ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Jun Wang,Menglei Zha,Hui Zhao,Wentong Yue,Decheng Wu,Kai Li
Kidney dysfunction is a clinical syndrome that can subsequently result in lethal kidney failure. The exploration of emerging bioimaging contrast agents with translational potential is highly challenging for a feasible diagnosis of kidney dysfunction. Herein, a class of renal-clearable gadolinium nanoparticles (Gd@PEG NPs) with an ultrasmall size of ∼5 nm, good monodispersity, and T1 relaxivity are synthesized using mesoporous silica nanoparticles as the template. Assisted by such renal-clearable Gd@PEG NPs, the diagnosis of kidney dysfunction in a mice model with a damaged kidney has been achieved through in vivo noninvasive magnetic resonance imaging. As a result, this work paves the way to synthesize monodispersible ultrasmall Gd contrast agents, facilitating the exploration of translational strategies for an in vivo analysis of kidney dysfunction.
研究领域:
医学影像学
·
纳米技术
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Shujuan Xu,Lianjun He,Keke Ding,Lingling Zhang,Xinhui Xu,Sheng Wang,Xueyi Qian
Purpose Tanshinone IIA (Tan IIA), a compound extracted from Salvia miltiorrhiza, can improve type II diabetes, while the molecular mechanisms underlying Tan IIA-mediated protective effects in diabetic nephropathy are unclear. This study explored the protective actions of Tan IIA on renal tissues in streptozotocin (STZ)-induced diabetic nephropathy.Materials and Methods Tan IIA (2, 4, 8 mg/kg/day) was daily administered to STZ-treated rats by intraperitoneal injection for 42 days. The morphologic pathology was evaluated by hematoxylin-eosin and Masson’s trichrome staining, and transmission electron microscopy. The protein expression levels in renal tissues were evaluated by Western blotting and immunohistochemistry; the mRNA expression level was determined by quantitative real-time PCR.Results Tan IIA at 2 and 4 mg/kg attenuated the increase in the levels of uric acid and blood urea nitrogen and restored the reduction in the superoxide dismutase activity in the serum of the diabetic rats. Tan IIA at 2 and 4 mg/kg, but not 8 mg/kg, ameliorated the thickening of renal tubule in the diabetic rats; Tan IIA at 2 and 4 and 8 mg/kg attenuated the thickening of glomerular basement membrane and the collagen deposition in the renal tissues of the diabetic rats. Tan IIA treatment at 2, 4, 8 mg/kg decreased the expression levels of transforming growth factor-beta1, TSP-1, Grp78 and CHOP in the diabetic rats. Tan IIA at 2 and 4 and 8 mg/kg attenuated the increase in the protein levels of p-PERK, p-elf2α and ATF-4 from the renal tissues of diabetic rats, while the protein level of AFT-6 and the mRNA expression levels of XBP-1t, XBP-1s and p58IPK in the renal tissues were not affected by STZ or Tan IIA treatment.Conclusion Tan IIA-mediated protective effects on the STZ-induced diabetic nephropathy may be associated with the reduced endoplasmic reticulum stress via attenuating PERK signaling activities.
