1.Optical coherence tomography imaging features of Coats disease and their correlation with macular fibrosis
Ziyi ZHOU ; Guorui DOU ; Hongxiang YAN ; Guoheng ZHANG ; Jinting ZHU ; Dongjie SUN ; Zifeng ZHANG ; Manhong LI ; Yusheng WANG
Chinese Journal of Experimental Ophthalmology 2024;42(5):436-441
Objective:To analyze the optical coherence tomography (OCT) imaging characteristics in patients with Coats disease and their value in predicting macular fibrosis.Methods:A nested case-control study was performed.A total of 43 patients (43 eyes) diagnosed with Coats disease through color fundus photography, ocular B-scan ultrasonography, fundus fluorescein angiography, and spectral-domain OCT examination were enrolled from January 2008 to October 2021 at the Xijing Hospital.Among them, there were 40 males and 3 females, aged from 2 to 60 years old, with a median age of 13 years.Macular fibrosis was used as an indicator of poor prognosis, and patients were divided into two groups based on whether macular fibrosis occurred at the end of follow-up.The differences in OCT characteristics between two groups were compared and logistic regression analysis was used to identify the risk factors for macular fibrosis.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Xijing Hospital of Fourth Military Medical University (No.KY20202009-C-1).Results:The OCT clinical features of 43 cases of Coats disease included intraretinal hard exudates in 43 eyes (100%), subretinal fluid in 21 eyes (48.8%), macular cysts in 17 eyes (27.9%), subretinal exudates in 9 eyes (20.9%), anterior retinal hyperreflective dots in 7 eyes (16.3%), epiretinal membrane in 21 eyes (48.8%), and intraretinal fluid in 22 eyes (51.2%).In color fundus photos of 41 eyes, 38 eyes (93.0%) had hard exudates distributed in the posterior pole and 27 eyes (65.9%) had the mid-peripheral region.OCT examination showed that hard exudates were distributed in the inner nuclear layer in 35 eyes (81.4%) and the outer nuclear layer in 33 eyes (76.7%).Among 21 eyes with exudative retinal detachment detected by OCT, 9 eyes (42.9%) were detected by fundus photography and 18 eyes (85.7%) were detected by B-scan ultrasonography.The proportions of eyes with subretinal fluid and subretinal exudates were higher in the macular fibrosis group than in the non-macular fibrosis group, and the differences were statistically significant ( χ2=20.755, P<0.001; χ2=6.133, P=0.013).Logistic regression analysis showed that the presence of subretinal fluid was a risk factor for macular fibrosis (odds ratio=48.345, 95% confidence interval: 4.272-547.066, P=0.002). Conclusions:OCT examination can detect subretinal fluid, subretinal exudates, macular cysts, macular exudates, and hyperreflective spots in the retina of patients with Coats disease.Subretinal fluid is a risk factor for macular fibrosis.
2.Monitoring and Analysis of Blood Concentrations of Seven New Antiepileptic Drugs on 6 537 Cases in A Grade-A Tertiary Hospital in Beijing
Xintian LI ; Dongjie ZHANG ; Li YANG ; Zhigang ZHAO ; Shenghui MEI ; Jiping HUO
Herald of Medicine 2024;43(12):2026-2032
Objective To analyze the blood concentration monitoring results of 7 new antiepileptic drugs levetiracetam(LEV),oxcarbazepine(OXC),lamotrigine(LTG),topiramate(TPM),lacosamide(LCM),zonisamide(ZNS)and perampanel(PER)and provide a basis for clinical rational drug use.Methods Aretrospective analysis was conducted on the blood concentration monitoring results of 7 new antiepileptic drugs in a grade-A tertiary hospital in Beijing from November 2021 to March 2023,with a total of 6 537 valid concentration data collected.The patients were grouped according to age,gender and concomitant medication,and the blood drug concentration levels and compliance rates among the groups were analyzed and compared.Results The male to female patient ratio was 1.35∶1.There were statistically significant differences in the blood concentration distribution of OXC,LEV,LCM and TPM between genders(P<0.05).The blood concentration of LEV showed statistically significant differences between the pediatric group and the elderly group,as well as between the young adult group and the elderly group(P<0.05).The blood concentrations of OXC,ZNS and TPM showed statistically significant differences between the pediatric group and the young and middle-aged group,between the young and middle-aged group and the elderly group,and between the pediatric group and the young and middle-aged group,respectively(P<0.05).The highest and lowest overall compliance rates of blood concentration were observed for OXC and LCM,respectively.The compliance rates of OXC and TPM in the pediatric group were significantly higher than those in the young-middle-aged group,with statistically significant differences(P<0.05),while the compliance rate of LEV in the elderly group was significantly higher than that in the pediatric group and the young-middle-aged group,with a statistically significant difference(P<0.05).There were a total of 2 133 cases with combined drug use.LEV,OXC and LTG are frequently used and have good efficacy and weak interactions when added to treatment.Conclusion New antiepileptic drugs show a promising prospect in treatment,and therapeutic drug monitoring can further improve the effectiveness of individualized clinical treatment.
