[KLF6 Super-enhancer Regulates Cell Proliferation by Recruiting GATA2 and SOX10 in Human Hepatoma Cells].

Super-enhancer consists of a large cluster of transcription enhancers that regulates the expression of genes playing an important role in the growth and development of malignant tumors. Recently, several attempts for the identification of super-enhancers have been made, but their functional role in tumor cells remains unclear. This paper aims at elucidating the functional properties of KLF6 super-enhancer related to the growth regulation of HepG2 cells, in relation to transcription factors (TFs). First, some TFs specifying KLF6 super enhancer were identified using CRISPR/Cas9 system and siRNA. Then, their effects on the expression of the target gene KLF6 were assessed. Last, their influence on the proliferation of tumor cells was considered using the MTT method. The study shows that the active enhancers of KLF6 super-enhancer recruit GATA2 and SOX10 TFs to control the expression of the target gene, KLF6. Our findings suggest that the activity of KLF6 super-enhancer is regulated by two TFs (GATA2 and SOX10), and its targeting may be a potential therapeutic strategy for the liver cancer therapy.

Preventive effect of subacidic 1% NaF-HF gel on dental caries in 6- to 7-year-old schoolchildren: a randomized controlled trial.

Objective: This study aimed to examine and compare the anti-caries effects of slightly acidic 1% NaF-HF gel when applied once or twice (7-day or 6-month interval) to mandibular first molars in 6- to 7-year-old children. Method and materials: This was a 1-year, multi-arm, placebo-controlled, double-blind, parallel-group randomized trial. In total, 1,077 schoolchildren from eight primary schools were allocated to one of the four study groups (group 1, single application; group 2, two applications with a 7-day interval; group 3, two applications with a 6-month interval; group 4, placebo control). The occlusal surfaces of permanent mandibular first molars were examined by three calibrated examiners who were blind to the group allocation at baseline and the end of the study. Caries reduction and prevented fraction was assessed. Results: A total of 986 children completed the study. There was a statistically significant difference in the mean D1MFT increment across the groups (P < .001). The mean D1MFT increment was 0.37 in group 1 (single application), 0.18 in group 2 (two applications with a 7-day interval), 0.21 in group 3 (two applications with a 6-month interval), and 0.56 in the control group. The mean D2MFT increments (0.22 in group 1, 0.06 in group 2, 0.18 in group 3, and 0.50 in the control group) also showed a statistically significant difference across the groups (P < .001). Conclusion: Subacidic 1% NaF-HF gel exerts a high preventive effect on caries (more than 40%) when applied twice at a 7-day interval in 6- to 7-year-old schoolchildren who do not use fluoride toothpaste in areas where drinking water is not fluoridated.

Wireless Ultrasound Surgical System with Enhanced Power and Amplitude Performances.

A wireless ultrasound surgical system (WUSS) with battery modules requires efficient power consumption with appropriate cutting effects during surgical operations. Effective cutting performances of the ultrasound transducer (UT) should be produced for ultrasound surgical knives for effective hemostasis performance and efficient dissection time. Therefore, we implemented a custom-made UT with piezoelectric material and re-poling process, which is applied to enhance the battery power consumption and output amplitude performances of the WUSS. After the re-poling process of the UT, the quality factor increased from 1231.1 to 2418 to minimize the unwanted heat generation. To support this UT, we also developed a custom-made generator with a transformer and developed 2nd harmonic termination circuit, control microcontroller with an advanced reduced instruction set computer machine (ARM) controller, and battery management system modules to produce effective WUSS performances. The generator with a matching circuit in the WUSS showed a peak-to-peak output voltage and current amplitude of 166 V and 1.12 A, respectively, at the resonant frequency. The performance with non-contact optical vibrators was also measured. In the experimental data, the developed WUSS reduced power consumption by 3.6% and increased the amplitude by 20% compared to those of the commercial WUSS. Therefore, the improved WUSS performances could be beneficial for hemostatic performance and dissection time during surgical operation because of the developed UT with a piezoelectric material and re-poling process.

Development of an Accurate Resonant Frequency Controlled Wire Ultrasound Surgical Instrument.

