1.Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis
Yixin CHEN ; Bingfa LI ; Jing QUAN ; Zhe LI ; Yan LI ; Yinbo TANG
Neurospine 2024;21(2):642-655
Objective:
The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.
Methods:
By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.
Results:
The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.
Conclusion
In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
2.Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis
Yixin CHEN ; Bingfa LI ; Jing QUAN ; Zhe LI ; Yan LI ; Yinbo TANG
Neurospine 2024;21(2):642-655
Objective:
The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.
Methods:
By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.
Results:
The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.
Conclusion
In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
3.Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis
Yixin CHEN ; Bingfa LI ; Jing QUAN ; Zhe LI ; Yan LI ; Yinbo TANG
Neurospine 2024;21(2):642-655
Objective:
The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.
Methods:
By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.
Results:
The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.
Conclusion
In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
4.Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis
Yixin CHEN ; Bingfa LI ; Jing QUAN ; Zhe LI ; Yan LI ; Yinbo TANG
Neurospine 2024;21(2):642-655
Objective:
The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.
Methods:
By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.
Results:
The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.
Conclusion
In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
5.Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis
Yixin CHEN ; Bingfa LI ; Jing QUAN ; Zhe LI ; Yan LI ; Yinbo TANG
Neurospine 2024;21(2):642-655
Objective:
The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.
Methods:
By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.
Results:
The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.
Conclusion
In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
6.Preliminary study of stereotactic cardiac radioablation in radiotherapy of ventricular arrhythmia
Jing LI ; Qingyong CHEN ; Guangjun LI ; Yan LI ; Yingjie ZHANG ; Changhu LI ; Long BAI ; Renming ZHONG ; Yinbo HE ; Sen BAI ; Qing YANG ; Feng XU
Chinese Journal of Radiation Oncology 2022;31(3):260-265
Objective:To introduce the stereotactic cardiac radioablation (SCRA) based on the stereotactic body radiotherapy (SBRT), and comprehensively evaluate the new approach by short-term effectiveness and safety.Methods:Patients with ventricular arrhythmia (VA) were evaluated and included in this clinical trial, who were immobilized by vacuum bag and performed simulation with 4-dimensional computed tomography (4DCT). In this study, the planning target volume (PTV) was set as the target to design a SBRT plan using volumetric modulated arc therapy (VMAT), which was evaluated by dose parameters such as R 50%, homogeneity index and conformity index, etc. The results of Holter and echocardiography were monitored during the follow-up and compared with the data before treatment. Results:Three subjects with ventricular tachycardia (VT) and one with premature ventricular contraction (PVC) received the same prescription of 25 Gy in a single fraction. The average volume of PTV was 71.4 cm 3(60.3-89.4 cm 3). The average time of beam delivery was 12.0 min (4.5-21.0 min). And the short-term follow-up lasted for an average of 18 weeks (14-25 weeks), which showed significant decrease in both VT and PVC load without complications. Conclusion:This study reports the implementation method of SCRA and proves its short-term effectiveness and safety, but the effects and standards of the key radiotherapy techniques still need to be explored.
7.Thoughts on the strategy and mechanism for the regular prevention and control of COVID-19
Yinbo LUO ; Yang WU ; Man LIU ; QI CHEN ; Jiafa LIU ; Xuhua GUAN ; Yeqing TONG
Journal of Public Health and Preventive Medicine 2020;31(6):1-5
Since the outbreak of the COVID-19 at the end of December 2019, Hubei province has actively adopted a series of prevention and control measures such as “quarantine, treatment, testing, and containment”, and have basically blocked the spread of COVID-19. However, with the development of overseas epidemics and the occurrence of case clusters in local areas, we not only face the threat of imported cases, but also face the urgent need to resume normal work and daily life. This puts forward higher requirements for regular prevention and control of COVID-19. Therefore, we should more deeply understand the significance of regular prevention and control as well as the epidemic situation in our province, summarize experience and lessons, and adhere to the prevention and control strategy of “government-led, group-specialist combination, and specialized-oriented”. Meanwhile, it is necessary to implement the working requirement that combines regular prevention and control surveillance with rapid emergency response to local COVID-19 outbreaks. Furthermore, we should establish a regular multi-point trigger early warning mechanism for COVID-19, strengthen the reserve of emergency supplies and carry out training and drills on epidemic prevention and control across the province to make full preparations for the coming autumn and winter epidemics. The most important is to reform the system of disease prevention and control and public health, comprehensively improve the ability of prevention and treatment, and promote the modernization of public health governance.
