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Role of ferroptosis in fibrosis: From mechanism to potential therapy

中华医学杂志(英文版) 2024年第7期137卷 806-817页

作者： Qiu Xuemeng Bi Qing Wu Jiyue Sun Zejia Wang Wei department of Urology Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China Urinary and nephropathy Center Institute of Urology

Fibrosis, which is a manifestation of the physiological response to injury characterized by excessive accumulation of extracellular matrix components, is a ubiquitous outcome of the repair process. However, in cases of repetitive or severe injury, fibrosis may become dysregulated, leading to a pathological state and organ failure. In recent years, a novel form of regulated cell death, referred to as ferroptosis, has been identified as a possible contributor to fibrosis; it is characterized by iron-mediated lipid peroxidation. It has garnered attention due to the growing body of evidence linking ferroptosis and fibrogenesis, which is believed to be driven by underlying inflammation and immune responses. Despite the increasing interest in the relationship between ferroptosis and fibrosis, a comprehensive understanding of the precise role that ferroptosis plays in the formation of fibrotic tissue remains limited. This review seeks to synthesize previous research related to the topic. We categorized the different direct and indirect mechanisms by which ferroptosis may contribute to fibrosis into three categories: (1) iron overload toxicity; (2) ferroptosis-evoked necroinflammation, with a focus on ferroptosis and macrophage interplay; and (3) ferroptosis-associated pro-fibrotic factors and pathways. Furthermore, the review considers the potential implications of these findings and highlights the utilization of ferroptosis-targeted therapies as a promising strategy for mitigating the progression of fibrosis. In conclusion, novel anti-fibrotic treatments targeting ferroptosis could be an effective treatment for fibrosis.

关键词： Ferroptosis Fibrosis Anti-fibrotic Iron metabolism Necroinflammation Epithelial-mesenchymal transition

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Characteristics and quality of clinical practice guidelines for diabetic kidney disease: a systematic review

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Journal of Traditional Chinese Medicine 2024年第3期44卷 609-619页

作者： WANG Yuhuang ZHANG Le ZHANG Zhengshan YAO Zhi LI Xiyao SUN Luying LIAO Xing department of nephropathy and Endocrine Dongzhimen HospitalBeijing University of Chinese Medicine Centre for Evidence-Based Chinese Medicine Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical Sciences department of Endocrine One Zone Fangshan HospitalBeijing University of Chinese Medicine

OBJECTIVE: To assess the quality of Clinical practice guidelines(CPGs) in the context of diabetic kidney disease(DKD) and determine whether any factors affect the quality. METHODS: We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of ***. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1(lowest possible quality) to 7(highest possible quality). Moreover, an overall recommendation for use was also assigned(“recommended”, “recommended with modifications” or “not recommended”). RESULTS: A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development(33%), followed by application(36%), and stakeholder involvement(51%). The highest average score was for scope and purpose(79%), followed by clarity of presentation(75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. CONCLUSIONS: According to the AGREE II evaluation, more than one in four CPGs for DKD had poor methodolo

关键词： appraisal of guidelines for research and evaluation II diabetic nephropathies practice guideline quality assessment systematic review

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Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

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World Journal of Clinical Cases 2024年第1期12卷 188-195页

作者： Shi-Yuan Liu Hao Chen Li-Jia He Chun-Kai Huang Pu Wang Zhang-Ru Rui Jue Wu Yang Yuan Yue Zhang Wen-Ju Wang Xiao-Dan Wang Central Laboratory Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan ProvinceYan'an Hospital Affiliated to Kunming Medical UniversityKunming 650051Yunnan ProvinceChina department of nephropathy Yan'an Hospital Affiliated to Kunming Medical UniversityKunming 650051Yunnan ProvinceChina

BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.

关键词： Lupus nephritis Macrophage Podocyte Repeat renal biopsy Thrombotic microangiopathy Case report

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Potential efficacy and mechanism of medicinal plants on chronic kidney disease-associated vascular calcification:a review

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Traditional Medicine Research 2024年第9期9卷 21-31页

作者： Han-Qing Zhang Shuang Wu Xin Chen Ya-Xuan Fang Qiu-Mei Lan Zi-Jun Zhou Yan-Heng Qiao Jie Li Yan-Ru Zhao Ming Pei Bo Yang department of nephropathy First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300381China National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Tianjin 300381China

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.

