Molecular Events in Response to Triclosan-Induced Oxidative Stress in CRISPR/Cas9-Mediated p53-Targeted Mutants in Daphnia magna.

Triclosan (TCS), a widely used antimicrobial agent, has been implicated in the oxidative stress induction and disruption of cellular processes in aquatic organisms. As TCS is ubiquitous in the aquatic environment, many previous studies have documented the effects of exposure to TCS on aquatic organisms. Nevertheless, most of the research has concentrated on the molecular and physiological responses of TCS, but there are still limited studies on the function of specific genes and the consequences of their absence. In this study, we focused on p53, a gene that is crucial for molecular responses such as autophagy and apoptosis as a result of TCS exposure. In order to ascertain the role and impact of the p53 gene in TCS-induced molecular responses, we examined the molecular responses to TCS-induced oxidative stress in wild-type (WT) and CRISPR/Cas9-mediated p53 mutant (MT) water fleas. The result has been accomplished by examining changes in molecular mechanisms, including in vivo end points, enzyme activities, adenosine triphosphate release rate, and apoptosis, to determine the role and impact of the p53 gene on TCS-induced molecular responses. The results indicated that the sensitivity of MT water fleas to TCS was greater than that of WT water fleas; however, the difference in sensitivity was significant at short exposures within 48 h and decreased toward 48 h. Accordingly, when we confirmed the oxidative stress after 24 h of exposure, the oxidative stress to TCS exposure was stronger in the MT group, with an imbalance of redox. To identify the mechanisms of tolerance to TCS in WT and MT Daphnia magna, we checked mitochondrial and ER-stress-related biomarkers and found an increase in apoptosis and greater sensitivity to TCS exposure in the MT group than in the WT. Our results suggest that the absence of p53 caused alterations in molecular processes in response to TCS exposure, resulting in increased sensitivity to TCS, and that p53 plays a critical role in response to TCS exposure.

Dendropanoxide Attenuates High Glucose-induced Oxidative Damage in NRK-52E Cells via AKT/mTOR Signaling Pathway.

Hyperglycemia is a potent risk factor for the development and progression of diabetes-induced nephropathy. Dendropanoxide (DPx) is a natural compound isolated from Dendropanax morbifera (Araliaceae) that exerts various biological effects. However, the role of DPx in hyperglycemia-induced renal tubular cell injury remains unclear. The present study explored the protective mechanism of DPx on high glucose (HG)-induced cytotoxicity in kidney tubular epithelial NRK-52E cells. The cells were cultured with normal glucose (5.6 mM), HG (30 mM), HG + metformin (10 µM), or HG + DPx (10 µM) for 48 h, and cell cycle and apoptosis were analyzed. Malondialdehyde (MDA), advanced glycation end products (AGEs), and reactive oxygen species (ROS) were measured. Protein-based nephrotoxicity biomarkers were measured in both the culture media and cell lysates. MDA and AGEs were significantly increased in NRK-52E cells cultured with HG, and these levels were markedly reduced by pretreatment with DPx or metformin. DPx significantly reduced the levels of kidney injury molecule-1 (KIM-1), pyruvate kinase M2 (PKM2), selenium-binding protein 1 (SBP1), or neutrophil gelatinase-associated lipocalin (NGAL) in NRK-52E cells cultured under HG conditions. Furthermore, treatment with DPx significantly increased antioxidant enzyme activity. DPx protects against HG-induced renal tubular cell damage, which may be mediated by its ability to inhibit oxidative stress through the protein kinase B/mammalian target of the rapamycin (AKT/mTOR) signaling pathway. These findings suggest that DPx can be used as a new drug for the treatment of high glucose-induced diabetic nephropathy.

Nutritional value and in situ degradability of fruit-vegetable byproducts and their feeding effects on performance of growing Hanwoo steers.