研究领域:
药理学
·
肾病学
·
糖尿病研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Dong-Yang Zhang,Tianhui Tu,Muhammad Rizwan Younis,Kathy S. Zhu,Hengke Liu,Shan Lei,Junle Qu,Jing Lin,Peng Huang
Rationale: Acute kidney injury (AKI) is associated with aberrant generation of oxidative species and inflammation, leading to high mortality of in-hospitalized patients. Although N -acetylcysteine (NAC) showed positive effects in alleviating contrast-induced AKI, the clinical applications are strongly restrained due to the low bioavailability, low renal accumulation, short renal retention time, and high dosage-induced toxicity. Methods: We addressed the clinical dilemma of NAC by developing ultrasmall gold nanoclusters (1-2 nm) capped with NAC (denoted as Au NCs-NAC) as a nanozyme-based antioxidant defense system for AKI alleviation. Rhabdomyolysis-induced AKI mice model was developed, and the same dose of free NAC (as a control) and NAC onto Au NCs (Au NCs-NAC) was used for in vivo investigation of AKI restoration. Results: The as-developed gold nanozyme exhibited high bioavailability and good physicochemical stability as compared to NAC. Meanwhile, Au NCs-NAC showed broad-spectrum antioxidant activity of Au NCs-NAC, offering in vitro renoprotective effects, as well as macrophages by relieving inflammation under hydrogen peroxide or lipopolysaccharide stimulation. Notably, owing to the smaller size than kidney threshold (5.5 nm), Au NCs-NAC displayed preferential renal enrichment (< 2 h) and longer retention (> 24 h) in AKI mice as revealed by fluorescence imaging, thereby largely enhancing the restoration of renal function in AKI mice than free NAC by protecting the kidneys from oxidative injury and inflammation without systemic toxicity, as demonstrated by tissues staining, inflammatory cytokines and biomarkers detection, and mice survival rate. Conclusion: Owing to the synergistic anti-inflammatory/antioxidative effects, and enhanced bioavailability and renal accumulation/retention, Au NCs-NAC displayed far superior therapeutic performance than NAC alone. This work will facilitate the development of high-performance antioxidative nanoplatforms, as well as overcome the clinical limitations of small molecular drugs for AKI treatment and other inflammatory diseases.
研究领域:
肾病学
·
药学
·
纳米技术
·
生物医学工程
·
临床研究
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Kai Shen,Shuqi He,WenDa Li,Siyi Song,Qianxia Lin,Huoxi Jin
Hypertensive kidney injury is significantly associated with oxidative stress, inflammation and gut microbiota. Collagen peptide and taurine (Tau) are key natural compounds known for their antioxidant, anti-inflammatory, and intestinal flora improvement. However, the potential synergistic actions of combining collagen peptides with Tau on hypertensive kidney damage remain unclear. Therefore, our study investigated the effects of collagen peptide LALFVPR (LR-7) derived from Harpadon nehereus in conjunction with Tau on renal injury in high salt (HS)-induced hypertension. The results showed that combination of LR-7 and Tau significantly alleviated renal fibrosis, glomerular atrophy, and impaired renal function in hypertensive mice. Furthermore, this combination outperformed individual treatments with either LR-7 or Tau alone in enhancing antioxidant enzyme activity while decreasing inflammatory factors and adhesion molecules levels in the kidneys. Moreover, LR-7 and Tau synergistically ameliorated HS-induced intestinal flora disturbance by promoting microbial diversity and adjusting the ratio of beneficial and harmful bacteria. Our research is pioneering in demonstrating that LR-7 combined with Tau may exert a synergistic effect on mitigating kidney damage in HS-induced hypertension through the gut-renal axis. This investigation provides a new strategy for utilizing combinations of food-derived functional compounds to effectively address complications arising from hypertension.
研究领域:
药理学
·
肾病学
·
营养学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Ting Zhou,Yanzhi Dong,Xiaoyi Wang,Ruxia Liu,Ran Cheng,Jinbin Pan,Xuejun Zhang,Shao-Kai Sun
Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T 1 relaxivity (12.52 m m −1 s −1 ), a small hydrodynamic size (6.43 nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.
研究领域:
医学影像学
·
生物材料学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Zhangning Fu,Yanji Chu,Xiaodong Geng,Yingchao Ma,Kun Chi,Chengcheng Song,Shenglong Liao,Quan Hong,Di Wu,Yapei Wang
Acute kidney injury (AKI) has emerged as a major public health problem affecting millions of people worldwide without specific and satisfactory therapies due to the lack of an effective delivery approach. In the past few decades, hydrogels present infinite potential in localized drug delivery, while their poor adhesion to moist tissue and isotropic diffusion character always restrict the therapeutic efficiency and may lead to unwanted side effects. Herein, we proposed a novel therapeutic strategy for AKI via a customizable artificial kidney capsule (AKC) together with a mesenchymal stem cell (MSC)-laden hydrogel. Specifically, an elastic capsule owning an inner chamber with the same size and shape as the kidney is designed and fabricated through three-dimensional (3D) modeling and printing, serving as an outer wrap for kidney and cell-laden hydrogels. According to the in vitro experiment, the excellent biocompatibility of gelatin-based hydrogel ensures viability and proliferation of MSCs. In vivo mice experiments proved that this concept of AKC-assisted kidney drug delivery could efficiently reduce epithelial cell apoptosis and minimize the damage of the renal tubular structure for mice suffering AKI. Such a strategy not only provides a promising alternative in the treatment of AKI but also offers a feasible and versatile approach for the repair and recovery of other organs.
