Toxics
·
2023
·Vol. 11
·期 9
·799
·
IF 4.6
Hangwei Wang,Zhanren Liu,Shaojie Liu,Ruoru Yang,Yifei Wang,Yiying Gu,Min Wu,Ruihua Dong,Bo Chen
This study aimed to assess the therapeutic efficacy of catechin against experimentally induced kidney stones resulting from co-exposure to melamine (MEL) and cyanuric acid (CYA) in male Sprague–Dawley rats. To induce nephrolithiasis, a combination of MEL and CYA (1:1 ratio, each at a dose of 31.5 mg/kg bw/day) was administered to the rats for 28 consecutive days. After nephrolithiasis was successfully induced, the rats were randomly divided into two groups: a treatment group and a sham group. The treatment group was given a daily oral dose of 50 mg/kg of catechin for 28 days, while the sham group received no intervention. Urine and blood samples were collected throughout the treatment period, and kidney samples were taken on day 28. Our findings demonstrated that treatment with catechin significantly reduced crystal deposition and pathological damage in the rats from nephrolithiasis. Additionally, renal injury markers were significantly decreased in the treatment group compared to the sham group. These findings suggest that catechin has potential therapeutic benefits in treating nephrolithiasis induced by co-exposure to MEL and CYA.Keywords:melamine;cyanuric acid;nephrolithiasis;catechin
研究领域:
毒理学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Xue-Wu Chen,Jun Long,Quan Zhang,Linghong Huang,Xin-Yuan Sun
s: Background: Calcium oxalate (CaOx) crystal deposition and its resultant cellular oxidative damage and inflammation are important causes of renal stone formation. It is clinically important to conduct research on multifunctional anti-stone drugs targeting these predisposing factors. Methods: We modified natural Undaria pinnatifida polysaccharide (UPP0) by sulfation via the sulfur trioxide-pyridine method, resulting in four sulfated polysaccharides with varying sulfate group (–OSO3–) contents: 1.59% (UPP0), 6.03% (UPP1), 20.83% (UPP2), and 36.39% (UPP3), and compared their differences in the inhibition of crystalline formation, renal injury, and inflammation in the process of renal stone formation at chemical and cellular levels. Results: The UPPS were able to inhibit the nucleation, growth and aggregation of CaOx crystals in vitro. Among them, UPP3 with the maximum sulfate group content showed the greatest crystallization inhibition ability. The nucleation inhibition and aggregation inhibition of UPP3 at a concentration of 0.5 mg/mL were as high as 80.21% and 72.34%, respectively. The CaOx crystal size regulated by UPP3 was significantly reduced from 25.9 ± 2.8 μm to 5.9 ± 1.2 μm. Furthermore, UPPS were observed to up-regulate the expression of the antioxidant enzyme superoxide dismutase (SOD) in cells, reduce the levels of ROS and malonaldehyde (MDA), enhance lysosomal integrity, decrease intracellular Ca2+ levels, inhibit the decline in mitochondrial membrane potential, reduce the production of cellular inflammatory factors (TNF-α, MCP-1, IL-18, and IL-1β), and ultimately inhibit cell apoptosis. Conclusion: UPPS combine multiple biological functions of crystallization regulation, antioxidant and anti-inflammatory, and have important potential in the prevention of kidney stones. Sulfation modification can improve the biological activity of UPP0 and provide a reference for screening and optimization methods of stone drugs.
