1.Visualization analysis of macrophage polarization in tissue repair process
Jinxia CHANG ; Yufei LIU ; Shaohui NIU ; Chang WANG ; Jianchun CAO
Chinese Journal of Tissue Engineering Research 2025;29(7):1486-1496
BACKGROUND:During tissue repair and regeneration,macrophages exhibit multiple activities such as promoting inflammation,anti-inflammation,fibrosis,and wound healing at various stages of tissue damage.The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE:To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods,as well as the research level of global scientific and clinical workers in this field. METHODS:Using bibliometric analysis methods,this study employed Citespace literature visualization analysis software and VOSviewer tools,retrieving related literature from 2013 to 2023 in the Web of Science Core Collection's Science Citation Index Expanded(SCI-Expanded)and Social Sciences Citation Index Expanded(SSCI-Expanded)databases.The analysis results were presented in a dynamic map format,revealing the main trends and focuses of the research. RESULTS AND CONCLUSION:The number of publications in this field had dramatically increased from 2013 to 2023,with a significant rise starting in 2017.Chinese researchers had the highest number of publications,with 642 papers,while American researchers began focusing on this field early on.Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area.Shanghai Jiao Tong University had produced the most publications.In recent years,keywords such as"hyaluronic acid"and"regulation"had been prevalent.Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms,interactions with other cell types,and its behavior under specific pathological conditions.The main research areas include the role of macrophages in wound healing,cardiovascular diseases,chronic inflammation,tumor microenvironments,and regenerative medicine.A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration,thereby improving patient treatment outcomes.
2.Improvement effect and mechanism of paeoniflorin on glucose metabolism,inflammation and oxidative stress in rats with gestational diabetes mellitus
Guiying LIU ; Li NIU ; Xueyun CHANG ; Xiuyun ZHOU
China Pharmacy 2024;35(12):1476-1481
OBJECTIVE To explore the effect of paeoniflorin on glucose metabolism, inflammation and oxidative stress in rats with gestational diabetes mellitus (GDM) and its potential mechanism based on nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1)/nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 (NQO1) signaling pathway. METHODS The female rats fed with high fat and high sugar diet and the male rats fed with an ordinary diet were caged, the successfully conceived rats were collected, and streptozotocin was injected intraperitoneally once to induce the GDM model. The successfully modeled rats were randomly divided into the model group, metformin hydrochloride group (200 mg/kg metformin by gavage), paeoniflorin low-, high-dose groups (45, 90 mg/kg paeoniflorin by gavage, respectively), paeoniflorin+ML385 group (90 mg/kg paeoniflorin by gavage and intraperitoneal injection of 30 mg/kg Nrf2 inhibitor ML385), with 12 rats in each group; in addition, another 12 conceived rats fed with an ordinary diet were selected as the control group. The rats in each drug group were given the corresponding drug/normal saline, once a day, for 2 consecutive weeks. Glucose metabolism indexes [fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR)], serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α)] and renal tissue oxidative stress indexes [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px)] were detected; the pathological changes of renal tissue were observed, and the protein expressions of Nrf2, HO-1 and NQO1 in renal tissue were detected. RESULTS Compared with the control group, the renal tissue lesions of the model group were obvious, including glomerular atrophy, edema degeneration of renal tubular epithelial cells and a large number of inflammatory cell infiltration; the levels of FBG and FINS, HOMA-IR, the levels of IL-6 and TNF-α in serum, and the level of MDA in renal tissue were significantly increased (P<0.05), while the levels of SOD and GSH-Px and the protein expressions of Nrf2, HO-1 and NQO1 in renal tissue were significantly decreased (P<0.05). Compared with the model group, the renal tissue lesions of rats in paeoniflorin low-dose and high-dose groups were reduced, the above quantitative indexes were significantly improved, and the improvement effect was better in high-dose group (P<0.05), while ML385 could significantly reverse the improvement effect of paeoniflorin on the above indexes (P<0.05). CONCLUSIONS Paeoniflorin can improve the abnormal glucose metabolism, inflammation and oxidative stress damage of renal tissue in GDM rats, which may be related to the activation of Nrf2/HO-1/NOQ1 signaling pathway.
