3 Biotech
·
2021
·Vol. 11
·期 12
·1-13
·
IF 2.406
Tang Miaolong,Cai Jimin,Wang Yan,Huan Zhirong,Yao Hao,Xu Ce,Ge Xin,Song Sheng
Hemorrhage shock (HS) is a major threat to patients with trauma and spontaneous bleeding, resulting in multi-organ failure including the kidney. Tyrosine kinase nonreceptor 1 (TNK1) has been shown to be upregulated in the kidney of experimental HS and patients with severe trauma . The study aims to investigate the role of TNK1 and the underlying mechanism in HS-induced kidney injury. A model of HS was established with femoral artery bloodletting, followed by resuscitation in Sprague–Dawley rats. Renal expression of TNK1 was abnormally induced by HS in rats. Knockdown of TNK1 alleviated HS-induced cell apoptosis and the level of proinflammatory cytokines (TNF-α, IL-6 and IL-1β) in the kidney. The expression of M1 macrophage markers (CD86 and iNOS) and the activation of STAT1 were inhibited by TNK1 knockdown in HS rats. In vitro, human monocyte THP-1 cells were treated with 20 ng/mL interferon-gamma plus 100 ng/mL lipopolysaccharide to induce M1 polarization. TNK1 knockdown exerted inhibitory effect on macrophage M1 polarization, M1-type inflammatory cytokine production and STAT1 activation in THP-1 cells. In conclusion, downregulation of TNK1 alleviates HS-induced kidney injury by suppressing macrophage M1 polarization, inflammation and kidney cell apoptosis, in which the deactivation of STAT1 signaling may be involved.
研究领域:
医学
·
免疫学
·
分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Xu Wenhao,Ye Shiqi,Liu Wangrui,Guo Huaqi,Zhang Linhui,Wei Shiyin,Anwaier Aihetaimujiang,Chang Kun,Malafaia Guilherme,Zhang Hailiang,Ye Dingwei,Wei Gang
In recent years, the environmental health issue of microplastics has aroused an increasingly significant concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, little is known about the essential effects of PS-MPs with high-fat diet (HFD) on renal development and microenvironment. In this study, we provided the single-cell transcriptomic landscape of the kidney microenvironment induced by PS-MPs and HFD in mouse models by unbiased single-cell RNA sequencing (scRNA-seq). The kidney injury cell atlases in mice were evaluated after continued PS-MPs exposure, or HFD treated for 35 days. Results showed that PS-MPs plus HFD treatment aggravated the kidney injury and profibrotic microenvironment, reshaping mouse kidney cellular components. First, we found that PS-MPs plus HFD treatment acted on extracellular matrix organization of renal epithelial cells, specifically the proximal and distal convoluted tubule cells, to inhibit renal development and induce ROS-driven carcinogenesis. Second, PS-MPs plus HFD treatment induced activated PI3K-Akt, MAPK, and IL-17 signaling pathways in endothelial cells. Besides, PS-MPs plus HFD treatment markedly increased the proportions of CD8 + effector T cells and proliferating T cells. Notably, mononuclear phagocytes exhibited substantial remodeling and enriched in oxidative phosphorylation and chemical carcinogenesis pathways after PS-MPs plus HFD treatment, typified by alterations tissue-resident M2-like PF4 + macrophages. Multispectral immunofluorescence and immunohistochemistry identified PF4 + macrophages in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissues, indicating that activate PF4 + macrophages might regulate the profibrotic and pro-tumorigenic microenvironment after renal injury. In conclusion, this study first systematically revealed molecular variation of renal cells and immune cells in mice kidney microenvironment induced by PS-MPs and HFD with the scRNA-seq approach, which provided a molecular basis for decoding the effects of PS-MPs on genitourinary injury and understanding their potential profibrotic and carcinogenesis in mammals. Graphical Abstract
研究领域:
环境健康
·
分子生物学
·
免疫学
·
肾病学
·
癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Danping Liu,Yi Wang,Hongyi Zhao,Xiuwen Xia,Jie Zhou,Li Xie,Pei Guo,Weihong Li
