Apigenin attenuates tetrabromobisphenol A-induced cytotoxicity in neuronal SK-N-MC cells.

Tetrabromobisphenol A (TBBPA) is a reactive brominated flame retardant widely used in various industrial and household products. This compound is persistent in the environment and accumulates in living organisms through the food chain, and is toxic to animals and human beings. Studies have shown that TBBPA is toxic to various human cell lines, including neuronal cells. Apigenin is a dietary flavonoid that exhibits various beneficial health effects on biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated the cytoprotective effects of apigenin against TBBPA-mediated cytotoxicity in SK-N-MC cells. Our results demonstrated that treatment of SK-N-MC cells with apigenin increased the cell viability, which was decreased by TBBPA, and reduced apoptosis and autophagy induced by TBBPA. Although we did not observe any change in the levels of IL-1ß and nitrite in cultured cells after TBBPA treatment, apigenin was found to decrease the production of these pro-inflammatory mediators. Apigenin decreased the intracellular Ca2+ concentration, NOX4 level, oxidative stress, and mitochondrial membrane potential loss and increased the mitochondrial biogenesis and nuclear Nrf2 levels that were reduced by TBBPA. Finally, apigenin treatment decreased Akt and ERK induction in cells exposed to TBBPA. Based on these results, apigenin could be a promising candidate for designing natural drugs to treat or prevent TBBPA-related neurological disorders.

Protective effects of sciadopitysin against methylglyoxal-induced degeneration in neuronal SK-N-MC cells.

The accumulation of advanced glycation end products (AGEs) causes metabolic dysfunction and neuronal cell damage. Methylglyoxal (MG) is a major glycating agent that reacts with basic residues present in proteins and promotes the formation of AGEs. Sciadopitysin, a type of biflavonoid, exerts protective effects against neuronal cell damage; however, the underlying mechanisms have not been studied. This study aimed to investigate the mechanisms underlying the protective effects of sciadopitysin against MG-mediated cytotoxicity in SK-N-MC neuroblastoma cells. Our results demonstrated that pretreatment of SK-N-MC cells with sciadopitysin improved the cell viability that was inhibited by MG and inhibited the apoptosis induced by MG. Sciadopitysin attenuated intracellular Ca2+ , NOX4 levels, oxidative stress, and MG-protein adduct levels, and increased nuclear Nrf2 and glyoxalase 1 levels in the presence of MG. These results suggest that sciadopitysin exerts neuroprotective effects against MG-induced death of human SK-N-MC cells via its antioxidative action. This study highlights sciadopitysin as a promising candidate for antioxidant therapy and designing natural drugs against AGE-induced neurodegenerative disorders.

The influence of positive end-expiratory pressure (PEEP) in predicting fluid responsiveness in patients undergoing one-lung ventilation.

Background: Dynamic preload parameters such as pulse pressure variation (PPV) and stroke volume variation (SVV) have widely been used as accurate predictors for fluid responsiveness in patients under mechanical ventilation. To circumvent the limitation of decreased cyclic change of intrathoracic pressure, we performed an intermittent PEEP challenge test to evaluate whether PPV or SVV can predict fluid responsiveness during one-lung ventilation (OLV). Methods: Forty patients undergoing OLV were analyzed. Baseline hemodynamic variables including PPV and SVV and respiratory variables were recorded after chest opening in lateral position under OLV (T1). Five minutes after application of PEEP 10 cmH2O, the parameters were recorded (T2). Thereafter, PEEP was withdrawn to 0 cmH2O for 5 minutes (T3), and fluid loading was performed with balanced crystalloid solution 6 mL/kg of ideal body weight for 5 minutes. Five minutes after completion of fluid loading, all variables were recorded (T4). The patient was classified as fluid responder if SV increased ≥10% after fluid loading and as non-responder if SV increased <10%. Results: Prediction of fluid responsiveness was evaluated with area under the receiver operating characteristic (ROC) curve (AUC). Change in stroke volume variation (ΔSVV) showed AUC of 0.9 (P < 0.001), 95% CI = 0.82-0.99, sensitivity = 88%, specificity = 82% for discrimination of fluid responsiveness. Change in pulse pressure variation (ΔPPV) showed AUC of 0.88 (P < 0.001), 95% CI = 0.78-0.97, sensitivity = 83%, specificity = 72% in predictability of fluid responsiveness. Cardiac index and stroke volume were well maintained after PEEP challenge in non-responders while they increased in responders. Conclusions: ΔPPV and ΔSVV induced by PEEP challenge are reliable parameters to predict fluid responsiveness as well as very good predictors of fluid unresponsiveness during OLV.

