BIOMEDICINE & PHARMACOTHERAPY
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2019
·
IF 3.743
Zixing Ma,Tengfei Yu,Yan Wu,Dandan Liu,Xiaofei Zhang,Xin Miao,Haiyan Xing,Gang Li
This study is to determine the pharmacological effects of nano-lanthanum hydroxide (nano-LH) in the treatment of hyperphosphatemia, in comparison with other phosphate binders. Rat models of chronic renal failure and hyperphosphatemia were induced by adenine, which were treated with nano-LH (0.15, 0.10, and 0.05 g/Kg/d), lanthanum carbonate (0.30 g/Kg/d), and normal-size lanthanum hydroxide (0.10 g/Kg/d), respectively. To investigate the therapeutic effects, the serum levels of phosphorus, Scr, Ucr, BUN, UUN, PTH, and other hyperphosphatemia-related biochemical indicators were determined. A novel phosphorus-binding agent, nano-LH, was synthesized herein, which was rod-like particle with the length of 30–50 nm, width of 10–20 nm, and diameter of 5–10 nm. In vitro phosphorus binding experiments showed that nano-LH had better binding rate. Pharmacodynamic experiments confirmed that the therapeutic effects of lanthanum-hydroxide (0.10 g/kg/d) were superior to other existing phosphate binders in rat models of hyperphosphatemia, in lowering the blood phosphate level and improving the renal function. In the term of drug safety, our preliminary results showed that the nano-LH at appropriate dose did not cause death cases in mice, and the serum levels of alkaline phosphatase and lactate dehydrogenase were not significantly changed, indicating good oral safety. Nano-LH has high potency compared with several phosphate binders, which might be a promising therapeutic agent for the treatment of hyperphosphatemia in clinic.
研究领域:
药理学
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肾病学
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材料科学
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DOI
PubMed
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2024
·Vol. 121
·期 42
·e2405860121
·
IF 9.4
Sze Hang Kwok,Yuejiang Liu,David Bilder,Jung Kim
Tumors can induce systemic disturbances in distant organs, leading to physiological changes that enhance host morbidity. In Drosophila cancer models, tumors have been known for decades to cause hypervolemic “bloating” of the abdominal cavity. Here we use allograft and transgenic tumors to show that hosts display fluid retention associated with autonomously defective secretory capacity of fly renal tubules, which function analogous to those of the human kidney. Excretion from these organs is blocked by abnormal cells that originate from inappropriate activation of normally quiescent renal stem cells (RSCs). Blockage is initiated by IL-6-like oncokines that perturb renal water-transporting cells and trigger a damage response in RSCs that proceeds pathologically. Thus, a chronic inflammatory state produced by the tumor causes paraneoplastic fluid dysregulation by altering cellular homeostasis of host renal units.
研究领域:
医学
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细胞生物学
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遗传学
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DOI
高影响因子
PHARMACEUTICAL BIOLOGY
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2020
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IF 2.971
Xuemei Liu,Deliang Liu,Youyou Shuai,Huilin Li,Hengxia Zhao,Xin Qu,Shufang Chu,Xuewen Zhang
Context HuoxueJiangtang decoction (ZY) is a traditional Chinese medicine for the treatment of diabetes.Objective The protective effect of ZY on renal injury in diabetic nephropathy rats was investigated in this study.Materials and methods Fifty 4-week-old SPF Wistar male rats were selected to construct diabetic nephropathy model rats (DN) group by continuous high-fat feeding for 4 weeks, followed by a tail vein injection of 30 mg/kg streptozotocin for 1 week. The experimental rats were divided into six groups of 10 rats: normal (control), DN, DN + ZY, DN + metformin, DN + metformin + ZY, and DN + metformin + captopril (positive control) groups. Among the groups, 6.25 g/kg ZY, 250 mg/kg metformin, and 17.5 mg/kg captopril were given to the rats by gavage once a day for 16 weeks. Blood glucose, dietary behaviour, biochemical indicators, and gene expression changes were measured in each group.Results Metformin + ZY treatment significantly lowered blood glucose, water intake, urine total protein, urine albumin, urine volume, serum triglyceride, and serum cholesterol levels in the DN group. The pathological changes of kidney tissue showed that the DN + metformin + ZY group had a protective effect on kidney tissue damage. And ZY and metformin + ZY treatments repaired the expression of genes in the DN group.Discussion and conclusion The ZY and metformin combined treatment showed a clear therapeutic effect on kidney damage in DN. This study provides a potential mechanism for the treatment of diabetic nephropathy with ZY combined with metformin.
