BIOCHEMICAL PHARMACOLOGY
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2025
·
IF 5.6
Jing Zhang,Xuewei Yang,Xing Zhao,Gang Luo,Hong Jiang
Renal fibrosis is recognized as a critical pathway leading to end-stage renal disease in nearly all cases of chronic kidney disease (CKD). Analysis of the gene expression omnibus (GEO) database revealed that the transcription factor Krüppel-like factor 3 (KLF3) was elevated in kidney tissues of CKD patients, however, its specific role in CKD-associated renal fibrosis is yet to be deciphered. This study aimed to investigate the function of KLF3 on unilateral ureteral obstruction (UUO) mice and transforming growth factor-β1 (TGF-β1)-stimulated HK2 cells. Our data demonstrated that KLF3 was remarkably upregulated in the renal cortex of UUO mice and TGF-β1-treated HK-2 cells. We further confirmed that the upregulation of KLF3 was associated with its N6-methyladenosine (m6A) methylation modification. Knockdown of METTL14 reduced m6A methylation level of KLF3 and inhibited its mRNA stability. In vivo results suggested that KLF3 knockdown alleviated the pathological changes in renal tissues triggered by UUO. Additionally, KLF3 silencing mitigated renal fibrosis both in vivo and in vitro , as accompanied by decreased expression of Collagen I, Vimentin, α-SMA and Fibronectin. Mechanistically, KLF3 transcription activated dimethylarginine dimethylaminohydroxylase 2 (DDAH2) and upregulated its expression. Rescue experiments substantiated that DDAH2 overexpression eliminated the effect of KLF3 knockdown on renal fibrosis. Collectively, our findings suggest that inhibition of KLF3 may serve as a potential strategy to prevent CKD-associated renal fibrosis.
研究领域:
分子生物学
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肾脏病学
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DOI
PubMed
高影响因子
JOURNAL OF LIPOSOME RESEARCH
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2025
·
IF 4.3
Qinyang Hua,Qilong Wang,Xue Wang,Xia Jiang,Mingjie Gong,Jiaying Li,Tingyuan Li,Xiaowen Wang,Xia Cao,Jiangnan Yu,Elmurat Toreniyazov,Bin Zong,Ximing Xu,Feng Shi,Michael Adu-Frimpong
The clinical application of Isoquercitrin (IQ) is limited by its low water solubility and short retention time in the body, despite its diverse pharmacological effects. To address these issues, we prepared polyethylene glycol (PEG)-modified IQ liposomes (IQ-L) using the thin film dispersion method and optimized the formulation through a combination of One Factor at a Time (OFAT) method and response surface experiments. Characterization of the IQ-L that was prepared using the optimal formulation revealed a particle size of 185.48 nm, a polydispersity index of 0.252, a zeta potential of −33.88 mV, and an impressive encapsulation efficiency of 97.84%. In vitro release studies showed a significantly higher cumulative release rate for IQ-L compared to free IQ. Pharmacokinetic evaluations in rats demonstrated a 4.54-fold increase in the area under the concentration-time curve, a 1.63-fold prolongation of the half-life, and a 2.07-fold increase in peak concentration for IQ-L compared to unmodified IQ. Moreover, assessments of renal function in a mouse model indicated promising therapeutic effects. In summary, the PEG-modified liposome system greatly improved the solubility and in vivo retention time of IQ, thus making it a potential clinical agent for the treatment of chronic kidney disease (CKD).
研究领域:
药剂学
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肾脏病学
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Physiological Investigation
·
2024
·Vol. 67
·期 2
·69
·
IF 0
Wang Chunli,Xu Mingzhi,Bai Yafei,Pan Mingjiao,Qi Yonghui,Chen Ruman
Vascular calcification (VC), a major complication in chronic kidney disease (CKD), is predominantly driven by osteoblastic differentiation. Recent studies have highlighted the crucial role of microRNAs in CKD’s pathogenesis. Here, our research focused on the effects of miR-204-5p and its molecular mechanisms within VC. We initially found a notable decrease in miR-204-5p levels in human aortic vascular smooth muscle cells stimulated with inorganic phosphate, using this as a VC model in vitro. Following the overexpression of miR-204-5p, a decrease in VC was observed, as indicated by alizarin red S staining and measurements of calcium content. This decrease was accompanied by lower levels of the osteogenic marker, runt-related transcription factor 2, and higher levels of α-smooth muscle actin, a marker of contractility. Further investigation showed that calcium/calmodulin-dependent protein kinase 1 (CAMK1), which is a predicted target of miR-204-5p, promotes VC. Conversely, overexpressing miR-204-5p reduced VC by suppressing CAMK1 activity. Overexpressing miR-204-5p also effectively mitigated aortic calcification in an in vivo rat model. In summary, our research indicated that targeting the miR-204-5p/CAMK1 pathway could be a viable strategy for mitigating VC in CKD patients.
