Urolithiasis最新文献

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Based on network pharmacology, the mechanism of Dioscin in alleviating renal tubular epithelial cell injury induced by calcium oxalate crystals was explored. 基于网络药理学,探讨薯蓣皂苷减轻草酸钙晶体致肾小管上皮细胞损伤的作用机制。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-12-12 DOI: 10.1007/s00240-024-01673-1
Hu Liang, Yuexian Xu, Shuai Sun, Yang Chen, Wei Wang, Zongyao Hao
{"title":"Based on network pharmacology, the mechanism of Dioscin in alleviating renal tubular epithelial cell injury induced by calcium oxalate crystals was explored.","authors":"Hu Liang, Yuexian Xu, Shuai Sun, Yang Chen, Wei Wang, Zongyao Hao","doi":"10.1007/s00240-024-01673-1","DOIUrl":"10.1007/s00240-024-01673-1","url":null,"abstract":"<p><p>The commencement of kidney stone formation involves a crucial initial phase characterized by injury to renal tubular cells caused by calcium oxalate (CaOx). Dioscin (Dio) has been acknowledged for its potent anti-inflammation and anti-apoptotic properties; nevertheless, the impact and underlying Investigation into the molecular basis underlying the action of Dioscin in mitigating inflammation and apoptotic induced by exposure to calcium oxalate crystals in renal tissues remain unexplored. To comprehend the precise mechanism of Dioscin in the treatment of crystalline nephropathy, we conducted experiments utilizing a murine model of CaOx crystal deposition, induced by intraperitoneal administration of glyoxylate. An in vitro model was constructed using HK-2 cells exposed to calcium oxalate monohydrate (COM). To evaluate the effect of Dioscin on calcium oxalate crystal deposition by ROS assay, Western blotting, immunohistochemistry, Periodic Acid-Schiff staining (PAS) staining, hematoxylin-eosin (H&E) staining. Using network pharmacology and molecular docking methods, we explored the molecular mechanism of Dioscin in the treatment of CaOx-induced renal tubular epithelial cell injury. Subsequently, we conducted experiments to verify our findings. We observed a significant protective effect of Dioscin treatment against kidney oxidative stress and inflammation induced by CaOx. Then we predicted through network pharmacology that Dioscin exerts its anti-apoptotic effect through the NF-kappa B signaling pathway. Then we verified in vitro and in vivo that administration of Dioscin can alleviate the elevation of TLR4 and activation of the NF-kappa B signaling pathway induced by calcium oxalate, as well as attenuate renal apoptosis. Instead, the beneficial impact of this protection of Dioscin was reversed after overexpression of the TLR4. Dioscin has the potential to alleviate the activation of the NF-kappa B signaling pathway through TLR4, thereby exerting anti-inflammatory and anti-apoptotic effects. This study provides new ideas for the prevention and treatment of kidney stones.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"53 1","pages":"3"},"PeriodicalIF":2.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Annexin-derived self-assembling peptide nanostructures for alleviation of calcium oxalate -induced renal injury. 膜联蛋白衍生的自组装肽纳米结构减轻草酸钙诱导的肾损伤。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-12-12 DOI: 10.1007/s00240-024-01678-w
Sarmistha Saha, Abhijit Mishra
{"title":"Annexin-derived self-assembling peptide nanostructures for alleviation of calcium oxalate -induced renal injury.","authors":"Sarmistha Saha, Abhijit Mishra","doi":"10.1007/s00240-024-01678-w","DOIUrl":"https://doi.org/10.1007/s00240-024-01678-w","url":null,"abstract":"<p><p>The formation of polycrystalline aggregates in the glomerulus or other components of the urinary system is indisputably the most critical step in the formation of kidney stones and calcium oxalate monohydrate (CaC<sub>2</sub>O<sub>4</sub>·H<sub>2</sub>O) is the most prevalent form. On the other hand, Annexin A1 (ANXA1), a calcium-binding protein, markedly increased on the apical surface of renal cells in CaC<sub>2</sub>O<sub>4</sub>-induced nephrolithiasis. In this regard, we identified the peptide motif responsible for calcium binding and redesigned it into a self-assembling peptide sequence without disturbing its binding selectivity for the CaC<sub>2</sub>O<sub>4</sub> interface. We developed a salt-dependent strategy to produce self-assembling spherical peptide nanoparticles by using aqueous solutions of R8 peptide and 16-amino acid designed peptide of net charge of -3 (WAEEFLKWLAFIEEFF). Peptide nanoparticles restored cell viability and reduced oxidative stress in MDCK cells triggered by CaC<sub>2</sub>O<sub>4</sub> crystals (80 µg cm<sup>- 2</sup>) via Nrf2-HO-1 pathway activation. Peptide nanoparticles led to significant protection in urinary biochemistry and reducing calcifications without any toxicity.