CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Huijuan Ma,Qi Shu,Peiyao Wang,Ruilin Qin,Sijia Li,Huan Xu
Exposure to formaldehyde (FA) has been indicated to be positively correlated with increased incidence of allergic asthma in many epidemiological and experimental studies. However, few studies have ever addressed the molecular basis of the correlation. In the present study, it was found that inhaling 2.0 mg/m 3 FA for 2 weeks could exacerbate the pulmonary inflammation and mucus over-accumulation in OVA-induced murine asthmatic model. The pro-inflammatory cytokines, such as IL-1β, TNF-α, IL-6 and IL-8, were increased in lung and serum of FA-exposed asthmatic mice. The contribution of HIF-1α signaling in FA-exacerbated allergic asthma was confirmed by bioinformatic analysis. HIF-1α and its downstream proteins, which are known as mediators of glycolysis, were found to be upregulated by 50 μM FA, and the FA-enhanced of glycolysis was reversed by inhibition of HIF-1α with PX-478 in vitro and YC-1 in vivo . Furthermore, it was confirmed that inhibition of HIF-1α signaling could restrain the macrophagic inflammatory responses and asthma exacerbation induced by FA. Collectively, these results revealed that FA could exacerbate asthma through the potentiation of HIF-1α-mediated inflammatory responses in macrophages, which also indicated the universal roles of FA-triggered macrophage metabolic and functional alterations in inflammatory or allergic diseases.
研究领域:
免疫学
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呼吸病学
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毒理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Dian-Chao Cao,Yan Liang,Yang Guo,Dong-Yang Wu,Na-Na Wang,Yan-Mei Li,Hong-Fang Sun,Qin Wang,Xia Zhang,Yong-Liang Chi,Pei-Pei Sun,You-Jie Li,Ran-Ran Wang,Ping-Yu Wang,Shu-Yang Xie,Ning Xie
Purpose This study aims to develop an innovative delivery system, (Q+M/MnOx)@Clip, to enhance the bioavailability and therapeutic efficacy of quercetin both in tumor treatment and pain alleviation.Methods The (Q+M/MnOx)@Clip system was evaluated to enhance the release of quercetin, investigate its ability to target cancer cells, alleviate tumor hypoxia, and improve the efficacy of chemodynamic therapy (CDT). Tumor hypoxia markers and immune response activation were assessed, along with the impact on pain relief biomarkers.Results (Q+M/MnOx)@Clip successfully mitigated tumor hypoxia, facilitated controlled Q release, and enhanced CDT in vitro and in vivo. The system demonstrated a dual therapeutic effect: anti-tumor immunity and significant cancer pain relief by reducing HIF-1α and VEGF-A levels.Conclusion The novel (Q+M/MnOx)@Clip system represents a promising advancement in nanomedicine, improving the bioavailability of quercetin and offering a more effective approach to cancer treatment by downregulation of HIF-1α and VEGF-A. This study demonstrates the potential for combining anti-tumor immunity with pain relief for triple-negative breast cancer therapy.
研究领域:
肿瘤学
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 40
·期 8
·1153-1161
·
IF 2.997
Zhang Youyou,Yu Yalei,Zhang Jie,Guan Chuhuai,Liu Liang,Ren Liang
Early diagnosis of cantharidin-induced myocardial injury is the key to reduce the fatality rate in clinical practice. The purpose of the present study was to explore biomarkers that can be used for the prediction and diagnosis of cantharidin-induced myocardial injury. Of 65 male Sprague-Dawley rats weighing 200-230 g, 25 rats were divided into five groups according to the administration dose of cantharidin (0, 1.34, 2.67, 4 and 5.34 mg/kg; n = 5 per group) and the other 40 rats were treated with 2.67 mg/kg cantharidin and divided into nine groups according to the administration time (0, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours; n = 4 per group). Pathological changes of hypoxia, necrosis and inflammation were confirmed in heart samples that were exposed to cantharidin by hematoxylin-eosin staining and overall scores of pathological changes among heart samples in cantharidin exposure groups showed an increasing trend compared with in the control group. Coexpression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and caspase9 was shown in the myocardium by immunofluorescence staining. Western blotting results showed that expression of VEGF, HIF-1α and caspase9 in cantharidin-treated rat hearts showed an increasing trend compared with in the control group. Results of enzyme-linked immunosorbent assay suggested that plasma levels of troponin T (TN-T), VEGF and HIF-1α were elevated at different intervals after cantharidin administration, and VEGF and HIF-1α had a significant linear relationship with TN-T that was verified by multiple linear regression analysis. Preliminary results serve to illustrate that TN-T, VEGF and HIF-1α might be valuable molecular markers in cantharidin-induced myocardial injury and that diagnostic accuracy needs to be studied further.