3.Application of double mediastinal drainage tubes in elderly patients with intrathoracic anastomotic leak after thoracoscopic Ivor-Lewis surgery
Chuanfei ZHAN ; Shilin CHEN ; Xiaokang SHEN ; Dongjie FENG ; Xiaojun WANG ; Weizhong SHEN ; Feng JIANG ; Qin ZHANG ; Lin XU
Chinese Journal of Geriatrics 2024;43(1):56-59
Objective:To investigate the clinical significance of intraoperative prepositioning of dual mediastinal drains in elderly patients developing anastomotic leakage(AL)after a total endoscopic Ivor-Lewis procedure.Methods:This retrospective case-control study analyzed the clinical data of 500 elderly patients who underwent total endoscopic Ivor-Lewis surgery for esophageal or cardia cancer from January 2020 to December 2022.In the control group, one mediastinal drainage tube was placed intraoperatively, while in the study group, two mediastinal drainage tubes were placed.Both groups had a chest tube placed conventionally.The study compared the incidence of anastomotic leak(AL)at 1 month postoperatively, inflammatory indexes in patients with AL, grading of AL, rate of nasal fistula placement, incision infection, anastomotic stenosis, and incidence of hoarseness.Additionally, it compared ICU occupancy, ventilator use, and ICU length of stay between the two groups.Results:The analysis included clinical data from 455 elderly patients.Among the patients who developed AL, the study group had significantly lower peak body temperature[(39.58±1.03)℃ vs.(38.05±0.56)℃, t=4.298, P<0.05], white blood cell count[(18.63±3.35)×10 9/L vs.(14.28±2.78)×10 9/L, t=3.450, P<0.05], and C-reactive protein(CRP)levels[(154.66±41.64)mg/L vs.(122.19±31.29)mg/L, t=2.131, P<0.05]. The study group also had a significantly lower grading of AL and rate of nasal fistula placement(82.4% vs.30.0%, P<0.05). In terms of ICU indicators, the study group had a significantly lower ICU admission rate(64.7% vs.10.0%, P<0.05), shorter period of ventilator use[(6.47±8.15)days vs.(0.90±2.23)days, t=2.62, P<0.05], and shorter ICU stay[(11.70±8.89)days vs.(4.70±6.27)days, t=2.184, P<0.05]. Conclusions:Double mediastinal drainage tubes, have been found to significantly alleviate inflammation, decrease the rate of nasal fistula placement and ICU admission, and shorten the length of ICU stay in elderly patients.Therefore, they are considered safe and deserving of clinical promotion.
