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Introduction: T2 gallbladder cancer (GBC) is the only stage showing a survival benefit after complete surgical resection, but recurrence rates remain high. Although human epidermal growth factor receptor 2 (HER2) has emerged as a therapeutic target, its role in T2 GBC remains unclear. This study investigated the status and prognostic impact of HER2 expression on T2 GBC., Materials and Methods: HER2 expression and amplification were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively, in 90 patients with T2 GBC who underwent radical cholecystectomy. We evaluated HER2 status according to the breast and gastric cancer guidelines and analyzed the effect of relevant prognostic factors on survival., Results: HER2 positive status was observed in 11.11% (10/90) and 8.89% (8/90) of cases based on gastric and breast cancer guidelines, respectively. Poor differentiation and a higher level of perineural invasion were independent prognostic factors of disease-free survival (DFS). Old age, male sex, presence of lymph node metastasis, poor differentiation, high levels of perineural invasion, and HER2 positivity based on breast cancer guidelines were identified as independent prognostic factors of overall survival (OS). Patients with HER2-positive T2 GBC according to breast cancer guidelines had worse OS., Conclusions: HER2 positivity based on breast- but not gastric-cancer guidelines was associated with poorer survival. These results provide a criterion for the evaluation of HER2 and a rationale for therapeutic strategies targeting HER2 in T2 GBC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)

Catechins in green tea possess various health benefits. Enzymatic treatment improves physiological activities by inducing bioconversion of catechins. Here, we investigated the effect of green tea infusion (GT) after tannase treatment, which transforms (-)-epigallocatechin gallate (EGCG) to gallic acid (GA) and (-)-epigallocatechin (EGC), on adipocyte differentiation and mature adipocyte metabolism. The optimal conditions for tannase-mediated improvement in GA and EGC yields in GT were investigated using response surface methodology. Yields of GA and EGC were 43-fold (0.43 mg/mL) and 1.66-fold higher (1.11 mg/mL), respectively, compared to GT without tannase treatment. The optimal reaction conditions for tannase-mediated biotransformation were observed on 0.54 mg mL -1 of tannase, reaction time (86.79 min), and reaction temperature at 22.59 °C. GT and tannase-treated GT (TANs) upregulated adiponectin, uncoupling protein 1, adipose triglyceride lipase, and hormone-sensitive lipase gene expression in differentiated 3T3-L1 adipocytes, with TAN inducing better effects than GT, which implies that tannase treatment improved the beneficial effect of GT on adipocyte metabolism. Thus, tannase-mediated bio-transformation is an attractive candidate for preparing GT with enhanced anti-obesity properties., Competing Interests: Declaration of Competing Interest All authors read and approved the final manuscript. The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recent research revealed that doxorubicin (DOX) decreased expression of programmed death-ligand 1 (PD-L1) in cancer cells. However, the detailed mechanisms underlying this effect are not well established. Here, we demonstrate that doxorubicin down-regulates PD-L1 expression through induction of AU-rich element (ARE) binding protein tristetraprolin (TTP) in cancer cells. PD-L1 mRNA contain three AREs within its 3'UTR. Doxorubicin induced expression of TTP, increased TTP binding to the 3rd ARE of the PD-L1 3'UTR, and increased decay of PD-L1 mRNA. Inhibition of TTP abrogates the inhibitory effect of doxorubicin on PD-L1 expression. Our data suggest that TTP plays a key role in doxorubicin-mediated down-regulation of PD-L1 by enhancing degradation of PD-L1 mRNA in cancer cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 3 (PFKFB3) catalyzes the first committed rate-limiting step of glycolysis and is upregulated in cancer cells. The mechanism of PFKFB3 expression upregulation in cancer cells has not been fully elucidated. The PFKFB3 3'-UTR is reported to contain AU-rich elements (AREs) that are important for regulating PFKFB3 mRNA stability. However, the mechanisms by which PFKFB3 mRNA stability is determined by its 3'-UTR are not well known. We demonstrated that tristetraprolin (TTP), an ARE-binding protein, has a critical function regulating PFKFB3 mRNA stability. Our results showed that PFKFB3 mRNA contains three AREs in the 3'-UTR. TTP bound to the 3rd ARE and enhanced the decay of PFKFB3 mRNA. Overexpression of TTP decreased PFKFB3 expression and ATP levels but increased GSH level in cancer cells. Overexpression of PFKFB3 cDNA without the 3'-UTR rescued ATP level and GSH level in TTP-overexpressing cells. Our results suggested that TTP post-transcriptionally downregulated PFKFB3 expression and that overexpression of TTP may contribute to suppression of glycolysis and energy production of cancer cells in part by downregulating PFKFB3 expression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The domain switching properties of the ferroelectric Pb(Zr(0.2)Ti(0.8))O(3) (PZT) thin films with two types of crystallographic orientations were investigated by electrostatic force microscopy (EFM). The crystallographic orientations of the PZT thin films were random on the (111)Pt/MgO(100) and c-axis preferred on the (100)Pt/MgO(100), respectively. When dc bias was applied to the films for writing in micro-scale area, electrostatic force images showed that the domain switching was hard in the PZT thin films with random orientation, while the pattern could clearly be written in the PZT films with c-axis orientation. The differences in the domain switching properties of each PZT thin film were investigated in the crystallographic orientations point of view, and the domain switching dynamics were also measured by investigating the nano-sized dot switching behavior with respect to the width of the applied voltage pulse.