One-time ozone treatment improves the postharvest quality and antioxidant activity of Actinidia arguta fruit.

The major aim of this study was to check the effect of one-time ozonation on selected quality parameters and antioxidant status of Actinidia arguta fruit. For this purpose, A. arguta fruit was ozonated with gas at a concentration of 10 and 100 ppm, which was carried out successively for 5, 15 and 30 min. Next, the selected quality attributes, antioxidants level as well as NADPH and mitochondrial energy metabolism in mini-kiwi fruit after ozonation were analysed. Our research has shown that ozonation reduced the level of yeast and mould without affecting the content of soluble solids or acidity. In turn, ozonation clearly influenced the antioxidant activity and the redox status of the fruit. The ozonated fruit was characterised by a lower level of ROS due to the higher level of low molecular weight antioxidants, as well as the higher activity of superoxide dismutase and catalase. In addition, improved quality and antioxidant activity of the fruit were indirectly due to improved energy metabolism and NADPH level. The ozonated fruit showed a higher level of ATP, due to both higher activity of succinate dehydrogenase and higher availability of NADH. Moreover, the increased level of NAD+ and the activity of NAD+ kinase and glucose-6-phosphate dehydrogenase contributed to higher levels of NADPH in the fruit.

Almond oil restores blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism.

OBJECTIVES: Favism is a metabolic disease and this study aimed to compare between olive oil and almond oil to ameliorate blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology in favism rats. METHODS: Animals were 36 male albino rats. They classified to 2 equal (normal and favism) groups. Normal group classified to 3 equal subgroups; Control, Olive oil, and Almond oil subgroups: normal rats orally administrated with 1 mL/100 g of saline, olive oil, and almond oil, respectively. Favism group was subdivided into 3 equal subgroup; favism, favism + olive oil, and favism + almond oil subgroups: favism rats orally administrated with no treatment, 1 mL/100 g olive oil, and 1 mL/100 g almond oil, respectively. All treatments were administrated orally by oral gavage once a day for 1 month. RESULTS: The hemoglobin, hematocrite, the blood cells, glucose and glucose-6-phosphate dehydrogenase, aspartate and alanine aminotransferase, total proteins, albumin, and globulin in serum were decreased in favism. The glutathione, superoxide dismutase, and glutathione peroxidase in blood and liver were decreased in favism while alkaline phosphatase and total bilirubin in serum were increased in favism. The blood and liver malondialdehyde was increased in favism. Furthermore, oral administration with both oils in favism rats restored all these parameters to be approached the control levels. Also, both oils preserved blood and liver DNA and liver histology. CONCLUSIONS: Almond oil restored blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism.

Protective role of melatonin against adipose-hepatic metabolic comorbidities in experimentally induced obese rat model.

BACKGROUND: Adipose and hepatic metabolic dysfunctions are critical comorbidities that also aggravate insulin resistance in obese individuals. Melatonin is a low-cost agent and previous studies suggest that its use may promote metabolic health. However, its effects on some comorbidities associated with obesity are unknown. Herein, we investigated the hypothesis that melatonin supplementation would attenuate adipose-hepatic metabolic dysfunction in high fat diet (HFD)-induced obesity in male Wistar rats. MATERIALS AND METHODS: Twenty-four adult male Wistar rats (n = 6/group) were used: Control group received vehicle (normal saline), obese group received 40% high fat diet, melatonin-treated group received 4 mg/kg of melatonin, and obese plus melatonin group received 40% HFD and melatonin. The treatment lasted for 12 weeks. RESULTS: HFD caused increased food intake, body weight, insulin level, insulin resistance and plasma and liver lipid but decreased adipose lipid. In addition, HFD also increased plasma, adipose and liver malondialdehyde, IL-6, uric acid and decreased Glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and circulating obestatin concentration. However, these deleterious effects except food intake were attenuated when supplemented with melatonin. CONCLUSION: Taken together, the present results indicate that HFD exposure causes adipose-hepatic metabolic disturbance in obese animals, which are accompanied by oxidative stress and inflammation. In addition, the present results suggest that melatonin supplementation attenuates adipose-hepatic metabolic dysfunction, accompanying obesity by suppression of oxidative stress/inflammation-dependent mechanism and increasing circulating obestatin.

Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is a natural herbal medicine widely used clinically with numerous pharmacological activities including anti-cancer. Specifically, several studies reported that free anthraquinones from Rhubarb suppressed the proliferation of hepatoma cells. Nonetheless, recent studies revealed that Rhubarb caused hepatotoxicity in vivo, confirming its "two-way" effect on the liver. Therefore, the efficacy and safety of Rhubarb in the in vivo treatment of liver cancer should be further elucidated. AIM OF THE STUDY: This study investigated the presence of hepatoprotection or hepatotoxicity of Rhubarb in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. MATERIAL AND METHODS: A total of 112 male Sprague-Dawley rats weighing 190-250 g were enrolled. The rats were induced hepatocarcinogenesis using diethylnitrosamine (0.002 g/rat) until 17 weeks. Starting at week 11, Rhubarb granules (4 g/kg and 8 g/kg) were intragastrically administered daily for 7 weeks. All rats were euthanized at week 20 and the livers were analyzed via non-targeted metabolomics analysis. We established hepatic glucose 6 phosphate (6PG) levels and glucose 6 phosphate dehydrogenase (G6PD) activities to assess the pentose phosphate pathway (PPP). And the liver injuries of rats were analyzed via histological changes, hepatic function, as well as hepatic protein levels of alpha-fetoprotein (AFP), pyruvate kinase isozyme type M2 (PKM2), and proliferating cell nuclear antigen (PCNA). Furthermore, polydatin (0.1 g/kg/d) as a specific inhibitor of G6PD was used to treat rats. Notably, their histological changes, hepatic function, hepatic 6PG levels, hepatic G6PD activities, PCNA levels, and PKM2 levels were recorded. RESULTS: Non-targeted metabolomics revealed that Rhubarb regulated the PPP in the liver of Rhubarb-DEN-treated rats. Besides, Rhubarb activated the oxidative branch of the PPP by activating G6PD (a rate-limiting enzyme in the oxidative PPP) in the liver of Rhubarb-DEN-treated rats. Meanwhile, Rhubarb promoted DEN-induced hepatocarcinogenesis. Moreover, polydatin attenuated the promoting effect of Rhubarb on DEN-induced hepatocarcinogenesis. CONCLUSIONS: Rhubarb promoted DEN-induced hepatocarcinogenesis by activating the PPP, indicating that the efficacy and safety of Rhubarb in the treatment of liver cancer deserve to be deliberated.

Contrasting anther glucose-6-phosphate dehydrogenase activities between two bean varieties suggest an important role in reproductive heat tolerance.

Common beans (Phaseolus vulgaris) are highly sensitive to elevated temperatures, and rising global temperatures threaten bean production. Plants at the reproductive stage are especially susceptible to heat stress due to damage to male (anthers) and female (ovary) reproductive tissues, with anthers being more sensitive to heat. Heat damage promotes early tapetal cell degradation, and in beans this was shown to cause male infertility. In this study, we focus on understanding how changes in leaf carbon export in response to elevated temperature stress contribute to heat-induced infertility. We hypothesize that anther glucose-6-phosphate dehydrogenase (G6PDH) activity plays an important role at elevated temperature and promotes thermotolerance. To test this hypothesis, we compared heat-tolerant and susceptible common bean genotypes using a combination of phenotypic, biochemical, and physiological approaches. Our results identified changes in leaf sucrose export, anther sugar accumulation and G6PDH activity and anther H2 O2 levels and antioxidant-related enzymes between genotypes at elevated temperature. Further, anther respiration rate was found to be lower at high temperature in both bean varieties. Overall, our results support the hypothesis that enhanced male reproductive heat tolerance involves changes in the anther oxidative pentose phosphate pathway, which supplies reductants to critical H2 O2 scavenging enzymes.

Supercritical carbon dioxide extracts of small cardamom and yellow mustard seeds have fasting hypoglycaemic effects: diabetic rat, predictive iHOMA2 models and molecular docking study.