关键词： chronic kidney disease chronic kidney disease-mineral and bone disorder(CKD-MBD) vascular calcification medicinal plants herbal monomers

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Exploring the medication pattern and mechanism of action of traditional Chinese medicine in treating polycystic ovary syndrome with kidney deficiency and blood stasis based on data mining and network pharmacology

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Medical Data Mining 2024年第1期7卷 40-52页

作者： Li-Jun Zhou Yi-Ling Liu department of Gynaecology and Obstetrics Chongqing Ba’nan District Traditional Chinese Medicine HospitalChongqing 401320China department of nephropathy Endocrinology Suzhou Hospital of Integrated Traditional Chinese and Western MedicineSuzhou 215000China.

Background:Using network pharmacology to explore the potential molecular mechanism of traditional Chinese medicine in treating polycystic ovary syndrome(PCOS)with kidney deficiency and blood stasis syndrome.Method:Collect the related literature materials of PCOS with kidney deficiency and blood stasis syndrome treated by traditional Chinese medicine in four databases in recent ten years,extract the information of prescriptions and complete the frequency analysis.Traditional Chinese Medicine Systems Pharmacology Database was used to screen out the effective components.Use Online Mendelian Inheritance in Man and other databases to screen PCOS disease targets.The intersection targets obtained by clustering prescription and PCOS disease targets were submitted to STRING database for protein-protein interaction network analysis,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathways were analysed by Metascape.Result:There are 155 kinds of traditional Chinese medicines used in the literature.The most commonly utilized ones are Cuscutae Semen,Angelicae Sinensis Radix,and Rehmanniae Radix Praeparata.The results of the cluster analysis indicated that the plants most commonly found throughout the prescription were Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.GO results show that biological processes include cell reaction to organic nitrogen compounds and cell reaction to nitrogen compounds.The functional display of GO molecule includes cytokine receptor binding,signal receptor regulator activity and so on.Kyoto Encyclopedia of Genes and Genomes results show that the possible mechanisms of action are cancer pathway,an endocrine resistance signal pathway.Conclusion:Through data mining,the cluster prescription for PCOS with kidney deficiency and blood stasis syndrome is Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.The network pharmacology research of cluster prescription shows that the main drug components for treating PCOS with kidney deficiency and blood stasis syndrome are quercetin,kaempferol,luteolin,tan

关键词： polycystic ovary syndrome data mining syndrome of kidney deficiency and blood stasis network pharmacology

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Superhydrophobic Surface-Assisted Preparation of Microspheres and Supraparticles and Their Applications

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Nano-Micro Letters 2024年第4期16卷 110-138页

作者： Mengyao Pan Huijuan Shao Yue Fan Jinlong Yang Jiaxin Liu Zhongqian Deng Zhenda Liu Zhidi Chen Jun Zhang Kangfeng Yi Yucai Su Dehui Wang Xu Deng Fei Deng Institute of Fundamental and Frontier Sciences University of Electronic Science and Technology of ChinaChengdu 611731People’s Republic of China School of Materials Science and Engineering Sun Yat-Sen UniversityGuangzhou 510275People’s Republic of China Shenzhen Institute for Advanced Study University of Electronic Science and Technology of ChinaShenzhen 518110People’s Republic of China Pharmaceutical Glass Co.Ltd Zibo 256100People’s Republic of China department of nephropathy School of MedicineSichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduPeople’s Republic of China department of Nephrology Sichuan Provincial People’s Hospital Jinniu HospitalChengdu Jinniu District People’s HospitalChengduPeople’s Republic of China

Superhydrophobic surface(SHS) has been well developed, as SHS renders the property of minimizing the water/solid contact interface. Water droplets deposited onto SHS with contact angles exceeding 150°, allow them to retain spherical shapes, and the low adhesion of SHS facilitates easy droplet collection when tilting the substrate. These characteristics make SHS suitable for a wide range of applications. One particularly promising application is the fabrication of microsphere and supraparticle materials. SHS offers a distinct advantage as a universal platform capable of providing customized services for a variety of microspheres and supraparticles. In this review, an overview of the strategies for fabricating microspheres and supraparticles with the aid of SHS, including cross-linking process, polymer melting,and droplet template evaporation methods, is first presented. Then, the applications of microspheres and supraparticles formed onto SHS are discussed in detail, for example, fabricating photonic devices with controllable structures and tunable structural colors, acting as catalysts with emerging or synergetic properties, being integrated into the biomedical field to construct the devices with different medicinal purposes, being utilized for inducing protein crystallization and detecting trace amounts of analytes. Finally,the perspective on future developments involved with this research field is given, along with some obstacles and opportunities.

