1.β-sitosterol, an important component in the fruits of Alpinia oxyphylla Miq., prolongs lifespan of Caenorhabditis elegans by suppressing the ferroptosis pathway.
Junyi LI ; Siyuan CHEN ; Liyao XIE ; Jin WANG ; Ao CHENG ; Shaowei ZHANG ; Jiyu LIN ; Zhihan FANG ; Yirui PAN ; Chonghe CUI ; Gengxin CHEN ; Chao ZHANG ; Li LI
Journal of Southern Medical University 2025;45(8):1751-1757
OBJECTIVES:
To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis.
METHODS:
C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs).
RESULTS:
Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans.
CONCLUSIONS
BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals
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Caenorhabditis elegans/physiology*
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Ferroptosis/drug effects*
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Alpinia/chemistry*
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Sitosterols/pharmacology*
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Longevity/drug effects*
;
Fruit/chemistry*
;
Humans
2.Establishment and preliminary application of the Mini-FERO form for formative evaluation in the standardized training for radiation oncology resident physicians
Cui GAO ; Yirui ZHAI ; Yongming ZHANG ; Runye WU ; Yuan TANG ; Wenyang LIU ; Pan MA ; Lei DENG ; Qingfeng LIU ; Wenqing WANG ; Ye-Xiong LI ; Shulian WANG ; Bo CHEN
Chinese Journal of Radiation Oncology 2023;32(10):928-933
Objective:To establish the first Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale in China and evaluate its preliminary application value in the standardized training for radiation oncology resident physicians.Methods:Based on the educational curriculum and examination requirements for the standardized training for radiation oncology resident physicians, as well as the standardized Mini-Clinical Evaluation Exercise (Mini-CEX) scale commonly used in clinical practice, the Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale was developed to facilitate the standardized training for resident physicians in the field of radiation oncology. In this prospective study, a randomization method using a random number table was employed to select a cohort of 26 resident physicians who completed their rotations in Department of Radiation Oncology at the Cancer Hospital, Chinese Academy of Medical Sciences from March 1, 2021 to December 31, 2021. The Mini-FERO scale was administered in the initial, middle, and final stages during the rotation period. The differences in evaluation scores before and after the assessments were analyzed by paired t-test. Furthermore, participating resident physicians and supervising teachers provided satisfaction ratings, and a comprehensive evaluation of the Mini-FERO scale was conducted. Results:The average scores of the three examinations of 26 resident physicians demonstrated a successive improvement, with individual performance in each assessed category also showing progressive enhancement. The second evaluation exhibited a more pronounced score increase compared to the first evaluation, with a mean improvement of (1.43±1.02) points ( t=7.13, P<0.001); while the third evaluation had a mean improvement of (0.41±0.50) points ( t=4.07, P<0.001) compaired to the second evaluation, with a mean difference of (1.02±1.15) points between the two ( t=4.53, P<0.001). The average time required for the assessments was (34.31±24.46) min. Overall satisfaction ratings from the evaluated resident physicians for the Mini-FERO scale were (8.42±0.85) points, and supervising teachers reported an overall satisfaction rating of (8.45±0.85) points. The satisfaction rate was 96% (25/26). Conclusions:In this study, the Mini-FERO scale was successfully developed and validated in the context of clinical teaching practice for radiation oncology resident physicians. The Mini-FERO scale is proven to be a feasible tool for assessing the gradual improvement of resident physicians throughout their learning process in the field of radiation oncology. Importantly, it offers the advantages of short assessment time, thereby avoiding additional burden on supervising teachers. The adoption of the Mini-FERO scale addresses current limitations of lacking of formative evaluation in the standardized training for radiation oncology resident physicians.
