Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males: potential mechanism of resistance to weight loss among Japanese obese smokers

<p>Abstract</p> <p>Background</p> <p>The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels.</p> <p>Methods</p> <p>We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS).</p> <p>Results</p> <p>In subjects with BMI below 25 kg/m², both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m², smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS.</p> <p>Conclusions</p> <p>Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than non-smokers.</p

Pengaruh Dimensi Benda Uji Terhadap Kuat Tekan Beton

Kuat tekan adalah karakteristik mekanik utama dari beton yang dapat diketahui melalui penelitian uji tekan di laboratorium terhadap benda uji. Baik dalam bentuk kubus ataupun silinder dengan ukuran standar: 10cm x 10cm x 10cm dan 15cm x 15cm untuk kubus dan 10cm x 20cm dan 15cm x 30cm untuk silinder. Untuk mendapatkan informasi mengenai kecendrungan harga kuat tekan beton dengan variasi dimensi benda uji, telah dilakukan penelitian-penelitian di laboratoriun untuk mendapatkan komposisi campuran tertentu pada umur beton 28 hari, variasi ukuran benda uji dibuat: 10cm x 10cm x 10cm, 12,5cm x 12,5cm x 12,5cm dan 15cm x 15cm x 15cm untuk kubus dan 10cm x 20cm, 12,5cm x 25cm dan 15cm x 30cm untuk silinder. Dengan jumlah benda uji masing-masing 20 buah untuk setiap ukuran benda uji. Melalui prosedur standar pengujian kuat tekan dan menggunakan formula-formula baku perhitungan tekan rata-rata diperoleh informasi bahwa peningkatan ukuran dimensi benda uji menghasilkan penurunan kuat tekan rata-rata, untuk benda uji kubus dengan ukuran masing-masing: 10cm x 10cm x 10cm, 12,5cm x 12,5cm x 12,5cm dan 15cm x 15cm x 15cm diperoleh kuat tekan rata-rata masing-masing: 32,86MPa, 31,26MPa dan 31,036MPa. Sedangkan untuk silinder dengan kururan 10cm x 20cm, 12,5cm x 25cm dan 15cm x 30cm diperoleh kuat tekan rata-rata masing-masing: 31,47MPa, 30,85MPa dan 30,44MPa

Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice

Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH

Febrile neutropenia and periodontitis: lessons from a case periodontal treatment in the intervals between chemotherapy cycles for leukemia reduced febrile neutropenia

Oral and systemic infections arising from the oral cavity are significant problems in clinical management of patients undergoing leukemia treatment. However, there is significant disparity in the reported incidences of development of periodontal infections. Evidence is limited to those showing the systemic influence of periodontal infection in neutropenic patients. This study indicated an association between febrile neutropenia (FN) and periodontitis in a case in which periodontal treatment in the intervals between chemotherapy cycles reduced FN in subsequent courses of chemotherapy and hematopoietic transplantation (HCT). Periodontal treatment was performed in a 61-year-old man with advanced periodontitis, who received HCT following three cycles of chemotherapy. After recovery from neutropenia induced by initial chemotherapy, periodontal treatment was performed in each chemotherapy interval period. Following extraction of teeth with severe advanced periodontitis, all teeth were subjected to periodontal pocket curettage and root planning, which are common periodontal treatments to reduce periodontal pockets harboring anaerobic periodontal bacteria, before HCT. Periodontal treatment successfully reduced periodontal pockets from 4.1 +/- 1.5 mm to 3.0 +/- 0.6 mm, which was almost within the healthy range (< 3.0 mm), before HCT. The frequency of FN decreased significantly with increasing cycles of chemotherapy, and decreases in FN corresponded to progress of periodontal treatment. Blood cultures obtained a total of 12 times throughout leukemia treatment were all negative. The observations reported here indicate the importance of periodontal treatment in clinical management of patients undergoing leukemia treatment to prevent FN, although all blood cultures were negative

Spry2 is a novel therapeutic target for periodontal tissue regeneration through fibroblast growth factor receptor signaling and epidermal growth factor signaling

Sprouty2 (Spry2) inhibits the activation of the extracellular signal-regulated kinase (ERK) pathway via receptor tyrosine kinase signaling. In a recent paper published in Journal of Cellular Biochemistry, we demonstrated that transfection of a dominant-negative mutant of Spry2 enhanced fibroblast growth factor (FGF)- and epidermal growth factor (EGF)-induced ERK activation in osteoblasts. In contrast, it decreased their activation in gingival epithelial cells. Consistent with these observations, the sequestration of Spry2 increased osteoblast proliferation by FGFR and EGFR stimulation, whereas it decreased gingival epithelial cell proliferation via the ubiquitination and degradation of EGF receptors (EGFR). In addition, reduction of Spry2 activity upregulated Runx2 expression and downregulated Twist, a negative regulator of Runx2 through FGFR and EGFR signaling, resulting in enhanced osteoblastogenesis in osteoblasts. Furthermore, we also found that suppression of Spry2 upregulated cell proliferation and migration in human periodontal ligament cell lines when they were stimulated by both FGF and EGF, and led to a shift in macrophage polarization, exerted immunosuppressive and tissue-repairing effects in macrophages. These results suggest that the application of a Spry2 inhibitor may effectively resolve inflammation by periodontitis and allow periodontal ligament and alveolar bone to grow and block the ingrowth of gingival epithelial cells in bony defects, biologically mimicking the barrier effect seen in conventional GTR. This approach has potential for developing a new regeneration strategy

Focal adhesion kinase mediates human leukocyte histocompatibility antigen class II-induced signaling in gingival fibroblasts

Background and Objective: The role of human leukocyte antigen class II molecules on nonantigen-presenting cells has been a matter of controversy. We previously reported that human leukocyte antigen class II molecules on human gingival fibroblasts do not present antigens, but transduce signals into the cells by making a complex with antigenic peptide T-cell receptor or by stimulating cell surface human leukocyte antigen-DR molecules with human leukocyte antigen-DR antibody (L243), which mimics the formation of the human leukocyte antigen class II-antigenic peptide T-cell receptor complex, resulting in the expression of several cytokines. The aim of this study was to detect human leukocyte antigen class II-associated molecules mediating human leukocyte antigen class II-induced signals into the cells. Material and Methods: Antibody-based protein-microarray analysis was performed to detect activated signaling molecules in gingival fibroblasts stimulated via human leukocyte antigen class II molecules. Then, we examined if these molecules structurally associate with human leukocyte antigen class II and actually transduce signals into the cells. Results: Stimulation of human leukocyte antigen class II on gingival fibroblasts by L243 resulted in enhanced phosphorylation of focal adhesion kinase. Focal adhesion kinase was co-immunoprecipitated with human leukocyte antigen-DR by L243. Stimulation of gingival fibroblasts with L243 induced phosphorylation of focal adhesion kinase. Luteolin, a putative focal adhesion kinase inhibitor, suppressed phosphorylation of focal adhesion kinase and dose dependently inhibited human leukocyte antigen class II-induced cytokine production. Conclusion: Focal adhesion kinase is structurally associated with human leukocyte antigen-DR and mediates human leukocyte antigen class II-induced signals in gingival fibroblasts