), Cleaved-Caspase3, and Bcl-2 associated X protein (Bax). 【Results】 More than 95% of stem cells were purified for further experiments. Cell proliferation of CD133+-Huh7 was significantly inhibited by FOD, with the significant suppression at the concentration of 100 μg/mL for 72 h compared with negative control group (P<0.05). The apoptosis rate was significantly upregulated than that in the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and Cleaved-Caspae3 increased via FAS/FADDD and P53 axis. 【Conclusion】 FOD can significantly inhibit the proliferation and promote the apoptosis of CD133+-Huh7.
9.Optic cup and disc segmentation model based on linear attention and dual attention.
Zijun LAN ; Jun XIE ; Yan GUO ; Zhe ZHANG ; Bin SUN
Journal of Biomedical Engineering 2023;40(5):920-927
Glaucoma is one of blind causing diseases. The cup-to-disc ratio is the main basis for glaucoma screening. Therefore, it is of great significance to precisely segment the optic cup and disc. In this article, an optic cup and disc segmentation model based on the linear attention and dual attention is proposed. Firstly, the region of interest is located and cropped according to the characteristics of the optic disc. Secondly, linear attention residual network-34 (ResNet-34) is introduced as a feature extraction network. Finally, channel and spatial dual attention weights are generated by the linear attention output features, which are used to calibrate feature map in the decoder to obtain the optic cup and disc segmentation image. Experimental results show that the intersection over union of the optic disc and cup in Retinal Image Dataset for Optic Nerve Head Segmentation (DRISHTI-GS) dataset are 0.962 3 and 0.856 4, respectively, and the intersection over union of the optic disc and cup in retinal image database for optic nerve evaluation (RIM-ONE-V3) are 0.956 3 and 0.784 4, respectively. The proposed model is better than the comparison algorithm and has certain medical value in the early screening of glaucoma. In addition, this article uses knowledge distillation technology to generate two smaller models, which is beneficial to apply the models to embedded device.
Humans
;
Optic Disk/diagnostic imaging*
;
Glaucoma/diagnosis*
;
Algorithms
;
Diagnostic Techniques, Ophthalmological
;
Databases, Factual
10.A comparative study of iodine content in serum, plasma and whole blood
Liting YANG ; Zijun YAO ; Zhen WANG ; Han ZHANG ; Yan WANG ; Huailan GUO
Chinese Journal of Endemiology 2023;42(6):502-506
Objective:To evaluate the consistency of individual iodine nutrition levels by serum iodine, plasma iodine and whole blood iodine, and to provide reference for iodine-related epidemiological investigation.Methods:Healthy adults aged 18 - 59 years were recruited from the Research Center of Environment and Health in Water Source Area of South-to-North Water Diversion of Hubei University of Medicine. Whole blood sample was collected and serum and plasma were separated. The content of iodine in serum, plasma and whole blood was determined by inductively coupled plasma mass spectrometry (ICP-MS), and the linear relationship, precision and accuracy of the standard curve of the detection method were evaluated. The difference of three kinds of blood iodine levels was analyzed by variance analysis of compatibility group design, and Passing-Bablok regression and Bland-Altman plot were used to evaluate the consistency between serum iodine and plasma iodine.Results:The linear range of iodine in serum, plasma and whole blood was 0.0 - 25.0 μg/L, and the correlation coefficients ( R2) were all > 0.999. The relative standard deviation of 8 mixed blood samples ranged from 1.9% to 4.3% ( n = 6), and the determination results of blood iodine certified standard substances were all within the reference range. The recovery rate of the added standard ranged from 99% to 106%. The iodine levels in serum, plasma and whole blood of 50 volunteers were (57.31 ± 8.06), (57.49 ± 8.50) and (33.89 ± 5.40) μg/L, respectively, and there was no statistically significant difference between serum iodine and plasma iodine ( P = 0.904). The results of Passing-Bablok regression showed that there was no statistically significant difference in bias between serum iodine and plasma iodine ( P = 0.538). The Bland-Altman plot indicated that the difference between serum iodine and plasma iodine was within the consistency limit. Conclusion:The results of plasma iodine and serum iodine are in good agreement, and plasma iodine can be used as an evaluation index of individual iodine nutrition level. But there is no consistency between whole blood iodine and serum iodine.

Result Analysis
Print
Save
E-mail