4.Clinical observation of acupotomology combined with Bushenzhuanggu prescription in the treatment of residual lumbar pain after PKP for osteoporotic vertebral compression fracture
Liao ZHANG ; Keshang FU ; Junxiang HU ; Huajie LIN ; Dongjie ZHU
China Modern Doctor 2024;62(9):22-25
Objective To investigate the clinical effect of acupotomology combined with Bushenzhuanggu prescription in the treatment of residual lumbar pain after percutaneous kyphoplasty(PKP)for osteoporotic vertebral compression fractures.Methods A total of 77 patients with PKP postoperative residual lumbar pain admitted to the Department of Orthopedics,Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from January 2018 to December 2021 were randomly divided into control group and observation group.Patients in control group were treated with calcitriol soft capsules and calcium carbonate D3 tablets,and patients in observation group were treated with acupotomy combined with Bushenzhuanggu prescription.The pain degree,lumbar function and self-care ability of the two groups were compared.Results After treatment,the pain level,lumbar function,and self-care abilityof the two groups of patients improved compared to before treatment.Compared with control group,the visual analogue score(VAS)score and Oswestry disability index(ODI)index of observation group decreased more significantly,and the difference was statistically significant(P<0.05);The Barthel index of observation group increased more significantly in the early stage(3 days and 1 month after treatment),with a statistically significant difference(P<0.05).However,there was no statistically significant difference in Barthel index between the two groups at 3 months after treatment(P>0.05).Conclusion Acupotomy combined with Bushenzhuanggu prescription has satisfactory clinical efficacy in the treatment of residual lumbar pain after PKP operation of osteoporotic vertebral compression fracture.It can significantly reduce pain,improve lumbar function,shorten the improvement time of patients'self-care ability,improve patients'quality of life,and effectively promote patients'rapid recovery.
5.Analysis of 15 children with type Ⅳ branchial cleft cyst treated with endoscopic transoral approach
Qingchuan DUAN ; Fengzhen ZHANG ; Guixiang WANG ; Dongjie SENG ; Hongbo REN ; Enle QIAN ; Jie ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(10):1042-1047
Objective:To analyze the clinical characteristics and endoscopic surgical procedures of the second branchial cleft cyst type Ⅳ in children.Methods:A retrospective review was conducted on 15 pediatric cases with type Ⅳ second branchial cleft cysts treated at the Beijing Children′s Hospital affiliated with Capital Medical University and Henan Children′s Hospital from September 2019 to November 2023. All patients underwent excision via a two-person, three-hand endoscopic transoral approach. The cohort included 12 males and 3 females, with an age range of 10 months to 10 years and 5 months, and a median age of (59.20±32.05) months. The clinical data of initial symptoms, sides, imaging features, treatment methods, complications, length of hospital stay, prognosis and outcome were recorded and analyzed. SPSS 22.0 software was used for statistical analysis.Results:Of the 15 children, 13 cases presented with snoring as the primary symptom, 1 case with dysphagia, and 1 case was asymptomatic and was found unintentionally. The mean disease duration was (6.74±9.05) months (range, from 3 days-2 years). MRI revealed cystic lesions on the right side in 12 cases and on the left side in 3 cases, characterized by uniform long T2 signal, equal T1 or short T1 signal. The cysts appeared dumbbell-shaped in 10 cases with the pharyngeal constrictor muscle as the waist, the posterior outside of the mass was adjacent to the internal carotid artery. The remaining 5 cases showed an isolated cyst located inside the pharyngeal constrictor muscle. The intraoperative MRI findings were consistent. Partial cystectomy was performed in 10 cases near the internal carotid artery, leaving only the portion with a clear arterial pulse intact. Five cases with isolated cysts on the medial side of the pharyngeal constrictor muscle were totally removed. The average length of hospital stay was (4.53±0.52) days (4-5 days). All patients were followed up for 7-56 months [median (30±15.12) months] with no recurrence of symptoms observed.Conclusions:The second branchial cleft cyst type Ⅳ in children is characterized by prominent pharyngeal cystic mass, with snoring as a predominant initial symptom, MRI provides excellent diagnostic value. The two-person, third-hand endoscopic transoral approach for cyst excision is feasible, safe, and offers the benefits of minimal invasiveness and reduced hospitalization time.
