Pub Date : 2024-12-01Epub Date: 2024-07-25DOI: 10.1080/0886022X.2024.2319330
Asmaa Adel, Manal Abdul-Hamid, Samraa H Abdel-Kawi, Mohamed A Abdelaziz, Hader I Sakr, Osama M Ahmed
Aim: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl4) in Wistar rats.
Methods: Following an intraperitoneal injection of CCl4 (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 106 cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.
Results: In CCl4-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl4-injected rats considerably reduced the previously noted abnormalities.
Conclusions: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl4 injections.
目的:本研究探讨了大鼠和小鼠骨髓间充质干细胞(BM-MSCs)对四氯化碳(CCl4)导致的Wistar大鼠肾损伤和毒性的可能治疗作用:雄性 Wistar 大鼠腹腔注射四氯化碳(0.5 mL/kg b.w.,每周两次)八周后,每周静脉注射大鼠和小鼠间充质干细胞(1 × 106 cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week)四周。使用苏木精和伊红(H&E)、马森三色染色(MT)技术和电子显微镜分析对肾功能进行评估,并对肾脏样本进行检查。肾脏环氧化酶-2(COX-2)、蛋白 53(p53)和肿瘤坏死因子-α(TNF-α)通过免疫组化染色技术进行检测。此外,还鉴定了肾组织中氧化应激和抗氧化防御系统的生物指标:结果:注射了 CCl4 的大鼠血清肌酐、尿素和尿酸水平显著升高,肾脏脂质过氧化物(LPO)也显著升高,而肾脏中的超氧化物歧化酶、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽(GSH)转移酶和 GSH 水平显著下降。从组织学角度看,肾脏显示出多种结构异常,如肾小球萎缩、肾小管扩张、炎性白细胞浸润、成纤维细胞增殖和胶原蛋白含量升高。COX-2 和 TNF-α 等炎性细胞因子以及促凋亡介质 p53 均显著上调。用注射了四氯化碳的小鼠和大鼠的骨髓间充质干细胞处理大鼠,大大减少了之前提到的异常情况:结论:通过增强抗氧化防御、减少细胞凋亡和炎症,小鼠和大鼠的骨髓间充质干细胞能够增强注射了四氯化碳的大鼠的肾功能和组织学完整性。
{"title":"Bone marrow-derived mesenchymal stem cells reduce CCl<sub>4</sub>-induced kidney injury and fibrosis in male Wistar rats.","authors":"Asmaa Adel, Manal Abdul-Hamid, Samraa H Abdel-Kawi, Mohamed A Abdelaziz, Hader I Sakr, Osama M Ahmed","doi":"10.1080/0886022X.2024.2319330","DOIUrl":"10.1080/0886022X.2024.2319330","url":null,"abstract":"<p><strong>Aim: </strong>This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl<sub>4</sub>) in Wistar rats.</p><p><strong>Methods: </strong>Following an intraperitoneal injection of CCl<sub>4</sub> (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 10<sup>6</sup> cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.</p><p><strong>Results: </strong>In CCl<sub>4</sub>-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl<sub>4</sub>-injected rats considerably reduced the previously noted abnormalities.</p><p><strong>Conclusions: </strong>By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl<sub>4</sub> injections.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored.
Aims: To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3.
Methods: Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated β-galactosidase (SA-β-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification.
Results: The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process.
Conclusions: Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.
{"title":"LPS-induced senescence of macrophages aggravates calcification and senescence of vascular smooth muscle cells via IFITM3.","authors":"Ya-Ping Fang, Xin Yang, Ying Zhang, Xiao-Dong Zhu, Xiao-Xu Wang, Yan Liu, Wen Shi, Jia-Yi Huang, Yu Zhao, Xiao-Liang Zhang","doi":"10.1080/0886022X.2024.2367708","DOIUrl":"10.1080/0886022X.2024.2367708","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored.</p><p><strong>Aims: </strong>To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3.</p><p><strong>Methods: </strong>Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated β-galactosidase (SA-β-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification.</p><p><strong>Results: </strong>The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process.</p><p><strong>Conclusions: </strong>Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs <i>via</i> IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN.
