[Sleep Strategies for Shift Work Nurses].

To meet the demands of a 24/7 society, shift work is necessary. Shift work is outside the traditional regular 9-to-5 work schedule, is characterized by irregular working hours, and exists in various industries. However, this abnormal working time can disrupt the natural day and night rhythm, and if poorly adjusted, it can lead to shift work sleep disorder (SWSD). SWSD is associated with multiple health risks, including impaired cognitive function, increased risk of accidents, and various metabolic and cardiovascular diseases. The frontline nurses typically work shifts to provide comprehensive patient care. This article aims to discuss sleep physiology, apply existing literature to discuss the impact on nurses resulting from shift work, and further offer strategies to regulate sleep to promote physical and mental health. These strategies range from organizational interventions (e.g., optimizing shift schedules) to individual interventions (e.g., lifestyle changes) and the use of chronobiological techniques (e.g., light therapy) to promote the adjustment of circadian rhythms, etc.

Risk factors for cerebral palsy in children in Taiwan.

AIM: To determine the significant risk factors of cerebral palsy (CP) in Taiwanese children and the associations between infant-related and parent-related factors. METHOD: Data from 1 459 093 infants and their parents in Taiwan's national databases collected between 2009 and 2016 were used. The cohort with CP included children diagnosed with CP between birth and age 3 years; a total of 3254 children with CP were included in the final analysis. Hierarchical logistic regression models were used to estimate the odds ratio for the risk factors of CP. RESULTS: The hierarchical logistic regression models indicated that significant risk factors associated with CP are suburban location, low income, maternal and paternal diabetes mellitus, paternal substance abuse, paternal seizure disorder, male sex, birth by Cesarean section, singleton birth, low birthweight, being born extremely and very preterm, intraventricular hemorrhage, and periventricular leukomalacia, as well as tube feeding, ventilator use, and dopamine administration within 6 months of age. INTERPRETATION: In addition to common maternal and infant risk factors, we identified significant paternal risk factors associated with CP, including diabetes mellitus, seizure disorder, and substance abuse. The combination of maternal, paternal, and infant risk factors in CP holds great promise for early identification and intervention.

Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation.

Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from energy substrates to oxygen to produce adenosine triphosphate. Mitochondria also regulate cell proliferation, metastasis, and deterioration. The flow of electrons in the mitochondrial respiratory chain generates reactive oxygen species (ROS), which are harmful to cells at high levels. Oxidative stress caused by ROS accumulation has been associated with an increased risk of cancer, and cardiovascular and liver diseases. Glutathione (GSH) is an abundant cellular antioxidant that is primarily synthesized in the cytoplasm and delivered to the mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within the mitochondria. A long-term imbalance in the ratio of mitochondrial ROS to mGSH can cause cell dysfunction, apoptosis, necroptosis, and ferroptosis, which may lead to disease. This study aimed to review the physiological functions, anabolism, variations in organ tissue accumulation, and delivery of GSH to the mitochondria and the relationships between mGSH levels, the GSH/GSH disulfide (GSSG) ratio, programmed cell death, and ferroptosis. We also discuss diseases caused by mGSH deficiency and related therapeutics.

Nomogram for Predicting the Risk of Complications in Hospitalized Children With Peripheral Intravenous Catheters.

OBJECTIVE: The aim of the study is to identify the hospitalized children at risk of peripheral intravenous catheter (PIVC) complications by severity prediction. METHODS: The study included the data of 301 hospitalized children with PIVC complications in 2 tertiary teaching hospitals. A researcher-designed tool was used to collect risk factors associated with PIVC complications. Predictors of PIVC complications at univariate analysis and multivariable logistic regression analysis by backward stepwise. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing complications. RESULTS: A total of 182 participants (60.5%) had a moderate injury from PIVC complications. Multivariable logistic regression analysis indicated that the vascular condition, limb immobilization, needle adjustment in venipuncture, infusion length, infusion speed, and insertion site were independent predictors. The nomogram for assessing the severity of PIVC complications indicated good predictive accuracy (area under the curve = 0.79) and good discrimination (concordance index = 0.779). Decision curve analysis demonstrated that the nomogram was a good clinical value with a wide range of threshold probabilities (4%-100%). CONCLUSIONS: The risk prediction model has good predictive performance, and the nomogram provides an easy-to-use visualization to identify the severity of PIVC complications and guide timely nursing care management.

