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.Antibody threshold and demographic characteristics of low-titer group O whole blood donors in Jiangsu
Tao FENG ; Rui ZHU ; Wenjia HU ; Ling MA ; Hong LIN ; Xi YU ; Chun ZHOU ; Nizhen JIANG
Chinese Journal of Blood Transfusion 2025;38(9):1225-1229
Objective: To investigate the distribution of IgM anti-A/B titers among group O whole blood donors in Jiangsu, establish a low-titer threshold, and analyze the demographic characteristics of low-titer donors, so as to provide data for recruiting low-titer group O whole blood (LTOWB) donors. Methods: Plasma samples from 1 009 group O whole blood donors were tested for IgM anti-A and anti-B titers using the microplate technique. The distribution of antibody titers was analyzed to establish a low-titer threshold. The distribution trends of titers across different demographic groups were also analyzed. Results: The peak titer for anti-A, anti-B were 64 (31.5%), 4 (23.8%), respectively, The proportion of donors with both anti-A and anti-B titers below 64 was 97.3% (982/1 009). The mean anti-A titer was higher than anti-B titer. Anti-A titers were higher in female donors than in male donors (P<0.05). The anti-A titers differed significantly among different age groups (P<0.05). However, no significant difference in titers was observed based on the number of donations (P>0.05). Conclusion: A titer of 64 can be used as the reference threshold of LTOWB in Jiangsu. Male donors of appropriate age are more suitable than female donors for establishing an emergency panel of LTOWB mobile donors.
3.Relationship between LMAN2 expression in HR-positive breast cancer tissues and patient prognosis and its effect on proliferation and migration of MCF-7 cells
YAN Changjiao ; HUANG Meiling ; XIAO Jingjing ; LING Rui
Chinese Journal of Cancer Biotherapy 2024;31(1):47-53
[摘 要] 目的:探究甘露糖结合凝集素2(LMAN2)在激素受体(HR)阳性乳腺癌组织中的表达水平与乳腺癌患者预后的关系及其对MCF-7 细胞增殖和迁移的影响。方法:通过TCGA、Bc-GenExMiner、GEPIA和Kaplan-Meier Plotter数据库分析LMAN2在乳腺癌组织和正常乳腺组织中的差异性表达及其与患者预后的关系。采用小RNA干扰技术将si-LMAN2#1、si-LMAN2#2及si-NC转染至MCF-7细胞,将过表达LMAN载体(pc-LMAN)及空载体pcDNA3.1阴性对照(pc-NC)转染至MCF-7细胞,实验分为si-LMAN2#1、si-LMAN2#2、si-NC、pc-LMAN2和pc-NC组。通过qPCR和WB实验检测各组细胞中LMAN2 mRNA和蛋白的表达水平,CCK-8、克隆形成、Transwell迁移、WB等实验检测敲低和过表达LMAN 2对MCF-7细胞增殖、克隆形成、迁移及AKT信号通路相关蛋白表达的影响。结果:LMAN2在乳腺癌组织中的表达水平显著高于正常乳腺组织(P<0.001)。HR阳性乳腺癌组织中LMAN2表达水平显著高于HR阴性乳腺癌组织(P<0.001);LMAN2高表达与HR阳性乳腺癌患者不良预后有关联。敲低LMAN2可显著降低MCF-7细胞的增殖和迁移能力(P<0.01或P<0.001),过表达LMAN2可显著提高MCF-7细胞的增殖和迁移能力(均P<0.001)。敲低LMAN2组MCF-7细胞中PTEN和P21蛋白表达水平均显著升高,p-AKT蛋白表达水平显著降低(均P<0.01)。结论:LMAN2在乳腺癌组织和HR阳性乳腺癌组织中高表达,且与不良预后有关联。LMAN2高表达与MCF-7细胞增殖和迁移有关联,其作用机制可能涉及AKT信号通路。
4.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
5.Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling.
Yong RAO ; Rui SU ; Chenyan WU ; Xingxing CHAI ; Jinjian LI ; Guanyu YANG ; Junjie WU ; Tingting FU ; Zhongping JIANG ; Zhikai GUO ; Congjun XU ; Ling HUANG
Acta Pharmaceutica Sinica B 2024;14(1):304-318
Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.
