BMC Nephrology
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2025
·Vol. 26
·期 1
·1-14
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IF 2.4
Lou Yunpeng,Shi Hongguang,Sha Ning,Li Feifei,Gu Xiaofeng,Lin Huiyan
Background Ursodeoxycholic acid (UDCA), traditionally recognized for its hepatoprotective effects, has also shown potential in protecting kidney injury. This study aimed to evaluate the protective effects of UDCA against sepsis-induced acute kidney injury (AKI) and to elucidate the underlying mechanisms.Methods Sixty male C57BL/6 N mice were utilized to establish a sepsis-induced AKI model through intravenous injection of lipopolysaccharides (LPS, 10 mg/kg). UDCA (15, 30, and 60 mg/kg) was administered intraperitoneally once daily for 7 days before LPS injection. Kidney injury was evaluated by HE staining and biochemical markers, including serum creatinine (Cr), blood urea nitrogen (BUN), urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and retinol binding protein (RBP). Oxidative stress parameters and nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway, pro-inflammatory cytokines and nuclear factor-kappa B (NF-κB) pathway were also evaluated. Additionally, HK-2 cells were treated with LPS in vitro, and cell viability and apoptosis were detected using CCK-8 kit and flow cytometer, respectively.Results UDCA significantly attenuated LPS-induced renal histopathological damage and improved renal function, as evidenced by reduction in serum Cr, BUN, and urinary protein levels. UDCA also up-regulated the protein expression of zonula occludens-1 (ZO-1) and Ezrin in the kidney, and reduced the urinary levels of NGAL, KIM-1, NAG, and RBP. Moreover, UDCA inhibited NF-κB p65 phosphorylation and reduced pro-inflammatory cytokines levels (TNF-α, IL-1β, and IL-6) in both serum and kidney. UDCA alleviated oxidative stress by activating the Nrf2/HO-1 pathway in the kidney. In vitro, UDCA reduced LPS-induced cell injury and apoptosis in HK-2 cells, with these protective effects being blocked by the Nrf2 inhibitor ML385.Conclusion sOur present study demonstrated that UDCA exerts protective effects against sepsis-induced AKI by attenuating oxidative stress and inflammation, primarily through the activation of the Nrf2/HO-1 pathway and inhibition of the NF-κB pathway. These findings highlight the therapeutic potential of UDCA in preventing sepsis-induced AKI.
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Bin Wang,Wei Wang,Jingyu Li,Jianjun Li
The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization. The results showed that moderate FSS stimulation significantly upregulated the expression of ZFP36L2 in MC3T3-E1 cells ( p < 0.01). The overexpression of ZFP36L1 markedly enhanced the levels of osteogenic differentiation markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), Osterix, and collagen type I alpha 1 (COL1A1) ( p < 0.01). ZFP36L2 accelerated the degradation of HDAC1 by specifically binding to its 3’ UTR region, thereby fulfilling its function at the post-transcriptional regulatory gene level and promoting the osteogenic differentiation and mineralization fate of cells. Mechanical unloading notably diminished/elevated the expression of ZFP36L2/HDAC1, decreased bone mineral density and bone volume fraction, hindered the release of osteogenic-related factors and vascular endothelial growth factor in callus tissue ( p < 0.01), and was detrimental to fracture healing. Collectively, proper stress stimulation plays a crucial role in facilitating osteogenesis through the promotion of ZFP36L2 and subsequent degradation of HDAC1. Targeting ZFP36L2-HDAC1 axis may provide promising insights to enhance bone defect healing.