Polygonum barbatum extract reduces colorectal cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition via YAP and ß-catenin pathway regulation.

Colorectal cancer (CRC) is the third most common cancer worldwide with novel therapeutic developmental challenges. Polygonum barbatum has anticancer potential, but its mechanism(s) are unclear. This study investigates the inhibitory effect of P. barbatum on human CRC cells. Polygonum barbatum extract (PBE) and quercetin standard HPLC fingerprints were determined using analytical RP-HPLC and evaluations were completed using the human colon cancer cell line HCT-116 (KRASG13D mutation) and HT-29 (BRAF mutation) cells. Post-PBE treatment, cell viability, colony formation, migration, invasion, and apoptosis, as well as changes in the whole-transcriptome of cells were analyzed. PBE significantly reduced CRC cell growth, migration, and invasion, and the genes responsible for extracellular matrix (ECM) organization, cell motility, and cell growth were suppressed by PBE. The differentially expressed genes revealed that PBE treatment exerted a significant effect on the ECM interaction and focal adhesion pathways. Epithelial-to-mesenchymal transition markers, N-cadherin, vimentin, SLUG, and SNAIL, were shown to be regulated by PBE. These effects were associated with blockade of the Yes-associated protein and the GSK3ß/ß-catenin axis. PBE exerts a significant inhibitory effect on CRC cells and may be applicable in clinical trials.

Long-term patient-reported donor-site morbidity after free peroneal fasciocutaneous flap in head and neck reconstruction.

OBJECTIVE: Fasciocutaneous free flap based on the peroneal artery (boneless version) is an option in our practice for head and neck reconstruction. However, the associated donor-site morbidity has rarely been discussed. Thus, this study investigated the long-term patient-reported donor-site morbidity associated with peroneal flaps. METHODS: In this single-center, retrospective, observational study, 39 patients who underwent a free peroneal flap were enrolled. We evaluated donor-site morbidity with a modified questionnaire from Enneking et al. and Bodde et al. RESULTS: Patient-reported daily life limitation was relatively low (5/39; 12.9%). Donor-site morbidities, namely pain (4/39; 10.3%), sensory disturbance (9/39; 23.1%), and walking limitation (9/39; 23.1%) were reported; most were rated minimal in severity. Among patients with walking limitation, muscle weakness (3/39; 7.7%), ankle instability (6/39; 15.4%), and gait alternation (6/39; 15.4%) were reported. Six patients developed claw toe. CONCLUSION: Balancing successful reconstruction and donor-site morbidity is challenging. This long-term patient-reported survey revealed that harvesting peroneal flaps resulted in minimal or minor donor-site morbidity with no obvious impacts on the patients' daily quality of life. Although free radial forearm flaps and anterolateral thigh flaps are standard, free peroneal flaps have been proven reliable, with acceptable donor-site morbidity.

Selenium modulates AR/IGF-1R/EGFR and TROP2 signaling pathways and improves anticancer efficacy in murine mammary carcinoma 4T1.

The micronutrient selenium (Se) has been shown to exert potential anticancer properties. This study aimed to evaluate the effects of Se (in Se yeast form) on the selenoproteins (SELENO), AR/IGF-1R/EGFR, PI3K/Akt/mTOR and Ras/Raf/ERK cascades, and immune checkpoint blockade in TNBC murine 4T1 cells. We also assessed the effects of combination treatment with chemotherapeutic doxorubicin and Se on trophoblast cell surface antigen 2 (TROP2) levels. Compared with the control groups, cells incubated with Se (0.25, 0.5, 0.75, 1.0, 1.5 µg Se/mL) have lower viability, raised intracellular Se concentrations and SELENO expression, and higher malondialdehyde products in a dose-dependent manner. Se induced the inactivation of AR/IGF-1R/EGFR and downregulation of the PI3K/Akt/mTOR and Ras/Raf/ERK signaling molecules. Se-treated cells also exhibited decreased mitochondrial membrane potential, reduced levels of the cell cycle regulatory protein cyclin D1, cancer stemness, metastatic and EMT-related markers, and increased apoptosis. Subsequently, Se treatment significantly suppressed PD-1/PD-L1 and CTLA-4 mRNA levels and proteins. Doxorubicin decreased 4T1 cell viability and TROP2 expression levels, but the addition of Se to doxorubicin contributed to further reductions. Similar responses to Se treatment were also observed in the human MDA-MB-231 and MCF-7 breast cancer cells. These results show that Se upregulates SELENO and anti-AR/IGF-1R/EGFR signaling in TNBC cells, thus inducing oxidative stress-dependent apoptosis and cell cycle arrest, stemness, EMT, and metastasis, as well as blocking the immune checkpoint molecules. TROP2 down-regulation with Se is also a potential anti-TNBC therapeutic target.