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"53 1","pages":"5"},"PeriodicalIF":2.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A mouse model for the study of diet-induced changes in intestinal microbiome composition on renal calcium oxalate crystal formation. 研究饮食诱导肠道微生物组组成变化对肾脏草酸钙晶体形成的小鼠模型。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-12-12 DOI: 10.1007/s00240-024-01672-2
Sarah Hanstock, Demian Ferreira, Hans Adomat, Felipe Eltit, Qiong Wang, Dalia Othman, Breanna Nelson, Ben Chew, Aaron Miller, Genelle Lunken, Dirk Lange
{"title":"A mouse model for the study of diet-induced changes in intestinal microbiome composition on renal calcium oxalate crystal formation.","authors":"Sarah Hanstock, Demian Ferreira, Hans Adomat, Felipe Eltit, Qiong Wang, Dalia Othman, Breanna Nelson, Ben Chew, Aaron Miller, Genelle Lunken, Dirk Lange","doi":"10.1007/s00240-024-01672-2","DOIUrl":"https://doi.org/10.1007/s00240-024-01672-2","url":null,"abstract":"<p><p>Currently available animal models for calcium oxalate kidney stones are limited in their translational potential. Particularly with increasing interest in gut microbiota involvement in kidney stone disease, there are limited animal models which can be used. As such, we have developed a novel diet-induced hyperoxaluria murine model which addresses some of the shortcomings of other currently available models. Mice C57BL/6 mice were fed a 1.5% sodium oxalate supplemented chow for two weeks and showed no morbidity or mortality. Mice fed the sodium oxalate diet consistently had renal calcium oxalate crystal deposits as confirmed by polarized light microscopy, and energy-dispersive X-ray spectroscopy. We developed a isotope dilution high-performance liquid chromatography/mass spectrometry protocol which confirmed that our model produced both urinary and enteric hyperoxaluria. 16 S ribosomal RNA sequencing of stool samples and cecal contents showed that sodium oxalate is a disruptor of the gut microbiome, and may interfere with commensal microbes in the gut microbiome. With consistent results this mouse model is superior to other models of kidney stone disease, as this model can be applied to investigate topics of oxalate absorption, transport, metabolism, excretion, crystal formation, the gut microbiome and testing of various therapeutic agents for translation to early stages of renal crystal formation in kidney stone disease.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"53 1","pages":"4"},"PeriodicalIF":2.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A systematic scoping review of Jackstone Calculi: clinical presentation and management. Jackstone结石的临床表现和治疗。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-11-30 DOI: 10.1007/s00240-024-01670-4
Baian Wei, Yiwen Pan, Shu Gan
{"title":"A systematic scoping review of Jackstone Calculi: clinical presentation and management.","authors":"Baian Wei, Yiwen Pan, Shu Gan","doi":"10.1007/s00240-024-01670-4","DOIUrl":"10.1007/s00240-024-01670-4","url":null,"abstract":"<p><p>Jackstone calculi are a rare and distinctive type of urinary stone characterized by their radiating spicule structure. They are primarily found in the bladder, and also occur in the renal pelvis. Because jackstone calculi are infrequently encountered in clinical practice, studies on their pathophysiology and clinical implications are relatively limited. This systematic scoping review aims to consolidate existing knowledge, find the deficiencies of current research, and provide a reference for further research. A comprehensive search was conducted using PubMed and Embase databases with the terms \"Jackstone\" and \"jack stone[Title/Abstract]\". The search strategy employed was: (jack stone[Title/Abstract]) OR (Jackstone) NOT (dog). And a dual-review process was used