PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Hongmin Lu,Yue Zhang,Xin Zhang,Ruoqi Wang,Tiantian Guo,Qi Wang,Hongjing Zhao,Mingwei Xing
Environmental pollution caused by arsenic or its compounds is called arsenic pollution. Arsenic pollution mainly comes from people mining and smelting arsenic compounds. In addition, arsenic compounds' widespread use and production of arsenic-containing pesticides, arsenic-rich water used to irrigate farms, or high arsenic levels in foods caused by coal burning are all sources of arsenic contamination. Arsenic contamination poses a significant threat to global public health. It is reported that exposure to arsenic can induce severe renal injury. However, the underlying mechanism needs to be clarified. In this study, the arsenic exposure model in vivo and in vitro was used to explore the mechanism of arsenic-induced renal injury, especially the role of ferroptosis and its regulatory mechanism, and then to evaluate its anti-pollution effect by supplementing zinc. The results showed that arsenic significantly induced ferroptosis, characterized by up-regulating the expression of YAP and TFR in kidney and CIK cells and then increasing the levels of Fe 2+ and ROS, lipid peroxidation, and iron metabolism. Microscopic observation revealed the shrinkage of mitochondria and the increase in membrane density. In addition, molecular docking and inhibitor experiments further confirmed that arsenic is involved in the process of ferroptosis by activating YAP and TFR. These results clarify the harmful effects of arsenic on carp kidneys and its mechanism and highlight the critical interactions between the YAP-TFR pathway, ROS, and ferroptosis. Importantly, this study found that zinc can reduce ferroptosis caused by the arsenic-activated YAP-TFR pathway by inhibiting YAP activation and lipid peroxidation.
研究领域:
环境科学
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毒理学
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水生生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Siqi Yu,Fudong Wang,Yuan Zhang,Xiaofeng Wang,Hongyu Zhao,Qiang Zheng
Autophagy inhibition induced by paraquat (PQ) poisoning is an important factor causing multi-organ damage, including renal tissue. Dihydrocapsaicin (DHC), the main active ingredient in chili peppers, was reported to induce autophagy, but its effect on PQ-induced AKI remains unclear. Rats were intraperitoneally injected with 25 mg/kg PQ to establish AKI rat model followed immediately by DHC administration (2.5, 5, or 10 mg/kg, i.p.). Rat renal tubular epithelial cells were exposed to PQ (300 μM) in combination with DHC (25, 50, or 100 μM) for 24 h. The results showed that DHC treatment attenuated PQ-induced renal injury and dysfunction while suppressing apoptosis and oxidative stress in vivo and in vitro . Furthermore, DHC administration induced autophagy—a protective mechanism against oxidative stress and apoptosis—as demonstrated by: 1) increased autophagosome/autophagolysosome formation, 2) upregulated LC3-II and autophagy-related gene 7 expressions and reduced p62 protein level. Blocking of autophagy by 3-methyladenine (3-MA) reversed the effects of DHC. Interestingly, transcription factor sex determining region Y-box 9 (Sox9) and autophagy inducer Sestrin2 RNA levels were increased by DHC treatment. Sox9 activated Sestrin2 transcription through direct binding to its promoter region. Sox9 or Sestrin2 silencing reversed the effects of DHC. Collectively, our findings demonstrate that DHC attenuates PQ-induced AKI via Sox9/Sestrin2 axis-mediated autophagy, indicating therapeutic utility of DHC against AKI.
研究领域:
药理学
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毒理学
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分子生物学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2025
·
IF 4.2
He Li,Peipei Meng,Yuhang Meng,Yige Yang,Wensheng Zheng,Hongdong Huang,Zhigang Zhao
Renal fibrosis represents a critical pathological hallmark in progressive chronic kidney disease (CKD), yet effective therapeutic strategies remain elusive. Emerging evidence suggests that impaired mitophagy contributes to its pathogenesis. This study investigated whether ruxolitinib alleviates renal fibrosis by enhancing PINK1/Parkin-mediated mitophagy. Network pharmacology was employed to explore the potential regulatory mechanisms of ruxolitinib in renal fibrosis treatment, revealing that ruxolitinib might exert therapeutic effects through modulation of inflammation, oxidative stress and mitophagy. Subsequent in vivo and in vitro studies demonstrated that ruxolitinib treatment not only attenuated renal fibrosis progression but also reduced inflammatory responses and oxidative stress while enhancing mitophagic activity. Mechanistically, the enhancement of mitochondrial autophagy and the amelioration of renal fibrosis by ruxolitinib might be mediated via the PINK1/Parkin pathway. These results suggest that ruxolitinib may ameliorate renal fibrosis by activating PINK1/Parkin-mediated mitophagy, providing new perspectives for CKD therapeutic development.