研究领域:
分子生物学
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病理学
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心血管科学
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遗传学
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DOI
ANALYTICA CHIMICA ACTA
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2025
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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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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Wentao Zhou,Caini Yu,Tingting Meng,Qi Jiang,Fangying Yu,Hong Yuan
Cellular senescence disrupts tissue homeostasis and diminishes physiological integrity, leading to the accumulation of senescent cells (SCs) in multiple senescence‐associated diseases such as chronic kidney disease (CKD). Treatment of SCs has been approved to be a feasible approach to these diseases. However, curing SCs in different cell types remains challenging. In this study, we leveraged the high expression of glutaminase (GLS) in SCs to develop a drug delivery system utilizing γ-poly glutamic acid (γ-PGA) conjugated with octadecylamine (ODA) to encapsulate rapamycin (RP), resulting in a GLS-responsive drug delivery system, designated as RPPO. In a model of drug induced senescence, the γ-PGA component of RPPO was degraded by cellular GLS, facilitating the release of encapsulated RP and rejuvenating SCs by restoring the autophagic capacity. Additionally, in a model of CKD in mice, RPPO enhanced recovery by rejuvenating SCs, reducing fibrosis, and alleviating inflammation. Thus, this senescent cell-responsive drug delivery system presents a novel approach for the treatment of CKD.
研究领域:
医学
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药学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2016
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IF 3.169
Yong-hui Li,Yin-feng Tan,Hong-die Cai,Jun-qing Zhang
Alpinia oxyphylla (Zingiberaceae) is a well-known medicinal plant. Its fruit (“Yi-Zhi-Ren” in Chinese) is used as an anti-diuretic and traditionally used for the treatment of enuresis and reduce urination. Chronic kidney disease (CKD) is a disease with the characteristic of the slowly loss of kidney function and has a prevalence of up to 7–10% in adults. Recent advances in its etiology and pathogenesis are providing more speculative hypotheses focused on integral systems. Using a UPLC–QTOF-MS/MS-based metabolomic platform, we explored the changes of metabolic profiling in plasma/urine simultaneously between chronic kidney disease (CKD) induced from adenine excess and the protective effects of A. oxyphylla extract (AOE). The total twenty-one metabolites (twelve in urine and nine in plasma), up-regulated or down-regulated, were identified and contributed to CKD progress. Among these biomarkers, agmatine, CAMP, 7-methylguanine, hippuric acid, indoxyl sulfate, asparagines, kynurenic acid and p -cresol sulfate were restored back to the control-like level after the treatment of AOE (p < 0.05 or 0.01), These findings may be promising to yield a valuable insight into the pathophysiology of CKD and serve as characteristics to explain the mechanisms of AOE.