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PROCESS SAFETY AND ENVIRONMENTAL PROTECTION
·
2024
·
IF 6.9
Qing Shao,Yiyi Yi,Yuxiang Xie,Jingyi Guo,Haike Yang,Yiqun Chen,Jian Shi,Zizheng Liu
Three zirconium-loaded zeolite (Zr-Z) composites—namely, Zr 4+ -Z, ZrO 2 -Z, and ZrMo 2 O 8 -Z—were prepared by co-precipitation of Zr 4+ , ZrO 2 , and ZrMo 2 O 8 , respectively, with artificial zeolite, and these composites were used for the efficient removal of a representative phosphonate, i.e., 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP). The adsorption efficiency of the three composites for HEDP at an initial concentration of 2 mg/L was more than double that of artificial zeolite. Pseudo-second-order kinetics could fit the adsorption process of the three composites well. The heterogeneous adsorption by Zr 4+ -Z, ZrO 2 -Z, and ZrMo 2 O 8 -Z was determined by using the Sips model. And the theoretical maximum HEDP-adsorption capacities of Zr 4+ -Z, ZrO 2 -Z and ZrMo 2 O 8 -Z were 3.52 mg P/g, 3.38 mg P/g and 3.77 mg P/g, respectively, at 308 K. At pH 4–9, the three Zr-Z composites could achieve efficient and stable HEDP adsorption. Among Co-existing ions (Cl − , HCO 3 − , NO 3 − , SO 4 2− , Ca 2+ , Mg 2+ ), 50 mM HCO 3 − hindered adsorption due to its competition with HEDP. The characterization results show that the adsorption mechanism involved hydrogen bonds, electrostatic attraction, and ligand exchange. In addition, the reusability and column adsorption performance of the Zr-Z composites were explored for the efficient removal of the organic phosphonate HEDP from wastewater in practical applications.
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ENZYME AND MICROBIAL TECHNOLOGY
·
2024
·
IF 3.4
Quan Luo,Guan Zhou,Zhongxia Li,Jiangpeng Dong,Hang Zhao,Huifang Xu,Xuefeng Lu
The chiral amine ( R )-2-(1-aminoethyl)-4-fluorophenol has attracted increasing attentions in recent years in the field of pharmaceuticals because of its important use as a building block in the synthesis of novel anti-tumor drugs targeting tropomyosin receptor kinases. In the present study, a ω-transaminase (ωTA) library consisting of 21 ( R )-enantioselective enzymes was constructed and screened for the asymmetric biosynthesis of ( R )-2-(1-aminoethyl)-4-fluorophenol from its prochiral ketone. Using ( R )-α-methylbenzylamine, D-alanine, or isopropylamine as amino donor, 18 ωTAs were identified with target activity and the enzyme AbTA, which was originally identified from Arthrobacter sp. KNK168, was found to be a potent candidate. The E. coli whole cells expressing AbTA could be used as catalysts. The optimal temperature and pH for the activity were 35–40 °C and pH8.0, respectively. Simple alcohols (such as ethanol, isopropanol, and methanol) and dimethyl sulfoxide were shown to be good cosolvents. High activities were detected when using ethanol and dimethyl sulfoxide at the concentrations of 5–20%. In the scaled-up reaction of 1-liter containing 13 mM ketone substrate, about 50% conversion was achieved in 24 h. 6.4 mM ( R )-2-(1-aminoethyl)-4-fluorophenol was generated. After a simple and efficient process of product isolation and purification (with 98.8% recovery), 0.986 g yellowish powder of the product ( R )-2-(1-aminoethyl)-4-fluorophenol with high ( R )-enantiopurity (up to 100% enantiomeric excess) was obtained. This study established an overall process for the biosynthesis of the high value pharmaceutical chiral amine ( R )-2-(1-aminoethyl)-4-fluorophenol by ωTA. Its applicable potential was exemplified by gram-scale production.
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
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2024
·
IF 3.8
Rui Feng,Zhou Fang,Wei Wang,Tianbo Li,Xiaoyan Hu,Xinlong Yan,Zhongdong Zhang
Direct hydroxylation of benzene to phenol is an environmentally friendly strategy to produce phenol compared with the conventional process. In this work, vanadium-modified titanium silicate-1 (TS-1) with enhanced Lewis acid and charge density were prepared as catalysts for efficient hydroxylation of benzene to phenol in the presence of hydrogen peroxide as an oxidant under mild conditions. The hierarchical TS-1 zeolites with a high framework Ti content were synthesized in the presence of NH4HCO3, and then vanadium doping was used to change the acidity and charge density. It was found that NH4HCO3 favored the titanium substitution of framework sites and nanocrystal stacking of TS-1. Vanadium doping increased the amount of Lewis acid sites and the charge density associated with the framework Ti. The enhancement in acid and electron characteristics boosted the intrinsic catalytic reactivity of Ti-OOH species, which further improved the performances toward benzene hydroxylation. The presented strategy and mechanistic results clarified the relationship between the structure and acidity in TS-1 zeolite. It was also verified that hydroxyl radicals (•OH) rather than superoxide radicals (•O2–) were the reactive agents responsible for the consecutive selective oxidation of benzene.