Ethnopharmacological relevance Wenyang-Tianjing-Jieyu Decoction (WTJD) is a traditional Chinese herbal formula with a history of ethnopharmacological use for depression, specifically targeting the Kidney-Yang deficiency (KYD) subtype. Its therapeutic rationale is well-documented in classical Chinese materia medica. However, the molecular mechanisms underpinning its clinical efficacy remain largely unelucidated. Aim of the study This study aimed to investigate the therapeutic effects and elucidate the underlying molecular mechanisms of WTJD, a traditional herbal formula, in ameliorating KYD-type depression in a rat model. Materials and methods The chemical profile of WTJD was characterized using UPLC-Q-Exactive/MS. Using a rat model of KYD-type depression established by combining Phellodendri chinensis Cortex decoction gavage, cold exposure, and chronic unpredictable mild stress (CUMS), we evaluated the therapeutic effects of WTJD. This randomized controlled study included five groups (n = 7/group): Control, Model, Fluoxetine, WTJD-Medium, and WTJD-High, with a 3-week intervention period. Furthermore, we integrated network pharmacology with hippocampal transcriptomics to identify key therapeutic targets, which converged on the FOXO signaling pathway. Finally, the predicted mechanism was validated by assessing key protein phosphorylation, nuclear translocation, hippocampal neurogenesis, and synaptic plasticity. Moreover, the regulatory mechanism was further corroborated in vitro using LPS-induced PC12 cells treated with WTJD-containing serum and the AKT inhibitor MK-2206. Results WTJD administration significantly ameliorated both the KYD phenotype and depressive-like behaviors in the rat model. Strikingly, both network pharmacology and hippocampal transcriptomic analyses converged on the FOXO signaling pathway as the central therapeutic target. Mechanistically, it was confirmed that WTJD activated the FOXO pathway by inhibiting AKT phosphorylation, which in turn promoted the nuclear translocation of FOXO4. Consistently, in vitro assays demonstrated that WTJD-containing serum protected PC12 cells and rescued downstream gene expression by modulating the FOXO signaling pathway, effects that were mimicked by AKT inhibition. This cascade of molecular events ultimately restored impaired adult hippocampal neurogenesis and synaptic plasticity. Conclusion WTJD ameliorates KYD-type depression by modulating the hippocampal FOXO signaling pathway to restore neurogenesis and synaptic plasticity. These results validate the FOXO pathway as a high-value target for subtype-specific antidepressant drug design.
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2024
·
IF 4.2
Liu Yang,Yan Xu,Jian Pan,Renjie Li,Chao Lan,Dongshan Zhang
Background Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity, as well as increased medical expenses. The molecular mechanisms underlying ischemia-reperfusion (I/R)-induced AKI remain unclear.Methods and Results We applied an RT-qPCR assay to measure the expression of mmu-lncRNA129814, hsa-lncRNA582795, and miRNA-494-5p, immunoblotting to detect IL-1α and cleaved caspase-3 expression, and TUNEL staining and flow cytometry (FCM) to evaluate apoptosis. The experiments were conducted using BUMPT and HK-2 cells, as well as C57BL/6J mice. Mechanistically, mmu-lncRNA129814 could sponge miRNA-494-5p and upregulate IL-1α expression to promote cell apoptosis. Furthermore, knockdown of mmu-lncRNA129814 ameliorated I/R-induced progression of AKI by targeting the miRNA-494-5p/IL-1α pathways. Interestingly, hsa-lncRNA582795, a homolog of mmu-lncRNA129814, also promoted I/R-stimulated HK-2 cell apoptosis and AKI progression by regulating the miRNA-494-5p/IL-1α axis. Finally, we found that patients with I/R-induced AKI exhibited significantly elevated plasma and urinary levels of hsa-lncRNA582795 compared to those who underwent ischemia-reperfusion without developing AKI. Spearman’s test demonstrated a significant correlation between serum creatinine and plasma hsa-lncRNA582795 in I/R patients. Plasma hsa-lncRNA582795 showed high sensitivity but low specificity (86.7%) compared to urinary hsa-lncRNA582795.Conclusion The mmu-lncRNA129814/hsa-lncRNA582795/miRNA-494-5p/IL-1α axis was found to modulate the progression of ischemic AKI, and hsa-lncRNA582795 could act as a diagnosis biomarker and potential therapy target of I/R-induced AKI.