Methods: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed.
Results: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value.
Conclusion: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.
{"title":"The correlation between anti-phospholipase A2 receptor antibodies and hypercoagulability in patients with idiopathic membranous nephropathy.","authors":"Yunyun Liu, Yujie Tang, Wei-Bo Le, Dacheng Chen, Dandan Liang, Feng Xu, Shaoshan Liang, Yongzhong Zhong, Caihong Zeng","doi":"10.1080/0886022X.2024.2374448","DOIUrl":"10.1080/0886022X.2024.2374448","url":null,"abstract":"<p><strong>Background: </strong>Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN.</p><p><strong>Methods: </strong>A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed.</p><p><strong>Results: </strong>Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value.</p><p><strong>Conclusion: </strong>Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-07-05DOI: 10.1080/0886022X.2024.2374013
Jian-Hua Dong, Minghong Zhang, Xi Yang, Bian Wu, Li Huang, Chuan Li, Yongchun Ge
Objective: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning.
Methods: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed.
Results: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1β were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal.
Conclusion: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.
{"title":"Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute bipyridine herbicide poisoning.","authors":"Jian-Hua Dong, Minghong Zhang, Xi Yang, Bian Wu, Li Huang, Chuan Li, Yongchun Ge","doi":"10.1080/0886022X.2024.2374013","DOIUrl":"10.1080/0886022X.2024.2374013","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning.</p><p><strong>Methods: </strong>A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed.</p><p><strong>Results: </strong>Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1β were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal.</p><p><strong>Conclusion: </strong>Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China.
Methods and results: A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively.
Conclusions: The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.
{"title":"Changes in the spectrum of biopsy-proven renal diseases over 11 years: a single-center study in China.","authors":"Yujia Wang, Liyin Zhang, Li Yuan, Qionghong Xie, Shaojun Liu, Chuan-Ming Hao","doi":"10.1080/0886022X.2024.2381614","DOIUrl":"10.1080/0886022X.2024.2381614","url":null,"abstract":"<p><strong>Background: </strong>There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China.</p><p><strong>Methods and results: </strong>A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively.</p><p><strong>Conclusions: </strong>The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-07-21DOI: 10.1080/0886022X.2024.2379008
Mohammad Alhilal, Huseyin Serkan Erol, Serkan Yildirim, Ahmet Cakir, Murat Koc, Suzan Alhilal, Esra Dereli, Omer Alkanoglu, Volkan Ay, Ismail Can, Mesut Bunyami Halici
Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.
尽管人们一直在努力寻找治疗败血症相关性急性肾损伤(SA-AKI)的有效药物,但 SA-AKI 患者的死亡率并没有降低。我们的研究通过靶向炎症、氧化应激和细胞凋亡,评估了异黄酮欧沙金(OSJ)对大鼠 SA-AKI 的保护作用。通过盲肠结扎和穿刺(CLP)技术诱导大鼠发生多微生物败血症。用生化方法评估了肾组织中氧化应激的标志物。使用免疫组化和免疫荧光检测方法评估了白细胞介素-33(IL-33)、8-羟基脱氧鸟苷(8-OHdG)、Caspase-3 和肾损伤分子-1(KIM-1)的表达,分别作为肾组织中炎症、DNA 损伤、细胞凋亡和 SA-AKI 的指标。通过对 OSJ 与小鼠 IL-33(PDB 代码:5VI4)结合模式的分子对接研究,CLP 技术显著(p p p p)。因此,OSJ可通过抑制IL-33/LPO/8-OHdG/caspase-3途径和改善抗氧化系统来防止SA-AKI。
{"title":"Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats.","authors":"Mohammad Alhilal, Huseyin Serkan Erol, Serkan Yildirim, Ahmet Cakir, Murat Koc, Suzan Alhilal, Esra Dereli, Omer Alkanoglu, Volkan Ay, Ismail Can, Mesut Bunyami Halici","doi":"10.1080/0886022X.2024.2379008","DOIUrl":"10.1080/0886022X.2024.2379008","url":null,"abstract":"<p><p>Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats <i>via</i> the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (<i>p</i> < 0.001) increased lipid peroxidation (LPO) levels and significantly (<i>p</i> < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (<i>p</i> < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found <i>via</i> a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-07DOI: 10.1080/0886022X.2024.2386154
Yayun He, Xia Wu, Yunhai Tang
Background: This cohort study aimed to explore the relationship between hydration status and the risk of diabetic kidney disease (DKD) as well as all-cause death in DKD patients.