OBJECTIVE: This study was conducted to evaluate nutritional value and in situ degradability of fruit-vegetable byproducts and their feeding effects on performance of growing Hanwoo steers. METHODS: Nutritional value and in situ degradability of cabbage, Chinese cabbage and fruit-vegetable byproducts were assessed. In vivo feeding trial was also performed for 12 weeks. Thirty-six growing steers were randomly allocated into three groups according to body weight (BW) and age in 12 pens (4 replications/treatment) and assigned to one of the three dietary treatments: control (byproduct 0%), FV-B (fruit-vegetable byproduct 20%), and CA-B (cabbage peel 15% plus Chinese cabbage peel 15%, total byproduct 30%). RESULTS: The crude protein contents of cabbage, Chinese cabbage and fruit-vegetable byproducts were 18.69%, 20.20%, and 10.07%, respectively. Concentrations of neutral detergent fiber (NDF) were higher in cabbage (22.31%) and Chinese cabbage (28.83%) than fruit-vegetable (13.94%). Higher concentrations of non-fiber carbohydrate were observed for fruit-vegetable (66.72%) than cabbage (44.93%) and Chinese cabbage byproducts (24.69%). The effective degradability (ED) of both dry matter (DM) and NDF for fruit-vegetable byproduct (DM, 84.69%; NDF, 85.62%) was higher (p<0.05) than cabbage (DM, 68.47%; NDF, 55.97%) and Chinese cabbage byproducts (DM, 68.09%; NDF, 54.22%). The DM intake was not different among treatments because the amount of feed was kept constant according to the BW of growing steers to prevent overweight during the growing period. The average daily gain during the whole experimental period was not different among treatments (1.26, 1.25, and 1.34 kg/d for control, FV-B, and CA-B). The ED of both DM and NDF degradability of the total mixed ration (TMR) diets were very similar among treatments. Feed conversion ratio during the whole period showed no significant difference among treatments. CONCLUSION: This study demonstrates that fruit-vegetable and cabbage byproducts up to 20% and 30% (as fed basis), respectively can be included in TMR diets for growing beef cattle.

Cardiovascular effects of linalyl acetate in acute nicotine exposure.

BACKGROUD: Smoking is a risk factor for cardiovascular diseases as well as pulmonary dysfunction. In particular, adolescent smoking has been reported to have a higher latent risk for cardiovascular disease. Despite the risk to and vulnerability of adolescents to smoking, the mechanisms underlying the effects of acute nicotine exposure on adolescents remain unknown. This study therefore evaluated the mechanism underlying the effects of linalyl acetate on cardiovascular changes in adolescent rats with acute nicotine exposure. METHODS: Parameters analyzed included heart rate (HR), systolic blood pressure, lactate dehydrogenase (LDH) activity, vascular contractility, and nitric oxide levels. RESULTS: Compared with nicotine alone, those treated with nicotine plus 10 mg/kg (p = 0.036) and 100 mg/kg (p = 0.023) linalyl acetate showed significant reductions in HR. Moreover, the addition of 1 mg/kg (p = 0.011), 10 mg/kg (p = 0.010), and 100 mg/kg (p = 0.011) linalyl acetate to nicotine resulted in significantly lower LDH activity. Nicotine also showed a slight relaxation effect, followed by a sustained recontraction phase, whereas nicotine plus linalyl acetate or nifedipine showed a constant relaxation effect on contraction of mouse aorta (p < 0.001). Furthermore, nicotine-induced increases in nitrite levels were decreased by treatment with linalyl acetate (p < 0.001). CONCLUSIONS: Taken together, our findings suggest that linalyl acetate treatment resulted in recovery of cell damage and cardiovascular changes caused by acute nicotine-induced cardiovascular disruption. Our evaluation of the influence of acute nicotine provides potential insights into the effects of environmental tobacco smoke and suggests linalyl acetate as an available mitigating agent.

[Retracted] Slug contributes to cancer progression by direct regulation of ERα signaling pathway.