3.Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children
Cui-Li LIANG ; Guo-Chang LIU ; Jing CHENG ; Hui-Lin NIU ; Wen FU ; Li-Yu ZHANG ; Wei JIA ; Wen ZHANG ; Li LIU
Chinese Journal of Contemporary Pediatrics 2024;26(2):158-163
Objective To investigate the value of the human chorionic gonadotropin(hCG)stimulation test in the diagnosis of disorder of sexual development(DSD)in children.Methods A retrospective analysis was conducted on 132 children with DSD.According to the karyotype,they were divided into three groups:46,XX group(n=10),46,XY group(n=87),and sex chromosome abnormality group(n=35).The above groups were compared in terms of sex hormone levels before and after hCG stimulation test,and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed.Results There was no significant difference in the multiple increase of testosterone after stimulation among the three groups(P>0.05).In the 46,XY group,the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes.Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue(P<0.05).Conclusions The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD,and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.[Chinese Journal of Contemporary Pediatrics,2024,26(2):158-163]
4.Alvianolic acid B exerts a protective effect on random skin flaps through autophagy mediated by activation of TFE3
Zhong-Bing HAN ; Hui-Wen YANG ; Hai-Zhou NIU ; Kuan-Kuan ZHANG ; Yang-Yang LIU ; Pan-Pan XU ; Ling-Ti KONG ; Chang-Chun ZHANG
Chinese Pharmacological Bulletin 2024;40(10):1912-1920
Aim To observe the role of salvianolic acid B(Sal B)in enhancing the survival of random skin flaps and to preliminarily explore its potential mecha-nisms.Methods The appearance,degree of edema,color and hair condition of the skin flap were evaluated seven days after operation.The vascular network and blood flow of random flaps were measured by laser Doppler flow measurement.HE staining was used to detect the growth of microvessels in random flaps.The expressions of VEGF and CD34 were detected by im-munohistochemistry,the expressions of RIPK1,2 and LC3 Ⅱ were detected by immunofluorescence,and the effects of autophagy related proteins and signaling path-ways were detected by Western blot.Results The ex-perimental results showed that Sal B induced autophagy in the random skin flaps,promoted angiogenesis,and reduced oxidative stress and necrotic apoptosis,signifi-cantly increasing the survival rate of the flaps.Immu-nohistochemistry,immunofluorescence staining,and Western blot confirmed that Sal B induced autophagy in the random skin flaps by activating TFE3 protein.Conclusion Sal B can promote autophagy in cells of random skin flaps and reduce their necrotic apoptosis by activating TFE3 protein.
5.Healthy Lifestyle and the Risk of Metabolic Dysfunction-Associated Fatty Liver Disease: A Large Prospective Cohort Study
Qing CHANG ; Yixiao ZHANG ; Tingjing ZHANG ; Zuyun LIU ; Limin CAO ; Qing ZHANG ; Li LIU ; Shaomei SUN ; Xing WANG ; Ming ZHOU ; Qiyu JIA ; Kun SONG ; Yang DING ; Yuhong ZHAO ; Kaijun NIU ; Yang XIA
Diabetes & Metabolism Journal 2024;48(5):971-982
Background:
The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD.
Methods:
A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors.
Results:
The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle.
Conclusion
Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.
