Gut Microbiome-Serum Metabolism Revealed the Allergenicity of Ferulic Acid Combined with Glucose-Modified ß-Lactoglobulin.

A novel strategy combining ferulic acid and glucose was proposed to reduce ß-lactoglobulin (BLG) allergenicity and investigate whether the reduction in allergenicity was associated with gut microbiome and serum metabolism. As a result, the multistructure of BLG changed, and the modified BLG decreased significantly the contents of IgE, IgG, IgG1, and mMCP-1 in serum, improved the diversity and structural composition of gut microbiota, and increased the content of short-chain fatty acids (SCFAs) in allergic mice. Meanwhile, allergic mice induced by BLG affected arachidonic acid, tryptophan, and other metabolic pathways in serum, the modified BLG inhibited the production of metabolites in arachidonic acid metabolism pathway and significantly increased tryptophan metabolites, and this contribution helps in reducing BLG allergenicity. Overall, reduced allergenicity of BLG after ferulic acid was combined with glucose modification by regulating gut microbiota, the metabolic pathways of arachidonic acid and tryptophan. The results may offer new thoughts alleviating the allergy risk of allergenic proteins.

Rheology, physicochemical properties, and microstructure of fish gelatin emulsion gel modified by γ-polyglutamic acid.

In this work, the effect of the addition of γ-polyglutamic acid (γ-PGA) on the rheology, physicochemical properties, and microstructure of fish gelatin (FG) emulsion gel was investigated. Samples of the emulsion gel were evaluated for rheological behavior and stability prior to gelation. The mechanical properties and water-holding capacity (WHC) of the emulsion were determined after gelation. The microstructure of the emulsion gel was further examined using confocal laser scanning microscopy (CLSM). The results indicated a gradual increase in the apparent viscosity and gelation temperature of the emulsion at a higher concentration of γ-PGA. Additionally, frequency scan results revealed that on the addition of γ-PGA, FG emulsion exhibited a stronger structure. The emulsion containing 0.1% γ-PGA exhibited higher stability than that of the control samples. The WHC and gel strength of the emulsion gel increased on increasing the γ-PGA concentration. CLSM images showed that the addition of γ-PGA modified the structure of the emulsion gel, and the droplets containing 0.1% γ-PGA were evenly distributed. Moreover, γ-PGA could regulate the droplet size of the FG emulsion and its size distribution. These findings suggest that the viscoelasticity and structure of FG emulsion gels could be regulated by adjusting the γ-PGA concentration. The γ-PGA-modified FG emulsion gel also exhibited improved rheology and physicochemical properties. The results showed that γ-PGA-modified FG emulsion gel may find potential applications in food, medicine, cosmetics, and other industries.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

Modification of ibuprofen to improve the medicinal effect; structural, biological, and toxicological study.

Ibuprofen is classified as a non-steroidal anti-inflammatory drug (NSAID) that is employed as an initial treatment option for its non-steroidal anti-inflammatory, pain-relieving, and antipyretic properties. However, Ibuprofen is linked to specific well-known gastrointestinal adverse effects like ulceration and gastrointestinal bleeding. It has been linked to harmful effects on the liver, kidney, and heart. The purpose of the study is to create novel and potential IBU analogue with reduced side effects with the enhancement of their medicinal effects, so as to advance the overall safety profile of the drug. The addition of some novel functional groups including CH3, F, CF3, OCF3, Cl, and OH at various locations in its core structure suggestively boost the chemical as well as biological action. The properties of these newly designed structures were analyzed through chemical, physical, and spectral calculations using Density Functional Theory (DFT) and time-dependent DFT through B3LYP/6-31 g (d,p) basis set for geometry optimization. Molecular docking and non-bonding interaction studies were conducted by means of the human prostaglandin synthase protein (PDB ID: 5F19) to predict binding affinity, interaction patterns, and the stability of the protein-drug complex. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and PASS (Prediction of Activity Spectra for Substances) predictions were employed to evaluate the pharmacokinetic and toxicological properties of these structures. Importantly, most of the analogues displayed reduced hepatotoxicity, nephrotoxicity, and carcinogenicity in comparison to the original drug. Moreover, molecular docking analyses indicated improved medicinal outcomes, which were further supported by pharmacokinetic calculations. Together, these findings suggest that the modified structures have reduced adverse effects along with improved therapeutic action compared to the parent drug.

