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ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 341-353页

作者： Zhibin YAN Ying SHI Runling YANG Jijun XUE caiyun fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhou310018China State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou University Lanzhou 730000China Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical Sciences2019RU066Lanzhou UniversityLanzhou 730000China

Kidney fibrosis is an inevitable result of various chronic kidney diseases(CKDs)and significantly contributes to end-stage renal failure.Currently,there is no specific treatment available for renal fibrosis.ELA13(amino acid sequence:RRCMPLHSRVPFP)is a conserved region of ELABELA in all vertebrates;however,its biological activity has been very little studied.In the present study,we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1(TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion(UUO)mice.Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum,and reduce the expression of fibrosis biomarkers confirmed by Masson staining,immunohistochemistry,real-time polymerase chain reaction(RT-PCR),and western blot.Inflammation biomarkers were increased after UUO and decreased by administration of ELA13.furthermore,we found that the levels of essential molecules in the mothers against decapentaplegic(Smad)and extracellular signal-regulated kinase(ERK)pathways were reduced by ELA13 treatment in vivo and in vitro.In conclusion,ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

关键词： ELA13 Kidney fibrosis Inflammation Smad Extracllular signal-regulated kinase(ERK)

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Advances in the research and application of neurokinin-1 receptor antagonists

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 91-105页

作者： Xiangyu HONG Junjie MA Shanshan ZHENG Guangyu ZHAO caiyun fu College of Life Sciences and Medicine Zhejiang Sci-Tech UniversityHangzhou310018China

Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis.These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers,as well as the underlying mechanisms.furthermore,the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized,such as solid dispersion systems,nanonization,and nanoencapsulation.As a radiopharmaceutical therapeutic,the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors.However,combining NK-1R antagonists with other drugs can produce a synergistic effect,thereby enhancing the therapeutic effect,alleviating the symptoms,and improving patients’quality of life in several diseases and cancers.

关键词： Neurokinin-1 receptor(NK-1R)antagonist Pathophysiological disorder Tumor target Bioavailability Nanoencapsulation Synergistic therapy

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Age-induced changes in lung microenvironment: from melanoma dormancy to outgrowth

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Signal Transduction and Targeted Therapy 2023年第2期8卷 333-334页

作者： Juan Jin Li Li caiyun fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech University310018HangzhouChina

In a recent study published in Nature,Mitchell E.Fane et al.revealed the critical role of the aged microenvironment in the reactivation of melanoma cells from dormancy.1 The authors found that age-induced lung fibroblast secretory changes promoted growth activation of dormant melanoma cells in the lung,and age-induced skin microenvironment changes suppressed melanoma growth but promoted melanoma cell dissemination(Fig.1).

关键词： melanoma lung microenvironment

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Therapeutic potential for targeting Annexin A1 in fibrotic diseases

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Genes & Diseases 2022年第6期9卷 1493-1505页

作者： Zhibin Yan Xurui Cheng Tao Wang Xiangyu Hong Gang Shao caiyun fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhouZhejiang 310018PR China Department of Oncology No.903 Hospital of PLA Joint Logistic Support ForceXi Hu Affiliated Hospital of Hangzhou Medical CollegeHangzhouZhejiang 310013PR China

Annexin A1,a well-known endogenous anti-inflammatory mediator,plays a critical role in a variety of pathological processes.Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases.Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis.However,the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive,and even the functions of Annexin A1 in fibrotic diseases are still paradoxical.This review focuses on the roles of Annexin A1 in the development of fibrosis of lung,liver,heart,and other tissues,with emphasis on the therapy potential of Annexin A1 in fibrosis,and presents future research interests and directions in fibrotic diseases.

关键词： Annexin A1 Anti-inflammatory Fibrosis Fibrotic diseases Sequence alignment

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Therapeutic peptides: current applications and future directions

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Signal Transduction and Targeted Therapy 2022年第3期7卷 686-712页

作者： Lei Wang Nanxi Wang Wenping Zhang Xurui Cheng Zhibin Yan Gang Shao Xi Wang Rui Wang caiyun fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech University310018 HangzhouChina State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210046China Department of Oncology No.903 Hospital of PLA Joint Logistic Support ForceXi Hu Affiliated Hospital of Hangzhou Medical CollegeHangzhou 310013China Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical Sciences2019RU066Lanzhou University730000 LanzhouChina Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College100050 BeijingChina

Peptide drug development has made great progress in the last decade thanks to new production,modification,and analytic technologies.Peptides have been produced and modified using both chemical and biological methods,together with novel design and delivery strategies,which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field.

关键词： directions overcome continued

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Gasdermin:a novel therapeutic target for tumour treatment by activating anti-tumour immunity

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1855-1856页

作者： caiyun fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhou 310018China

A very recent study by Zhang et al.published in Nature demonstrates that gasdermin E(GSDME,also known as DFNA5)is a tumour suppressor by activating caspaseindependent pyroptosis to enhance anti-tumour immunity.1 In the meantime,a study by Wang et al.published in Nature also demonstrates the anti-tumour effect caused by gasdermin A3(GSDMA3)to induce pyroptosis requires both cytotoxic T cells and CD4+T helper cells.2 The authors intriguingly showed that pyroptosis-induced inflammation triggers robust anti-tumour immunity,thus gasdermin is a promising novel therapeutic target for tumour treatment(Fig.1).