to screen titles and abstracts, resulting in 15 articles meeting the inclusion criteria for this review. The selected studies provided insights into the pathophysiology, clinical presentation, diagnostic imaging, and management of jackstone calculi. These stones typically exhibit a protein-rich, X-ray lucent core surrounded by concentric layers of calcium oxalate monohydrate.Common clinical symptoms include pain, hematuria, and urinary obstruction. Diagnostic imaging, particularly CT scans, is crucial for identifying these stones. The treatment of jackstone should pay attention to that it may be a Secondary outcome.Jackstone calculi, while rare, present unique diagnostic and therapeutic challenges due to their distinct structure and formation mechanisms. This review consolidates current knowledge and underscores the need for further research to better understand their pathophysiology and optimize management strategies. Identifying and addressing these gaps will enhance clinical outcomes and patient care.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"53 1","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic insights into kidney stone formation: a Mendelian randomization study of protein quantitative trait loci. 肾结石形成的遗传洞察:蛋白质数量性状位点的孟德尔随机化研究。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-11-30 DOI: 10.1007/s00240-024-01667-z
Haoxiang Huang, Bohong Chen, Cong Feng, Wei Chen, Dapeng Wu
{"title":"Genetic insights into kidney stone formation: a Mendelian randomization study of protein quantitative trait loci.","authors":"Haoxiang Huang, Bohong Chen, Cong Feng, Wei Chen, Dapeng Wu","doi":"10.1007/s00240-024-01667-z","DOIUrl":"https://doi.org/10.1007/s00240-024-01667-z","url":null,"abstract":"<p><p>Kidney stones are a common urological condition caused by a complex interaction of genetic, metabolic, and environmental factors. Recent genomic research has shed light on the genetic basis of kidney stone susceptibility.This study aims to identify protein quantitative trait loci (pQTL) associated with kidney stone formation and explore their causal relationships using Mendelian randomization.We conducted two-sample Mendelian Randomization (MR) analyses utilizing Genome-Wide Association Study (GWAS) summary data to assess the causal impact of pQTL on kidney stone formation. Data sources included the UK Biobank dataset \"ukb-b-8297\" and an external validation dataset \"ukb-b-13537\". We employed inverse variance weighting (IVW) as the primary MR method, supplemented by sensitivity analyses such as MR-PRESSO, Leave-One-Out, and Cochran Q tests to validate the robustness of our findings.Our analyses identified significant associations between several pQTL and kidney stones. Key proteins such as CD27, CXCL9, and TNFRSF1A exhibited significant centrality in the protein-protein interaction (PPI) network, suggesting their critical roles in kidney stone pathogenesis. The KEGG pathway enrichment analysis revealed significant pathways, including cytokine-cytokine receptor interaction and osteoclast differentiation, highlighting the involvement of immune response and inflammatory processes in kidney stone formation.This study underscores the significance of pQTL in kidney stone research, identifying key proteins and pathways that may serve as biomarkers or therapeutic targets. The findings provide insights into the genetic and molecular mechanisms underlying kidney stone formation, offering potential avenues for future research and therapeutic interventions.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"53 1","pages":"2"},"PeriodicalIF":2.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
UrologiQ: AI-based accurate detection, measurement and reporting of stones in CT-KUB scans. UrologiQ:基于人工智能的 CT-KUB 扫描中结石的精确检测、测量和报告。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-11-28 DOI: 10.1007/s00240-024-01671-3
Abhijith Yenikekaluva, Syed Furqan Azeez, Apeksha Sakegaonkar, Aamir Mohammed Shariff, Mehul Wankhede, Shivam Gaikwad, Viharika Pavuluri, S H Anand, Jithunath Madathiparambil Ramanathan