Oleuropein attenuates the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-perturbing effects on pancreatic ß-cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting compound and persistent organic pollutant that has been associated with diabetes in several epidemiological studies. Oleuropein, a major phenolic compound in olive fruit, is a superior antioxidant and radical scavenger. This study aimed to examine the effects of oleuropein against TCDD-induced stress response in a pancreatic beta cell line, INS-1 cells. Cells were pre-incubated with various concentrations of oleuropein and then stimulated with TCDD (10 nM) for 48 hrs. When treated with TCDD, INS-1 cells produced robust amounts of prostaglandin E2 (PGE2) compared to the untreated control, and this increase was inhibited by oleuropein treatment. TCDD increased Ca2+-independent phospholipase A2 (iPLA2ß) level, but had no effect on Group 10 secretory phospholipase A2 (PLA2G10) level, while oleuropein deceased the levels of iPLA2ß and PLA2G10 in the presence of TCDD. Cyclooxygenase-1 (COX-1) was significantly increased by TCDD treatment and attenuated with oleuropein pretreatment. Oleuropein decreased TCDD-mediated production of JNK, TNF-α, and ROS. In addition, oleuropein increased Akt and GLUT2 levels suppressed by TCDD in INS-1 cells. Thus, the results suggest that oleuropein prevents pancreatic beta cell impairment by TCDD.

Changes in dental hygiene students' working posture following digital sound feedback.

INTRODUCTION: This study aimed to observe changes in working posture by measuring the REBA (Rapid Entire Body Assessment) score of dental hygiene students according to digital sound feedback linked with a smartphone application. METHODS: This study was conducted on 28 fourth-year dental hygiene students who received theoretical and practical training on dental posture in the second year and then practised on mannequins and patients for about four semesters. Periodontal instrumentation was performed freely by applying digital sound notification feedback for four weeks after baseline, 30 minutes per week. REBA was measured after performing periodic structure construction without providing digital sound notification feedback for the last 1-2 minutes. Follow-up was conducted the same way 2-3 weeks after the intervention period. RESULTS: The REBA score for total, neck and trunk of all subjects showed statistically significant decreases post-intervention compared with the baseline scores (total p < .001, neck p < .001 and trunk p = .042). CONCLUSIONS: A digital sound feedback system was shown to be effective in encouraging correct working posture in dental hygiene students by helping them improve their REBA scores.

Efficacy of mobile health care in patients undergoing fixed orthodontic treatment: A systematic review.

OBJECTIVES: We performed a systematic review of studies that assessed the efficacy of mobile health care in patients undergoing fixed orthodontic treatment, in an attempt to obtain contemporary evidence on the clinical impact of mobile health care on the patients' oral health and orthodontic treatment outcomes. METHODS: A systematic literature search was conducted using the PRISMA guidelines. We performed a comprehensive search using multiple databases (Cochrane Library, MEDLINE, EMBASE, Scopus, Google Scholar and Web of Science) with no restrictions on the language of publication or publication status up until 23 April 2019 to identify eligible studies. RESULTS: We included 11 unique studies. In this review, 9 of the 11 selected studies showed positive effects of mobile healthcare intervention, which resulted in reduced scores of oral hygiene and periodontal indices and white-spot lesions, as well as decreased duration of treatment, sagittal distance and intensity of self-reported pain. CONCLUSIONS: Mobile health care can be utilized as an adjuvant intervention to improve treatment outcomes in patients undergoing fixed orthodontic treatment. Oral healthcare experts should consider novel interventions using mobile devices in addition to the conventional mode of intervention.

Efficacy of intermittent epidural dexamethasone bolus for zoster-associated pain beyond the acute phase.

Herpes zoster develops when latent varicella zoster virus is reactivated in the trigeminal or dorsal root ganglions. Zoster-associated pain (ZAP) is neuropathic pain caused by the herpes zoster virus. Histological studies of postherpetic neuralgia patients suggest that inflammation is involved in ZAP. The effectiveness of local anesthetic and steroid epidural injections in ZAP patients has been reported. However, most studies included patients with acute herpes zoster, and the safety and therapeutic effects of different doses of epidural steroids in ZAP patients remain elusive. In this study, we randomly assigned 42 patients with severe ZAP beyond the acute phase, as determined by a numeric rating scale (NRS) score ≥7, to receive continuous epidural infusion of local anesthetics with either a one-time 5-mg dose or intermittent repeated doses (15 mg total) of dexamethasone. We found that intermittent repeated epidural dexamethasone bolus resulted in reduced NRS scores and an increased likelihood of complete remission in ZAP patients without any adverse effects. Thus, our results suggest that intermittent repeated epidural dexamethasone administration is safe and effective for treatment of ZAP beyond the acute phase.