研究领域:
医学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Hui Zhang,Xin-Yuan Sun,Jian-Ming Ouyang
The adhesion and endocytosis of renal epithelial cells to urinary microcrystals are closely related to kidney stone formation; however, the mechanism of cell state changes that affect adhesion and endocytosis remains unclear. In this study, a damaged cell model was established using oxalate to impair human kidney proximal tubular epithelial cells (HK-2). Then, we used four degraded Porphyra yezoensis polysaccharides (PYPs), namely, PYP1, PYP2, PYP3, and PYP4, with molecular weight of 576.2, 49.5, 12.6, and 4.02 kDa, respectively, to repair the damaged cells. After repairing the damaged HK-2 cells by PYPs, the cell morphology gradually recovered to near normal; the cell migration speed increased; the phosphatidylserine eversion ratio and osteopontin expression decreased; and the intracellular adenosine triphosphate was promoted. The adhesion and endocytosis of calcium oxalate monohydrate (COM) crystals were closely related to cell state. Normal cells could endocytose crystals more than the damaged cells, whereas damaged cells could adhere to crystals more than the normal cells. The cells repaired by PYPs inhibited the adhesion of nano-COM crystals and promoted the endocytosis of the adherent crystals, thereby reducing the adhesion of crystals on the cell surface under both effects. As the molecular weight of PYP decreased, the ability of PYP to repair cells, inhibit crystal adhesion, and promote endocytosis of cells was enhanced; that is, PYP4, which had the lowest molecular weight, exhibited the best biological activity. Therefore, PYPs, especially PYP4, may become an optional green drug to inhibit the formation and recurrence of calcium oxalate stones.
研究领域:
药理学
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肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Wei-Bo Huang,Guo-Jun Zou,Gu-Hua Tang,Xin-Yuan Sun,Jian-Ming Ouyang
The original Laminaria polysaccharide (LP0) was sulfated using the sulfur trioxide-pyridine method, and four sulfated Laminaria polysaccharides (SLPs) were obtained, namely, SLP1, SLP2, SLP3, and SLP4. The sulfated (–OSO3–) contents were 8.58%, 15.1%, 22.8%, and 31.3%, respectively. The structures of the polysaccharides were characterized using a Fourier transform infrared (FT-IR) spectrometer and nuclear magnetic resonance (NMR) techniques. SLPs showed better antioxidant activity than LP0, increased the concentration of soluble Ca2+ in the solution, reduced the amount of CaOx precipitation and degree of CaOx crystal aggregation, induced COD crystal formation, and protected HK-2 cells from damage caused by nanometer calcium oxalate crystals. These effects can inhibit the formation of CaOx kidney stones. The biological activity of the polysaccharides increased with the content of –OSO3−, that is, the biological activities of the polysaccharides had the following order: LP0 < SLP1 < SLP2 < SLP3 < SLP4. These results reveal that SLPs with high –OSO3− contents are potential drugs for effectively inhibiting the formation of CaOx stones.
研究领域:
药理学
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材料科学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2020
·
IF 4.089
Si Li,Weiwei Tang,Peng Shi,Mengya Li,Jie Sun,Junbo Gong
The therapeutics for nephrolithiasis have created an awareness of the potential effects of crystal modifiers on the biocrystallization process. The crystallization of calcium oxalate, a primary constituent of kidney stones, is confirmed to be inhibited by natural or synthetic modifiers, but the induction of calcium oxalate dihydrate and trihydrate, which is likewise effective for retardation of stone formation, is rarely focused on. Herein, we performed a systematic investigation of the effect of gallic acid, a natural polyphenol, on the nucleation of calcium oxalate from both experimental and simulation approaches. Our results reveal that the solution species of gallic acid alter the nucleation pathways of calcium oxalate and induce the formation of different types of amorphous structures corresponding to calcium oxalate hydrates. Different species of gallic acid regulate the formation of three types of amorphous calcium oxalates (ACOs) by incorporating the proper water contents and specific interactions. Fluorescence microscopy further demonstrates clearly the incorporation of gallic acid in the nucleated calcium oxalate precipitates. These findings unveil the nucleation mechanism of different calcium oxalate hydrates with the inclusion of modifiers and provide insights for an understanding of stone formation and its potential inhibitors.