关键词： Superhydrophobic surface Microspheres and supraparticles Photonic devices Catalysts Biomedical and trace detections

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Decoding m^(6)A mRNA methylation by reader proteins in liver diseases

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Genes & Diseases 2024年第2期11卷 711-726页

作者： Lijiao Sun Xin Chen Sai Zhu Jianan Wang Shaoxi Diao Jinyu Liu Jinjin Xu Xiaofeng Li Yingyin Sun Cheng Huang Xiaoming Meng Xiongwen Lv Jun Li Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Institute of Innovative DrugsSchool of PharmacyAnhui Medical UniversityHefeiAnhui 230032China The Key Laboratory of Anti-inflammatory and Immune Medicines Anhui Medical UniversityMinistry of EducationHefeiAnhui 230032China Institute for Liver Diseases of Anhui Medical University ILD-AMUAnhui Medical UniversityHefeiAnhui 230032China department of nephropathy The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032China

N6-methyladenosine(m^(6)A)is a dynamic and reversible epigenetic regulation.As the most prevalent internal post-transcriptional modification in eukaryotic RNA,it participates in the regulation of gene expression through various mechanisms,such as mRNA splicing,nuclear export,localization,translation efficiency,mRNA stability,and structural transformation.The involvement of m^(6)A in the regulation of gene expression depends on the specific recognition of m^(6)A-modified RNA by reader proteins.In the pathogenesis and treatment of liver disease,studies have found that the expression levels of key genes that promote or inhibit the development of liver disease are regulated by m^(6)A modification,in which abnormal expression of reader proteins determines the fate of these gene transcripts.In this review,we introduce m^(6)A readers,summarize the recognition and regulatory mechanisms of m^(6)A readers on mRNA,and focus on the biological functions and mechanisms of m^(6)A readers in liver cancer,viral hepatitis,non-alcoholic fatty liver disease(NAFLD),hepatic fibrosis(HF),acute liver injury(ALI),and other liver diseases.This information is expected to be of high value to researchers deciphering the links between m^(6)A readers and human liver diseases.

关键词： IGF2BPs Liver diseases m^(6)A modification m^(6)A reader mRNA metabolism YTH domain protein

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Protective effect of modified Huangqi Chifeng decoction(加味黄芪赤风汤)on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 324-333页

作者： LI Liusheng ZHAO Mingming CHANG Meiying SI Yuan ZHAO Jinning YANG Bin ZHANG Yu department of Oncology Beijing Hospital of Integrated Traditional Chinese and Western MedicineBeijing 100039China department of nephropathy Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China Xin-Huangpu Joint Innovation Institute of Chinese Medicine Guangzhou 510070China department of Pathology Xiyuan Hospital China Academy of Chinese Medical SciencesBeijing 100091China department of Experimental Research Center Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China

OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,lipopolysaccharide,and carbon tetrachloride 4 method was employed.The rats were then randomly assigned to the control,model,telmisartan,and high-,medium-,and low-dose MHCD groups,and were administered the respective treatments via intragastric administration for 8 weeks.The levels of 24-h urinary protein,serum creatinine(CRE),and blood urea nitrogen(BUN)were measured in each group.Pathological alterations were detected.IgA deposition was visualized through the use of immunofluorescence staining.The ultrastructure of the kidney was observed using a transmission electron microscope.The expression levels of interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-β1(TGF-β1)were examined by immunohistochemistry and quantitative polymerase chain reaction.Levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor-kappa B(NF-κB)P65,were examined by immunohistochemistry,Western blotting,and quantitative polymerase chain reaction.RESULTS:The 24-h urine protein level in each group increased significantly at week 6,and worsen from then on.But this process can be reversed by treatments of telmisartan,and high-,medium-,and low-dose of MHCD,and these treatments did not affect renal function.Telmisartan,and high-,and medium-dose of MHCD reduced IgA deposition.Renal histopathology demonstrated the protective effect of high-,medium-,and low-dose of MHCD against kidney injury.The expression levels of MCP-1,IL-6,and TGF-β1 in kidney tissues were downregulated by low,medium and high doses of MHCD treatment.Additionally,treatment of low,medium and high doses of MHCD decreased the protein and mRNA levels of TLR4,MyD88,and NF-κB.CONCLUSIONS:MHCD exerted nephroprotective effects on IgAN rats,and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-