研究领域:
药理学
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细胞生物学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Haijing Tian,Ruo Wu,Qi Lv,Jie Shi,Xiaoqin Guo,Duo Li,Chunli Liu,Qi Li,Weijia Zheng,Haojun Fan,Xuexin Duan,Qiannan Xue
Blood potassium and creatinine levels are critical indicators for managing chronic kidney disease (CKD). In response to the need for home monitoring and emergency care, point-of-care diagnostic technologies based on microsystems have emerged, nevertheless they remain limited in portability and speed for direct in whole blood samples measurement. To enable direct blood detection of potassium and creatinine for effective CKD management, this study presents a novel on-chip self-driven dual-channel optical microsensor designed for real-time monitoring of potassium and creatinine levels in whole blood. Utilizing 3D printing technology to design and fabricate microstructures, and integrating microchannels with a filtration layer, this microsensor requires only 10 μL of blood for single-pass sample filtration and dual-parameter detection. A novel passive blood sample pumping method is proposed, utilizing internal and external pressure differentials along with internal hydrophilic properties to facilitate sample flow into the detection chambers. Light-emitting diodes (LEDs) and photodiodes, positioned on either side of the detection chamber, are employed to measure the concentrations of blood indicators. The detection results can be instantly handheld read and uploaded to the cloud via intelligent terminal, enabling seamless follow-up diagnostics and treatment. Through multiple rounds of testing on animal serum samples, whole blood samples, and real porcine blood samples, this microsensor demonstrated excellent linearity and accuracy. This innovative microsensor, designed for direct testing from a minimal volume of whole blood, holds significant potential for improving CKD management, offering a portable, reliable alternative for preoperative diagnostics and home-based chronic disease monitoring.
研究领域:
医学工程
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生物医学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Huaxi Liu,Weijie Chen,Chunyang Tian,Yijian Deng,Liangwo Xu,Wenkun Ouyang,Renjie Qiu,Yanting You,Pingping Jiang,Lin Zhou,Jingru Cheng,Hiu Yee Kwan,Xiaoshan Zhao,Xiaomin Sun
Background IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p -Akt. Conclusion This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.
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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中医药
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Juan Chen,Zi-yun Hu,Yu Ma,Shan Jiang,Jiu-yu Yin,Yu-kai Wang,Yong-gui Wu,Xue-qi Liu
Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae ( Euodia rutaecarpa (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-β1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-β1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.
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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糖尿病
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 1
·e70051
·
IF 4.2
Qiwen Shi,Tao Zhou,Wenjun Hou,Yuqi Zhou,Shufen Deng,Ying Song
Diabetes nephropathy (DN) is a severe diabetic chronic microvascular complication and the major cause of end-stage renal disease (ESRD). Our study aimed to investigate the effects of isoliquiritigenin (ISL) a natural flavonoid compound on DN and to explore the underlying mechanisms. The db/db mice were received intragastric treatments of ISL (5, 10, or 20 mg/kg), vehicle or positive drug metformin (300 mg/kg) once a day for 12 weeks, and the db/m mice treated with vehicle were used as controls. ISL significantly ameliorated pathological changes and functional injury in the kidneys of db/db mice in a dose-dependent manner. The administration of 20 mg/kg ISL reduced the levels of serum creatinine (Scr; 49.0 ± 1.7 vs. 56.9 ± 2.9 μmol/L; p < 0.01), blood urine nitrogen (BUN; 9.6 ± 1.3 vs. 12.0 ± 1.1 mmol/L; p < 0.05), albumin to creatinine ratio (ACR; 1925.8 ± 798.1 vs. 4269.4 ± 925.6 μg/mg; p < 0.01) and urinary albumin (276.2 ± 39.9 vs. 576.9 ± 108.9 μg; p < 0.05). Further study identified advanced glycation end product (AGE)–receptor for AGE (RAGE) axis as a target of ISL. ISL (20 mg/kg) lowered renal AGE level (2.5 ± 0.5 vs. 3.8 ± 0.6 μg/mg; p < 0.01) and RAGE expression, leading to improvements in renal fibrosis, oxidative stress, and inflammation. To sum up, our study demonstrated that ISL displayed preventive effects on the experimental model of DN through suppressing AGE–RAGE pathway, and provided some insights into the application of ISL in DN treatment.
