ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2025
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IF 11.3
Wen Xie,Yajing Zhang,Yu He,Hang Su,Jinni Zhang,Canrong Chen,Peisi Xie,Jing Chen,Zian Lin,Zongwei Cai
Imidacloprid (IMI), a neonicotinoid insecticide extensively applied in agriculture, is among the most frequently detected pesticides in food. However, the long-term impact of chronic dietary exposure to environmentally relevant IMI doses on kidney health has not been fully elucidated, particularly regarding its nephrotoxic mechanisms. To address this gap, chronic exposure to IMI was administered to mice through supplementation of their feed with environmentally relevant doses (approximately 100 and 1000 μg/kg/day) for 24 weeks to investigate its nephrotoxicity and underlying mechanisms. Toxicological analysis revealed that chronic IMI exposure led to renal dysfunction, histopathological alterations, and excessive apoptosis in mice. Mechanistic investigations suggested that IMI might inhibit AMP-activated protein kinase (AMPK) activity through both direct and indirect pathways. Direct inhibition occurred through the binding of IMI and its metabolites to AMPK, reducing its phosphorylation activity. Indirect inhibition involved excessive production of reactive oxygen species, which suppressed AMPK phosphorylation, leading to sustained purine metabolism dysregulation in the renal system. Consequently, the kidneys showed an aggravated redox imbalance, heightened inflammatory states, and increased cellular apoptosis. The results of this study are intended to raise awareness of pesticide use and food safety among agricultural workers and consumers.
研究领域:
毒理学
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环境科学
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生物化学
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药理学
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食品安全
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分子生物学
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DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
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2024
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IF 4
Yexi Peng,Yuming Qi,Mingze Xu,Yiqiao Chen,Xiaoxian Wang,Xingya Jiang,Bujie Du
Noninvasive fluorescence imaging of renal function is a valuable technique for understanding kidney disease progression and the development of renal medicine. This technique requires sensitive imaging probes for reporting renal dysfunction accurately at early stage. Herein, a molecularly engineered imaging probe (800CW–PEG45–COOH) was synthesized by simply PEGylating conventional near-infrared fluorophore IRDye800CW with NH2–PEG45–COOH (molecular weight ∼2100 Da) for early detection and staging of renal dysfunction through noninvasive real-time kidney imaging. 800CW–PEG45–COOH not only cleared through the kidney efficiently (>90% injection dosage at 24 h postinjection) but was also found to be freely filtered by glomeruli without renal tubular reabsorption and secretion. Despite this simple construction strategy, the transport of 800CW–PEG45–COOH within the kidneys was extremely sensitive to the alteration of the glomerular filtration rate (GFR), which enabled it to detect renal dysfunction much earlier than commonly used serum biomarkers and stage kidney function impairments (mild vs severe dysfunction) via imaging-based kidney clearance kinetics. This work not only provides a promising optical imaging probe for the noninvasive evaluation of kidney function but also highlights the utility of PEGylation in enhancing the performance of conventional organic dyes in biomedical applications.
研究领域:
生物医学工程
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肾病学
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医学成像
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Wenjing Pu,Xuesheng Chu,Shiwen Xu,Xueyan Dai,Li Xiao,Ting Cui,Bingyan Huang,Guoliang Hu,Caiying Zhang
Molybdenum (Mo) is an essential nutrient in living organisms. Although numerous researchers have noticed the health damage caused by excessive Mo, the underlying mechanism of excessive Mo-induced nephrotoxicity remains poorly understood. A gene crosstalk called competitive endogenous RNAs (ceRNAs) can interpret many regulatory mechanisms molecularly. But there are few researches have tried to explain the damage mechanism of excess Mo to organisms through ceRNAs network. To clarify this, the study explored the changes in lncRNAs and miRNAs expression profiles in the kidney of ducks exposed to excess Mo for 16 weeks. The sequencing results showed that Mo exposure caused differential expression of 144 lncRNAs and 14 miRNAs. The occurrence of inflammation through the JAK/STAT axis was observed and the lncRNA-00072124/miR-308/OSMR axis was verified by a double luciferase reporter assay. Overexpression of miR-308 and RNA interference of OSMR reduced Mo-induced inflammatory factors, while miR-308 knockdown showed the opposite effect. Simultaneously, lncRNA-00072124 affected OSMR function as a ceRNA. Taken together, these results concluded that Mo exposure activated the JAK/STAT axis and induced inflammation mediated by the lncRNA-00072124/miR-308/OSMR crosstalk. The results might provide new views for revealing the toxic effects of excess Mo in duck kidneys.