研究领域:
毒理学
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药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2024
·
IF 2.7
Hongmei Chang,Siqi Zhao,Yuzhu Lei,Yunhua Hu,Yizhong Yan,Guanling Song
Titanium dioxide nanoparticles (nano-TiO 2 ) can cause a reduction in sperm counts, and lactate production in Sertoli cells plays a key role in spermatogenesis. The aim of this study was to evaluate the effect of nano-TiO 2 on lactate production in mouse Sertoli cell line (TM4 cells) and to investigate whether the effect is mediated through the PI3K/AKT/HIF-1α pathway. After TM4 cells were treated with different concentrations of nano-TiO 2 for 48 h, cell viability, contents of glucose and lactate, and the expression levels of GLUT3 and key enzymes (HK1, HK2, PFKM, ENO1, LDH) during lactate production were detected. PI3K/AKT/HIF-1α pathway proteins were measured. In addition, PI3K agonist (IGF-1) was added to explore whether nano-TiO 2 regulates HIF-1α through PI3K/AKT pathway, thereby affecting the production of lactate in TM4 cells. The results showed that nano-TiO 2 significantly inhibited TM4 cell viability, increased glucose content, decreased lactate content, and downregulated the expression levels of GLUT3 and key enzymes during lactate production. Meanwhile, nano-TiO 2 decreased the expression of PI3K/AKT pathway phosphorylated proteins and HIF-1α, and IGF attenuated this effect of nano-TiO 2 . Collectively, nano-TiO 2 downregulated the expression level of proteins and enzymes related to lactate production in TM4 cells by inhibiting PI3K/AKT/HIF-1α pathway, resulting in the decrease of lactate production in TM4 cells.
研究领域:
生殖生物学
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细胞生物学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2025
·
IF 2.5
Zi-qing Wang,Li-ping Hao,Zi-xuan Meng,Hao-ran Zhang,Wei-jun Kang,Lian-feng Ai
An LC-MS/MS method was developed and validated for simultaneously quantifying 25-hydroxyvitamin D2, D3, and 1α,25-dihydroxyvitamin D3 in human serum. Protein in 200 μL serum was precipitated with acetonitrile. After centrifugation, the metabolites were derivatized using (diacetoxyiodo)benzene (PIA) and 4-(4-dimethylaminophenyl)-1,2,4-triazolidine-3,5-dione (DMAT) and then quantified by the LC-MS/MS system. The limits of detection (LODs) for the three substances were 10, 10, and 5 pg/mL, and the limits of quantification (LOQs) were 20, 20, and 10 pg/mL. The standard curves for these compounds showed linear regression coefficients (R2)>0.998 over specific concentration ranges. Recoveries were 94.36 %–102.34 % for 25(OH)D2, 92.43 %–103.41 % for 25(OH)D3, and 88.98 %–94.36 % for 1α,25(OH)2D3. The mean serum levels in 109 subjects (consisting of 61 healthy adult males and 59 healthy adult females) were 2.0 ± 1.5 ng/ml (25(OH)D2), 16.4 ± 6.1 ng/ml (25(OH)D3) and 36.6 ± 15.1 pg/ml (1α, 25(OH)2D3).Derivatization of vitamin D metabolites using PIA and DMAT is useful for rapidly determining the serum 25(OH) D2, 25(OH) D3 and 1α,25(OH)2D3 concentrations simultaneously in human serum.