In the present investigation, the supercritical carbon dioxide (SC-CO2) extracts of small cardamom (SC) and yellow mustard (YM) seeds have been investigated for their efficacies in combating type 2 diabetes in streptozotocin-induced Wistar albino rats. Fasting blood glucose (FBG) levels in the rats were monitored on days 8, 15 and 21. On day 15, FBG level reduced appreciably by 31·49 % in rats treated with SC seed extract and by 32·28 % in rats treated with YM seed extract, comparable to metformin (30·70 %) and BGR-34 (a commercial polyherbal drug) (31·81 %) administered rats. Either extract exhibited desirable effects on hepatic glucose-6-phosphatase, glucose-6-phosphate dehydrogenase (G6PD) and catalase activities in controlling diabetes. A molecular docking exercise was conducted to identify specific compounds in the extracts which possessed augmenting effect on G6PD. The results revealed that all the bioactive compounds in the extracts have binding affinities with the enzyme and contributed to the antidiabetic efficacies of the extracts as G6PD augmenters. The effects of the extracts on insulin sensitivity and glucose uptake were investigated using non-invasive modelling by iHOMA2 software. This in vitro approach indicated that extract administration resulted in increased both insulin sensitivity of the liver and glucose uptake in the gut. The findings of the present study attest these SC-CO2 extracts of the spices as safe alternatives of metformin and BGR-34 in combating type 2 diabetes and could be safely subjected to clinical studies. These extracts could also be employed in designing proactive food supplements in mitigating the metabolic disorder.

Genetic Factors and Delayed TSB Monitoring and Treatment as Risk Factors Associated with Severe Hyperbilirubinemia in Term Neonates Admitted for Phototherapy.

OBJECTIVES: This study aimed to determine whether maternal-fetal blood group isoimmunization, breastfeeding, birth trauma, age when first total serum bilirubin (TSB) was measured, age of admission, and genetic predispositions to hemolysis [due to genetic variants of glucose-6-phosphate dehydrogenase (G6PD) enzyme], and reduced hepatic uptake and/or conjugation of serum bilirubin [due to genetic variants of solute carrier organic anion transporter protein family member 1B1 (SLCO1B1) and uridine diphosphate glucuronosyltransferase family 1 member A1 (UGT1A1)] were significant risk factors associated with severe neonatal hyperbilirubinemia (SNH, TSB ≥ 342µmol/l) in jaundiced term neonates admitted for phototherapy. METHODS: The inclusion criteria were normal term neonates (gestation ≥ 37 weeks). Parents/care-givers were interviewed to obtain data on demography, clinical problems, feeding practice and age when first TSB was measured. Polymerase chain reaction-restriction fragment length polymorphism method was used to detect common G6PD, UGT1A1 and SLCO1B1 variants on each neonate's dry blood specimens. RESULTS: Of 1121 jaundiced neonates recruited, 232 had SNH. Logistic regression analysis showed that age (in days) when first TSB was measured [adjusted odds ratio (aOR) = 1.395; 95% confidence interval (CI) 1.094-1.779], age (in days) of admission (aOR = 1.127; 95% CI 1.007-1.260) and genetic mutant UGT1A1 promoter A(TA)7TAA (aOR = 4.900; 95% CI 3.103-7.739), UGT1A1 c.686C>A (aOR = 6.095; 95% CI 1.549-23.985), SLCO1B1 c.388G>A (aOR = 1.807; 95% CI 1.242-2.629) and G6PD variants and/or abnormal G6PD screening test (aOR = 2.077; 95% CI 1.025-4.209) were significantly associated with SNH. CONCLUSION: Genetic predisposition, and delayed measuring first TSB and commencing phototherapy increased risk of SNH.

Effects of ribwort plantain (Plantago lanceolata) extract on blood parameters, immune response, antioxidant enzyme activities, and growth performance in rainbow trout (Oncorhynchus mykiss).

In this study, we examined changes occurred in blood parameters, immune responses, antioxidant enzyme activities, and growth performance of rainbow trout (Oncorhynchus mykiss) administered with ribwort plantain (RP) through feed. Fish (mean weight 36.56 ± 1.99 g) were fed a diet supplemented with an aqueous methanolic extract of RP at variable doses, 0 (control), 1 (RP1), 2 (RP2), and 3 g kg-1 (RP3) for 90 days. The final weight, weight gain, and specific growth rate were significantly increased in RP1, RP2, and RP3 treatment groups compared to that of the control. Among examined blood parameters, hemoglobin value in RP1 group (9.77 ± 0.10 g dl-1) only was significantly high on the 30th day of the study. When immune response parameters were evaluated, we observed that oxidative radical production and lysozyme activities were affected positively in experimental groups (P < 0.05). The highest oxidative radical production was determined in fish of RP3 group. Glutathione peroxidase and glucose 6 phosphate dehydrogenase were increased in RP3 group compared to control and other treatment groups. Based on these results, it is concluded that ribwort plantain promotes growth, enhances immune responses and antioxidant enzyme activities in rainbow trout, and therefore, may be used in aquaculture.