6.Effects and regulatory mechanisms of FAM3C expression on proliferation, migration, and invasion of pancreatic cancer cells
Leisheng WANG ; Yue TAO ; Shuo ZHANG ; Enhong CHEN ; Dongjie YANG ; Youzhao HE ; Yong MAO ; Hao HU
Chinese Journal of Hepatobiliary Surgery 2024;30(7):531-536
Objective:To analyze the expression of sequence similarity family 3 member C (FAM3C) in pancreatic cancer and its effects on pancreatic cancer cell proliferation, migration, invasion and the underlying mechanisms.Methods:Tissue samples from four pancreatic cancer patients undergoing surgical resection at Affiliated Hospital of Jiangnan University from July 2022 to June 2023 were collected. Expression of FAM3C was assessed in both cancer and adjacent tissues using polymerase chain reaction and Western blot techniques. High FAM3C-expressing pancreatic cancer cells PANC-1 and MIA PaCa-2 were selected for further experiments involving FAM3C-siRNA and methyltransferase-like protein 3 (METTL3)-siRNA groups, alongside a negative control group. Cell counting, Transwell assays, and co-immunoprecipitation with methylation antibodies were utilized to evaluate the proliferation, migration, invasion, and methylation status of FAM3C.Results:The relative expression of FAM3C mRNA in cancer tissues of the four patients with pancreatic cancer was higher than that in adjacent tissues (1.29±0.19 vs 0.47±0.17, t=-6.48, P=0.001). Compared with the negative control group A, the proliferation ability of the FAM3C-siRNA interference group decreased, and the number of migrating and invasive cells decreased (all P<0.05). In the negative control group B of PANC-1 cells, the relative expression of FAM3C mRNA in IgG-treated cells was lower than that in the methylated antibody-treated group (1.05±0.53 vs 30.57±1.09, t=-42.04, P=0.001). After PANC-1 cells were treated with methylated antibodies, the relative expression of FAM3C mRNA in the negative control group B was higher than that in the METTL3-siRNA interference group (30.57±1.09 vs 18.17±0.50, t=17.89, P=0.001). Compared with the negative control group B, the proliferation ability, migration and invasion cell numbers of PANC-1 cells in the METTL3-siRNA interference group were reduced (all P<0.05). The results of MIA PaCa-2 and PANC-1 cells were consistent. Conclusions:FAM3C is highly expressed in pancreatic cancer and promotes the proliferation, migration and invasion of pancreatic cancer cells. METTL3 affects FAM3C expression by methylation and proliferation, migration and invasion of pancreatic cancer cells.
7.Dachaihu decoction protects intestinal mucosal barrier in severe heat stroke rats by inhibiting Toll-like receptor 4/nuclear factor-κB signaling pathway
Dongjie CHEN ; Yonglian HUANG ; Xiaohong PENG ; Yaxiu HUANG ; Fagen HUANG ; Aiting ZHANG ; Ping WANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2023;30(5):592-596
