Luteolin, a flavone, has been shown to exhibit anticancer properties. Here, we investigated whether luteolin affects epithelial–mesenchymal transition (EMT) and invasiveness of pancreatic cancer cell lines and their underlying mechanism. Pancreatic cancer cell lines PANC-1 and SW1990 were used in our study, and their EMT characters, matrix metalloproteinase (MMP) expression level, invasiveness, and signal transducer and activator of transcription 3 (STAT3) activity were determined after luteolin treatment. We also treated pancreatic cancer cells with interleukin-6 (IL-6) to see whether IL-6-induced activation of STAT3, EMT, and MMP secretion was affected by luteolin. We found that luteolin inhibits EMT and MMP2, MMP7, and MMP9 expression in a dose-dependent manner, similar to STAT3 signaling. Through Transwell assay, we found that invasiveness of pancreatic cancer cells was inhibited by luteolin. EMT characters and MMP secretion increase with STAT3 activity after IL-6 treatment and these effects, caused by IL-6, were inhibited by luteolin. We concluded that luteolin inhibits invasiveness of pancreatic cancer cells, and we speculated that luteolin inhibits EMT and MMP secretion likely through deactivation of STAT3 signaling. Luteolin has potential antitumor effects and merits further investigation.

Moderate-severe pain after surgical procedures is associated with decreased quality of life and increased costs. this study aimed to identify the incidence and predictive factors of moderate-severe postoperative pain within 48 hours following video-assisted thoracoscopic surgery (VATS) in a tertiary hospital. A retrospective cohort analysis was performed using medical records of adult patients who underwent VATS between January 2015 and December 2016. Logistic regression was performed to identify predictive factors for moderate-severe pain (visual analogue scale, VAS ≥ 4) within 24 hours and within 48 hours postoperatively. Of the 1164 participants, the incidence of moderate-severe pain was 12.7% within the first 24 hours and 15.6% within the first 48 hours after surgery. In multivariable analysis, the independent risk factors related to moderate-severe pain within 24 hours after surgery were younger age, increased body mass index, preoperative pain within 1 month and history of smoking. The risk factors for moderate-severe acute pain within 48 hours were almost the same, except that the number of chest tubes were also included. Moderate-severe postoperative pain following VATS is not rare, and presence of several risk factors deserves more aggressive pain management strategies perioperatively. Moderate-severe pain after surgical procedures is associated with prolonged hospital stays, readmissions, patient dissatisfaction, development of chronic pain, decreased quality of life and increased costs 1,2. It is widely accepted that better management of postoperative pain results in better patients' recovery. Video assisted thoracoscopic surgery (VATS), compared to conventional thoracotomy, is notable for less tissue trauma, improved postoperative respiratory function, and increased tolerability for the patients 3. Although potentially less postoperative pain was generally expected as one of the benefits of VATS 4 , many patients still suffer moderate to severe pain postoperatively 2,5-7. There are several reasons contributing to this unsatisfactory situation, one of them being that some patients may have certain risk factors for occurrence of more severe postoperative pain 8. Early identification of patients at risk may help to allow early application of effective treatment strategies to prevent unexpected suffering in these patients. Previously, several studies have focused on the predictors of postoperative pain and demographic, social psychological and clinical factors have been identified contributing to the development of severe postoperative pain 5,6,8,9. However, most of them are cohorts with mixed surgical procedures while VATS is not included. Moreover, various subtypes of VATS (uniportal, multiportal and robotic) exist currently, and the lack of guideline results in variation of analgesia regimens and effectiveness of analgesia in different medical centers 10. To date, the predictive factors of moderate-severe postoperative pain following VATS were not reported, which is important for individual-specific pa...

The activation of hepatic stellate cells (HSCs) is a prominent event in liver fibrogenesis. However, how HSCs are activated in the hypoxic microenvironment remains unclear. Here, we found that hypoxia increased autophagy in rat HSCs. Moreover, hypoxia induced an elevation of the intracellular calcium concentration ([Ca 2+ ] i ), which was abolished by the cytosolic Ca 2+ chelator or the phospholipase C (PLC)-specific inhibitor. Furthermore, hypoxia-induced autophagy involved the calcium-dependent activation of the 5ʹ-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) and protein kinase C-theta (PKCh) pathways. In addition, hypoxia-mediated activation of HSCs depended on autophagy.Our results suggest that autophagy induction via the calcium-dependent AMPK-mTOR and PKCh pathways might lead to the activation of HSCs during hypoxic stress.

The hedgehog signaling pathway was first discovered in the 1980s. It is a stem cell-related pathway that plays a crucial role in embryonic development, tissue regeneration, and organogenesis. Aberrant activation of hedgehog signaling leads to pathological consequences, including a variety of human tumors such as pancreatic cancer. Multiple lines of evidence indicate that blockade of this pathway with several small-molecule inhibitors can inhibit the development of pancreatic neoplasm. In addition, activated hedgehog signaling has been reported to be involved in fibrogenesis in many tissues, including the pancreas. Therefore, new therapeutic targets based on hedgehog signaling have attracted a great deal of attention to alleviate pancreatic diseases. In this review, we briefly discuss the recent advances in hedgehog signaling in pancreatic fibrogenesis and carcinogenesis and highlight new insights on their potential relationship with respect to the development of novel targeted therapies.