研究领域:
再生医学
·
组织工程
·
肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Yong-Yu Yang,Ling Ye,Jing Chen,Yue Qiu,Ya-ling Yin,Peng Li
Cisplatin-induced acute kidney injury (AKI) is associated with high morbidity and mortality worldwide, but the underlying mechanisms are not fully understood. Downstream-of-kinase 3 (Dok3), a member of the Dok family of adaptor proteins plays a critical role in inflammatory response and immune regulation ; however, the role of Dok3 in cisplatin-induced AKI remains unclear. This study explored the effect and potential molecular mechanisms of Dok3 in cisplatin-induced AKI using Dok3 knockout (Dok3 −/− ) and control mice (129S) with or without administration of a single intraperitoneal injection of cisplatin. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, lactate dehydrogenase (LDH) release, and Hoechst staining. Inflammatory factors were measured using ELISA kits. Protein and gene expression levels were measured by western blot analysis and real-time PCR, respectively. The results showed that Dok3 was expressed in renal tubular epithelial cells. Dok3 expression was decreased in kidneys of mice treated with cisplatin and cisplatin-treated HK2 cells. Dok3 −/ − mice showed lower creatinine levels and NGAL expression, and increased survival rates compared to 129S mice. Cisplatin-induced production of TNF-α and IL-6, and renal tubular cell apoptosis was attenuated in Dok3 − / − mice. In vitro experiments demonstrated that HK2 cells overexpressing Dok3 exhibited exacerbated cisplatin-induced apoptosis and production of TNF-α and IL-6. These findings demonstrate that Dok3 regulates cisplatin-induced AKI by regulating apoptosis and inflammation.
研究领域:
药理学
·
肾病学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2022
·
IF 5.202
Yi-Fan Yang,Wei-Guo Li,Ping-Ping Wen,Pan-Pan Jia,Yong-Zhi Li,Tian-Yun Li,De-Sheng Pei
How local groundwater induces chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is still elusive. This study aims to elucidate the impacts of Sri Lanka's local groundwater in a CKDu prevalent area and reveal the possible pathogenic mechanism of CKDu using zebrafish models. The drinking water from the local underground well in Vavuniya was sampled and the water quality parameters including Na + , Mg 2+ , K + , Ca 2+ , Cl − , NO 3− , SO 4 2− , and F − were analyzed. Then, local groundwater exposure to zebrafish larvae and 293T cells was performed, and water with high hardness and fluoride was prepared as parallel groups. Our result showed that exposure to Sri Lanka's local groundwater caused developmental toxicity, kidney damage, and pronephric duct obstruction as well as abnormal behavior in zebrafish. Similar results were also found after exposure to water with high hardness and fluoride in zebrafish. Further, the expression levels of marker genes related to renal development and functions ( foxj1a, dync2h1, pkd2, gata3 , and slc20a1 ) were significantly altered, which is also confirmed in the 293T cells. Taken together, those results indicated that Sri Lanka's local groundwater in a CKDu prevalent area could cause kidney damage, implying that high water hardness and fluorine might be the inducible environmental factors for the etiological cause of CKDu.