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ACS Nano
·
2025
·
IF 16
Jinzhao Liu,Meicen Wu,Chang Yang,Yang Zhou,Xinran Qi,Kang Chen,Xiaoping Zhang,Ni Fan,Changyou Zhan,Weiping Wang
Metastasis and immune escape play crucial roles in the progression of colon cancer. Current chemotherapy and immunotherapy treatments have limited effectiveness in reversing the immunologically cold microenvironment. Therefore, it is essential to investigate efficient strategies to enhance the antitumor immunity. In this study, ferroptosis suppressor protein 1 (FSP1) siRNA and photosensitizer Verteporfin were incorporated into the lipid nanoparticle (LNP) formulation for synergistic colon cancer immunotherapy. We first screened the photosensitive LNP formulations using different types of light-responsive small molecules. The selected photosensitive LNPs were further optimized by modulating surface properties to improve cellular uptake and endosomal escape levels in colon cancer cells. Upon light irradiation, the engineered photosensitive LNPs promoted synergistic ferroptosis by FSP1 gene silencing and oxidative stress, thereby causing immunogenic cell death to stimulate dendritic cell maturation and cytotoxic T lymphocyte response. In a bilateral tumor model, photosensitive LNPs exhibited potent antitumor efficacy and robust immunostimulatory effect upon light irradiation, enabling safe and efficient colon cancer treatment. This study demonstrates a synergistic potential between FSP1 gene silencing and photodynamic therapy, expanding the applications of photosensitive LNPs in clinical cancer treatment.
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ACS Sensors
·
2025
·
IF 9.1
Lingxuan Qu,Lingyi Meng,Xilin Sun,Wei Cui,Jin Shi,Yuqi Wang,Qingshuang Hu,Shuping Xu,Bingxin Sun,Chongyang Liang
Aiming at realizing field detection during HIV-1 patient screening in developing countries and point of care testing (POCT) of virus levels in HIV-1 patients receiving medication, an urgent demand for portable nucleic acid detection technology with low cost and sensitivity is raised. To solve this, a CRISPR/Cas13a-based electrochemical detection platform by a multiple combined crRNAs strategy is developed. This sensing platform is based on the Ion Current Rectification regulation through a Porous Anodic Alumina membrane decorated with ssRNA chains, which are trans-cleavage substrates for activated Cas13a and become shorter when the target gene exists, resulting in an altered motion of transmembrane ions. This platform was proven to be feasible and ultrasensitive for tracing the HIV-1 virus by multiple applicable crRNAs combination, and its clinical sample detection limit arrives at 60 copies/μL for HIV-1 patients’ serum samples. Importantly, this method is amplification-free, and its sensitivity is beyond the nonamplification fluorescence-based nucleic acid strategy by one order of magnitude. This sensor is facile to use and cost-effective, and can also be extended to other RNA-based pathogenic microorganism detections. This POCT method facilitates self-monitoring of drug resistance in HIV-1 patients, regardless of medication status.
