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
·
生物物理学
·
化学
·
医学
✓ 已验证
DOI
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
MOLECULES
·
2023
·Vol. 28
·期 24
·7977
·
IF 4.6
Jia-Rui Yue,Jian-Mei Lu,Qing-Fei Fan,Peng Sun,Yang-Jian Li,Shi-Lin Zhou,Xin-Yue Wang,Jun-Mei Niu,You-Kai Xu,Jing Zhou
The polysaccharides extracted fromAspidopterys obcordataare thought to have anti-urolithiasis activity in Drosophila kidney stones. This study aimed to assess the effects of different extraction solvents on the yield, chemical composition, and bioactivity of polysaccharides fromA. obcordata.A. obcordatapolysaccharides were extracted by using four solutions: hot water, HCl solution, NaOH solution, and 0.1 M NaCl. The results revealed that the extraction solvents significantly influenced the extraction yields, molecular weight distribution, monosaccharide compositions, preliminary structural characteristics, and microstructures of polysaccharides. The NaOH solution’s extraction yield was significantly higher than the other extraction methods. Vitro antioxidant activity assays revealed that the NaOH solution extracted exhibited superior scavenging abilities towards DPPH and ABTS radicals and higher FRAP values than other polysaccharides. The vitro assays conducted for calcium oxalate crystallization demonstrated that four polysaccharides exhibited inhibitory effects on the nucleation and aggregation of calcium oxalate crystals, impeded calcium oxalate monohydrate growth, and induced calcium oxalate dihydrate formation. The NaOH solution extracted exhibited the most pronounced inhibition of calcium oxalate crystal nucleation, while the hot water extracted demonstrated the most significant suppression of calcium oxalate crystal aggregation. Therefore, it can be inferred that polysaccharides extracted with NaOH solution exhibited significant potential as a viable approach for extracting polysaccharides from stems due to their superior yield and the remarkable bioactivity of the resulting products.Keywords:Aspidopterys obcordataHemsl.;polysaccharides;extraction;antioxidant activity;oxalate crystallization
研究领域:
生药学
·
生物化学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2023
·Vol. 12
·期 5
·1031
·
IF 5.2
Jing-Hong Liu,Yu-Yun Zheng,Jian-Ming Ouyang
The antioxidant activities of seven degraded products (GLPs) with different molecular weights (Mw) of polysaccharides fromGracilaria lemaneiformiswere compared. TheMwof GLP1–GLP7 were 106, 49.6, 10.5, 6.14, 5.06, 3.71 and 2.42 kDa, respectively. The results show that GLP2 withMw= 49.6 kDa had the strongest scavenging capacity for hydroxyl radical, DPPH radical, ABTS radical and reducing power. WhenMw< 49.6 kDa, the antioxidant activity of GLPs increased with the increase inMw, but whenMwincreased to 106 kDa, their antioxidant activity decreased. However, the ability of GLPs to chelate Fe2+ions increased with the decrease in polysaccharideMw, which was attributed to the fact that the polysaccharide active groups (–OSO3–and –COOH) were easier to expose, and the steric hindrance was smaller when GLPs chelated with Fe2+. The effects of GLP1, GLP3, GLP5 and GLP7 on the crystal growth of calcium oxalate (CaOx) were studied using XRD, FT-IR, Zeta potential and thermogravimetric analysis. Four kinds of GLPs could inhibit the growth of calcium oxalate monohydrate (COM) and induce the formation of calcium oxalate dihydrate (COD) in varying degrees. With the decrease inMwof GLPs, the percentage of COD increased. GLPs increased the absolute value of the Zeta potential on the crystal surface and reduced the aggregation between crystals. Cell experiments showed that the toxicity of CaOx crystal regulated by GLPs to HK-2 cells was reduced, and the cytotoxicity of CaOx crystal regulated by GLP7 with the smallestMwwas the smallest, which was consistent with the highest SOD activity, the lowest ROS and MDA levels, the lowest OPN expression level and the lowest cell necrosis rate. These results suggest that GLPs, especially GLP7, may be a potential drug for the prevention and treatment of kidney stones.Keywords:Gracilaria lemaneiformispolysaccharide;antioxidant activity;cytotoxicity;calcium oxalate;molecular weight
研究领域:
药理学
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Qing-zhu Zhang,Hui-yuan Xu,Chao-yan Feng,Chu-hao Zhang,Kun Ren,Ying-ni Pan,Dong-mei Wang,Shu-meng Ren,Xiao-qiu Liu
Ethnopharmacological relevance The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus , with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones ( Lin Zheng ). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. Aim of study This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. Materials and methods The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD 3 were compared in vivo . Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. Results There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L - Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy ( P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. Conclusion The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.
