Krü ppel-like factor 4 (KLF4) is a transcription factor that plays an important role in cell differentiation, proliferation, and survival, especially in the context of cancers. This study revealed that KLF4 activates glycolytic metabolism in breast cancer cells by up-regulating the platelet isoform of phosphofructokinase (PFKP). KLF4 activated the transcription of the PFKP gene by directly binding to the PFKP promoter. Whereas glucose uptake and lactate production were inhibited by the knockdown of KLF4, they were activated by the overexpression of KLF4. Unlike PFKP, the expressions of the other isoforms of phosphofructokinase and glycolytic genes were unaffected by KLF4. The human breast cancer tissues showed a close correlation between KLF4 and PFKP expression. This study also showed that PFKP plays a critical role in cell proliferation in breast cancer cells. In conclusion, it is suggested that KLF4 plays a role in maintenance of high glycolytic metabolism by transcriptional activation of the PFKP gene in breast cancer cells.Breast cancer is the most common type of cancer in women in Western countries (1). Breast cancer shows elevated glycolytic metabolism, which is one of the common characteristics of the malignant cancers (2). The increase in glycolytic rate is a result of the up-regulation of the metabolic transporters and glycolytic enzymes whose expressions are controlled by the transcriptional regulation of genes as well as post-translational modifications of the enzymes (2, 3).The conversion of fructose 6-phosphate to fructose 1,6-bisphosphate is the first committed step in the glycolytic pathway catalyzed by phosphofructokinase (PFK-1) (4, 5). PFK-1 is a complex tetrameric enzyme and exists in three isoforms: liver (PFKL), muscle (PFKM), and platelet (PFKP). The activity of PFK-1 is regulated by both quantitative changes and isozymic alterations secondary to altered gene expression during neoplastic transformation in vivo and in vitro (6, 7). The expression of PFK-1 is up-regulated in cancer cells, where glycolysis is enhanced (7,8). Although an increase in PFKP expression is a characteristic feature of malignant tissues (8), little is known about how PFKP expression is regulated during the development and progression of cancers or the change of cancer phenotypes.Krüppel-like factor 4 (KLF4) is a transcriptional factor that modulates the expression of several genes that are involved in cell cycle regulation and differentiation (9, 10). The KLF4 levels rise following DNA damage, cell cycle arrest in response to serum withdrawal, and contact inhibition (10). Elevated KLF4 level has also attributed to certain types of cancers. KLF4 mRNA and protein are overexpressed in up to 70% of breast cancers (11,12). The increased nuclear expression of KLF4 is considered to be associated with the aggressiveness of breast cancer phenotypes (12). KLF4 has been found to be overexpressed in oral and skin squamous carcinoma cells as well (13). In addition, KLF4 exhibits potent transforming activity when expressed in cult...

This study evaluated the antibacterial effects of a natural Curcuma xanthorrhiza extract (Xan) on a Streptococcus mutans biofilm by examining the bactericidal activity, inhibition of acidogenesis and morphological alteration. Xan was obtained from the roots of a medicinal plant in Indonesia, which has shown selective antibacterial effects on planktonic S. mutans. S. mutans biofilms were formed on slide glass over a 72 h period and treated with the following compounds for 5, 30, and 60 min: saline, 1% DMSO, 2 mg/ml chlorhexidine (CHX), and 0.1 mg/ml Xan. The Xan group exposed for 5 and 30 min showed significantly fewer colony forming units (CFU, 57.6 and 97.3%, respectively) than those exposed to 1% DMSO, the negative control group (P<0.05). These CFU were similar in number to those slides exposed to CHX, the positive control group. Xan showed similar bactericidal effect to that of CHX but the dose of Xan was one twentieth that of CHX. In addition, the biofilms treated with Xan and CHX maintained a neutral pH for 4 h, which indicates that Xan and CHX inhibit acid production. Scanning electron microscopy showed morphological changes in the cell wall and membrane of the Xan-treated biofilms; an uneven surface and a deformation in contour. Overall, natural Xan has strong bactericidal activity, inhibitory effects on acidogenesis, and alters the microstructure of S. mutans biofilm. In conclusion, Xan has potential in anti-S. mutans therapy for the prevention of dental caries.