关键词： glomerulonephritis IGA toll-like receptor 4 myeloid differentiation factor 88 NF-kappa B signal transduction inflammation renal fibrosis modified Huangqi Chifeng decoction

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Exploring the mechanism of hirudin in the treatment of diabetic kidney disease using network pharmacology combined with molecular docking verification

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Journal of Traditional Chinese Medicine 2022年第4期42卷 586-594页

作者： PANG Xinxin ZHU Qing PENG Zining ZHANG Yage SHI Xiujie HAN Jiarui department of nephropathy Henan Provincial Hospital of Traditional Chinese MedicineZhengzhou 450002China

OBJECTIVE:To explore the mechanism of hirudin in the treatment of diabetic kidney disease(DKD).METHOD:Cytoscape software was used to analyze the network between hirudin targets and active components in the treatment of DKD.The biological function and mechanism of effective targets of hirudin for DKD treatment were analyzed by the Database for Annotation,Visualization and Integrated Discovery(DAVID)database.Molecular docking technology was used to simulate the docking of key targets,and the DKD rat model was used to verify the first 4 key targets with high"Hydrogen number"among the top 10 targets verified by molecular docking.RESULTS:Total of 12334 DKD targets were screened in Gene Cards,OMIM and other databases,Hirudin and DKD had 247 common target genes,and the protein interaction network got 2115 edges.The DAVID database was used for the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis,confirming that hirudin in treatment of DKD involves multiple signaling pathways such as the forkhead box O signaling pathway,the phosphatidylinositol 3-kinase-protein kinase B signaling pathway,the vascular endothelial-derived growth factor signaling pathway and other signaling pathways.The top ten key targets of hirudin in treatment of DKD were verified by molecular docking.Animal experiments showed that hirudin could decrease the expression of caspase-3 in renal tissue of DKD rats,and increase the expression of RAC-alpha serine/threonineprotein kinase,Catalase,and Heat shock protein HSP 90-alpha in renal tissue of DKD rats.CONCLUSION:This study preliminarily reveals that hirudin treats DKD through multiple targets and pathways,and molecular docking and animal experiments indicates the feasibility of this study.Hirudin may be directly or indirectly involved in the regulation of cell metabolism,oxidative stress and other mechanisms in the treatment of DKD,which will lay the foundation for future molecular biological experiments of hirudin in the treatment of DKD.

关键词： hirudins diabetic kidney disease network pharmacology molecular docking simulation

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Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway

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中国结合医学杂志:英文版 2023年第10期29卷 875-884页

作者： WANG Ruo-lin LIU Shu-hua SHEN Si-heng JIAN Lu-yong YUAN Qi GUO Hua-hui HUANG Jia-sheng CHEN Peng-hui HUANG Ren-fa nephropathy department Shenzhen Hospital(Futian)of Guangzhou University of Chinese MedicineShenzhenGuangdong Province518034China The Third Clinical Medical School Guangzhou University of Chinese MedicineGuangzhou510006China

Objective: To investigate protective effect of Cordyceps sinensis(CS) through autophagyassociated adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway in acute kidney injury(AKI)-induced acute lung injury(ALI). Methods: Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline(NS)-treated sham group(sham group), NS-treated ischemia reperfusion injury(IRI) group(IRI group), and low-(5 g/kg·d) and high-dose(10 g/kg·d) CS-treated IRI groups(CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry(W/D) ratio of lung, levels of serum creatinine(Scr), blood urea nitrogen(BUN), inflammatory cytokines such as interleukin-βand tumor necrosis factor-α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde(MDA) and myeloperoxidase(MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 Ⅱ/light chain 3 Ⅰ(LC3-Ⅱ/LC3-Ⅰ), uncoordinated-51-like kinase 1(ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively. Results: The renal IRI induced pulmonary injury following AKI,resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO(P<0.01);all of these were reduced in the CS groups(P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower(P<0.05 or P<0.01), while those of LC3-Ⅱ/LC3-Ⅰ, ULK1, and AMPK were significantly higher in the CS2 group(P<0.05 or P<0.01). Conclusion:CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.

关键词： autophagy ischemic reperfusion injury acute kidney injury acute lung injury Cordyceps sinensis Chinese medicine

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