다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Curcumin: an inflammasome silencer.

Role of the NLRP3 inflammasome in autoimmune diseases.

Gouty arthritis is characterized by the deposition of monosodium urate (MSU) within synovial joints and tissues due to increased urate concentrations. In this study, we explored the effect of the natural compound curcumin on the MSU crystal-stimulated inflammatory response. THP-1-derived macrophages and murine RAW264.7 macrophages were pretreated with curcumin for 1 h and then stimulated with MSU suspensions for 24 h. The protein level of TLR4, MyD88, and IκBα, the activation of the NF-κB signaling pathway, the expression of the NF-κB downstream inflammatory cytokines, and the activity of NLRP3 inflammasome were measured by western blotting and ELISA. THP-1 and RAW264.7 cells were loaded with MitoTracker Green to measure mitochondrial content, and MitoTracker Red to detect mitochondrial membrane potential. To measure mitochondrial reactive oxygen species (ROS) levels, cells were loaded with MitoSOX Red, which is a mitochondrial superoxide indicator. The effects of curcumin on mouse models of acute gout induced by the injection of MSU crystals into the footpad and synovial space of the ankle, paw and ankle joint swelling, lymphocyte infiltration, and MPO activity were evaluated. Curcumin treatment markedly inhibited the degradation of IκBα, the activation of NF-κB signaling pathway, and the expression levels of the NF-κB downstream inflammatory genes such as IL-1β, IL-6, TNF-α, COX-2, and PGE2 in the MSU-stimulated THP-1-derived macrophages. Curcumin administration protected THP-1 and RAW264.7 cells from MSU induced mitochondrial damage through preventing mitochondrial membrane potential reduction, decreasing mitochondria ROS, and then inhibited the activity of NLRP3 inflammasome. Intraperitoneal administration of curcumin alleviated MSU crystal-induced paw and ankle joint swelling, inflammatory cell infiltration, and MPO activity in mouse models of acute gout. These results correlated with the inhibition of the degradation of IκBα, the phosphorylation levels of NF-κB subunits (p65 and p50), and the activity of NLRP3 inflammasome. Curcumin administration effectively alleviated MSU-induced inflammation by suppressing the degradation of IκBα, the activation NF-κB signaling pathway, the damage of mitochondria, and the activity of NLRP3 inflammasome. Our results provide a new strategy in which curcumin therapy may be helpful in the prevention of acute episodes of gout.

/pdf/curcumin-attenuates-msu-crystal-induced-inflammation-by-3jg6t4o79h.pdf

Curcumin attenuates MSU crystal-induced inflammation by inhibiting the degradation of IκBα and blocking mitochondrial damage

Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome

GSDMD-miR-223-NLRP3 axis involved in B(a)P-induced inflammatory injury of alveolar epithelial cells.

Role of angiotensin-converting enzyme 2 in fine particulate matter-induced acute lung injury.

Myocardial fibrosis (MF) is a common pathological feature of many heart diseases and seriously threatens the normal activity of the heart. Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a novel dammarane-type saponin, was obtained from the hydrolysates of total gypenosides. It has been reported to exert a beneficial anti-inflammatory effect. In our study, we attempted to investigate the efficiency and possible molecular mechanism of Gyp I in cardiac injury treatment induced by ISO. In vitro, Gyp I was found to increase the survival rate of H9c2 cells and inhibit apoptosis. Combined with molecular docking and Western blot analysis, Gyp I was confirmed to regulate the TLR4/NF-κB/NLRP3 signaling pathway. In vivo, C57BL6 mice were subcutaneously injected with 10 mg/kg ISO to induce heart failure. Mice were given a gavage of Gyp I (10, 20, or 40 mg/kg/d for three weeks). Pathological alterations, fibrosis-, inflammation-, and apoptosis-related molecules were examined. By means of cardiac function detection, biochemical index analysis, QRT-PCR monitoring, histopathological staining, immunohistochemistry, and Western blot analysis, it was elucidated that Gyp I could improve cardiac dysfunction, alleviate collagen deposition, and reduce myocardial fibrosis (MF). In summary, we reported for the first time that Gyp I showed good myocardial protective activity in vitro and in vivo, and its mechanism was related to the TLR4/NF-κB/NLRP3 signaling pathway.

/pdf/gypensapogenin-i-ameliorates-isoproterenol-iso-induced-ezoygnaq.pdf

Gypensapogenin I Ameliorates Isoproterenol (ISO)-Induced Myocardial Damage through Regulating the TLR4/NF-κB/NLRP3 Pathway

Recent studies have revealed that tumor-associated macrophages are the most abundant stromal cells in the tumor microenvironment and play an important role in tumor initiation and progression. Furthermore, the proportion of macrophages in the tumor microenvironment is associated with the prognosis of patients with cancer. Tumor-associated macrophages can polarize into anti-tumorigenic phenotype (M1) and pro-tumorigenic phenotype (M2) by the stimulation of T-helper 1 and T-helper 2 cells respectively, and then exert opposite effects on tumor progression. Besides, there also is wide communication between tumor-associated macrophages and other immune compositions, such as cytotoxic T cells, regulatory T cells, cancer-associated fibroblasts, neutrophils and so on. Furthermore, the crosstalk between tumor-associated macrophages and other immune cells greatly influences tumor development and treatment outcomes. Notably, many functional molecules and signaling pathways have been found to participate in the interactions between tumor-associated macrophages and other immune cells and can be targeted to regulate tumor progression. Therefore, regulating these interactions and CAR-M therapy are considered to be novel immunotherapeutic pathways for the treatment of malignant tumors. In this review, we summarized the interactions between tumor-associated macrophages and other immune compositions in the tumor microenvironment and the underlying molecular mechanisms and analyzed the possibility to block or eradicate cancer by regulating tumor-associated macrophage-related tumor immune microenvironment.

/pdf/the-role-of-macrophages-mediated-communications-among-cell-1st3tgmu.pdf

Mengyuan Li

Papers

Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome

GSDMD-miR-223-NLRP3 axis involved in B(a)P-induced inflammatory injury of alveolar epithelial cells.

Role of angiotensin-converting enzyme 2 in fine particulate matter-induced acute lung injury.

Gypensapogenin I Ameliorates Isoproterenol (ISO)-Induced Myocardial Damage through Regulating the TLR4/NF-κB/NLRP3 Pathway

The role of macrophages-mediated communications among cell compositions of tumor microenvironment in cancer progression