Methods: Weighted univariable and multivariable logistic regression models were used to explore the association between hydration status and DKD risk in diabetic population while weighted univariable and multivariable Cox regression models were used to identify the association between hydration status and all-cause mortality in DKD patients. Kaplan-Meier curve was plotted to present the survival probability of patients with different hydration status. Estimates were presented as odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI).
Results: The mean follow-up time was 79.74 (±1.89) months. There were 2041 participants with DKD, and 2889 participants without. At the end of the follow-up, 965 participants were alive. The risk of DKD was increased as the increase of osmolarity level (OR = 1.07, 95%CI: 1.05-1.08). The elevated risk of DKD was observed in patients with impending dehydration (OR = 1.49, 95%CI: 1.19-1.85) or current dehydration (OR = 2.69, 95%CI: 2.09-3.46). The association between increased osmolarty level and elevated risk of all-cause mortality in DKD patients was statistically different (HR = 1.02, 95%CI: 1.01-1.03). Current dehydration was correlated with increased all-cause mortality risk in DKD patients (HR = 1.27, 95%CI: 1.01-1.61). Compared to DKD patients with normal hydration, the survival probability of DKD patients with current dehydration was significant lower (p < 0.001).
Conclusion: Increased osmolarity level was associated with increased risk of DKD and elevated risk of all-cause mortality in DKD patients.
{"title":"Association between hydration status and the risk and all-cause mortality of diabetic kidney disease.","authors":"Yayun He, Xia Wu, Yunhai Tang","doi":"10.1080/0886022X.2024.2386154","DOIUrl":"10.1080/0886022X.2024.2386154","url":null,"abstract":"<p><strong>Background: </strong>This cohort study aimed to explore the relationship between hydration status and the risk of diabetic kidney disease (DKD) as well as all-cause death in DKD patients.</p><p><strong>Methods: </strong>Weighted univariable and multivariable logistic regression models were used to explore the association between hydration status and DKD risk in diabetic population while weighted univariable and multivariable Cox regression models were used to identify the association between hydration status and all-cause mortality in DKD patients. Kaplan-Meier curve was plotted to present the survival probability of patients with different hydration status. Estimates were presented as odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI).</p><p><strong>Results: </strong>The mean follow-up time was 79.74 (±1.89) months. There were 2041 participants with DKD, and 2889 participants without. At the end of the follow-up, 965 participants were alive. The risk of DKD was increased as the increase of osmolarity level (OR = 1.07, 95%CI: 1.05-1.08). The elevated risk of DKD was observed in patients with impending dehydration (OR = 1.49, 95%CI: 1.19-1.85) or current dehydration (OR = 2.69, 95%CI: 2.09-3.46). The association between increased osmolarty level and elevated risk of all-cause mortality in DKD patients was statistically different (HR = 1.02, 95%CI: 1.01-1.03). Current dehydration was correlated with increased all-cause mortality risk in DKD patients (HR = 1.27, 95%CI: 1.01-1.61). Compared to DKD patients with normal hydration, the survival probability of DKD patients with current dehydration was significant lower (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Increased osmolarity level was associated with increased risk of DKD and elevated risk of all-cause mortality in DKD patients.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This systematic review aimed to statistically profile the medication burden and associated influencing factors, and outcomes in patients with dialysis-dependent chronic kidney disease (DD-CKD). Studies of medication burden in patients with DD-CKD in the last 10 years from 1 January 2013 to 31 March 2024 were searched from PubMed, Embase, and Cochrane databases. Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) methodology checklist was used to evaluate quality and bias. Data extraction and combining from multiple groups of number (n), mean, and standard deviation (SD) were performed using R programming language (version4.3.1; R Core Team, Vienna, Austria). A total of 10 studies were included, and the results showed a higher drug burden in patients with DD-CKD. The combined pill burden was 14.57 ± 7.56 per day in hemodialysis (HD) patients and 14.63 ± 6.32 in peritoneal dialysis (PD) patients. The combined number of medications was 9.74 ± 3.37 in HD and 8 ± 3 in PD. Four studies described the various drug classes and their proportions, in general, antihypertensives and phosphate binders were the most commonly used drugs. Five studies mentioned factors associated with medication burden. A total of five studies mentioned medication burden-related outcomes, with one study finding that medication-related burden was associated with increased treatment burden, three studies finding that poor medication adherence was associated with medication burden, and another study finding that medication complexity was not associated with self-reported medication adherence. Limitations: meta-analysis was not possible due to the heterogeneity of studies.