Our developed wire ultrasound surgical instrument comprises a bolt-clamped Langevin ultrasonic transducer (BLUT) fabricated by PMN-PZT single crystal material due to high mechanical quality factor and electromechanical coupling coefficient, a waveguide in the handheld instrument, and a generator instrument. To ensure high performance of wire ultrasound surgical instruments, the BLUT should vibrate at an accurate frequency because the BLUT's frequency influences hemostasis and the effects of incisions on blood vessels and tissues. Therefore, we implemented a BLUT with a waveguide in the handheld instrument using a developed assembly jig process with impedance and network analyzers that can accurately control the compression force using a digital torque wrench. A generator instrument having a main control circuit with a low error rate, that is, an output frequency error rate within ±0.5% and an output voltage error rate within ±1.6%, was developed to generate the accurate frequency of the BLUT in the handheld instrument. In addition, a matching circuit between the BLUT and generator instrument with a network analyzer was developed to transfer displacement vibration efficiently from the handheld instrument to the end of the waveguide. Using the matching circuit, the measured S-parameter value of the generator instrument using a network analyzer was -24.3 dB at the resonant frequency. Thus, our proposed scheme can improve the vibration amplitude and accuracy of frequency control of the wire ultrasound surgical instrument due to developed PMN-PZT material and assembly jig process.

Efficacy of nerve-sparing radical hysterectomy vs. conventional radical hysterectomy in early-stage cervical cancer: A systematic review and meta-analysis.

The aim of the present study was to compare the oncological outcome of nerve-sparing radical hysterectomy (NSRH) and conventional radical hysterectomy (CRH) for early-stage cervical cancer using a meta-analysis. A systematic review and meta-analysis was conducted, including 4 randomized controlled trials (RCT), 8 case-control and 11 comparative cohort studies comparing the morbidity, pelvic dysfunctions and oncological outcome between the two surgical methods. A total of 23 studies were included in this meta-analysis. The studies reported data of patients affected by cervical cancer; were written in English; included ≥20 patients; and reported data of patients with a comparison of clinical outcomes between NSRH and CRH. Data were extracted and risk of bias was assessed by four independent reviewers. A total of 1,796 patients were included: 884 patients (49.2%) undergoing NSRH and 912 (50.8%) undergoing CRH. The meta-analyses were conducted using Review Manager version 5.3 software, which is designed for conducting Cochrane reviews. As regards perioperative parameters, NSRH was found to be associated with a lower intraoperative blood loss and a shorter length of hospital stay in comparison with CRH. Patients undergoing NSRH experienced lower incidence of urinary, colorectal and sexual dysfunction compared with patients undergoing CRH. However, the resected parametrial width was favorable in patients with CRH, suggesting that NSRH was inferior to CRH in terms of radicality. The 5-year disease-free and overall survival rates were similar between the two groups. In this systematic review and meta-analysis, the collected data to date demonstrated that the nerve-sparing approach guarantees minimized surgical-related pelvic dysfunction, with similar oncological outcomes as CRH. However, further RCTs should be conducted to confirm the superiority and safety of NSRH.

Effects of Parity and Breast Feeding Duration on the Risk of Osteoporosis in Postmenopausal Korean Women: A Systematic Review and Meta-Analysis.

OBJECTIVES: To summarize the evidence regarding the association of parity and breast feeding duration with the risk of osteoporosis in postmenopausal Korean women. This was because studies have been inconsistent regarding the effect of parity and breast feeding duration on the risk of osteoporosis. METHODS: A systematic literature search of relevant studies published by December 26, 2018 was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL, RISS, KISS, KMbase, and KoreaMed. Outcome estimates of odds ratio (OR) or standardized mean difference were pooled with fixed or random-effect model. In case of heterogeneity, subgroup analysis was conducted. RESULTS: Seven cross-sectional studies (with 3,813 subjects) were included in the analysis. OR for osteoporosis was 1.43 (95% confidence interval [CI] = 1.09-1.88, P = 0.010) in postmenopausal women with higher parity compared to those with less parity. Moreover, OR for osteoporosis was 1.93 (95% CI = 1.28-2.93, P = 0.002) in postmenopausal women with longer durations of breast feeding than in those with shorter durations of breast feeding. CONCLUSIONS: This study revealed that duration of breast feeding increased the risk of osteoporosis in postmenopausal Korean women. More cohort studies with high quality research designs are needed to confirm our results.

Comparison of vaginal hysterectomy and laparoscopic hysterectomy: a systematic review and meta-analysis.

