Ultrasound Plus Vacuum-System-Assisted Biocatalytic Synthesis of Octyl Cinnamate and Response Surface Methodology Optimization.

Cinnamic acid is one of the phenolic compounds that is isolated from cinnamon, or other natural plants, and has a wide range of physiological activities. However, the application of cinnamic acid is limited due to its poor solubility and low oral bioavailability. In this study, the feasibility of producing octyl cinnamate by ultrasonic assistance, combined with a rotary evaporation under vacuum, was studied using methyl cinnamate and octanol as the starting materials. A Box-Behnken design (BBD) was employed to evaluate the effects of the operation parameters, including reaction temperature (55-75 °C), reaction time (4-12 h), and ultrasonic power (90-150 W) on the production of octyl cinnamate. Meanwhile, the synthesis process was further optimized by the modeling response surface methodology (RSM). The data indicated that octyl cinnamate was efficiently synthesized from methyl cinnamate and octanol using the ultrasound plus vacuum system; further, this system was superior to the conventional method. According to the RSM model for the actual experiments, a reaction temperature of 74.6 °C, a reaction time of 11.1 h, and an ultrasound power of 150 W were determined to be the best conditions for the maximum molar conversion of octyl cinnamate (93.8%). In conclusion, the highly efficient synthesis of octyl cinnamate by a rotary evaporator with an ultrasound plus vacuum system was achieved via RSM optimization.

Kinetic study and performance comparison of TiO2-mediated visible-light-responsive photocatalysts for the inactivation of Aspergillus niger.

Fungi are highly survived with exceptional resistance to environmental stress. Conventional fungicides are quite efficient, but the increase in use raises severe environmental problems. In this study, environmentally friendly TiO2-mediated visible-light-responsive photocatalysts, namely N-TiO2, N-T-TiO2, C-TiO2, and Pd-C-TiO2, were used to compare the performance of disinfecting a mold fungi Aspergillus niger. Key parameters, including photocatalyst dosage, the initial fungal concentration, and visible-light intensity, affecting the disinfecting process, was investigated. A new developed Light-responsive Modified Hom's (LMH) kinetic model incorporating visible-light intensity and photocatalyst light-absorption coefficient was firstly used to predict such photocatalytic process in fungal inactivation. Among the photocatalysts, Pd-C-TiO2 showed the highest inactivation performance against fungi, followed by C-TiO2, N-T-TiO2, and N-TiO2. In general, inactivation increased with increasing photocatalyst dosage and light intensity while decreased with increasing initial fungal concentration. For kinetic modeling, the LMH model supports the hypothesis that photocatalyst performance toward visible-light-driven fungal inactivation primarily depends on the light-absorption capacity of the photocatalyst. In conclusion, mold fungi Aspergillus niger are effectively disinfected by TiO2-mediated visible-light-responsive photocatalysts, and such fungal inactivation process could be predicted by LMH kinetic model.

Comparison of Artificial Neural Networks and Response Surface Methodology towards an Efficient Ultrasound-Assisted Extraction of Chlorogenic Acid from Lonicera japonica.

Chlorogenic acid (CGA), a bioactive compound commonly found in plants, has been demonstrated possessing nutraceutical potential in recent years. However, the more critical issue concerning how to improve production efficacy of CGA is still limited. It is a challenge to harvest a large amount of CGA without prolonging extraction time. In this study, the feasibility of using ultrasound for CGA extraction from Lonicera japonica was investigated. A central composite design (CCD) was employed to evaluate the effects of the operation parameters, including temperature, ethanol concentration, liquid to solid ratio, and ultrasound power on CGA yields. Meanwhile, the process of ultrasound-assisted extraction was optimized through modeling response surface methodology (RSM) and artificial neural network (ANN). The data indicated that CGA was efficiently extracted from the flower of Lonicera japonica by ultrasound assistance. The optimal conditions for the maximum extraction of CGA were as follows: The temperature at 33.56 °C, ethanol concentration at 65.88%, L/S ratio at 46:1 mL/g and ultrasound power at 150 W. ANN possessed greater optimization capacity than RSM for fitting experimental data and predicting the extraction process to obtain a maximum CGA yield. In conclusion, the process of ultrasound-assisted extraction can be well established by a methodological approach using either RSM or ANN, but it is worth mentioning that the ANN model used here showed the superiority over RSM for predicting and optimizing.