8.The epidemiological characteristics of COVID-19 in Hubei Province, China
Qi CHEN ; Yang WU ; Chuding CHEN ; Man LIU ; Rui YANG ; Siquan WANG ; Xingxing LU ; Yinbo LUO ; Yeqing TONG ; Xuhua GUAN
Journal of Public Health and Preventive Medicine 2020;31(3):1-5
Objective To understand the epidemiological characteristics of the novel coronavirus diseases 2019 (COVID-19), and to scientifically guide the prevention and control of COVID-19 in Hubei Province. Methods All COVID-19 cases reported online in Hubei Province as of March 31, 2020 were extracted from Hubei's Infectious Disease Information System. The epidemic curve, age and sex characteristics, and spatiotemporal distribution characteristics of the COVID-19 cases were analyzed. Results As of March 31, 2020, a total of 70 764 cases were reported in Hubei Province, including 49 195 confirmed cases. A total of 4 579 deaths occurred among the confirmed cases, and the reported case fatality rate was 6.47%. The peak of the onset of symptoms occurred from January 20 to February 14, 2020. The sex ratio of male to female of the confirmed cases was 0.99: 1, and most were 30-69 years old. The cases diagnosed before January 5 were mainly reported by Wuhan City. From January 6 to January 31, all counties and districts in the province reported that the incidence of confirmed COVID-19 cases began to rise, and about 50% counties reported that the morbidity rate of confirmed COVID-19 cases was over 10 cases per 100 000. The morbidity rate of COVID-19 cases rose rapidly between February 1-15, and then gradually reached its peak after February 16. Conclusion Wuhan City of Hubei Province first discovered and reported the COVID-19 outbreak. The onset of symptoms peaked in January 20 to February 14, and the 30-69 years old group was the key population. Many measures such as restricting personnel movement, reducing contact, and strengthening health education played an important role in controlling the outbreak of COVID-19 in Hubei.
9.MRI findings of primary Rosa-i Dorfman disease in the central nervous system
Chunmiao LIN ; Jianhua YUAN ; Xiangyang GONG ; Zhongxiang DING ; Yinbo WU ; Wanyuan CHEN
Journal of Practical Radiology 2019;35(11):1728-1731
Objective To investigate the imaging features of primary Rosa-i Dorfman disease (RDD)in the central nervous system and to increase the understanding of the disease.Methods The MRI findings of 5 cases with primary RDD of the central nervous system were analyzed retrospectively,and the related literatures were reviewed.Results Four cases located in the cranium,1 case located in the spinal cord,and 5 tumors were attached to the brain (ridge)membrane.The tumor was equal and low signal on T1 WI,and equal or slightly high signal on T2 WI.Obvious enhancement could be seen on enhance study,and obvious enhancementwas visible in adjacent brain (ridge)membrane,in which 1 case involved the skull,with thickening and strengthening of the skull.Tumors were attached to the meninges in a wide range,the local meninges of 3 cases were penetrated by tumor.Conclusion If young and middle-aged males have no obvious specific clinical manifestations,the images of MRI are single or multiple lesions that are closely related to the brain (ridge)membrane in larger extent and easily penetrate the brain (ridge)membrane,the possibility of RDD should be considered.
10.Expression difference of DNA mismatch repair gene hMLH1 and hMSH2 between schistosomiasis-associated colorectal cancer and sporadic colorectal cancer.
Yinbo CHEN ; Zhuo LIU ; Jun QIAN ; Haiyang FENG ; Dechuan LI ; Yongtian FAN
Chinese Journal of Gastrointestinal Surgery 2016;19(1):75-79
OBJECTIVETo investigate the expression difference of DNA mismatch repair gene hMLH1 and hMSH2 between schistosomiasis-associated colorectal cancer and sporadic colorectal cancer.
METHODClinical and pathological data of colorectal cancer patients receiving operations in Zhejiang Cancer Hospital between January 2008 and December 2010 were retrospectively analyzed. Patients were divided into schistosomiasis group(n=80) and sporadic group (n=258) according to the preoperative history and pathologic results. Pathological specimens were collected and tissue chips were made to analyze the expression of hMLH1 and hMSH2 by immunohistochemistr.
RESULTSCompared with sporadic group, older age [(62.2 ± 9.6) year vs. (57.2 ± 11.7) year, P=0.000)], lower platelet level [(197.0 ± 59.6) × 10(9)/L vs. (217.0 ± 84.3) × 10(9)/L, P=0.02] and lower WBC level [(5.9 ± 1.9) × 10(9)/L vs. (6.6 ± 2.8) × 10(9)/L, P=0.02] were found in schistosomiasis group. Ratio of low differentiation-undifferentiation tumor was significantly higher in schistosomiasis group [44.2% (34/77) vs. 4.9% (12/247), P<0.05]. Lower positive rate of hMLH1 expression [77.5% (62/80) vs. 98.1% (253/258), P=0.000] and hMSH2 expression [75.0% (60/80) vs. 95.3% (246/258), P=0.000] was found in schistosomiasis group compared with sporadic group. Concurrent schistosomiasis was one of the risk factors of hMLH1/hMSH2 deficiency (RR: 0.913, 95% CI: 0.836-0.997, P=0.043), but not an independent factor (RR: 0.951, 95% CI: 0.867-1.043, P=0.286).
CONCLUSIONSchistosomiasis is associated with lower positive expression of hMLH1 and hMSH2, which indicates that hMLH1/hMSH2 deficiency may be a potential mechanism of schistosomiasis inducing carcinogenesis of colorectal cancer.
Adaptor Proteins, Signal Transducing ; Colorectal Neoplasms ; DNA Mismatch Repair ; Humans ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Nuclear Proteins ; Polymerase Chain Reaction ; Schistosomiasis


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