Comparison of the outcomes of anterolateral thigh flap and peroneal flap in total laryngectomy reconstruction.

Background: We usually use an ALT or peroneal flap in total laryngectomy reconstruction, depending on the surgeons' preference. No direct comparison of the outcomes of the ALT flap and peroneal flap exists. Methods: From 2014 to 2022, we reviewed patients who had total laryngectomy and were reconstructed with an ALT flap and peroneal flap. Patient characteristics and surgical outcomes were collected and compared. Results: The peroneal group had a significantly higher risk of neopharynx leakage (40% vs. 13.2%, p = .020) and late pharyngocutaneous fistula formation (30% vs. 5.3%, p = .009) than the ALT group. Peroneal flap was found to be the only independent risk factor for neopharynx leakage (p = .025, odds ratio [OR] = 5.5) and late pharyngocutaneous fistula formation (p = .02, OR = 7.7) in multivariate logistic regression. Conclusion: In the reconstruction of total laryngectomy, the ALT flap is preferable over the peroneal flap.

Impact of sleep-wake features on fatigue among female shift work nurses.

BACKGROUND: Sleep disturbance and fatigue are prevalent in nurses. Little is known about the characteristics of shift work nurses' sleep-wake features and their subsequent impact on work performance. The study aimed to describe the characteristics of the sleep-wake index, reaction time, saliva cortisol level, and fatigue severity among female shift work nurses. METHODS: This is a cross-sectional exploratory study. A convenience sample of 152 female nurses (8-hour day-evening-night, n = 70; 12-hour day-night, n = 82) participated in this study from nine intensive care units (ICUs) from two teaching hospitals in Beijing, China. A consecutive 7-day actigraphy data were used to analyse sleep-wake indexes, including total sleep time (TST) and circadian activity rhythms (CAR). Before and after shifts, the following data were collected, psychomotor vigilance task for reaction time, saliva cortisol for the level of alertness, and self-reported fatigue severity with the Lee Fatigue Scale-Short Form. RESULTS: All nurses reported clinically significant fatigue severity. Compared with the 8-hour shift nurses, the 12-hour shift nurses had significantly more TST (456 vs. 364 min), higher saliva cortisol levels before the day shift (0.54 vs. 0.31), but longer reaction time before the night shift (286 vs. 277 ms). In both shifts, those with better CAR had significantly longer TST. CONCLUSION: Female nurses experienced fatigue and desynchronized CAR, especially nurses on a 12-hour shift. The CAR-friendly shift work schedule is needed to minimize the health and safety impacts of circadian misalignment for nurses.Key messagesThis is the first use of consecutive 7-day actigraphy data to explore the link between sleep disturbances as a stressor to CAR, salivary cortisol, and reaction time among clinical nurses.CAR may be a helpful indicator for overworked nurses, and it can serve as a modifiable target for interventions to enhance nurses' well-being.

Volcanic contribution to the 1990s North Pacific climate shift in winter.

It is debatable whether external forcing can change the state of the climate. By investigating decadal changes with and without including the 1990s stratospheric volcanic aerosols, we explored the volcanic eruptions contribution to decadal climate regime shifts occurring in boreal winter over the North Pacific. The volcanic eruptions contribution can be characterized as a series of rapid changes, including the strengthening and poleward shift of the midlatitude westerly jet stream. In addition to the short-lived radiative effects primarily induced by the 1991 Mount Pinatubo eruption, the volcanically driven decadal change can be observed in the mid-to-late 1990s, suggesting a time-lagged characteristic of the volcanic climate impact. Compared with the decadal change irrelevant to volcanic eruption, the decadal state more dramatically enters into the next phase when volcanic forcing is included. The climate oscillation-related pattern shifts that occurred across the 1990s can provide insights into volcanically induced changes in decadal atmospheric circulation.

Bioactive Compounds of Underground Valerian Extracts and Their Effect on Inhibiting Metabolic Syndrome-Related Enzymes Activities.