Is Tube Thermosoftening Helpful for Videolaryngoscope-Guided Nasotracheal Intubation?: A Randomized Controlled Trial.

BACKGROUND: Thermosoftening of the endotracheal tube (ETT) and telescoping the ETT into a rubber catheter have been suggested as a method for reducing epistaxis during nasotracheal intubation (NTI). However, thermosoftening technique is known to make it difficult to navigate the ETT into trachea without the use of Magill forceps during NTI. The cuff inflation technique has been suggested as an effective alternative to the use of Magill forceps to improve the oropharyngeal navigation of the ETT, irrespective of their stiffness, during direct laryngoscope-guided NTI. We evaluated whether thermosoftening of the ETT telescoped into rubber catheters has an additional benefit in reducing nasal injury. Simultaneously, we also evaluated whether thermosoftening of the ETT worsened orotracheal navigability during cuff inflation-supplemented videolaryngoscope-guided NTI. METHODS: One hundred forty patients were randomly assigned to 1 of the 2 groups depending on whether the ETT was softened by warming or not. The primary outcome was the incidence of epistaxis during NTI. The secondary outcome was nasotracheal navigability of the ETT, assessed by navigation grade and time required for insertion of ETT in each phase (from nose to oropharynx, from oropharynx to glottic inlet aided by cuff inflation if needed, and from glottic inlet to trachea). RESULTS: The ETTs were successfully inserted through the selected nostril of all 140 patients. In the thermosoftening group, the incidence and severity of epistaxis was significantly lower (7% vs 51%; difference of 44.2%; 95% confidence interval, 29.9%-56.2%; P < .001), and the ETT passed through the nasal cavity with lower resistance (P = .001) and less time (P < .001) when compared to the control group. No difference was found in the ease of ETT insertion (navigation grade and time required) from the oropharynx to the glottic inlet (P > .99 and P = .054, respectively) and from the glottic inlet to the trachea (P > .99 and P = .750, respectively) between the 2 groups. In both groups, all ETTs could be navigated into the trachea without the use of Magill forceps. CONCLUSIONS: Supplemented with cuff inflation during videolaryngoscope-guided NTI, thermosoftening of the ETT telescoped into rubber catheters has a substantial benefit because it significantly reduces the incidence of epistaxis without worsening the oropharyngeal navigability of the ETT.

Catalpol protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytotoxicity in osteoblastic MC3T3-E1 cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that produces a wide variety of adverse effects in humans. Catalpol, a major bioactive compound enriched in the dried root of Rehmannia glutinosa, is a major iridoid glycoside that alleviates bone loss. However, the detailed mechanisms underlying the effects of catalpol remain unclear. The present study evaluated the effects of catalpol on TCDD-induced cytotoxicity in osteoblastic MC3T3-E1 cells. Catalpol inhibited TCDD-induced reduction in cell viability and increases in apoptosis and autophagic activity in osteoblastic MC3T3-E1 cells. Additionally, pretreatment with catalpol significantly decreased the nitric oxide and nitrite levels compared with a control in TCDD-treated cells and significantly inhibited TCDD-induced increases in the levels of cytochrome P450 1A1 and extracellular signal-regulated kinase. Pretreatment with catalpol also effectively restored the expression of superoxide dismutase and extracellular signal-regulated kinase 1 and significantly enhanced the expression of glutathione peroxidase 4 and osteoblast differentiation markers, including alkaline phosphatase and osterix. Taken together, these findings demonstrate that catalpol has preventive effects against TCDD-induced damage in MC3T3-E1 osteoblastic cells.

Relationships between dental hygienists' work environment and patient safety culture.