{"title":"Medication burden in patients with dialysis-dependent CKD: a systematic review.","authors":"Xuemei Liu, Ping Chen, Yun Liu, Xiaoyan Jia, Dongmei Xu","doi":"10.1080/0886022X.2024.2353341","DOIUrl":"10.1080/0886022X.2024.2353341","url":null,"abstract":"<p><p>This systematic review aimed to statistically profile the medication burden and associated influencing factors, and outcomes in patients with dialysis-dependent chronic kidney disease (DD-CKD). Studies of medication burden in patients with DD-CKD in the last 10 years from 1 January 2013 to 31 March 2024 were searched from PubMed, Embase, and Cochrane databases. Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) methodology checklist was used to evaluate quality and bias. Data extraction and combining from multiple groups of number (<i>n</i>), mean, and standard deviation (SD) were performed using R programming language (version4.3.1; R Core Team, Vienna, Austria). A total of 10 studies were included, and the results showed a higher drug burden in patients with DD-CKD. The combined pill burden was 14.57 ± 7.56 per day in hemodialysis (HD) patients and 14.63 ± 6.32 in peritoneal dialysis (PD) patients. The combined number of medications was 9.74 ± 3.37 in HD and 8 ± 3 in PD. Four studies described the various drug classes and their proportions, in general, antihypertensives and phosphate binders were the most commonly used drugs. Five studies mentioned factors associated with medication burden. A total of five studies mentioned medication burden-related outcomes, with one study finding that medication-related burden was associated with increased treatment burden, three studies finding that poor medication adherence was associated with medication burden, and another study finding that medication complexity was not associated with self-reported medication adherence. Limitations: meta-analysis was not possible due to the heterogeneity of studies.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-05-27DOI: 10.1080/0886022X.2024.2356022
Yanmei Li, Xiaonan Feng, Na Chen, Shuhua Song, Min Yu, Yan Wang, Hongxia Zhang, Li Wang, Menghua Chen, Na Tian
Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.
{"title":"Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients.","authors":"Yanmei Li, Xiaonan Feng, Na Chen, Shuhua Song, Min Yu, Yan Wang, Hongxia Zhang, Li Wang, Menghua Chen, Na Tian","doi":"10.1080/0886022X.2024.2356022","DOIUrl":"10.1080/0886022X.2024.2356022","url":null,"abstract":"<p><p>Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, <i>p</i> < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, <i>p</i> = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, <i>p =</i> .010), and lower (each 1-absolute unit decrease) <i>Kt</i>/<i>V</i> values (95% CI 0.859-0.984, <i>p =</i> .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, <i>n</i> = 35; non-sSHPT group, <i>n</i> = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; <i>p</i> < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabry disease, a lysosomal storage disease, is an uncommon X-linked recessive genetic disorder stemming from abnormalities in the alpha-galactosidase gene (GLA) that codes human alpha-Galactosidase A (α-Gal A). To date, over 800 GLA mutations have been found to cause Fabry disease (FD). Continued enhancement of the GLA mutation spectrum will contribute to a deeper recognition and underlying mechanisms of FD. In this study, a 27-year-old male proband exhibited a typical phenotype of Fabry disease. Subsequently, family screening for Fabry disease was conducted, and high-throughput sequencing was employed to identify the mutated gene. The three-level structure of the mutated protein was analyzed, and its subcellular localization and enzymatic activity were determined. Apoptosis was assessed in GLA mutant cell lines to confirm the functional effects. As a result, a new mutation, c.777_778del (p. Gly261Leufs*3), in the GLA gene was identified. The mutation caused a frameshift during translation and the premature appearance of a termination codon, which led to a partial deletion of the domain in C-terminal region and altered the protein's tertiary structure. In vitro experiments revealed a significant reduction of the enzymatic activity in mutant cells. The expression was noticeably decreased at the mRNA and protein levels in mutant cell lines. Additionally, the subcellular localization of α-Gal A changed from a homogeneous distribution to punctate aggregation in the cytoplasm. GLA mutant cells exhibited significantly higher levels of apoptosis compared to wild-type cells.
