Improved bone regeneration through amniotic membrane loaded with buccal fat pad-derived MSCs as an adjuvant in maxillomandibular reconstruction

BackgroundHuman amniotic membranes (HAMs), as a biological membrane with healing, osteogenic, and cell therapy potential, has been in the spotlight to enhance the outcomes of treating bone defects. Present study aims to clinically assess the potential of HAM loaded with buccal fat pad-derived stem cells (BFSCs) as an osteogenic coverage for onlay bone grafts to maxillomandibular bone defects.Materials and methodsNine patients with jaw bone defects were enrolled in the present study. The patients were allocated to two study groups: Iliac crest bone graft with HAM coverage (n = 5), and Iliac bone grafts covered with HAM loaded with BFSCs (n = 4). Five months following the grafting and prior to implant placement, cone beam computed tomography was performed for radiomorphometric analysis.ResultsThe mean increase in bone width was found to be significantly greater in the HAM + BFSCs group (4.42 ± 1.03 mm versus 3.07 ± 0.73 mm, p < 0.05). Further, the changes in vertical dimension were greater in the HAM + BFSCs group (4.66 ± 1.06 mm versus 4.14 ± 1.03 mm, p > 0.05).ConclusionCombined use of HAM with mesenchymal stem cells may enhance bone regeneration specifically in the horizontal dimension. Moreover, this methodology reduces the amount of harvested autogenous bone and diminish secondary bone resorption.     

Nuclear receptors and metabolism: from feast to famine

The ability to adapt to cycles of feast and famine is critical for survival. Communication between multiple metabolic organs must be integrated to properly metabolise nutrients. By controlling networks of genes in major metabolic organs, nuclear hormone receptors (NHRs) play central roles in regulating metabolism in a tissue-specific manner. NHRs also establish daily rhythmicity by controlling the expression of core clock genes both centrally and peripherally. Recent findings show that many of the metabolic effects of NHRs are mediated through certain members of the fibroblast growth factor (FGF) family. This review focuses on the roles of NHRs in critical metabolic organs, including adipose tissue, liver and muscle, during the fed and fasted states, as well as their roles in circadian metabolism and downstream regulation of FGFs.     

Interferon Alpha-2b Therapy in Chronic Hepatitis Delta

Background:

Approximately 5% of hepatitis B virus (HBV) carriers are coinfected with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis and end stage liver disease in chronic HBsAg carriers. The only approved therapy for chronic hepatitis delta is interferon alpha (IFN α) in either pegylated or conventional forms. Although higher doses and longer durations of IFN α therapy in HBV/HDV coinfected patients are currently applied, yet treatment response is low.

Objectives:

We aimed to determine the efficacy of IFN α-2b therapy in patients with HBV/HDV coinfection.

Patients and Methods:

In this cross sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV RNA were recruited and treated for three year duration with 5 million units (MU) of IFN α-2b, three times weekly or one year with 5 MU of IFN α-2b daily. Sustained virological response (SVR) was defined as a negative qualitative HDV RT-PCR, 6 months after treatment cessation.

Results:

Overall, 3 (15%) subjects achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%) patients did not clear HDV during the treatment.

Conclusions:

HDV coinfection with HBV had very low response rate to high doses and long durations of IFN α-2b therapy.     

Glucocorticoid receptor signaling is essential for mesoderm formation and muscle development in zebrafish

Glucocorticoid receptor (GR) signaling is thought to play a key role in embryogenesis, but its specific developmental effects remain unclear. Cortisol is the primary ligand for GR activation in teleosts, and in zebrafish (Danio rerio), the prehatch embryo content of this steroid is of maternal origin. Using early zebrafish developmental stages, we tested the hypothesis that GR signaling is critical for embryo growth and hatching. In zebrafish, maternal GR mRNA is degraded quickly, followed by zygotic synthesis of the receptor. GR protein is widely expressed throughout early development, and we were able to knockdown this protein using morpholino oligonucleotides. This led to a more than 70% reduction in mRNA abundance of matrix metalloproteinase-13 (mmp13), a glucocorticoid-responsive gene. The GR morphants displayed delayed somitogenesis, defects in somite and tail morphogenesis, reduced embryo size, and rarely survived after hatch. This correlated with altered expression of myogenic markers, including myogenin, myostatin, and muscle-specific myosin heavy chain and troponin genes. A key finding was a 70-90% reduction in the mRNA abundance of bone morphogenetic proteins (BMP), including bmp2a, bmp2b, and bmp4 in GR morphants. Bioinformatics analysis confirmed multiple putative glucocorticoid response elements upstream of these BMP genes. GR morphants displayed reduced expression of BMP-modulated genes, including eve1 and pax3. Zebrafish GR mRNA injection rescued the GR morphant phenotype and reversed the disrupted expression of BMP and myogenic genes. Our results for the first time indicate that GR signaling is essential for zebrafish muscle development, and we hypothesize a role for BMP morphogens in this process.