Following the publication of the above paper, it was drawn to the Editor's attention by concerned readers that ß­actin bands shown in Figs. 1, 2 and 4 were strikingly similar, where the experimental conditions reported in Fig. 4 differed from those in Figs. 1 and 2; moreover, the Slug protein bands featured in Figs. 4a and 5a were remarkably similar in spite of the different experimental conditions that were reported in the respective figure legends, and the shape of the vimentin protein bands in Fig. 5e bore a strong similarity to the Slug protein bands that were featured in Fig. 2c, in spite of the bands being of slightly different sizes and arranged in a different orientation.  Although the possibility of publishing a corrigendum was considered, software analysis of the highlighted bands performed independently by the Editorial Office demonstrated that the bands in question were likely to have been matching bands. Therefore, given the number of potential concerns that were identified with the assembly of various of the figures in this paper, the Editor of International Journal of Oncology has decided not to proceed with a corrigendum, and has determined that the paper should instead be retracted from the Journal on account of an overall lack of confidence in the originally presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 46: 1461­1472, 2015; DOI: 10.3892/ijo.2015.2878].

A randomized controlled trial of pectoralis major myofascial release massage for breastfeeding mothers: breast pain, engorgement, and newborns' breast milk intake and sleeping patterns.

PURPOSE: Supportive interventions to improve breastfeeding practice are needed in nursing. This study investigated the effects of pectoralis major myofascial release massage (MRM) on breast pain and engorgement among breastfeeding mothers and on breast milk intake and sleep patterns among newborns. METHODS: Breastfeeding mothers who had delivered between 37 and 43 weeks and had 7-to 14-dayold newborns were recruited from a postpartum care center in Gunpo, Korea. Participants were randomized to the MRM or control group. The outcome variables were breast pain and breast engorgement among breastfeeding mothers and breast milk intake and sleep time among newborns. The experimental treatment involved applying MRM to separate the pectoralis major muscle and the underlying breast tissue in the chest. After delivery, the first MRM session (MRM I) was provided by a breast specialist nurse, and the second (MRM II) was administered 48 hours after MRM I. RESULTS: Following MRM, breast pain (MRM I: t=-5.38, p<.001; MRM II: t=-10.05, p<.001), breast engorgement (MRM I: right, t=-1.68, p =.100; left, t=-2.13, p=.037 and MRM II: right, t=-4.50, p<.001; left, t=-3.74, p<.001), and newborn breast milk intake (MRM I: t=3.10, p=.003; MRM II: t=3.09, p=.003) differed significantly between the groups. CONCLUSION: MRM effectively reduced breast engorgement and breast pain in breastfeeding mothers, reducing the need for formula supplementation, and increasing newborns' breast milk intake. Therefore, MRM can be utilized as an effective nursing intervention to alleviate discomfort during breastfeeding and to improve the rate of breastfeeding practice (clinical trial number: KCT0002436).

Prediction of total digestible nutrient and crude protein requirements according to daily weight gain, and behavioral measurements of Hanwoo heifers.

OBJECTIVE: This study was conducted to investigate the effects of energy and protein levels in the diet of Hanwoo heifers on growth response and animal behavior. METHODS: Forty heifers were randomly allocated into three experimental groups according to the target daily weight gain in 8 pens (T-0.2, 2 replications; T-0.4 and -0.6, 3 replications) based on similar body weight (BW) and age in months. The target average daily gain (ADG) was set at 0.2 (T-0.2), 0.4 (T-0.4), and 0.6 kg/d (T-0.6), and feed was based on National Institute of Animal Science (NIAS, 2017). In order to minimize hunger stress of T-0.2 and -0.4, the feeding ratio of rice straw was set to 55%, 50%, and 45% for T-0.2, -0.4 and T-0.6, respectively, so that the dry matter (DM) intake for all treatment groups was uniform but the energy and protein levels in the diet were adjusted differently. A total of 6 items (lying, standing, eating, rumination, walking and drinking) of animal behavior were analyzed. RESULTS: During the whole period of the experiment, the ADG of the T-0.2, -0.4 and -0.6 treatments were 0.48, 0.56, and 0.65 kg/d (p<0.05), respectively, showing higher gain than the predicted value, especially for the low target ADG group. Based on these results, regression equations for the total digestible nutrient (TDN) and crude protein (CP) requirements were derived. No behavioral differences were found according to the energy and protein levels in the diet because the DM intake was kept constant by adjusting the roughage and concentration ratio. However, eating time was longer (p<0.05) at T-0.2 than T-0.6 during the whole day. CONCLUSION: Through this study, it was possible to derive regression equations for predicting TDN and CP requirements according to the target ADG and BW.