3.Long-term study of pathological changes of living renal grafts from elderly relatives in young recipients
Jiali FANG ; Zheng CHEN ; Junjie MA ; Guanghui LI ; Lu XU ; Lei ZHANG ; Wei YIN ; Xingqiang LAI ; Yuhe GUO ; Yirui ZHANG ; Guanghui PAN
Organ Transplantation 2019;10(2):175-
Objective To investigate the safety of young recipients undergoing living donor renal transplantation from elderly relative donors through long-term follow-up of the pathological changes. Methods According to the age of donors, 28 young recipients were divided into the observation group (
4.Comparative observation of the clinical effect of immediate recovery of fluid resuscitation in traumatic shock and delayed resuscitation
Pan WANG ; Yirui CAO ; Jian CHENG ; Li DA ; Qiang HUANG ; Liming TAN
Clinical Medicine of China 2018;34(4):368-371
Objective To investigate the clinical value of immediate fluid resuscitation and delayed resuscitation in patients with traumatic shock. Methods The patients with traumatic shock treated in the Critical Care Medicine Department of People's Hospital of Wenjiang District from March 2014 to March 2017 were selected. According to the number of admission cases,one hundred and twenty patients with traumatic shock were randomly divided into two groups,60 cases in each group. The control group was given early immediate fluid resuscitation,the observation group was given delayed resuscitation,and the blood coagulation and blood routine indexes of the two groups were compared before and after the fluid resuscitation in the two groups,and the amount of fluid rehydration and the fatality rate in the two groups of patients with 1 h shock were observed,and the incidence rate of acute respiratory distress syndrome ( ARDS) and multiple organ dysfunction syndrome (MODS) were compared. Results After treatment,the blood clotting and blood routine indexes of the two groups were improved (P<0. 05),of which the thromboplastin time (PT) ((11. 04±1. 17) s),activated partial thromboplastin time (APTT) ((28. 12±5. 93) s) in the observation group in the observation group were lower than those of the control group( (15. 12±1. 26) s,(36. 17±9. 05) s) (t = -15. 37,-9. 81,P<0. 05),platelet countPLT) ((146. 92±16. 85)×109 / L) was higher than that of the control group ((114. 18±10. 69)×109 / L ) (t= -9. 77,P<0. 05),and the blood routine hemoglobin (Hb) ((112. 21±9. 46) g/ L),and the base surplus (BE)((-5. 30 ± 2. 45) mmol/ L ) were all higher than those of the control group ((92. 95 ± 11. 20) g/ L, (-8. 27±3. 53) mmol/ L ) (t= -11. 46,-8. 99,P<0. 05),blood lactic acid (BL) ((2. 79±1. 12) mmol/ L ) was lower than that of the control group ((3. 54±1. 37) mmol/ L) (t = -8. 99,P<0. 05). The volume of 1 h infusion of shock in the observation group ((569. 96±187. 34) ml ) was lower than that of the control group((1957. 35±204. 14) ml) (t = 8. 725,P<0. 05). The incidence of ARDS (3. 33% (2/ 60)),MOD(3. 33%(2/ 60)) and fatality(1. 67%(1/ 60)) were lower than those of the control group(8. 33%(5/ 60),6. 67%(4/60),6. 67%(4/ 60) ( χ2 = 2. 725,3. 214,2. 985,P< 0. 05) . Conclusion The early stage of traumatic shock delayed fluid resuscitation is conducive to the protection of the blood coagulation function of patients,to improve blood indicators,to reduce the amount of 1 h infusion and to reduce the incidence of ARDS and MODS.
5.Clinical effect of intraoperative electron beam radiotherapy in treatment of unresectable locally advanced pancreatic cancer
Miaoli ZHENG ; Yongwen SONG ; Qinfu FENG ; Yingtai CHEN ; Yirui ZHAI ; Minghui LI ; Hui FANG ; Jianwei ZHANG ; Pan MA ; Chengfeng WANG
Chinese Journal of Radiation Oncology 2017;26(4):405-409
Objective To assess the prognostic benefits of intraoperative radiotherapy (IORT) with electron beam among patients with unresectable locally advanced pancreatic cancer.Methods Between January 2009 and December 2014,167 patients with unresectable locally advanced pancreatic cancer received IORT with electron beam (10-20 Gy) in our hospital.After surgery,12 patients were treated with external beam radiotherapy,56 patients with chemoradiotherapy (CRT),and 17 patients with chemotherapy.Overall survival (OS),local recurrence,and toxicities were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis,and the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100%.The median OS time was 10.3 months,and the 2-year OS rate was 22%.The median progression-fiee survival (PFS) time was 6.3 months,and the 2-year PFS rate was 9.9%.The cancer-specific survival (CSS) time was 11.2 months,and the 2-year CSS rate was 23.6%.In the patients treated with IORT alone at doses of<15 Gy,15 Gy and>15 Gy,the median OS times were 6.2 months vs.9.1 months vs.22.2 months,and the 1-year OS rates were 10.0% vs.39.6% vs.74.4% (P=0.000).Among the patients receiving postoperative adjuvant therapy,those treated with IORT+CRT had the best survival,with a median OS time of 11.6 months (P=0.033).The univariate analysis showed that IORT dose (P =0.000),tumor size (P =0.006),and IORT applicator diameter (P =0.007) were prognostic factors.The multivariate analysis showed that IORT dose (P=0.000) and IORT combined with CRT (P=0.006) were independent prognostic factors.Conclusions IORT with electron beam is an effective and safe treatment strategy for unresectable locally advanced pancreatic cancer.After protecting surrounding organs,increasing the IORT dose can improve the survival.IORT combined with CRT should be recommended because it improves survival for unresectable locally advanced pancreatic cancer without increasing toxicities.
6.Pathological changes of renal grafts from elderly donor kidney in young recipients
Jiali FANG ; Zheng CHEN ; Junjie MA ; Guanghui LI ; Lu XU ; Lei ZHANG ; Yuhe GUO ; Yirui ZHANG ; Guanghui PAN
Organ Transplantation 2015;(5):335-339
Objective To study the pathological changes of renal grafts from elderly donor in young recipients and to investigate the safety of kidney transplantation from elderly donors.Methods Fourteen elderly kidney donors (with the age >55 years old)and fourteen young recipients (with the age <30 years old)underwent living related donor renal transplantation at the Department of Transplantation of the Second Affiliated Hospital of Guangzhou Medical University from January 2008 to December 2008 were enrolled as the object of study.Every elderly donor kidney was performed time-zero biopsy and every young recipient was performed routine renal graft biopsy 6 months after transplantation.The pathological and structural changes of kidney tissues after renal transplantation from elderly donors were observed.Results The histopathological changes occurred at 6 months after transplantation from elderly kidney donors to young recipients.Compared with those before transplantation,the severity of renal arteriolar lesion and the index of renal arteriolar sclerosis alleviated after transplantation (P <0.05 ), and the ratio of glomerulosclerosis did not change after transplantation (P >0.05 ).The expression of fibronectin (FN)decreased after transplantation,but the difference had no statistical significance (P >0.05 ).The expression of laminin (LN ) decreased after transplantation (P <0.05).Conclusions The histopathological structure of renal graft from elderly donors in young recipients has improved.