{"title":"UrologiQ: AI-based accurate detection, measurement and reporting of stones in CT-KUB scans.","authors":"Abhijith Yenikekaluva, Syed Furqan Azeez, Apeksha Sakegaonkar, Aamir Mohammed Shariff, Mehul Wankhede, Shivam Gaikwad, Viharika Pavuluri, S H Anand, Jithunath Madathiparambil Ramanathan","doi":"10.1007/s00240-024-01671-3","DOIUrl":"10.1007/s00240-024-01671-3","url":null,"abstract":"<p><p>Kidney stone disease is becoming increasingly common worldwide, with its prevalence increasing annually across all age groups, races, and geographic regions. This sharp increase may be due to significant changes in dietary habits. Early and accurate detection of kidney stones is crucial for timely intervention and prevention of complications. This article discusses the role of artificial intelligence (AI) in detecting kidney stones and managing surgical treatments. Recent advances in AI techniques have introduced new tools that improve the diagnosis and analysis of medical images. AI can use CT-KUB image data to accurately detect the location of kidney stones and measure their size more efficiently than manual methods. AI-based detection methods ensure greater precision and consistency in stone identification and measurement. These improvements can help doctors plan treatments more effectively, resulting in a higher success rate for patients. Integrating AI into kidney stone detection and analysis significantly improves treatment planning and patient management, leading to better patient outcomes and overall quality of healthcare.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"52 1","pages":"170"},"PeriodicalIF":2.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Changes in blood gas in supine and prone positions in percutaneous stone surgery: does position have any advantage for hemodynamics? 更正:经皮结石手术中仰卧位和俯卧位的血气变化:体位对血液动力学有好处吗?
IF 2 2区 医学
Urolithiasis Pub Date : 2024-11-28 DOI: 10.1007/s00240-024-01660-6
Erdal Yilmaz, Ibrahim Senocak, Mirac Ataman, Ercan Yuvanc
{"title":"Correction: Changes in blood gas in supine and prone positions in percutaneous stone surgery: does position have any advantage for hemodynamics?","authors":"Erdal Yilmaz, Ibrahim Senocak, Mirac Ataman, Ercan Yuvanc","doi":"10.1007/s00240-024-01660-6","DOIUrl":"10.1007/s00240-024-01660-6","url":null,"abstract":"","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"52 1","pages":"171"},"PeriodicalIF":2.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the molecular interactions between nephrolithiasis and carotid atherosclerosis: asporin as a potential biomarker. 探索肾结石与颈动脉粥样硬化之间的分子相互作用:作为潜在生物标志物的porin。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-11-26 DOI: 10.1007/s00240-024-01665-1
Yibo Hua, Zijian Zhou, Suyu Miao, Zijie Wang, Rijin Song, Xianghu Meng
{"title":"Exploring the molecular interactions between nephrolithiasis and carotid atherosclerosis: asporin as a potential biomarker.","authors":"Yibo Hua, Zijian Zhou, Suyu Miao, Zijie Wang, Rijin Song, Xianghu Meng","doi":"10.1007/s00240-024-01665-1","DOIUrl":"10.1007/s00240-024-01665-1","url":null,"abstract":"<p><p>Increasing evidence suggested nephrolithiasis has a close linkage with carotid atherosclerosis (CAS), with Randall's plaque (RP) being a precursor to kidney stones. Our study aimed to examine the crosstalk genes and potential molecular mechanisms between RP and CAS. We obtained microarray data for RP and CAS from the Gene Expression Omnibus (GEO) and used weighted gene co-expression network analysis (WGCNA) and differential gene expression (DEG) analysis to identify shared genes. By integrating WGCNA and DEG analysis, Asporin (ASPN) was identified as the key gene connecting RP and CAS, with its diagnostic potential assessed via a receiver operating characteristic (ROC) curve. Immune infiltration studies showed a significant correlation between ASPN and various immune cells in RP and CAS. ASPN was found to be less expressed in RP and CAS tissues compared to normal tissues, as confirmed by immunohistochemistry (IHC) and quantitative reverse-transcription PCR (qRT-PCR). The rat model confirmed the human tissue findings. ASPN can elucidate the shared pathogenic mechanisms underlying the two conditions, including immune response and osteoblast differentiation.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"52 1","pages":"169"},"PeriodicalIF":2.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The potential role of Sodium/Glucose Cotransporter 2 inhibitors in the treatment of cystinuria. 钠/葡萄糖共转运体 2 抑制剂在治疗胱氨酸尿症中的潜在作用。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-11-26 DOI: 10.1007/s00240-024-01666-0
