TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.

BACKGROUND: Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells. RESULTS: A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells. CONCLUSIONS: These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells.

TonEBP expression is essential in the IL-1ß-induced migration and invasion of human A549 lung cancer cells.

Lung cancer has the highest mortality rate among all cancers, in part because it readily metastasizes. The tumor microenvironment, comprising blood vessels, fibroblasts, immune cells, and macrophages [including tumor-associated macrophages (TAMs)], is closely related to cancer cell growth, migration, and invasion. TAMs secrete several cytokines, including interleukin (IL)-1ß, which participate in cancer migration and invasion. p21-activated kinase 1 (PAK1), an important signaling molecule, induces cell migration and invasion in several carcinomas. Tonicity-responsive enhancer-binding protein (TonEBP) is also known to participate in cancer cell growth, migration, and invasion. However, the mechanisms by which it increases lung cancer migration remain unclear. Therefore, in this study, we aimed to elucidate the mechanisms by which IL-1ß and TonEBP affect lung cancer cell migration and invasion. We found that A549 cocultured-MΦ-secreted IL-1ß induced A549 cell migration and invasion via the PAK1 pathway. TonEBP deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1ß-induced migration and invasion. PAK1 phosphorylation, which was promoted by IL-1ß, was reduced when TonEBP was depleted. These results suggest that TonEBP plays an important role in IL-1ß induction and invasiveness of A549 cells via the PAK1 pathway. These findings could be valuable in identifying potential targets for lung cancer treatment.

Properties of Surface Heating Textile for Functional Warm Clothing Based on a Composite Heating Element with a Positive Temperature Coefficient.

A high-stretch positive temperature coefficient (PTC) surface heating textile (PTC-SHT) was fabricated using a composite of PTC powder and multiwall carbon nanotubes (MWCNTs). The PTC-SHT (heating area = 100 × 100 mm2) was produced by screen-printing the PTC-MWCNT composite paste onto a high-stretch textile with embroidered electrodes. Overall, the temperature increased to 56.1 °C with a power consumption of 5 W over 7 min. Subsequently, the surface temperature of the PTC-SHT remained constant despite the continued decrease in power consumption. This indicated that heating was accompanied by an increase in resistance of the PTC-SHT, which is typical of this process-i.e., heating to a constant temperature under a constant voltage over an extended period of time. In addition, 4.63 W power was required to heat the PTC-SHT surface from an external temperature of 5 to 45 °C in 10 min, after which stable low-temperature heat generation behavior was observed at a constant temperature of 50 °C, which was maintained over 40 min. In contrast, negative temperature coefficient (NTC) behavior has been observed in an NTC-SHT consisting of only MWCNTs, where a slow heating rate in the initial stage of power application and a continuous increase in surface temperature and power consumption were noted. The PTC-SHT consumed less power for heat generation than the NTC-SHT and exhibited rapid heating behavior in the initial stage of power application. The heat generation characteristics of the PTC-SHT were maintained at 95% after 100,000 cycles of 20% stretch-contraction testing, and the heating temperature remained uniformly distributed within ± 2 °C across the entire heating element. These findings demonstrated that an SHT with PTC characteristics is highly suitable for functional warm clothing applications that require low power consumption, rapid heating, stable warmth, and high durability.

TonEBP suppresses adipocyte differentiation via modulation of early signaling in 3T3-L1 cells.