7.Application of ImmuKnow immune cell function assay in monitoring of immune function after renal transplantation
Lei ZHANG ; Zheng CHEN ; Yirui ZHANG ; Yuhe GUO ; Junjie MA ; Jiali FANG ; Guanghui LI ; Lu XU ; Guanghui PAN
Organ Transplantation 2015;(6):429-433
Objective To investigate the application value of ImmuKnow immune cell function assay in monitoring of immune function changes after renal transplantation.Methods One hundred and six patients with uraemia undergoing renal transplantation in the Department of Organ Transplantation of the Second Affiliated Hospital of Guangzhou Medical University from January 201 3 to December 201 4 were included.Blood specimens were collected before transplantation and at the occurrence of infection or acute rejection during 1 2 months after transplantation.ImmoKnow was used to determine the adenosine triphosphate (ATP)content in CD4 +T cells.The ATP content of patients with renal transplantation at different clinical conditions were observed and compared,including periopreative group,stable group,acute rejection group and infecticn group (including severe pneumonia).The ratio of T cell subsets (CD4 +T cells,CD8 +T cells)and natural killer (NK)cells in peripheral blood were detected.Pearson correlation analysis was used to detect the association between ATP and the blood trough concentration of tacrolimus (FK506)and ciclosporin (CsA).Results The ATP content of the patients in the infection group was lower than that of the patients in the stable group (P <0.001 ).The ATP content of patients with severe pneumonia was lower than that of patients with other infections (P <0.05).The percentage of CD4 +T cells of the patients in the infection group was lower than that of the patients in the postoperative stable group (P <0.05 ). The ATP content was not associated with the postoperative blood trough concentration of FK506 and CsA.Conclusions ImmuKnow assay may be used to monitor the postoperative immune function of patients after renal transplantation.The detection of ATP content in CD4 + T cells has hinting and pre-warning function for postoperative infection,especially for severe pneumonia.
8.Safety and feasibility of autologous bone marrow mesenchymal stem cells in treating chronic allograft nephropathy
Lei ZHANG ; Zheng CHEN ; Sisheng XIE ; Junjie MA ; Jiali FANG ; Guanghui LI ; Lu XU ; Yirui ZHANG ; Yuhe GUO ; Guanghui PAN
Chinese Journal of Tissue Engineering Research 2014;(32):5140-5145
BACKGROUND:Chronic al ograft nephropathy is a complication of kidney transplantation and most of patients wil eventual y develop transplant kidney dysfunction. Bone marrow mesenchymal stem cells as a low immunogenicity special cellpopulation have been shown to have differentiation, transdifferentiation, paracrine and other basic functions, which have been successful used in other clinical areas. Based on this characteristic, bone marrow mesenchymal stem cells may play a therapeutic role in chronic al ograft nephropathy. OBJECTIVE:To study the safety and feasibility of autologus bone marrow mesenchymal stem cells transplantation via renal artery infusion and subsequent intravenous infusion guided by the digital subtraction angiography in the treatment of chronic al ograft nephropathy. METHODS:Eleven patients with chronic al ograft nephropathy who were confirmed from March 2011 to January 2013 were enrol ed, and then received transplant renal artery infusion once guided by the digital subtraction angiography and subsequent intravenous infusion twice of bone marrow mesechymal stem cells. Changes in serum creatinine, blood urea nitrogen, creatinine clearance, cystatin C, 24-hour urine protein, andβ2 microglobulin in the blood and urinary were monitored in patients up to 1 year after treatment. RESULTS AND CONCLUSION:Bleeding, transplant renal artery embolization, pseudoaneurysm and other related complications were not found in any of the 11 patients. The levels of serum creatinine, blood urea nitrogen and cystatin C were significantly decreased at 1 week and 1 month after celltherapy (P<0.05), while after 3 months of treatment, there was no difference before and after treatment (P>0.05). The creatinine clearance at 1 week and 1 month after treatment showed a remarkable increase, which were significantly different from that before treatment (P<0.05), but after 3 months of treatment, the difference was not significant (P>0.05). The level of 24-hour urine protein was significantly decreased after 7 days of treatment (P<0.05), and no difference was found after 1 month (P>0.05). The level ofβ2 microglobulin in the blood and urinary had no changes before and after treatment. These findings indicate that guided by the digital subtraction angiography, bone marrow mesenchymal stem cells via the renal artery infusion and subsequent intravenous infusion can improve kidney function of patients, but the celldosage and infusion method remain to be solved.

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