Diabetes & Vascular Disease Research
·
2024
·
IF 2.8
Yuxin Hu,Zhen Li,Hongxue Li,Qian Xu,Chengye Xu,Wenjian Lin,Xuefei Ma,Ming Hao,Hongyu Kuang
Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1β, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage.
研究领域:
眼科学
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神经科学
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细胞生物学
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炎症
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产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2024
·Vol. 24
·期 1
·1-15
·
IF 3.3
He Yu,Liu Fei,He Mingjuan,Long Fayu,Hu Ding,Chen Jingwen,Fang Miao,Wang Zhenlong
The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.
研究领域:
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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生物信息学
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骨生物学
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网络医学
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DOI
高影响因子
International Journal of Medical Sciences
·
2020
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IF 2.523
Ke Li,Wenhua Zhan,Min Jia,Yufeng Zhao,Yingguang Liu,Rajiv Kumar Jha,Liansuo Zhou
Background : Combination chemotherapy plays an important role in the clinical therapy of non-small cell lung cancer (NSCLC). However, the pharmacokinetic differences between drugs are an insurmountable barrier in traditional treatment. For the synergistic therapy of NSCLC, synergistic nanoparticles (EDS NPs) loaded with both an EGFR inhibitor and doxorubicin (DOX) were designed and prepared. Methods : Erlotinib, apatinib and icotinib were evaluated for optimal combination with DOX in treatment of NSCLC via CCK-8 assay. Then the cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were applied to coencapsulate DOX and EGFR inhibitor to form the EDS NPs. EDS NPs were evaluated in NSCLC cell lines (A549, NCI-H1975 and PC9) and NSCLC xenograft mouse models. Results : Icotinib was found to be the optimal synergistic drug in combination with DOX in the tested. Subsequently, icotinib and DOX were coencapsulated in the NPs. EDS NPs were roughly spherical with an average size of 65.7±6.2 nm and possessed stable loading and releasing properties. In the in vitro investigation, EDS NPs could efficiently deliver payloads into cells, exhibited cytotoxicity and produced strong anti-migration properties. In vivo hypotoxicity was confirmed by acute toxicity and hemolytic assays. The in vivo distribution showed that EDS NPs could enhance accumulation in tumors and decrease nonspecific accumulation in normal organs. EDS NPs significantly promoted the in vivo synergistic effects of icotinib and DOX in the mouse model. Conclusions : The study suggests that EDS NPs possess noteworthy potential for development as therapeutics for NSCLC clinical chemotherapy.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Shikun Wei,Pengcheng Xu,Zexin Yao,Xiao Cui,Xiaoxuan Lei,Linlin Li,Yunqing Dong,Weidong Zhu,Rui Guo,Biao Cheng
Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains ( E. coli, S. aureus and P. aeruginosa ) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1β and IL-6), enhanced anti-inflammatory factors (TGF-β1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.
研究领域:
生物医学工程
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药学
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伤口愈合
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糖尿病研究
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传染病学
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产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2023
·Vol. 23
·期 1
·1-14
·
IF 3.9
Zhang Ke,Ji Xiawei,Song Zhengyang,Song Wenjing,Huang Qunjia,Yu Tiantian,Shi Dibang,Wang Fangyan,Xue Xiangyang,Guo Junping
Background Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms. Methods Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Ι and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA). Results CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD + levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Ι inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Ι were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Ι. Conclusion Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Ι.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
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IF 7.9
MinChao Feng,BaiJun Qin,Fang Luo,Hui Li,KunRong Liu,Kai Li,DongYang Wu,XiPing Tang,Guozhong Chen
Background Safer and more effective drugs are needed for the treatment of acute pancreatitis (AP). Qingjie Huagong decoction (QJHGD) has been applied to treat AP for many years and has shown good clinical effects. However, the potential mechanism has not yet been determined. Purpose To investigate the role and underlying mechanism of the effects of QJHGD on AP both in vitro and in vivo . Methods QJHGD was characterized by UHPLC-Q-Orbitrap-MS. The protective effect of QJHDG and the underlying mechanism were investigated in MPC-83 cells in vitro . A caerulein-induced AP model was established to evaluate the protective effect of QJHGD in mice. CCK-8 assays were used to detect cell viability. The contents of inflammatory mediators were determined by ELISA. Expression levels of circRNA, miRNA and mRNA were determined by qRT-PCR. Protein expression was determined using Western blot . Pancreatic tissues were assessed by hematoxylin and eosin staining as well as immunohistochemical and immunofluorescence analyses. Pull-down and luciferase activity assays were performed to determine the regulatory relationships of circHipk3, miR-193a-5p and NLRP3. Results Our results confirmed that mmu-miR-193a-5p was sponged by mmu-circHipk3, and NLRP3 was a target of miR-193a-5p. In vitro experiments showed that QJHGD enhanced MPC-83 cell viability by regulating circHipk3 sponging mir-193a-5 targeting NLRP3 and inhibiting pyroptosis-related factors. Finally, we showed that QJHGD ameliorated pancreatic tissue injury in AP mice via this pathway. Conclusion This study demonstrate that QJHDG exerted its anti-AP effects via the circHipk3/miR-193a-5p/NLRP3 pathway, revealing a novel mechanism for the therapeutic effect of QJHDG on AP.
