Therapeutic evaluation of galangin on cartilage protection and analgesic activity in a rat model of osteoarthritis

BACKGROUND Osteoarthritis (OA) is a form of arthritis due to degradation of articular cartilage. OA is asso ciated with stiffness, joint pain, and dysfunction, affecting adults worldwide. Galangin is a bioactive fla vonoid that exerts several therapeutic and biological activities. Anti-hyperglycemic, anti-inflammatory, anti-cancer, and anti-apoptotic activities of galangin have been reported in several studies. In the present study, rats were divided into normal control, OA (control), galangin 10 mg/kg (low-dose), galangin 100 mg/kg (high-dose), and celecoxib 30 mg/kg (positive control) groups. All doses were administered orally for 14 consecutive days. The urinary type II collagen (mCTX-II) level as well as reactive oxygen spe cies, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, superoxide dismutase, catalase, lipid peroxidation, reduced glutathione, and glutathione peroxidase levels were measured. In addition, the CTX-II mRNA and protein expression levels were measured. RESULTS Galangin supplementation significantly reduced the mCTX-II level compared with controls. Galangin treatment significantly reduced reactive oxygen species, lipid peroxidation, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha levels, but increased catalase, superoxide dismutase, glu tathione peroxidase, and reduced glutathione levels. Galangin treatment significantly reduced the CTX-II mRNA and protein expression levels. The low CTX-II level in tissue indicated the inhibition of cartilage degradation. CONCLUSIONS In summary, supplementation with galangin was effective against OA. The identification of potential therapeutic agents that inhibit inflammation may be useful for the management and prevention of OA

Dihydrotestosterone regulating apolipoprotein M expression mediates via protein kinase C in HepG2 cells.

BACKGROUND: Administration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C). However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM), a constituent of HDL, was affected by dihydrotestosterone (DHT). METHODS: HepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC), phorbol-12-myristate-13-acetate (PMA), blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis. RESULTS: Addition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 µM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI) were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice. CONCLUSIONS: DHT directly and selectively down-regulated the level of ApoM mRNA and the secretion of ApoM by protein kinase C but independently of the classical androgen receptor.

Inhibition of the EGFR with nanoparticles encapsulating antisense oligonucleotides of the EGFR enhances radiosensitivity in SCCVII cells.

The aim of this study is to evaluate the effects of antisense epidermal growth factor receptor (EGFR) nanoparticles on cell survival and radiosensitivity in the head and neck squamous cell carcinoma cell line SCCVII. Experiments were performed using the murine head-and-neck tumor cell line, SCCVII. Nanoparticle encapsulated antisense EGFR oligonucleotides were combined with radiotherapy and the relative radiosensitivity of the cells was assessed in vitro by MTT and standard colony formation. The proportion of apoptotic cells and cell cycle stages were analyzed by flow cytometry. C3H/He mice with SCCVII tumor heterografts were treated with antisense-EGFR-nanoparticles or RT alone, or with combinations of concomitant and sequential therapy. The relative radiosensitivity of the tumors was assessed in vivo by growth delay assays. The SCCVII cells were resistant to anti-EGFR nanoparticles or radiation therapy alone, but a synergic inhibition effect was observed when the therapies were combined. When the SCCVII cells were pre-treated with 2 mug of antisense-EGFR nanoparticles for 24 h and X-irradiated (4 Gy), flow cytometry analysis revealed cell cycle arrest in G(1) phase and an increased proportion of apoptotic cells. Our results show that antisense EGFR nanoparticles enhance radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance. Collectively, these findings may have therapeutic implications because EGFR inhibition may improve the therapeutic efficacy of radiation even in the tumor cells that are resistant to anti-EGFR therapy.

Esophageal foreign body as a cause of upper gastrointestinal hemorrhage: case report and review of the literature.

Foreign body ingestion is a common complaint in the emergency department. Severe upper gastrointestinal (GI) hemorrhage is a rare complication of foreign body ingestion and is always considered to signal aortoesophageal fistula (AEF). We report a rare case of a 65-year-old man with upper GI hemorrhage caused by an ingested duck bone 10 days previously. Instead of AEF, massive erosion and edema were found in the esophagus, highlighting the potentially complex pathology of foreign body ingestion. A literature review of the recognized clinical features of esophageal foreign body is described. Some practical points and pitfalls in the management of esophageal foreign body are presented. For patients with a history of esophageal foreign body ingestion, the clinician must maintain a high index of suspicion and must endeavor to obtain a full history.