1.Research progress on the regulation of ferroptosis by lipid droplet metabolism
Quan-ao JIANG ; Ran DENG ; Shi-lin XIA ; Xiao-man JIANG ; Jing XU ; Hong WU
Acta Pharmaceutica Sinica 2024;59(7):1897-1904
As a novel iron-dependent form of cell death, ferroptosis is characterized by the excessive accumulation of phospholipids containing polyunsaturated fatty acids (PUFA) on the cell membrane and peroxidation. Lipid droplets are always in the dynamic transition of generation and decomposition, play a central role in regulating lipid metabolism, and are always in the dynamic transition of generation and decomposition. Lipid droplet metabolism is closely related to the occurrence of ferroptosis and plays an important role in the disease caused by ferroptosis. This review firstly focuses on the lipid droplet metabolism process and its effects on the storage and release of PUFA, and further elucidates the regulatory mechanism and key regulatory proteins of lipid drop metabolism on ferroptosis, in order to reveal the intrinsic relationship between lipid droplets and ferroptosis, and provide a new strategy for disease prevention and treatment.
2.The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells
Zhuo CHEN ; Meng-Wei YAO ; Xiang AO ; Qing-Jia GONG ; Yi YANG ; Jin-Xia LIU ; Qi-Zhou LIAN ; Xiang XU ; Ling-Jing ZUO
Chinese Journal of Traumatology 2024;27(1):1-10
Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.
3.Effect of CXCL7/CXCR2 axis on synaptic plasticity in obesity-related cognitive dysfunction
Jia HU ; Ao-Xue XU ; Rui HU ; Qi XUE ; Chun-Xia HUANG ; Ye ZHANG
Chinese Pharmacological Bulletin 2024;40(5):881-886
Aim To explore the effect of CXCL7/CX-CR2 axis on obesity-related cognitive dysfunction at both animal and cellular levels.Methods The novel object recognition test was performed to assess the cog-nition.After the preparation of the frozen sections,the activation of microglia and astrocytes in hippocampi and the level of PSD95 were determined by immunoflu-orescence staining.The content of CXCL7 in hipp-ocampi was determined by enzymelinked immunosor-bent assay.The dendritic spine density of hippocampal neurons was observed by Golgi staining.Furthermore,HT22 cells were treated with the recombinant mouse CXCL7 and/or si-RNA targeting CXCR2.After the treatment,the levels of CXCL7 and PSD95 were ob-served by immunocytochemistry staining.Results Compared with animals in the control group,there was significantly decreased discrimination index,increased activation of microglia and astrocytes,decreased con-tent of PSD95,decreased density of dendritic spine,and increased content of CXCL7 in hippocampi in the DIO group.Compared with animals in the DIO group,there were significantly increased discrimination index in the AWL group.In HT22 cells,the level of PSD95 significantly decreased in the Ctrl+CXCL7 group com-pared with the control group.This decrease was attenu-ated in the si-CXCR2+CXCL7 group compared with the Ctrl+CXCL7 group.Conclusion Chronic high-fat diet induces neuroinflammation and subsequently induces cognitive dysfunction,which may be related to the synaptic plasticity mediated by the CXCL7/CXCR2 axis.