BACKGROUND: Patient safety culture is a core factor in increasing patient safety, is related to the quality of medical service, and can lower the risk of patient safety accidents. However, in dentistry, research has previously focused mostly on reporting of patient safety accidents. Dental professionals' patient safety culture must therefore first be assessed, and related factors analyzed to improve patient safety. METHODS: This cross-sectional study completed a survey on 377 dental hygienists working in dental settings. To assess patient safety culture, we used a survey with proven validity and reliability by translating the Hospital Survey on Patient Safety Culture (HSOPS) developed by Agency for Healthcare Research and Quality (AHRQ) into Korean. Response options on all of the items were on 5-point Likert-type scales. SPSS v21 was used for statistical analysis. The relationships between workplace factors and patient safety culture were examined using t-tests and one-way analysis of variance (ANOVA) tests(p < 0.05). RESULTS: The work environment of dental hygienists has a close relationship with patient safety. Dental hygienists working ≥40 h/week in Korea had a significantly lower for patient safety grade than those working < 40 h/week. When the number of patients per day was less than 8, the safety level of patients was significantly higher. And significant differences were found depending on institution type, institution size. CONCLUSIONS: In order to establish high-quality care and patient safety system practical policies must be enacted. In particular, assurance in the quality of work environment such as sufficient staffing, appropriate work hours, and enough rest must first be realized before patient safety culture can easily be formed.

Tetrabromobisphenol A Promotes the Osteoclastogenesis of RAW264.7 Cells Induced by Receptor Activator of NF-kappa B Ligand In Vitro.

BACKGROUND: Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism. METHODS: RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured. RESULTS: The presence of 20 µ TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 µ TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. CONCLUSION: This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production.

Efficacy of forced-air warming and warmed intravenous fluid for prevention of hypothermia and shivering during caesarean delivery under spinal anaesthesia: A randomised controlled trial.

BACKGROUND: Peri-operative hypothermia and shivering are frequent events in patients during caesarean delivery under spinal anaesthesia. OBJECTIVE: We assessed the efficacy of combined pre-anaesthetic forced-air warming in combination with warmed intravenous fluid infusion for preventing hypothermia and shivering during caesarean delivery under spinal anaesthesia. DESIGN: A randomised controlled study. SETTING: A tertiary care teaching hospital from July 2017 to April 2018. PATIENTS: A total of 50 pregnant women, American Society of Anaesthesiologists physical status 2, aged 20 to 45 years, scheduled for caesarean delivery under spinal anaesthesia. INTERVENTION: Patients were enrolled and randomised into two groups: an active warming group (n = 25), which received combined pre-anaesthetic whole body forced-air warming for 15 min and prewarmed intravenous fluids, and a control group, which received no active warming or warmed fluids (C group; n = 25). Spinal anaesthesia was induced with 10 mg bupivacaine containing fentanyl (10 µg). MAIN OUTCOME MEASURES: Tympanic membrane temperature and shivering severity were measured at baseline and every 10 min during surgery, and then every 10 min for 1 h postoperatively. Neonatal outcomes (tympanic membrane temperature at birth, umbilical venous blood pH, Apgar score) were also recorded. RESULTS: The incidences of peri-operative hypothermia (0 vs. 48%, P < 0.001) and shivering (22 vs. 52%, P = 0.031) were significantly lower in the active warming than in the C group. The maximum temperature change was also significantly lower in the active warming than in the C group. Maternal thermal comfort scores were higher in the active warming than in the C group. Neonatal parameters were not significantly different between the groups. CONCLUSION: The combination of pre-anaesthetic forced-air warming and warmed intravenous fluid infusions appears to be effective for preventing hypothermia and shivering during caesarean delivery under spinal anaesthesia. TRIAL REGISTRATION: This trial was registered with Clinical Trials.gov (identifier: NCT03256786).

Biochanin A prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced adipocyte dysfunction in cultured 3T3-L1 cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant. TCDD accumulates in the food chain, mainly in the fatty tissues of the human body where it causes various toxic effects. Biochanin A is a natural organic compound in the class of phytochemicals known as flavonoids. We investigated whether biochanin A suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. In the present study, biochanin A suppressed TCDD-induced loss of lipid accumulation. Pretreating the cells with biochanin A increased the levels of the adipogenesis-associated factors peroxisome proliferator-activated receptor γ and adiponectin, which were inhibited by TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with biochanin A. Biochanin A also inhibited the TCDD-driven decrease in production of insulin receptor substrate-1 and glucose transporter 4. These results suggest a preventive effect of biochanin A against TCDD in the development of insulin resistance and diabetes. TCDD increased production of intracellular calcium ([Ca2+]i), prostaglandin E2, cytosolic phospholipase A2, and cyclooxygenase-1, while reducing the level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha. However, biochanin A inhibited these TCDD-induced effects. We conclude that biochanin A is an attractive compound for preventing TCDD-induced wasting syndrome.