A Low Dose of Aripiprazole Has the Strongest Sensitization Effect Among 19 Repositioned Bipolar Drugs in P-gp-overexpressing Drug-resistant Cancer Cells.

BACKGROUND/AIM: We investigated drugs that could sensitize P-glycoprotein (P-gp)-overexpressing drug-resistant cancer cells to vincristine (VIC) or eribulin treatment and assessed their associated mechanisms of action. MATERIALS AND METHODS: We investigated 15 bipolar drugs (quetiapine, risperidone, clozapine, asenapine, iloperidone, paliperidone, ziprasidone, trifluoperazine, loxapine succinate, pilocarpine, valproic acid, carbamazepine, levetiracetam, topiramate, and felbamate) to identify drugs with a sensitizing effect on VIC-resistant KBV20C cells at relatively low doses. Fluorescence-activated cell sorting (FACS), annexin V analyses, and rhodamine uptake tests were performed to further investigate the mechanism of action. RESULTS: We found that co-treatment with half the tested drugs (quetiapine, iloperidone, trifluoperazine, loxapine, risperidone, ziprasidone, or felbamate) at low doses could highly sensitize VIC-resistant KBV20C cells. With lower amounts of the bipolar drugs or VIC, we found that among the 15 bipolar drugs tested, 2 combinations (VIC-quetiapine and VIC-trifluoperazine) had much higher sensitization effects, suggesting that lower effective doses were sufficient for sensitizing P-gp-overexpressing resistant cells compared to those required with the other drugs. Furthermore, when we compared quetiapine and trifluoperazine to previously known bipolar drugs (fluphenazine, thioridazine, pimozide, or aripiprazole), we found that aripiprazole, administered at lower doses, had a much higher sensitization effect. We also demonstrated that co-treatment with another anti-mitotic drug (eribulin) increased the sensitization of KBV20C cells similar to VIC. We also found that aripiprazole had higher P-gp-inhibitory activity than the other bipolar drugs, indicating that this activity was involved in the higher level of VIC-aripiprazole sensitization. CONCLUSION: Co-treatment of anti-mitotic drug-resistant cancer cells with a low dose of aripiprazole had the strongest sensitization effect and is highly dependent on P-gp-inhibitory activity.

IgG4-Related Lung Disease without Elevation of Serum IgG4 Level: A Case Report.

Since IgG4-related pancreatitis was first reported in 2001, IgG4-related disease has been identified in other organs such as salivary gland, gallbladder, thyroid, retroperitoneum and kidney; but lung invasion is rare. A 63-year-old man presented with hemoptysis at the pulmonary clinic and chest computed tomography revealed about 4.1 cm irregular shaped mass with spiculated margin at the left upper lobe. Despite no elevation of serum IgG4 level, he was finally diagnosed as IgG4-related lung disease by transthoracic needle biopsy. After treatment with oral glucocorticoids, hemoptysis disappeared and the size of lung mass was decreased.

Slug contributes to cancer progression by direct regulation of ERα signaling pathway.