研究领域:
中医药学
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糖尿病研究
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肾脏病学
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DOI
高影响因子
Biomed Research International
·
2022
·Vol. 2022
·期 1
·1254824
·
IF 3.246
Jielun Yu,Lichun Zhang,Xiaoshuang Li,Kaixuan Lv,Shiyu Sun,Weihua Wu,Lifeng Ping,Guifang Guo,Wei Tan,Shoudong Guo,Kezhou Wang,Aihua Zhao,Nana Yang
Background . This study was designed to investigate differences in biochemical parameters between mouse and humans after paraquat (PQ) poisoning and develop a suitable animal model for studying organ damage after PQ poisoning. The prognostic factors of PQ-poisoned patients were further analyzed. Methods . Thirty C57BL/6J mice were randomly divided into five groups (control, sham, and 3 PQ doses), and the mouse model was established by intragastric administration of PQ. Physiological indexes such as the body weight, mental state, and mortality rate were observed. Biochemical parameters were analyzed 24 h after PQ poisoning. We also performed a retrospective analysis of clinical data from 29 patients with PQ poisoning admitted to the Emergency Department of the Affiliated Hospital of Taishan Medical College between April 2016 and February 2018. Biochemical parameters were compared between the mouse model and patients with PQ poisoning. Results . In the PQ poisoning mouse model, the lethal dose group PQ360 showed remarkable increases in serum levels of potassium (K + ), carbon dioxide (CO 2 ), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) compared with the nonlethal dose PQ100 and PQ200 groups. The biochemical results of the patients showed that K + and Cl - levels were significantly reduced in the death group compared to the survival group. Levels of ALT, AST, blood urea nitrogen (BUN), and amylase were higher, and the neutrophil-to-lymphocyte ratio (NLR) was increased in the death group compared with the survival group. Conclusions . The combination of age, PQ dosage, K + , Cl - , BUN, ALT, AST, amylase, and NLR can be used to more accurately predict the outcome of patients with PQ poisoning. C57 mice are an appropriate animal model to study liver and kidney functions following PQ exposure.
研究领域:
毒理学
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医学
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实验动物学
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DOI
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
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
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2025
·
IF 4.5
Jinyao Liu,Yingying Pang,Wenyan Li,Juanjuan Sun,Yujie He,Yonghong Guo,Jing Dong
Linezolid, an oxazolidinone antibiotic, is used in patients with liver or kidney disease. However, the effects and mechanisms of hepatic impairment or renal failure on the pharmacokinetics of linezolid and its metabolites (PNU-142586 and PNU-142300) remain unclear. We used carbon tetrachloride-induced impaired hepatic function and 5/6 nephrectomy-induced renal failure rat models to investigate linezolid and metabolite pharmacokinetics. Isolated primary rat hepatocytes were used to evaluate the impact of hepatic impairment or renal failure on linezolid metabolism. Uptake and efflux transport studies were also conducted. The influence of hepatic impairment or renal failure on the pharmacokinetics of linezolid and two metabolites did not differ between intragastric gavage and intravenous administration in rats. Linezolid did not accumulate in the brain, heart, lung, liver, kidney, and small intestinal tissues of the hepatic impairment or renal failure rats. And PNU-142300 did not accumulate in the liver or kidney tissue. Compared to the isolated normal rat hepatocytes, the in vitro hepatic clearance of linezolid in hepatic impairment and renal failure rat hepatocytes decreased by 61.3% and 44.1%, respectively. Organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, Na+-taurocholate co-transporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multidrug resistance-associated protein 2 (MRP2), or multidrug resistance protein 1 (MDR) did not mediate linezolid transport. Hepatic impairment primarily increases linezolid exposure through reduced hepatic metabolism, whereas renal failure increases both linezolid and two metabolites exposure through reduced hepatic metabolism and renal glomerular filtration. These findings guide adjusting the dose of linezolid in patients with hepatic and renal insufficiency.