Geniposide ameliorated fluoxetine-suppressed neurite outgrowth in Neuro2a neuroblastoma cells.

AIM: Fluoxetine (FXT), a selective serotonin reuptake inhibitor (SSRI), is one of the most common psychiatric medications clinically prescribed; while over-produced serotonin may suppress neurite development. The role of major iridoids like geniposide (GPS) and genipin (GNP) from Gardenia jasminoides Ellis fruit (family Rubiaceae) in ameliorating the anti-neurite outgrowth effect of FXT is poorly understood. In this study, the effects of these iridoids on FXT-suppressed neurite outgrowth in Neuro2a neuroblastoma cells were investigated. MAIN METHODS: Neuro2a cells were treated with FXT and GPS. The effect of GPS-FXT co-treatment on neurite outgrowth was observed using inverted phase-contrast microscope imaging system, while neurite outgrowth markers - microtubule-associated protein-2 (MAP2) and growth-associated protein 43 (GAP43) were analyzed using RT-PCR, Western blot and immunofluorescence staining. The transcription factor-cAMP response element binding (CREB), and signaling pathways - mitogen-activated protein kinase (MAPK) and protein kinase B/mammalian target of rapamycin (AKT/mTOR) were also analyzed with the help of Western blot. KEY FINDINGS: The results showed that FXT decreased the neurite outgrowth in Neuro2a cells and also downregulated gene and protein expression of MAP2 and GAP43. It also downregulated the protein expression of phosphorylated-CREB, MAPK, and AKT/mTOR signaling pathways. In contrast, GPS counteracted the effects of FXT. GPS-FXT co-treatment increased the percentage of neurite-bearing cells by 3.6-fold at 200 µM as compared to FXT treatment only. SIGNIFICANCE: This study has provided the possible molecular mechanism showing how FXT exerted its detrimental side-effects on the neurite differentiation, and via the same mechanism how GPS attenuated these side effects.

Analysis of emergency dental revisits in Taiwan (1999-2012) from Taiwanese National Health Insurance Research Database (NHIRD).

BACKGROUND/PURPOSE: Inadequate diagnosis, treatment, and palliative care provided in the emergency department could let the patients revisit shortly after being seen. The aim of this study was to evaluate the emergency dental revisits by using Taiwanese National Health Insurance Research Database (NHIRD). MATERIALS AND METHODS: The Dental dataset from NHIRD was used to analyze the demographic characteristics of emergency dental revisits in Taiwanese population from 1999 to 2012. In addition, the conditions of emergency dental revisits were also identified based on the International Classification of Diseases, Ninth Revision (ICD-9). RESULTS: Total 169,437 individuals had sought for emergency dental treatment from 1999 to 2012. In addition, 9624 individuals (5.68%) had repeated emergency dental visits within 1 year. The top 3 dental conditions were diseases of pulp and periapical tissues (ICD-9: 522), gingival and periodontal diseases (ICD-9: 523), and diseases of the oral soft tissues, excluding lesions specific for gingiva and tongue (ICD-9: 528). Males paid emergency dental revisits more than twice a year outnumber female counterparts (aOR = 1.252, 95% CI: 1.116-1.404). The higher odds ratio for emergency dental revisits over twice a year were found in 0-6 years, 35-49 years, 50-69 years, and ≧ 70 years subgroup as compared the reference of 20-34 years group. However, there were no significant differences for the stratification by year, day, region, and payroll bracket. CONCLUSION: Taken together, this data demonstrated the current situation of emergency dental revisits in Taiwan. It would raise the important issue about how to reduce the unnecessary repeated emergency visits.

