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101.
Lu Wang Bin Deng Panpan Yan Huanghui Wu Chunhui Li Hongrui Zhu Jiwei Du Lichao Hou 《Journal of cellular and molecular medicine》2021,25(7):3449-3459
Tumour necrosis factor-α (TNF-α), a crucial cytokine, has various homeostatic and pathogenic bioactivities. The aim of this study was to assess the neuroprotective effect of ketamine against TNF-α-induced motor dysfunction and neuronal necroptosis in male C57BL/6J mice in vivo and HT-22 cell lines in vitro. The behavioural testing results of the present study indicate that ketamine ameliorated TNF-α-induced neurological dysfunction. Moreover, immunohistochemical staining results showed that TNF-α-induced brain dysfunction was caused by necroptosis and microglial activation, which could be attenuated by ketamine pre-treatment inhibiting reactive oxygen species production and mixed lineage kinase domain-like phosphorylation in hippocampal neurons. Therefore, we concluded that ketamine may have neuroprotective effects as a potent inhibitor of necroptosis, which provides a new theoretical and experimental basis for the application of ketamine in TNF-α-induced necroptosis-associated diseases. 相似文献
102.
Simon Trapp Ali A. Aghdassi Juliane Glaubitz Matthias Sendler Frank Ulrich Weiss Jens Peter Kühn Marie-Luise Kromrey Ujjwal M. Mahajan Petra Pallagi Zoltán Rakonczay Jr Viktória Venglovecz Markus M. Lerch Peter Hegyi Julia Mayerle 《Journal of cellular and molecular medicine》2021,25(10):4658-4670
Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) are an established risk factor for cystic fibrosis (CF) and chronic pancreatitis. Whereas patients with CF usually develop complete exocrine pancreatic insufficiency, pancreatitis patients with CFTR mutations have mostly preserved exocrine pancreatic function. We therefore used a strain of transgenic mice with significant residual CFTR function (CFTRtm1HGU) to induce pancreatitis experimentally by serial caerulein injections. Protease activation and necrosis were investigated in isolated acini, disease severity over 24h, pancreatic function by MRI, isolated duct stimulation and faecal chymotrypsin, and leucocyte function by ex vivo lipopolysaccharide (LPS) stimulation. Pancreatic and lung injury were more severe in CFTRtm1HGU but intrapancreatic trypsin and serum enzyme activities higher than in wild-type controls only at 8h, a time interval previously attributed to leucocyte infiltration. CCK-induced trypsin activation and necrosis in acini from CFTRtm1HGU did not differ from controls. Fluid and bicarbonate secretion were greatly impaired, whereas faecal chymotrypsin remained unchanged. LPS stimulation of splenocytes from CFTRtm1HGU resulted in increased INF-γ and IL-6, but decreased IL-10 secretion. CFTR mutations that preserve residual pancreatic function significantly increase the severity of experimental pancreatitis—mostly via impairing duct cell function and a shift towards a pro-inflammatory phenotype, not by rendering acinar cells more susceptible to pathological stimuli. 相似文献
103.
Yuchuan Jiang Peng Chen Kaishun Hu Guanqi Dai Jinying Li Dandan Zheng Hui Yuan Lu He Penghui Xie Mengxian Tu Shuang Peng Chen Qu Wenyu Lin Raymond T. Chung Jian Hong 《Journal of cellular and molecular medicine》2021,25(3):1568-1582
The pro-inflammatory and pro-fibrotic liver microenvironment facilitates hepatocarcinogenesis. However, the effects and mechanisms by which the hepatic fibroinflammatory microenvironment modulates intrahepatic hepatocellular carcinoma (HCC) progression and its response to systematic therapy remain largely unexplored. We established a syngeneic orthotopic HCC mouse model with a series of persistent liver injury induced by CCl4 gavage, which mimic the dynamic effect of hepatic pathology microenvironment on intrahepatic HCC growth and metastasis. Non-invasive bioluminescence imaging was applied to follow tumour progression over time. The effect of the liver microenvironment modulated by hepatic injury on sorafenib resistance was investigated in vivo and in vitro. We found that the persistent liver injury facilitated HCC growth and metastasis, which was positively correlated with the degree of liver inflammation rather than the extent of liver fibrosis. The inflammatory cytokines in liver tissue were clearly increased after liver injury. The two indicated cytokines, tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), both promoted intrahepatic HCC progression via STAT3 activation. In addition, the hepatic inflammatory microenvironment contributed to sorafenib resistance through the anti-apoptotic protein mediated by STAT3, and STAT3 inhibitor S3I-201 significantly improved sorafenib efficacy impaired by liver inflammation. Clinically, the increased inflammation of liver tissues was accompanied with the up-regulated STAT3 activation in HCC. Above all, we concluded that the hepatic inflammatory microenvironment promotes intrahepatic HCC growth, metastasis and sorafenib resistance through activation of STAT3. 相似文献
104.