Effects of dietary exogenous xylanase supplementation on growth performance, intestinal health, and carbohydrate metabolism of juvenile large yellow croaker, Larimichthys crocea.

An 8-week feeding trial was conducted to evaluate the effects of dietary xylanase supplementation on growth performance, digestive enzyme activity, intestinal morphology parameter, intestinal microbiome diversity, and carbohydrate metabolism for juvenile large yellow croaker (Larimichthys crocea). Four levels of xylanase were added to basal diets (0, 600, 1200, and 1800 U kg-1). The results indicated that fish fed the 1200 U kg-1 xylanase diet had higher weight gain than those fed the 0 and 600 U kg-1 xylanase diet. The highest intestinal folds and microvillous height were observed at fish fed the 1200 U kg-1 xylanase diet. High-throughput sequencing revealed that the majority of reads derived from the large yellow croaker digesta belonged to members of Proteobacteria followed by Chloroflex, Bacteroidetes, Spirochaetae, and Firmicute. Supplementation of xylanase in diets increased the relative abundance of Bacteroides and Gemmatimonadete. The higher hepatic glucokinase (GK) and glucose-6-phosphate dehydrogenase (G6PD) activities were observed in fish fed the xylanase supplementation diet. Accordingly, dietary xylanase supplementation upgraded the relative expressions of gk and g6pd genes in liver. In conclusion, optimum dietary xylanase supplementation (600-1200 U kg-1) could improve the growth performance, optimize the intestinal morphology structure and microbiota constitution, and enhance the ability of carbohydrate utilization of juvenile large yellow croaker.

Discovery of Small-Molecule Activators for Glucose-6-Phosphate Dehydrogenase (G6PD) Using Machine Learning Approaches.

Glucose-6-Phosphate Dehydrogenase (G6PD) is a ubiquitous cytoplasmic enzyme converting glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway (PPP). The G6PD deficiency renders the inability to regenerate glutathione due to lack of Nicotine Adenosine Dinucleotide Phosphate (NADPH) and produces stress conditions that can cause oxidative injury to photoreceptors, retinal cells, and blood barrier function. In this study, we constructed pharmacophore-based models based on the complex of G6PD with compound AG1 (G6PD activator) followed by virtual screening. Fifty-three hit molecules were mapped with core pharmacophore features. We performed molecular descriptor calculation, clustering, and principal component analysis (PCA) to pharmacophore hit molecules and further applied statistical machine learning methods. Optimal performance of pharmacophore modeling and machine learning approaches classified the 53 hits as drug-like (18) and nondrug-like (35) compounds. The drug-like compounds further evaluated our established cheminformatics pipeline (molecular docking and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis). Finally, five lead molecules with different scaffolds were selected by binding energies and in silico ADMET properties. This study proposes that the combination of machine learning methods with traditional structure-based virtual screening can effectively strengthen the ability to find potential G6PD activators used for G6PD deficiency diseases. Moreover, these compounds can be considered as safe agents for further validation studies at the cell level, animal model, and even clinic setting.

Protective role of glutamine against cadmium-induced testicular dysfunction in Wistar rats: Involvement of G6PD activity.