Trends, demographics, and conditions of emergency dental visits in Taiwan 1997-2013: A nationwide population-based retrospective study.

BACKGROUND/PURPOSE: The disparate or irregular dental care was associated with acute clinical problems that may lead to care seeking for emergency visits. The aim of this study was to determine the time trends, demographics, and conditions of emergency dental (ED) visits in Taiwan. METHODS: This cross-sectional study was conducted to analyze the insurance reimbursement of dental care services in National Health Insurance Research Database. The demographic characteristics and age-period effects of ED visits were estimated by multivariate Poisson regression. In addition, the top causes of ED visits were evaluated and stratified by traumatic and non-traumatic conditions. RESULTS: The prevalence of ED visits were 3.18, 5.44, and 4.83 (per 10,000 persons) in 1997, 2002, and 2013, respectively. The primary diagnosis code for ED visits was 522 'pulp and periapical tissues'. Pulpitis (522.0), cellulitis (528.3), acute periodontitis (523.3), and caries (521.0) were the top 4 non-traumatic reasons for seeking ED visits. The top 3 traumatic conditions were open wound of internal structures of mouth without mention of complication (873.6), open wound of face without mention of complication (873.4), and loss of teeth due to trauma (525.1). The higher prevalence of ED visits were found in male (aRR = 1.50, 95% CI: 1.49-1.51), 6 y/o group (aRR = 1.56, 95% CI: 1.53-1.59), east region (aRR = 1.27, 95% CI: 1.25-1.29), and dependent coverage group (aRR = 1.16, 95% CI: 1.14-1.19). CONCLUSION: Taken together, these demographic data could serve as a reference for the authorities concerned to improve the current situation of ED in Taiwan.

An Efficient Approach for Lipase-Catalyzed Synthesis of Retinyl Laurate Nutraceutical by Combining Ultrasound Assistance and Artificial Neural Network Optimization.

Although retinol is an important nutrient, retinol is highly sensitive to oxidation. At present, some ester forms of retinol are generally used in nutritional supplements because of its stability and bioavailability. However, such esters are commonly synthesized by chemical procedures which are harmful to the environment. Thus, this study utilized a green method using lipase as a catalyst with sonication assistance to produce a retinol derivative named retinyl laurate. Moreover, the process was optimized by an artificial neural network (ANN). First, a three-level-four-factor central composite design (CCD) was employed to design 27 experiments, which the highest relative conversion was 82.64%. Further, the optimal architecture of the CCD-employing ANN was developed, including the learning Levenberg-Marquardt algorithm, the transfer function (hyperbolic tangent), iterations (10,000), and the nodes of the hidden layer (6). The best performance of the ANN was evaluated by the root mean squared error (RMSE) and the coefficient of determination (R²) from predicting and observed data, which displayed a good data-fitting property. Finally, the process performed with optimal parameters actually obtained a relative conversion of 88.31% without long-term reactions, and the lipase showed great reusability for biosynthesis. Thus, this study utilizes green technology to efficiently produce retinyl laurate, and the bioprocess is well established by ANN-mediated modeling and optimization.

RSM and ANN modeling-based optimization approach for the development of ultrasound-assisted liposome encapsulation of piceid.