Objective To explore the effect of Dachaihu decoction on the Toll-like receptor 4/nuclear factor-κB(TLR4/NF-κB)signaling pathway and gastrointestinal mucosal barrier in rats with severe heat stroke.Methods Sixty SPF grade Sprague-Dawley(SD)male rats were divided into normal control group,model group,Dachaihu decoction standard dose group and Dachaihu decoction high dose group of 15 rats in each group.The heat stroke model was replicated in the rats at temperature(40.5±0.5)℃and humidity(65.0±2.0)%;the normal control group was not treated.From 6 hours after mold making,drug intervention was carried out in the Dachaihu decoction high dose group and the Dachaihu decoction standard dose group of 3.38 g·kg-1·d-1 and 1.69 g·kg-1·d-1,every 8 hours for 2 days.Equal amounts of normal saline were administered to the normal control group and model group.At 6,24 and 48 hours after the molding,5 mL abdominal main artery blood from 5 rats were randomly collected from each group,and the blood was obtained by enzyme-linked immunosorbent assay(ELISA)to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),D-lactic acid,intestinal fatty acid-binding protein(I-FABP).At the same time,the ileum tissue was retained,and the protein expression of TLR4 and NF-κB in intestinal tissue was determined by Western blotting.Some of the ileal tissue was obtained for hematoxylin-eosin(HE)staining,and the intestinal histopathological changes were observed under light microscopy.Results The normal control group of rats had no significant change,and the other three groups showed heatstroke symptoms after mold making.The overall mortality in drug group were significantly lower than that in the model group[3.3%(1/30)vs.20.0%(3/15),P<0.05].Compared with the normal control group,the serum IL-1,TNF-α,I-FABP,D-lactic acid and the protein expression levels of TLR4 and NF-κB in the model group,Dachaihu decoction standard dose group and Dachaihu decoction high dose group all increased.Compared with the model group,at 24 hours and 48 hours after molding in the Dachaihu decoction standard dose group and Dachaihu decoction high dose group,the serum IL-1,TNF-α,I-FABP,D-lactic acid and the protein expression levels of TLR4 and NF-κB significant decreased[24 hours:TNF-α(ng/L):69.20±4.32,59.37±4.31 vs.76.99±5.02,IL-1(ng/L):132.68±4.93,112.59±9.64 vs.146.75±10.12,I-FABP(mmol/L):504.35±22.23,453.37±32.38 vs.542.58±13.83,D-lactic acid(mmol/L):114.55±8.52,90.57±3.09 vs.127.87±8.37,protein expression of TLR4(A value):1.50±0.08,1.23±0.01 vs.1.86±0.08,protein expression of NF-κB(A value):1.61±0.05,1.21±0.05 vs.1.97±0.08;48 hours:TNF-α(ng/L):58.46±5.13,38.98±5.53 vs.90.21±3.02,IL-1(ng/L):119.12±4.57,84.12±5.08 vs.170.20±6.21,I-FABP(mmol/L):436.04±27.63,321.85±22.03 vs.618.79±12.31,D-lactic acid(mmol/L):87.35±6.84,70.38±4.33 vs.154.14±10.83,protein expression of TLR4(A value):1.19±0.05,1.10±0.13 vs.2.09±0.06,protein expression of NF-κB(A value):1.15±0.09,0.97±0.08 vs.2.20±0.02,all P<0.05].The expression levels of TNF-α,I-FABP,TLR4 and NF-κB protein in Dachaihu decoction high dose group decreased significantly at 24 hours and 48 hours compared with the standard dose group,however,IL-1 and D-lactic acid decreased significantly at 48 hours after molding(all P<0.05).The pathology observation showed that,compared with the model group,the intestinal mucosa villus,the lamina propria drop and haemorrhage was decreased in the Dachaihu decoction standard dose group and Dachaihu decoction high dose group.Telangiectasia was reduced and no ulcer formation was observed.Conclusion Dachaihu decoction can inhibit TLR4/NF-κB signaling pathway,reduce intestinal inflammatory response,thus reduce gastrointestinal damage,and protect the gastrointestinal mucosal barrier in rats with severe heatstroke.