研究领域:
肾病学
·
分子生物学
·
医学遗传学
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DOI
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 41
·期 4
·1383-1392
·
IF 5.104
Deng Qing-Ping,Wang Mao-Jie,Zeng Xing,Chen George Gong,Huang Run-Yue
Background: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. Methods: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα). The animal model was confirmed by the hematoxylin and eosin (H&E) method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST), alanine amino transferase (ALT), urea and creatinine were carried out. Results: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS) as well as proliferating cell nuclear antigen (PCNA), recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. Conclusions: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Rui Hao,Tian Li,Beibei Zhou,Jiaxin Shao,Weibo Zhao,Beibei Jiao,Xia Sun,Jian Zhang
Background : Bushen Huoxue Formula (BSHXF), a traditional Chinese medicine, effectively treats premature ovarian insufficiency (POI) by modulating of lipid metabolism. Purpose : This study aimed to investigate the underlying mechanism through which BSHXF improves POI by regulating lipid metabolism. Methods Network pharmacology identified potential pathways associated with BSHXF in POI. A POI rat model was induced using subcutaneous corticosterone injections and treated with BSHXF to assess its efficacy. The impact of BSHXF on lipid metabolism, autophagy, and the LRP6/β-catenin signaling pathway was evaluated in these rats. Additionally, palmitic acid (PA)-induced granulosa cells (KGN cells) were used in vitro . A LRP6 inhibitor (Salinomycin sodium salt, Sal) was applied to these cells, followed by a series of molecular biology experiments to elucidate the specific regulatory role of BSHXF on lipid metabolism. Results : Network pharmacology analysis indicated that the Wnt/β-catenin signaling pathway is a potential target of BSHXF in POI. In vivo , BSHXF alleviated POI-like symptoms in rats, reduced lipid accumulation, suppressed excessive autophagy, and activated the LRP6/β-catenin signaling pathway. In vitro , Sal inhibited the ability of BSHXF-containing serum to activate LRP6/β-catenin signaling, reduce lipid accumulation, and counteract excessive autophagy in PA-induced KGN cells. This was accompanied by increased expression of LRP6 and β-catenin, enhanced lipogenesis, elevated lipid droplet formation, decreased lipid catabolism, and oxidation, and enhanced autophagic flux. Cycloheximide chase and Western blot analyses further confirmed that BSHXF stabilizes LRP6 by inhibiting its ubiquitin-proteasomal degradation. Conclusions : BSHXF activates LRP6/β-catenin signaling pathway by inhibiting the ubiquitination degradation of LRP6, thereby improving POI. This study reveals that BSHXF may improve POI by modulating LRP6 stability, thereby affecting lipid metabolism.
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产品关联
DOI
PubMed
高影响因子
Journal of Biophotonics
·
2023
·
IF 2.8
Kexin Hu,Qimeng Sun,Ruifen Chen,Tinghao Xu,Yuncheng Li,Lili Chen,Aidong Wang,Hejing Qi,Danni Shao,Huanning Yue,Yaning Wang,Ziqi Tang,Yi Wang,Chunfeng Liu,Haijun Lv,Fen Wang,Huizhong Xu
Recently, fluorescent covalent staining methods have been developed for visualization of anatomical structures in cells and tissues. Coupled with expansion microscopy, these stains revealed various ultrastructural details. However, the covalently stainable chemical groups have been limited to amines, carbohydrates, and thiols. Here, we developed procedures for covalently labeling tissues for carboxylate and phosphate groups, utilizing carbodiimide crosslinker chemistry. In porcine kidney tissues, the carboxylate and phosphate stain provides 1.8–4.8-fold higher signal intensity than those from the three existing stains. In cancer cells, such stain allows 2–8-fold more accurate identification of nucleoli than the amine stain. In expansion microscopy samples, such stain reveals a variety of sub-cellular structures in tissues when combined with the amine stain. Such stain also allows imaging of lipid-based structures in cultured cells. With these advantages, this new covalent staining method further expands the toolset for fluorescent visualization of histology.