Effect of pre-warming on perioperative hypothermia during holmium laser enucleation of the prostate under spinal anesthesia: a prospective randomized controlled trial.

BACKGROUND: The purpose of this study is to assess whether the application of preoperative forced air warming set to high temperature (> 43 °C) for brief period can increase temperature on admission to the postanesthesia care unit (PACU) and prevent hypothermia or shivering during holmium laser enucleation of the prostate performed under spinal anesthesia. METHODS: Fifty patients were enrolled were assigned randomly to receive passive insulation (control group, n = 25) or forced-air skin surface warming for 20 min before spinal anesthesia (pre-warming group, n = 25). The primary outcome was temperature at PACU admission. RESULTS: The pre-warming group had a significantly higher temperature on admission to the PACU than the control group (35.9 °C [0.1] vs 35.6 °C [0.1], P = 0.023; 95% confidence interval of mean difference, 0.1 °C-0.5 °C). The trend of decreasing core temperature intraoperatively was not different between groups (P = 0.237), but intraoperative core temperature remained approximately 0.2 °C higher in the pre-warming group (P = 0.005). The incidence of hypothermia on admission to the PACU was significantly lower in the pre-warming group (56% vs 88%, P = 0.025). Shivering occurred in 14 patients in the control group, and 4 patients in the pre-warming group (P = 0.007). CONCLUSION: Brief pre-warming at 45 °C increased perioperative temperature and decreased the incidence of hypothermia and shivering. However, it was not sufficient to modify the decline of intraoperative core temperature or completely prevent hypothermia and shivering. Continuing pre-warming to immediately before induction of spinal anesthesia or combining pre-warming with intraoperative active warming may be necessary to produce clearer thermal benefits in this surgical population. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov, NCT03184506 , 5th June 2017.

Effects of bergenin on methylglyoxal-induced damage in osteoblastic MC3T3-E1 cells.

Bergenin is the main chemical constituent of plants in the genus Bergenia, which are used in traditional medicines. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is the major precursor for forming advanced glycation end products (AGEs). Pretreating MC3T3-E1 cells with bergenin prevented MG-induced protein adduct formation. Bergenin inhibited the MG-induced soluble receptor for AGE (sRAGE), interleukin, reactive oxygen species and mitochondrial superoxide production. Additionally bergenin increased glyoxalase I activity, glutathione, heme oxygenase-1 and nuclear factor erythroid 2-related factor 2 levels in the presence of MG. Pretreatment with bergenin before MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation, loss of adenosine triphosphate and reduced adenosine monophosphate-activated protein kinase. These results demonstrate that bergenin may prevent the development of diabetic osteopathy.

Cytoprotective effects of xanthohumol against methylglyoxal-induced cytotoxicity in MC3T3-E1 osteoblastic cells.

Methylglyoxal (MG) has been suggested to be a major source of intracellular reactive carbonyl compounds, and has been implicated in increasing the levels of advanced glycation end products in age-related diseases. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. In the present study, we investigated the effects of xanthohumol on MG-induced cytotoxicity in osteoblastic MC3T3-E1 cells. Xanthohumol attenuated MG-induced cytotoxicity, as evidenced by improved cell viability, and prevented MG-induced MG-protein adducts, inflammatory cytokines, reactive oxygen species and mitochondrial superoxide production. In addition, xanthohumol increased glyoxalase I activity, glutathione, heme oxygenase-1 and nuclear factor erythroid 2-related factor 2 levels in the presence of MG. Pretreatment with xanthohumol before MG exposure reduced MG-induced mitochondrial dysfunction. Furthermore, xanthohumol treatment resulted in a significant reduction in the levels of endoplasmic reticulum stress and autophagy induced by MG. Notably, the autophagy-reducing effect of xanthohumol was abolished after the addition of Ex527, a selective inhibitor of sirtuin 1, suggesting that xanthohumol is an effective sirtuin 1 activator for reducing autophagy. Taken together, our findings suggest xanthohumol as a promising new strategy for preventing diabetic osteopathy.

The protective effects of sciadopitysin against methylglyoxal-induced cytotoxicity in cultured pancreatic ß-cells.