研究领域:
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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炎症
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中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2016
·Vol. 40
·期 10
·8397-8407
·
IF 3.277
Beibei Lu,Lei Li,Jianning Wu,Lulu Wei,Jun Hou,Zhiyong Liu,Xuhong Guo
Well-defined dual pH and temperature responsive triblock star-shaped amphiphilic copolymers of β-cyclodextrin-g-poly(2-hydroxyethylmethacrylate)-b-poly(N-isopropylacrylamide)-b-poly(2-(dimethylamino)ethylmethacrylate) (β-CD-g-(PHEMA-b-PNIPAM-b-PDMAEMA)) were synthesized by the combination of reversible addition–fragmentation chain transfer (RAFT) polymerizations. The chemical structures and compositions of these copolymers were characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), and gel permeation chromatography (GPC) measurements. Subsequently, the obtained triblock copolymers could self-assemble into micelles in aqueous solution owing to their amphiphilic property resulting from the hydrophobic β-CD core and the hydrophilic PHEMA, PNIPAM, and PDMAEMA segments, which were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The triblock copolymer nanoparticles exhibited two separate lower critical solution temperatures (LCSTs) and these triblock copolymers in aqueous solutions were investigated at the different pH values of 5.0 and 7.4 as doxorubicin (DOX) delivery systems for controlled release. Polymeric micelles exhibited a pH controlled release performance. Investigation of DOX release from the micelles indicated that the release rate of the drug could be effectively controlled by altering the pH, encapsulating DOX in neutral surroundings (blood circulation or extracellular matrix) and triggering DOX release in acidic surroundings (intracellular endosomes). CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the polymeric micelles themselves had no associated cytotoxicity and possessed good biodegradability and biocompatibility and that the micelles identified the location of the DOX in the HeLa cells. On the other hand, the DOX-loaded micelles possessed a high cytotoxicity to HeLa cells and exhibited inhibition of the proliferation of HeLa cells. Hence, this type of biodegradable, biocompatible, and stimuli-responsive copolymer could serve as a promising material for drug delivery.