法布里病是一种溶酶体贮积病,是一种不常见的 X 连锁隐性遗传疾病,源于编码人类α-半乳糖苷酶 A(α-Gal A)的α-半乳糖苷酶基因(GLA)异常。迄今为止,已发现 800 多种 GLA 基因突变可导致法布里病(FD)。不断扩大 GLA 基因突变谱将有助于更深入地认识法布里病及其潜在机制。在本研究中,一名 27 岁的男性原患者表现出典型的法布里病表型。随后,进行了法布里病家族筛查,并采用高通量测序鉴定了突变基因。对突变蛋白的三级结构进行了分析,并确定了其亚细胞定位和酶活性。评估了GLA突变细胞系的凋亡情况,以确认其功能效应。结果,在 GLA 基因中发现了一个新的突变,即 c.777_778del (p. Gly261Leufs*3)。该突变导致翻译过程中的框架偏移和终止密码子的过早出现,从而导致 C 端区域结构域的部分缺失,并改变了蛋白质的三级结构。体外实验显示,突变体细胞的酶活性显著降低。突变体细胞系的 mRNA 和蛋白质水平的表达量明显下降。此外,α-Gal A 的亚细胞定位从均匀分布变为细胞质中的点状聚集。与野生型细胞相比,GLA突变型细胞的凋亡水平明显更高。
{"title":"Identification of a novel nonsense mutation in α-galactosidase A that causes Fabry disease in a Chinese family.","authors":"Yushi Peng, Meize Pan, Yuchen Wang, Zongrui Shen, Jian Xu, Fu Xiong, Hongbo Xiao, Yun Miao","doi":"10.1080/0886022X.2024.2362391","DOIUrl":"10.1080/0886022X.2024.2362391","url":null,"abstract":"<p><p>Fabry disease, a lysosomal storage disease, is an uncommon X-linked recessive genetic disorder stemming from abnormalities in the alpha-galactosidase gene (<i>GLA</i>) that codes human alpha-Galactosidase A (α-Gal A). To date, over 800 <i>GLA</i> mutations have been found to cause Fabry disease (FD). Continued enhancement of the <i>GLA</i> mutation spectrum will contribute to a deeper recognition and underlying mechanisms of FD. In this study, a 27-year-old male proband exhibited a typical phenotype of Fabry disease. Subsequently, family screening for Fabry disease was conducted, and high-throughput sequencing was employed to identify the mutated gene. The three-level structure of the mutated protein was analyzed, and its subcellular localization and enzymatic activity were determined. Apoptosis was assessed in <i>GLA</i> mutant cell lines to confirm the functional effects. As a result, a new mutation, c.777_778del (p. Gly261Leufs*3), in the <i>GLA</i> gene was identified. The mutation caused a frameshift during translation and the premature appearance of a termination codon, which led to a partial deletion of the domain in C-terminal region and altered the protein's tertiary structure. <i>In vitro</i> experiments revealed a significant reduction of the enzymatic activity in mutant cells. The expression was noticeably decreased at the mRNA and protein levels in mutant cell lines. Additionally, the subcellular localization of α-Gal A changed from a homogeneous distribution to punctate aggregation in the cytoplasm. <i>GLA</i> mutant cells exhibited significantly higher levels of apoptosis compared to wild-type cells.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}