Extractions of the underground parts of valerian were prepared with water and ethanol (25-95%) at 25-75 °C. Extraction yields, bioactive compounds, and the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability of lyophilized extracts were determined. The inhibitory effects of the extracts, valerenic acid derivatives and phenolic acids, on metabolic syndrome (MS)-related enzymes activities were further examined. Both roots and rhizomes extracted with 95% ethanol at 75 °C had the highest levels of bioactive compounds. The antioxidant capacity and inhibition of MS-related enzymes of the roots extract were better than those of the rhizomes. The roots extract more strongly inhibited pancreatic lipase (inhibition of 50% of enzyme activity (IC50), 17.59 mg/mL), angiotensin-converting enzyme (ACE, IC50, 3.75 mg/mL), α-amylase (IC50, 12.53 mg/mL), and α-glucosidase (IC50, 15.40 mg/mL). These four phenolic acids inhibited the activity of MS-related enzymes. Valerenic acid demonstrated more of an inhibitory ability for ACE (IC50, 0.225 mg/mL, except for caffeic acid) and α-glucosidase (IC50, 0.617 mg/mL) than phenolic acids. Valerian extract inhibited key enzyme activities that were associated with obesity (lipase), hypertension (ACE), and type 2 diabetes (α-amylase and α-glucosidase), suggesting that it is a potential candidate for the development of functional supplements.

Tracking westerly wind directions over Europe since the middle Holocene.

The variability of the northern westerlies has been considered as one of the key elements for modern and past climate evolution. Their multiscale behavior and underlying control mechanisms, however, are incompletely understood, owing to the complex dynamics of Atlantic sea-level pressures. Here, we present a multi-annually resolved record of the westerly drift over the past 6,500 years from northern Italy. In combination with more than 20 other westerly-sensitive records, our results depict the non-stationary westerly-affected regions over mainland Europe on multi-decadal to multi-centennial time scales, showing that the direction of the westerlies has changed with respect to the migrations of the North Atlantic centers of action since the middle Holocene. Our findings suggest the crucial role of the migrations of the North Atlantic dipole in modulating the westerly-affected domain over Europe, possibly modulated by Atlantic Ocean variability.

Targeting EGFR in Combination with Nutritional Supplements on Antitumor Efficacy in a Lung Cancer Mouse Model.

Selenium (Se) and fish oil (FO) exert anti-epidermal growth factor receptor (EGFR) action on tumors. This study aimed to compare the anti-cancer efficacy of EGFR inhibitors (gefitinib and erlotinib) alone and in combination with nutritional supplements of Se/FO in treating lung cancer. Lewis LLC1 tumor-bearing mice were treated with a vehicle or Se/FO, gefitinib or gefitinib plus Se/FO, and erlotinib or erlotinib plus Se/FO. The tumors were assessed for mRNA and protein expressions of relevant signaling molecules. Untreated tumor-bearing mice had the lowest body weight and highest tumor weight and volume of all the mice. Mice receiving the combination treatment with Se/FO and gefitinib or erlotinib had a lower tumor volume and weight and fewer metastases than did those treated with gefitinib or erlotinib alone. The combination treatment exhibited greater alterations in receptor signaling molecules (lower EGFR/TGF-ß/TßR/AXL/Wnt3a/Wnt5a/FZD7/ß-catenin; higher GSK-3ß) and immune checkpoint molecules (lower PD-1/PD-L1/CD80/CTLA-4/IL-6; higher NKp46/CD16/CD28/IL-2). These mouse tumors also had lower angiogenesis, cancer stemness, epithelial to mesenchymal transitions, metastases, and proliferation of Ki-67, as well as higher cell cycle arrest and apoptosis. These preliminary results showed the Se/FO treatment enhanced the therapeutic efficacies of gefitinib and erlotinib via modulating multiple signaling pathways in an LLC1-bearing mouse model.

Northern Hemisphere Urban Heat Stress and Associated Labor Hour Hazard from ERA5 Reanalysis.