Piceid, a naturally occurring derivative of resveratrol found in many plants, has recently been considered as a potential nutraceutical. However, its poorly water-soluble property could cause a coupled problem of biological activities concerning drug dispersion and absorption in human body, which is still unsolved now. Liposome, a well-known aqueous carrier for water-insoluble ingredients, is commonly applied in drug delivery systems. In this study, a feasible approach for solving the problem is that the targeted piceid was encapsulated into a liposomal formula as aqueous substrate to overcome its poor water-solubility. The encapsulation process was assisted by ultrasound, with investigation of lipid content, ultrasound power and ultrasound time, for controlling encapsulation efficiency (E.E%), absolute loading (A.L%) and particle size (PS). Moreover, both RSM and ANN methodologies were further applied to optimize the ultrasound-assisted encapsulation process. The data indicated that the most important effects on the encapsulation performance were found to be of lipid content followed by ultrasound time and ultrasound power. The maximum E.E% (75.82%) and A.L% (2.37%) were exhibited by ultrasound assistance with the parameters of 160mg lipid content, ultrasound time for 24min and ultrasound power of 90W. By methodological aspects of processing, the predicted E.E% and A.L% were respectively in good agreement with the experimental results for both RSM and ANN. Moreover, RMSE, R2 and AAD statistics were further used to compare the prediction abilities of RSM and ANN based on the validation data set. The results indicated that the prediction accuracy of ANN was better than that of RSM. In conclusion, ultrasound-assisted liposome encapsulation can be an efficient strategy for producing well-soluble/dispersed piceid, which could be further applied to promote human health by increased efficiency of biological absorption, and the process of ultrasound-mediated liposome encapsulation can be well established by a methodological approach using either RSM or ANN, but it is worth mentioning that the ANN model used here showed the superiority over RSM for predicting and optimizing encapsulation.

Novel Approach of Using Nutraceutic-Directed Caloric Antioxidant Density and Ion-Ratio for Evaluating Fruit's Health Quality.

Seven kinds of indigenous fruits and five imported fruits were compared for their "health quality." Methods including the calorific, antioxidant, and ion ratios were carried out. Results indicated the order of content (in mg/100g) was: Ca(2+) , Murcott orange (218.2) > Kiwifruit (200.0) > pineapple (138.5) > Golden kiwi (117.6); Mg(2+) , Pitaya (192.2), banana (88.0), Kiwifruit (63.4), and Golden kiwi (58.4); Zn(2+) , Pitaya (19.53) > pear (10.8) > Kiwifruit (6.09) > Irwin mango (4.58). Cu(2+) , Kiwifruit (0.70) > Red globe grape (0.67) > Golden kiwi (0.65) > Irwin mango (0.42) ≈ Pitaya (0.40). In terms of ion ratio, Pitaya showed Zn(2+) /Cu(2+) (48.8), Mg(2+) /Ca(2+) (6.7) and uniquely possessed selenium 0.002 mg/100 g; for pear, Zn(2+) /Cu(2+) = 37.2, while Kyoho grape, Red globe grape, and Golden kiwi revealed extremely high Fe(2+) /(Co(2+) +Ni(2+) ) ratios. On the other hands, Irwin mango and Pitaya astonishingly contained huge amount of inositol, reaching 3523.2 mg/100 g and 1998.7 mg/100 g, respectively. To evaluate the "health quality" of fruits, an overall ranking method by combining (a) the Function-directed Caloric Antioxidant Density (CAD) and (b) the ion ratio was developed. The finalized ranking of these selected fruits was: Pitaya > cherry > Irwin mango > Murcott orange = pineapple > banana > Golden kiwi > pear > Kiwifruit > Red globe grape > apple > Kyoho grape. Conclusively, this evaluation method is novel, contemporary and scientific, which could more clearly assess the "health quality" of fruits in view of nutritional, calorific, and antioxidant balance.

[Association of Ureaplasma urealyticum infection with bronchopulmonary dysplasia in very low birth weight infants with respiratory distress syndrome].

