1.Research progress on the molecular mechanism and therapeutic targets of ferroptosis in acute kidney injury
Yang ZHANG ; Fanyi HE ; Kongchun SUN ; Rui YANG ; Xuezhi YU ; Ling ZHANG ; Ruixiang CHEN ; Baochun SHEN
Organ Transplantation 2025;16(2):315-321
Acute kidney injury (AKI) is one of the most common and severe nephropathy syndromes in clinical practice and also one of the most common serious complications after organ transplantation, with high incidence and fatality. Iron is an essential trace element in the body. Ferroptosis is a form of programmed cell death induced by the accumulation of iron-mediated lipid peroxidation, and its occurrence is closely related to iron metabolism, lipid metabolism, amino acid metabolism and multiple signaling pathways. Recent studies have shown that ferroptosis plays a key role in the occurrence and development of AKI and provides therapeutic targets for AKI. This article summarizes the regulatory mechanism of ferroptosis and its role in AKI, as well as the compounds that play an important role in the prevention and treatment of AKI by inhibiting ferroptosis, providing new ideas for the future treatment and research of AKI.
2.Effects of Tao Hong Si Wu decoction on circular RNA expression profiles in rats with middle cerebral artery occlusion
Chang-Yi FEI ; Li-Juan ZHANG ; Ni WANG ; Fu-Rui CHU ; Chao YU ; Su-Jun XUE ; Ling-Yu PAN ; Dai-Yin PENG ; Xian-Chun DUAN
Chinese Pharmacological Bulletin 2024;40(5):954-963
Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treat-ment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mecha-nisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expres-sion profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 sig-nificantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respective-ly.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The com-prehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treat-ment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be a-chieved by regulating the expression of circRNAs.
3.Mechanism of effect of rosiglitazone on pancreatic cancer in diabetic mice based on impact of PPARy on glucose transport and metabolism
Rui-Ping HU ; Li-Feng SHANG ; He-Jing WANG ; Hong-Xia CHE ; Ming-Liang WANG ; Huan YANG ; Yuan-Yuan JIN ; Fei-Fei ZHANG ; Jian-Ling ZHANG
Chinese Pharmacological Bulletin 2024;40(7):1325-1334
Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P<0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P<0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.
4.Role and mechanism of neuronal restriction silencing factor REST/NRSF in regulation of epilepsy
Hui LIU ; Bai-Hui YU ; Ya-Qi WANG ; Yi-Ling CHEN ; Zi-Hao CHENG ; Jia-Rui MA ; Zi-Shuo KANG ; Fan ZHANG
Chinese Pharmacological Bulletin 2024;40(9):1727-1734
Aim To investigate the effect and role of neuronal restriction silencing factor(REST/NRSF)in epilepsy disorder.Methods Immunohistochemistry,immunofluorescence,Western blot and qPCR tech-niques were used to detect REST/NRSF expression levels in hippocampal tissues of mice induced by kainic acid and human brain tissue.Viral injections,EEG re-cordings and behavioral methods were used to test the effects on epileptic mice after knockdown and overex-pression of REST/NRSF in the hippocampal CA1 re-gion,respectively.Results The positive rate of REST/NRSF in the lesions of epileptic patients was significantly higher compared with that in the control group.The levels of REST/NRSF protein and mRNA in the CA1 region of the hippocampus of mice in the KA model group were significantly higher.Kv7.2 and Kv7.3 potassium channel mRNA expression levels were significantly down-regulated.Significant up-regu-lation of REST/NRSF expression levels was observed in mouse hippocampus after NMDA injection.Knock-down of REST/NRSF in the CA1 region of hippocam-pus significantly elevated the expression levels of Kv7.2 and Kv7.3 potassium channel mRNAs.The fre-quency of EEG spiking and sharp-wave issuance and epileptic seizure grade were significantly lower.Over-expression of REST/NRSF in the CA1 region of hippo-campus significantly reduced the mRNA expression lev-els of Kv7.2 and Kv7.3 potassium channels.The fre-quency of EEG spiking and sharp-wave issuance was significantly higher and epileptic symptoms were exac-erbated.Conclusion REST/NRSF in mouse hipp-ocampal brain regions is involved in epileptic disease development through transcriptional regulation of Kv7.2 and Kv7.3 potassium channels.
