Cathepsin B-Mediated NLRP3 Inflammasome Formation and Activation in Angiotensin II -Induced Hypertensive Mice: Role of Macrophage Digestion Dysfunction.

BACKGROUND/AIMS: Angiotensin II (Ang II) is an octapeptide hormone that plays a significant role in mediating hypertension. Although hypertension is considered a chronic inflammatory disease, the molecular basis of the sterile inflammatory response involved in hypertension remains unclear. METHODS: We investigated the role of macrophage NLRP3 inflammasomes in engulfing and digesting microbes, a key macrophage function, and in early onset of hypertension-associated macrophage injury using biochemical analyses, gene silencing, molecular biotechnology, immunofluorescence, and microbiology. RESULTS: Ang II stimulation decreased nitric oxide (NO) release and macrophage digestion in cultured THP-1 cells and markedly increased NLRP3 inflammasome formation and activation. NO release and macrophage digestion were restored by NLRP3 inflammasome inhibition with isoliquiritigenin and gene silencing. This Ang II-induced upregulation of NLRP3 inflammasomes in macrophages was attributed to lysosomal damage and release of cathepsin B. Mechanistically, losartan, a nonpeptide Ang II receptor antagonist, decreased Ang II-induced NLRP3 inflammasome activation, lysosomal membrane permeability, lysosomal cathepsin B release, and macrophage digestion dysfunction. Similarly, Ang II-induced macrophage microbe digestion and NO production, which were blocked by ATI gene silencing. In addition, in vivo experiments showed that the bacteria scavenging function was clearly decreased in macrophages from Ang II-induced hypertensive mice. CONCLUSION: Angiotensin II enhances lysosomal membrane permeabilization and the consequent release of lysosomal cathepsin B, resulting in activation of the macrophage NLRP3 inflammasome. This may contribute to NO mediation of dysfunction in digesting microbes.

[Mechanism of lysosome-mediated eradication activity of macrophages on specific anti-Helicobacter pylori of patchouli alcohol].

The aim of this paper is to investigate the effect of patchouli alcohol in enhancing Helicobater pylori's action in eradicating macrophages and its mechanism. H. pylori was co-cultured with macrophages at a ratio of MOI=100 in different concentrations of patchouli alcohol. The effect of patchouli alcohol in eradicating macrophages was detected by agar dilution method. The effect of patchouli alcohol on NO and myeloperoxidase (MPO) levels in macrophages were measured by H. pylori by biochemical methods. Patchouli alcohol effect on H. pylori-induced pro-inflammatory gene expression and protein secretion in macrophages were detected by RT-qPCR and ELISA method. The eradication of H. pylori has significantly enhanced, and the destabilization of lysosomes has been reversed. Meanwhile, patchouli alcohol has an effect in inhibiting pro-inflammation and oxidation. The mechanism of patchouli alcohol in eradicating H. pylori and resisting oxidative stress may be associated to the blocking of bacteria escape lysosome combination procedures.

Multidisciplinary treatment of giant presacral solitary fibrous tumour: a case report and literature review.

Solitary fibrous tumours (SFTs) usually occur at the pleura. Extrapleural sites, particularly giant extrapleural solitary fibromas, are more rarely observed in the clinic, and the clinical diagnosis and treatment of this disease is a focus of attention. Herein, the case of a 43-year-old male patient with giant presacral SFT successfully treated by open surgery, and with a final diagnosis confirmed by postoperative pathology and immunohistochemistry, is reported. The patient was followed-up regularly during 5 years after surgery, with no obvious surgical complications, and no tumour recurrence noted on pelvic magnetic resonance imaging. This case provides clinical information that may help in the diagnosis and treatment of complex SFT.

Preliminary proposal: a classification system for reconstruction with autologous femoral head after periacetabular tumors resection.

BACKGROUND: Although researchers have adopted various methods for the resection and reconstruction of periacetabular tumors, the total incidence rate of complications remains high. Aiming for preserving the acetabulum and reducing the risk of complications, we applied a surgery method using tumor-free autologous femoral head to reconstruct the defective acetabulum after resection of periacetabular tumors followed by performing a conventional total hip arthroplasty (THA). Moreover, we proposed a preliminary classification system for these surgery methods. METHODS: We retrospectively reviewed 6 patients treated with acetabulum reconstruction combined with autologous femoral head following peri-acetabulum resection between April 2010 and May 2018. All patients were diagnosed as periacetabular tumors including chondrosarcoma (n = 5) and chondroblastoma (n = 1). Clinical data such as age, diagnosis, complications, local recurrence or metastasis, and function (Musculoskeletal Tumor Society 1993, MSTS93) were documented. The average time of follow-up was 62.5 months (range, 17 to 106 months). RESULTS: A total of 5 patients survive with average MSTS93 score of 27.8 points (range, 26-30). One patient, suffering from multiple bone metastasis prior treatment, ended up dying. One who had received radiotherapy before surgery had poor incision healing. Further, a classification system was preliminary proposed in 2 patients involving the pubis (type A) and 4 patients involving ischium (type B). CONCLUSIONS: Based on the results, we preliminary proposed a classification system for reconstruction with autologous femoral head after periacetabular low malignant tumors resection. The clinical results suggested that surgery methods involving pubis (type A) and ischium (Type B) are safe and feasible. However, further researches should be conducted to verify our classification system.

lncRNA-TINCR Functions as a Competitive Endogenous RNA to Regulate the Migration of Mesenchymal Stem Cells by Sponging miR-761.

Mounting evidences have indicated that terminal differentiation-induced lncRNA (TINCR) contributes to various cellular processes, such as proliferation, apoptosis, autophagy, migration, invasion, and metastasis. However, the function of TINCR in regulating migration of MSCs is largely unknown. In this study, the effects of TINCR on the migration of rat MSCs from the bone marrow were studied by Transwell assays and wound healing assays. Our results suggested that TINCR positively regulated migration of rMSCs. miR-761 mimics suppressed rMSC migration, whereas miR-761 inhibitor promoted migration. Target prediction analysis tools and dual-luciferase reporter gene assay identified Wnt2 as a direct target of miR-761. miR-761 could inhibit the expression of Wnt2. Further, the investigation about the function of TINCR in miR-761-induced migration of rMSCs was completed. These results demonstrated that TINCR took part in the regulation of miR-761-induced migration in rMSCs through the regulation of Wnt2 and its Wnt2 signaling pathway. Taken together, our results demonstrate that lncRNA-TINCR functions as a competitive endogenous RNA (ceRNA) to regulate the migration of rMSCs by sponging miR-761 which modulates the role of Wnt2. These findings provide evidence that lncRNA-TINCR has a chance to serve as a potential target for enhancing MSC homing through the miR-761/Wnt2 signaling pathway.