研究领域:
材料科学
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生物物理学
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化学
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医学
✓ 已验证
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-24
·
IF 12.6
Tong Xin-Yi,Nong Wei-Jian,Tan Run-Min,Ouyang Jian-Ming
Objective This study aimed to compare the differences in pyroptosis and polarization of macrophages induced by different sizes of calcium oxalate monohydrate (COM) crystals and discuss the mechanism of kidney stone formation. Methods COM crystals with sizes of about 100 nm, 500 nm, 2.5 μm, and 10 μm were synthesized and characterized. THP-1 cells were induced to differentiate into macrophage-like cells. The damage of COM crystals to Mφs was evaluated by CCK-8 assay. The activation of the pyroptosis signaling pathway, cell morphology, and proportion of pyroptosis cells in Mφs induced by COM crystals were detected. Finally, the proportion of M1/M2 polarization was qualitatively and quantitatively assessed. Results COM-100 nm, COM-500 nm, COM-2.5 μm, and COM-10 μm all significantly induced the pyroptosis and polarization of Mφs. Among them, at the same cell viability, COM-10 μm induced the highest pyroptosis rate. The expression of NLRP3 and GSDMD-N induced by COM-10 μm increased by 81.43 ± 11.45% and 112.00 ± 9.87%, respectively, and the rate of caspase-1/PI double-positive pyroptosis cells was 22.2%. Meanwhile, COM-10 μm induced the highest proportion of M1 polarization (M1/M2 ratio was 209.90% ± 2.54%). Conclusion COM-10 μm significantly activates the classical caspase-1-mediated pyroptosis pathway and promotes M1 polarization in Mφs. Therefore, at the same cell viability, large-sized micro-COM is more capable of inducing inflammation than nano-COM. Graphical
研究领域:
纳米技术
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泌尿科学
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免疫学
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cells
·
2024
·Vol. 13
·期 24
·2070
·
IF 5.1
Wei-Jian Nong,Xin-Yi Tong,Jian-Ming Ouyang
Endoplasmic reticulum stress (ERS) can activate pyroptosis through CHOP and TXNIP; however, the correlation between this process and the formation of kidney stones has not been reported. The purpose is to investigate the effects of calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) on ERS and pyroptosis in HK-2 cells and to explore the formation mechanism of calcium oxalate stones. HK-2 cells were injured by 3 μm COM and COD. COM and COD significantly upregulated the expression levels of GRP78, CHOP, TXNIP, and pyroptosis-related proteins (NLRP3, caspase-1, GSDMD-N, and IL-1β). Fluorescence colocalization revealed that COM induced pyroptosis by inducing the interaction between TXNIP and NLRP3. Both COM and COD crystals can induce ERS and pyroptosis in HK-2 cells. COM induces the interaction with NLRP3 by the upregulation of CHOP and TXNIP and then promotes pyroptosis, while COD only promotes pyroptosis by the upregulation of CHOP. The cytotoxicity and the ability of COM to promote crystal adhesion and aggregation are higher than COD, suggesting that COM is more dangerous for calcium oxalate kidney stone formation.
研究领域:
细胞生物学
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肾脏病学
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泌尿科学
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分子生物学
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病理学
✓ 已验证
DOI
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2021
·
IF 4.219
Lei Yu,Xiuguo Gan,Yufeng Bai,Ruihua An
Kidney stone disease (KSD) is a common urinary disease with increasing prevalence worldwide. In this study, we investigated the effect of cyclic AMP responsive element binding protein (CREB) 1 in a KSD model of rat and calcium oxalate monohydrate (COM) crystals-treated NRK-52E cells. Rats were pretreated with lentivirus (LV)-CREB1 vector or LV-control vector and administrated with ethylene glycol + ammonium chloride to induce KSD. It was found that CREB1 was activated in the renal tissue of non-treated KSD rats. Pretreating with LV-CREB1 vector significantly enhanced CREB1 expression in KSD rats. Biochemical analysis for serum and urine showed that upregulation of CREB1 could improve the renal function of KSD rats. Histological analysis confirmed that upregulation of CREB1 alleviated the renal injury in KSD rats. Moreover, the upregulation of CREB1 suppressed the apoptosis in renal tissue of KSD rats through regulating apoptosis-associated proteins. Further study showed that the upregulation of CREB1 could attenuate the oxidative stress in KSD rats as well. More interestingly, the upregulation of CREB1 enhanced the activity of complex I and complex III and the expression of mitochondrial cytochrome c , implicating the effect of CREB1 on improving mitochondrial function in KSD rats. In vitro study confirmed that upregulation of CREB1 inhibited the apoptosis and oxidative stress, while improved the mitochondrial function of NRK-52E cells treated with COM crystals, demonstrating the protective effect of CREB1 on COM crystals-induced renal epithelial cell injury. Therefore, CREB1 might be served as a promising target in the prophylaxis and treatment of KSD.
