Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animal were reported as reservoirs. Antibodies to HEV and HEV RNA have been detected in some Chinese population and swine groups but few other domestic animals. In this study, to investigate the HEV prevalence, we tested sera from 788 pigs, 100 cows, 50 goats, 49 horses, 101 pet dogs, 105 chickens, 47 duck and 45 pigeons in eastern China for anti-HEV immunoglobulin G (IgG). We also tested 50% of the swine sera, all of sera from the other domestic animals and 13 Shanghai human sera which were positive for anti-HEV immunoglobulin M (IgM) for HEV RNA using reverse transcriptase-polymerase chain reaction. Our results indicated that 82.5% (222/269) of the sows, 53.9% (104/193) of the 4- to 6-month-old swine, 63.4% (168/265) of the 1- to 3-month-old swine, 55.7% (34/61) of the slaughterhouse swine, 24% (12/50) of the goats, 16.3% (8/49) of the horses, 17.8% (21/101) of the pet dogs, 6% (6/100) of the cows, 12.8% (6/47) of the ducks, 4.4% (2/45) of the pigeons and 1.9% (2/105) of the chickens exhibited positive for anti-HEV IgG. Inhibition assay confirmed the infection with HEV or HEV-like viruses in these domestic animals except pigeons and chickens. From the sera, we isolated 18 swine HEV strains, one horse HEV strain and two human HEV strains. Sequence analysis showed that the horse HEV isolate and one swine isolate belonged to genotype 3. The other isolates belonged to genotype 4. The two human isolates were phylogenetically closely related to eight of the swine isolates. In short, the presence of anti-HEV antibody had been confirmed in several species of domestic animals in eastern China and HEV RNA has been identified in swine, human and horse. This suggested that the authorities should pay more attention to the prevalence of HEV in eastern China.

Gliomas are highly malignant brain tumors that are highly invasive and resistant to conventional therapy. Receptor tyrosine kinases (RTKs) such as PDGFRα (platelet-derived growth factor receptor-α), which show frequent aberrant activation in gliomas, are associated with a process of epithelial–mesenchymal transition (EMT), a cellular alteration that confers a more invasive and drug-resistant phenotype. Although this phenomenon is well documented in human cancers, the processes by which RTKs including PDGFRα mediate EMT are largely unknown. Here, we report that SHP-2 (encoded by PTPN11) upregulates an EMT inducer, ZEB1, to mediate PDGFRα-driven glioma EMT, invasion and growth in glioma cell lines and patient-derived glioma stem cells (GSCs) using cell culture and orthotopic xenograft models. ZEB1 and activated PDGFRα were coexpressed in invasive regions of mouse glioma xenografts and clinical glioma specimens. Glioma patients with high levels of both phospho-PDGFRα (p-PDGFRα) and ZEB1 had significantly shorter overall survival compared with those with low expression of p-PDGFRα and ZEB1. Knockdown of ZEB1 inhibited PDGFA/PDGFRα-stimulated glioma EMT, tumor growth and invasion in glioma cell lines and patient-derived GSCs. PDGFRα mutant deficient of SHP2 binding (PDGFRα-F720) or phosphoinositide 3-kinase (PI3K) binding (PDGFRα-F731/42), knockdown of SHP2 or treatments of pharmacological inhibitor for PDGFRα-signaling effectors attenuated PDGFA/PDGFRα-stimulated ZEB1 expression, cell migration and GSC proliferation. Importantly, SHP-2 acts together with PI3K/AKT to regulate a ZEB1-miR-200 feedback loop in PDGFRα-driven gliomas. Taken together, our findings uncover a new pathway in which ZEB1 functions as a key regulator for PDGFRα-driven glioma EMT, invasiveness and growth, suggesting that ZEB1 is a promising therapeutic target for treating gliomas with high PDGFRα activation.

These results indicate that Lenti-HIF-1α can induce BMSC overexpression levels of angiogenic and osteogenic genes in vitro in the normoxic state. Further study will be focused on whether HIF-1α can also improve bone repair in vivo.

Stem cell–based bone tissue engineering has been recognized as a new strategy for maxillary sinus floor elevation. More rapid bone formation may enhance this technique when simultaneous dental implant placement is desired. Adipose tissue–derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) are the most well-characterized cell sources for bone regeneration, but comparative studies on the osteogenic potential of these cells have yielded conflicting conclusions. This study aimed to compare the rapid bone formation capacity of ADSCs and BMSCs in a canine sinus floor augmentation model. In in vitro studies, BMSCs had a higher proliferative ability and greater osteogenic differentiation potential at both the mRNA and protein levels. When GFP-labeled cells on calcium phosphate cement (CPC) scaffolds were implanted subcutaneously into nude mice, both ADSCs and BMSCs survived for 4 wks, but only BMSCs formed new bone. Furthermore, according to sequential fluorescence labeling results for the canine sinus, BMSCs promoted rapid and greater bone regeneration during the entire observation period. In contrast, obvious mineralization was detected starting from 3 wks after implantation in the ADSC group. These results suggest that BMSCs might be more useful than ADSCs for rapid bone regeneration for sinus augmentation with simultaneous implant placement.