Positive Effect of Incubated Adipose-Derived Mesenchymal Stem Cells on Microfat Graft Survival.

Autologous fat grafting is commonly used for soft tissue augmentation, but its unpredictably high resorption rate remains a major limitation. Although adipose-derived mesenchymal stem cells (ASCs) are an attractive candidate for enhancing graft retention, their poor posttransplantation viability limits their application. The authors aimed to evaluate the effect of incubated ASCs on microfat graft survival in an immunocompromised mouse model. Lipoaspirates for microfat injection were collected from the wasted lower abdominal adipose tissues of 5 patients who had undergone breast reconstructive surgery with an abdominal flap. Adipose-derived mesenchymal stem cells were also isolated and proliferated from these fat tissues. Sixty athymic mice were randomly allocated to a control group (microfat grafting alone; n = 30) or ASCs group (microfat grafting plus simultaneous human ASCs injection; n = 30). The volume and weight of survived fat were measured at 8 and 16 weeks, and histopathological and immunologic staining was performed at 16 weeks. The survived fat volume of the ASCs group was significantly greater than that of the control group at 8 and 16 weeks, whereas the weight of survived fat tissues did not significantly differ. Histologic evaluation of the harvested fat indicated significantly higher levels of adipocytes, and fewer cysts and fibrosis in the tissues in the ASCs group than in the control group. The ASCs group also exhibited a significantly higher number of capillary vessels than the control group on CD31 and alpha-smooth muscle actin staining. In conclusion, transplanted fat survival is markedly higher when simultaneous microfat graft and ASCs injection were performed, as compared with that in the classical microfat graft alone method in mice; this improvement was primarily attributed to the increased ability to produce blood vessels.

Shaofu Zhuyu decoction ameliorates obesity-mediated hepatic steatosis and systemic inflammation by regulating metabolic pathways.

Shaofu Zhuyu decoction (SFZYD, also known as Sobokchugeo-tang), a classical prescription drug in traditional East Asian medicine, has been used to treat blood stasis syndrome (BSS). Hepatic steatosis is the result of excess caloric intake, and its pathogenesis involves internal retention of phlegm and dampness, blood stasis, and liver Qi stagnation. To evaluate the effects of treatment with SFZYD on obesity-induced inflammation and hepatic steatosis, we fed male C57BL/6N mice a high fat diet (HFD) for 8 weeks and then treated them with SFZYD by oral gavage for an additional 4 weeks. The results of histological and biochemical examinations indicated that SFZYD treatment ameliorates systemic inflammation and hepatic steatosis. A partial least squares-discriminant analysis (PLS-DA) scores plot of serum metabolites showed that HFD mice began to produce metabolites similar to those of normal chow (NC) mice after SFZYD administration. We noted significant alterations in the levels of twenty-seven metabolites, alterations indicating that SFZYD regulates the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism. Increases in the levels of TCA cycle intermediate metabolites, such as 2-oxoglutaric acid, isocitric acid, and malic acid, in the serum of obese mice were significantly reversed after SFZYD treatment. In addition to inducing changes in the above metabolites, treatment with SFZYD also recovered the expression of genes related to hepatic mitochondrial dysfunction, including Ucp2, Cpt1α, and Ppargc1α, as well as the expression of genes involved in lipid metabolism and inflammation, without affecting glucose uptake or insulin signaling. Taken together, these findings suggest that treatment with SFZYD ameliorated obesity-induced systemic inflammation and hepatic steatosis by regulating inflammatory cytokine and adipokine levels in the circulation and various tissues. Moreover, treatment with SFZYD also reversed alterations in the levels of metabolites of the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism.

Effects of fibrin-binding oligopeptide on osteopromotion in rabbit calvarial defects.

PURPOSE: Fibronectin (FN) has been shown to stimulate bone regeneration in animal models. The aim of this study was to evaluate the capacity of bovine bone mineral coated with synthetic oligopeptides to enhance bone regeneration in rabbit calvarial defects. METHODS: Oligopeptides including fibrin-binding sequences of FN repeats were synthesized on the basis of primary and tertiary human plasma FN structures. Peptide coated and uncoated bone minerals were implanted into 10 mm calvarial defects in New Zealand white rabbits, and the animals were sacrificed at 4 or 8 weeks after surgery. After specimens were prepared, histologic examination and histomorphometric analysis were performed. RESULTS: At 4 weeks after surgery, the uncoated groups showed a limited amount of osteoid formation at the periphery of the defect and the oligopeptide coated groups showed more osteoid formation and new bone formation in the center of the defect as well as at the periphery. At 8 weeks, both sites showed increased new bone formation. However, the difference between the two sites had reduced. CONCLUSIONS: Fibrin-binding synthetic oligopeptide derived from FN on deproteinized bovine bone enhanced new bone formation in rabbit calvarial defects at the early healing stage. This result suggests that these oligopeptides can be beneficial in reconstructing oral and maxillofacial deformities or in regenerating osseous bone defects.

Luteolin suppresses cisplatin-induced apoptosis in auditory cells: possible mediation through induction of heme oxygenase-1 expression.

Luteolin has been shown to possess antitumorigenic, antioxidant, and anti-inflammatory properties. In the present study, we investigated the protective mechanism of luteolin against cisplatin-induced apoptosis in auditory (House Ear Institute-Organ of Corti 1 [HEI-OC1]) cells. Luteolin was found to induce the expression of heme oxygenase-1 (HO-1) in a dose- and time-dependent manner. Luteolin also activated the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway, which plays an important role in the expression of HO-1. Luteolin protected the cells against cisplatin-induced apoptotic cell death. The protective effect of luteolin was abrogated by zinc protoporphyrin IX (ZnPP IX), an HO inhibitor, and antisense oligodeoxynucleotides against the HO-1 gene. Furthermore, pretreatment with luteolin inhibited the activation of caspase-3 and the mitochondrial dysfunction, and the effect of luteolin on the activation of caspase-3 disappeared in the presence of ZnPP IX or PD098059. These results demonstrate that the expression of HO-1 by luteolin is mediated by the ERK pathway, and also that the activating of HO-1 inhibits cisplatin-induced apoptosis in HEI-OC1 1 cells.

Brazilin and the extract from Caesalpinia sappan L. protect oxidative injury through the expression of heme oxygenase-1.

In this study, we examined the protective effects of Caesalpinia sappan L. and its major component, brazilin, against tert-butylhydroperoxide (t-BHP)-induced cell death in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. We found that the extract of C. sappan L. and brazilin induced antioxidant response element (ARE)-luciferase activity and heme oxygenase-1 (HO-1) expression in a concentration-dependent manner. The inductive effect of brazilin was more potent than the extract of C. sappan L. and the expression of HO-1 reached a peak at 12 h after brazilin treatment. The extract and brazilin protected the cells against t-BHP-induced cell death. Their protective effects were abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. These results demonstrate that the extract of C. sappan L. and brazilin induce the expression of HO-1 and the enzyme diminishes t-BHP-induced cell death in HEI-OC1 cells.