Journal of Proteomics
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2024
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IF 2.8
Yan Cai,Weifu Ren,Siqian Li,Rijing Liao,Qi Bian
Idiopathic membranous nephropathy (IMN) is an antibody-mediated and kidney-specific autoimmune disease, with the antigen phospholipase A2 receptor 1 (PLA2R1) accounting for approximately 70% of IMN cases. Although a variety of new podocyte target antigens and their autoantibodies have been identified, they are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. N-glycans play vital roles in renal system and their pathobiological relevance has become increasingly recognized in many kidney diseases, but not fully explored in IMN. To find possible glyco-signatures for PLA2R1-related IMN diagnosis, we herein established a comprehensive workflow for total serum N-glycome analysis based on our recently developed mass spectrometry (MS)-based N-glycan purification method, named Ultrafast Glycoprotein Immobilization for Glycan extraction (UltraGIG). A total of 191 N-glycans were identified from IMN patients, representing the largest N-glycome dataset in IMN. Compared to healthy controls, up-regulation of sialylation and core-fucosylation as well as down-regulation of galactosylation were observed in PLA2R1-positive IMN patients, and up-regulation of hyper-galactosylation was specific for PLA2R1-negative IMN patients. A six-glycan marker panel consisting of H4N3S1, H4N3F1, H6N4S2, H6H5F1S2, H6N5 and H6N6F1S1, was proposed to aid in the accurate diagnosis of PLA2R1-related IMN, which provided new insights into IMN biomarker study . Significance PLA2R1-related IMN is a kidney-specific autoimmune disease with a high risk of developing end-stage renal disease (ESRD) and even kidney failure. Current biomarkers are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. An in-depth MS analysis of total serum N-glycome of PLA2R1-related IMN patients was conducted for the first time. We generated the largest dataset of serum N-glycome for IMN to date, and proposed a novel six-glycan marker panel that may help the accurate diagnosis of PLA2R1-related IMN.
研究领域:
医学
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肾脏病学
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蛋白质组学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inorganic and Organometallic Polymers and Materials
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2024
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IF 3.9
Zhao Qiong,Duan Jianying
Membranous glomerulonephritis (MN) is clinically marked by significant proteinuria or nephrotic syndrome, and pathologically by a uniform thickening of the glomerular capillary basement membrane due to diffuse subepithelial immune complex deposition without notable cell proliferation. In this study, we synthesized a novel therapeutic agent, compound 1, designed for synergistic use with Eculizumab (Ecu) in MN treatment. To optimize the delivery and therapeutic effect of this combination, we developed an advanced composite drug carrier, mPEG-pHPMA@CP1@1@Ecu, incorporating methoxy polyethylene glycol (mPEG) and poly(2-hydroxypropyl methacrylamide) (pHPMA) with a metal-organic framework known as CP1. Structural and compositional integrity of this carrier was rigorously characterized. Our studies demonstrated that mPEG-pHPMA@CP1@1@Ecu could significantly mitigate hypoxia-induced renal tubular epithelial cell damage, highlighting the synergistic potential of compound 1 and Ecu. This new carrier system shows promising therapeutic potential for MN management.
研究领域:
医学
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药学
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生物材料科学
✓ 已验证
产品关联
DOI
高影响因子
Small
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2024
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IF 13
Man Zhang,Fangying Shi,Yijie Chen,Chenyu Yang,Xiangmin Zhang,Chunhui Deng,Nianrong Sun
Multidimensional metabolic analysis has become a new trend in establishing efficient disease monitoring systems, as the constraints associated with relying solely on a single dimension in refined monitoring are increasingly pronounced. Here, coordination polymers are employed as derivative precursors to create multishell hollow hybrids, developing an integrated metabolic monitoring system. Briefly, metabolic fingerprints are extracted from hundreds of serum samples and urine samples, encompassing not only membranous nephropathy but also related diseases, using high-throughput mass spectrometry. With optimized algorithm and initial feature selection, the established combined panel demonstrates enhanced accuracy in both subtype differentiation (over 98.1%) and prognostic monitoring (over 95.6%), even during double blind test. This surpasses the serum biomarker panel (≈90.7% for subtyping, ≈89.7% for prognosis) and urine biomarker panel (≈94.4% for subtyping, ≈76.5% for prognosis). Moreover, after attempting to further refine the marker panel, the blind test maintains equal sensitivity, specificity, and accuracy, showcasing a comprehensive improvement over the single-fluid approach. This underscores the remarkable effectiveness and superiority of the integrated strategy in discriminating between MN and other groups. This work has the potential to significantly advance diagnostic medicine, leading to the establishment of more effective strategies for patient management.
研究领域:
医学诊断
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代谢组学
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疾病管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Ling Guo,Hanyu Yan,Qinqin Gong,Weili Zheng,Liang Zhong,Tao Gong,Xun Sun,Zhirong Zhang,Yuan Ping,Zilan Zhu,Jian Xu,Yongping Zhang
Membranous nephropathy (MN) is a common immune-mediated glomerular disease that requires the development of safe and highly effective therapies. Celastrol (CLT) has shown promise as a therapeutic molecule candidate, but its clinical use is currently limited due to off-target toxicity. Given that excess levels of reactive oxygen species (ROS) contributing to podocyte damage is a key driver of MN progression to end-stage renal disease, we rationally designed ROS-responsive cationic polymeric nanoparticles (PPS-CPNs) with a well-defined particle size and surface charge by employing poly(propylene sulfide)–polyethylene glycol (PPS–PEG) and poly(propylene sulfide)–polyethylenimine (PPS–PEI) to selectively deliver CLT to the damaged glomerulus for MN therapy. Experimental results show that PPS-CPNs successfully crossed the fenestrated endothelium, accumulated in the glomerular basement membrane (GBM), and were internalized by podocytes where rapid drug release was triggered by the overproduction of ROS, thereby outperforming nonresponsive CLT nanotherapy to alleviate subepithelial immune deposits, podocyte foot process effacement, and GBM expansion in a rat MN model. Moreover, the ROS-responsive CLT nanotherapy was associated with significantly lower toxicity to major organs than free CLT. These results suggest that encapsulating CLT into PPS-CPNs can improve efficacy and reduce toxicity as a promising treatment option for MN.
研究领域:
肾病学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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