Nan Wu Xiao-Fan Xu Jia-Qi Xin Jian-Wei Fan Yuan-Yuan Wei Qing-Xia Peng Li-Fang Duan Wei Wang Hong Zhang 《Journal of cellular and molecular medicine》2021,25(4):2213-2227
The activation of pancreatic stellate cells (PSCs) plays a critical role in the progression of pancreatic fibrosis. Nuclear factor-kappa B ( NF-κB) is associated with chronic pancreatitis (CP). Previous evidence indicated that NF-κB in acinar cells played a double-edged role upon pancreatic injury, whereas NF-κB in inflammatory cells promoted the progression of CP. However, the effects of NF-κB in PSCs have not been studied. In the present study, using two CP models and RNAi strategy of p65 in cultured PSCs, we found that the macrophage infiltration and MCP-1 expression were increased, and the NF-κBp65 protein level was elevated. NF-κBp65 was co-expressed with PSCs. In vitro, TGF-β1 induced overexpression of the TGF-β receptor 1, phosphorylated TGF-β1–activated kinase 1 (p-TAK1) and NF-κB in the PSCs. Moreover, the concentration of MCP-1 in the supernatant of activated PSCs was elevated. The migration of BMDMs was promoted by the supernatant of activated PSCs. Further knockdown of NF-κBp65 in PSCs resulted in a decline of BMDM migration, accompanied by a lower production of MCP-1. These findings indicate that TGF-β1 can induce the activation of NF-κB pathway in PSCs by regulating p-TAK1, and the NF-κB pathway in PSCs may be a target of chronic inflammation and fibrosis. 相似文献
105.
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107.
Xiaoyou Liu Jianmin Hu Guorong Liao Ding Liu Song Zhou Jie Zhang Jun Liao Zefeng Guo Yuzhu Li Siqiang Yang Shichao Li Hua Chen Ying Guo Min Li Lipei Fan Liuyang Li Ming Zhao Yongguang Liu 《Journal of cellular and molecular medicine》2023,27(20):3202-3212
The incidence of acute kidney injury (AKI) is on the rise and is associated with high mortality; however, there are currently few effective treatments. Moreover, the relationship between Tregs and other components of the immune microenvironment (IME) in the pathogenesis of AKI remains unclear. We downloaded four publicly accessible AKI datasets, GSE61739, GSE67401, GSE19130, GSE81741, GSE19288 and GSE106993 from the gene expression omnibus (GEO) database. Additionally, we gathered two kidney single-cell sequencing (scRNA-seq) samples from the Department of Organ Transplantation at Zhujiang Hospital of Southern Medical University to investigate chronic kidney transplant rejection (CKTR). Moreover, we also collected three samples of normal kidney tissue from GSE131685. By analysing the differences in immune cells between the AKI and Non-AKI groups, we discovered that the Non-AKI group contained a significantly greater number of Tregs than the AKI group. Additionally, the activation of signalling pathways, such as inflammatory molecules secretion, immune response, glycolytic metabolism, NOTCH, FGF, NF-κB and TLR4, was significantly greater in the AKI group than in the Non-AKI group. Additionally, analysis of single-cell sequencing data revealed that Tregs in patients with chronic kidney rejection and in normal kidney tissue have distinct biology, including immune activation, cytokine production, and activation fractions of signalling pathways such as NOTCH and TLR4. In this study, we found significant differences in the IME between AKI and Non-AKI, including differences in Tregs cells and activation levels of biologically significant signalling pathways. Tregs were associated with lower activity of signalling pathways such as inflammatory response, inflammatory molecule secretion, immune activation, glycolysis. 相似文献
108.
Zhixiang Cai Tao Yan Siwen Li Jianyi Zhang Xianyue Wang Li Li Huailing Wang Hanwei Chen Yukuan Tang 《Journal of peptide science》2023,29(1):e3447
Dandelion (Taraxacum officinale) is widely consumed as a health food and a traditional medicine. However, the protective effect of dandelion bio-active peptides (DPs) against polycyclic aromatic hydrocarbon-induced blood vessel inflammation and oxidative damage is not well documented. In the current study, four novel DPs were isolated using an activity tracking method. The protective activity of the DPs against benzo(a)pyrene (Bap)-induced human umbilical vein endothelial cell (HUVEC) damage was explored. The results indicated that DP-2 [cycle-(Thr-His-Ala-Trp)] effectively inhibited Bap-induced reactive oxygen species (ROS) and malondialdehyde (MDA) overproduction and reinforced antioxidant enzyme activity while inhibiting the production of inflammatory factors in HUVECs. Moreover, DP-2 increased NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and nuclear factor E2-releated factor 2 expression levels by activating the PI3K/Akt signaling pathway. In addition, DP-2 attenuated Bap-induced HUVEC apoptosis via the Bcl-2/Bax/cytochrome c apoptotic pathway. These results suggest that DP-2 is a promising compound for protecting HUVECs from Bap-induced inflammatory and oxidative damage. 相似文献
109.
110.
Tzu‐Ying Wang Jin‐Bin Wu Tsong‐Long Hwang Yueh‐Hsiung Kuo Jih‐Jung Chen 《化学与生物多样性》2010,7(7):1828-1834
The fruit of Tetradium ruticarpum is widely used in healthcare products for the improvement of blood circulation, headache, abdominal pain, amenorrhea, chill limbs, migraine, and nausea. A new quinolone, 2‐[(6Z,9Z)‐pentadeca‐6,9‐dienyl]quinolin‐4(1H)‐one ( 1 ), has been isolated from the fruits of T. ruticarpum, together with eleven known compounds. The structure of the new compound was determined by NMR and MS analyses. Rutaecarpine ( 4 ), evodiamine ( 5 ), and skimmianine ( 7 ) exhibited inhibition (IC50≤20.9 μM ) of O$\rm{{_{2}^{{^\cdot} -}}}$ generation by human neutrophils in response to N‐formyl‐L ‐methionyl‐L ‐leucyl‐L ‐phenylalanine/cytochalasin B (fMLP/CB). In addition, 1 , evocarpine ( 2 ), 4, 7 , and evodol ( 8 ) inhibited fMLP/CB‐induced elastase release with IC50 values ≤14.4 μM . 相似文献