Background. Liver transplantation is limited by the insufficiency of liver organ donors when treating end-stage liver disease or acute liver failure (ALF). Ectodermal mesenchymal stem cells (EMSCs) derived from nasal mucosa have emerged as an alternative cell-based therapy. However, the role of EMSCs in acute liver failure remains unclear. Methods. EMSCs were obtained from the nasal mucosa tissue of rats. First, EMSCs were seeded on the gelatin-chitosan scaffolds, and the biocompatibility was evaluated. Next, the protective effects of EMSCs were investigated in carbon tetrachloride- (CCl4-) induced ALF rats. Finally, we applied an indirect coculture system to analyze the paracrine effects of EMSCs on damaged hepatocytes. A three-step nontransgenic technique was performed to transform EMSCs into hepatocyte-like cells (HLCs) in vitro. Results. EMSCs exhibited a similar phenotype to other mesenchymal stem cells along with self-renewal and multilineage differentiation capabilities. EMSC-seeded gelatin-chitosan scaffolds can increase survival rates and ameliorate liver function and pathology of ALF rat models. Moreover, transplanted EMSCs can secrete paracrine factors to promote hepatocyte regeneration, targeted migration, and transdifferentiate into HLCs in response to the liver’s microenvironment, which will then repair or replace the damaged hepatocytes. Similar to mature hepatocytes, HLCs generated from EMSCs possess functions of expressing specific hepatic markers, storing glycogen, and producing urea. Conclusions. These results confirmed the feasibility of EMSCs in acute hepatic failure treatment. To our knowledge, this is the first time that EMSCs are used in the therapy of liver diseases. EMSCs are expected to be a novel and promising cell source in liver tissue engineering.
Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, characterized by high morbidity and mortality rates. Risk factors associated with HCC include cirrhosis, alcohol abuse, metabolic syndrome, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection. Unfortunately, the cure rate of HCC remains low, primarily due to difficulties in early-stage detection. The identification of effective therapeutic targets and novel biomarkers is thus imperative. However, the precise molecular mechanisms underlying HCC development remain elusive. Recent studies have indicated a significant correlation between DNA methylation and cancer development. Notably, bioinformatics analysis of human patient databases has revealed amplification of ASH1L, a histone methyltransferase and a homolog of drosophila ASH1, in tumor tissues. Alterations in ASH1L expression have been implicated in the pathogenesis of various diseases, including prostate cancer, lung cancer, uterine cancer, and leukemia. Its molecular mechanism and cellular functions are undergone extensive studies. Specifically, investigating the role of ASH1L in HCC development represents a promising avenue for understanding the underlying mechanisms. Building upon these backgrounds and considerations, this study aims to elucidate the detrimental effects of ASH1L on the prognosis of HCC patients following liver transplantation, as well as the potential underlying mechanisms. With using various approaches, ASH1L was found to be strongly correlated with HCC. Furthermore, ASH1L shows promise as a potential biomarker for early detection, prognosis prediction, and personalized treatment strategies for HCC.
after PNI, such as degeneration of nerve cells and disintegration of the axon, which result in neuropathic pain, permanent loss of sensation, and motor control. [2] Although peripheral nerves have the potential for axonal regeneration upon injury, clinical outcomes of long-distance PNI are not always satisfactory. [3] Nerve grafting remains the clinical gold standard for repairing large nerve gaps. [4] The technical support is very limited, because the autologous nerve graft is not readily available, and secondary surgery significantly increases surgical site morbidity of dysfunction. [5] Thus, it is necessary to take an alternative approach to recombine longdistance nerve gaps and guide nerve fibers orderly. An effective nerve grafting would achieve satisfactory functional recovery with few complications.Many studies have shown that synthetic or natural polymers nerve guidance conduits (NGC) were considered one of the most promising strategies for treating PNI. [6] So far biomimetic architecture, flexibility, and biodegradability are fundamental requirements for an ideal NGC. [7] Plenty of materials, such as synthetic poly-l-lactide acid (PLLA), [8] polycaprolactone (PCL), [9] and some natural biomaterials [10] including chitosan and fibrin, had been used for the fabrication of NGC. Among them, PCL is one of the most
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