Background/Objectives:Although obesity is associated with low-grade inflammation and metabolic disorders, clinical studies suggested some obese people were metabolically healthy with smaller adipocyte size compared with metabolically abnormal obese (MAO). This indicated adipocyte size may be an important predictor underlay the distinction between MAO and metabolically healthy obese. As recent study has shown that adipocytes expressed class II major histocompatibility complex (MHCII), which functioned as APCs during obesity. However, the relationship between adipocyte hypertrophy and MHCII expression was not involved. Here we hypothesize that hypertrophic adipocytes could be associated with upregulating MHCII to influence adipose tissue metabolism.Methods:Adipocytes were sorted by fluorescence-activated cell sorting (FACS) according to the cell size from MAO mice. The activation of MHCII, T cells and related signaling molecules were examined by FACS, ELISA and western blotting. 3T3-L1 cell line and primary adipocytes were used to examine the effect of free fatty acids (FFA) on adipocytes enlargement and MHCII expression.Results:MAO mice had a significant increase in adipocytes size and FFA concentration. The large adipocytes from both obese and non-obese mice expressed higher levels of MHCII than small adipocytes. Importantly, large adipocytes from obese mice stimulated CD4+ T cells to secrete more interferon (IFN)-γ. Furthermore, the activation of the JNK-STAT1 pathway was involved in upregulation of MHCII in large adipocytes. In vitro FFA treatment promoted adipocyte hypertrophy and expression of MHCII-associated genes.Conclusions:This study demonstrates that large adipocytes highly express MHCII and function as APC to stimulate IFN-γ-expressing CD4+ T cells, in which FFA may have important roles before IFN-γ elevated. These findings suggest that adipocyte hypertrophy, rather than overall obesity, is the major contributor to adipose tissue inflammation and insulin resistance.
The present work provides evidence that mouse miR-20a promotes adipocyte progenitor cells to differentiate and this function may depend upon its inhibitory effects on Kdm6b and TGF-β signaling.
Some anaerobes and facultative anaerobes have been used in tumor-specific gene therapy by reason of their selective growth in tumors. In this work, we aimed to evaluate the anticancer efficacy of attenuated Salmonella typhimurium as a carrier to deliver the Escherichia coli purine nucleoside phosphorylase (ePNP) gene for GDEPT (gene-directed enzyme-prodrug therapy). A live attenuated purine-auxotrophic strain of S. typhimurium (SC36) was used to carry the pEGFP-C1-ePNP vector that contains a green fluorescent protein (GFP) and an ePNP gene under the control of the human cytomegalovirus (CMV) promoter. The function of the ePNP expression vector was confirmed in vitro using the enzymic conversion of 6-methylpurine 2 0 -deoxyriboside (MePdR) into 6-methylpurine. We also observed a high bystander effect induced by the ePNP/MePdR system with a very low proportion (1%) of ePNP-positive cells. The killing effect and increased apoptosis induced by SC/ePNP (SC36 carrying the ePNP expression vector) infection were detected by cytotoxicity assay and PI staining flow cytometry analysis, in combination with MePdR administration. Furthermore, SC/ePNP was administered orally into mice bearing melanomas or pulmonary tumors, and its anti-tumor effect was evaluated. When the tumor was huge (500 mm 3 ) at the beginning of MePdR administration, SC/ePNP plus MepdR significantly inhibited tumor growth by about 59-80% and prolonged survival of mice. Complete tumor regression and long-term cure were achieved by MePdR administration, even when the tumor was large (100 mm 3 ) at the beginning of MePdR treatment. Our data support a hopeful view that tumor-targeting SC36 could improve antitumor efficacy of the ePNP/MePdR system due to its preferential accumulation and anticancer activity in tumors.
The purpose of this study is to investigate whether a periosteum patch could enhance polyethylene terephthalate (PET) artificial ligament graft osseointegration in a bone tunnel. 12 female goats underwent ACL reconstruction with a PET artificial ligament graft in the right knees. Right knees in 6 goats were reconstructed with periosteum patch-enveloped PET grafts (Periosteum group) in the tibia bone tunnel, whereas the other 6 goats had no periosteum patch and served as the Control group. All the goats were sacrificed at 12 months after surgery. 3 tibial-graft complex samples in each group were harvested consecutively for microcomputed tomography (micro-CT) scan, magnetic resonance imaging (MRI) scan and histological evaluation. The other 3 tibial-graft complex samples in each group were harvested for biomechanical testing. The mean pull-out load of the Periosteum group (208?25?N) at 12 months was significantly higher than that of the Control group (107?13?N) (p=0.0044). According to the micro-CT scan, more new bone formation was observed at the graft-bone interface in the Periosteum group compared with the Control group. Furthermore, MRI showed that the Periosteum group appeared to have a better graft osseointegration within the bone tunnel compared with the Control group. Histologically, application of a periosteum patch induced more new bone and Sharpey?s fiber formation between the graft and bone tunnel compared with the controls. The study has shown that periosteum enveloping of the PET artificial ligament has a positive effect in the induction of artificial ligament osseointegration within the bone tunnel.
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