TonEBP belongs to the Rel family of transcription factors and plays important roles in inflammation as well as kidney homeostasis. Recent studies suggest that TonEBP expression is also involved in differentiation of several cell types such as myocytes, chondrocytes, and osteocytes. In this study, we investigated the roles of TonEBP during adipocyte differentiation in 3T3-L1 cells. TonEBP mRNA and protein expression was dramatically reduced during adipocyte differentiation. Sustained expression of TonEBP using an adenovirus suppressed the formation of lipid droplets as well as the expression of FABP4, a marker of differentiated adipocytes. TonEBP also inhibited the expression of PPARγ, a known master regulator of adipocytes. RNAi-mediated knock down of TonEBP promoted adipocyte differentiation. However, overexpression of TonEBP did not affect adipogenesis after the initiation of differentiation. Furthermore, TonEBP expression suppressed mitotic clonal expansion and insulin signaling, which are required early for adipocyte differentiation of 3T3-L1 cells. These results suggest that TonEBP may be an important regulatory factor in the early phase of adipocyte differentiation.

Efficacy of prolonged entecavir monotherapy in treatment-naïve chronic hepatitis B patients exhibiting a partial virologic response to entecavir.

BACKGROUND/AIMS: The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined. The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naïve chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy. METHODS: This study included 364 treatment-naïve CHB patients treated with ETV for ≥48 weeks and who received continuous ETV monotherapy for ≥96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log(10) IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48. RESULTS: Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for ≥96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up. CONCLUSIONS: Long-term ETV monotherapy is effective for achieving a VR in treatment-naïve CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response.

[Factors influencing the miss rate of polyps in a tandem colonoscopy study].

BACKGROUND/AIMS: The miss rate of colon polyps and its related factors have not been clearly identified yet. This study aims to review the miss rate of polyps both on the patient-level and on the polyp-level and to analyze the factors affecting the miss rate such as those related to the endoscopist, procedure, patient, and polyp. METHODS: From August 2011 to August 2013, patients who underwent elective second colonoscopy for resection of polyps, the sizes of which were not small enough to be resected by biopsy forceps alone at first colonoscopy, were enrolled retrospectively. RESULTS: The miss rate on the patient-level was 59.2% (234/395) and on the polyp-level was 27.9% (578/2,068). There was no significant difference in the miss rate depending on the experience of the endoscopists or characteristics of the patients. In terms of the procedure, the miss rate was higher when the colonoscopy was performed in the afternoon (OR 1.632, p=0.046). It was found that the miss rate of polyps increased when the polyps were small (OR 4.595, p<0.001 in <5 mm/OR 3.447, p<0.001 in 5-10 mm), flat or sessile (OR 2.406, p<0.001 in flat/OR 1.768, p=0.002 in sessile), and located in the left colon (OR 1.391, p=0.007). CONCLUSIONS: The experience of endoscopists did not have influence on the accuracy of polyp detection. However, the fatigue of endoscopists in the afternoon is considered to render polyp detection less accurate. Also, the large curves and folds of the sigmoid colon are regarded as a reason for the higher miss rate of polyps in the left colon.

A case of postural orthostatic tachycardia syndrome associated with migraine and fibromyalgia.

Postural orthostatic tachycardia syndrome (POTS) refers to the presence of orthostatic intolerance with a heart rate (HR) increment of 30 beats per minute (bpm) or an absolute HR of 120 bpm or more. There are sporadic reports of the autonomic nervous system dysfunction in migraine and fibromyalgia. We report a case of POTS associated with migraine and fibromyalgia. The patient was managed with multidisciplinary therapies involving medication, education, and exercise which resulted in symptomatic improvement. We also review the literature on the association between POTS, migraine, and fibromyalgia.

Treatment of tannery wastewater with high nitrogen content using anoxic/oxic membrane bio-reactor (MBR).

Bench scale membrane bio-reactors were operated to investigate the treatment efficiency of tannery wastewater with high organic and nitrogen contents and the optimum operating conditions were derived. The optimum ratio of the volume of anoxic denitrification tank to aerobic nitrification tank was 50% when denitification/nitrication MBR process was used to treat tannery wastewater. It was also found that supplementation of phosphorus to maintain COD:T-P ratio of 100:1 was needed to achieve the best performance. Under these conditions, the effluent COD and T-N were 160 and 54 mg/L, respectively which satisfied the effluent limits for the tannery wastewater.