Increased glycation of macromolecules via the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has shown an association with diabetes and its complications. In the present study, the protective effects of sciadopitysin against MG-induced oxidative cell damage were investigated in the insulin-producing pancreatic ß-cell line, RIN-m5F cells. When exposed to MG for 48 hours, RIN-m5F cells experienced significant loss of viability and impaired insulin secretion; however, treatment with sciadopitysin protected RIN-m5F cells against MG-induced cell death and decreased insulin secretion. Treatment of RIN-m5F cells with sciadopitysin prevented MG-induced production of interleukin-1ß, intracellular reactive oxygen species and cardiolipin peroxidation. Furthermore, sciadopitysin increased adenosine monophosphate-activated protein kinase phosphorylation of RIN-m5F cells. Treatment of cells with sciadopitysin increased the activity of glyoxalase I and decreased the levels of MG-protein adducts, indicating that sciadopitysin protects against MG-induced protein glycation by increasing MG detoxification. Taken together, the results indicated the potential utility of sciadopitysin as an intervention against MG-induced cell damage in pancreatic ß-cells.

Glabridin attenuates antiadipogenic activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in murine 3T3-L1 adipocytes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has various toxicological effects in adipose tissue. Evidence is accumulating that glabridin, a flavonoid extracted from licorice, has beneficial effects on the regulation of glucose homeostasis. In this study, we investigated whether glabridin suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. Glabridin effectively suppressed TCDD-induced loss of lipid accumulation in this model. Pretreating cells with glabridin increased the gene expression of not only the adipogenesis-associated key transcription factors peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha, but also lipoprotein lipase in the presence of TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with glabridin. Glabridin also inhibited the TCDD-driven decreased production of insulin receptor substrate 1 and glucose transporter 4. TCDD increased the production of mitochondrial superoxides, prostaglandin E2 , phospholipase A2 , cyclooxygenase-1 and intracellular calcium concentrations, while reducing the production of PPARγ coactivator 1 alpha and glycolysis. However, glabridin treatment reduced these TCDD-induced effects. We conclude that glabridin suppresses the TCDD-induced loss of lipid accumulation in 3T3-L1 adipocytes by regulating the levels of PPARγ, CCAAT/enhancer binding protein alpha, lipoprotein lipase, glucose uptake, prostaglandin E2 and energy metabolism. These results also provide in vitro evidence of the effects of glabridin on adipocyte metabolism, which suggests a protective effect against dioxin exposure in the development of insulin resistance and diabetes.

Xanthohumol ameliorates 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular toxicity in cultured MC3T3-E1 osteoblastic cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3-E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca2+ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased. TCDD treatment increased the mRNA levels of extracellular signal-regulated kinase 1 and nuclear factor kappa B, and significantly decreased the level of protein kinase B (AKT) in MC3T3-E1 osteoblastic cells. However, the presence of xanthohumol alleviated the pathological effects of TCDD. In addition, xanthohumol treatment significantly increased the expression of genes associated with osteoblast differentiation (alkaline phosphatase, osteocalcin, osteoprotegerin and osterix). We conclude that xanthohumol has a beneficial influence and may antagonize TCDD toxicity in osteoblastic cells.

27-Deoxyactein prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular damage in MC3T3-E1 osteoblastic cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that exerts its toxicity through a variety of signaling mechanisms. The present study evaluated the effects of 27-deoxyactein, one of the major constituents isolated from Cimicifuga racemosa, on TCDD-induced toxicity in osteoblastic MC3T3-E1 cells. TCDD reduced cell survival, markedly increased apoptosis, and enhanced autophagy activity. However, pre-treatment with 27-deoxyactein attenuated all TCDD-induced effects and significantly decreased intracellular calcium (Ca2+) concentrations, the collapse of the mitochondrial membrane potential (MMP), the level of reactive oxygen species (ROS), and cardiolipin peroxidation compared to the TCDD-treated controls. Additionally, TCDD-induced increases in the levels of aryl hydrocarbon receptor (AhR), cytochrome P450 1A1 (CYP1A1), and extracellular signal-regulated kinase (ERK) were significantly inhibited by 27-deoxyactein. The mRNA levels of superoxide dismutase (SOD), ERK1, and nuclear factor kappa B (NF-κB) were also effectively restored by pre-treatment with 27-deoxyactein. Furthermore, 27-deoxyactein significantly increased the expressions of genes associated with osteoblast differentiation, including alkaline phosphatase (ALP), osteocalcin, bone sialoprotein (BSP), and osterix. Taken together, the present findings demonstrate the preventive effects of 27-deoxyactein on TCDD-induced damage in osteoblasts.