研究领域:
环境科学
·
毒理学
·
水生生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Mu-Zi Li,Yi Zhao,Hao-Ran Wang,Milton Talukder,Jin-Long Li
Di (2-ethylhexyl) phthalate (DEHP) is an environmentally persistent and bioaccumulative plasticizer. Accumulation of DEHP in the body can eventually cause kidney damage. As a type of natural carotenoid, lycopene (LYC) has a potential protective effect on renal cells, but the protective mechanism has not yet been elucidated. The major goal of this study was to see how effective LYC was at treating DEHP-induced nephrotoxicity in mice. ICR mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) or LYC (5 mg/kg BW/day) for 28 days. Through histopathology and ultrastructure, we found that LYC attenuated DEHP-induced renal tubular cell and glomerular damage. LYC relieved DEHP-induced kidney injury evidenced by lower levels of blood urea nitrogen (Bun), creatinine (Cre), and uric acid (Uric). Meanwhile, the reduced expression of kidney injury molecule-1 (Kim-1) also supported it. Notably, LYC can alleviate the activity or content of cytochrome P450 system (CYP450s) interfered with by DEHP. In addition, LYC treatment reduced nuclear accumulation of DEHP-induced aromatic hydrocarbon receptor (AhR) and AhR nuclear transporter (Arnt), and its downstream target genes such as cytochrome P450-dependent monooxygenase (CYP) 1A1, 1A2, and 1B1 expression significantly decreased to normal in the LYC treatment group. In summary, LYC can mediate the AhR/Arnt signaling system to prevent kidney toxicity in mice caused by DEHP exposure.
研究领域:
毒理学
·
药理学
·
分子生物学
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 11
·3520
·
IF 4.927
Hongyu Zeng,Xiaoqing Zhang,Qianna Zhen,Yifan He,Haoran Wang,Yang Zhu,Qi Sun,Min Ding
A novel dual-template magnetic molecularly imprinted polymer (MMIP) was synthesized to extract normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT) from spot urine samples. As the adsorbent of dispersive solid-phase extraction (d-SPE), the MMIP was prepared using dopamine and MN as dual templates, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the crosslinking reagent and magnetic nanoparticles as the magnetic core. NMN, MN, 3-MT and creatinine (Cr) in spot urine samples were selectively enriched by d-SPE and detected by HPLC-fluorescence detection/ultraviolet detection. The peak area (A) ratios of NMN, MN and 3-MT to Cr were used for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). The results showed that the adsorption efficiencies of MMIP for target analytes were all higher than 89.0%, and the coefficient variation precisions of intra-assay and inter-assay for the analytes were within 4.9% and 6.3%, respectively. The recoveries of the analytes were from 93.2% to 112.8%. The MMIP was still functional within 14 days and could be reused at least seven times. The d-SPE and recommended solid-phase extraction (SPE) were both used to pretreat spot urine samples from 18 PPGLs patients and 22 healthy controls. The correlation coefficients of ANMN/ACrand AMN/ACrbetween d-SPE and SPE were both higher than 0.95. In addition, the areas under the receiver operator curves for spot urine ANMN/ACr, AMN/ACrand plasma free NMN and MN were 0.975, 0.773 and 0.990, 0.821, respectively, indicating the two methods had the similar performances. The d-SPE method took only 20 min, which was effective in clinical application.Keywords:magnetic molecularly imprinted polymer;normetanephrine;metanephrine;3-methoxytyramine;spot urine;PPGLs diagnosis
研究领域:
医学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Ying-Da Zang,Hai-Jie Wu,Xin-Yi Chen,Zhi-Ling Ma,Chuang-Jun Li,Jie Ma,Xiao-Guang Chen,Li Sheng,Sen Zhang,Dong-Ming Zhang
Cisplatin is a widely used drug for the clinical treatment of tumors. However, nephrotoxicity limits its widespread use. A series of compounds including eight analogs (G3-G10) and 40 simplifiers (G11-G50) were synthesized based on the total synthesis of Psiguamer A and B, which were novel meroterpenoids with unusual skeletons from the leaves of Psidium guajava. Among these compounds, (d)-G8 showed the strongest protective effect on cisplatin-induced acute kidney injury (AKI) in vitro and vivo, and slightly enhanced the antitumor efficacy of cisplatin. A mechanistic study showed that (d)-G8 promoted the efflux of cisplatin via upregulating the copper transporting efflux proteins ATP7A and ATP7B. It enhanced autophagy through the activation of the adenosine monophosphate–activated protein kinase (AMPK) signaling pathway. (d)-G8 showed no acute toxicity or apparent pathological damage in the healthy mice at a single dose of 1 g/kg. This study provides a promising lead against cisplatin-induced AKI.
研究领域:
药理学
·
药物化学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
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
危险品化学品经营许可证（带存储）