研究领域:
药理学
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代谢组学
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肾脏病学
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DOI
PubMed
高影响因子
JOURNAL OF PATHOLOGY
·
2022
·Vol. 258
·期 3
·213-226
·
IF 9.883
Zirong Lan,An Chen,Li Li,Yuanzhi Ye,Qingchun Liang,Qianqian Dong,Siyi Wang,Mingwei Fu,Yining Li,Xiaoyu Liu,Zhenyu Zhu,Jing-Song Ou,Xiaozhong Qiu,Lihe Lu,Jianyun Yan
Vascular calcification is an actively regulated process resembling bone formation and contributes to the cardiovascular morbidity and mortality of chronic kidney disease (CKD). However, an effective therapy for vascular calcification is still lacking. The ketone body β-hydroxybutyrate (BHB) has been demonstrated to have health-promoting effects including anti-inflammation and cardiovascular protective effects. However, whether BHB protects against vascular calcification in CKD remains unclear. In this study, Alizarin Red staining and calcium content assay showed that BHB reduced calcification of vascular smooth muscle cells (VSMCs) and arterial rings. Of note, compared with CKD patients without thoracic calcification, serum BHB levels were lower in CKD patients with thoracic calcification. Supplementation with 1,3-butanediol (1,3-B), the precursor of BHB, attenuated aortic calcification in CKD rats and VitD3-overloaded mice. Furthermore, RNA-seq analysis revealed that BHB downregulated HDAC9, which was further confirmed by RT-qPCR and western blot analysis. Both pharmacological inhibition and knockdown of HDAC9 attenuated calcification of human VSMCs, while overexpression of HDAC9 exacerbated calcification of VSMCs and aortic rings, indicating that HDAC9 promotes vascular calcification under CKD conditions. Of note, BHB treatment antagonized HDAC9-induced vascular calcification. In addition, HDAC9 overexpression activated the NF-κB signaling pathway and inhibition of NF-κB attenuated HDAC9-induced VSMC calcification, suggesting that HDAC9 promotes vascular calcification via activation of NF-κB. In conclusion, our study demonstrates that BHB supplementation inhibits vascular calcification in CKD via modulation of the HDAC9-dependent NF-κB signaling pathway. Moreover, we unveil a crucial mechanistic role of HDAC9 in vascular calcification under CKD conditions; thus, nutritional intervention or pharmacological approaches to enhance BHB levels could act as promising therapeutic strategies to target HDAC9 for the treatment of vascular calcification in CKD. © 2022 The Pathological Society of Great Britain and Ireland.
研究领域:
医学
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分子生物学
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DOI
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2025
·
IF 2.5
Hong Xu,Yiran Hua,Haiqin Li,Jianhua Wang,Gaohong Liu,Xiaochun Li
The chronic kidney disease (CKD) poses a serious threat to human health. Long-term monitoring of urine is important in the management of CKD. Currently, the accuracy and stability of smartphone-based colorimetric analysis of urine indicators are limited due to the impact of different image-taking conditions on captured digital images of urine test strips. Herein, an attachment-free colorimetric correction analysis system (CCAS for short), consisting of a self-designed urine test strip array and an Android application integrated with an image calibration algorithm, were proposed for quantitative analysis of nine urine indicators. With this system the impact of image-taking conditions on captured digital image were largely corrected, and thus the accuracy and stability for digital image colorimetric analysis of urine test strip were improved. The limits of detection of creatinine, nitrite, urinary calcium, microalbumin, bilirubin, protein, pH, haemoglobin, and glucose were 1.607 mmol/L, 1.232 μmol/L, 0.297 mmol/L, 11.116 mg/L, 1.155 μmol/L, 0.042 g/L, 0.044, 0.058 mg/L, and 0.122 mmol/L, respectively. The accuracy of CCAS was validated by analyzing artificial urine samples and 143 clinical urine samples. As an accurate, low-cost and reliable system, CCAS addresses specific needs for patients to monitor their urine whenever and wherever possible with only their own smartphone.
研究领域:
医学工程
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肾脏病学
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移动健康
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Xuemin Xian,Xin Zhao,Xingchen Zhou,Hanfang Liu,Changxi Li,Xinquan Wu,Yuhang Chen,Keyue Ye,Hongwei Yang,Mingxi Li,Jianyun Yan,Xiuli Zhang
Vascular calcification (VC) is a common complication of chronic kidney disease (CKD), with oxidative stress identified as a key contributor to VC progression. Honokiol (HKL), a biphenolic compound derived from plants, has been found to be effective in treating various models of cardiovascular disease through the mitigation of oxidative stress. However, its effects on VC remain unexplored. To elucidate the effects of HKL on VC, a CKD rat model, a vitamin D 3 -overload-induced mouse model of vascular calcification, and a high-phosphate-induced human vascular smooth muscle cell (VSMC) calcification model were established. Calcification levels were assessed using Alizarin Red staining, calcium quantification, and Western blotting of osteogenic markers. Oxidative stress was assessed by measuring reactive oxygen species. Furthermore, transcriptome sequencing was employed to identify molecules and pathways affected by HKL. HKL was found to significantly reduce calcification in both in vivo and in vitro models. It also mitigated oxidative stress induced by high phosphate in human VSMCs. Mechanistically, HKL upregulated heme oxygenase-1 (HMOX-1), thereby inhibiting oxidative stress and reducing calcification. Pharmacological inhibition of HMOX-1 counteracted the protective effect of HKL on vascular calcification. In summary, the findings suggest that HKL ameliorates VC by upregulating HMOX-1 and decreasing oxidative stress.