研究领域:
分析化学
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临床医学
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营养学
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产品关联
DOI
PubMed
高影响因子
NUTRITION RESEARCH
·
2019
·
IF 2.627
Jia Wang,Tian Gao,Feng Wang,Jie Xue,Hua Ye,Meilin Xie
Luteolin , a natural flavonoid , can attenuate hepatic lipid accumulation and insulin resistance in obese mice . Therefore, we hypothesized that luteolin may also improve the abnormal glucolipid metabolism of hypertrophic myocardial cells. This study aimed to investigate the effect and possible molecular mechanisms of luteolin. Hypertrophic H9c2 cells were induced by angiotensin II/hypoxia and simultaneously treated with 2 to 8 μg/mL luteolin for 24 h. Luteolin might dose-dependently decrease intracellular total protein, atrial natriuretic peptide , and free fatty acid levels , and increase supernatant glucose levels . Western blot assay showed that luteolin could inhibit the expressions of intracellular hypoxia inducible factor-1α (HIF-1α) and glucose transporter-4 (GLUT-4) proteins, and increase the expressions of intracellular peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase-1A (CPT-1A), and pyruvate dehydrogenase kinase-4 (PDK-4) proteins. These findings demonstrate that luteolin can improve abnormal glucolipid metabolism in angiotensin II/hypoxia-induced hypertrophic H9c2 cells, and its mechanisms are related to the inhibition of HIF-1α expression and subsequent modulation of PPARα-mediated target genes, including CPT-1A, PDK-4, and GLUT-4.
研究领域:
药理学
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心脏病学
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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
Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-13
·
IF 5.116
Chai Miaomiao,Gu Ce,Shen Qihua,Liu Jiaxing,Zhou Yi,Jin Ziyang,Xiong Wanli,Zhou Yan,Tan Wensong
Background and aim Inadequate vascularization is a challenge in bone tissue engineering because internal cells are prone to necrosis due to a lack of nutrient supply. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to construct prevascularized bone tissue in osteogenic induction medium (OIM) in vitro. The angiogenic capacity of HUVECs was limited in the coculture system. In this study, the effects of the components in the medium on HUVEC angiogenesis were analyzed. Methods The coculture system was established in OIM. Alizarin red staining and alkaline phosphatase staining were used to assess the osteogenic ability of MSCs. A Matrigel tube assay was used to assess the angiogenic ability of HUVECs in vitro. The proliferation of HUVECs was evaluated by cell counting and CCK-8 assays, and migration was evaluated by the streaked plate assay. The expression levels of angiogenesis-associated genes and proteins in HUVECs were measured by qRT-PCR and Western blotting, respectively. Results Dexamethasone in the OIM suppressed the proliferation and migration of HUVECs, inhibiting the formation of capillary-like structures. Our research showed that dexamethasone stimulated HUVECs to secrete tissue inhibitor of metalloproteinase (TIMP-3), which competed with vascular endothelial growth factor (VEGF-A) to bind to vascular endothelial growth factor receptor 2 (VEGFR2, KDR). This effect was related to inhibiting the phosphorylation of ERK and AKT, which are two downstream targets of KDR. However, under hypoxia, the enhanced expression of hypoxia-inducible factor-1α (HIF-1α) decreased the expression of TIMP-3 and promoted the phosphorylation of KDR, improving HUVEC angiogenesis in the coculture system. Conclusion Coculture of hypoxia-preconditioned HUVECs and MSCs showed robust angiogenesis and osteogenesis in OIM, which has important implications for prevascularization in bone tissue engineering in the future.