Transcriptome analysis of the cerebral cortex of acrylamide-exposed wild-type and IL-1ß-knockout mice.

Acrylamide is an environmental electrophile that has been produced in large amounts for many years. There is concern about the adverse health effects of acrylamide exposure due to its widespread industrial use and also presence in commonly consumed foods and others. IL-1ß is a key cytokine that protects the brain from inflammatory insults, but its role in acrylamide-induced neurotoxicity remains unknown. We reported recently that deletion of IL-1ß gene exacerbates ACR-induced neurotoxicity in mice. The aim of this study was to identify genes or signaling pathway(s) involved in enhancement of ACR-induced neurotoxicity by IL-1ß gene deletion or ACR-induced neurotoxicity to generate a hypothesis mechanism explaining ACR-induced neurotoxicity. C57BL/6 J wild-type and IL-1ß KO mice were exposed to ACR at 0, 12.5, 25 mg/kg by oral gavage for 7 days/week for 4 weeks, followed by extraction of mRNA from mice cerebral cortex for RNA sequence analysis. IL-1ß deletion altered the expression of genes involved in extracellular region, including upregulation of PFN1 gene related to amyotrophic lateral sclerosis and increased the expression of the opposite strand of IL-1ß. Acrylamide exposure enhanced mitochondria oxidative phosphorylation, synapse and ribosome pathways, and activated various pathways of different neurodegenerative diseases, such as Alzheimer disease, Parkinson disease, Huntington disease, and prion disease. Protein network analysis suggested the involvement of different proteins in related to learning and cognitive function, such as Egr1, Egr2, Fos, Nr4a1, and Btg2. Our results identified possible pathways involved in IL-1ß deletion-potentiated and ACR-induced neurotoxicity in mice.

Simulated in vitro gastrointestinal digestion of ß-lactoglobulin treated by ultrasound: Detection of peptides profile and the antioxidant activity.

The influence of ultrasonic pretreatment on the release and antioxidant activity of potential antioxidant peptides after in-vitro simulated gastrointestinal digestion of ß-lactoglobulin (BLG) were measured by HPLC-MS/MS, chemical and cellular-based assays. The gastrointestinal digest was fractionated into four fractions by Sephadex G-25 gel filtration column, and fractions showed a considerable ABTS·+ scavenging ability. The fraction with the strongest antioxidant activity was produced by ultrasonicated BLG after gastrointestinal digestion, which relies on ultrasonic-promoted proteolysis to produce many small-molecule antioxidant peptides. The best active fraction has better cellular antioxidant activity and protection of H2O2-induced oxidative HepG2 cell model, which significantly increases the activities of antioxidant enzyme, and is concentration-dependent. HPLC-MS/MS analysis showed that there were more potential antioxidant peptides in the best active fraction. This research will provide a basis for the further application of ultrasonic in dairy products, which can promote the release of more potential antioxidant peptides-derived from gastrointestinal digestion.

Mechanism of the Allergenicity Reduction of Ovalbumin by Microwave Pretreatment-Assisted Enzymolysis through Biological Mass Spectrometry.

Ovalbumin (OVA) is a major allergen in hen eggs. Enzymolysis has been demonstrated as an efficient method for reducing OVA allergenicity. This study demonstrates that microwave pretreatment (MP) at 400 W for 20 s assisting bromelain enzymolysis further decreases the allergenicity of OVA, which was attributed to the increase in the degree of hydrolysis and promoted the destruction of IgE-binding epitopes. The results showed that MP could promote OVA unfolding, expose hydrophobic domains, and disrupt tightly packed α-helical structures and disulfide bonds, which increased the degree of hydrolysis by 7.28% and the contents of peptides below 1 kDa from 43.55 to 85.06% in hydrolysates compared with that for untreated OVA. Biological mass spectrometry demonstrated that the number of intact IgE-binding epitope peptides in MP-assisted OVA hydrolysates decreased by 533 compared to that in hydrolysis without MP; consequently, their IgG/IgE binding rates decreased more significantly. Therefore, MP-assisted enzymolysis may provide an alternative method for decreasing the OVA allergenicity.

Liposomes encapsulation by pH driven improves the stability, bioaccessibility and bioavailability of urolithin A: A comparative study.