5.Short-term Effect of Venetoclax Combined with Azacitidine and"7+3"Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia
Xia-Xia LIU ; Xiao-Ling WEN ; Ruo-Qi LI ; Xia-Lin ZHANG ; Tian-Bo ZHANG ; Chun-Xia DONG ; Mei-Fang WANG ; Jian-Hua ZHANG ; Lin-Hua YANG ; Rui-Juan ZHANG
Journal of Experimental Hematology 2024;32(1):96-103
Objective:To compare the short-term effect and adverse reaction of venetoclax(VEN)combined with azacitidine(AZA)versus"7+3"regimen in newly diagnosed elder patients with acute myeloid leukemia(AML).Methods:From January 2021 to January 2022,the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed,including VEN+AZA group(41 cases)and"7+3"group(38 cases).The propensity score matching(PSM)method was used to balance confounding factors,then response,overall survival(OS),progression-free survival(PFS)and adverse reactions between the two groups were compared.Results:The ORR of VEN+AZA group and"7+3"group was 68%and 84%,respectively,and the CRc was 64%and 72%,respectively,the differents were not statistically significant(P>0.05).In the VEN+AZA group,there were 5 non-remission(NR)patients,4 with chromosome 7 abnormality(7q-/-7),and 1 with ETV6 gene mutation.Median followed-up time between the two groups was 8 months and 12 months,respectively,and the 6-months OS was 84%vs 92%(P=0.389),while 6-months PFS was 84%vs 92%(P=0.258).The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳmyelosuppression,and the incidence rate was not statistically different(P>0.05).The median time of neutrophil recovery in two groups was 27(11-70)d,25(14-61)d(P=0.161),and platelet recovery was 27(11-75)d,25(16-50)d(P=0.270),respectively.The infection rate of VEN+AZA group was lower than that of"7+3"group(56%vs 88%,P=0.012).The rate of lung infections of two groups was 36%and 64%,respectively,the difference was statistically significant(P=0.048).Conclusion:The short-term effect of VEN+AZA group and"7+3"regimens in eldrly AML patients are similar,but the VEN+AZA regimen had a lower incidence of infection.The presence of chromosome 7 abnormality(7q-/-7)may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.
6.The Optimal Storage Condition and Storage Time of Umbilical Cord Blood from Collection to Preparation
Rui GUO ; Jun-Ye YANG ; Ya-Bin ZHANG ; Xue-Ping HE ; Yong ZHANG ; Jun-Ling HAN ; Wen-Ling YANG ; Lu-Gui QIU
Journal of Experimental Hematology 2024;32(2):577-582
Objective:To explore the optimal storage condition and time of umbilical cord blood from collection to preparation.Methods:Collect cord blood samples from 30 healthy newborns,with each new born's umbilical cord blood was divided into two parts on average.One part was stored in cold storage(4 ℃)and the other was stored at room temperature(20-24 ℃).Samples were taken at 24,36,48,60 and 72 h,respectively,total nucleated cells(TNC)count and TNC viability was analyzed.Flow cytometry was used to detect the ratio of viable CD34+cells to viable CD45+cells and viability of CD34+cells,and colony-forming unit-granulocyte-macrophage(CFU-GM)count was performed by hematopoietic progenitor cell colony culture.The change trend of each index over time was observed,and the differences in each index was compared between cold storage and room temperature storage under the same storage time.Results:The TNC count(r4℃=-0.9588,r20-24℃=-0.9790),TNC viability(r4℃=-0.9941,r20 24 ℃=-0.9970),CD34+cells viability(r4℃=-0.9932,r20-24℃=-0.9828)of cord blood stored in cold storage(4 ℃)and room temperature storage(20-24 ℃)showed a consistent downward trend with the prolongation of storage time.The percentage of viable CD34+cells(r4℃=0.9169,r20-24 ℃=0.7470)and CFU-GM count(r4℃=-0.2537,r20-24℃=-0.8098)did not show consistent trends.When the storage time was the same,the TNC count,TNC viability,CD34+cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature.Under the same storage time(24,36,48,60 or 72 h),TNC viability in room temperature storage was significantly lower than that in cold storage(P<0.001),but TNC count,percentage of viable CD34+cells and CFU-GM count were not significantly different between room temperature storage and cold storage.When stored at room temperature for 24 h and 36 h,the viability of CD34+cells was significantly lower than that in cold storage(P<0.001,P<0.01),when the storage time for 48,60 and 72 h,there was no significant difference in the CD34+cells viability between room temperature storage and cold storage.Conclusion:It is recommended that cord blood be stored in cold storage(4 ℃)from collection to preparation,and processed as soon as possible.