研究领域:
肾病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Yuan Su,Si Li,Xin Li,Jing-Ying Zhou,Vraj P. Chauhan,Meng Li,Ya-Hui Su,Chun-Mei Liu,Yi-Fei Ren,Wu Yin,Jeffrey D. Rimer,Ting Cai
Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone-related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.
研究领域:
泌尿学
·
材料科学
·
生物物理学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Nephrology
·
2018
·Vol. 19
·期 1
·1-12
·
IF 2.395
Yang Huan,Male Musa,Li Yang,Wang Ning,Zhao Chenming,Jin Shan,Hu Juncheng,Chen Zhiqiang,Ye Zhangqun,Xu Hua
Background Substrate reduction therapy with analogs reduces the accumulation of substrates by inhibiting the metabolic pathways involved in their biosynthesis, providing new treatment options for patients with primary hyperoxalurias (PHs) that often progress to end-stage renal disease (ESRD). This research aims to evaluate the inhibition efficacy of Hydroxy-L-proline (HYP) analogs against calcium oxalate (CaOx) crystal formation in the Drosophila Melanogaster ( D. Melanogaster ) by comparing them with Pyridoxine (Vitamin B6). Methods Three stocks of Drosophila Melanogaster (W 118 , CG3926 RNAi, and Act5C-GAL4/CyO) were utilized. Two stocks (CG3926 RNAi and Act5C-GAL4 /CyO) were crossed to generate the Act5C > dAGXT RNAi recombinant line (F 1 generation) of D. Melanogaster which was used to compare the efficacy of Hydroxy-L-proline (HYP) analogs inhibiting CaOx crystal formation with Vitamin B 6 as the traditional therapy for primary hyperoxaluria. Results Nephrolithiasis model was successfully constructed by downregulating the function of the dAGXT gene in D. Melanogaster ( P -Value = 0.0045) . Furthermore, the efficacy of Hydroxy-L-proline (HYP) analogs against CaOx crystal formation was demonstrated in vivo using D. Melanogaster model; the results showed that these L-Proline analogs were better in inhibiting stone formation at very low concentrations than Vitamin B 6 (IC 50 = 0.6 and 1.8% for standard and dietary salt growth medium respectively) compared to N-acetyl-L-Hydroxyproline (IC 50 = 0.1% for both standard and dietary salt growth medium) and Baclofen (IC 50 = 0.06 and 0.1% for standard and dietary salt growth medium respectively). Analysis of variance (ANOVA) also showed that Hydroxy-L-proline (HYP) analogs were better alternatives for CaOx inhibition at very low concentration especially when both genetics and environmental factors are intertwined ( p < 0.0008) for the dietary salt growth medium and ( P < 0.063) for standard growth medium. Conclusion Addition of Hydroxy-L-Proline analogs to growth medium resulted in the reduction of CaOx crystals formation. These analogs show promise as potential inhibitors for oxalate reduction in Primary Hyperoxaluria.