BACKGROUND: There are various surgical approaches of hysterectomy for benign indications. This study aimed to compare vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH) with respect to their complications and operative outcomes. METHODS: We selected randomised controlled trials that compared VH with LH for benign gynaecological indications. We included studies published after January 2000 in the following databases: Medline, EMBASE, and CENTRAL (The Cochrane Library). The primary outcome was comparison of the complication rate. The secondary outcomes were comparisons of operating time, blood loss, intraoperative conversion, postoperative pain, length of hospital stay and duration of recuperation. We used Review Manager 5.3 software to perform the meta-analysis. RESULTS: Eighteen studies of 1618 patients met the inclusion criteria. The meta-analysis showed no differences in overall complications, intraoperative conversion, postoperative pain on the day of surgery and at 48 h, length of hospital stay and recuperation time between VH and LH. VH was associated with a shorter operating time and lower postoperative pain at 24 h than LH. CONCLUSIONS: When both surgical approaches are feasible, VH should remain the surgery of choice for benign hysterectomy.

Clinical application of serum anti-Müllerian hormone in women.

Anti-Müllerian hormone (AMH), a peptide growth factor of the transforming growth factor-ß family, is a reliable marker of ovarian reserve. Regarding assisted reproductive technology, AMH has been efficiently used as a marker to predict ovarian response to stimulation. The clinical use of AMH has recently been extended and emphasized. The uses of AMH as a predictive marker of menopause onset, diagnostic tool for polycystic ovary syndrome, and assessment of ovarian function before and after gynecologic surgeries or gonadotoxic agents such as chemotherapy have been investigated. Serum AMH levels can also be affected by environmental and genetic factors; thus, the effects of factors that may alter AMH test results should be considered. This review summarizes the findings of recent studies focusing on the clinical application of AMH and factors that influence the AMH level and opinions on the use of the AMH level to assess the probability of conception before reproductive life planning as a "fertility test."

Radiographic and histologic observations of sequential healing processes following ridge augmentation after tooth extraction in buccal-bone-deficient extraction sockets in beagle dogs.

OBJECTIVES: To evaluate dimensional ridge alterations and sequential healing processes following ridge augmentation after tooth extraction in damaged extraction sockets with buccal-bone-deficiency. MATERIAL AND METHODS: Bilateral dental roots of three mandibular premolars were extracted with entire removal of the buccal-bone plate in eight beagle dogs. Unilateral sites were grafted with biomaterials (test group) and contralateral sites were healed without grafting (control group). Observations were made after 1, 2, 4, and 8 weeks, and all sites were distributed evenly (n = 6 for each group and period). Radiographic/histomorphometric analyses were performed. RESULTS: In spontaneous healing of damaged extraction sockets, the dimension of regenerated alveolar ridge gradually increased until 4 weeks and then remained stable, but radiographic/histomorphometric analyses revealed evident dimensional shrinkage compared to the pristine tissue at 8 weeks in the coronal and middle areas. Bone grafting retained the pristine dimension of alveolar ridge, and newly formed bone area within the augmented space continuously expanded during the observational period to the outermost border of the space. CONCLUSIONS: Spontaneous healing of damaged extraction sockets caused substantial dimensional shrinkage. However, ridge augmentation can provide space into which new bone may grow continuously, resulting in the final dimensions comparable to those of the pristine alveolar ridge.

Beneficial effects of fresh and fermented kimchi in prediabetic individuals.

BACKGROUND: With the increased incidence of diabetes mellitus, the importance of early intervention in prediabetes has been emphasized. We previously reported that fermented kimchi, a traditional Korean food, reduced body weight and improved metabolic factors in overweight participants. We hypothesized that kimchi and its fermented form would have beneficial effects on glucose metabolism in patients with prediabetes. METHODS: A total of 21 participants with prediabetes were enrolled. During the first 8 weeks, they consumed either fresh (1-day-old) or fermented (10-day-old) kimchi. After a 4-week washout period, they switched to the other type of kimchi for the next 8 weeks. RESULTS: Consumption of both types of kimchi significantly decreased body weight, body mass index, and waist circumference. Fermented kimchi decreased insulin resistance, and increased insulin sensitivity, QUICKI and disposition index values (p = 0.004 and 0.028, respectively). Systolic and diastolic blood pressure (BP) decreased significantly in the fermented kimchi group. The percentages of participants who showed improved glucose tolerance were 9.5 and 33.3% in the fresh and fermented kimchi groups, respectively. CONCLUSIONS: Consumption of kimchi had beneficial effects on glucose metabolism-related and anthropometric factors in participants with prediabetes. Fermented kimchi had additional effects on BP and insulin resistance/sensitivity. The percentage of participants who showed improvement in glucose tolerance was high in the fermented kimchi group.