4.Efficacy and safety of azacitidine plus BUCY2 as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome
Sibin ZANG ; Ao ZHANG ; Linghui XIA ; Wei SHI
Chinese Journal of Organ Transplantation 2024;45(2):82-87
Objective:To evaluate the efficacy and safety of treating allogeneic hematopoietic stem cell transplantation (allo-HSCT) with azacitidine plus BUCY2 as a conditioning regimen for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).Method:From January 1, 2022 to July 15, 2023, a retrospective study was conducted for the relevant clinical data of 26 AML-MDS patients undergoing allo-HSCT with azacitidine plus BUCY2 as a conditioning regimen at Wuhan Union Hospital. There were 15 males and 11 females. For haploidentical transplantation, rabbit anti-human thymocyte immunoglobulin (ATG) was added. And tacrolimus + mycophenolale mofetil + recombinant humanized anti-CD25 monoclonal antibody injection (Xenopax) ± methotrexate were utilized for preventing GVHD. For human leukocyte antigen matched transplantation, cyclosporin A + methotrexate + Xenopax were employed for preventing GVHD. Incidence timing, severity, incidence rate of acute/chronic graft versus host disease (a/cGVHD), granulocyte/platelet engraftment time, infection type, overall survival and relapse date were recorded.Result:Granulocyte engraftment was attained with a median engraftment time of 12 (9~18) day and platelet engraftment with a median engraftment time of 16 (13~34) day. The incidence of acute graft-versus-host disease (aGVHD) was 63.14% (95% CI: 60.90%~65.37%), the incidence of grade Ⅲ aGVHD 6 (95% CI: 11.39%~13.23%) and the median onset time of aGVHD 49 (11~93) day post-transplantation. The incidence of chronic graft-versus-host disease (cGVHD) was 52.68% (95% CI: 49.23%~56.13%) and the incidence of moderate-severe cGVHD 11.43% (95% CI: 10.20%~12.66%). Infections were caused by cytomegalovirus (CMV) viremia (7 cases), bacteria (3 cases) and fungus (4 cases). Until the last follow-up, 23 recipients achieved relapse-free survival and continued MRD negativity. Death occurred due to recurrence (2 cases) and GVHD plus severe infection (1 case). Cumulative incidence of relapse (CIR) was 10.20% (95% CI: 9.21%~11.18%), 1-year overall survival (OS) 83.50% (95% CI: 67.90%~100%), GVHD/relapse-free survival (GRFS) 70.30% (95% CI: 52.30%~94.30%) and non-relapse mortality (NRM) 5.02% (95% CI: 4.53%-5.52%). Conclusion:Using azacitidine plus BUCY2 as a conditioning regimen, OS of allo-HSCT for AML-MDS is higher than that of traditional regimen. The risks of III-IV aGVHD, relapse and infection are safe and controllable.
5.ZHOU Peng's Experience in Treating Psoriasis Vulgaris of Blood Stasis Type Based on the Analysis of Dermoscopic Signs
Guo-Ao SHI ; Rui-Ming CHEN ; Xiang JI ; Zhong-Xian LI ; Yong-Qin XIONG ; Xia-Yun ZHOU ; Jing-Jing LI ; Peng ZHOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2109-2115
Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.
6.Simultaneous determination of 6 aconitum-type alkaloids in Xiaozhong ointment by ultra-high performance liquid chromatography triple quadrupole mass spectrometry
Tian-Li XIA ; De-Ping ZHAO ; Ao XUE ; Mei-Ling JIN ; Zi-Yue ZHU ; Qing LI ; Ning ZHANG ; Xia LEI
The Chinese Journal of Clinical Pharmacology 2024;40(9):1341-1344
Objective To establish a method for the simultaneous determination of aconitine,neoaconitine,hypaconitine,benzoyl aconitine,benzoyl mesaconine and benzoylhypacoitine in Xiaozhong ointment by UPLC-TQD-MS.Methods ACQUITY UPLC BEH C18 column(50 mm ×2.1 mm,1.7 μm),mobile phase 0.1%formic acid water(A)-acetonitrile(B),gradient elution,column temperature 40 ℃,flow rate 0.3 mL·min-1,injection volume 5 μL;electrospray ionization source(ESI+)and multiple reaction monitoring(MRM)were used for mass spectrometry analysis.Results The concentration of aconitine,new aconitine,hypaconitine,benzoyl aconitine,benzoyl new aconitine and benzoyl hypaconitine were 1.0-100.0 ng·mL-1,respectively,the average recovery were 98.62%-101.24%.The mass fractions of the six components were 0.18,0.33,0.38,0.43,0.28,0.06μg·g-1.Conclusion The method can be used to determine the content of 6 aconitine-type alkaloids in Xiaozhong ointment,and provide reference for the quality evaluation and clinical safe use of Xiaozhong ointment.