OBJECTIVE: To study the relationship between Ureaplasma urealyticum (UU) infection in the lower respiratory tract and the incidence of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS). METHODS: Seventy-three VLBW infants diagnosed with neonatal RDS, who had received at least one dose of pulmonary surfactant, as well as mechanical ventilation, and were hospitalized for over 28 days, were recruited. Endotracheal aspirates were obtained from the lower respiratory tract and examined by real-time PCR to detect UU DNA. The infants were divided into UU infection and non-UU infection groups according to examination results. Clinical characteristics and the incidence of BPD were compared between the two groups. RESULTS: Compared with the non-UU infection group, the UU infection group had a higher rate of maternal vaginal delivery, higher incidence of recurrent nosocomial pulmonary infection and premature rupture of membranes (PROM), and longer durations of PROM, oxygen supplementation, and hospital stay; in addition, the UU infection group had higher plasma IgM level, leukocyte count, and neutrophil count within 3 hours after birth. Among 73 VLBW infants, 45 developed BPD; the incidence of BPD in the UU infection group was 90% (19/21), versus 50% (26/52) in the non-UU infection group (P<0.01). CONCLUSIONS: UU infection in the lower respiratory tract increases the incidence of BPD in VLBW infants with RDS.

Beneficial effects of Camellia Oil (Camellia oleifera Abel.) on ketoprofen-induced gastrointestinal mucosal damage through upregulation of HO-1 and VEGF.

Nonsteroidal anti-inflammatory drugs, such as ketoprofen, are generally used to treat pain and inflammation and as pyretic agents in clinical medicine. However, the usage of these drugs may lead to oxidative injury to the gastrointestinal mucosa. Camellia oil ( Camellia oleifera Abel.) is commonly used in Taiwan and China as cooking oil. Traditional remedies containing this oil exert beneficial health effects on the bowel, stomach, liver, and lungs. However, the effects of camellia oil on ketoprofen-induced oxidative gastrointestinal mucosal lesions remain unknown. The objective of this study was to evaluate the effect of camellia oil on ketoprofen-induced acute gastrointestinal ulcers. The results showed that treatment of Int-407 cells with camellia oil (50-75 µg/mL) not only increased the levels of heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD) mRNA expression but also increased vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) protein secretion, which served as a mucosal barrier against gastrointestinal oxidative injury. Moreover, Sprague-Dawley (SD) rats treated with camellia oil (2 mL/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited COX-2 protein expression, inhibited the production of interleukin-6 (IL-6) and nitrite oxide (NO), reversed the impairment of the antioxidant system, and decreased oxidative damage in the gastrointestinal mucosa. More importantly, pretreatment of SD rats with camellia oil strongly inhibited gastrointestinal mucosal injury induced by ketoprofen, which was proved by the histopathological staining of gastrointestinal tissues. Our data suggest that camellia oil exerts potent antiulcer effects against oxidative damage in the stomach and intestine induced by ketoprofen.

Diallyl sulfide as a potential dietary agent to reduce TNF-α- and histamine-induced proinflammatory responses in A7r5 cells.

SCOPE: Oxidative stress-aggravated chronic inflammatory diseases of the airway are well documented; hence, treatment with antioxidants to ameliorate oxidative stress might be an effective strategy to reduce airway complications. The aim of this study was to investigate the effect and molecular mechanism of diallyl sulfide (DAS), which is a natural organosulfuric compound found in garlic, on the inhibition of tumor necrosis factor-alpha (TNF-α)- or histamine-induced inflammation in rat aortic smooth muscle A7r5 cells. METHODS AND RESULTS: A7r5 cells were coincubated with DAS before exposure to TNF-α or histamine. DAS significantly blocked the accumulation of the nuclear p65 protein in TNF-α-induced A7r5 cells by attenuating the TNF-α receptor complex through the dissociation of the TNF receptor-associated death domain and TNF receptor-associated factor 2. Moreover, DAS inhibited histamine-induced inflammation by decreasing reactive oxygen species (ROS) levels by enhancing the nuclear factor-erythroid 2-related factor 2-related antioxidative enzyme. DAS also inhibited inflammation by suppressing interleukin-1ß and TNF-α through the inhibition of ROS-induced PI3K/Akt and the downstream NF-κB and activator protein-1. CONCLUSION: Our results demonstrate that DAS is a potential phytochemical to inhibit TNF-α- and histamine-induced inflammation, suggesting that DAS might be an effective dietary agent for the prevention of oxidative stress-induced inflammation of the airway.