BACKGROUND: Endocrine disruptor such as cadmium has been widely reported to cause testicular toxicity, which contributes to recent decline in male fertility worldwide. Glutamine, the most abundant amino acid in the body has been demonstrated to exert protective effects in cellular toxicity. However, its role in testicular toxicity is unknown. The present study is therefore aimed at investigating the effects of glutamine supplementation on cadmium-induced testicular toxicity, and the possible involvement of glucose-6-phosphate dehydrogenase (G6PD) activity. MATERIALS AND METHOD: Male Wistar rats weighing 160-190 g were allotted into 4 groups (n = 5/group): The groups received vehicle (distilled water; p.o.), glutamine (1gkg-1; p.o.), cadmium chloride (5mgkg-1p.o.) and Cadmium chloride plus glutamine respectively, daily for 30 days. Biochemical and histological analyses were performed with appropriate method. RESULTS: Administration of cadmium significantly decreased body weight, sperm count, motility and viability, as well as altered sperm morphology and progressivity. Cadmium also caused atrophy of the seminiferous tubule in addition to disrupted testicular architecture, lumen, Sertoli cells and spermatogonia. Similarly, serum and testicular aspartate transaminase, and malondialdehyde significantly increased, and G6PD, glutathione, nicotinamide adenine dinucleotide phosphate and nitric oxide significantly decreased with corresponding decrease in follicle stimulating hormone, luteinizing hormone and testosterone in cadmium-treated animals compared with control groups. However, supplementation with glutamine attenuated these alterations. CONCLUSION: The present study demonstrates that cadmium induces testicular dysfunction that is attributable to defective G6PD and accompanied by increased lipid peroxidation and impaired NO-dependent endothelial function. Interestingly, glutamine supplementation ameliorates cadmium-induced testicular dysfunction through enhancement of G6PD activity.

l-glutamine supplementation exerts cardio-renal protection in estrogen-progestin oral contraceptive-treated female rats.

Glycogen and lipid disruptions represent a spectrum of metabolic disorders that are crucial risk factors for cardiovascular disease in estrogen-progestin oral contraceptive (COC) users. l-glutamine (GLN) has been shown to exert a modulatory effect in metabolic disorders-related syndromes. We therefore hypothesized that GLN supplementation would protect against myocardial and renal glycogen-lipid mishandling in COC-treated animals by modulation of Glucose-6-phosphate dehydrogenase (G6PD) and xanthine oxidase (XO) activities. Adult female Wistar rats were randomly allotted into control, GLN, COC and COC + GLN groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLN (1 g/kg), COC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and COC plus GLN respectively, daily for 8 weeks. Data showed that treatment with COC led to metabolically-induced obesity with correspondent increased visceral and epicardial fat mass. It also led to increased plasma, myocardial and renal triglyceride, free fatty acid, malondialdehyde (MDA), XO activity, uric acid content and decreased glutathione content and G6PD activity. In addition, COC increased myocardial but not renal glycogen content, and increased myocardial and renal glycogen synthase activity, increased plasma and renal lactate production and plasma aspartate transaminase/alanine aminotransferase (AST/ALT) ratio. However, these alterations were attenuated when supplemented with GLN except plasma AST/ALT ratio. Collectively, the present results indicate that estrogen-progestin oral contraceptive causes metabolically-induced obesity that is accompanied by differential myocardial and renal metabolic disturbances. The findings also suggest that irrespective of varying metabolic phenotypes, GLN exerts protection against cardio-renal dysmetabolism by modulation of XO and G6PD activities.

Taurine modulates hepatic oxidative status and gut inflammatory markers of European seabass (Dicentrarchus labrax) fed plant feedstuffs-based diets.

This study aimed to evaluate the effect of taurine (tau) supplementation to low fishmeal (FM) diets on growth performance, oxidative status, and immune response of European seabass juveniles. Four isoproteic (46% crude protein) and isolipidic (19% crude lipid) diets were formulated to contain either 25 or 12.5% FM and a mixture of plant feedstuffs, supplemented or not with 1% tau. Twelve groups of 20 fish (IBW = 9.4 g) were fed each diet for 9 weeks. Reduction of dietary FM from 25 to 12.5% impaired growth performance, feed efficiency, and protein efficiency ratio but had no effect on nitrogen retention (% N intake). Independently of FM level, dietary tau supplementation improved growth performance and nitrogen retention without affecting feed efficiency. Dietary FM level reduction increased liver G6PDH activity, but did not affect lipid peroxidation or activities of redox key enzymes. Contrarily, dietary tau supplementation decreased hepatic G6PDH and GPX activities and lipid peroxidation. Gene expression COX-2 was not affected either by FM or tau levels but TNF-α increased with the reduction of FM level but not with the tau level. Dietary tau supplementation decreased Casp3 and Casp9 expression regardless of dietary FM level. Overall, this study evidenced that dietary tau supplementation improved growth performance and antioxidant response and reduced intestine inflammatory and apoptosis processes.

