Engineering photocatalytic ammonia synthesis.

Photocatalytic ammonia synthesis (PAS) is an emerging zero carbon emission technology, which is critical for mitigating energy crises and achieving carbon neutrality. Herein, we summarize the recent advances and challenges in PAS from an engineering perspective based on its whole chain process, i.e., materials engineering, structure engineering and reaction engineering. For materials engineering, we discuss the commonly used photocatalytic materials including metal oxides, bismuth oxyhalides and graphitic carbon nitride and emerging materials, such as organic frameworks, along with the analysis of their characteristics and regulation methods to enhance the PAS performance. For structure engineering, the design of photocatalysts is described in terms of morphology, vacancy and band, corresponding to the crystal, atom and electron scales, respectively. Moreover, the structure-performance relationship of photocatalysts has been deeply explored in this section. For reaction engineering, we identify three key processes from the chemical reaction and mass transfer, i.e., nitrogen activation, molecule transfer and electron transfer, to intensify and optimize the PAS reaction. Hopefully, this review will provide a novel paradigm for the design and preparation of high-efficiency ammonia synthesis photocatalysts and inspire the practical application of PAS.

Dityrosine in food: A review of its occurrence, health effects, detection methods, and mitigation strategies.

Protein and amino acid oxidation in food products produce many new compounds, of which the reactive and toxic compound dityrosine, derived from oxidized tyrosine, is the most widely studied. The high reactivity of dityrosine enables this compound to induce oxidative stress and disrupt thyroid hormone function, contributing to the pathological processes of several diseases, such as obesity, diabetes, cognitive dysfunction, aging, and age-related diseases. From the perspective of food safety and human health, protein-oxidation products in food are the main concern of consumers, health management departments, and the food industry. This review highlights the latest research on the formation pathways, toxicity, detection methods, occurrence in food, and mitigation strategies for dityrosine. Furthermore, the control of dityrosine in family cooking and food-processing industry has been discussed. Food-derived dityrosine primarily originates from high-protein foods, such as meat and dairy products. Considering its toxicity, combining rapid high sensitivity dityrosine detection techniques with feasible control methods could be an effective strategy to ensure food safety and maintain human health. However, the current dityrosine detection and mitigation strategies exhibit some inherent characteristics and limitations. Therefore, developing technologies for rapid and effective dityrosine detection and control at the industrial level is necessary.

A GWAS-supported variant interacting with diabetes predicts risk of atherothrombotic stroke in Han Chinese population.

BACKGROUND: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. METHODS: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool. RESULTS: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR = 0.76, 95% CI = 0.58-0.99 and OR = 0.76, 95% CI = 0.58-0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR = 0.63, 95% CI = 0.45-0.88), no hypertension (OR = 0.66, 95% CI = 0.46-0.94), diabetes (OR = 0.33, 95% CI = 0.17-0.64), and smoking (OR = 0.65, 95% CI = 0.44-0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR = 4.48; 95% CI = 2.98-6.72) increased risk of AS. CONCLUSION: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population.

[γ-aminobutyric acid fortified rice alleviated oxidative stress and pancreatic injury in type 2 diabetic mice].