EGCG-rich green tea extract stimulates sRAGE secretion to inhibit S100A12-RAGE axis through ADAM10-mediated ectodomain shedding of extracellular RAGE in type 2 diabetes.

The receptor for advanced glycation of end products (RAGE) plays a critical role in the progression of type 2 diabetes (T2D). Soluble RAGE (sRAGE) is one of the RAGE variants, which acts as a decoy domain receptor and competes with RAGE, thus contributing to prevention of T2D. In this study, we conducted clinical trials of (-)-epigallocatechin-3-gallate (EGCG) rich green tea extract (300-900 mg/day) to investigate the effect of EGCG on relationship between S100A12 RAGE ligand and diverse sRAGE in T2D. Moreover, mechanism of sRAGE production also confirmed in vitro. Our data indicated that EGCG could stimulate sRAGE circulation but inhibited RAGE ligand in T2D, and ADAM10-mediated ectodomain shedding of extracellular RAGE was mainly involved in EGCG-stimulated sRAGE circulation. The present evidence indicates that EGCG has a potential to block S100A12-RAGE axis by stimulating sRAGE production through ADAM10-mediated ectodomain shedding of extracellular RAGE. Therefore, EGCG contributes to nutritional strategies for diabetes, not only because of its efficient antioxidant activity to scavenge free radicals, but also because of its ability stimulating sRAGE release in the circulation. Additionally, ADAM10-induced ectodomain shedding of extracellular RAGE leading to sRAGE circulation should be a potential of passive mechanism of sRAGE production to block S100A12-RAGE axis-related pathogenesis of proinflammation and diabetes.

Cytoprotective effects of hesperetin and hesperidin against amyloid ß-induced impairment of glucose transport through downregulation of neuronal autophagy.

SCOPE: This study investigated whether flavonoids, such as hesperetin and hesperidin, inhibited amyloid ß (Aß)-impaired glucose utilization through regulating cellular autophagy in insulin-stimulated neuronal cells. METHODS AND RESULTS: In this study, we used a toxic Aß1-42 peptide to impair insulin-stimulated glucose utilization in Neuro-2A cells, and this study also hypothesized that Aß-induced autophagy might be emerging as a key process regulating neuronal glucose uptake. Additionally, hesperetin and hesperidin were used to test the neuroprotective effect against Aß-induced impairment of glucose utilization. Our data found that Aß-stimulated autophagy activation promoted the phenomenon of impairment of neuronal energy metabolism, including glucose uptake, glucose transporters (GLUTs), and insulin signaling cascades. In this study, confocal images of autophagy punctate further confirmed that downregulation of Aß-stimulated autophagy could increase insulin-stimulated neuronal glucose uptake. Moreover, treatment with hesperetin and hesperidin improved Aß-impaired glucose utilization by inhibiting Aß-induced autophagy in neuronal cells. CONCLUSION: These findings suggest that downregulation of autophagy may be one of the approaches to control the impairment of energy metabolism leading to neuronal injury in the early development of Alzheimer's disease, and hesperetin or hesperidin may be a potential agent in the preventing of Alzheimer's disease progression.

Inhibition of advanced glycation endproduct formation by foodstuffs.

The Maillard reaction, which is generally termed nonenzymatic browning or glycation, has been implicated in accelerated aging and diabetic complications in vivo. Although the molecular basis of glycation-induced pathogenesis is not well understood, the following have been noted: (1) protein glycation leads to the formation and accumulation of toxic advanced glycation endproducts (AGEs); (2) AGEs can permanently alter the structure and function of body proteins; and (3) the interaction between AGE-modified proteins and AGE-specific receptors (RAGEs) on the cell surface induces the overproduction of reactive oxygen species (ROSs) and inflammatory mediators, which leads to cellular disorders in biological systems. To date, studies that have examined the contribution of protein glycation to disease-states have primarily focused on the deleterious effects and related mechanisms of these glycotoxins. However, it remains unknown whether phytochemicals exert protective effects against glycotoxin-induced damage. Thus, the development and investigation of AGE inhibitors, especially the natural anti-AGE agents without adverse effects, may provide a therapeutic approach for delaying and preventing premature aging and diabetic complications. In this review, we provide an outline of anti-glycation properties of foodstuffs and/or their active components, and discuss their mechanisms of action.

AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes.

The purpose of this study was to investigate the distinct roles of advanced glycation end products (AGEs) on insulin-mediated glucose disposal in 3T3-L1 adipocytes and C2C12 skeletal muscle cells. AGE-modified proteins, namely, GO-AGEs, were prepared by incubating bovine serum albumin (BSA) with glyoxal (GO) for 7 days. Glucose utilization rates and the expression of insulin signaling-associated proteins, including Akt, insulin receptor substrate-1, and glucose transporter 4, were determined. GO-AGEs caused insulin resistance (IR) by suppressing insulin-stimulated glucose uptake both in 3T3-L1 adipocytes and C2C12 muscle cells. Interestingly, an unexpected finding was that insulin-stimulated glucose transport in adipocytes was affected by GO-AGEs in a biphasic manner, with an initial steep increase (168%) during the first 8 h of incubation followed by a significantly impaired uptake after extended culture times (24-48 h, p < 0.05). Treatment with GO-AGEs for 24 h markedly accelerated lipid droplet formation compared to the BSA control; however, it was blocked by incubation with an anti-RAGE antibody. Our study suggests that GO-AGEs induce an early dramatic elevation of glucose transport in adipocytes that may be related to the activation of insulin signaling; however, subsequent IR may result from increased oxidative stress and proinflammatory TNF-α production.

The proglycation effect of caffeic acid leads to the elevation of oxidative stress and inflammation in monocytes, macrophages and vascular endothelial cells.

In this study, the effects of phenolic acids [caffeic acid (CA), ferulic acid, m-coumaric acid, and chlorogenic acid] on methylglyoxal (MG)-induced protein glycation were investigated in vitro. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and advanced glycation end products (AGEs)-specific fluorescence showed that MG-mediated protein modification was enhanced dose-dependently by CA (P<.05), whereas α-lipoic acid, glutathione and EDTA inhibited these changes. Electron paramagnetic resonance spectra showed that CA increased reactive oxygen species (ROS) production during glycation, suggesting the proglycation mechanism of CA is associated with its pro-oxidative properties. Additionally, fetal bovine serum (FBS) was utilized as the source of target proteins for evaluating the effects of CA in cells. Differential glycation of FBS samples was performed by incubating FBS with MG, CA or aminoguanidine (AG, an AGE inhibitor). FBS incubated with MG and CA (MG/CA-FBS) evoked the greatest deleterious responses, as follows: (1) inducing proinflammatory tumor necrosis factor (TNF)-α and interleukin-1ß expression and ROS production in monocytic THP-1 cells, (2) stimulating TNF-α secretion in RAW 264.7 macrophages and (3) causing oxidative DNA damage and inducing the expression of receptor for AGEs (RAGE), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. Furthermore, adhesion and transendothelial migration of monocytes were also significantly increased by MG/CA-FBS treatment compared to MG-FBS (P<.05). In conclusion, our data show that CA exhibits pro-oxidative and pro-glycative effects during the glycation process, suggesting a detrimental role for CA under high-glycotoxin conditions.

Silymarin: a novel antioxidant with antiglycation and antiinflammatory properties in vitro and in vivo.

