Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model.

Stem cells from the apical papilla(SCAPs) exhibit remarkable tissue repair capabilities, demonstrate anti-inflammatory and pro-angiogenic effects, positioning them as promising assets in the realm of regenerative medicine. Recently, the focus has shifted towards exosomes derived from stem cells, perceived as safer alternatives while retaining comparable physiological functions. This study delves into the therapeutic implications of exosomes derived from SCAPs in the methionine-choline-deficient (MCD) diet-induced mice non-alcoholic steatohepatitis (NASH) model. We extracted exosomes from SCAPs. During the last two weeks of the MCD diet, mice were intravenously administered SCAPs-derived exosomes at two distinct concentrations (50 µg/mouse and 100 µg/mouse) biweekly. Thorough examinations of physiological and biochemical indicators were performed to meticulously evaluate the impact of exosomes derived from SCAPs on the advancement of NASH in mice induced by MCD diet. This findings revealed significant reductions in body weight loss and liver damage induced by the MCD diet following exosomes treatment. Moreover, hepatic fat accumulation was notably alleviated. Mechanistically, the treatment with exosomes led to an upregulation of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the liver, enhancing hepatic fatty acid oxidation and transporter gene expression while inhibiting genes associated with fatty acid synthesis. Additionally, exosomes treatment increased the transcription levels of key liver mitochondrial marker proteins and the essential mitochondrial biogenesis factor. Furthermore, the levels of serum inflammatory factors and hepatic tissue inflammatory factor mRNA expression were significantly reduced, likely due to the anti-inflammatory phenotype induced by exosomes in macrophages. The above conclusion suggests that SCAPs-exosomes can improve NASH.

[Expression of Smad4 and Smad7 of BMP signaling pathway in oral squamous cell carcinoma].

PURPOSE: To observe the changes of the expressions of Smad4 and Smad7 in oral squamous cell carcinoma and adjacent normal tissue, and to investigate the effects of Smad4 and Smad7 on occurrence and development of oral squamous cell carcinoma (OSCC). METHODS: Seventy-two cases with OSCC which were pathologically confirmed were included in the study. Cancer tissue and adjacent normal tissue were taken to make slices. SP immunohistochemical method was used to detect the expression of Smad4 and Smad7 in oral squamous cell carcinoma and adjacent normal tissue. SPSS11.5 software package was used for statistical analysis. RESULTS: The positive expression rate of Smad4 protein was 69.44% in adjacent normal tissues, and it was 45.83% in oral squamous cell carcinoma(P<0.05). The positive expression rate of Smad4 was lower when the degree of differentiation decreased; The positive expression rate of Smad4 with lymph node metastasis was 22.50%, while it was 65.63% without lymph node metastasis(P<0.05). The positive expression rate of Smad7 protein in adjacent normal tissues was 19.44%, and it was 83.33% (P<0.05) in oral squamous cell carcinoma, the positive expression rate of Smad7 was higher when the degree of differentiation decreased. The positive expression rate of Smad7 with lymph node metastasis was 92.50%, while it was 68.75%(P<0.05) without lymph node metastasis. CONCLUSIONS: The expression of Smad4 is significantly reduced in cancer tissues and the expression is lower when the degree of differentiation decreased; the expression rate of Smad4 with lymph node metastasis is lower compared with those without lymph node metastasis. Smad7 has the opposite effect. Loss of expression of Smad4 may contribute to the development and metastasis of oral squamous cell carcinoma. Over-expression of Smad7 may promote the development and metastasis of oral squamous cell carcinoma. The inhibition of BMP/Smads signaling pathway may result in the occurrence and development of oral squamous cell carcinoma continually. Supported by Science and Technology Development Plan (2010GSF10239) of Shandong Province and Science and Technology Special Project of Shandong Province (2012G0021852).