In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

Objective By applying the long short-term memory(LSTM)neural network model and using lower body landmark coordinates obtained from a markerless motion capture system as inputs,to estimate ground reaction force(GRF)curves during running.Methods The video images and GRF data of 59 amateur runners during running were collected by the markerless motion capture system and three-dimensional(3D)force plates.The LSTM model was established,and the 3D coordinates of 11 lower body landmarks,obtained via the Theia3D markerless system,were used as inputs to estimate the 3D GRF curves during the stance of running.The estimation performance was evaluated using correlation coefficients r,root mean square error(RMSE),and normalized root mean square error(nRMSE)by comparing LSTM model estimation and force plate measurement.Statistical parametric mapping was used to analyze differences in GRF curves estimated by the LSTM model and measured by the force plate,while paired t-tests were used to assess differences in GRF characteristics between model estimation and actual measurement.Results A strong correlation(r＞0.85,P＜0.001)and lower error(RMSE＜0.3 body weight,nRMSE＜15％)was found between the LSTM model estimation and actual measurements.No significant difference was found in GRF curve intervals between LSTM model estimation and actual measurements.There was no significant difference in GRF characteristics between LSTM model estimation and actual measurements(P＞0.05).Conclusions Based on the LSTM model,the 3D GRF curves can be effectively estimated by lower body landmark coordinates obtained from the makerless motion capture system,thereby acquiring the highly accurate GRF characteristics.The LSTM model developed in this study can be used to monitor injury risks during running in outdoor environments.

Objective By applying the long short-term memory(LSTM)neural network model and using lower body landmark coordinates obtained from a markerless motion capture system as inputs,to estimate ground reaction force(GRF)curves during running.Methods The video images and GRF data of 59 amateur runners during running were collected by the markerless motion capture system and three-dimensional(3D)force plates.The LSTM model was established,and the 3D coordinates of 11 lower body landmarks,obtained via the Theia3D markerless system,were used as inputs to estimate the 3D GRF curves during the stance of running.The estimation performance was evaluated using correlation coefficients r,root mean square error(RMSE),and normalized root mean square error(nRMSE)by comparing LSTM model estimation and force plate measurement.Statistical parametric mapping was used to analyze differences in GRF curves estimated by the LSTM model and measured by the force plate,while paired t-tests were used to assess differences in GRF characteristics between model estimation and actual measurement.Results A strong correlation(r＞0.85,P＜0.001)and lower error(RMSE＜0.3 body weight,nRMSE＜15％)was found between the LSTM model estimation and actual measurements.No significant difference was found in GRF curve intervals between LSTM model estimation and actual measurements.There was no significant difference in GRF characteristics between LSTM model estimation and actual measurements(P＞0.05).Conclusions Based on the LSTM model,the 3D GRF curves can be effectively estimated by lower body landmark coordinates obtained from the makerless motion capture system,thereby acquiring the highly accurate GRF characteristics.The LSTM model developed in this study can be used to monitor injury risks during running in outdoor environments.

Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Objective::Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES.Methods::The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results::A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority <0.001, P for superiority = 0.02). Although without significant difference, the rate of TLF in MiStent was quantitatively lower than that in TIVOLI (3.70% vs. 6.60%; P = 0.17). Conclusion::Compared with TIVOLI BP-SES, the MiStent system was superior in in-stent LLL at 9 months and had a comparable clinical benefit at 1 year in de novo coronary lesions.

Objective::Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES.Methods::The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results::A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority <0.001, P for superiority = 0.02). Although without significant difference, the rate of TLF in MiStent was quantitatively lower than that in TIVOLI (3.70% vs. 6.60%; P = 0.17). Conclusion::Compared with TIVOLI BP-SES, the MiStent system was superior in in-stent LLL at 9 months and had a comparable clinical benefit at 1 year in de novo coronary lesions.

Objective:To investigate the relationship between systemic immune-inflammation index (SII) and the prognosis of esophageal cancer patients treated with radical radiotherapy and to predict the prognosis of the patients using the SII combined with clinical staging.Methods:A retrospective analysis was conducted for 248 patients with esophageal cancer who were admitted to the Department of Radiotherapy in the Fourth Hospital of Hebei Medical University between 2014 and 2016. These patients included 146 males and 102 females, with a median age of 67 years. Among them, 134 patients received concurrent chemotherapy and 114 patients received radiotherapy alone. The SII before radiotherapy was defined as platelet count × neutrophil count/lymphocyte count. The patients were divided into a low-SII group and a high-SII group according to the optimal cutoff value of pretreatment SII determined by the receiver operating characteristics (ROC) curve. Survival analysis was calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analysis. For these patients, the prognosis effects and the predictive value for survival of different SII levels combined with TNM staging were compared.Results:According to the ROC curves, the optimal cutoff value of SII before radiotherapy was 740.80. Based on this number, the patients were divided into a low-SII group (< 740.80, 150 cases) and a high-SII group (≥ 740.80, 98 cases). The objective response rate of the low-SII group was significantly higher than that of the high-SII group (86.0% vs 75.5%, χ2=4.39, P=0.036). The 1-, 3-, and 5-year overall survival (OS) rates of the low-SII group were 78.6%, 45.6%, and 32.3%, respectively. These rates were significantly higher than the corresponding rates of the high-SII group, which were 71.0%, 28.3%, and 16.4% ( χ2=11.22, P=0.001), respectively. Moreover, the 1-, 3- and 5-year progression-free survival (PFS) rates of the low-SII group were 67.0%, 36.9%, and 32.0%, respectively. Again, these rates were significantly higher than those of the high-SII group, which were 45.5%, 17.5%, and 12.5% ( χ2=15.38, P < 0.001), respectively. Multivariate analysis showed that TNM staging, treatment method, and SII were independent prognostic factors for OS and PFS ( HR=1.39-1.60, P<0.05). Patients with low SII and early clinical staging had a better prognosis than other subgroups ( χ2=13.68, 13.43, P=0.001). The area under curve (AUC) of SII combined with TNM staging (0.70) was higher than that of SII (0.63) and TNM staging (0.62) ( Z=2.48, 2.57, P < 0.05). Conclusions:Pretreatment SII has a high predictive value for the prognosis of esophageal cancer after radiotherapy, and higher SII indicates a worse prognosis. Thus, combining SII with TNM staging can improve the prediction accuracy of the prognosis of esophageal cancer patients.