研究领域:
细胞生物学
·
分子生物学
·
显微镜技术
·
组织学
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DOI
PubMed
高影响因子
JOURNAL OF FLUORESCENCE
·
2024
·
IF 2.6
Wang Yaru,Li Shuhuai,Ma Xionghui,Pang Chaohai,Wu Yuwei,Wang Mingyue,Li Bei,Liu Sixin
Fluorescence intensity and selective recognition ability are crucial factors in determining the analytical techniques for fluorescent probes. In this study, a core–shell fluorescent material, composed of silver nanoparticles@nitrogen-doped graphene quantum dots (Ag NPs@N/GQDs), was synthesised using mango leaves as the raw material through a thermal cracking method, resulting in strong fluorescence luminescence intensity. By employing noradrenaline as a template molecule and using a surface molecular imprinting technique, a molecularly imprinted membrane (MIP) was formed on the surface of the fluorescent material, that was subsequently eluted to obtain a highly specific, fluorescent probe capable of recognising noradrenaline. The probe captured various concentrations of noradrenaline using the MIP, which decreased the fluorescence intensity. Then a method for detecting trace amounts of noradrenaline was established. This method exhibited a linear range from 0.5 –700 pM with a detection limit of 0.154 pM. The proposed method was implemented in banana samples. Satisfactory recoveries were confirmed at four different concentrations. The method presented a relative standard deviation (RSD) of less than 5.0%.
研究领域:
分析化学
·
生物医学
·
食品科学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 46
·期 1
·e14007
·
IF 2.72
Jing Liu,Zhongan Zhu,Yuhang Yang,Michael Adu-Frimpong,Lin Chen,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu
A liposome of Licochalcone A (LCA-Liposomes) was purposively prepared to ameliorate the low in vivo availability and efficacy of LCA. Physical characterization of LCA-Liposomes was carried out mainly by determining particle size, morphology, zeta potential (Z-potential), and efficiency of LCA encapsulation (EE) via appropriate techniques. Also, the rate of LCA release in vitro and distribution in vivo (plasma and tissues) was evaluated. Evaluation of the antirenal activity of LCA-liposomes was carried out by establishing chronic renal failure (CRF) model in mice through intragastric administration of adenine (200 mg/kg) and subsequent determination of biochemical parameters and examination of tissue sections. Respectively, the mean size of liposomal particles, Z-potential and EE of LCA-Liposomes were 71.78 ± 0.99 nm, −38.49 ± 0.06 mV, and 97.67 ± 1.72%. Pharmacokinetic and tissue distribution studies showed that LCA-Liposomes could improve the availability of LCA in the blood and tissues, whereas during pharmacodynamics studies, the liposome effectively improved the therapeutic effect of LCA on CRF mice by potentially protecting the renal tissues while exhibiting antioxidant activity. In conclusion, LCA-Liposomes could effectively improve the bioavailability of LCA and provide platform for the development of LCA-related functional products. Practical applications As a traditional Chinese medicine, licorice is widely used in food and pharmaceutical industries. LCA is a small molecule flavonoid extracted from the root of licorice. In this study, LCA was loaded on liposome carriers, which significantly improved the water solubility and oral bioavailability, and proved that LCA-Liposomes have certain therapeutic effects on chronic renal failure, thereby providing a basis for the development of LCA into drugs or functional food in the future.