研究领域:
医学
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药理学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 4
·e23470
·
IF 4.4
Guangyu Zhou,Pai Liu,Chen Zhang,Qun Huang,Zixia Zhao,Si Wu,Detian Li,Hongbo Liu
Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with β-glycerophosphate (β-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and β-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that β-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in β-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.
研究领域:
心血管疾病
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慢性肾病
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分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xing Zhang,Ye Hu,Haofei Li,Junlin Chen,Chuhan Lv,Xiaobao Yang,Fanna Liu,Xin Chen,Hua Dong
Chronic kidney disease (CKD) is a major public health disease that threatens human life. To address the urgent need for high-risk populations and patients to monitor CKD in a non-invasive and real-time manner, a novel wearable porous eutectogel with high-performance NH 3 enrichment and sensing is developed for the first time to rapidly and precisely detect the NH 3 concentration in the breath. Herein an eutectogel (EG) containing N-acryloyl glycinamide (NAGA), glycerol (Gly), choline chloride (ChCl) and bromocresol green (BCG) is constructed via digital light processing (DLP) 3D printing. The abundant internal hydrogen bond network in EG/BCG material shows a strong affinity towards NH 3 , leading to remarkable NH 3 capture and enrichment when exposing to the exhaled breath. On the other hand, its porous structure increases significantly the residence time and absorption rate of NH 3 . As a consequence, this new NH 3 sensing material displays fast NH 3 response time (3 s), low detection limit (0.5 ppm), wide NH 3 sensing range (0–10 ppm), high specificity and high temperature/humidity stability, leading to obvious color change within the range of NH 3 concentration in the exhaled breath of healthy individuals and CKD patients. Simply by introducing EG/BCG into a regular medical mask, wearing it for 10 min and monitoring its color change, early screening and continuous monitoring of CKD become feasible by correlating NH 3 concentration with blood urea nitrogen (BUN) levels. With the aid of artificial intelligence (deep learning) algorithms, the detection accuracy of 96.5 % has been achieved in practical clinic test.
研究领域:
医学
·
材料科学
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人工智能
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产品关联
DOI
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 3
Jiaxin Peng,Jing Chen,Mengran Wu,Tao He,Xiaojuan Guo,Qiangguo Ao,Ling Chen
Acute kidney injury (AKI) is widely recognized as an important risk factor for chronic kidney disease (CKD), and preventing or delaying the AKI-CKD transition represents a critical therapeutic priority. Ergothioneine (EGT), a natural antioxidant, has demonstrated renal protective potential, but its role in attenuating the AKI-CKD transition remains unclear. To investigate this, an AKI-CKD mouse model was constructed by administering multiple small-dose injections of cisplatin. Mice were divided into control, AKI-CKD, and AKI-CKD + EGT groups. The protective function of EGT was assessed using biochemical indexes and histopathology. Proteomic analysis and network pharmacology were applied to identify potential EGT targets, which were further verified by molecular docking and Western blot. Results showed that EGT significantly mitigated renal damage in AKI-CKD mice. Proteomic analysis identified 35 differentially expressed proteins (DEPs) potentially associated with EGT treatment, with GO and KEGG enrichment implicating complement activation as a key pathway. Protein-protein interaction (PPI) network analysis, topology analyses, and molecular docking identified C4B and PON1 as potential core EGT targets. In conclusion, EGT attenuates AKI-CKD progression by targeting C4B and PON1, modulating complement activation and oxidative stress. These findings highlight the therapeutic potential of EGT and provide novel insights for drug development targeting the AKI-CKD transition.
研究领域:
生物学
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医学
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药理学
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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）