研究领域:
药理学
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肝脏病学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2025
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IF 5.1
Yijing Zhou,Chengli Lou,Xiuqin Xu,Bo Feng,Xiaoping Fan,Xiangjing Wang
Purpose Ursolic acid (UA) improves diabetic nephropathy (DN), but its regulatory mechanism requires further verification.Methods The bioactive component-target network of UA in DN was determined using a network pharmacology approach. DN mice (STZ-diabetic C57BL/6 mice, n = 8/group, 4 weeks) were treated with UA (25 mg/kg and 100 mg/kg) and the JAK agonist RO8191 (2 mg/kg). The DN cell model (high glucose-injured NRK-52E cells) was treated with UA (10 and 50 µM) and RO8191 (2 μM) for 24 h. The molecular mechanisms by which UA acts were further verified in vivo and in vitro.Results UA treatment ameliorated the general state of the DN mouse model, as characterized by the attenuation of weight loss and downregulation of fasting blood glucose (FBG) and fasting serum insulin (FINS) levels (all P < 0.05). Renal pathological changes and impaired renal function (increased levels of Scr, BUN, and UAER) were also improved by UA treatment (all P < 0.05). In vitro, UA increased the viability of DN cells in vitro (P < 0.001). Concurrently, UA remarkably downregulated the levels of ROS, SOD, and iron and up-regulated the levels of MDA, GPX4, and SLC7A11 (all P < 0.05) in vivo and in vitro. Mechanistically, activation of the JAK2-STAT3 pathway with the agonist RO8191 significantly reduced UA’s anti-ferroptosis and anti-oxidative effects of UA.Conclusion UA protected against DN by blocking JAK2/STAT3-mediated ferroptosis.
研究领域:
药理学
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分子生物学
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生物信息学
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糖尿病研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Yongmei Li,Fengxin Zheng,Shiqi Zhong,Kunlu Zhao,Hui Liao,Jiacheng Liang,Qiang Zheng,Huicong Wu,Shifan Zhang,Ying Cao,Ting Wu,Jianxin Pang
Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro . Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC 50 value of 7.37 ± 0.66 μM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.
研究领域:
肾病学
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药理学
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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
ANALYTICAL BIOCHEMISTRY
·
2024
·
IF 2.6
Nanfei Yang,Yuncheng Bei,Yahong Huang,Wei Zheng,Jiehua Ma,Jiangqiong Ke
Serum Cystatin C (CysC) is an impressive marker for early diagnosis of renal dysfunction. In this work, we established a novel electrochemical immunosensor based on Fe 3 O 4 /AuNPs-MWCNTs@PDA nanocomposite for the detection of CysC. The Fe 3 O 4 /AuNPs-MWCNTs@PDA nanozyme complex by polydopamine encapsulation can not only carry massive detection antibodies, but also bind the electroactive substance toluidine blue (TB) through electrostatic adsorption. By immobilizing AuNPs onto the electrode to bind the capture antibody (Ab1), we constructed a sandwich electrochemical immunosensor with low cost, high sensitivity, and repeatability. The detection range is 3.9–125.0 ng/mL with a significant linear relationship between the current peak difference (ip) and logarithm of the CysC concentration. Moreover, the detection limit of the immunosensor is 0.157 ng/mL. We have successfully utilized this novel immunosensor to detect CysC in human serum samples, and these results have implications for its potential use in clinical application.