关键词： immunity tumour al

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The independence of and associations among apoptosis,autophagy, and necrosis

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Signal Transduction and Targeted Therapy 2018年第1期3卷 151-161页

作者： Qi Chen Jian Kang caiyun fu College of Life Sciences Zhejiang Sci-Tech UniversityHangzhou 310018China Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine Hangzhou 310018China Cancer Signalling Laboratory Oncogenic Signalling and Growth Control ProgramPeter MacCallum Cancer Centre305 Grattan streetMelbourneVIC 3000Australia Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute University of California San Francisco555 Mission Bay Blvd.SouthSan FranciscoCA 94158USA Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province Hangzhou 310014China

Cell death is an essential biological process for physiological growth and development.Three classical forms of cell death—apoptosis,autophagy,and necrosis—display distinct morphological features by activating specific signaling pathways.With recent research advances,we have started to appreciate that these cell death processes can cross-talk through interconnecting,even overlapping,signaling pathways,and the final cell fate is the result of the interplay of different cell death programs.This review provides an insight into the independence of and associations among these three types of cell death and explores the significance of cell death under the specific conditions of human diseases,particularly neurodegenerative diseases and cancer.

关键词： diseases independence insight

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Apaf-1/caspase-4 pyroptosome:a mediator of mitochondrial permeability transition-triggered pyroptosis

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1084-1085页

作者： Gang Shao Lingfei Wang Xi Wang caiyun fu Department of Oncology No.903 Hospital of PLA Joint Logistic Support ForceXi Hu Affiliated Hospital of Hangzhou Medical CollegeHangzhouChina Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhouChina

In a recent paper in Cell Metabolism,Xu et al.provide new insights whether and how caspase-4/11 involves in pyroptotic cell death implicated in noninfective diseases.They discovered a novel mechanism of GSDME-dependent pyroptosis,which was induced by mitochondrial permeability transition(MPT)-activated Apaf-1/caspase-4 pyroptosome assembly.1 These findings provide important implications for understanding the pathogenesis of cholestatic liver failure(Fig.1).

关键词： al. caspase death

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红枣多糖的提取工艺优化研究

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保鲜与加工 2024年第6期24卷 48-54页

作者：李彬赵彩云吴斌郑力傅樱花新疆大学生命科学与技术学院新疆生物资源基因工程重点实验室新疆乌鲁木齐830017 新疆农业科学院农产品贮藏加工研究所新疆乌鲁木齐830002

红枣是新疆的主要干果之一,是膳食多糖的重要来源。为优化红枣多糖的提取条件,以新疆红枣为原料,通过单因素试验分析料液比、超声时间、水浴温度及水浴时间对红枣多糖得率的影响,并以多糖得率为响应值,进行响应面优化试验,最终确定红枣... 详细信息

红枣是新疆的主要干果之一,是膳食多糖的重要来源。为优化红枣多糖的提取条件,以新疆红枣为原料,通过单因素试验分析料液比、超声时间、水浴温度及水浴时间对红枣多糖得率的影响,并以多糖得率为响应值,进行响应面优化试验,最终确定红枣多糖最佳提取条件为:料液比1∶30(g/mL),超声时间20 min,水浴温度70℃,水浴时间3 h,该条件下红枣多糖得率为3.12%。研究结果为进一步利用红枣资源、开发健康产品奠定基础。

关键词：红枣多糖提取工艺响应面优化

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Synergistic effects of elevated homocysteine level and abnormal blood lipids on the onset of stroke

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Neural Regeneration Research 2013年第31期8卷 2923-2931页

作者： Lu Hao Liming Chen Xiaoyong Sai Zhefeng Liu Guang Yang Rongzeng Yan Lili Wang caiyun fu Xuan Xu Zhenzhen Cheng Qiang Wu Shuzhang Li Chinese PLA General Hospital Institute of Geriatrics Chinese PLA General Hospital Beijing Key Laboratory of Geriatrics

Hyperhomocysteinemia and abnormal blood lipids are independent risk factors for stroke. However, whether both factors exert a synergistic effect in the onset of stroke remains unclear. The present study is a retrospective analysJs of 2 089 cases of stroke and 2 089 control cases of simple in- tervertebral disk protrusion using a paired multivariate logistic regression method. Adjusting for known confounding variables including the patients＇ age, gender, smoking status, alcohol con- sumption status, patient and family medical history, and clinical biochemical indices, elevated ho- mocysteine level was related to the onset of stroke. Patients with elevated homocysteJne levels and abnormal blood lipids showed a 40.9 % increase in the risk for stroke compared to patients with normal homocysteine levels and blood lipids （odds ratio 1.409; 95% confidence interval 1.127-1.761）. These results indicate that elevated homocysteine and abnormal blood lipids exert synergistic effects in the onset of stroke. Patients with elevated homocysteine levels and abnormal blood lipids are predisposed to stroke.

关键词： neural regeneration stroke cysteine risk factor case-control study abnormal bloodmedication inpatients cardiovascular disease paired analysis grants-supportedneuroregenerationlipidspaper

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