研究领域:
药理学
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内分泌学
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肾病学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Renxiang Yuan,Shuqian Yang,Ding Wang,Caini Yu,Peirong Li,Qi Jiang,Yangqian Luo,Tingting Meng,Fuqiang Hu,Tong Yu,Yupeng Liu,Hong Yuan
Ischemia-reperfusion (IR)-induced acute kidney injury (AKI) is a life-threatening form of AKI frequently observed in clinical settings, such as hemorrhagic shock, kidney transplantation, and cardiovascular surgery. Targeting renal antioxidant therapy may represent an effective strategy against IR-induced AKI. Bilirubin (BR), a specific superoxide anion scavenger, faces limitations in clinical application due to its poor water solubility and hepatic metabolism pathway. In this study, we prepared bilirubin nanocrystals (BRNCs), which demonstrated potent antioxidant effects in vitro experiments. To enhance renal targeting, BRNCs were encapsulated in poly(ethylene glycol) (PEG)-modified lipid nanoparticle (BRNC-LNP). In vivo distribution studies revealed that BRNC-LNP effectively circumvented hepatic metabolism and exhibited enhanced renal accumulation compared to BRNC. In vivo efficacy evaluation revealed superior therapeutic outcomes with BRNC-LNP versus BRNC in AKI mice. These findings suggest that BRNC-LNP may serve as a promising therapeutic strategy for IR-induced AKI by reducing the level of hepatic metabolism and promoting renal targeting.
研究领域:
纳米医学
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药剂学
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肾脏病学
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抗氧化治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Tong Yu,Yeqing Wang,Yi Kong,Jianwei Wang,Hong Yun,Yunchao Wang,Fuqiang Hu,Zhongxin Zhu,Hong Yuan
Drug delivery system (DDS) is an important branch of pharmaceutics. Rational modification of the physicochemical properties of DDSs can further improve their targeting efficiency. Herein, a bionic DDS is reported for AKI that is scRNA-seq-guided, custom-designed, and prepared, targeting the Key Cell Subtype for Pathological Progression (KCS-PP) of acute kidney injury (AKI). Specifically, scRNA-seq is utilized to identify a specific renal tubular epithelial cell subtype (PTIs) as the KCS-PP for AKI from numerous cellular subtypes. Additionally, specific cell adhesion molecules (VCAM1 and ICAM1) are identified as the Targeting Drug Delivery Mediators (TDDMs) for PTIs from a list of 1000 marker genes of PTIs. Based on this progress, PTI-targeting bionic DDS, named BRNCs@AMMOs is custom-designed and prepared, and used them for AKI treatment in vitro and in vivo. In vitro, BRNCs@AMMOs shows that its adhesion ability in PTI model cells is 3.2 times that in normal cells. In vivo, 6 h after renal pelvis injection, the MFI of BRNCs@AMMOs-DiI in AKI kidneys is 3.7 times that of sham kidneys. The findings demonstrate that BRNCs@AMMOs exhibits prolonged retention in PTI model cells and AKI kidneys. Overall, the custom-designed and prepared PTI-targeting bionic DDS, may promote the customized design and preparation of DDSs for different diseases and targets, is reported.
研究领域:
药剂学
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药物递送
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分子医学
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纳米技术
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转化医学
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产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2025
·Vol. 43
·期 7
·e70100
·
IF 2.7
Jie Xiao,Weiwei He,Xiaoyang Fang,Rongrong Zhou,Ao Huang,Yikun Wang,Qing Du,Linben Xu,Fei Cheng,Hongliang Zeng
Smilax glabra Roxb. is a natural herb, exhibits significant uric acid lowering effect in clinical. However, the specific mechanism remains to be clarified. To study this problem, intraperitoneal injection of Potassium oxazinate (PO) and Hypoxanthine (HX) induced hyperuricemia in mice model, and mice were divided into control, model, and model plus ethanol extract (TFL), ethyl acetate extract (TFL_Y), n-butanol extract (TFL_Z), and residual aqueous extract (TFL_S) of Smilax glabra Roxb., And then a follow-up test. Furthermore, possible pharmacological components were detected by UPLC-Q-TOF-MS. The results showed that serum creatinine, blood urea nitrogen, d -lactate, lipopolysaccharide levels and xanthine oxidase. They could upregulate renal OAT1 and ABCG2, downregulate renal URAT1, reduce renal tubular dilation and interstitial inflammatory cell infiltration. Moreover, they could upregulate intestinal tight junction proteins, increase the number of intestinal goblet cells, and repair damage to the intestinal barrier. Moreover, 16S rRNA sequencing analysis showed that restored intestinal microbiota by increasing probiotic bacteria ( Candidatus Saccharimonas , Lachnospiraceae NK4A136_group ) and reducing pathogenic bacteria ( Helicobacter ). Furthermore, it was found that all control taint flavonoids such as Neoastalbin, Astibin, Neoiosastilbin, Isoastalbin, Engeletin, and Isoengeletin. Summary This study elucidates the multi-target mechanisms underlying the urate-lowering effects of Smilax glabra Roxb., including modulation of renal urate transporters (OAT1/ABCG2/URAT1), improvement of intestinal barrier function, and restoration of gut microbiota homeostasis. Flavonoid (e.g., neoastilbin and isoastilbin) were identified as the main active ingredients through UHPLC-Q-TOF-MS analysis. For the first time, we comprehensively revealed the “gut-kidney axis” mechanism of Smilax glabra Roxb., identified critical targets in renal transporters and gut microbiota, discovered bioactive flavonoid markers for quality control, and provided theoretical support for its clinical application and drug development.
