Ran Xue

Pancreatic stellate cell (PSC) is a type of pluripotent cell located between pancreatic lobules and the surrounding area of acinars. When activated, PSC can be transformed into myofibroblast-like cell. A number of evidences suggest that activated PSC is the main source of the accumulation of extracellular matrix (ECM) protein under the pathological conditions, which lead to pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have found that PSC also plays an important role in the endocrine cell function, islet fibrosis and diabetes. In order to provide new strategies for the treatment of pancreatic diseases, this paper systematically summarizes the recent researches about the biological behaviors of PSC, including its stem/progenitor cell characteristics, secreted exosomes, cellular senescence, epithelial mesenchymal transformation (EMT), energy metabolism and direct mechanical reprogramming.

Aim . Pancreatic cancer is one of the most quickly fatal cancers around the world. Burgeoning researches have begun to prove that mitochondria play a crucial role in cancer treatment. Mitofusin2 (Mfn2) plays an indispensable role in mitochondrial fusion and adjusting function. However, the role and underlying mechanisms of Mfn2 on cell autophagy of pancreatic cancer is still unclear. Our aim was to explore the effect of Mfn2 on multiple biological functions involving cell autophagy in pancreatic cancer. Methods . Pancreatic cancer cell line, Aspc‐1, was treated with Ad‐Mfn2 overexpression. Western blotting, caspase‐3 activity measurement, and CCK‐8 and reactive oxygen species (ROS) assay were used to examine the effects of Mfn2 on pancreatic cancer autophagy, apoptosis, cell proliferation, oxidative stress, and PI3K/Akt/mTOR signaling. The expression of tissue Mfn2 was detected by immunohistochemical staining. Survival analysis of Mfn2 was evaluated by OncoLnc. Results . Mfn2 improved the expression of LC3‐II and Bax and downregulated the expression of P62 and Bcl‐2 in pancreatic cancer cells. Meanwhile, Mfn2 also significantly inhibited the expression of p‐PI3K, p‐Akt, and p‐mTOR proteins in pancreatic cancer cells. In addition, Mfn2 inhibited pancreatic cancer cell proliferation and ROS production. Assessment of Kaplan‐Meier curves showed that Mfn2 − pancreatic cancer has a worse prognosis than Mfn2 + pancreatic cancer has. Conclusions . Our finding suggests that Mfn2 induces cell autophagy of pancreatic cancer through inhibiting the PI3K/Akt/mTOR signaling pathway. Meanwhile, Mfn2 also influences multiple biological functions of pancreatic cancer cells. Mfn2 may act as a therapeutic target in pancreatic cancer treatment.

Hyperglycemia has been widely considered as a key risk factor for diabetic encephalopathy which can cause neuronal apoptosis and cognitive deficits. The flavonoid compound, fisetin, possesses potential neuroprotective effects and also enhances learning and memory. However, the role of fisetin in hyperglycemia-induced neuronal cytotoxicity has not been fully elucidated. In the present study, HT22 murine hippocampal neuronal cell line was used to establish the injured cell model. Cell proliferation and cytotoxicity assay, hoechst 33258 staining, qRT-PCR, western blot analysis, and specific inhibitor was used to investigate the effect and molecular mechanisms of fisetin on high glucose (HG)-induced neurotoxicity in HT22 cells. Our results showed that 125 μM and 48 h of treatment was identified as optimal damage parameter of HG. Fisetin significantly improved HG-inhibited cell viability. The levels of LDH, MDA and SOD were noticeably modulated by fisetin, which alleviated HG-induced HT22 cell oxidative damage. Besides, the apoptosis of HT22 cells was rescued by fisetin pretreatment. In addition, fisetin also prevented HG-induced downregulation of the mRNA expression of Bdnf, Gdnf, Syp (Synaptophysin) and Gria1 (Glutamate Ionotropic Receptor AMPA Type Subunit 1) in cells. More importantly, the decreased phosphorylation of PI3K, Akt and CREB was rescued by fisetin treatment and that neuroprotective effect of fisetin was partially blocked by PI3K inhibitor, LY294002. These findings indicate that fisetin has potent neuroprotective effect and prevents HG-induced neurotoxicity by activation of PI3K/Akt/CREB pathway.