Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle α-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

The purpose of this study was to examine whether hesperidin inhibits bone loss in ovariectomized mice (OVX), an animal model of postmenopausal osteoporosis. Forty 8-wk-old female ddY mice were assigned to five groups: a sham-operated group fed the control diet (AIN-93G), an OVX group fed the control diet, an OVX+HesA group fed the control diet containing 0.5 g/100 g hesperidin, and an OVX+HesB group fed the control diet containing 0.7 g/100 g alpha-glucosylhesperidin and an OVX+17beta-estradiol (E(2)) group fed the control diet and administered 0.03 micro g E(2)/d with a mini-osmotic pump. After 4 wk, the mice were killed and blood, femoral, uterine and liver were sampled immediately. Hesperidin administration did not affect the uterine weight. In OVX mice, the bone mineral density of the femur was lower than in the sham group (P < 0.05) and this bone loss was significantly prevented by dietary hesperidin or alpha-glucosylhesperidin. The Ca, P and Zn concentrations in the femur were significantly higher in the hesperidin-fed and E(2) groups than in the OVX group. Histomorphometric analyses showed that the trabecular bone volume and trabecular thickness in the femoral distal metaphysis were markedly decreased (P < 0.05) by OVX, and alpha-glucosylhesperidin significantly prevented this bone loss. Furthermore, hesperidin decreased the osteoclast number of the femoral metaphysis in OVX mice, as did E(2). Serum and hepatic lipids were lower in mice that consumed the hesperidin-containing diets (P < 0.05) than in the OVX group fed the control diet. These results suggest a possible role for citrus flavonoids in the prevention of lifestyle-related diseases because of their beneficial effects on bone and lipids.

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Aim:The aim of our study is to elucidate the effects of EPA-or DHA-rich fish oil, and of the latter plus fenofibrate, on lipid metabolism in female KK mice. Methods: Female KK mice were fed purified experimental diets containing lard/safflower oil (4:6, Lard/SO), EPA-rich fish oil (EPA), DHA-rich fish oil (DHA), or DHA-rich fish oil plus 0.2% (w/w) fenofibrate (DHA FF) for 8 weeks. At the end of the experiments, we measured levels of plasma lipids, hepatic triglycerides, and cholesterol, as well as the hepatic mRNA expression of lipogenic and lipidolytic genes. Results: The final body weight of EPA-and DHA-fed groups was significantly lower than that of the Lard/SO-fed group, and that of the DHA FF-fed group was the lowest. All three fish oil treatments significantly reduced plasma insulin levels. Hepatic lipid levels significantly decreased in all three of these groups compared with the Lard/SO-fed group. Plasma adiponectin increased in both the EPAand DHA-fed groups, but the increase was suppressed in the DHA FF-fed group. Hepatocytes of Lard/SO-fed mice were filled with numerous fat droplets, but fat accumulation was inhibited in both EPA-and DHA-fed mice and was significantly prevented by fenofibrate treatment. SREBP-1c mRNA levels were decreased by about half in EPA-and DHA-fed mice compared with Lard/SO-fed mice. FAS, Insig-1, HMG-CoA reductase, and LDL-receptor mRNA levels also markedly decreased in both EPA-and DHA-fed mice, but there was no additional decrease in DHA FF fed mice. Fenofibrate treatment significantly induced mRNA expression of AOX and UCP-2, but not of PPAR . Conclusion: These data suggest that fish oil inhibited body weight gain and exhibited an anti-obesity effect through the inhibition of lipid synthesis in female KK mice. Furthermore, fenofibrate treatment markedly inhibited body weight gain by the induction of fatty acid oxidation. Plasma adiponectin levels did not increase in mice fed DHA-rich fish oil with fenofibrate, although white adipose tissue (WAT) weight significantly decreased. We considered that adiponectin sensitivity increased more in mice fed DHA-rich fish oil with fenofibrate than in mice fed DHA-rich fish oil alone.

