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Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono‐oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3‐kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL1 in breast cancer cell proliferation and to explore the potential molecular mechanism. We noticed that depletion of MICAL1 markedly reduced cell proliferation in breast cancer cell line MCF‐7 and T47D. This effect of MICAL1 on proliferation was independent of wnt/β‐catenin and NF‐κB pathways. Interestingly, depletion of MICAL1 significantly inhibited ROS production, decreased p‐ERK expression and unfavourable for proliferative phenotype of breast cancer cells. Likewise, MICAL1 overexpression increased p‐ERK level as well as p‐ERK nucleus translocation. Moreover, we investigated the effect of MICAL1 on cell cycle‐related proteins. MICAL1 positively regulated CDK4 and cyclin D expression, but not CDK2, CDK6, cyclin A and cyclin E. In addition, more expression of CDK4 and cyclin D by MICAL1 overexpression was blocked by PI3K/Akt inhibitor LY294002. LY294002 treatment also attenuated the increase in the p‐ERK level in MICAL1‐overexpressed breast cancer cells. Together, our results suggest that MICAL1 exhibits its effect on proliferation via maintaining cyclin D expression through ROS‐sensitive PI3K/Akt/ERK signalling in breast cancer cells.

Background/AimsLittle data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). MethodsWe retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. ResultsForty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group (P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. ConclusionsIEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients.

Background/Aims It is known that post-reflux swallow-induced peristaltic wave (PSPW) index represents the chemical clearance of the esophagus. However, few studies have explored why some reflux episodes could induce PSPW while others in the same patient could not. The purpose of this study is to investigate the characteristics of reflux episodes which could elicit PSPW. Methods In this study, 269 reflux episodes were detected, of which 90 with a PSPW and 179 without a PSPW. Comparisons were made between the characteristics of reflux episodes with a PSPW and without a PSPW. The characteristics were including nadir pH, pH drop, proximal extent (cm, sec), ascending velocity (cm/sec), volume clearance time, acid clearance time, percentage acidic (%), 15 to 60-minute acid burden (seconds), and 15-to 60-minute volume burden (seconds). The characteristics between the 2 groups were compared through performing Wilcoxon signed rank test. Results Reflux episodes followed by a PSPW were significantly associated with a higher proximal extent than those without a PSPW. After the reflux episodes, higher volume clearance time and larger volume burden were more likely to trigger a PSPW. However, there were no significant differences between the 2 groups in nadir pH, pH drop, ascending velocity, acid clearance time, percentage acidic, or acid burden. Conclusions The role of acid seems to be less important in a reflux episode inducing a PSPW. Proximal reflux episodes are more likely to induce a PSPW. The depression of volume clearance may also be an important factor in eliciting a PSPW.