6.Analysis of dosimetric parameters of acute radiation enteritis in cervical cancer patients treated with con-current chemoradiotherapy
Jing HU ; Xu WANG ; Xiaoqin GONG ; Rui LING ; Tao YOU ; Chunhua DAI ; Ye TIAN ; Fei CHEN
The Journal of Practical Medicine 2024;40(5):672-676
Objective To explore the correlation between intestinal dose and acute radiation enteritis(ARE)in patients with cervical cancer received concurrent chemoradiotherapy,and optimize the dose limit of intestinal tissue.Methods 158 cervical cancer patients received concurrent chemoradiotherapy from 2014 to 2019 were selected in this study.According to CTCAE 5.0,patients with ARE≥grade 2 were classified as ARE≥grade 2 group,otherwise classified as ARE
7.Characteristics of abnormal coronary aorta origin in adults and cause analysis of missed diagnosis by transthoracic echocardiography
Si-Yang ZUO ; Sen LI ; You-Xiang KANG ; Xiao-Ling ZHAO ; Li-Xing WANG ; Rui CHEN ; Zhi-Yu FENG
Chinese Medical Equipment Journal 2024;45(1):71-75
Objective To analyze the characteristics of adult anomalous aortic origin of coronary artery(AAOCA)and the causes of missed diagnosis by transthoracic echocardiography(TTE)so as to facilitate TTE in diagnosing adult AAOCA.Methods A total of 37 adult patients with AAOCA diagnosed by non-invasive coronary CT angiography(CCTA)and/or invasive coronary angiography(ICA)were selected as research samples at some hospital from January 2019 to December 2022,and their clinical symptoms and the findings of 12-lead electrocardiogram,cardiac enzymes and TTE were summarized;the patients were typed according to the site of origin of coronary artery anomalies,and the causes for the missed diagnosis of TTE were eplored.Chi-square test was used to compare the differences in TTE missed diagnoses.Results Of the 37 patients,31 ones had no or only mild symptoms;most ones had negative results in terms of 12-lead electrocardiography,cardiac enzymes,changes in the size of the cardiac chambers,segmental ventricular wall motion abnormalities and left ventricular systolic function.The patients with anomalous origin of the right coronary artery from left sinus(ARCA-L)gained the largest proportion of 59.45%(22/37);21 patients were diagnosed with anomalous origin of coronary artery arising from the opposite sinus(ACAOS)in the two examinations of TTE,of whom there were 19 cases of ARCA-L,and the detection rate of ACAOS by TTE was 87.5%;all the 13 patients origins in branches and high-grade openings were missed by TTE.The detection rate of ACAOS by TTE was significantly higher than that of coronary artery anomalies originating in branches and in high openings,and the difference was statistically significant(21/24 vs 0/13,P<0.001).Conclusion Most adult AAOCA patients lack specificity in symptoms and related examination results.TTE has a high detection rate of ACAOS,while it is easy to miss the diagnosis of coronary artery anomalies originating from branches and high openings.Ultrasonographers have to identify false negative AAOCA by multi-section and multi-angle scanning and color Doppler flow imaging in order to reduce the rate of missed diagnosis.[Chinese Medical Equipment Journal,2024,45(1):71-75]
8.16S rDNA Sequencing Reveals Effect of Tanreqing Injection on Pulmonary Flora in Rat Model of COPD
Qian LUO ; Rui FU ; Bo PENG ; Weiya CHEN ; Xiaolu WEI ; Tengfei CHEN ; Ling SONG ; Yunhang GAO ; Guangping ZHANG ; Hongping HOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):98-103
ObjectiveTo study the effect of Tanreqing injection (TRQ) on the pulmonary flora in the rat model of chronic obstructive pulmonary disease (COPD). MethodWistar rats were randomized into control, model, and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ (2 g·kg-1). At the end of the experiment, after blood collection from the abdominal aorta of the rats, the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected, and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal, and those of the model group showed neutrophil infiltration, telangiectasia, lung hemorrhage and emphysema in individual cases, and thickening of collagen fibers in the trachea. Compared with the model group, the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group, the model group showcased increased alveolar space (P<0.01), which was reduced in the TRQ group (P<0.05). Compared with the control group, the model group showed increased wall thickness (P<0.01), and the increase was attenuated in the TRQ group (P<0.01). TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level, the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas, compared with the control group. After treatment with TRQ, the relative abundance of g_Stenotrophomonas increased, and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group, and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD, which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.
9.The taste correction process of ibuprofen oral solution based on the combination of electronic tongue technology and artificial taste comprehensive evaluation
Rui YUAN ; Yun-ping QU ; Yan WANG ; Ya-xuan ZHANG ; Wan-ling ZHONG ; Xiao-yu FAN ; Hui-juan SHEN ; Yun-nan MA ; Jin-hong YE ; Jie BAI ; Shou-ying DU
Acta Pharmaceutica Sinica 2024;59(8):2404-2411
This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model:
10.Protective effect of sufentanil on rat model of off-pump coronary artery bypass grafting
Yan LU ; Zong-Fang PIAO ; Ling LI ; Li-Wei WANG ; Rui SU
The Chinese Journal of Clinical Pharmacology 2024;40(4):579-583
Objective To investigate the effects of sufentanil on myocardial cells and renal function in rat models of non-stopping coronary artery bypass grafting.Methods SD rats were randomly divided into sham group(only thoracectomy without coronary artery ligation),model group(ischemia perfusion model was constructed),experimental-L group(ischemia perfusion model+0.5 μg·kg-1 sufentanil)and experimental-H group(ischemia perfusion model+1μg·kg-1 sufentanil).The mice were sacrificed 6 h after operation.The expressions of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and interleukin-6(IL-6)in cardiomyocytes and renal cells were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of apoptosis-related proteins in cardiomyocytes and renal cells were detected by Western blot.Serum renal function was detected with serum renal function kit.Results The expression levels of TNF-α in myocardial cells were(50.41±6.03),(136.61±21.73),(102.36±12.84)and(74.21±16.32)pg·mg-1 in sham group,model group,experimental-L group and experimental-H group,respectively;the expression levels of cysteinyl aspartate specific proteinase-3(Caspase-3)were 0.31±0.02,1.26±0.18,0.83±0.12 and 0.67±0.08,respectively;blood urea nitrogen(BUN)levels were(5.94±1.12),(20.04±5.36),(16.84±4.19)and(10.96±3.64)μmol·L-1,respectively;the expression levels of TNF-α in renal cells were(146.49±16.13),(1 023.82±34.69),(841.65±49.66)and(324.84±48.93)pg·mg-1,respectively;the expression levels of Caspase-3 in renal cells were 0.48±0.06,1.15±0.17,0.96±0.06 and 0.74±0.07,respectively.The difference between experimental-H group and sham group,model group and experimental-L group were statistically significant(all P<0.05).Conclusion Sufentanil can significantly reduce the production of inflammatory factors and the expression of apoptotic proteins in rat cardiomyocytes,significantly improve the renal function of rats,and significantly reduce the production of inflammatory factors and the expression of apoptotic proteins in rat renal cells.

Result Analysis
Print
Save
E-mail