Dynamic expression of hepatic GP73 mRNA and protein and circulating GP73 during hepatocytes malignant transformation

Background:Hepatic Golgi protein-73(GP73)expression is related to hepatocellular carcinoma(HCC)progression.The aim of this study was to investigate the dynamic expression of GP73 mRNA and protein during hepatocytes malignant transformation.Methods:Human GP73 expressions in 88 HCC tissues and their self-control surrounding tissues were examined by immunohistochemistry,and survival time of HCC patients was evaluated by the Kaplan-Meier method.HCC model of Sprague-Dawley rats was made by diet containing 2-fluorenylacetamide.The rats were divided into the control,hepatocyte degeneration,precanceration,and HCC groups to observe GP73 protein and mRNA alterations during hepatocytes malignant transformation.Results:The GP73 expression was significantly higher in the cancerous tissues than that in the surrounding tissues,with shorter survival time,and the positive rates of GP73 protein in human HCC tissues were 53.3%at stage I,84.0%at stage II,84.6%at stage III,and 60.0%at stage IV,respectively.The positive rates of hepatic GP73 protein and mRNA in the rat models were none in the control group,66.7%and 44.4%in the hepatocytes degeneration group,88.9%and 77.8%in the hepatocytes precanceration group,and 100%in the HCC group,respectively.There was a positive correlation(r=0.91,P<0.01)between hepatic GP73 and serum GP73 during rat hepatocytes malignant transformation.Conclusions:Abnormal GP73 expression may be a sensitive and valuable biomarker in hepatocarcinogensis.

Quantitative analysis of hepatic hypoxia-inducible factor-1α and its abnormal gene expression during the formation of hepatocellular carcinoma

BACKGROUND:Hepatic hypoxia-inducible factor-1(HIF-1) is activated in the progression of hepatocellular carcinoma (HCC).This study aimed to investigate the dynamic alterations of HIF-1αand its gene expression so as to explore the relationship between HIF-1αexpression and hepatocarcinogenesis at the early stage of HCC. METHODS:A hepatoma model was made with 2-fluorenyl- acetamide(2-FAA)in male Sprague-Dawley rats.Morphological changes of rat hepatocytes were assessed pathologically (HE staining).The dynamic expression of hepatic and circulating HIF-1αwas quantitatively analyzed by ELISA. The gene fragments of hepatic HIF-1αmRNA were amplified by RT-PCR and confirmed by sequencing.The cellular distribution of hepatic HIF-1αexpression was confirmed by immunohistochemistry. RESULTS:Histological examination confirmed granulelike degeneration to atypical hyperplasia and HCC development in rat hepatocytes and progressive increases in the levels of hepatic and circulating HIF-1αand its gene expression during the course.The levels of HIF-1α expression in the liver and blood of rats with hepatoma were significantly higher than those in normal ratsand those with degeneration.Immunohistochemical analysis confirmed the positive expression and hepatocyte distribution of HIF-1αin the development of rat hepatoma. A positive relationship was found between HIF-1α expression in the liver and blood(P<0.01). CONCLUSIONS:The above observations support the hypothesis that the overexpression of HIF-1αand its gene are closely associated with the malignant transformation of hepatocytes and play an important role at the stage of hepatocarcinogenesis.

Extensible and swellable hydrogel-forming microneedles for deep point-of-care sampling and drug deployment

Microneedles are considered to be an effective,convenient,non-invasive,biosafety and compliant medical technology for vaccinations,biomarker testing,medical aesthetics and other related fields.Nonetheless,further clinical and commercial translation of regular microneedles is hampered by challenges in manufacturability,cost variability,insufficient comfort,contamination and so on.Recent innovations in functional biomaterials and chemical engineering technologies have been applied to develop extensible and swellable hydrogel-forming microneedles,achieving precise and controlled drug delivery and localized sampling from the target tissues.In this review,we systematically summarize the latest development of the extensible and swellable hydrogel-forming microneedles,including deep point-of-care testing,drug deployment,wound healing and mucoadhesion improvement.In addition,further analysis of the challenges and prospects for clinical application of current strategies is well presented.It is believed that the combined efforts of engineering,material,pharmaceutical and clinical research will contribute to the future success of this clinical and commercial translation.