Polymeric immunoglobulin receptor (pIgR) mediates the transfer of polymeric immunoglobulin to protect organisms and is one of the most important mucosal effectors. In this study, the developmental stage- and tissue-specific expression of pIgR were observed before virus inoculation in olive flounder. pIgR was gradually expressed until the formation of immune tissue, exhibiting high expression in the late juvenile period; thereafter, pIgR expression gradually decreased and exhibited high expression in the spleen and skin. Moreover, pIgR expression after viral hemorrhagic septicemia virus infection was high in the kidney and spleen tissues at high density and low at low density. The results of this study can provide a basis for future studies on breeding density, virus expression, and immune system studies in fish.
Metformin is the most widely used anti-diabetic drug that helps maintain normal blood glucose levels primarily by suppressing hepatic gluconeogenesis in type II diabetic patients. We previously found that metformin induces apoptotic death in H4IIE rat hepatocellular carcinoma cells. Despite its anti-diabetic roles, the effect of metformin on hepatic de novo lipogenesis (DNL) remains unclear. We investigated the effect of metformin on hepatic DNL and apoptotic cell death in H4IIE cells. Metformin treatment stimulated glucose consumption, lactate production, intracellular fat accumulation, and the expressions of lipogenic proteins. It also stimulated apoptosis but reduced autophagic responses. These metformin-induced changes were clearly reversed by compound C, an inhibitor of AMP-activated protein kinase (AMPK). Interestingly, metformin massively increased the production of reactive oxygen species (ROS), which was completely blocked by compound C. Metformin also stimulated the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Finally, inhibition of p38MAPK mimicked the effects of compound C, and suppressed the metformin-induced fat accumulation and apoptosis. Taken together, metformin stimulates dysregulated glucose metabolism, intracellular fat accumulation, and apoptosis. Our findings suggest that metformin induces excessive glucose-induced DNL, oxidative stress by ROS generation, activation of AMPK and p38MAPK, suppression of autophagy, and ultimately apoptosis.
Kidney disease affects a significant portion of the global population, yet effective therapies are lacking despite advancements in identifying genetic causes. This limitation can be attributed to the absence of adequate in vitro models that accurately mimic human kidney disease, hindering targeted therapeutic development. However, the emergence of human induced pluripotent stem cells (PSCs) and the development of organoids using them have opened up a way to model kidney development and disease in humans, as well as validate the effects of new drugs. To fully leverage their capabilities in these fields, it is crucial for kidney organoids to closely resemble the structure and functionality of adult human kidneys. In this review, we aim to discuss the potential of using human PSCs or adult kidney stem cell-derived kidney organoids to model genetic kidney disease and renal cancer.
The sea cucumber, Apostichopus japonicus, is one of the most valuable aquatic species. The color of body wall and appearance are important for the value of sea cucumbers. To examine expression pattern of long-chain acyl-coenzyme A dehydrogenase (LCAD), nuclear distribution C-containing protein 3 (NUDCD3), and receptor tyrosine kinase Tie-1 (TIE1), previously reported as differently expressed genes during the pigmentation of sea cucumber, we analyzed the temporal profiles of LCAD, NUDCD3, and TIE1 mRNAs in LED-exposed and light-shielded A. japonicus. Real-time quantitative PCR revealed that the LCAD, NUDCD3, and TIE1 mRNAs from the juveniles at 40-60 days post-fertilization (dpf) exhibited increasing patterns as compared to those of an early developmental larva (6-dpf). At 60-dpf juveniles, the LCAD and TIE1 mRNA levels of LED-exposed individuals were higher than those of light-shielded ones, whereas at 40-dpf and 50-dpf juveniles, the NUDCD3 mRNA expression was higher in the light-shielded condition (p<0.05). In the pigmented juveniles (90-dpf), the LCAD and TIE1 mRNA levels tended to show higher levels in red individuals than those in green ones, but there was a conversely higher level of NUDCD3 mRNA in green larva. In situ examination of LCAD and NUDCD3 mRNAs in light-shielded 6-dpf larva revealed that both genes are mainly expressed in the internal organs compared to the body surface. Together, these results may provide insights into the differential gene expression of LCAD, NUDCD3, and TIE1 during pigmentation process of the sea cucumber.