7.The Relationship Between Serum CysC,β2-MG and the Efficacy of Demethylation Therapy in Patients with Acute Myeloid leukemia
Cai-Hong ZHANG ; Rui-Jun SU ; Bin-Tao HUANG ; Zhi-Ling WANG
Journal of Experimental Hematology 2024;32(4):1005-1010
Objective:To analyze the relationship between serum cystatin C(CysC),β2-microglobulin(β2-MG)and the efficacy of demethylation therapy in patients with acute myeloid leukemia(AML).Methods:A prospective cohort study was conducted on 98 AML patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from February 2019 to January 2022.All patients were treated with decitabine(DAC)+HAG regimen,28 days as a course and treated for 3-4 courses.At the end of each course of treatment,the treatment effect of the patients was evaluated,and the patients who achieved complete remission(CR)transferred to consolidation therapy,while the patients who did not reach CR at the end of the course of treatment were considered as treatment failure.The examination items before treatment include routine blood parameters,serum CysC,and β2-MG,and general clinical data of the patients were collected.According to the statistical results,logistic regression model was used to analyze the relationship between serum CysC,β2-MG and the efficacy of demethylation therapy in AML patients.The ROC curves were drawn,and the predictive efficacy of serum CysC,β2-MG on demethylation therapy in AML patients was evaluated by the area under the curve(AUC).Results:Of the 98 AML patients enrolled in the study,5 cases were excluded during the treatment period,and 93 cases finally completed the chemotherapy courses.Among them,23 patients achieved CR after the initial induction chemotherapy(course 1-2),and 11 patients achieved CR after the re-induction chemotherapy(course 3-4).The success rate of demethylation therapy was 36.56%(34/93).Compared with the patients in treatment success group,patients in treatment failure group had a higher proportion of intermediate-and adverse-risk,lower levels of platelet(PLT)and hemoglobin(Hb),and higher expression levels of serum CysC and β2-MG,all of which were statistically significant(P<0.05).Logistic regression analysis showed that high expression of serum CysC,β2-MG and adverse-risk were independent risk factors for failure of demethylation treatment in AML patients(OR>1,P<0.05).The ROC curves showed that the AUC values of serum CysC,β2-MG alone and combined in predicting the efficacy of demethylation therapy in AML patients were 0.788,0.785 and 0.834,respectively.Conclusion:The failure of demethylation therapy in AML patients is related to the high expression of serum CysC and β2-MG,and detection of serum CysC and β2-MG before treatment can predict the risk of demethylation therapy failure in AML patients.
8.Generation and Evaluation of Human Umbilical Cord Derived Mesenchymal Stem Cells with Antioxidant Capacity
Xiao-Yu ZHANG ; Pei-Lin LI ; Jie TANG ; Zhi-Ling LI ; Rui-Cong HAO ; Xiao-Tong LI ; Wen-Jing ZHANG ; Shi-Rong ZHAO ; Li DING ; Wen-Qing WU ; Heng ZHU
Journal of Experimental Hematology 2024;32(6):1888-1895
Objective:To prepare mesenchymal stem cells with antioxidant capacity (AO-MSC ) from human umbilical cords and evaluate its cell biological properties.Methods:In control group,mesenchymal stem cells (MSC) were isolated by digesting human umbilical cord Wharton's Jelly tissues with 0.2% collagenase Ⅱ,and the released cells were collected and cultured in an animal serum-free culture medium.In AO-MSC group,incompletely collagenase Ⅱ-digested tissue debris were allowed to adhere to flusk flat bottoms and the AO-MSC was harvested by adherent culture. The conventional digestion and culture method was used as control.MSC colony forming ability was evaluated by fibroblast colony forming assay (CFU-F).MSC proliferative capacity was evaluated by CCK-8 assay.The MSC surface markers were detected by using flow cytometry and immunofluorescence staining.The adipogenic and osteogenic capacity of MSC was evaluated by multi-differentiation in vitro,and the mRNA expression of genes that control adipogenic and osteogenic differentiation was detected by real-time fluorescence quantitative PCR (RT-qPCR );Moreover,the mRNA expression of antioxidant substances such as SOD-1,GSH,GAT,and NQO1 in MSC was also evaluated by RT-qPCR.Results:The AO-MSC isolated by this strategy reached a confluence of 80%-90% at around 18 days and grew in a swirling pattern.Flow cytometry and immunofluorescence staining assays showed that CD73,CD29,CD105,CD90 were highly expressed and CD31,CD45,HLA-DR were scarcely expressed in AO-MSC.AO-MSC exhibited stronger self-renewal and differentiation ability compared to MSC.However,the in vitro adipogenic-osteogenic capacity of MSC in the control group was stronger than that of AO-MSC.RT-qPCR assay showed that AO-MSC expressed higher mRNA levels of antioxidant substances compared to MSC.Conclusion:Human AO-MSC is successfully prepared from human umbilical cord without animal serum.