OBJECTIVE: To investigate the effects of gamma aminobutyric acid(GABA) fortified rice diet intervention on oxidative stress and pancreatic injury in type 2 diabetes mellitus(T2 DM) mice. METHODS: Of the 70 male ICR mice, 10 were randomly selected as blank control group and they were always fed with the normal white rice feed. The remaining 60 mice were fed with high-fat white rice for 9 weeks. They were fasted for 12 h and injected intraperitoneally with streptozocin(STZ) at a dose of 50 mg/kg body weigh for two consecutive days. The control group was injected with the corresponding volume of normal saline. Subsequently, 50 T2 DM mice with successful modeling were randomly divided into 5 groups according to blood glucose, 10 in each group: T2 DM model control group, germinated brown rice positive control group(GABA content is 0. 2 g/kg feed), GABA-fortified rice low, medium and high dose group(GABA content was 0. 02, 0. 1 and 0. 2 g/kg feed respectively) and each target diet was fed for 6 weeks. Oral glucose tolerance test was performed one week before the end of the experiment to observe the hypoglycemic effect of different doses of GABA fortified rice. After the end of the experiment, HE staining was used to observe the morphology of pancreas. At the same time, the redox indicators from plasma and pancreas of reactive oxygen species(ROS), malondialdehyde(MDA), total antioxidant capacity(T-AOC), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) were examined in each group; The mRNA expressions of oxidative stress-related genes including glycogen synthase kinase-3ß(GSK-3ß), nuclear transcription factor 2(Nrf2), heme oxygenase 1(HO-1) and NAD(P)H: quinone oxidoreductase1(NQO1), insulin secretion related genes including pancreatic and duodenal homeobox 1(PDX-1), mus musculus v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A(MafA), glucokinase(GCK), glucose transporter 2(GLUT2) and the apoptosis associated genes including b-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax) and caspase-3 in pancreas were assayed by real-time fluorescent quantitative PCR. RESULTS: The intervention of GABA fortified rice could alleviate the improvement of the blood glucose level and the lack of insulin secretion in T2 DM mice and relieve plasma and pancreatic oxidative stress. besides, The intervention of GABA fortified rice could up-regulate the expression of insulin secretion-related genes PDX-1, GCK, GLUT2, inhibit the expression of pro-apoptotic gene caspase-3 and promote the expression of anti-apoptosis gene Bcl-2. There was a dose-response relationship between the above result and the 0. 2 g/kg dose group was the most significant, which achieved similar result to germinated brown rice. CONCLUSION: GABA-fortified rice can significantly improve the plasma and pancreatic redox status of STZ-induced T2 DM mice, regulate the expression levels of oxidative stress-related genes and apoptosis-related genes, thereby protect pancreatic tissue morphology, improve pancreatic insulin secretion and thereby alleviate glucose metabolism.

Polysaccharides Extracted from Rhizoma Pleionis Have Antitumor Properties In Vitro and in an H22 Mouse Hepatoma Ascites Model In Vivo.

Malignant ascites is a highly severe and intractable complication of advanced or recurrent malignant tumors that is often immunotherapy-resistant. Rhizoma Pleionis is widely used in traditional medicine as an antimicrobial and anticancer agent, but its effectiveness in treating malignant ascites is unclear. In the current study, we investigated the effect of polysaccharides isolated from Rhizoma Pleionis (PRP) on murine hepatocarcinoma H22 cells in an ascites model. We have found that the main components of PRP, that presented a relative molecular weight of 383.57 kDa, were mannose and glucose. We also found that PRP reduced the occurrence of abdominal ascites and increased survival in our mouse model. An immune response in the ascites tumor model was observed by performing a lymphocytes proliferation experiment and an E-rosette test. The ratios of CD8+ cytotoxic T cells and NK cells in the spleen were examined by flow cytometry, and the mRNA expression of Foxp3+in CD4⁺CD25⁺ (T regulatory Tregs) was measured by RT-PCR (reverse transcription-polymerase chain reaction). The levels of the cytokines TNF-α (tumor necrosis factor), VEGF (vascular endothelial growth factor), IL-2 (interleukin), and IFN-γ (interferon) in the serum and ascites supernatants were measured by ELISA. The expression of Foxp3 and Stat3 in peritoneal cells in the mouse model was measured by immunocytochemistry. The results indicated that PRP increased H22 tumor cell apoptosis in vivo by activating and enhancing the immune response. Furthermore, the effects of PRP on the proliferation of H22 cells were assessed by the CCK8 assay, Hoechest 33258, and TUNEL staining in vitro. We found that PRP suppressed the proliferation of H22 tumor cells but had no effect on BRL (Big rat liver) -3A rat hepatoma normal cells in vitro. Next, we investigated the underlying immunological mechanism by which PRP inhibits malignant ascites. PRP induced tumor cell apoptosis by inhibiting the Jak1⁻Stat3 pathway and by activating Caspase-3 and Caspase-8 to increase the Bax/Bcl-2 ratio. Collectively, our results indicate that PRP exhibits significant antitumor properties in H22 cells in vivo and in vitro, indicating that PRP may be used as a new therapeutic drug for cancer treatment.

[Dityrosine administration induces myocardium injury and inflammatory response in mice].