研究领域:
组织工程
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细胞生物学
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2020
·
IF 8.352
Yanxin Chen,Mengqi Ye,Liwan Song,Junwen Zhang,Yao Yang,Sha Luo,Minjie Lin,Qianwen Zhang,Shengyu Li,Yajiao Zhou,Anqi Chen,Ying An,Wen Huang,Tengxiao Xuan,Yugui Gu,Huacheng He,Jiang Wu,Xiaokun Li
Skin wounds, especially chronic wounds such as pressure and diabetic ulcers, are posing a huge threat to healthcare systems worldwide. Thus, novel strategies to realize effective wound therapy are nowadays extremely needed. Herein, we are the first to report a combination therapy of electric stimulation and heat for wound healing just using a facile piezoelectric and photothermal dual functional film. The film, name as [email protected] , is simply fabricated by coating polydopamine on a chitosan film. [email protected] generates electric voltages under mechanical pressure and shows photothermal effect with irradiation of near-infra red (NIR) light. In vivo experiment with rat full-thickness wound model validates that [email protected] with NIR can effectively promote wound regeneration due to the generation of electric stimulation and heat on wounds. The healing mechanism of [email protected] is further investigated, and the result demonstrates that [email protected] enhances wound healing through a pathway in which heat shock protein 90 (Hsp90) and hypoxia-inducible factor 1α (HIF-1α) participate. These results indicate that [email protected] is a promising wound dressing candidate for clinical application in the future.
研究领域:
材料科学
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生物医学工程
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伤口愈合
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治疗学
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产品关联
DOI
高影响因子
JOURNAL OF GENE MEDICINE
·
2017
·Vol. 19
·期 12
·e2998
·
IF 2.524
Yunna Chen,Li Sun,Dongdong Guo,Ziteng Wu,Weidong Chen
Background Drug resistance cancer cells have become a major problem in chemotherapy. To solve this problem, the co-delivery of small interefering RNA (siRNA) and 5-fluorouracil chitosan nanoparticles was employed, aiming to reverse the multidrug resistance of gastric cancer SGC-7901 cells in vitro . Methods Chitosan nanoparticles were prepared using an ionic gel method. siRNA nanoparticles were characterized by gel retardation assays. Particle size and zeta potential were measured to confirm nanoparticle formation. The transfection efficiency of siRNA was determined by flow cytometry and high-content screening. Western blotting and a quantitative real-time-polymerase chain reaction were used to assess the silencing efficiency of siRNA. Accumulation and efflux experiments for rhodamine-123, cell migration experiments, cell sensitivity analyses and cell apoptosis assays were used to determine whether siRNA could reverse multidrug resistance. A systemic toxicity assay was used to evaluate the safety of nanoparticles. Results Compared to naked siRNA, the co-delivery system demonstrated a higher transfection efficiency and gene silencing efficiency by inhibiting the efflux of P-glycoprotein and cell migration. Moreover, the combination treatment with siRNA and 5-fluorouracil co-delivered by chitosan nanoparticles can increase the sensitivity of drug resistance cells and cell apoptosis. Finally, the safety of nanoparticles was evaluated in vivo and the results obtained suggested that nanoparticles did not have any obvious toxicity. Conclusions Co-delivery of siRNA and 5-fluorouracil chitosan nanoparticles is an attractive strategy for overcoming multidrug resistance.
研究领域:
肿瘤学
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药学
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分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2019
·
IF 3.585
Xue-Ying Wang,Dan Mo,Wen Tian,Xiao-Xiao Liu,Ya-Guang Zhou,Yang Sun,Ying-Da Feng,Xiong Xiao,Xiao-Wei Hao,Hui-Nan Zhang,Chen Li,Wei Cao,Xiao-Qiang Li
Hypoxic pulmonary vasoconstriction (HPV) can be modulated by Rho/Rho kinase signaling, which can alter HPV vascular function via regulating myosin light chain phosphorylation, in a manner generally believed to be Ca 2+ -independent. We hypothesized that the RhoA/ROCK signaling pathway also can regulate HPV vascular function via a Ca 2+ -dependent mechanism, signaling through the functional transient receptor potential canonical (TRPC) channels. In this study, male BALB/c mice were exposed to normoxic or 10% oxygen (hypoxic) conditions for six weeks, after which systolic pressure and right ventricular hypertrophy were assessed. Transient intracellular calcium was monitored using a fluorescence imaging system. Muscle tension was measured with a contractile force recording system, and protein expression was assessed by immunoblotting . We found that the expressions of RhoA and ROCK were increased in mouse pulmonary arteries (PAs) under conditions of chronic hypoxia . Inhibition of the RhoA/ROCK signaling pathway prevented the development of hypoxic pulmonary hypertension (HPH), as evidenced by significantly reduced PA remodeling and pulmonary vasoconstriction. Immunoblotting results revealed that inhibition of the RhoA/ROCK signaling pathway significantly decreased the expression of HIF-1α. Knockdown of HIF-1α down-regulated the expression and function of the TRPC1 and TRPC6 channels in PASMCs under conditions of hypoxia. Contraction of the PAs and a Ca 2+ influx into PASMCs through either receptor- or store-operated Ca 2+ channels were also increased after hypoxia. However, RhoA/ROCK inhibitors markedly attenuated these changes. These results indicate that inhibition of the RhoA/ROCK signaling pathway ameliorates HPH via HIF-1α-dependent functional TRPCs.