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BIORESOURCE TECHNOLOGY
·
2025
·
IF 9
Chengyu Yang,Jie Wei,Yixuan Li,Yuanhao Peng,Xuan Wu,Xianrui Zhang,Yingxin Ding,Shumi Lu,Chongling Feng,Chao Huang
Aging-induced surface passivation of nano zero-valent iron (nZVI) significantly diminishes its reactivity for Cr(VI) reduction, thereby impeding its practical application in environmental remediation. Herein, we propose a novel system integrating aged nZVI (AnZVI), Shewanella oneidensis MR-1, and the endogenous electron shuttle riboflavin (RF) to overcome the passivation limitations and enhance Cr(VI) removal. Remarkably, the AnZVI/MR-1/RF system achieved complete removal of 20 mg L − 1 Cr(VI) within 3 h, outperforming AnZVI/MR-1 and AnZVI alone by 23.8 % and 36.6 %, respectively. Mechanistic investigations revealed that RF mediated direct interfacial contact between AnZVI and MR-1, promoting microbial reduction of the AnZVI passivation layer. Electrochemical analyses confirmed RF’s critical role as an electron mediator in accelerating charge transfer between AnZVI and MR-1. Three-dimensional fluorescence mapping (3D-EEM) analysis revealed microbial extracellular polymeric substances (EPS) contributions to chromium immobilization processes. The immobilization of chromium is primarily attributed to the reduction of Cr(VI) to insoluble Cr(III) species, in conjunction with adsorption and surface complexation mechanisms. TEM validated a significant reduction in the thickness of the iron passivation layer, resulting in the exposure of the underlying Fe⁰ core and a resultant enhancement in reductive capacity. This work provides a robust strategy to overcome AnZVI’s limitations by coupling microbial activity with electron shuttling, offering new insights into sustainable remediation via biotic-abiotic synergies.
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Marine Drugs
·
2025
·Vol. 23
·期 8
·294
·
IF 5.4
Jing Lu,Pujing Shi,Yutian Cao,Bingxin Shi,Huilin Shen,Shuai Zhao,Yuchen Gao,Huibing Chi,Lei Wang,Yawei Shi
Mussels are nutrient-rich but perishable, resulting in substantial resource loss. A protease-producing strain (Bacillus velezensisZ-1,Mytilus edulis) isolated from marine sludge was used to hydrolyze mussels, producing Y-1, a hydrolysate with antioxidant activity. In this study, ultrafiltration, gel chromatography, and LC-MS/MS were employed to isolate and identify bioactive peptides from the hydrolysate. The results revealed that the hydrolysate exhibited antioxidant activity, pancreatic cholesterol esterase inhibitory activity, pancreatic lipase inhibitory activity, and α-glucosidase inhibitory activity. Molecular docking using AutoDock Tools 1.5.6 was performed to analyze the interactions of peptides with CD38 and Keap1, leading to the identification of five potentially bioactive peptides: VPPFY, IMLFP, LPFLF, FLPF, and FPRIM. These peptides formed hydrogen bonds and hydrophobic interactions with CD38 and Keap1, demonstrating strong DPPH radical scavenging and superoxide anion radical scavenging capacities. This study highlights the multifunctional bioactive potential of these peptides, offering insights into their therapeutic applications. The findings provide a novel approach for the effective utilization of mussel resources and highlight their potential application value in the development of functional foods.
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ACS Omega
·
2025
·
IF 4.3
Suyun Rao,Ke Xiao,Xuhui Chen,Xufang Sun
Diabetic retinopathy (DR) is a major cause of vision impairment, with diabetic retinal neurodegeneration (DRN) identified as an early pathological feature. Although dopamine (DA) has demonstrated protective effects in various neurodegenerative diseases, its role in DRN is inadequately understood. This study provides evidence that DA can alleviate DRN impairment and elucidates the underlying mechanisms. Diabetes was induced in C57BL/6 mice through a single large dose injection of streptozotocin, and the dopamine precursor l-DOPA was administered via intraperitoneal injection daily for 2 weeks to therapeutically supplement dopamine levels. The results indicated that l-DOPA treatment significantly restored retinal thickness, enhanced the amplitude of oscillatory potentials, and alleviated retinal glial cell activation compared to diabetic mice. In vitro, DA treatment of SH-SY5Y cells under high-glucose stress led to a significant increase in superoxide dismutase activity, with a reduction in malondialdehyde levels, lipid peroxide, and iron ion concentration. Additionally, the expression of GPX4, SLC7A11, ferritin, Nrf2, and HO-1 proteins was upregulated, while the expression of NCOA4 was downregulated. Importantly, the protective effects of DA were significantly attenuated by the Nrf2 inhibitor ML385, confirming the involvement of the Nrf2/HO-1 pathway in DA’s protective mechanism. These findings suggest that DA alleviates oxidative stress, reduces ferroptosis, and improves the retinal function in DRN through the activation of the Nrf2/HO-1 pathway, indicating that DA may represent a novel therapeutic strategy for treating DRN.