OBJECTIVE: To study the effects of oxidized tyrosine products and dityrosine on the myocardial injury and inflammatory response in 10-week-gavaged mice. METHODS: A total of 30 female Kunming mice were assigned to three groups: gavagedwith saline( Con), oxidized tyrosine products( O-Tyr) and dityrosine( Dityr) for 320µg/kg BW for 10 weeks. Levels of oxidized protein products( DT, AOPPs, 3-NT) and lipid peroxidation products( MDA), oxidative stress( T-AOC and GSH/GSSG), markers of myocardium injury( CK, CK-MB, cTnI and Ca~(2+)-ATPase), markers of inflammatory factor( CRP and TNF-α) were investigated and the genes related to inflammatory response were detected by Real-time quantitative( PCR). RESULTS: 10 weeks of gavage experiments enhanced the levels of dityrosine( DT), advanced oxidation protein products( AOPPs), 3-nitrotyrosine( 3-NT), and malondialdehyde( MDA), and decreased total antioxidant capacity( T-AOC) and the ratio of reduced glutathione to oxidized glutathione( GSH/GSSG) in mice plasma and myocardium. Besides, O-Tyr and Dityr increased the levels of creatine kinase( CK), creatine kinase isoenzymes( CK-MB), cardiac troponin I( cTnI) in plasma anddecreased the activities of Ca~(2+)-ATPase in myocardium. O-Tyr and Dityr increased the levels of C-reactive protein( CRP) and tumour necrosis factor α( TNF-α) in plasma. The gene expression of inflammatory response were up-regulated. CONCLUSION: O-Tyr and Dityr increase the accumulation of myocardial protein oxidation and lipid peroxidation products and induce oxidative damage to myocardium. O-Tyr and Dityr may cause myocardial tissue injury and inflammatory response. Dityrosine, as the main component of tyrosine oxidative products, may play a major role in the process of oxidized tyrosine products causing myocardial injury in mice.

Dietary oxidized tyrosine (O-Tyr) stimulates TGF-ß1-induced extracellular matrix production via the JNK/p38 signaling pathway in rat kidneys.

Oxidized tyrosine (O-Tyr) products have been detected in commercial food and have been demonstrated to induce liver injury in our previous study, but the precise mechanisms of the impact induced by dietary O-Tyr are still unclear. Kidney plays an important role in the metabolism of protein. Accumulation of O-Tyr products, especially the dityrosine (Dityr) and advanced oxidation protein products (AOPPs), in vivo was shown to be associated with many kidney diseases. Therefore, this study determined whether chronic exposure to dietary O-Tyr impaired renal function in rats. After O-Tyr treatment for 24 weeks, rats exhibited oxidative stress and protein oxidation in the kidneys, accompanied with inflammatory reaction and renal dysfunction. Elevated extracellular matrix (ECM) contents and the histological examination (HE and Masson stain) results indicated renal fibrosis. The Real-time PCR and Western blotting assay showed that O-Tyr activated phosphorylation of JNK/p38 and up-regulated the expression of transforming growth factor-ß1 (TGF-ß1) and Smad 2/3. These results suggest that dietary O-Tyr could induce oxidative stress, inflammation and renal fibrosis through JNK/p38/TGF-ß1 signaling pathway. Dityr (accounting for 22 % of the total O-Tyr material) may be responsible for the O-Tyr-induced injury. This study also provides a modified procedure for separation and purification of Dityr, the main oxidized product in O-Tyr.

Dityrosine administration induces dysfunction of insulin secretion accompanied by diminished thyroid hormones T3 function in pancreas of mice.