研究领域:
生物医学工程
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分析化学
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临床诊断
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DOI
PubMed
高影响因子
THERAPEUTIC DRUG MONITORING
·
2025
·
IF 2.4
Ma Zhiyuan,Bai Mengru,Shen Shuying,Zhou Junshan,Dong Rong,Zhang Jiangjun,Weng Yayun,Li Li,Li Yongchen,Liu Dan,Yan Wei,Lin Nengming,Xia Jianmei
Background: Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (C trough ) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course. Methods: A high-performance liquid chromatography-tandem mass spectrometry assay was developed and validated to measure the nirmatrelvir/ritonavir C trough . Correlation analyses were performed to identify the variables influencing nirmatrelvir/ritonavir C trough . Results: Among the 110 patients, 100% had plasma concentrations above the antiviral in vitro 90% effective concentration. The median C trough of nirmatrelvir was 4.55 mcg/mL (15.6× 90% effective concentration), ranging from 0.65 to 12.44 mcg/mL. Nirmatrelvir C trough in normal and mild renal impairment cohorts were comparable (4.09 ± 1.97 mcg/mL and 4.57 ± 2.21 mcg/mL) but significantly increased in the moderate renal impairment cohort (6.41 ± 2.31 mcg/mL). Sex, age, and obesity were not significantly associated with nirmatrelvir exposure. Conclusions: Nirmatrelvir C trough was high in Chinese patients with COVID-19, and therapeutic drug monitoring should not be routinely recommended, except in patients with renal impairment.
研究领域:
药理学
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传染病
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临床研究
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2019
·Vol. 10
·期 11
·7142-7151
·
IF 3.241
Wenwen Zhao,Xi Zeng,Fancheng Meng,Xiaolin Bi,Dahai Xu,Xiuping Chen,Qiu Li,Yantao Han
We report here an acidic polysaccharide, namely RSP-3, which ameliorates acute kidney injury and is obtained from Sanguisorba officinalis. We extracted and purified two polysaccharides from this herb based on the acidity and screened them for their effect in regulating the immunological activity of macrophages. Among them, RSP-3 exhibited significant anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated macrophages by decreasing TNF-α and IL-6 levels. Subsequently, we found that RSP-3 suppressed ER stress, reduced ROS production and blocked NF-κBp65 translocation. After fully characterizing RSP-3 with a series of analytical technologies, we tested its anti-acute kidney injury (AKI) effect in vivo. In a murine AKI model induced by LPS, treatment with RSP-3 effectively ameliorated renal function. Besides, it decreased the levels of TNF-α and IL-6 in serum and reduced macrophage infiltration in injured kidney tissue. In sum, RSP-3, with a significant protective effect against AKI by showing anti-inflammatory activity, may become a meaningful drug candidate for treatment of AKI.
研究领域:
药理学
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免疫学
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分子生物学
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肾病学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 16
·e70800
·
IF 4.2
Xiangling Yi,Liming Wang,Xiao-yue Wang,Yu Fang,Jiarui Liu,Kehong Chen,Ya-ni He,Jia Chen
Renal recovery following acute kidney injury (AKI) is a key determinant of long-term prognosis, while non-recovery significantly increases the risk of chronic kidney disease and progression to end-stage renal disease. Although cell cycle arrest is implicated in renal non-recovery and fibrosis, its association with decoy receptor 2 (DcR2) remains unclear. In this study, we evaluated 139 patients with biopsy-confirmed AKI, defining renal non-recovery as a ≥ 50% increase in baseline serum creatinine (Cr) or the initiation of dialysis. Patients were divided into recovery ( n = 79) and non-recovery ( n = 60) groups. Urinary DcR2/creatinine (uDcR2/Cr) levels were significantly higher in non-recovery cases, with an area under the curve of 0.733 and a diagnostic cut-off of 378 ng/gCr. Elevated uDcR2/Cr predicted poor renal survival and was independently correlated with non-recovery. In mouse models of ischemia–reperfusion-induced AKI, increased urinary and tubular DcR2 levels were also associated with impaired recovery. Proteomics analysis revealed GSK3b enrichment in cell cycle pathways. Functional studies showed that DcR2 mediated cell cycle arrest through GSK3b/cyclin D1 signalling. In conclusion, DcR2 functions as a biomarker of cell cycle arrest and renal recovery, offering both diagnostic and mechanistic insights, and may serve as a potential therapeutic target in AKI.
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产品关联
DOI
PubMed
高影响因子
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