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ENVIRONMENTAL RESEARCH
·
2025
·
IF 7.7
Xiang Li,Ping Zhang,Rui Wang,Meng Zhu,Xiaobo Gong,Yucheng Liu
The degradation of separation performance caused by the high abrasion of the continuous separation process puts forward more requirements for the adaptability and durability of the oil-water separation membranes. Herein, inspired by the mortise and tenon (MT) structures of ancient Chinese wooden frame buildings, a superhydrophilic and underwater superoleophobic stainless steel mesh (SSM) membrane with HKUST-1-copper hydroxide (CuOH) interlocking micro-nanostructures (HKUST-1/CuOH) was prepared via electrodeposition and hydrothermal growth techniques. The homogeneous growth of HKUST-1 and CuOH with superhydrophilicity and MT structures provides ultral wettability and durability for the HKUST-1/SSM/CuOH membrane. The optimal HKUST-1/SSM/CuOH membrane exhibited a water contact angle of 0° and an underwater oil contact angle of 156°. The flower-like microstructures improve acid and alkali tolerance, organic solvent tolerance, NaCl solution tolerance, thermal resistance, and UV aging performances. In addition, the HKUST-1 and CuOH coatings showed superior and durable antibacterial performance of the HKUST-1/SSM/CuOH membrane. This membrane with an MT structure demonstrated excellent reusability, showing a water flux of 23818 L·m –2 ·h –1 and UWOCA of 152.09° after 20 cycles. The proposed method is a promising candidate for unrelenting superhydrophobicity and high permeability in oily water treatment.
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BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Lei Wang,Yufeng Bai,Dan Ma,Wenxiu Liu,Zhiyu Shi,Chunnan Liu,Meng Zhao,Huiying Wang,Liying Luo,Jinyu Chi
Hypertension is a risk factor for cardiovascular diseases, primarily through its induction of pathological vascular and ventricular remodeling. TEA domain transcription factor 3 (TEAD3) is a transcription factor highly expressed in myocardial tissues. PDZ domain-containing 1 (PDZK1) has been reported to protect blood vessels. This study discovered decreased expression of TEAD3 and PDZK1 in the aortic tissues of spontaneously hypertensive rats (SHRs). TEAD3 overexpression in SHR vascular smooth muscle cells (VSMCs) driven by the SM22α promoter was achieved through adeno-associated virus delivery. TEAD3 overexpression alleviated aortic remodeling by reducing elastic fiber and collagen deposition. This improvement in vascular structure attenuated hypertension. Subsequently, ventricular remodeling was alleviated by reducing periaortic myocardial fibrosis and left ventricular posterior wall thickness. To elucidate the underlying mechanisms, we overexpressed TEAD3 or PDZK1 in SHR-derived VSMCs via adenoviral infection. Both interventions suppressed VSMC proliferation and migration. Crucially, TEAD3 overexpression upregulated PDZK1 expression, and DNA pull-down assays confirmed direct binding of TEAD3 protein to the PDZK1 promoter. PDZK1 knockdown abolished the anti-proliferative and anti-migratory effects of TEAD3. Further analysis suggested that PDZK1 exerted its protective role by inhibiting the phosphoinositide-3-kinase adaptor protein 1-mediated PI3K/Akt pathway. In conclusion, this study reveals that TEAD3-PDZK1 axis attenuates the abnormal proliferation and migration of VSMCs, which ameliorates aortic and left ventricular remodeling in hypertensive conditions. These findings establish a molecular basis for developing targeted therapies against hypertension-induced cardiovascular remodeling.
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