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
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
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
·
材料科学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 10
·3524-3546
·
IF 6.6
Jing-Hong Liu,Jian-Ming Ouyang
Objective: The first objective is to study the synergistic inhibition of calcium oxalate (CaOx) formation by Laminarin polysaccharides (DLP and SDLP, before and after sulfation) and potassium citrate (K3cit) and determine the synergistic protection of renal epithelial cells (HK-2 cells) caused by CaOx crystal damage. The second objective is to explore new ways to prevent and treat kidney stones. Methods: The CaOx crystals regulated by five additives (K3cit group, DLP group, SDLP group, DLP–K3cit synergistic group and SDLP–K3cit synergistic group) were characterized by FT-IR, XRD, SEM, zeta potential, ICP, and TGA. The protective effect of each additive group on HK-2 cells damaged by nano-calcium oxalate monohydrate (nano-COM) was compared by detecting cell viability, the cell reactive oxygen species level, the cell survival rate, and mitochondrial membrane potential. Results: When DLP or SDLP acted synergically with K3cit, the synergistic group induced the same amount of COD at a lower concentration or more COD formation at the same concentration, highlighting the synergistic enhancement effect of 1 + 1 > 2. At 0.3 g L−1, the COD contents induced by DLP, SDLP, K3cit, DLP–K3cit, and SDLP–K3cit synergistic groups were 20.3%, 75.8%, 75.4%, 87.3%, and 100%, respectively. The synergistic group increased the concentration of soluble Ca2+ ions in the supernatant, increased the absolute value of the zeta potential on the surface of CaOx crystals, and inhibited the aggregation among the crystals. TGA and DTG analyses established the adsorption of polysaccharides in the crystals. Cell experiments showed the ability of the synergistic group to significantly inhibit the damage of nano-COM crystals on HK-2 cells, reduce the level of reactive oxygen species and mortality, and improve cell viability and the mitochondrial membrane potential. Conclusions: The synergistic group can more effectively induce COD formation and cell protection than the standalone polysaccharide group or K3cit group. The synergistic groups, especially SDLP–K3cit, may be a potential drug for inhibiting the formation of CaOx kidney stones.
研究领域:
医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
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
·
泌尿科学
·
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
Small
·
2024
·
IF 13
Yu He,Ejun Peng,Xiaozhuo Ba,Jian Wu,Wen Deng,Qiu Huang,Yonghua Tong,Haojie Shang,Zichen Zhong,Xiao Liu,Yanlong Zhang,Tao Ye,Xiaoqi Yang,Kangyang Wang,Yabin Xie,Kehua Jiang,Ding Xia,Zhiqiang Chen,Kun Tang
Emerging studies have demonstrated that M1 macrophage polarization and oxidative stress play important roles in calcium oxalate (CaOx) induced kidney injury, which leads to increased crystals deposition. ROS scavenging nanozymes and kidney-targeted nanoparticles for antioxidant drugs delivery have emerged as an arisen methodology for kidney injury therapy. However, cell membrane biomimetic-modified nanozymes as anti-inflammatory drug delivery systems for the treatment of kidney injury is rarely reported. Herein, the ROS responsive red blood cell-membrane-coated resatorvid-loaded cerium oxide nanoparticles (RBCM@CeO 2 /TAK-242) are constructed to suppress CaOx induced kidney injury and crystals deposition. In vitro, RBCM@CeO 2 /TAK-242 shows effective internalization by renal tubular epithelial cells, along with demonstrated antioxidative, anti-inflammatory, and macrophage reprogramming effects. Glyoxalate(Gly)-induced renal CaOx crystals mouse model is established, RBCM@CeO 2 /TAK-242 shows excellent injured kidney targeting and biosafety, and could effectively suppress CaOx induced kidney injury and crystals deposition. RBCM@CeO 2 /TAK-242 has a dual protective effect by both inhibiting oxidative stress and modulating macrophage polarization in vivo. In addition, RNA seq analysis reveals that RBCM@CeO 2 /TAK-242 protects against CaOx induced kidney injury via suppressing the TLR4/NF-κB pathway. This study provides an innovative strategy for RBCM@CeO 2 /TAK-242 as injured kidney targeting and dual protective effects for the treatment of CaOx induced kidney injury and crystals deposition.
研究领域:
纳米技术
·
药理学
·
肾脏生理学
·
炎症
·
氧化应激
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Han Li,Yushan Li,Huailing Diao,Haipeng Ren,Jianming Chen,Jinfeng Wang,Qingtao Liu,Xungai Wang
Wild silk cocoons are light-weight composite structures with unique properties. One such property is the intriguing CO 2 gating property (i.e., unidirectional flow of CO 2 ) exhibited by the wild Antheraea pernyi ( A. pernyi ) silkworm cocoon. This study investigated the hierarchical structural and compositional features of A. pernyi cocoons and their impact on CO 2 adsorption. For the first time, soap-film flowmeter testing method and gas permeability testing method were used to quantitatively demonstrate the A. pernyi cocoons’ CO 2 adsorption property and selectivity for gas mixture. The results showed that the multi-layered composite structure of A. pernyi cocoons, coupled with calcium oxalate crystals, play a crucial role in their CO 2 adsorption and separation performance. These findings shed light on the unique functional design of wild silk cocoons and provide a new biomimetic approach for developing materials and structures to address global challenges such as CO 2 capture and storage.
研究领域:
材料科学
·
环境科学
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仿生学
·
气体分离
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 6
·805
·
IF 4.3
Tian-Qu He,Zhi Wang,Chuang-Ye Li,Yao-Wang Zhao,Xin-Yi Tong,Jing-Hong Liu,Jian-Ming Ouyang
Purpose:Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored.Methods:The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell–crystal adhesion were examined in the presence ofLaminarinpolysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions.Results:Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP.Conclusions:SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal–cell adhesion interactions and the risks of kidney stone formation.
研究领域:
药理学
·
泌尿学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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