研究领域:
毒理学
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分子生物学
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动物科学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2022
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IF 4.319
Lei Lei,Jing Zhao,Xue-Qi Liu,Juan Chen,Xiang-Ming Qi,Ling-Ling Xia,Yong-Gui Wu
Introduction Kidney tubular epithelial injury is one of the key factors in the progression of diabetic nephropathy (DN). Wogonin is a kind of flavonoid, which has many pharmacological effects, such as anti-inflammation, anti-oxidation and anti-fibrosis. However, the effect of wogonin in renal tubular epithelial cells during DN is still unknown.Materials and Methods STZ-induced diabetic mice were given doses of wogonin (10, 20, and 40 mg/kg) by intragastric administration for 16 weeks. The metabolic indexes from blood and urine and pathological damage of renal tubules in mice were evaluated. Human tubular epithelial cells (HK-2) were cultured in high glucose (HG) condition containing wogonin (2μM, 4μM, 8μM) for 24 h. Tubular epithelial cell inflammation and autophagic dysfunction both in vivo and in vitro were assessed by Western blot, qRT-PCR, IHC, and IF analyses.Results The treatment of wogonin attenuated urinary albumin and histopathological damage in tubulointerstitium of diabetic mice. We also found that wogonin down-regulated the expression of pro-inflammatory cytokines and autophagic dysfunction in vivo and in vitro. Molecular docking and Cellular Thermal Shift Assay (CETSA) results revealed that mechanistically phosphoinositide 3-kinase (PI3K) was the target of wogonin. We then found that inhibiting PI3K eliminated the protective effect of wogonin. Wogonin regulated autophagy and inflammation via targeting PI3K, the important connection point of PI3K/Akt/NF-κB signaling pathway.Conclusion Our study is the first to demonstrate the novel role of wogonin in mitigating tubulointerstitial fibrosis and renal tubular cell injury via regulating PI3K/Akt/NF-κB signaling pathway-mediated autophagy and inflammation. Wogonin might be a latent remedial drug against tubular epithelial injury in DN by targeting PI3K.
研究领域:
药理学
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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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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2024
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IF 27.4
Ying Kong,Xu Chen,Feng Liu,Jiageng Tang,Yijing Zhang,Xiangxiang Zhang,Luyao Zhang,Tong Zhang,Yaqi Wang,Mengxiao Su,Qixin Zhang,Hanxiang Chen,Di Zhou,Fan Yi,Hong Liu,Yi Fu
As a central metabolic molecule, nicotinamide adenine dinucleotide (NAD + ) can potentially treat acute kidney injury (AKI) and chronic kidney disease (CKD); however, its bioavailability is poor due to short half-life, instability, the deficiency of targeting, and difficulties in transmembrane transport. Here we designed a physiologically adaptive gallic acid-NAD + nanoparticle, that had ultrasmall size and pH-responsiveness, passed through the glomerular filtration membrane to reach injured renal tubules, and efficiently delivered NAD + into the kidneys. With an effective accumulation in the kidneys, it restored renal function, immune microenvironment homeostasis, and mitochondrial homeostasis of AKI mice via the NAD + -Sirt1 axis, and exerted strong antifibrotic effects on the AKI-to-CKD transition by inhibiting TGF-β signaling. It also exhibited excellent stability, biodegradable, and biocompatible properties, ensuring its long-term safety, practicality, and clinical translational feasibility. The present study shows a potential modality of mitochondrial repair and immunomodulation through nanoagents for the efficient and safe treatment of AKI and CKD. This article is protected by copyright. All rights reserved
研究领域:
肾病学
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药学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2018
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IF 2.746
Yifan Zhang,Bei Wang,Huayu Xiong,Wei Wen,Nan Cheng
A ratiometric fluorescence nanoprobe, consisted of water-soluble fluorescent carbon dots (CDs) and 3‑mercapropionic acid-coated cadmium telluride quantum dots (CdTe QDs), was constructed for the detection of epinephrine (EP) and norepinephrine (NE). Under single-wavelength excitation (370 nm), the hybrid nanoprobe possessed dual emission peaks at 460 and 610 nm belongs to CDs and CdTe QDs, respectively. CdTe QDs fluorescence was quenched by EP or NE via electron transfer from QDs to the oxidation products of catecholamines , while the fluorescence intensity of CDs remained almost constant, which provided a ratiometric fluorescence assay for the catecholamines detection. The relative fluorescence intensity ratios were directly proportional to the concentration of catecholamines. Meanwhile, some structural analogues of the target molecules, including dopamine hydrochloride and isoprenaline hydrochloride, had no significant interference for the detection mode. The novel fluorescence detection platform was rapid and convenient, and applied to the detection of EP and NE in human serum samples with satisfactory results.