The current study was designed to evaluate the effects of silymarin (SM) on advanced glycation endproduct (AGE) formation and monocyte activation induced by S100b, a specific ligand of receptor for AGEs. The in vivo verification of antiglycation, antioxidant, and antiinflammatory capacities was examined by 12 weeks of SM administration in streptozotocin-diabetic rats. In vitro glycation assays demonstrated that SM exerted marked inhibition during the late stages of glycation and subsequent crosslinking. Dual action mechanisms, namely, antioxidant and reactive carbonyl trapping activities, may contribute to its antiglycation effect. SM produced a significant decrease in monocytic interleukin-1ß and COX-2 levels and prevented oxidant formation caused by S100b, which appeared to be mediated by inhibition of p47phox membrane translocation. Chromatin immunoprecipitation demonstrated that S100b increased the recruitment of nuclear factor-kappaB transcription factor as well as cAMP response element-binding-binding protein and coactivator-associated arginine methyltransferase-1 cofactors to the interleukin-1ß promoter, whereas these changes were inhibited with SM treatment. In vivo, SM reduced tissue AGE accumulation, tail collagen crosslinking, and concentrations of plasma glycated albumin. Levels of oxidative and inflammatory biomarkers were also significantly decreased in SM-treated groups compared with the diabetic group. These data suggest that SM supplementation may reduce the burden of AGEs in diabetics and may prevent resulting complications.

Anti-inflammatory effect of the 5,7,4'-trihydroxy-6-geranylflavanone isolated from the fruit of Artocarpus communis in S100B-induced human monocytes.

The fruit of Artocarpus communis Moraceae, a traditional starch crop, is a rich source of phytochemicals, such as flavonoids and their derivatives. The aim of this study was to investigate whether 5,7,4'-trihydroxy-6-geranylflavanone (AC-GF), a geranyl flavonoid derivative isolated from the fruits of A. communis, could decrease the activation of inflammatory mediators induced by S100B (ligand of receptor for advanced glycation end products, RAGE) in THP-1 monocytes. According to the results, low levels of AC-GF (≤2.5 µM) showed a great inhibitory effect on gene expression of RAGE and down-regulated both TNF-α and IL-1ß secretion and gene expression (p < 0.05). AC-GF also decreased reactive oxygen species (ROS) production in response to S100B (p < 0.05). Additionally, Western blotting revealed that AC-GF could effectively attenuate RAGE-dependent signaling, including expression of protein kinase C (PKC) and p47phox, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), and particularly NF-κB activation (p < 0.05). In conclusion, this is the first report that AC-GF possesses great antioxidant and anti-inflammatory properties in vitro. This finding may contribute to increased implication and utilization of the fruit of A. communis Moraceae in functional foods.

[Value of blood apoH gene expression and urinary NAG and RBP in early diagnosis of renal function damage in neonates].

OBJECTIVE: To study the value of apolipoprotein H (apoH) gene expression in peripheral blood mononuclear cell (PBMC) and urinary N-Acetyl-beta-D-Glucosaminidase (NAG) and retinal-binding protein (RBP) in the early diagnosis of renal function damage in neonates. METHODS: Sixty sick neonates who renal function damage probably occurred were enrolled. The blood and urinary samples were collected twice within 48 hrs following admission, with an interval of 12-24 hrs. Expression of apoH gene in PBMC was determined with RT-PCR. The levels of blood urea nitrogen (BUN) and creatinine, and urinary activities of NAG and RBP were measured with enzymatic reaction. RESULTS: The abnormal rates of blood apoH and urinary NAG and RBP were 73.3%, 83.3% and 76.7%, respectively in the first detection. The second detection for blood apoH and urinary NAG and RBP showed abnormal rates of 70.0%, 66.7% and 76.7%, respectively. There were no significant differences in the abnormal rates between the three markers either in the first or the second detection (P>0.05). Beside there were no significant significances in the abnormal rates between urinary NAG and blood BUN in the second detection, the abnormal rates of blood apoH and urinary NAG and RBP in both detections were significantly higher than those of BUN or creatinine (P<0.01 or 0.05). CONCLUSIONS: There are identical values of blood apoH gene expression and urinary NAG and RBP in the early diagnosis of renal function damage in neonates. The above three markers are more sensitive to early renal function damage than blood BUN and creatinine.