Urolithin A (UroA) is gut metabolites of ellagitannins possessing a vast range of biological activities, but its poor water solubility and low bioavailability hinder its potential applications. This study utilized the pH dependent dissolution characteristics of UroA and employed a simple pH-driven method to load UroA into liposomes. The characterization and stability of obtained liposomes under different conditions were evaluated, and their oral bioavailability was tested by pharmacokinetics, and compared with UroA liposomes prepared using traditional thin film dispersion (TFM-ULs). Results indicated that liposomes could effectively encapsulate UroA. The UroA liposomes prepared by the pH-driven method (PDM-ULs) showed lower particle size, polydispersity index, zeta potential, and higher encapsulation efficiency than TFM-ULs. Interestingly, better thermal stability, storage stability, in vitro digestion stability, and higher bioaccessibility were also found on PDM-ULs. Moreover, pharmacokinetic experiments in rats demonstrated that PDM-ULs could significantly improve the bioavailability of UroA, with an absorption efficiency 1.91 times that of TFM-ULs. Therefore, our findings suggest that liposomes prepared by pH-driven methods have great potential in improving the stability and bioavailability of UroA.

Deletion of IL-1ß exacerbates acrylamide-induced neurotoxicity in mice.

Acrylamide is a neurotoxicant in human and experimental animals. Interleukin-1ß (IL-1ß) is a proinflammatory cytokine known as a critical component of brain reaction to any insult or neurodegenerative pathologies, though its role in electrophile-induced neurotoxicity remains elusive. The aim of this study was to investigate the role of IL-1ß in acrylamide-induced neurotoxicity in mice. Ten-week-old male wild-type and IL-1ß knock-out mice were allocated into 3 groups each and exposed to acrylamide at 0, 12.5, 25 mg/kg body weight by oral gavage for 28 days. Compared with wild-type mice, the results showed a significant increase in landing foot spread test and a significant decrease in density of cortical noradrenergic axons in IL-1ß KO mice exposed to acrylamide at 25 mg/kg body weight. Exposure to acrylamide at 25 mg/kg significantly increased cortical gene expression of Gclc, Gpx1, and Gpx4 in wild-type mice but decreased them in IL-1ß KO mice. The same exposure level significantly increased total glutathione and oxidized glutathione (GSSG) in the cerebellum of wild-type mice but neither changed total glutathione nor decreased GSSG in the cerebellum of IL-1ß KO mice. The basal level of malondialdehyde in the cerebellum was higher in IL-1ß KO mice than in wild-type mice. The results suggest that IL-1ß protects the mouse brain against acrylamide-induced neurotoxicity, probably through suppression of oxidative stress by glutathione synthesis and peroxidation. This unexpected result provides new insight on the protective role of IL-1ß in acrylamide-induced neurotoxicity.

Role of Nrf2 in 1,2-dichloropropane-induced cell proliferation and DNA damage in the mouse liver.

1,2-Dichloropropane (1,2-DCP) is recognized as the causative chemical of occupational cholangiocarcinoma in printing workers in Japan. However, the cellular and molecular mechanisms of 1,2-DCP-induced carcinogenesis remains elusive. The present study investigated cellular proliferation, DNA damage, apoptosis, and expression of antioxidant and proinflammatory genes in the liver of mice exposed daily to 1,2-DCP for 5 weeks, and the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in these responses. Wild-type and Nrf2-knockout (Nrf2-/-) mice were administered 1,2-DCP by gastric gavage, and then the livers were collected for analysis. Immunohistochemistry for BrdU or Ki67 and TUNEL assay revealed that exposure to 1,2-DCP dose-dependently increased proliferative cholangiocytes, whereas decreased apoptotic cholangiocytes in wild-type mice but not in Nrf2-/- mice. Western blot and quantitative real-time PCR showed that exposure to 1,2-DCP increased the levels of DNA double-strand break marker γ-H2AX and mRNA expression levels of NQO1, xCT, GSTM1, and G6PD in the livers of wild-type mice in a dose-dependent manner, but no such changes were noted in Nrf2-/- mice. 1,2-DCP increased glutathione levels in the liver of both the wild-type and Nrf2-/- mice, suggesting that an Nrf2-independent mechanism contributes to 1,2-DCP-induced increase in glutathione level. In conclusion, the study demonstrated that exposure to 1,2-DCP induced proliferation but reduced apoptosis in cholangiocytes, and induced double-strand DNA breaks and upregulation of antioxidant genes in the liver in an Nrf2-dependent manner. The study suggests a role of Nrf2 in 1,2-DCP-induced cell proliferation, antiapoptotic effect, and DNA damage, which are recognized as key characteristics of carcinogens.