Oxidized tyrosine products are commonly found in food with high protein content and have been demonstrated to cause damage of liver and kidney in our previous studies. Dityrosine (Dityr) is a typical oxidized tyrosine product. Due to its structural homology with thyroid hormones T3, we assumed that one of the endocrine systems most likely considered in connection with its disruption by Dityr may be the T3 action. T3 plays important roles in insulin synthesis, and thyroid hormone resistance (RTH) is associated with the impairment of glucose metabolism. Therefore, this study determined whether Dityr exposure impaired T3 function in pancreas leading to glucose metabolism disruption. After 10-week gavage with Dityr, mice exhibited impaired glucose tolerance and disturbed energy metabolism. The elevated free THs content in plasma, the up-regulation of THs synthesis-specific genes expressions in thyroid glands, and the increased thyroid follicles histology shapes and areas indicated that Dityr enhanced the THs synthesis in thyroid glands. In addition, Dityr-induced RTH, which reflected as elevated plasma free THs in the presence of unsuppressed thyroid stimulating hormone. The mRNA downregulation of membrane transporter of T3 (MCT8) and co-activator factors (RXRα, Src-1), together with the decreased protein level of thyroid hormone receptor ß1 (TRß1) in pancreas illustrated that the activation ability of T3 to downstream gene involved in insulin synthesis was suppressed by Dityr. In MIN-6 cell experiment, T3 improved glucose-stimulated insulin secretion by upregulating mRNA levels of insulin synthesis-related genes (Ins2, MafA, Pdx1) and T3 action-related genes, as well as increasing protein level of TRß1. These data suggest that Dityr suppress T3-regulated insulin synthesis stimulated by glucose via an indirect way of decreasing sensibility to T3 in pancreas. All these findings indicate that Dityr can disrupt THs function in pancreas leading to glucose metabolism disorder.

Type 1 5'-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells.

3,3',5-triiodothyronine (T3) is largely generated from thyroxine (T4) by the catalysis of deiodinases in peripheral tissues. Emerging evidences have indicated its broad participation in regulating various metabolic process via protecting tissues from oxidative stress and improving cellular antioxidant capacity. However, the potential correlation between the oxidative stress and conversion of T4 to T3 is still unclear. In the present study, the effects of T3 and T4 on redox homeostasis in HepG2 cells pre-treated with H2O2 was investigated. It revealed that T3 significantly rescued the apoptotic cell death, consistent with an upregulation of cell antioxidant ability and reduction of ROS accumulation while T4 did not. Afterwards, we examined the enzyme activity and mRNA expression of type 1 5'-deiodianse (DIO1), T3 and rT3 level and found that H2O2 reduced both DIO1 activity and expression in a dose-dependent manner, which consequently declined T3 and rT3 generation. Alpha-lipoic acid (LA) treatment notably restored DIO1 activity, T3 and rT3 level, as well as transcriptional abnormalities of inflammation-associated genes. It suggests that oxidative stress may reduce DIO1 activity by an indirect way like activating cellular inflammatory responses. All these results indicate that the oxidative stress downregulates the conversion of T4 to T3 through DIO1 function in HepG2 cells.

Resveratrol restores the circadian rhythmic disorder of lipid metabolism induced by high-fat diet in mice.

Circadian rhythmic disorders induced by high-fat diet are associated with metabolic diseases. Resveratrol could improve metabolic disorder, but few reports focused on its effects on circadian rhythm disorders in a variety of studies. The aim of the present study was to analyze the potential effects of resveratrol on high-fat diet-induced disorders about the rhythmic expression of clock genes and clock-controlled lipid metabolism. Male C57BL/6 mice were divided into three groups: a standard diet control group (CON), a high-fat diet (HFD) group and HFD supplemented with 0.1% (w/w) resveratrol (RES). The body weight, fasting blood glucose and insulin, plasma lipids and leptin, whole body metabolic status and the expression of clock genes and clock-controlled lipogenic genes were analyzed at four different time points throughout a 24-h cycle (8:00, 14:00, 20:00, 2:00). Resveratrol, being associated with rhythmic restoration of fasting blood glucose and plasma insulin, significantly decreased the body weight in HFD mice after 11 weeks of feeding, as well as ameliorated the rhythmities of plasma leptin, lipid profiles and whole body metabolic status (respiratory exchange ratio, locomotor activity, and heat production). Meanwhile, resveratrol modified the rhythmic expression of clock genes (Clock, Bmal1 and Per2) and clock-controlled lipid metabolism related genes (Sirt1, Pparα, Srebp-1c, Acc1 and Fas). The response pattern of mRNA expression for Acc1 was similar to the plasma triglyceride. All these results indicated that resveratrol reduced lipogenesis and ultimately normalized rhythmic expression of plasma lipids, possibly via its action on clock machinery.

Elevated plasma dityrosine in patients with hyperlipidemia compared to healthy individuals.