8.Study on the Anti-tumor Activity of Components of Ganoderma Lucidum on the Three-dimensional Culture Model of Colorectal Cancer HCT116 Cells
PAN Haitao ; CHEN Dongjie ; ZHANG Guoliang ; HU Lingjuan ; WANG Xiaotong ; ZHONG Yi ; YANG Jihong ; LI Zhenhao
Chinese Journal of Modern Applied Pharmacy 2023;40(13):1795-1809
OBJECTIVE To investigate the anti-tumor effects of the components of Ganoderma lucidum(Gc) based on the two-dimensional(2D) and three-dimensional(3D) culture of colorectal cancer HCT116 cells. METHODS The chemical compositional of the three components was identified by UPLC-Q-TOF-MS. An in vitro 3D culture model of HCT116 cells was established by using Matrigel as the matrix material, and the effects of Gc1, Gc2, Gc3, and 5-fluorouracil(5-FU) on the proliferation of HCT116 cells in 2D and 3D culture models were evaluated, and the effects of Gc3 on cell-cycle, apoptosis, drug resistance, lipid metabolism, and 5-FU's anti-tumor activity were evaluated. Cell viability was detected by CCK-8 assay. mRNA expression level of the cells was analyzed by Real-time PCR. Proteins expression level of the cells was analyzed by Western blotting. HPLC was used to detect the content of 5-FU in cells. RESULTS A total of 76, 69, and 17 compounds were identified from Gc1, Gc2, and Gc3, respectively. Compared with 2D culture, the proliferation rate of HCT116 cells was decreased in the 3D culture model, and the expression of cell cycle-promoters CDK2, CDK4, CDK6, and fatty acid synthesizer FASN, SREBP1 were significantly down-regulated. On the contrary, the expression of cell cycle-suppressor p21, p27, and lipid droplet breakdown proteins ATGL and drug resistance gene ITGB1, CDH1, ABCB1, and ABCC1 mRNA were significantly up-regulated. Gc1, Gc2, Gc3 and 5-FU inhibited the proliferation of both 2D and 3D cultured HCT116 cells in a dose dependent manner after incubation for 48 h, and the inhibitory effect of Gc3 was significantly stronger than Gc1 and Gc2. Gc3 could not only reduce the expression of CDK2, CDK4, Bcl-xl, ATGL, and LC3B proteins, but also increase the expression of p21, p27, Bax, Cleaved caspase-3, and Cleaved PARP1 proteins, and overexpression of LC3B or ATGL attenuated Gc3-induced cytotoxicity in 3D cultured HCT116 cells. In addition, Gc3 significantly inhibited the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA, and increased the intracellular 5-FU content, and enhanced the anti-tumor activity. CONCLUSION Gc3 significantly inhibit the proliferation of 3D-cultured HCT116 cells by inhibiting cell autophagy and lipid droplet breakdown, and enhance the anti-cancer activity of 5-FU by inhibiting the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA.
9.Effects of class Ⅲ traction assisted by implant anchorage on unilateral cleft and palate patients in treatment of skeletal class Ⅲ malocclusion
Dongjie ZHANG ; Zhanyi YE ; Fan LI ; Baojun LONG
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(6):482-487
Objective:To evaluate and compare the outcomes of maxillary protraction treatment assisted by temporary anchorage devices (TADs) and removable biteplate in cleft lip and palate patients using cephalometric analysis.Methods:Fifty-four cleft lip and palate patients were divided into 3 groups based on different maxillary protraction treatments: bitepalate removable appliance group (group A), maxillary protraction treatment assisted by TADs group (group B) and control group (group C). Lateral cephalograms were taken at the start and the end of maxillary protraction. Skeletal, dental and soft tissue changes were measured using Dolphin software and compared between groups.Results:The average protraction time of groups A and B were (8.51±1.33) and (9.20±1.45) months ( P=0.146), respectively. A point moved forward by 4.08 mm in group A and 4.83 mm in group B were noted, without significant differences between the two groups. Compared to group C, ANB and wits was highly improved after protraction in groups A and B. U6-VRmx increased by 0.46 mm and U1-pp increased by 0.63 mm in group B, both of which were significantly smaller than those of group A (both P<0.05), suggesting that maxillary protraction treatment assisted by TADs could reduce molar advancement and upper incisor protrusion. Conclusions:Both maxillary protraction treatment assisted by TADs and removable biteplate could significantly improve skeletal class Ⅲ malocclusion in unilateral cleft and palate patients. Maxillary protraction treatment assisted by TADs could reduce molar advancement and upper incisor protrusion.
10.Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease.
Jie TONG ; Dongjie LI ; Hongbo MENG ; Diyang SUN ; Xiuting LAN ; Min NI ; Jiawei MA ; Feiyan ZENG ; Sijia SUN ; Jiangtao FU ; Guoqiang LI ; Qingxin JI ; Guoyan ZHANG ; Qirui SHEN ; Yuanyuan WANG ; Jiahui ZHU ; Yi ZHAO ; Xujie WANG ; Yi LIU ; Shenxi OUYANG ; Chunquan SHENG ; Fuming SHEN ; Pei WANG
Acta Pharmaceutica Sinica B 2022;12(9):3650-3666
Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.


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