研究领域:
药剂学
·
药理学
·
分子药理学
·
药物代谢
·
纳米医学
·
中药药理学
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DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Wenhao Dong,Yipeng Ren,Zhixue Bai,Jun Jiao,Yuan Chen,Bingkai Han,Qiang Chen
An innovative epinephrine sensor was fabricated by integrating tetrahexahedral (THH) Au-Pd core–shell nanocrystals on reduced graphene oxide (rGO) nanosheets . Furthermore, the nanocomposites combined the large specific areas of rGO with the high-index facets and excellent electrocatalytic activity of the THH Au-Pd nanocrystals, and the nanocomposites were an essential adapter for detecting epinephrine. In the present work, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to identify and characterize these unique nanocomposites, and the results revealed that a unique THH Au-Pd/rGO core–shell nanostructure was synthesized successfully. To further explore the electrochemical behaviors of these nanomaterials at a GC electrode, we applied cyclic voltammetry (CV), differential pulse voltammetry (DPV) and amperometry to study the conductivity and electrocatalytic activity of the proposed sensor, and the results suggested that the sensor based on Au-Pd/rGO presented a lower limit of detection (0.0012 μM at a signal to noise ratio of 3), wide linear detection range (0.001 µM to 1000 µM), and extraordinary selectivity and reproducibility. Moreover, the data showed that the sensor possessed good stability and acceptable accuracy to detect epinephrine in human serum samples. In summary, this work is not only a potential way to manufacture various nonenzymatic sensors but also a significant contribution to further studies in catalysis, cell fuel cells and other relevant applications.
研究领域:
材料科学
·
分析化学
·
生物医学工程
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DOI
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 23
·7307
·
IF 4.412
Dong Zhang,Mojiao Zhao,Yumei Li,Dafang Zhang,Yong Yang,Lijing Li
Xanthine oxidase (XOD) inhibition has long been considered an effective anti-hyperuricemia strategy. To identify effective natural XOD inhibitors with little side effects, we performed a XOD inhibitory assay-coupled isolation of compounds fromSmilacis Glabrae Rhizoma(SGR), a traditional Chinese medicine frequently prescribed as anti-hyperuricemia agent for centuries. Through the in vitro XOD inhibitory assay, we obtained a novel XOD inhibitor, 5-O-caffeoylshikimic acid (#1, 5OCSA) with IC50of 13.96 μM, as well as two known XOD inhibitors, quercetin (#3) and astilbin (#6). Meanwhile, we performed in silico molecular docking and found 5OCSA could interact with the active sites of XOD (PDB ID: 3NVY) with a binding energy of −8.6 kcal/mol, suggesting 5OCSA inhibits XOD by binding with its active site. To evaluate the in vivo effects on XOD, we generated a hyperuricemia mice model by intraperitoneal injection of potassium oxonate (300 mg/kg) and oral gavage of hypoxanthine (500 mg/kg) for 7 days. 5OCSA could inhibit both hepatic and serum XOD in vivo, together with an improvement of histological and multiple serological parameters in kidney injury and HUA. Collectively, our results suggested that 5OCSA may be developed into a safe and effective XOD inhibitor based on in vitro, in silico and in vivo evidence.Keywords:Smilacis Glabrae Rhizoma;5-O-caffeoylshikimic acid;potassium oxonate;hyperuricemia;XOD inhibitor
研究领域:
药理学
·
药物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2017
·
IF 3.234
Xueting Bai,Junying Wang,Xiaoyu Mu,Jiang Yang,Haixia Liu,Fujuan Xu,Yaqi Jing,Lingfang Liu,Xuhui Xue,Haitao Dai,Qiang Liu,Yuan-Ming Sun,Changlong Liu,Xiao-Dong Zhang
Two-dimensional WS2 materials have attracted wide attention in condensed physics and materials science due to its unique geometric and electronic structures. Particularly, WS2 shows extraordinary catalytic activities when its size decreases to ultrasmall, which provides potential opportunities for medical applications. In this work, WS2 quantum dots with strong catalytic properties were used for in vitro and in vivo protection from ionizing radiation induced cell damages. WS2 quantum dots possess unique optical properties of blue photoluminescence emission and excitation-wavelength dependent emission profiles. In vitro studies showed that cell viability can be considerably improved and cellular reactive oxygen species (ROS) can be removed by WS2 quantum dots. In vivo studies showed WS2 quantum dots can effectively protect the hematopoietic system and DNA from damages caused by high-energy radiation through removing whole-body excessive ROS. Furthermore, WS2 quantum dots showed nearly 80% renal clearance within 24 h post injection and did not cause any obvious toxicities in up to 30 days after treatment.
研究领域:
材料科学
·
生物医学工程
·
辐射防护
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
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