BACKGROUND: Dityrosine, the modification of tyrosine residues, may contribute to metabolic disorders. This study was undertaken to investigate plasma dityrosine concentrations in patients with hyperlipidemia and to examine the correlation between dityrosine and lipid profiles. METHODS: Fluorescence spectrophotometry was used to measure dityrosine in the plasma of healthy subjects (n = 203) and dyslipidemic subjects, which included patients with mild hyperlipidemia (n = 246) and hyperlipidemia (n = 179). Advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were also assayed in all subjects. RESULTS: Dityrosine levels were higher by 9.3 and 22.9% in mildly hyperlipidemic and hyperlipidemic patients, respectively, compared to controls after adjustment for age, gender, and BMI. AOPP and MDA levels showed similar trends. The levels of dityrosine related positively (p < 0.05) to total cholesterol (r = 0.362), triglycerides (r = 0.449), and low-density lipoprotein cholesterol (r = 0.359). Moreover, plasma dityrosine (r = 0.408), AOPP (r = 0.488), and MDA (r = 0.181) levels were elevated with an increase in the atherosclerosis index in the subjects. CONCLUSIONS: These findings suggest that dityrosine formation may be an early event in the pathological process of hyperlipidemia. Dityrosine as a biomarker detected by fluorescence spectrophotometry might be a useful tool to evaluate the plasma redox state in hyperlipidemia.

[Effects of tyrosine oxidation products on redox state in myocardium of rats].

OBJECTIVE: To explore the effects of tyrosine oxidized products (TOP) on the redox state of rats myocardium and investigate the oxidative damage mechanism. METHODS: Male SD Rats were randomly assigned to three groups and treated respectively with normal diet (Group C), 440 mg/kg TOP (Group TOP), 440 mg/kg tyrosine oxidized products plus 5 mg/kg lipoic acid (Group TOP + LA). Indicators of oxidative stress in blood and myocardial were measured at the end of 6 weeks, 12 weeks and 24 weeks. RT-PCR was used to detect mRNA expression of Nrf2, Trx, NF-κB and AP-1 in myocardium. RESULTS: Compared to the control group (Group C), reactive oxygen species (ROS), carbonyl (PC), malondialdehyde (MDA), dityrosine (Dityr), 3-nitrotyrosine (3-NT) in rats blood and myocardium were all significantly increased in the TOP group (P < 0.05). Total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reducing glutathione (GSH) and oxidized glutathione (GSSG) levels all decreased significantly (P < 0.05). The mRNA expression of Nrf2, Trx-1, NF-κB, AP-1 RNA significantly up-regulated (P < 0.05) in the TOP group compared to the control. CONCLUSION: Tyrosine oxidized products impairs antioxidant defense system and lead to accumulation of protein oxidation products in rats myocardium. Moreover, lipoic acid performs a positive effect in the protective reaction, which may adjusted by regulation of redox signaling pathway.

Antioxidant and antibacterial activities of extracts from Conyza bonariensis growing in Yemen.

This study aims to examine the antioxidant and antibacterial activities and phenolic contents of Conyza bonariensis growing in Yemen. The whole plants of C. bonariensis were ultrasonically extracted by ethanol. The antioxidant activity of the extract was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ß-carotene bleaching (BCB). The effectiveness of the extract on the growth inhibition of some indicators of foodborne illness bacteria were investigated by agar well diffusion assay. The total phenols (TP), total flavonoids (TF), total tannins (TT), and total anthocyanins (TA) were determined by Folin-Ciocalteu method, aluminium chloride method, Folin and Ciocalteu method, and pH-differential method, respectively. The extract of C. bonariensis possessed TP 144.1 mg/g, TF 143 mg/g, TT 0.99mg/g, and TA 0.97mg 100g, with 94.57% inhibition of DPPH and 92.47% inhibition of BCB, and strong inhibitory effects against tested bacteria, which was approximate to those of peel extract of Punica granatum.

Increased oxidative stress and the apoptosis of regulatory T cells in obese mice but not resistant mice in response to a high-fat diet.

High fat feeding induces a variety of obese and lean phenotypes in inbred rodents. Obesity is a pro-inflammatory state, and regulatory T cells (Tregs) are essential negative regulators of inflammation. We aimed to determine the involvement of Tregs in the mice susceptible or resistant to high-fat diet (HFD). In the study, diet-induced obese (DIO) mice experienced significant increases in weight gain, energy intake, fat masses, plasma lipid and proinflammatory cytokines in comparison with control and diet-resistant (DR) mice. Also, Tregs production decreased in DIO mice. HFD diminished mitochondrial transmembrane potential (MTP) in the spleen Tregs of DIO mice and reinforced apoptosis compared with that in DR mice. Moreover, HFD significantly decreased antioxidant enzymes expressions and increased reactive oxygen species (ROS) productions in the Tregs of DIO mice, but not in those of DR mice, which should provide valuable evidence for unraveling the pathogenesis of inflammation found in this obese mice model.