Wilson Sui, Heiko Yang, Manoj Desai, Thomas Chi, Marshall Stoller
{"title":"The potential role of Sodium/Glucose Cotransporter 2 inhibitors in the treatment of cystinuria.","authors":"Wilson Sui, Heiko Yang, Manoj Desai, Thomas Chi, Marshall Stoller","doi":"10.1007/s00240-024-01666-0","DOIUrl":"10.1007/s00240-024-01666-0","url":null,"abstract":"<p><p>The Maillard reaction is a non-enzymatic reaction between an amino acid and carbohydrate. We hypothesized that continuous washing of cystine stones with glucose could theoretically prevent growth of an existing cystine stone or even reduce its size leading to a decrease in stone events. Sodium/Glucose Cotransporter 2 (SGLT2) inhibitors, well known for inducing glucosuria, were used to test this hypothesis in an initial series of patients. Patients with cystinuria from September 2019 to May 2023 who received off-label dapaglifozin (Farxiga™) were identified. Patients were allowed to continue thiol and alkalinizing agents per standard of care. A symptomatic stone event was defined by stone passage or surgical intervention. Ten cystinuric patients were prescribed SGLT2 inhibitors with a median follow up of 13.5 months. Each patients' historic stone event rate was compared to the event rate while prescribed SGLT2 medication. Overall, 70% of patients experienced fewer stone events and half had stable stone volume during therapy. Eight patients had negative cystine capacity at baseline, yet seven experienced fewer stone events while on medication: four experienced no stone growth. One patient was taken off the SGLT2 inhibitor due to an adverse reaction; three others experienced mild, self-resolving effects and yet stayed on the medication. Cystinuric patients treated with a SGLT2 inhibitor experienced fewer stone events while on medication compared to their historic rates and exhibited decreased or stable stone growth. There were few medication related side effects. SGLT2 inhibitors may be a promising long-term therapy for patients with cystinuria.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"52 1","pages":"168"},"PeriodicalIF":2.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identifying therapeutic targets for kidney stone disease through proteome-wide Mendelian randomization and colocalization analysis. 通过全蛋白质组孟德尔随机化和共定位分析确定肾结石病的治疗靶点。
IF 2 2区 医学
Urolithiasis Pub Date : 2024-11-25 DOI: 10.1007/s00240-024-01669-x
Zilong Liang, Conglei Hu, Haofeng Pang, Yi Sha, Liping Yao, Fei Liu
{"title":"Identifying therapeutic targets for kidney stone disease through proteome-wide Mendelian randomization and colocalization analysis.","authors":"Zilong Liang, Conglei Hu, Haofeng Pang, Yi Sha, Liping Yao, Fei Liu","doi":"10.1007/s00240-024-01669-x","DOIUrl":"10.1007/s00240-024-01669-x","url":null,"abstract":"<p><p>Kidney stone disease (KSD) is facing rising global prevalence and recurrence rates. Mendelian randomization aids in drug repurposing and the discovery of therapeutic targets. This study utilized Mendelian randomization (MR) to identify protein targets for KSD treatment and assess potential adverse drug reactions. A proteome-wide MR study assessed plasma proteins' causal relationship with KSD risk. Data from UK Biobank Proteomics Profiling Project (2940 proteins) and FinnGen R10 for KSD (10,556 cases, 400,681 controls) were analyzed. Colocalization analysis identified shared causal variants. Additionally, a Phenome-wide association study (PheWAS) used the FinnGen to explore adverse reactions of druggable proteins. MR study found ITIH4, F12, FKBPL positively correlated with KSD risk, while DAG1, ITIH1, LTB, CACYBP negatively correlated (Pfdr < 0.05). Colocalization analysis and PheWAS identified CACYBP as the most promising druggable protein for the prevention or treatment of nephrolithiasis recurrence. This study identified genetic protein biomarkers for KSD risk and explored potential drug side effects, offering new insights and targets for prevention and treatment.</p>","PeriodicalId":23411,"journal":{"name":"Urolithiasis","volume":"52 1","pages":"167"},"PeriodicalIF":2.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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