7.Exploring the factors affecting music-related quality of life in post-lingual deaf adults with cochlear implants
Ye YANG ; Xiaoyun QIAN ; Liguo GENG ; Yaofeng JIANG ; Junyan GAO ; Li HUANG ; Ao LI ; Ning ZHAO ; Yuqin XU ; Guangjie ZHU ; Xia GAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(1):27-33
Objective:To observe the feelings of listening to music and the importance of music in the daily life of post-lingual deaf adults with cochlear implants, and to explore the relevant influencing factors.Methods:This was a cross-sectional survey study. From January 2021 to August 2021,the Music-Related Quality of Life Scale was used to evaluate the music needs and music experiences of 63 post-lingual deaf adults who met the inclusion criteria, including 27 males and 36 females, aged (40.7±12.3) years, at the time of surgery (36.8±13.1) years, and with a preoperative hearing aid ineffective time of (3.9±5.8) years. Indicators analyzed included age, duration of ineffective preoperative hearing aid wear, preoperative music preference, duration of postoperative cochlear implant use, current hearing aid modality, and auditory rehabilitation outcomes. Whether the six factors mentioned above constituted an influence on the subjects′ music listening was investigated using SPSS 25.0 statistical software.Results:All of the observations in the scale were correlated with a single factor. The two sub-dimensions of music experience section were related to the effect of auditory rehabilitation. In the importance section, the effect of auditory rehabilitation was the influential factor of the dimension of "participation importance", and the preoperative enjoyment of music was the relevant influential factor of the dimension of "perceived importance". There was a significant difference between the groups when they were grouped by the above factors ( P value<0.05), while there was no statistically significance between the groups when they were grouped by other factors ( P value>0.05). Conclusions:Post-lingual deaf adults show the need and attempt to listen to music after cochlear implantation. The effectiveness of auditory rehabilitation and the degree of music preference preoperatively are two important factors that influence music listening in implant recipients. Once the level of auditory communication has been restored to a certain degree, it is important to pay more attention to the needs of music for implant recipients and train them in time, especially for those with music preferences preoperatively.
8.Key microbial monitoring and clinical analysis of bloodstream infections and CRO colonization after hematopoietic stem cell transplantation in hematological patients
Ao ZHANG ; Chenjing QIAN ; Ruowen WEI ; Shan JIANG ; Jun FANG ; Wei SHI ; Linghui XIA
Chinese Journal of Hematology 2024;45(2):134-140
Objective:To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients.Methods:We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison.Results:The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM ( P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM ( P=0.035) . Conclusion:This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.
9.New perspectives on the therapeutic potential of quercetin in non-communicable diseases:Targeting Nrf2 to counteract oxidative stress and inflammation
Zhang LI ; Xu LI-YUE ; Tang FEI ; Liu DONG ; Zhao XIAO-LAN ; Zhang JING-NAN ; Xia JIA ; Wu JIAO-JIAO ; Yang YU ; Peng CHENG ; Ao HUI
Journal of Pharmaceutical Analysis 2024;14(6):805-822
Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.
10.Effects of high salt diet on renal vascular reactivity in mice detected by laser speckle contrast imaging.
Li-Xia HU ; Shao-Peng JIANG ; Ao XIAO ; Xin-Xin MENG ; Ming-Xiao WANG
Acta Physiologica Sinica 2024;76(6):979-986
The aim of this study was to conduct in vivo experiments using laser speckle contrast imaging (LSCI) technology to investigate the effects of high salt diet on renal vascular reactivity in mice. LSCI is a technology for monitoring blood flow based on the laser speckle principle. It has been widely used to detect microcirculatory functions in tissues such as the skin and brain. The kidneys are located behind the peritoneum, and their position is easily affected by the movement of abdominal organs. Measuring renal microcirculation in a living individual is difficult. The present study used a self-made kidney cup to isolate the kidney and fix its position relatively, and then applied LSCI technology to explore the effect of high salt diet (8% Na+) on renal vascular reactivity in male and female mice in vivo. The results showed that a short-term high salt diet (1 week) did not affect the systolic blood pressure of the tail artery, while significantly increased glomerular filtration rate (GFR) and renal blood flow (RBF). Compared with the normal salt diet group, the high salt diet group showed a significant decrease in the ratio of post-occlusive reactive hyperemia (PORH) in male mice, while there was no significant change in the PORH ratio in female mice. These results suggest that, although a short-term high salt diet does not cause changes in blood pressure, it has already affected renal vascular reactivity and has gender differences in its effects. Furthermore, the present study provides a basis for renal microcirculation assessment using LSCI in vivo.
Animals
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Mice
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Male
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Female
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Kidney/blood supply*
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Renal Circulation/physiology*
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Laser Speckle Contrast Imaging
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Sodium Chloride, Dietary/adverse effects*
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Microcirculation/physiology*
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Mice, Inbred C57BL

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