Propensity to high-fat diet-induced obesity in mice is associated with the indigenous opportunistic bacteria on the interior of Peyer's patches.

Indigenous opportunistic bacteria on the interior of the Peyer's patches play a key role in the development of the mucosal immune, but their population composition has been ignored. The present study was conducted to test the hypothesis that the changes in the composition of indigenous opportunistic bacteria in the Peyer's patches are associated with obesity. C57BL/6J-male mice had been fed either a control diet or a high-fat diet. After 25 weeks, mice in high-fat diet exhibit either an obesity-prone (OP) or an obesity-resistant (OR) phenotype. Control diet group (CT) and OR group had a significant larger bacteria diversity than that in the OP group. Allobaculum and Lactobacillus were significantly decreased in high-fat diet induced OP mice compared with CT and OR mice, whereas Rhizobium and Lactococcus was significantly increased. The result of quantitative real-time PCR was consistent with that of 454 pyrosequencing. Significant correlations between mRNA expression of inflammation marks and the top 5 abundance genera bacteria on the interior of Peyer's patches were observed by Pearson's correlation analysis. Taken together, the indigenous opportunistic bacteria on the interior of Peyer's patches plays a major role in the development of inflammation for an occurrence of obesity.

[Comparison of serum lipid and protein oxidation products levels in patients with different types of dyslipidemia].

OBJECTIVE: To explore serum redox status differences among different types of dyslipidemia patients. METHOD: One hundred and nineteen healthy people and two hundred and ninety four dyslipidemic participants on clinical examination were divided into six groups: control group, hypercholesterolemia (HTC), hypertriglyceridemia (HTG), combined hyperlipidemia (CH), low level of high-density lipoprotein cholesterol (LHDL) and hyperlipidemia with LHDL (HBL + LHDL) according to blood lipid profiles. Malonaldehyde (MDA), total antioxidant capacity (T-AOC), advanced oxidation protein products (AOPP) and dityrosine (DT) in serum were measured. RESULTS: In all participants, the T-AOC, AOPP and DT levels in HTG, CH and HBL + LHDL groups were significantly (P < 0.05) higher than that in controls, further, LHDL with or without hyperlipidemia had elevated (P < 0.05) MDA level compared with control, HTC and HTG groups, whereas levels of AOPP and DT in LHDL were not different with controls. Triglycerides values showed a positive correlation with MDA, T-AOC, AOPP and DT. CONCLUSION: Level of serum oxidative stress was higher in hyperlipidemia patients than in healthy people, and high triglycerides levels were more likely to cause an imbalance in redox status.

Increased serum and urinary microRNAs in children with idiopathic nephrotic syndrome.

BACKGROUND: MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). METHODS: We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. RESULTS: The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P < 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86-0.94; P < 0.0001) and 40.7 (95% CI, 6.06-103; P < 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. CONCLUSIONS: We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.

Antibacterial activity and dual mechanisms of peptide analog derived from cell-penetrating peptide against Salmonella typhimurium and Streptococcus pyogenes.