Effects of multi-layer graphene capping on Cu interconnects.

The benefits of multi-layer graphene (MLG) capping on Cu interconnects have been experimentally demonstrated. The resistance of MLG capped Cu wires improved by 2-7% compared to Cu wires. The breakdown current density increased by 18%, suggesting that the MLG can act as an excellent capping material for Cu interconnects, improving the reliability characteristics. With a proper process optimization, MLG capped Cu interconnects could become a promising technology for high density back end-of-line interconnects.

Fermented kimchi reduces body weight and improves metabolic parameters in overweight and obese patients.

Kimchi is a traditional fermented Korean food that has garnered international interest due to its various beneficial effects. Focusing on the effect of fermentation, this study hypothesized that consumption of fermented kimchi would have more beneficial effects compared with that of fresh kimchi on metabolic parameters that are related to cardiovascular disease and metabolic syndrome risks in overweight and obese subjects. Twenty-two overweight and obese patients with body mass indexes greater than 25 kg/m(2) were randomly assigned to two 4-week diet phases separated by a 2-week washout period (crossover design). During each diet phase, the subjects consumed either fresh or fermented kimchi. Anthropometric data showed significant decreases in body weight, body mass index, and body fat in both groups, and the fermented kimchi group showed a significant decrease in the waist-hip ratio and fasting blood glucose. Net differences in the systolic blood pressure, diastolic blood pressure, percent body fat, fasting glucose, and total cholesterol in the fermented kimchi group were significantly greater than those in the fresh kimchi group. There was also a tendency for a decrease in fasting insulin after consumption of fermented kimchi. Therefore, the ingestion of fermented kimchi had positive effects on various factors associated with metabolic syndrome, including systolic and diastolic blood pressures, percent body fat, fasting glucose, and total cholesterol, compared with the fresh kimchi. These results suggest that the maturity of kimchi (fresh vs fermented) may affect obesity, lipid metabolism, and inflammatory processes.

Capsaicin attenuates palmitate-induced expression of macrophage inflammatory protein 1 and interleukin 8 by increasing palmitate oxidation and reducing c-Jun activation in THP-1 (human acute monocytic leukemia cell) cells.

Capsaicin, a spicy component of hot peppers, has been shown to improve inflammatory disease and obesity. In this study, we tested the hypothesis that the anti-inflammatory activity of capsaicin can be used to improve free fatty acid (FFA)-induced inflammation by reducing gene expression of macrophage inflammatory protein 1 (MIP-1) and interleukin 8 (IL-8) in THP-1 (human acute monocytic leukemia cell) macrophages. To investigate whether capsaicin ameliorates palmitate-induced MIP-1 and IL-8 gene expressions, we treated THP-1 cells with palmitate in the presence or absence of capsaicin and measured MIP-1 and IL-8 by real-time polymerase chain reaction. To elucidate the mechanism by which capsaicin effects on palmitate-induced MIP-1 and IL-8 gene expressions, we performed immunoblotting with stress kinase-related antibodies and measured palmitate oxidation and palmitate oxidation-related gene expression. Palmitate and stearate but not the unsaturated FFA oleate significantly increased MIP-1 and IL-8 expressions in THP-1 macrophages. Treatment with capsaicin or FFA oxidation stimulators inhibited palmitate-induced MIP-1 and IL-8 expressions in THP-1 macrophages. Capsaicin increased the gene expression of carnitine palmitoyltransferase 1 and the ß-oxidation of palmitate. Furthermore, capsaicin significantly reduced palmitate-stimulated activation of c-Jun N-terminal kinase, c-Jun, and p38. Our data suggest that the attenuation of palmitate-induced MIP-1 and IL-8 gene expressions by capsaicin is associated with reduced activation of c-Jun N-terminal kinase, c-Jun, and p38 and preserved ß-oxidation activity.

Intake of brown rice lees reduces waist circumference and improves metabolic parameters in type 2 diabetes.

