HIF-1α promotes the migration and invasion of hepatocellular carcinoma cells via the IL-8-NF-κB axis.

BACKGROUND: Hypoxia plays a critical role in many cancers. Hypoxia inducible factor-1α (HIF-1α) is an important mediator of the hypoxia response. It regulates the expression of various chemokines involved in tumor growth, angiogenesis and metastasis but the associated pathway needs further investigation. METHODS: The expression level of HIF-1α was determined in hepatocellular carcinoma (HCC) cells. The correlation of interleukin-8 (IL-8) and HIF-1α was assessed by knocking down HIF-1α. These cells were also used to assess its influence on HCC cell migration and invasion was checked. Pyrrolidinedithiocarbamate (PDTC), an inhibitor of NF-κB, was used to confirm the associated signaling pathway. RESULTS: HIF-1α was significantly expressed in HCC cells and found to promote HCC cell migration and invasion in an IL-8-dependent manner. NF-κB was confirmed to be involved in the process. CONCLUSIONS: HIF-1α promotes HCC cell migration and invasion by modulating IL-8 via the NF-κB pathway.

Effectiveness of the small private online course-based flipped teaching program for enhancing nursing students' self-directed learning ability in the Surgical Nursing course: A practical study.

Small private online course-based flipped teaching is an innovative hybrid instructional approach that merges online and offline activities, fostering autonomous learning among students prior to class and facilitating the assimilation of knowledge within the confines of the classroom. To determine the effectiveness of the small private online course-based flipped teaching model on undergraduate nursing students' self-directed learning abilities, we performed a practice version of the small private online course-based flipped teaching program as a quasi-experiment, specifically designed for the Surgical Nursing course and assessed its effectiveness in students' self-directed learning abilities. To this end, a total of 264 students from the 2019 nursing major cohort were selected. Three classes comprising 131 students were randomly selected as the experimental group, and three other classes, comprising 133 students, were set as the control group. The results revealed no significant differences in the scores of self-directed learning abilities between the experimental and control groups before the experiment. After the experiment, the average scores on each dimension of the self-directed learning abilities improved significantly, and the final score of the experimental group was higher than that of the control group. The small private online course-based flipped teaching model can promote undergraduate nursing students' self-directed learning abilities, owing to its practicality and feasibility for the selected course.

Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22.

BACKGROUND: Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy (PHx). At present, there is a lack of recognized safe, effective, and stable drugs to promote liver regeneration. It has been reported that vagus nerve signaling is beneficial to liver regeneration, but the potential mechanism at play here is not fully understood. AIM: To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx. METHODS: A PHx plus hepatic vagotomy (Hv) mouse model was established. The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice. In order to further investigate the role of interleukin (IL)-22 in liver regeneration inhibition mediated by Hv, the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured. The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx. RESULTS: Compared to control-group mice, Hv mice showed severe liver injury and weakened liver regeneration after PHx. Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3 (STAT3) pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx. Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury, while treatment with IL-22 binding protein (an inhibitor of IL-22 signaling) reduce the concentration of IL-22 induced by PHx, inhibits the activation of the STAT3 signaling pathway in the liver after PHx, thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice. CONCLUSION: Hv attenuates liver regeneration after hepatectomy, and the mechanism may be related to the fact that Hv downregulates the production of IL-22, then blocks activation of the STAT3 pathway.

Blocking the Hepatic Branch of the Vagus Aggravates Hepatic Ischemia-Reperfusion Injury via Inhibiting the Expression of IL-22 in the Liver.

Liver ischemia-reperfusion injury (IRI) is an inevitable process during liver transplantation, hemorrhagic shock, resection, and other liver surgeries. It is an important cause of postoperative liver dysfunction and increased medical costs. The protective effects of the vagus nerve on hepatic IRI have been reported, but the underlying mechanism has not been fully understood. We established a hepatic vagotomy (Hv) mouse model to study the effect of the vagus on liver IRI and to explore the underlying mechanism. Liver IRI was more serious in mice with Hv, which showed higher serum ALT and AST activities and histopathological changes. Further experiments confirmed that Hv significantly downregulated the expression of IL-22 protein and mRNA in the liver, blocking the activation of the STAT3 pathway. The STAT3 pathway in the livers of Hv mice was significantly activated, and liver injury was clearly alleviated after treatment with exogenous IL-22 recombinant protein. In conclusion, Hv can aggravate hepatic IRI, and its mechanism may be related to inhibition of IL-22 expression and downregulation of the STAT3 pathway in the liver.

[Dual regulation effect of somatostatin on immunity in patients with severe sepsis caused by abdominal diseases].

OBJECTIVE: to investigate the effect of somatostatin on inflammatory immune disorders and prognosis in patients with severe sepsis caused by abdominal diseases. METHODS: fifty-three patients with severe abdominal sepsis (age > 18 years, APACHE-II score > 15) from June 2005 to June 2009 were randomly divided into Somatostatin group (n = 23) and SSC Group (n = 30). Fifteen healthy volunteers of the same age range were chosen as Control group. The SSC group was treated with classical SSC therapy, and the Somatostatin Group was treated with the same regime plus 14-peptide somatostatin continuous infusion at the dose of 6 mg/24 h for 7 days. The serum levels of interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) were determined by using ELISA. CD(4)(+), CD(8)(+) T cell subsets were determined by fluorescence activated cell sorter(FACS) and CD(4)(+)/CD(8)(+) was calculated. APACHE-II score was observed on admission (d1) and day 3, 7 and 14 after treatment. Morality rates in 28 days in two groups were recorded. RESULTS: compared with Control group, IL-10 and TNF-α levels were significantly elevated in patients with severe abdominal sepsis (P < 0.05), while CD(4)(+), CD(8)(+) T cell and CD(4)(+)/CD(8)(+) decreased significantly (P < 0.05). Compared with the Somatostatin group CD(4)(+), CD(8)(+) T cell and CD(4)(+)/CD(8)(+) on d7 and d14 in SSC Group were significantly increased (P < 0.05), while IL-10 and TNF-α decreased significantly(P < 0.05). APACHE-II scores on d3, d7, d14 of Somatostatin group were significantly lower than those of SSC group, and 28 d mortality rate also declined. CONCLUSIONS: in patients with severe abdominal sepsis, systemic inflammatory response and immune suppression exist simultaneously. Somatostatin has a dual immunomodulatory activity in these patients.