研究领域:
高分子化学
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材料科学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 5
·1305-1319
·
IF 4.414
Cheng Shen,Chen Chen,Wang Liling
Given that the role of Gelsemine in neuroinflammation has been demonstrated, this research aimed to investigate the effect of Gelsemine on neonatal hypoxic-ischemic (HI) brain injury. An in vivo HI brain injury neonatal mouse model and an in vitro oxygen–glucose deprivation (OGD) cell model were established and pretreated with Gelsemine. The brain infarct volume, neuronal loss and apoptosis, as well as spatial learning and memory were examined by TTC staining, Nissl’s staining, TUNEL staining and Morris water maze test. Immunohistochemical staining was applied to detect the microglia cells and astrocytes in the mouse brain tissue. The cell viability was analyzed by CCK-8 assay. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), TNF-α, IL-1β, and IL-6 were determined via ELISA. The lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) level in OGD-treated cells were detected by colorimetry and DCFH-DA staining. Nrf2, HO-1, and inflammation-related factors were analyzed by immunofluorescence, qRT-PCR, or western blot. Gelsemine reduced the infarct volume and neuronal loss and apoptosis, yet improved spatial learning and memory impairment of HI-injured mice. Gelsemine inhibited the elevated MDA, TNF-α, IL-1β, IL-6, LDH and ROS levels, promoted the reduced SOD level and viability, and strengthened the up-regulation of HO-1 and Nrf2 in brain tissues and OGD-treated cells. However, Nrf2 silencing reversed the effects of Gelsemine on the Nrf2/HO-1 pathway, inflammation, and oxidative stress in OGD-treated cells. Gelsemine produces neuroprotective effects on neonatal mice with HI brain injury by suppressing inflammation and oxidative stress via Nrf2/HO-1 pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Cureus Journal of Medical Science
·
2024
·
IF 1
Ye-Ran Mao,Ling-Yi Zhu,Ruo-Fei Du,Xiao-Yu Liu,Zhidan Liu,Li Li
Background and objectives: In ancient China, bee venom was widely used to treat various diseases. Although using bee venom is not currently a mainstream medical method, some have applied it to treat certain conditions, including idiopathic facial paralysis (IFP). Recently, melittin (Mel), the main active component of bee venom, has been shown strong anti-inflammatory and analgesic effects. However, how bee venom improves neurological dysfunction in facial paralysis remains unknown. This study aimed to investigate the anti-neurotraumatic effect of Mel on Schwann cells (SCs), the main cells of the neuron sheath, injured by oxidative stress. Methods: A model of hypoxic SCs was established, and CCK-8 assay, siRNA transfection, enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, western blot, immunofluorescence, and cell ultrastructure analyses were conducted to investigate the mitigation of hypoxia-induced damage to SCs in vitro, revealing the effects of Mel on oxidative stress injury in SCs. Results: The overexpression of HIF-1α in CoCl 2 -induced SCs (p < 0.05) indicated the establishment of an SCs hypoxia model. The proliferation and regeneration process of the hypoxic SCs enhanced in the Mel-treated group compared to the CoCl 2 group has been proven through the CCK-8 experiment (p < 0.0001) and S-100 mRNA expression detection (p < 0.0001). The increased level of reactive oxygen species (ROS) (p < 0.001) and decreased superoxide dismutase (SOD) levels (p < 0.05) in the CoCl 2 -induced SCs indicated that Mel can alleviate the oxidative stress damage to SCs induced by CoCl 2 . Mel alleviated oxidative stress and inflammation in hypoxic SCs by reducing pro-inflammatory cytokines IL-1β (p < 0.0001) and TNF-α (p < 0.0001). In addition, Mel augmented cellular vitality and regulated indicators related to oxygen metabolism, cell repair, neurometabolism, and vascular endothelial formation after hypoxia, such as C-JUN (p < 0.05), glial cell line-derived neurotrophic factor (GDNF; p < 0.001), vascular endothelial growth factor (VEGF; p < 0.05), hypoxia-inducible factor 1-alpha (HIF-1α; p < 0.05), interleukin-1 receptor type 1 (IL-1R1; p < 0.05), enolase1 (ENO1; p < 0.05), aldose reductase (AR; p < 0.01), SOD (p < 0.05), nerve growth factor (NGF; p < 0.05), and inducible nitric oxide synthase (iNOS; p < 0.05). In terms of its mechanism, Mel inhibited the expression of proteins associated with the NF-κB pathway such as IKK (p < 0.01), p65 (p < 0.05), p60 (p < 0.001), IRAK1 (p < 0.05), and increased IKB-α (p < 0.0001). Moreover, knocking out of IL-1R1 in the si-IL-1R1 group enhanced the therapeutic effect of Mel compared to the Mel-treated group (all of which p < 0.05). Conclusion: This research provided evidence of the substantial involvement of IL-1R1 in oxidative stress damage caused by hypoxia in SCs and proved that Mel alleviated oxidative stress injury in SCs by targeting IL-1R1 to downregulate the NF-κB-mediated inflammatory response. Mel could potentially serve as an innovative therapeutic approach for the treatment of IFP.
研究领域:
神经科学
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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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炎症
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氧化应激
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面瘫
✓ 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）