研究领域:
药理学
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遗传学
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分子生物学
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肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2022
·Vol. 28
·期 1
·1-20
·
IF 6.376
Ming Shaoxiong,Tian Jia,Ma Ke,Pei Chengbin,Li Ling,Wang Zeyu,Fang Ziyu,Liu Min,Dong Hao,Li Weijian,Zeng Jianwen,Peng Yonghan,Gao Xiaofeng
Background Kidney stones are composed of approximately 70–80% calcium oxalate. However, the exact mechanism of formation of calcium oxalate kidney stones remains unclear. In this study, we investigated the roles of endoplasmic reticulum stress (ERS), reactive oxygen species (ROS), and the NF-κB signalling pathway in the pathogenesis of oxalate-induced renal tubular epithelial cell injury and its possible molecular mechanisms. Methods We established a model to evaluate the formation of kidney stones by intraperitoneal injection of glyoxylic acid solution into mice and assessed cell morphology, apoptosis, and the expression levels of ERS, ROS, and NF-κB signalling pathway-related proteins in mouse renal tissues. Next, we treated HK-2 cells with potassium oxalate to construct a renal tubular epithelial cell injury model. We detected the changes in autophagy, apoptosis, and mitochondrial membrane potential and investigated the ultrastructure of the cells by transmission electron microscopy. Western blotting revealed the expression levels of apoptosis and autophagy proteins; mitochondrial structural and functional proteins; and ERS, ROS, and NF-κB (p65) proteins. Lastly, we studied the downregulation of NF-κB activity in HK-2 cells by lentivirus interference and confirmed the interaction between the NF-κB signalling and ERS/ROS pathways. Results We observed swelling of renal tissues, increased apoptosis of renal tubular epithelial cells, and activation of the ERS, ROS, and NF-κB signalling pathways in the oxalate group. We found that oxalate induced autophagy, apoptosis, and mitochondrial damage in HK-2 cells and activated the ERS/ROS/NF-κB pathways. Interestingly, when the NF-κB signalling pathway was inhibited, the ERS/ROS pathway was also inhibited. Conclusion Oxalate induces HK-2 cell injury through the interaction between the NF-κB signalling and ERS/ROS pathways.
研究领域:
肾病学
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细胞生物学
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分子生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2023
·
IF 4
Kun Ma,Jialuo He,Huimin Yuan,Jiayu He,Ming Xiang
Osteoporosis (OP) has been a global health concern, and calcium supplements are still an effective method to relieve the disease. In this study, we investigated the pharmaceutical properties, antiosteoporosis, and adverse effects of a novel calcium supplement named compound calcium carbonate granule (CCCG). The dissolution rate, stability of vitamin D3, and drug permeability of the calcium supplements were explored. And the osteoporosis was constructed in mice with retinoic acid (100 mg/kg/d) for 21 days, and orally treated with CCCG (0.34, 0.68, and 1.36 g/kg/d) for 36 days to evaluate the efficacy against osteoporosis and the occurrence of kidney stones. The results showed that CCCG exhibited higher dissolution rate and better vitamin D3 stability than the standard calcium carbonate granule. CCCG also displayed more absorption in Caco-2 cell model. On the other hand, CCCG alleviated the deterioration in femur microstructure and oxidative stress in the liver and kidney, and increased the expression of bone metabolic markers. CCCG also exhibited lower risk of nephrolithiasis than the commercial calcium carbonate granule. In summary, from the perspectives of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative of commonly used ones. Practical Application. Calcium carbonate is widely used to supplement calcium, primarily because of its high calcium load, low cost, and good efficacy. Now, we provided a new calcium supplement named CCCG, which was prepared by inclusion and complexation techniques. Vitamin D3 in CCCG was made into vitamin D-β-cyclodextrin inclusion complex by inclusion technology, which improved the stability of vitamin D3. And calcium carbonate was converted to a water-soluble calcium citrate complex via complexation techniques to accelerate the release of calcium ions and minimize the risk of kidney stone formation. From the perspective of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative for the supplemental and preventive treatment of osteoporosis.
研究领域:
药剂学
·
药理学
·
骨科
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营养学
·
动物模型
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）