9.Comparison of different methods for HbA 1c measurement
Yichuan SONG ; Anping XU ; Mo WANG ; Jie SHI ; Rui ZHAO ; Ling JI ; Rui ZHANG
Chinese Journal of Laboratory Medicine 2024;47(10):1197-1205
Objectives:To compare the HbA 1c results on capillary electrophoresis (CE), cation exchange-high performance liquid chromatography (CE-HPLC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods:902 normal samples without hemoglobin variants and 83 samples with hemoglobin variants were collected in 2020. The variants were divided into α-chain, β-chain, γ-chain, and δ-chain variants. The 902 samples without hemoglobin variants were measured by CE, CE-HPLC, and MALDI-TOF MS. Three methods were used for measuring α-chain, β-chain, and γ-chain compared with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) reference method. According to the EP9-A3 guideline, Passing-Bablok regression and concordance correlation coefficient (CCC) were performed for correlation and consistency, respectively. The imprecision was assessed by coefficient of variance (CV). The mean relative bias was calculated and compared with the lowest biological variation bias of 2.3%.Results:All three methods met the acceptance of imprecision requirements (<2%). The R 2 and CCC for the normal samples were all above 0.95 between the pairwise comparison of CE, CE-HPLC, and MALDI-TOF MS. The mean relative bias between MALDI-TOF MS and CE-HPLC was higher than the lowest biological variation bias of 2.3%. The R 2 results between CE and LC-MS/MS results of α-chain, β-chain, γ-chain variants were>0.95, and the mean relative biases for γ-chain variants exceeded the lowest biological variation bias of 2.3%. A bad correlation ( R2=0.66) for β-chain variants was shown between CE-HPLC and LC-MS/MS and the mean relative biases of all variant samples exceeded 2.3%. MALDI-TOF MS showed good correlations with LC-MS/MS for three groups, and the mean relative biases for γ-chain variants were higher than 2.3%. Conclusion:MALDI-TOF MS and CE-HPLC with CE had good comparability in the measurement of HbA 1c in normal samples, butthe three methods showed interferences from different types of Hb variants and the CE method was affected with less interference.
10.Setup error analysis during proton and heavy ion therapy for head and head neck tumor patients with fixation by thermoplastic film combined with styrofoam
Zhu-Lei LIU ; Rui-Rui BU ; Dan ZHOU ; Yao LI ; Ling-Min WU ; Dong-Peng ZHANG ; Jiang-Bing ZHANG ; Dan YOU
Chinese Medical Equipment Journal 2024;45(7):56-61
Objective To analyze the setup errors during proton and heavy ion therapy for head and head neck tumor patients fixed by thermoplastic film combined with styrofoam.Methods Totally 20 patients undergoing proton and heavy ion therapy at some hospital from January to December 2018 were selected retrospectively,of whom 10 ones had head tumors with clinical targets located in the head and the other 10 cases had head and neck tumors with clinical targets distributed in the head and neck.All the 20 patients were fixed with thermoplastic film combined with styrofoam.The head and neck images of the patients acquired after image guidance were aligned with the CT localization-based digitally reconstructed radiograph images,and the setup errors at six-dimensional directions(left-right translation,head-foot translation,forward-backward translation,isocentric rotation,pitch rotation and transverse-roll rotation)were recorded in the first five and the last five times of radiotherapy treatment.The data were processed by using the SPSS 23.0 statistical software and EXCEL.Results There were no significant differences between the head tumor patients in the setup errors at the six directions during the first and last five times of radiotherapy(P>0.05).The head and neck tumor patients did not have obvious differences in the setup errors at the the directions of left-right translation,forward-backward translation,isocentric rotation and transverse-roll rotation(P>0.05),while did at the directions of head-foot translation and pitch rotation(P<0.05).The head and head neck tumor patients with the fixation by thermoplastic film combined with styrofoam had their setup errors at the six directions meet clinical requirements after calibration by the six-dimensional treatment table.Conclusion The fixation mode by thermoplastic film and styrofoam behaves well to enhance the setup repeatability for head tumor patients at the six-dimensional directions,while not so well for head neck tumor patients at the directions of head-foot translation and pitch rotation.Proper measures have to be taken to decrease the setup errors during proton and heavy ion therapy for head and head neck tumor patients.[Chinese Medical Equipment Journal,2024,45(7):56-61]

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