Exposure to Benzo[a]pyrene Decreases Noradrenergic and Serotonergic Axons in Hippocampus of Mouse Brain.

Epidemiological studies showed the association between air pollution and dementia. A soluble fraction of particulate matters including polycyclic aromatic hydrocarbons (PAHs) is suspected to be involved with the adverse effects of air pollution on the central nervous system of humans. It is also reported that exposure to benzopyrene (B[a]P), which is one of the PAHs, caused deterioration of neurobehavioral performance in workers. The present study investigated the effect of B[a]P on noradrenergic and serotonergic axons in mouse brains. In total, 48 wild-type male mice (10 weeks of age) were allocated into 4 groups and exposed to B[a]P at 0, 2.88, 8.67 or 26.00 µg/mice, which is approximately equivalent to 0.12, 0.37 and 1.12 mg/kg bw, respectively, by pharyngeal aspiration once/week for 4 weeks. The density of noradrenergic and serotonergic axons was evaluated by immunohistochemistry in the hippocampal CA1 and CA3 areas. Exposure to B[a]P at 2.88 µg/mice or more decreased the density of noradrenergic or serotonergic axons in the CA1 area and the density of noradrenergic axons in the CA3 area in the hippocampus of mice. Furthermore, exposure to B[a]P dose-dependently upregulated Tnfα at 8.67 µg/mice or more, as well as upregulating Il-1ß at 26 µg/mice, Il-18 at 2.88 and 26 µg/mice and Nlrp3 at 2.88 µg/mice. The results demonstrate that exposure to B[a]P induces degeneration of noradrenergic or serotonergic axons and suggest the involvement of proinflammatory or inflammation-related genes with B[a]P-induced neurodegeneration.

Methionine restriction constrains lipoylation and activates mitochondria for nitrogenic synthesis of amino acids.

Methionine restriction (MR) provides metabolic benefits in many organisms. However, mechanisms underlying the MR-induced effect remain incompletely understood. Here, we show in the budding yeast S. cerevisiae that MR relays a signal of S-adenosylmethionine (SAM) deprivation to adapt bioenergetic mitochondria to nitrogenic anabolism. In particular, decreases in cellular SAM constrain lipoate metabolism and protein lipoylation required for the operation of the tricarboxylic acid (TCA) cycle in the mitochondria, leading to incomplete glucose oxidation with an exit of acetyl-CoA and α-ketoglutarate from the TCA cycle to the syntheses of amino acids, such as arginine and leucine. This mitochondrial response achieves a trade-off between energy metabolism and nitrogenic anabolism, which serves as an effector mechanism promoting cell survival under MR.

Ultrasonic treatment regulates the properties of gelatin emulsion to obtain high-quality gelatin film.

Gelatin emulsion was an important process for preparing gelatin films. A gelatin film with water resistance and ductility could be prepared using gelatin emulsion, whereas the prepared gelatin film has several defects (e.g., low tensile strength and poor thermal stability). This study aimed to modify gelatin emulsion through ultrasonic treatment, then gelatin film was prepared by the modified gelatin emulsion. The results showed that: under the condition of ultrasonic treatment for 12 min at 400 w, zeta potential and viscosity of gelatin emulsion were the largest; thickness, water vapor permeability (WVP) and water solubility (WS) of corresponding gelatin film were the lowest, and the tensile strength (TS), elongation at break (EAB), denaturation temperature (Tm) and enthalpy value (ΔH) of corresponding gelatin film were the highest. The above result suggested that ultrasonic treatment can be used to prepare a gelatin film with better quality by regulating the properties of gelatin emulsion, and a certain correlation was found between the properties of gelatin emulsion and the properties of gelatin film.

A comparative study on the allergenic potential of ß-lactoglobulin conjugated to glucose, caffeic acid and caffeoyl glucopyranose.