Hormone therapy targeting estrogen receptor α (ERα) is the most effective treatment for breast cancer. However, this treatment eventually fails as the tumor develops resistance. Although reduced expression of ER-α is a known contributing factor to endocrine resistance, the mechanism of ER-α downregulation in endocrine resistance is still not fully understood. The present study shows that Slug has an inverse relationship with ERα in breast and prostate cancer patient samples. Also the inhibition of Slug blocks mammary stem cell activity in primary mammary epithelial cells. We hypothesize that Slug may be a key transcription factor in the regulation of ERα expression. To understand the Slug-ERα signaling pathway, we employed resistant cell line MCF-TAMR (ERα relatively negative) derived from its parental MCF-7 (ERα positive) cell line and assessed changes in cell phenotype, activity and response to therapy. Conversely, we performed knockdown of Slug in the high-Slug expressing cell line MDA-MB-231 and assessed reversal of the mesenchymal phenotype. Microarray analysis showed that Slug is overexpressed in high grade breast and prostate cancer tissues. Additionally, Slug overexpression leads to drug resistance. Furthermore, we demonstrated that Slug binds directly to ERα promoter E-boxes and represses ERα expression. This resulted in decrease in epithelial-to-mesenchymal transition in cancer cells. These findings demonstrate that Slug, by regulation of ERα expression, contributes to tumor progression and could serve as an important target for cancer therapy.

Agranulocytosis induced by ethambutol in a patient with pulmonary tuberculosis.

We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of 70/µL. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months.

Nanoscale observation of surface potential and carrier transport in Cu2ZnSn(S,Se)4 thin films grown by sputtering-based two-step process.

Stacked precursors of Cu-Zn-Sn-S were grown by radio frequency sputtering and annealed in a furnace with Se metals to form thin-film solar cell materials of Cu2ZnSn(S,Se)4 (CZTSSe). The samples have different absorber layer thickness of 1 to 2 µm and show conversion efficiencies up to 8.06%. Conductive atomic force microscopy and Kelvin probe force microscopy were used to explore the local electrical properties of the surface of CZTSSe thin films. The high-efficiency CZTSSe thin film exhibits significantly positive bending of surface potential around the grain boundaries. Dominant current paths along the grain boundaries are also observed. The surface electrical parameters of potential and current lead to potential solar cell applications using CZTSSe thin films, which may be an alternative choice of Cu(In,Ga)Se2.PACS number: 08.37.-d; 61.72.Mm; 71.35.-y.

Tracheal intubation with rocuronium using a "modified timing principle".

BACKGROUND: Rapid sequence induction (RSI) is indicated in various situations. Succinylcholine has been the muscle relaxant of choice for RSI, and rocuronium has become an alternative medicine for patients who cannot be administered succinylcholine for various reasons. Although rocuronium has the most rapid onset time among non-depolarizing muscle relaxants, the standard dose of rocuronium (0.6 mg/kg) takes 60 seconds to achieve appropriate muscle relaxation. We evaluated intubating conditions using the "modified timing principle" with rocuronium and succinylcholine. METHODS: In this prospective controlled blinded study, all patients received 1.5 µg/kg fentanyl intravenously with preoxygenation for 2 minutes and were randomized to receive 0.6 mg/kg rocuronium followed by 1.5 mg/kg propofol or 1.5 mg/kg propofol and 1.5 mg/kg succinylcholine. The rocuronium group was intubated just after confirming loss of consciousness, and the succinylcholine group was intubated 1 minute after injecting succinylcholine. Intubation condition, timing of events, and complications were recorded. RESULTS: All patients were successfully intubated in both groups. Apnea time of the rocuronium group (38.5 seconds) was significantly shorter than that in the succinylcholine group (100.7 seconds). No significant differences were observed in loss of consciousness time or intubation time. The succinylcholine group tended to show better intubation conditions, but no significant difference was observed. None of the patients complained awareness of the intubation procedure or had respiratory difficulty during a postoperative interview. CONCLUSIONS: The modified RSI with rocuronium showed shorter intubation sequence, acceptable intubation conditions, and a similar level of complications compared to those of conventional RSI with succinylcholine.