研究领域:
药理学
·
民族药理学
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泌尿学
·
传统中药
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生物化学
·
分子生物学
✓ 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
CRYSTENGCOMM
·
2021
·Vol. 23
·期 48
·8588-8600
·
IF 3.545
Jing Zhang,Wenjun Zhang,Christine V. Putnis,Lijun Wang
As one of the most ubiquitous biominerals, calcium oxalate (CaOx) exhibits different hydrate phases. Although the monohydrate (whewellite, COM) is the thermodynamically favorable phase at ambient temperatures, the metastable dihydrate (weddellite, COD) can still stably exist in pathological mineralization but the stabilization mechanisms remain unclear. Herein, the in situ phase transformation of nano-sized COD to COM in the presence of citrate (CA) and zinc ions (Zn2+) as stabilizers was observed by time-resolved atomic force microscopy (AFM) and Raman spectroscopy. By a combination of zeta potential measurement, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), we demonstrate that CA can form a protective layer on the surface of nano-sized COD crystals to inhibit aggregation and delay the phase transformation of COD to COM. Due to the stabilizing/destabilizing effect of CA on the specific faces of COD, atypical-shaped COD crystals form. In addition, Zn2+ can substitute Ca2+ sites within the COD unit cell, shrinking the COD structure by compressing the “zeolite-like” channels to reduce weakly-bonded interchannel H2O molecules. This generates relatively smaller and more stable COD crystals with a typical pyramid shape to further retard COM formation. The obtained results provide new insights into modulating the stability of the metastable CaOx phases for potential control over pathological mineralization.
研究领域:
生物矿化
·
病理学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL UROLOGY AND NEPHROLOGY
·
2020
·Vol. 52
·期 7
·1227-1234
·
IF 1.843
Wang Zhenghao,Bai Yunjin,Wang Jiahao,Wang Jia
Objective To investigate the effect of α-lipoic acid (α-LA) in the prevention and treatment of ethylene glycol-induced calcium oxalate deposition in a rat model and preliminary exploration of the mechanism. Methods Sixty male Wistar rats were divided randomly and equally into six groups including two α-LA prevention groups, two α-LA therapeutic groups, one controlled group and one intervention group. Besides controlled group, other group received 1% glycol solution and 2 ml 2% ammonium chloride for 4 weeks as a stone inducer. The prevention groups received 0.1 and 0.2 mg/kg body weight/day/rat α-LA as food supplement during inducing stone and therapeutic groups received 0.1 and 0.2 mg/kg body weight/day/rat α-LA for 4 weeks after 4 weeks stone inducing. Results The volume of urine, the pH and magnesium levels in the preventive and therapeutic groups were higher in a dose-independent manner ( p < 0.05), and urinary calcium was lower ( p < 0.05). Antioxidant stress enzyme activity (glutathione, superoxide dismutase, catalase) in serum and kidney homogenates in the preventive and therapeutic groups underwent significant regeneration ( p < 0.05) and malondialdehyde levels and the production of free radical moieties decreased. Pathological observation demonstrated that there was deformation due to renal tubular expansion in the control group, greater visible inflammatory cell infiltration into the interstitial spaces and partial destruction of the glomerular structures. α-lipoic acid improved the lesions to varying degrees. The extent of crystal deposition was lower in the preventive and therapeutic groups compared with the control group ( p < 0.05). Conclusion The present study indicated that α-LA provides both preventive and therapeutic effects against the deposition of calcium oxalate crystals in rats.