Treatment with myo-inositol attenuates binding of the carbohydrate-responsive element-binding protein to the ChREBP-ß and FASN genes in rat nonalcoholic fatty liver induced by high-fructose diet.

Dietary supplementation with the major lipotrope myo-inositol (MI) potently reduces triglyceride (TG) content and expression levels of the fatty acid synthesis genes, for example, fatty acid synthase (FASN), in rat nonalcoholic fatty liver induced by high-fructose diet. Fatty acid synthesis genes are regulated by the carbohydrate-responsive element-binding protein (ChREBP) that exists in 2 isoforms: ChREBP-α and ChREBP-ß. The gene encoding the latter isoform is more responsive to fructose. Because MI repressed the induction of fatty acid synthesis gene expression by high-fructose diet, we hypothesized that MI may reduce binding of ChREBP to the carbohydrate response elements (ChoREs) in the ChREBP-ß gene as well as in fatty acid synthesis genes in the liver. Rats were fed high-glucose, high-fructose, or high-fructose diets supplemented with MI (0.05% and 0.25%) for 2 weeks. Hepatic TG content and expression levels of the glucose-6-phosphate dehydrogenase, malic enzyme 1, FASN, acetyl-CoA carboxylase alpha, S14, and ChREBP-ß were remarkably elevated in rats fed with high fructose compared with the corresponding levels in high-glucose group. Notably, elevated values of these parameters in high-fructose group were reduced by MI. Similarly, high-fructose-induced ChREBP binding to the ChoREs of the ChREBP-ß and FASN genes was nominally decreased by MI. This study showed that treatment with MI reduced elevated TG content and expression of genes related to fatty acid synthesis, such as FASN and ChREBP-ß, in rat nonalcoholic fatty liver induced by high-fructose diet. Furthermore, MI treatment nominally decreased increased binding of ChREBP to the ChoREs of ChREBP-ß and FASN genes.

Redox status on different regions of the central nervous system of obese and lean rats treated with green tea extract.

OBJECTIVES: The purpose of this study was to evaluate some indicators of redox status, and inflammation on different regions of the central nervous system (CNS) of obese rats treated with green tea (GT). We hypothesized that obesity could affect the redox balance in different brain regions due to the diverse nature of the cells as well as the selective neuronal vulnerability to oxidative stress, and GT could triggers benefits effects restoring the redox status. METHODS: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight) and obesity was induced by cafeteria diet (8 weeks). After this period, the animals were killed and brain tissue (cerebral cortex, cerebellum, and brainstem) was removed to evaluate oxidative stress and inflammation (cytokine release). RESULTS: We showed that the cafeteria diet had little effect on redox balance in the cerebral cortex and cerebellum; however, the brainstem was the region of the CNS most sensitive to cafeteria diet-induced redox unbalance. GFAP expression was increased in the cerebral cortex of obese rats and reduced by GT. It was also evident that GT treatment had numerous beneficial effects against oxidative damage to biomolecules in all brain regions analyzed. DISCUSSION: Our study established that different CNS regions show selective neuronal vulnerability when exposed to a diet enriched with fats and sugars, and the beneficial effect of GT was similar among these regions. We conclude that GT could be a good strategy for improving and maintaining brain function under healthy and pathological conditions.

Identification of Genetic Risk Factors for Neonatal Hyperbilirubinemia in Fujian Province, Southeastern China: A Case-Control Study.