Increasing surface air temperature is a fundamental characteristic of a warming world. Rising temperatures have potential impacts on human health through heat stress. One heat stress metric is the wet-bulb globe temperature, which takes into consideration the effects of radiation, humidity, and wind speed. It also has broad health and environmental implications. This study presents wet-bulb globe temperatures calculated from the fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis and combines it with health guidelines to assess heat stress variability and the potential for reduction in labor hours over the past decade on both the continental and urban scale. Compared to 2010-2014, there was a general increase in heat stress during the period from 2015 to 2019 throughout the northern hemisphere, with the largest warming found in tropical regions, especially in the northern part of the Indian Peninsula. On the urban scale, our results suggest that heat stress might have led to a reduction in labor hours by up to ~20% in some Asian cities subject to work-rest regulations. Extremes in heat stress can be explained by changes in radiation and circulation. The resultant threat is highest in developing countries in tropical areas where workers often have limited legal protection and healthcare. The effect of heat stress exposure is therefore a collective challenge with environmental, economic, and social implications.

Antitumorigenic Effect of Tramadol and Synergistic Effect With Doxorubicin in Human Breast Cancer Cells.

BACKGROUND: Breast cancer in women is one of the leading causes of cancer mortality worldwide, and curative therapy is the main focus of clinical treatment. Anesthetic-analgesic techniques might alter stress responses and immunity and thereby influence outcomes in cancer patients. This study investigated the effect of tramadol on breast cancer progression and metastasis. METHODS: The effects of tramadol on two different subtypes of human breast adenocarcinoma cell lines, MDA-MB-231 and MCF-7, were studied with regard to cell growth, migration, colony formation and invasion and normoxic or hypoxic microenvironment for the expression of hypoxia-inducible factor-1α, reactive oxygen species, epithelial-mesenchymal transition related and cyclin-related proteins. The co-administration of tramadol and doxorubicin was studied to determine whether the effective doxorubicin dose might be reduced in combination with tramadol. RESULTS: The results showed that tramadol inhibited cell growth at concentrations more than 0.5 and more than 1.0 mg/mL in MDA-MB-231 and MCF-7 cells, respectively. Additionally, cell migration, colony formation and invasion were inhibited in a dose-dependent manner by tramadol in both cell lines. The combination of tramadol and doxorubicin induced synergistic effects in MDA-MD-231 cells and, with specific dosage combinations in MCF-7 cells. CONCLUSIONS: Tramadol may regulate epithelial-mesenchymal transition and possess cytotoxic effects in breast cancer cells. Tramadol inhibits the progression of breast cancer cells and might be a candidate for combination therapy, especially for triple-negative breast cancer, and is a promising treatment strategy for breast cancer.

Research Priorities of Applying Low-Cost PM2.5 Sensors in Southeast Asian Countries.

The low-cost and easy-to-use nature of rapidly developed PM2.5 sensors provide an opportunity to bring breakthroughs in PM2.5 research to resource-limited countries in Southeast Asia (SEA). This review provides an evaluation of the currently available literature and identifies research priorities in applying low-cost sensors (LCS) in PM2.5 environmental and health research in SEA. The research priority is an outcome of a series of participatory workshops under the umbrella of the International Global Atmospheric Chemistry Project-Monsoon Asia and Oceania Networking Group (IGAC-MANGO). A literature review and research prioritization are conducted with a transdisciplinary perspective of providing useful scientific evidence in assisting authorities in formulating targeted strategies to reduce severe PM2.5 pollution and health risks in this region. The PM2.5 research gaps that could be filled by LCS application are identified in five categories: source evaluation, especially for the distinctive sources in the SEA countries; hot spot investigation; peak exposure assessment; exposure-health evaluation on acute health impacts; and short-term standards. The affordability of LCS, methodology transferability, international collaboration, and stakeholder engagement are keys to success in such transdisciplinary PM2.5 research. Unique contributions to the international science community and challenges with LCS application in PM2.5 research in SEA are also discussed.

A Case of Delayed Tension Pneumocephalus in a Patient Undergoing Facial Cosmetic Surgery.

There has been a recognizable surge in cosmetic surgery in recent years, partly influenced by social media, and the easy accessibility to such medical procedures. As with all types of surgery, the risks of complications are real, and in this specific setting, they tend to occur in a younger age group. Here, we discuss a rare complication and subsequent presentation of tension pneumocephalus, following an episode of cardiac arrest in a 58 year old female, during elective cosmetic-facial surgery. Typically, pneumocephalus develops when there are skull or facial bone fractures, and presents characteristically with leakage of cerebrospinal fluid from the ears and/or nose. The absence of the typical clinical signs and the lack of a clinical history or radiologically evidence of skull or facial bone fractions, may result in a delayed diagnosis, permanent brain injury and death. Awareness of such an unusual complication is therefore crucial when considering any surgery to the head and face (including cosmetic surgery), or following prolonged resuscitative efforts, which may well develop days after the inciting event.

