Melatonin and verteporfin synergistically suppress the growth and stemness of head and neck squamous cell carcinoma through the regulation of mitochondrial dynamics

The prevalence of head and neck squamous cell carcinoma (HNSCC) has continued to rise for decades. However, drug resistance to chemotherapeutics and relapse, mediated by cancer stem cells (CSCs), remains a significant impediment in clinical oncology to achieve successful treatment. Therefore, we focused on analyzing CSCs in HNSCC and demonstrated the effect of melatonin (Mel) and verteporfin (VP) on SCC-25 cells. HNSCC CSCs were enriched in the reactive oxygen species-low state and in sphere-forming cultures. Combination treatment with Mel and VP decreased HNSCC viability and increased apoptosis without causing significant damage to normal cells. Sphere-forming ability and stem cell population were reduced by co-treatment with Mel and VP, while mitochondrial ROS level was increased by the treatment. Furthermore, the expression of mitophagy markers, parkin and PINK1, was significantly decreased in the co-treated cells. Mel and VP induced mitochondrial depolarization and inhibited mitochondrial function. Parkin/TOM20 was localized near the nucleus and formed clusters of mitochondria in the cells after treatment. Moreover, Mel and VP downregulated the expression of markers involved in epithelial-mesenchymal transition and metastasis. The migration capacity of cells was significantly decreased by co-treatment with Mel and VP, accompanied by the down-regulation of MMP-2 and MMP-9 expression. Taken together, these results indicate that co-treatment with Mel and VP induces mitochondrial dysfunction, resulting in the apoptosis of CSCs. Mel and VP could thus be further investigated as potential therapies for HNSCC through their action on CSCs.     

Effects of the frequency of ostomy management reinforcement education on self-care knowledge,self-efficacy,and ability of stoma appliance change among Korean hospitalised ostomates

Patients who undergo stoma surgery experience difficulties in adapting physically and psychologically. The priority is to support them in learning self-care for successful rehabilitation and psychosocial adaption to a new life. In order to do this, it is important to provide ostomates with repetitive reinforcement education on self-care in a continuous and individual manner, not just to increase knowledge or perform related skills. This study aims to evaluate the effects of ostomy management reinforcement education (OMRE) in ostomates and to identify the optimal frequency of reinforcement education using an equivalent control group post-test design. Participants were 60 ostomates admitted to a university hospital after ostomy formation surgery, and they were randomly assigned to a control and two experimental groups of this study. The OMRE was given to the control group (n = 20), experimental group 1 (n = 20), and experimental group 2 (n = 20) once, twice, and three times, respectively. Participants' self-care knowledge, self-efficacy, and ability of stoma appliance change were evaluated before and after the OMRE. Major results of this study were as follows: the self-care knowledge score of post-test was higher than the pretest in the control, experimental 1, and experimental two groups (P < 0.001). The self-efficacy score of post-test was higher than the pretest in the control, experimental 1, and experimental 2 groups (P < 0.001). The self-care knowledge score according to the frequency of OMRE did not differ among the control, experimental 1, and experimental 2 groups (F = 1.921, P = 0.156). The self-efficacy score according to the frequency of OMRE was significantly different between the control and experimental groups (F = 8.616, P = 0.001), but there was no difference between the experimental 1 and experimental 2 groups (Scheffe's post-hoc analysis: a < b, c). The ability of stoma appliance change score according to the frequency of OMRE was significantly different between the control and experimental groups (F = 49.546, P < 0.001), but there was no difference between the experimental 1 and experimental 2 groups (Scheffe's post-hoc analysis: a < b, c). Results of this study suggested that the OMRE was effective for promoting hospitalised ostomates' self-care knowledge, self-efficacy, and ability of stoma appliance change, and two sessions of the OMRE was the most effective. Findings of this study may be useful in planning education programmes designed to improve self-care ability for hospitalised ostomates.     

Vasoactive intestinal peptide decreases inflammation and tight junction disruption in experimental necrotizing enterocolitis

Background and PurposeExcessive inflammatory cell infiltration and accumulation in the intestinal mucosa are pathological features of necrotizing enterocolitis (NEC) leading to intestinal barrier disruption. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent that regulates intestinal epithelial barrier homeostasis. We previously demonstrated that VIP-ergic neuron expression is decreased in experimental NEC ileum, and this may be associated with inflammation and barrier compromise. We hypothesize that exogenous VIP administration has a beneficial effect in NEC.MethodsNEC was induced in C57BL/6 mice by gavage feeding, hypoxia, and lipopolysaccharide administration between postnatal day (P) 5 and 9. There were four studied groups: Control (n = 6): Breast feeding without stress factors; Control + VIP (n = 5): Breast feeding + intraperitoneal VIP injection once a day from P5 to P9; NEC (n = 9): mice exposed to NEC induction; NEC + VIP (n = 9): NEC induction + intraperitoneal VIP injection. Terminal ileum was harvested on P9. NEC severity, intestinal inflammation, (IL-6 and TNFα), and Tight junctions (Claudin-3) were evaluated.ResultsNEC severity and intestinal inflammation were significantly decreased in NEC + VIP compared to NEC. Tight junction expression was significantly increased in NEC + VIP compared to NEC.ConclusionVIP administration has a beneficial therapeutic effect in NEC by reducing inflammation and tight junction disruption.