研究领域:
药理学
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民族药理学
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植物化学
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微生物学
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肾脏病学
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代谢性疾病
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOLOGY
·
2024
·
IF 3.2
Nan Yang,Yue Zhang,Peiyao Ren,Li Zhao,Danna Zheng,Lanjun Fu,Juan Jin
Although LncRNA AA465934 expression is reduced in high glucose (HG)-treated podocytes, its role in HG-mediated podocyte injury and diabetic nephropathy (DN) remains unknown. Herein, we investigated the role of AA465934 in HG-mediated podocyte injury and DN using a spontaneous type II diabetic nephropathy (T2DN) model. The model was created by injecting AA465934 overexpressed adeno-associated virus (AAV) or control into mice. The levels of renal function, proteinuria, renal structural lesions, and podocyte apoptosis were then examined. Furthermore, AA465934 and autophagy levels, as well as tristetraprolin (TTP) and high mobility group box 1 (HMGB1) expression changes were detected. We also observed podocyte injury and the binding ability of TTP to E3 ligase proviral insertion in murine lymphomas 2 (PIM2), AA465934, or HMGB1. According to the results, AA465934 improved DN progression and podocyte damage in T2DN mice. In addition, AA465934 bound to TTP and inhibited its degradation by blocking TTP-PIM2 binding. Notably, TTP knock-down blocked the ameliorating effects of AA465934 and TTP bound HMGB1 mRNA, reducing its expression. Overexpression of HMGB1 inhibited the ability of AA465934 and TTP to improve podocyte injury. Furthermore, AA465934 bound TTP, inhibiting TTP-PIM2 binding, thereby suppressing TTP degradation, downregulating HMGB1, and reversing autophagy downregulation, ultimately alleviating HG-mediated podocyte injury and DN. Based on these findings, we deduced that the AA465934/TTP/HMGB1/autophagy axis could be a therapeutic avenue for managing podocyte injury and DN.
研究领域:
分子生物学
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肾病学
·
糖尿病研究
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DOI
高影响因子
FITOTERAPIA
·
2025
·
IF 2.6
Weijian Qu,Yi Lan,Zhuoqing Cheng,Han Yuan,Honghong Zhan,Xiaozhong Lan,Zhihua Liao,Guowei Wang,Min Chen
Diabetic kidney disease (DKD) is a common complication in patients with diabetes, and glycolipid metabolism disorders are an important cause of DKD. The root of Oxybaphus himalaicus (Edgew.) Heimerl is a traditional Tibetan medicine commonly used to treat kidney-related diseases. Nevertheless, contemporary pharmacological investigations into O. himalaicus , especially those associated with the treatment of renal disorders, remain scarce. The objective of this research was to explore the pharmaceutical impacts and mechanisms of action of O. himalaicus in the treatment of DKD. The active fraction and potential pharmacological effects of O. himalaicus were determined through network pharmacology. Then, in vivo and in vitro efficacy and mechanism studies were conducted through streptozotocin-induced DKD mice and high glucose-induced HK-2 cells. Network pharmacology research speculated the ethyl acetate (EA) fraction as the main active component of O. himalaicus for treating DKD. In vivo and in vitro experiments showed that EA reduces renal lipotoxicity by upregulating PPARα pathway proteins, enhancing fatty acid oxidation (FAO), and downregulating inflammatory factors such as TNF-α and IL-6. Molecular docking studies revealed that the active components of EA with a high affinity for PPARα are mainly rotenoid compounds. EA mitigates DKD through the activation of PPARα, which serves to augment FAO, abate lipid accumulation, and impede the expression of inflammatory factors. Among these, rotenoids may be the main active components that exert pharmacological effects.
研究领域:
药理学
·
内分泌学
·
肾脏病学
✓ 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）