PPARγ (peroxisome proliferator-activated receptor-γ) is a master transcription factor involved in adipogenesis through regulating adipocyte-specific gene expression. Recently, lipin1 was found to act as a key factor for adipocyte maturation and maintenance by modulating the C/EBPα (CCAAT/enhancer-binding protein α) and PPARγ network; however, the precise mechanism by which lipin1 affects the transcriptional activity of PPARγ is largely unknown. The results of the present study show that lipin1 activates PPARγ by releasing co-repressors, NcoR1 (nuclear receptor co-repressor 1) and SMRT (silencing mediator of retinoid and thyroid hormone receptor), from PPARγ in the absence of the ligand rosiglitazone. We also identified a novel lipin1 TAD (transcriptional activation domain), between residues 217 and 399, which is critical for the activation of PPARγ, but not PPARα. Furthermore, this TAD is unique to lipin1 since this region does not show any homology with the other lipin isoforms, lipin2 and lipin3. The activity of the lipin1 TAD is enhanced by p300 and SRC-1 (steroid receptor co-activator 1), but not by PCAF (p300/CBP-associated factor) and PGC-1α (PPAR co-activator 1α). The physical interaction between lipin1 and PPARγ occurs at the lipin1 C-terminal region from residues 825 to 926, and the VXXLL motif at residue 885 is critical for binding with and the activation of PPARγ. The action of lipin1 as a co-activator of PPARγ enhanced adipocyte differentiation; the TAD and VXXLL motif played critical roles, but the catalytic activity of lipin1 was not directly involved. Collectively, these data suggest that lipin1 functions as a key regulator of PPARγ activity through its ability to release co-repressors and recruit co-activators via a mechanism other than PPARα activation.

Introduction. Refractory shockable rhythm has a high mortality rate and poor neurological outcome. Treatments for refractory shockable rhythm presenting after defibrillation and medical treatment are not definite. We conducted research on the application of double simultaneous defibrillation (DSiD) for refractory shockable rhythms. Methods. This is a retrospective pilot study performed using medical records from 1 January 2016 to 31 December 2017. The prephase was from January to December 2016. The post-phase was from January to December 2017. During the prephase, we conducted conventional defibrillation with one defibrillator, and during the post-phase, we conducted DSiD using two defibrillators. Primary outcome was survival to hospital discharge. Secondary outcomes included survival to hospital admission and good neurological outcome at 12 months. Statistical analysis was conducted using Fisher’s exact test. Data were regarded statistically significant when p<0.05. Result. A total of 38 patients were included. Twenty-one patients underwent conventional defibrillation, and 17 underwent DSiD. The DSiD group had a higher survival to admission rate (14/17 (82.4%) vs. 6/21 (28.6%), p=0.001) and showed a trend for higher survival to discharge (7/17 (41.2%) vs. 3/21 (14.3%), p=0.078). Good neurological outcome at 12 months of the DSiD group was higher than that of the conventional defibrillation group, but the difference was not statistically significant (5/17 (29.4%) vs 2/21 (9.5%), p=0.207). Conclusion. In patients with refractory shockable rhythms, DSiD has increased survival to hospital admission and a trend of increased survival to hospital discharge. However, DSiD did not improve neurological outcome at 12 months.

a b s t r a c tPhosphoglucomutase (PGM)1 catalyzes the reversible conversion reaction between glucose-1-phosphate (G-1-P) and glucose-6-phosphate (G-6-P). Although both G-1-P and G-6-P are important intermediates for glucose and glycogen metabolism, the biological roles and regulatory mechanisms of PGM1 are largely unknown. In this study we found that T553 is obligatory for PGM1 stability and the last C-terminal residue, T562, is critical for its activity. Interestingly, depletion of PGM1 was associated with declined cellular glycogen content and decreased rates of glycogenolysis and glycogenesis. Furthermore, PGM1 depletion suppressed cell proliferation under long-term repetitive glucose depletion. Our results suggest that PGM1 is required for sustained cell growth during nutritional changes, probably through regulating the balance of G-1-P and G-6-P in order to satisfy the cellular demands during nutritional stress.