Puerariae radix (PR), the root of Pueraria labata (Willd.) Ohwi, a wild creeper leguminous plant, is one of the earliest and most important crude herbs used in Chinese medicine for various medicinal purposes. PR contains a high amount of isoflavonoids such as daidzein and genistein, which are known to prevent bone loss induced by estrogen deficiency. We have demonstrated that soybean isoflavones prevent bone loss in an osteoporotic animal model. To examine the possible role of PR in bone metabolism, female mice were ovariectomized (OVX), and some OVX mice were fed a diet containing low, middle, and high doses (5%, 10%, and 20% of diet, respectively) of PR for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight. The total femoral bone mineral density (BMD) was significantly reduced by OVX, and the decrease in BMD caused by OVX was significantly inhibited by intake of the diet with the low dose of PR and completely prevented by the middle dose of PR. Histological analysis of the femoral metaphysis showed that intake of the diet with the middle dose of PR completely prevented decrease in trabecular bone volume (BV/TV) and trabecular thickness (Tb.Th) and restored the increase in trabecular separation (Tb.Sp) in OVX mice. In contrast, intake of the diet with the high dose of PR further increased BV/TV and Tb.Th and decreased Tb.Sp in OVX mice compared with that in the sham-operated mice. These results suggest that PR may represent a potential alternative medicine for hormone replacement therapy (HRT) in the prevention of osteoporosis in postmenopausal women.

We studied 1809 patients with oral cancer who visited and were treated, in 2002, at the 148 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons. Of these institutions, 39 are dental university hospitals, 44 are medical university hospitals, 64 are general hospitals, and for 1 institution, the classification was not known. The patients consisted of 1071 (59.2%) males and 738 (40.8%) females (male: female ratio, 1.45:1), who had a average age of 65.2 years. The tongue (40.2%) was the most common site affected, followed by the gingiva (32.7%), buccal mucosa (10.1%), and oral floor (9.0%). There were 6 cases of multiple intraoral cancers. On histopathological examinations, squamous cell carcinoma (88.7%) was the most common type found, followed by adenoid cystic carcinoma (2.1%), and mucoepidermoid carcinoma (1.7%). Cases classified as T2N0 were the most common (32.1%), followed by T1N0 (21.4%), T4N0 (8.0%), and T2N1 (7.6%). Distant metastasis occurred in 17 patients (1.0%). Nonepithelial tumors, among which malignant melanoma was the most common type, accounted for 1.8% of the tumors. The sizes of the nonepithelial malignant tumors ranged from 1.0 to 7.0 cm, with an average size of 3.7 cm.

Aims/IntroductionDiabetes mellitus and periodontitis are closely related. A huge number of reports has addressed the effect of periodontal intervention therapy on glycemic control, but no reports have addressed the effect of glycemic intervention therapy on periodontal disease in type 2 diabetic patients. The aim of this study was to examine the effect of improved glycemic control by glycemic intervention therapy on periodontitis in type 2 diabetic patients.Materials and MethodsA total of 35 patients underwent intervention therapy to improve glycemic control without periodontal treatment. Glycohemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), bleeding on probing (BOP), probing pocket depth (PPD) and intraoral community periodontal index (CPI) codes of the World health Organization (WHO) were examined at baseline, and 2 and 6 months after the intervention therapy to improve glycemic control.ResultsAfter the improvement of glycemic control, BOP lesions improved, but deep PPD lesions and WHO CPI codes did not improve. Subanalyses showed that effective glycemic control (average HbA1c reduction 1.8%) improved BOP lesions, but did not affect deep PPD lesions and WHO CPI codes. In addition, high BOP lesions at baseline responded more effectively to glycemic intervention. Further analysis of CPI codes in all individual periodontal sites independent of WHO CPI codes in 35 patients showed that only gingival inflammation without a deep periodontal pocket improved after glycemic intervention.ConclusionsEffective glycemic control improves BOP lesions in type 2 diabetic patients with periodontitis through ameliorating inflammation at the gingival sites of periodontal tissue. This trial was registered with the University Hospital Medical Information Network (no. UMIN000007670).