Intake of whole grains has been associated with lower risks of type 2 diabetes and cardiovascular disease. Brown rice is unrefined whole grain and is produced by removing the outermost layers containing the germ and bran, which are rich in nutrients including dietary fiber, vitamins, minerals, and other unmeasured dietary constituents. The lees of brown rice (LB) are by-products of its fermentation in the process of manufacturing takju, a Korean turbid rice wine. In this study, we hypothesized that intake of LB would reduce waist circumference, a strong risk factor for cardiovascular disease in type 2 diabetic patients. A randomized, double-blind, placebo-controlled study was scheduled for 12 weeks. Thirty subjects were randomly assigned to receive a supplement prepared from the LB or from a mixed-grain dietary product (MG). Body weight, waist circumference, body composition, lipid profiles, and other laboratory parameters were measured. The LB group showed greater reduction in waist circumference (LB: 87.9 ± 8.8 to 85.1 ± 9.0 cm; MG: 86.9 ± 8.8 to 86.0 ± 9.3 cm; P = .032). In addition, the consumption of LB resulted in a significantly greater decrease in the level of aspartate transaminase (LB: 25.4 ± 8.5 to 21.0 ± 5.1 IU/mL; MG: 22.5 ± 5.3 to 22.4 ± 5.7 IU/mL; P = .044) and alanine transaminase (LB: 28.6 ± 11.3 to 21.9 ± 8.2 IU/mL; MG: 24.4 ± 7.5 to 24.5 ± 9.9 IU/mL; P = .038). Consumption of the LB was associated with a decreased waist circumference in type 2 diabetic patients. Further study is required to evaluate the metabolic effect of the extract of the LB in type 2 diabetes.

Health locus of control and assimilation of cervical cancer information in Deaf women.

This study assessed the relationship between Deaf women's internal health locus of control (IHLC) and their cervical cancer knowledge acquisition and retention. A blind, randomized trial evaluated Deaf women's (N = 130) baseline cancer knowledge and knowledge gained and retained from an educational intervention, in relation to their IHLC. The Multidimensional Health Locus of Control scales measured baseline IHLC, and a cervical cancer knowledge survey evaluated baseline to post-intervention knowledge change. Women's IHLC did not significantly predict greater cervical cancer knowledge at baseline or over time. IHLC does not appear to be a characteristic that must be considered when creating Deaf women's cancer education programs.

The impact of cervical cancer education for deaf women using a video educational tool employing American sign language, open captioning, and graphics.

BACKGROUND: Deaf women encounter barriers to accessing cancer information. In this study, we evaluated whether deaf women's knowledge could be increased by viewing a graphically enriched, American Sign Language (ASL) cervical cancer education video. METHODS: A blind, randomized trial evaluated knowledge gain and retention. Deaf women (n = 130) completed questionnaires before, after, and 2 months after viewing the video. RESULTS: With only a single viewing of the in-depth video, the experimental group gained and retained significantly more cancer knowledge than the control group. CONCLUSIONS: Giving deaf women access to the ASL cervical cancer education video (http://cancer.ucsd.edu/deafinfo) significantly increased their knowledge of cervical cancer.

Conjugated linoleic acid inhibits proliferation and modulates protein kinase C isoforms in human prostate cancer cells.

Prostate cancer is the second most common cancer in men. The disease etiology is poorly understood, but diet and lifestyle are contributory factors. Conjugated linoleic acids (CLAs), naturally occurring fatty acids in ruminant food products, have antitumor properties in animal models of cancer and antiproliferative effects on cancer cells in vitro. The cellular mechanisms by which CLAs elicit these effects are unclear, particularly for prostate cancer cells. We have previously identified protein kinase C (PKC) isoforms, alpha, delta, iota, mu, and zeta in LNCaP prostate cancer cells. The objective of this study was to determine the effects of CLAs (individual cis-9, trans-11 and trans-10, cis-12 isoforms and a 50:50 mixture) on PKC isoform abundance in LNCaP cells. Confluent cells were treated with 6, 25, and 50 microM CLA for 0.5, 6, and 24 h. Cytosol and membrane protein fractions were assayed for PKC isoforms (mainly alpha and delta but also iota, mu, and zeta) by Western blot analysis using specific antibodies. CLAs clearly modulated the abundance of these PKC isoforms, both positively and negatively, depending on the isoform, concentration of CLAs, and period of treatment. Increased PKC-delta and decreased PKC-iota membrane abundance was consistent with CLAs eliciting increased apoptosis and, in part, with their antitumor effects.

Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity.

The mechanisms governing positive selection of T cells in the thymus are still incompletely understood. Here, we describe a N-ethyl-N-nitrosourea induced recessive mouse mutant, Ms. T-less, which lacks T cells in the peripheral blood because of a complete block of thymocyte development at the CD4(+)CD8(+) stage. Single nucleotide polymorphism mapping and candidate gene sequencing revealed a nonsense mutation in the inositol (1,4,5) trisphosphate 3 kinase B (Itpkb) gene in Ms. T-less mice. Accordingly, Ms. T-less thymocytes do not show detectable expression of Itpkb protein and have drastically reduced basal inositol (1,4,5) trisphosphate kinase activity. Itpkb converts inositol (1,4,5) trisphosphate to inositol (1,3,4,5) tetrakisphosphate, soluble second messengers that have been implicated in Ca(2+) signaling. Surprisingly, Ca(2+) responses show no significant differences between wild type (WT) and mutant thymocytes. However, extracellular signal-regulated kinase (Erk) activation in response to suboptimal antigen receptor stimulation is attenuated in Ms. T-less thymocytes, suggesting a role for Itpkb in linking T cell receptor signaling to efficient and sustained Erk activation.

Cardiac responses of Pacific oyster Crassostrea gigas to agents modulating cholinergic function.

To examine the functional effects of cholinergic modulation compounds in oyster hearts and to explore their possible use in monitoring intoxication with acetylcholine-esterase (AChE) inhibitors such as organophosphates, tests were performed with in situ oyster heart preparations. The endogenous cholinergic agonist acetylcholine (ACh), AChE-resistant synthetic agonist carbachol, and the reversible carbamate type of AChE inhibitor physostigmine, all potently depressed spontaneous cardiac contractility. The depression was reversed by extensive washout, or prevented by muscarinic cholinergic antagonist atropine. The irreversible organophosphate type AChE inhibitor parathion or its active metabolite paraoxon at concentrations up to 100 microM failed to depress cardiac contractility. While other reversible AChE inhibitors such neostigmine and pyridostigmine also depressed the contractility, organophosphate AChE inhibitors malathion, diazinon, or phenthoate did not. Despite the differential effect in depressing cardiac function between the reversible and irreversible inhibitors, both of these inhibitors effectively inhibited cardiac AChE activity. The results suggest that the activation of muscarinic cholinergic receptors is coupled to inhibitory cardiac modulation, and organophosphate AChE inhibitors may inhibit only an AChE isozyme located at sites that are not important for control of cardiac activity in oysters.

Regulation of selenoprotein GPx4 expression and activity in human endothelial cells by fatty acids, cytokines and antioxidants.

Phospholipid hydroperoxide glutathione peroxidase (GPx4) is the only antioxidant enzyme known to directly reduce phospholipid hydroperoxides within membranes and lipoproteins, acting in conjunction with alpha-tocopherol to inhibit lipid peroxidation. Peroxidation of lipids has been implicated in a number of pathophysiological processes, including inflammation and atherogenesis. We investigated the relative positive and negative effects of specific polyunsaturated fatty acids (PUFAs) and inflammatory cytokines on the activity and gene expression of the selenium-dependant redox enzyme GPx4. In human umbilical vein endothelial cells (HUVEC), GPx4 mRNA levels and activity were increased optimally by 114 nM selenium (as sodium selenite). Docosahexaenoic acid (DHA) and conjugated linoleic acid (CLA) further increased mRNA levels whereas arachidonic acid (ARA) had no effect; enzyme activity was decreased by DHA, was unaffected by CLA or was increased by ARA. GPx4 protein levels increased with selenium, ARA and DHA addition but not with CLA. Interleukin-1beta (IL-1beta) increased GPx4 mRNA, protein and activity whereas TNFalpha at 1 ng/ml increased activity while at 3 ng/ml it reduced activity and mRNA. Conversely, alpha-tocopherol reduced mRNA levels without affecting activity. These results indicate that lipids, cytokines and antioxidants modulate GPx4 in a complex manner that in the presence of adequate selenium, may favour protection against potentially proatherogenic processes.