A number of research have proven that antimicrobial peptides are of greatest potential as a new class of antibiotics. Antimicrobial peptides and cell-penetrating peptides share some similar structure characteristics. In our study, a new peptide analog, APP (GLARALTRLLRQLTRQLTRA) from the cell-penetrating peptide ppTG20 (GLFRALLRLLRSLWRLLLRA), was identified simultaneously with the antibacterial mechanism of APP against Salmonella typhimurium and Streptococcus pyogenes. APP displayed potent antibacterial activity against Gram-negative and Gram-positive strains. The minimum inhibitory concentration was in the range of 2 to 4 µM. APP displayed higher cell selectivity (about 42-fold increase) as compared to the parent peptide for it decreased hemolytic activity and increased antimicrobial activity. The calcein leakage from egg yolk L-α-phosphatidylcholine (EYPC)/egg yolk L-α-phosphatidyl-DL-glycerol and EYPC/cholesterol vesicles demonstrated that APP exhibited high selectivity. The antibacterial mechanism analysis indicated that APP induced membrane permeabilization in a kinetic manner for membrane lesions allowing O-nitrophenyl-ß-D-galactoside uptake into cells and potassium release from APP-treated cells. Flow cytometry analysis demonstrated that APP induced bacterial live cell membrane damage. Circular dichroism, fluorescence spectra, and gel retardation analysis confirmed that APP interacted with DNA and intercalated into the DNA base pairs after penetrating the cell membrane. Cell cycle assay showed that APP affected DNA synthesis in the cell. Our results suggested that peptides derived from the cell-penetrating peptide have the potential for antimicrobial agent development, and APP exerts its antibacterial activity by damaging bacterial cell membranes and binding to bacterial DNA to inhibit cellular functions, ultimately leading to cell death.

Alterations of the gut microbiota in high-fat diet mice is strongly linked to oxidative stress.

Alterations of the gut microbiota induced by diet exert a strong influence on the development of metabolic syndrome. In this study, we prove the hypothesis that the long-term high-fat diet (HFD) may influence gut microbiota directly and/or indirectly by changing the redox state. Lipoic acid (LA), as a universal antioxidant, was used to improve the redox state. Reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) were analyzed to profile oxidative stress states. PCR-denaturing gradient gel electrophoresis (DGGE) was used to describe gut flora structures, while plate count was employed for the quantitative analysis of Escherichia coli, lactobacilli, and enterococcus. The influence of redox state on the vitality of gut-derived bacteria was measured in vitro. ROS and MDA, which significantly decreased in LA mice compared with HFD mice, showed a strong positive association with E. coli and enterococcus (P < 0.05) and a negative association with lactobacilli (P < 0.05). Increased T-AOC in LA mice showed a high positive association with lactobacilli (P < 0.05) and a negative correlation with E. coli and enterococcus. These correlations implied that the dietary effects on the gut microbiota were conferred, at least in part, through an effect on oxidative stress. This study provides evidence that modulation of the redox state by an antioxidant has the potential to improve gut microbiota, which has relevance for metabolic health.

Inhibition of Fe-induced colon oxidative stress by lactobacilli in mice.

Iron (Fe) can promote hydrogen peroxide (H(2)O(2)) and hydroxyl radical generation in the colonic surface and promote growth of Fe-dependent bacteria. Some Lactobacillus strains are resistant to oxygen free-radicals, allowing them to survive in a Fe-modulated mucosal environment and influence colon microbial ecology and redox state. Here, we investigated the capacity of lactobacilli with different antioxidant abilities to modify the bacterial profile and prevent oxidative stress in the colon of Fe-overloaded mice. Survival time of Lactobacillus rhamnosus LGG (LGG) in the presence of H(2)O(2) and hydroxyl radical was significantly longer compared with the mid- and non-antioxidative strains, Lactobacillus paracasei Fn032 and Lactobacillus plantarum Fn001, respectively. Different Lactobacillus strains are specific in free-radical scavenging activities of their cell-free extracts, which increased to varying extent depending on strains when bacteria were exposed to simulated gastric and pancreatic juice. Fe-overloaded mice showed increased colonic luminal ferrous Fe content, Enterococcus and Escherichia coli concentrations, mucosal malondialdehyde and free-radicals, and decreased mucosal total antioxidative capacity and oxidative enzymatic activity. Translocation of endotoxin to the liver was also significantly increased (P < 0.05). Lactobacilli inhibited ferrous Fe accumulation, especially in LGG and Fn032. LGG significantly inhibited the increase of colonic mucosal free-radicals and malondialdehyde content (P < 0.05). Fn032 only inhibited malondialdehyde (P < 0.05). LGG and Fn032 significantly inhibited increases in colonic Enterococcus (P < 0.05). Fn001 showed no significant antioxidative ability in vivo. The difference of these effects in vivo were well agreed with scavenging activities against reactive oxygen species (ROS) of simulated gastrointestinals fluid pretreated cells in vitro. In conclusion, ROS scavenging activities was essential for Lactobacillus to prevent oxidative stress in vivo and inhibition of ROS-producing bacterial growth and mucosal barrier injury.