To date, the genetic risk factors for neonatal hyperbilirubinemia remain unknown in Southeastern China. This case-control study aimed to identify the genetic risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China. A total of 286 hyperbilirubinemic newborns were enrolled as a case group, and 250 randomly selected newborns without jaundice or with a bilirubin level that was lower than the threshold required for phototherapy served as controls. The serum levels of total bilirubin, unconjugated bilirubin, and direct bilirubin were measured, and the common genetic loci in UGT1A1, OATP1B1, and HO-1 genes were genotyped. Higher incidence of ABO incompatibility and G6PD deficiency was detected in the case group compared to the control group (P < 0.01). There were significant differences in the frequencies of rs4148323 and rs1805173 genotypes between the case and control groups (P < 0.05). At the rs4148323 locus, the frequencies of GA heterozygotes and AA mutant homozygotes were higher in the case group than in the control group (P < 0.05), and at the rs1805173 locus, the frequencies of LS, MS, and SS genotypes were higher in the case group than in the control group (P < 0.05). A higher frequency of rs4148323 A allele and rs1805173 S allele was detected in the case group compared to the control group (P = 0). Additionally, multivariate logistic regression analysis identified that the mutant genotype of rs4148323 in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and SS genotype at rs1805173 locus of the HO-1 gene were genetic risk factors of neonatal hyperbilirubinemia. Our data demonstrate that G211 mutation in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and the SS genotype of the repeats in the promoter region of the HO-1 gene are risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China.

Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the Canton mutant and several other common G6PD mutants. AG1 reduces oxidative stress in cells and zebrafish. Furthermore, AG1 decreases chloroquine- or diamide-induced oxidative stress in human erythrocytes. Our study suggests that a pharmacological agent, of which AG1 may be a lead, will likely alleviate the challenges associated with G6PD deficiency.

Effect of partial dietary replacement of fishmeal by yellow mealworm (Tenebrio molitor) larvae meal on the innate immune response and intestinal antioxidant enzymes of rainbow trout (Oncorhynchus mykiss).

The present study investigated the effects of 25 and 50% dietary inclusion of yellow mealworm, Tenebrio molitor (TM), larvae on the intestinal antioxidant enzymes, lipid peroxidation and immune system of rainbow trout, Oncorhynchus mykiss. Fish were fed for 90 days with a control diet (TM0) or with 2 test diets (TM25 and TM50) where 35 and 67% of the fishmeal was replaced by TM larvae meal respectively. At the end of the growth trial, humoral immune parameters were assessed in the sera of the fish and the activities of antioxidant enzymes were measured in intestine homogenates. The present results show a strong increase of the activity of the antioxidant intestinal enzymes and reduction of lipid peroxidation. Increased trypsin inhibition and faster antibacterial activity of the serum were also detected. These evidences could be due to the physiological similarities between the exoskeleton of parasites and insects. The present findings reinforce the previous results which revealed a positive effect of the dietary TM on rainbow trout growth and further confirm its adequacy for fishmeal partial replacement in aquafeed.

Global gene expression analysis in liver of db/db mice treated with catalpol.

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg-1), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg-1) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP+), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.

DHEA Treatment Effects on Redox Environment in Skeletal Muscle of Young and Aged Healthy Rats.

BACKGROUND: Dehydroepiandrosterone (DHEA) is an important precursor of active steroid hormone, produced abundantly by the adrenal cortex with an age-dependent pattern. OBJECTIVE: We investigated whether chronic DHEA administration impacts on redox status and on Akt protein activation in skeletal muscle during the aging process (3 and 24 months-old rats). METHODS: Rats received one weekly dose/5 weeks of DHEA (10 mg/kg) or vehicle. Gastrocnemius muscle was removed to evaluate glutathione system, hydrogen peroxide, antioxidant enzymes, and expression of Akt kinase protein. RESULTS: In the 3-months-old rats DHEA induced an increase in hydrogen peroxide when compared both to its control (276%) and the 24-months-old DHEA group (485%). Moreover, in the 24- months-old rats DHEA caused an increase in GSSG (41 and 28%), a decrease in reduced-GSH (55 and 51%), and a more oxidized redox status (reduction in GSH/GSSG ratio, 47 and 65 %) when compared to 3-month-old DHEA and to 24-months-old control groups, respectively. Both older groups had increased G6PDH (2.7 fold) and GST (1.7 fold) activities when compared to younger groups, independently of any DHEA treatment. However, there was no modulation of Akt protein (phosphorylated/total isoform). CONCLUSION: The results show that chronic DHEA administration to 3 and 24-months-old rats may not present positive effects regarding the redox environment in skeletal muscle without modulation of pro-survival Akt kinase. Due to the large-scale self-administration of DHEA as an "anti-aging" dietary supplement, it is crucial to investigate its molecular mechanisms over oxidative stressinduced related diseases.