The effect of bright light therapy in migraine patients with sleep disturbance: A prospective, observational cohort study protocol.

Background: Migraine is a common disabling disorder, and its substantial burden is associated with a considerable negative impact on the patients' quality of life. Moreover, aging patients with migraine have more cognitive complaints. Additionally, the elderly are more likely to have sleep disturbances, which may also predict the risk of incident dementia. Migraines are reported to be closely associated with sleep and circadian rhythms. Sleep disturbance is a well-known trigger for migraine episodes; moreover, shift work or jet lag reportedly triggers some migraines. The hypothalamus is thought to be the migraine generator; sleep and circadian activity rhythm are also controlled by the hypothalamus. Evidence suggests an influence of both sleep and circadian system on migraine. Previously, light therapy has been show to stabilize sleep architecture and further improve insomnia related to circadian rhythm disorders. However, the beneficial effect of light therapy on migraine with sleep disturbance has not yet been determined. We aim to explore the effects of light therapy for migraine combined with sleep disturbance. Methods and analysis: This project is a 2-year, randomized, double-blind, placebo-controlled clinical trial. The study design includes a 4-week monitoring period (baseline and pretest), a 4-week treatment period, and a posttest. The study participants will undergo assessments on headache frequency and severity and subjective and objective (wrist actigraphy and polysomnography) sleep disturbances, and quality of life and a series of blood tests for serum biomarkers. Discussion: This study will establish evidence-based alternative medicine for the preventive effect of bright light therapy in migraine patients with sleep disturbances. Moreover, our data will be useful to comprehend the biochemical mechanism of light therapy in migraine prevention.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04890691.

Role of eccentricity in early Holocene African and Asian summer monsoons.

The effect of precession on paleoclimate changes depends on eccentricity. However, whether and to what degree eccentricity relates to millennial-scale monsoonal changes remain unclear. By investigating climate simulations with a fixed precession condition of 9 ka before the present, we explored the potential influence of eccentricity on early-Holocene changes in the Afro-Asian summer monsoons. Compared with the lower eccentricity of the present day, higher eccentricity in the early Holocene strengthened the continental summer monsoons, Pacific anticyclone, and Hadley circulation, particularly over the ocean. Over Africa, the eccentricity-induced "dry-gets-wetter" condition could be related to the Green Sahara, suggesting a superimposed effect of precession. Over the western Pacific, the tropical response to eccentricity may have been competitive in terms of what an extremely high obliquity may have caused. A downscaled modulation of eccentricity in relation to precession and obliquity cannot be ignored when paleomonsoon records are studied. Regarding early-Holocene monsoonal changes in South Asia, however, a high eccentricity may have had only a secondary effect on enhancing the monsoonal precipitation in the southern edge of the Tibetan Plateau, exhibiting the weak power of candle-like heating. This suggested that sizable monsoonal changes over the northern Indian Ocean and India-Pakistan region are unrelated to early-Holocene eccentricity.

4-Acetylantrocamol LT3 Inhibits Glioblastoma Cell Growth and Downregulates DNA Repair Enzyme O6-Methylguanine-DNA Methyltransferase.

Glioblastoma multiforme (GBM) is a deadly malignant brain tumor that is resistant to most clinical treatments. Novel therapeutic agents that are effective against GBM are required. Antrodia cinnamomea has shown antiproliferative effects in GBM cells. However, the exact mechanisms and bioactive components remain unclear. Thus, the present study aimed to investigate the effect and mechanism of 4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from Antrodia cinnamomeamycelium, in vitro. U87 and U251 cell lines were treated with the indicated concentration of 4AALT3. Cell viability, cell colony-forming ability, migration, and the expression of proteins in well-known signaling pathways involved in the malignant properties of glioblastoma were then analyzed by CCK-8, colony formation, wound healing, and western blotting assays, respectively. We found that 4AALT3 significantly decreased cell viability, colony formation, and cell migration in both in vitro models. The epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), Hippo/yes-associated protein (YAP), and cAMP-response element binding protein (CREB) pathways were suppressed by 4AALT3. Moreover, 4AALT3 decreased the level of DNA repair enzyme O6-methylguanine-DNA methyltransferase and showed a synergistic effect with temozolomide. Our findings provide the basis for exploring the beneficial effect of 4AALT3 on GBM in vivo.