研究领域:
生物化学
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分析化学
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医学检测
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DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
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IF 2.5
Yuan Ning,Ping Chen,Zhengnan Shen,Xing Liu,Huan Gu
Cisplatin (CDDP) is commonly used as an anticancer drug in clinical practice, but severe nephrotoxicity restricts it from exerting anticancer effects. Natural drugs, such as resveratrol, can alleviate the side effects of cisplatin, but their low solubility and gastrointestinal effects prevent them from working. Herein, we developed nanoparticles for kidney injury consisting of a biocompatible material, zein, as a carrier. HA-Zein/Res NPs were fabricated using low-molecular-weight hyaluronic acid coatings. This preparation is non-cytotoxic to renal tubular epithelial cells and can be used with confidence. Low-molecular-weight hyaluronic acid has inflammation-targeting properties and CDDP damage causes renal inflammation. Owing to this property of the low-molecular-weight hyaluronic acid coating, in vivo imaging experiments in mice demonstrated that the HA-Zein/Res NPs enabled more nanoparticles to accumulate in the renal sites affected by inflammation. Efficient resveratrol delivery alleviated kidney injury, and experiments demonstrated that HA-Zein/Res NPs could treat kidney injury while reducing the serum creatinine and urea nitrogen levels in mice. Collectively, these results indicated that this nanomaterial is a promising agent for reducing the clinical nephrotoxicity of cisplatin.
研究领域:
药学
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生物医学工程
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毒理学
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产品关联
DOI
PubMed
高影响因子
Translational Research
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2024
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IF 6.4
Shan-Shan Li,Qiao-Juan Liu,Jia-Xin Bao,Meng-ting Lu,Bing-Quan Deng,Wen-Wen Li,Chang-Chun Cao
Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence ‘YEVEDYR’) from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to β-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro , overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.
研究领域:
药理学
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肾病学
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分子生物学
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药物发现
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2020
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IF 4.96
Xue-qi Liu,Juan Jin,Zeng Li,Ling Jiang,Yu-hang Dong,Yu-ting Cai,Ming-fei Wu,Jia-nan Wang,Tao-tao Ma,Jia-gen Wen,Ming-ming Liu,Jun Li,Yong-gui Wu,Xiao-ming Meng
Acute kidney injury (AKI), characterized by a rapid decline in renal function, is triggered by an acute inflammatory response that leads to kidney damage . An effective treatment for AKI is lacking. Using in vitro and in vivo AKI models, our laboratory has identified a series of anti-inflammatory molecules and their derivatives. In the current study, we identified the protective role of rutaecarpine (Ru) on renal tubules. We obtained a series of 3-aromatic sulphonamide-substituted Ru derivatives exhibiting enhanced renoprotective and anti-inflammatory function. We identified Compound-6c(Cpd-6c) as having the best activity and examined its protective effect against cisplatin nephropathy both in vivo and in vitro in cisplatin-stimulated tubular epithelial cells (TECs). Our results showed that Cpd-6c restored renal function more effectively than Ru, as evidenced by reduced blood urea nitrogen and serum creatinine levels in mice. Cpd-6c alleviated tubular injury, as shown by PAS staining and molecular analysis of kidney injury molecule-1 (KIM-1), with both prevention and treatment protocols in cisplatin-treated mice. Moreover, Cpd-6c decreased kidney inflammation , oxidative stress and programmed cell death . These results have also been confirmed in cisplatin-treated TECs. Using web-prediction algorithms, molecular docking, and cellular thermal shift assay (CETSA), we identified phosphodiesterase 4B (PDE4B) as a Cpd-6c target. In addition, we firstly found that PDE4B was up-regulated significantly in the serum of AKI patients. After identifying the function of PDE4B in cisplatin-treated tubular epithelial cells by siRNA transfection or PDE4 inhibitor rolipram , we showed that Cpd-6c treatment did not protect against cisplatin-induced injury in PDE4B knockdown TECs, thus indicating that Cpd-6c exerts its renoprotective and anti-oxidative effects via the PDE4B-dependent pathway. Collectively, Cpd-6c might serve as a potential therapeutic agent for AKI and PDE4B may be highly involved in the initiation and progression of AKI.
