New anti-inflammatory limonoids from the fruits of Melia azedarach.

The phytochemical study of the fruits of Melia azedarach (Meliaceae) led to the isolation and characterisation of two novel natural limonoids1-deoxy- 3, 20-dicinnamoyl-11-methoxy-meliacarpinin (1) and 12ß- O- methyl nimbolinin A (2), along with twelve known limonoids. Its structure was identified by 1D- and 2D-NMR, HR-ESI-MS and comparison with published data. The anti-inflammatory effect of the compounds was measured in vitro in RAW 264.7 cells by evaluating the production of NO stimulated by LPS. Compounds 1, 8 and 14 indicated significant anti-inflammatory effect with inhibition rate of 11.76, 8.45 and 6.59 µM, respectively. Limonoid 1 significantly inhibited the production of NO, TNF-α and IL-1ß in RAW 264.7 cells. Therefore, limonoid derivative may be a promising source of bioactive metabolite for inflammatory diseases.

Chordoma of petrosal mastoid region: A case report.

BACKGROUND: Chordoma is a rare low-grade malignant tumor originating from embryonic notochordal tissue mainly occurring in the axial bone, mostly in the spheno-occipital junction and sacrococcyx, which accounts for approximately 1% of all malignant bone tumors and 0.1%-0.2% of intracranial tumors. Chordoma in the petrous mastoid region is rare. CASE SUMMARY: We describe a 36-year-old male patient with chordoma in the left petrous mastoid region. The main clinical manifestations were pain and discomfort, which lasted for 2 years. Magnetic resonance imaging showed a lobulated mass in the left petrous mastoid with an unclear boundary and obvious enhancement. The tumor was completely removed after surgical treatment, and a histological examination confirmed that the tumor was a chordoma. During 5 years of follow-up, no clinical or radiological evidence of recurrence or metastasis was found. CONCLUSION: Chordoma in the petrosal mastoid region is rare but should be included in differential diagnosis of petrosal mastoid tumors.

Diffuse xanthoma in early esophageal cancer: A case report.

BACKGROUND: Gastrointestinal xanthomas are asymptomatic and infrequent non-neoplastic lesions that commonly occur in the stomach with Helicobacter pylori-associated gastritis and rarely in the esophagus. To date, there have been no reports of esophageal xanthoma combined with esophageal cancer. Herein, we present the first case in the literature of a diffuse xanthoma complicated with early esophageal cancer. Moreover, this combination makes the endoscopic diagnosis difficult if it is not in mind. CASE SUMMARY: A 68-year-old man visited our department with a 2-mo history of epigastric discomfort. He underwent surgery for gastric cancer 6 years ago. Esophagogastroduodenoscopy showed a semi-circumferential irregular yellowish-colored and granular lesion in the esophagus (30-35 cm from the incisors). Using magnifying endoscopy with narrow band imaging, aggregated minute and yellowish-colored spots with tortuous microvessels on the surface were observed, and background coloration was clearly seen in the lesion. As endoscopic biopsy suggested a histologically high-grade dysplasia; the lesion was completely resected en bloc by endoscopic submucosal dissection (ESD). The resected specimen was confirmed to be a squamous cell carcinoma in situ with extensive foamy cells in the superficial mucosal layer. Immunohistochemically, the observed foamy cells were strongly positive for CD68, which is characteristic of xanthoma. The clinical course was favorable, and no recurrence was observed 2 years and 7 mo after ESD. CONCLUSION: Diffuse xanthoma concurrent with early esophageal cancer is extremely rare. The characteristic endoscopic features may assist endoscopists in diagnosing similar lesions.

Tumor necrosis factor receptor-associated factor (TRAF) 6 inhibition mitigates the pro-inflammatory roles and proliferation of rheumatoid arthritis fibroblast-like synoviocytes.

BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a crucial role in RA through producing inflammatory cytokines and proteases which could cause cartilage destruction. We showed previously that elevated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium correlated significantly with the severity of synovitis and the number of infiltrated inflammatory cells. The aims of this study are to detect the roles of TRAF6 in RA-FLSs. METHODS: Synovium were collected by closed needle biopsy from inflamed knees of active RA patients, and FLSs were isolated by modified tissue culture method. Expression of TRAF6 and CD55 in RA synivium was tested by double immunofluorescence (IF) staining. TRAF6 in RA-FLSs was inhibited using Lentiviral-TRAF6-shRNA transfection. Real-time PCR and ELISA were used to detect the mRNA expression and secretion of matrix metalloproteinase (MMP) and pro-inflammatory cytokines. Cell Counting Kit-8 was used to detect cell proliferation, flow cytometry was used to detect cell cycle, and Annexin V assay was used to detect cell apoptosis. RESULTS: We showed that in the intimal and subintimal area of RA synovium, TRAF6 was expressed obviously not only in CD55+ cells, but also in some other CD55- cells. TRAF6 expression in RA-FLSs was suppressed effectively by Lentiviral-TRAF6-shRNA transfection. Inhibition of TRAF6 in RA-FLSs mitigated the mRNA levels and secretion of pro-inflammatory cytokines and MMPs, such as IL-1ß, IL-8, IL-6, TNF-α, MMP-13, and MMP-3. In addition, it decreased the proliferation of RA-FLSs, blocked RA-FLSs in G0/G1-phase, and inhibited the cells to go into S-phase and G2/M-phase, but not facilitated apoptosis of RA-FLSs. CONCLUSION: TRAF6 plays direct roles in the pro-inflammatory effects and proliferation of RA-FLSs. TRAF6 may serve as a potential treatment target in RA.

Bone Marrow Stromal Cells Combined With Sodium Ferulate and n-Butylidenephthalide Promote the Effect of Therapeutic Angiogenesis via Advancing Astrocyte-Derived Trophic Factors After Ischemic Stroke.

Being a potential candidate for stroke treatment, bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) have been demonstrated to be able to enhance angiogenesis and proliferation of reactive astrocytes, which subsequently leads to the amelioration of neurological injury. Increasing evidence further indicates that combining BM-MSCs with certain agents, such as simvastatin, may improve therapeutic effects. Sodium ferulate (SF) and n-butylidenephthalide (BP), two main components of Radix Angelica Sinensis, are proven to be important regulators of stem cells in cell migration, differentiation, and pluripotency maintenance. This study aimed to investigate whether combining BM-MSCs with SF and BP had better therapeutic effect in the treatment of stroke, and the underlying molecular basis for the therapeutic effects was also investigated. The results showed that combination treatment notably reduced neurological injury after stroke and increased the expression of astrocyte-derived vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and von Willebrand factor-positive vascular density in the ischemic boundary zone as evaluated by immunofluorescence staining. After treatment with BM-MSCs plus SF and BP, astrocytes showed increased expression of VEGF and BDNF by upregulating protein kinase B/mammalian target of rapamycin (AKT/mTOR) expression in an oxygen- and glucose-deprived (OGD) environment. Human umbilical vein endothelial cells (HUVECs) incubated with the conditioned medium (CM) derived from OGD astrocytes treated with BM-MSCs plus SF and BP showed significantly increased migration and tube formation compared with those incubated with the CM derived from OGD astrocytes treated with BM-MSCs alone. These results demonstrate that combination treatment enhances the expression of astrocyte-derived VEGF and BDNF, which contribute to angiogenesis after cerebral ischemia, and the underlying mechanism is associated with activation of the astrocytic AKT/mTOR signaling pathway. Our study provides a potential therapeutic approach for ischemic stroke.

Ras activation mediates WISP-1-induced increases in cell motility and matrix metalloproteinase expression in human osteosarcoma.

WISP-1 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of matrix cellular proteins. Osteosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effect of WISP-1 on migration activity in human osteosarcoma cells is mostly unknown. In this study, we first found that the expression of WISP-1 in osteosarcoma patients was significantly higher than that in normal bone and corrected with tumor stage. Exogenous treatment of osteosarcoma cells with WISP-1 promoted cell motility and matrix metalloproteinase (MMP)-2 and MMP-9 expression. In addition, the Ras and Raf-1 inhibitor or siRNA abolished WISP-1-induced cell migration and MMP expression. On the other hand, activation of the Ras, Raf-1, MEK, ERK, and NF-κB signaling pathway after WISP-1 treatment was demonstrated, and WISP-1-induced expression of MMPs and migration activity were inhibited by the specific inhibitor, and mutant of MEK, ERK, and NF-κB cascades. Taken together, our results indicated that WISP-1 enhances the migration of osteosarcoma cells by increasing MMP-2 and MMP-9 expression through the integrin receptor, Ras, Raf-1, MEK, ERK, and NF-κB signal transduction pathway.