6.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
7. Eplerenone protects contralateral kidney tissue from obstruction in pregnant rats with chronic kidney disease
Chang XU ; Wen-Ping ZHOU ; Jie-Qi NIU ; Hong-Shuang WANG ; Meng-Juan ZHANG ; Jia-Zhi LIU ; Chang XU ; Qing-You XU ; Wen-Ping ZHOU ; Jie-Qi NIU ; Yun-Zhao XIONG ; Yan ZHONG ; Zheng WANG ; Qing-You XU ; Yun-Zhao XIONG ; Yan ZHONG ; Xiang-Ting WANG ; Zheng WANG ; Hong-Shuang WANG ; Meng-Juan ZHANG ; Jia-Zhi LIU
Chinese Pharmacological Bulletin 2023;39(8):1534-1540
Aim To study the protective effect of eplerenone on the contralateral kidney in pregnant rats with chronic kidney disease (CKD) and its mechanism. Methods Female Wistar rats were randomly divided into sham-operation group, sham-operation pregnancy group, model group and eplerenone group. The rats in the model group and eplenone group had ligation unilateral ureter, and the rats in the eplenone group were treated with 100 mg • kg
8.Sampling data of fresh frozen plasma, cryoprecipitates and leukocyte-free platelet quality monitoring in Hebei Province from 2015 to 2021: a retrospective analysis
Ying CHANG ; Zixuan ZHANG ; Xiaotong ZHANG ; Hongwei NIU ; Jianpeng ZHAO ; Chunfang LI ; Lexia LIU ; Wei ZHANG ; Fengxia YANG ; Xiaohong SUN
Chinese Journal of Blood Transfusion 2023;36(6):519-528
【Objective】 To form the sampling data interval by retrospectively analyzing the sampling data of quality monitoring of fresh frozen plasma, cryoprecipitates and leukocyte-free platelets in all blood stations in Hebei Province during the past 7 years. 【Methods】 The data of blood component sampling from 12 blood station quality control laboratories in Hebei from 2015 to 2021 were collected. The FⅧ content and plasma protein content of fresh frozen plasma, the FⅧ content and fibrinogen content of cryoprecipitates, and the leukocyte residuals, red blood cell mixed and platelet content of leukocyte-free platelets were taken as the objects for discrete point and fitted curve analysis. 【Results】 The FⅧ level of fresh frozen plasma: (1.36±1.1) IU/mL, 5 blood stations showed a representative overall high or low or fluctuated characteristics; Fresh frozen plasm-plasma protein items: overall mean ±SD: (61.13±16.7) g/L, four blood stations showed scattered distribution or continuous high value scattered points; Cryoprecipitates FⅧ: the overall mean ±SD: (134.25±58.7) IU/mL, four blood stations showed the differentiation characteristics of continuous high, low or stable in the middle; Cryoprecipitates-fibrinogen items: the overall mean ±SD: (215.27±83.5) mg, five blood stations showed the overall high or low and fluctuated. Leukocyte-free apheresis platelet-to-leukocyte residual items: overall mean ±SD: 0.37±0.96 (×106/bag), two blood stations showed a relatively high representative overall characteristics, and the rest were concentrated between 0 and 1; The total mean ±SD of platelet-to-red blood cell mixture without leukocyte was 2.45±2.82 (×109/bag), with obvious segmented concentrated distribution, and scattered distribution in 3 blood centers. Platelet content: the overall mean ±SD was 3.14±1.55 (×1011/bag), many deviations were noticed in 3 blood stations, and 1 blood station showed representative overall high characteristics. 【Conclusion】 This analysis shows that the distribution status of each blood station in different items is similar. The distribution status of discrete point groups and the change trend of the concentrated part of the fitting curve show that there are some differences in the monitoring level between the quality control laboratories of each blood station, and the update of detection instruments and reagents and the selection of detection methods greatly affect the test results. The summary data presented the index interval framework formed in the past 7 years, which helped to understand the difference between the results of each laboratory, correct the accuracy of the test results, better play the guiding role of quality monitoring in the blood preparation process, and continue to enhance the standardization of the whole process of blood collection and supply in the province.
9.Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis.
Qian YU ; Chang LI ; Qinghui NIU ; Jigang WANG ; Zhaodi CHE ; Ke LEI ; He REN ; Boyi MA ; Yixing REN ; Pingping LUO ; Zhuming FAN ; Huan ZHANG ; Zhaohui LIU ; George L TIPOE ; Jia XIAO
Acta Pharmaceutica Sinica B 2023;13(6):2628-2644
The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

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