研究领域:
心血管生理学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Xiao-Yi Chen,Qian-Long Wang,Wei-Xue Huang,Long-Wei Li,Lan-Cong Liu,Yi Yang,You-Jiao Wu,Shan-Shan Song,Hao Ma,Hua Zhou,Pei Luo
Bacterial peritonitis is a severe disease that diagnosis remains challenging for clinicians. Measuring biomarkers might be a rapid diagnostic method. The objective of this study was to analyze and evaluate the dynamic changes in HIF-1α concentration in serum exosomes during bacterial peritonitis. The pre-clinical application value of serum exosomal HIF-1α was evaluated via imipenem and cilastatin sodium (ICS) intervention in the bacterial peritonitis model. The new colorimetric method to quantitate dynamic expression changes of HIF-1α in serum exosomes during bacterial peritonitis was established by our team via using the gold seed-coated with aptamer-functionalized Au @ Au core-shell peroxidase mimic. The typical inflammatory cytokines of bacterial peritonitis were also measured. Following intramuscular administration with ICS, In-Vivo Xtreme imaging system was used to visualize abdominal infection extent. Meanwhile, HIF-1α concentration in rat serum exosomes and pro-inflammatory factors levels in serum were detected. The serum typical inflammatory cytokines levels were elevated in GFP-labeled E.coli induced bacterial peritonitis. The serum exosomal HIF-1α levels clearly increased at 12 h, reached the peak during 24–48 h, and then gradually decreased at 72 h. Following intramuscular administration with ICS, the abdominal infection extent, HIF-1α concentration in serum exosomes, and the serum pro-inflammatory factors levels were reduced at 24 h in GFP-labeled E. coli induced bacterial peritonitis model. The serum exosomal HIF-1α can be used as a biomarker in the early stage of bacterial peritonitis, which might provide the basic research in the pre-clinical for further predicting and monitoring the pathological process of bacterial peritonitis.
研究领域:
医学诊断
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药理学
·
传染病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Dong Wenpei,Song Zhicheng,Liu Suihong,Yu Ping,Shen Zhipeng,Yang Jianjun,Yang Dongchao,Hu Qinxi,Zhang Haiguang,Gu Yan
Application of synthetic or biological meshes is the main therapy for the repair and reconstruction of abdominal wall defects, a common disease in surgery. Currently, no ideal materials are available, and there is an urgent need to find appropriate ones to satisfy clinical needs. Electrospun scaffolds have drawn attention in soft tissue reconstruction. In this study, we developed a novel method to fabricate a composite electrospun scaffold using a thermoresponsive hydrogel, poly (N-isopropylacrylamide)-block-poly (ethylene glycol), and a biodegradable polymer, polylactic acid (PLA). This scaffold provided not only a high surface area/volume ratio and a three-dimensional fibrous matrix but also high biocompatibility and sufficient mechanical strength, and could simulate the native extracellular matrix and accelerate cell adhesion and proliferation. Furthermore, rat adipose-derived stem cells (ADSCs) were seeded in the composite electrospun scaffold to enhance the defect repair and regeneration by directionally inducing ADSCs into endothelial cells. In addition, we found early vascularization in the process was regulated by the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. In our study, overexpression of HIF-1α/VEGF in ADSCs using a lentivirus system promoted early vascularization in the electrospun scaffolds. Overall, we expect our composite biomimetic scaffold method will be applicable and useful in abdominal wall defect regeneration and repair in the future.
研究领域:
组织工程
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生物材料
·
再生医学
·
外科研究
✓ 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）