研究领域:
药理学
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肾病学
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分子生物学
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炎症研究
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药物开发
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2019
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IF 3.585
Guangxu Cao,Shuang Li,Hezhan Shi,Peidi Yin,Jialing Chen,Huifeng Li,Ying Zhong,Li-Ting Diao,Bin Du
Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant features of TIF. MicroRNAs play critical roles during EMT in TIF. However, whether miRNAs can be used as therapeutic targets in TIF therapy remains undetermined. We found that miR-30e, a member of the miR-30 family, is deregulated in TGF-β1-induced PTCs, TIF mice and human fibrotic kidney tissues. Moreover, transcription factors that induce EMT, such as snail, slug, and Zeb2, were direct targets of miR-30e. Using a cell-based miR-30e promoter luciferase reporter system, Schisandrin B (Sch B) was selected for the enhancement of miR-30e transcriptional activity. Our results indicate that Sch B can decrease the expression of snail, slug, and Zeb2, thereby attenuating the EMT of PTCs during TIF by upregulating miR-30e, both in vivo and in vitro. This study shows that miR-30e can serve as a therapeutic target in the treatment of patients with TIF and that Sch B may potentially be used in therapy against renal fibrosis
研究领域:
肾病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
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IF 4
Zhixuan Xie,Luping Wang,Binqi Wang,Xueli Man,Yifei Wang,Taian Jin,Jiahui Ma,Eman Shawky,Samah Elsohafy,Tingfang Ma,Jianhua Li,Juan Jin,Qiang He,Jingkui Tian
Diabetic kidney disease (DKD), a prevalent microvascular complication affecting over 40 % of diabetes patients globally, imposes substantial burdens on healthcare systems through its dual impact on renal function deterioration and cardiovascular mortality. Silkworm pupae (SWP) is an ancient functional food documented in Chinese Materia Medica and Southeast Asian dietary practices, has recently emerged as a research focus due to its unique composition of chitin-derived peptides, antioxidant flavonoids, and angiotensin-converting enzyme inhibitory components. Building upon existing evidence of SWP's anti-inflammatory properties, this investigation evaluated the renoprotective effects of SWP in two representative stages—C2 (the fragile and soft stage) and C4 (nearly eclosion). The results indicated that SWP alleviated renal dysfunction and renal fibrosis through inhibiting apoptosis in DM mice. Notably, C2-stage extracts outperformed C4 counterparts in restoring podocyte integrity. These findings position SWP as a nutraceutical intervention for DKD management.
研究领域:
医学
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营养学
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药理学
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产品关联
DOI
高影响因子
Pharmacology Research & Perspectives
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2025
·Vol. 13
·期 3
·e70094
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IF 2.3
Lei Zhu,Mengru Ding,Lina Liu,Pingchuan Yuan,Taili Shao,Chunyan Liu,Chuanhu Xi,Jun Han,Yuyan Zhou,Donglin Zhang,Guodong Wang
Diabetic nephropathy (DN) is a common complication of diabetes mellitus, with oxidative stress playing a critical role in its development. Burdock fructooligosaccharide (BFO), a major compound in Burdock, exhibits antioxidative effects. However, its mechanisms of action and effects on diabetic nephropathy are not clear enough. This study aims to explore the mechanisms of BFO and its impact on streptozotocin-induced diabetic nephropathy in mice. Male C57BL/6J mice were randomly divided into normal control, DN, and BFO groups. Relevant serum biochemical parameters were detected using kits. Renal injury was evaluated through fluorescence microscopy, histopathology, and transmission electron microscopy. Nrf2/HO-1 signaling was analyzed via quantitative real-time PCR, western blotting, and immunohistochemistry. In DN mice, BFO significantly reduced fasting blood glucose, kidney index, urine protein, serum creatinine, blood urea nitrogen, total cholesterol, triglyceride, and low-density lipoprotein cholesterol, while significantly increasing high-density lipoprotein, SOD, and CAT levels. Additionally, BFO protected against streptozotocin-induced renal injury, restored podocyte function, increased both mRNA and protein expression of Nrf2, HO-1, and Bcl-2, and decreased those of Bax. In conclusion, BFO can be used to treat streptozotocin-induced renal injury in mice and is a promising candidate for diabetic nephropathy treatment.
研究领域:
药理学
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分子生物学
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糖尿病研究
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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）