Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines.

Osteoarthritis (OA) is a common rheumatic disease associated with imbalanced cartilage homeostasis which could be corrected by mesenchymal stem cells (MSCs) therapy. However, MSCs from different origins might exhibit distinct differentiation capacities. This study was undertaken to compare the therapeutic efficacies between MSCs from cord blood (CB-MSCs) and bone marrow (BM-MSCs) on OA treatment. The surface phenotypes and multipotent capacities of CB-MSCs and BM-MSCs were first characterized. The coculture commitment system was subsequently utilized for comparing the patterned molecules in stage-specific chondrogenesis of committed MSCs. For examining the therapeutic efficacies, committed CB-MSCs and BM-MSCs were encapsulated in neo-cartilage and subjected into pro-inflammatory cytokine environment. Finally, chondrogenic and inflammatory cytokine profiles in committed MSCs were evaluated. CB-MSCs and BM-MSCs were both negative for hematopoietic markers and positive for adhesion and mesenchymal cell markers. The CB-MSCs showed a markedly higher chondrogenic potential and relatively lower osteogenic and adipogenic capacities than BM-MSCs. During chondrogenesis, the committed CB-MSCs also showed significant increases in cell proliferation, adhesion molecules, signaling molecules, and chondrogenic-specific gene expressions in a coculture system. For the therapeutic efficacies, the committed CB-MSCs could strongly recover the pro-inflammatory cytokines diminished-Col II and proteoglycan expressions in a 3D arthritic model. The IL-10, ICAM-1 and TGF-ß1 were also up-regulated in committed CB-MSCs analyzed by using cytokine profiling. Our data demonstrate that CB-MSCs possess specific advantages in cartilage regeneration over BM-MSCs. The CB-MSCs showed a better therapeutic potential that can contribute to advanced cell-based transplantation for clinical OA therapy.

Fenofibrate lowers lipid accumulation in myotubes by modulating the PPARα/AMPK/FoxO1/ATGL pathway.

Fenofibrate, a fibric acid derivative, is known to possess lipid-lowering effects. Although fenofibrate may activate peroxisome proliferator-activated receptor (PPAR)α and regulate the transcription of several genes, the underlying mechanisms are poorly understood. In this study, we demonstrated that incubation of C2C12 myotubes with fenofibrate increased adipose triglyceride lipase (ATGL) expression and suppressed fatty acid synthase (FAS) level, thereby decreasing intracellular triglyceride accumulation when cells were incubated at high-glucose condition. Fenofibrate increased the phosphorylation of AMP-activated protein kinase (AMPK), which subsequently increased fatty acid ß-oxidation. AMPK phosphorylation was reduced by pretreatment with GW9662 (a PPARα inhibitor), suggesting that AMPK may be a downstream effector of PPARα. Pretreatment with compound C (an AMPK inhibitor) or GW9662 blocked fenofibrate-induced ATGL expression and the lipid-lowering effect. Our results suggest that AMPK is as an upstream regulator of ATGL. With further exploration, we demonstrated that fenofibrate stimulated FoxO1 translocation from the cytosol to nuclei by immunefluorescence assay, chromatin immuneprecipitation assay, and reporter assay. Furthermore, oral administration of fenofibrate ameliorated the body weight, visceral fat and serum biochemical indexes in db/db mice. Taken together, our results suggest that the lipid-lowering effect of fenofibrate was achieved by activating PPARα and AMPK signaling pathway that resulted in increasing ATGL expression, lipolysis, and fatty acid ß-oxidation.

Decline of hepatitis B carrier rate in vaccinated and unvaccinated subjects: sixteen years after newborn vaccination program in Taiwan.

Taiwan was an endemic area for hepatitis B virus (HBV) infection, and related liver diseases cause a significant drain of public resources. To control the endemic, a nation-wide newborn vaccination program was started in 1985. We reviewed the results of the annual survey for HBV surface antigen (HBsAg) performed in freshmen class of two high schools in Hualien, eastern Taiwan, from 1991 to 2001. A total of 10,194 students, most of them 15 years old, were tested for serum HBsAg using enzyme immunoassays. There is a significant trend (P < 0.0001) of decreasing HBsAg carrier rate from 20.3 to 4.4% in males and 14.3% to 2.4% in females, respectively, over 11 years. The HBsAg carrier rate was 16.0-20.3% in students surveyed during 1991-1993 (born more than 6 years before the start of the national vaccination program), which decreased to 7.7-11.9% during 1994-1999 (born 1-6 years before the program). It further declined to 4.7% and 3.4% in 2000 and 2001 (born after the start of the program). The HBsAg carrier rate in male students was significantly higher than that in female students in most of the years. The HBV newborn vaccination program not only successfully prevented most of the perinatal transmission of HBV but also reduced horizontal transmission of HBV to children born up to 6 years before the start of the program. Also, the protection persisted for at least 15 years.

Trend of hepatitis B virus infection in freshmen classes at two high schools in Hualien, Taiwan from 1991 to 1999.

Taiwan is an endemic area of hepatitis B virus (HBV) infection. A nationwide mass vaccination program to prevent HBV infection was started in 1985. Perinatal and horizontal transmission of HBV decreased substantially after the launching of this program. However, the influence of this program on children born before 1985 has not been studied. From 1991 to 1999, annual surveys of hepatitis B virus surface antigen (HBsAg) and antibody (anti-HBs) were carried out in freshmen at two high schools in Hualien, Taiwan. The average age was 16 years old. Although these students were born 2-10 years after the start of the national HBV vaccination program, there is a significant trend of decreasing HBsAg carrier rate (from 21.0% to 10.5% in males and 14.3% to 4.7% in females) and increasing anti-HBs rate (from 56.6% to 67.8% in males and 70.3% to 75.9% in females) over the 9 years. With yearly comparison, the carrier rate of HBsAg started to show significant decrease since 1994, while the anti-HBs began to rise significantly after 1996, especially in male students. The HBsAg carrier rate in male students was significantly higher, while the anti-HBs rate was significantly lower, than that in female students in most of the years. It is concluded that the effect of HBV vaccination also reduced horizontal transmission of HBV to children born up to 7 years before the start of the program.