研究领域:
医学
·
药理学
·
泌尿学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Dali Zhuo,Xiaoyu Dong,Linghuan Li,Ronghua Zeng,Chao Tan,Hong Luo,Zhirong Zou
Calcium ion (Ca 2+ ) is one of the important nutrients for humans, excessive and insufficient intake may both cause diseases, so that it is of great importance to analysis of Ca 2+ in our daily life. In this work, a portable gas pressure meter-based method was developed for the detection of Ca 2+ in water samples and calcium gluconate oral liquids. Ca 2+ in solution was extracted and precipitated by the addition of Na 2 C 2 O 4 , CaC 2 O 4 precipitate was formed and then filtered from the complicated matrix through a filter membrane. The filter membrane (containing CaC 2 O 4 precipitate) was then treated by H 2 SO 4 solution, CaC 2 O 4 precipitate was dissolved during this step and H 2 C 2 O 4 was formed. In a sealed bottle-in-bottle reaction device, H 2 C 2 O 4 reacted with acidic KMnO 4 solution to generate CO 2 gas, causing a significant gas pressure increase and it was readout by a hand-held pressure meter. A standard curve with linear range of 1–80 mmol L −1 and a limit of detection of 0.4 mmol L −1 were obtained. This system was subsequently applied to the detection of Ca 2+ in several water samples and oral liquids, recoveries of 92–110 % were obtained for their spiked samples. Only a few reaction bottles and a gas pressure meter were required in this system. It is a low-cost, sensitive, rapid and easy-used analytical method for on-site determination of Ca 2+ .
研究领域:
分析化学
·
营养学
·
环境监测
✓ 已验证
产品关联
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Si Li,Xiang Kang,Qing He,Weiwei Tang,Junbo Gong
Designing (macro)molecules controlling crystallization is an essential approach to regulate structure and properties of crystalline materials and circumvent detrimental mineralization in nature, biological, and synthetic systems. Here we discovered four novel, natural polyphenols, including gallic acid, ellagic acid, punicalagin, and tannic acid, as a new class of inhibitors for nucleation and crystal growth of calcium oxalate (CaOx), a primary constitution of kidney stones. Study of time-resolved growth reveals that polyphenols regulate the kinetics of crystal-liquid interface acting as a dual role of growth promoter and inhibitor which displays a new record of growth promotion up to 75% or complete suppression, dependent upon the modifier concentration. Time-elapsed in situ atomic force microscopy measurements unveil these modifiers regulate the growth mode from spiral-mediated to generation of two-dimensional (2D) islands and layer spreading mechanism, leading to formation of step bunches growing out of (0 1 0) surface and forming macroscopically crystal whiskers. The governing regime between growth promotion and inhibition is determined by inhibitors concentration but can be influenced by crystallization driving force. Such unique growth mechanism of crystal whiskers may also provide potential implications for understanding and synthesizing branched and hierarchical structures of biomimetic materials.
研究领域:
生物化学
·
材料科学
·
医学
✓ 已验证
DOI
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
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOINORGANIC CHEMISTRY AND APPLICATIONS
·
2023
·
IF 3.8
Bao-Li Heng,Fan-Yu Wu,Jing-Hong Liu,Jian-Ming Ouyang
Objective. This study aimed to investigate the growth of calcium oxalate (CaOx) crystals regulated by Auricularia auricular polysaccharides (AAPs) with different viscosity-average molecular weights (), the toxicity of AAP-regulated CaOx crystals toward HK-2 cells, and the prevention and treatment capabilities of AAPs for CaOx stones. Methods. The scavenging capability and reducing capacity of four kinds of AAPs ( of 31.52, 11.82, 5.86, and 3.34 kDa) on hydroxyl, ABTS, and DPPH free radicals and their capability to chelate divalent iron ions were detected. AAP-regulated CaOx crystals were evaluated by using zeta potential, thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. The cytotoxicity of AAP-regulated crystals was evaluated through examination of cell viability, cell death, malondialdehyde (MDA) content, and cell surface hyaluronic acid (HA) expression. Results. The in vitro antioxidant activities of the four AAPs were observed in the following order: AAP0 < AAP1 < AAP2 < AAP3. Thus, AAP3, which had the smallest , had the strongest antioxidant activity. AAPs can inhibit the growth of CaOx monohydrate (COM), induce the formation of CaOx dihydrate (COD), and reduce the degree of crystal aggregation, with AAP3 exhibiting the strongest capability. Cell experiments showed the lowest cytotoxicity in AAP3-regulated CaOx crystals, along with the lowest MDA content, HA expression, and cell mortality. In addition, COD presented less cytotoxicity than COM. Meanwhile, the cytotoxicity of blunt crystals was less than that of sharp crystals. Conclusion. AAPs, particularly AAP3, showed an excellent antioxidative capability in vitro, and AAP3-regulated CaOx crystals presented minimal cytotoxicity.
研究领域:
药理学
·
肾病学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）