This work intends to perform a comparative study on the allergenic potential of ß-lactoglobulin (BLG)-glucose, BLG-caffeic acid and BLG-caffeoyl glucopyranose conjugates. The modifications changed the molecular weight and multi-structure of BLG and destroyed the allergenic epitope, which resulted in a decrease in the IgE binding level and the release ability of histamine and IL-6 in KU812 cells. Compared with BLG, the conjugates reduced the serum levels of IgG, IgE, ß-Hex and IL-4 in vivo, while increasing the level of interferon-γ, which caused an imbalance of Th1/Th2 immune response. Meanwhile, these conjugates not only increased the relative abundance of allergy-related gut flora, such as Lachnospiraceae, norank_o_Clostridia_UCG-014, Erysipelotrichaceae, Turicibacter and Lachnospiraceae_NK4A136_group, but also improved the level of short-chain fatty acids (SCFAs). Caffeoyl glucopyranose with a large molecular weight and long carbon chains exerted a great influence on the allergy-related gut flora and SCFAs. Therefore, the changes in the Th1/Th2 balance and SCFA level produced by the allergy-related gut flora were responsible for reducing the potential allergy of BLG.

Hypoglycemic and H2O2-induced oxidative injury protective effects and the phytochemical profiles of the ethyl acetate fraction from Radix Paeoniae Alba.

Radix Paeonia Alba (RPA) is often used as food and medicine. This study aimed to enrich and identify the antioxidant and hypoglycemic bioactive compounds from RPA. The results indicated that the ethyl acetate fraction (EAF) showed the highest total phenolic content, DPPH, ABTS+ scavenging ability, and α-glucosidase inhibition ability (IC50 = 7.27 µg/ml). The EAF could alleviate H2O2-induced oxidative stress in HepG2 cells by decreasing the MDA and ROS levels, improving cell apoptosis, increasing the enzyme activity of GPX-Px, CAT, SOD, Na+/K+-ATP, and Ca2+/Mg2+-ATP, and stimulating T-AOC expression, which also enhanced the glucose uptake of insulin-resistant HepG2 cells. In addition, the EAF significantly reduced the fasting blood glucose level and improved glucose tolerance in diabetic mice. An HPLC-QTOF-MS/MS analysis displayed that procyanidin, digallic acid isomer, methyl gallate, tetragalloylglucose isomer, dimethyl gallic acid, and paeoniflorin were the major compounds in the EAF. These findings are meaningful for the application of the EAF in the medicinal or food industry to prevent and treat oxidative stress and diabetes mellitus.

Mitigation of Paeoniae Radix Alba extracts on H2O2-induced oxidative damage in HepG2 cells and hyperglycemia in zebrafish, and identification of phytochemical constituents.

Paeoniae Radix Alba (PRA), as a Traditional Chinese Medicine, is widely used in Chinese cuisine due to high health-benefits and nutrition, but the effect of different polarity of solvents on the extraction of antioxidant and hypoglycemic constituents, as well as the major active compounds remain unclear. In this research, 40, 70, and 95% ethanol were firstly applied to extract the polyphenols from PRA, the extraction yields, total phenolics, and total flavonoids content, free radical scavenging ability, α-glucosidase inhibition ability, and anti-glycation ability of extracts were evaluated spectroscopically. The oxidative damage protection, hypoglycemic activity, and alleviation on peripheral nerve damage were evaluated by H2O2-induced HepG2 cells and hyperglycemic zebrafish models. UPLC-QTOF-MS/MS was used to identify the major chemical constituents. The results showed that 40, 70, and 95% ethanol exhibited insignificant difference on the extraction of phenolics and flavonoids from PRA. All extracts showed promising DPPH⋅ and ABTS⋅+ scavenging ability, α-glucosidase inhibition and anti-glycation ability. In addition, PRA extracts could restore the survival rate of HepG2 cells induced by H2O2, and alleviate the oxidative stress by reducing the content of MDA and increasing the levels of SOD, CAT, and GSH-Px. The 70% ethanol extract could also mitigate the blood glucose level and peripheral motor nerve damage of hyperglycemic zebrafish. Thirty-five compounds were identified from 70% ethanol extract, gallotannins, gallic acid and its derivatives, and paeoniflorin and its derivatives were the dominant bioactive compounds. Above results could provide important information for the value-added application of PRA in functional food and medicinal industry.

Molecular structure, IgE binding capacity and gut microbiota of ovalbumin conjugated to fructose and galactose:A comparative study.

Ovalbumin (OVA) was modified by fructose (Fru) and galactose (Gal) to study the structure, IgG/IgE binding capacity and effects on human intestinal microbiota of the conjugated products. Compared with OVA-Fru, OVA-Gal has a lower IgG/IgE binding capacity. The reduction of OVA is not only associated with the glycation of R84, K92, K206, K263, K322 and R381 in the linear epitopes, but also with conformational epitope changes, manifested as secondary and tertiary structural changes caused by Gal glycation. In addition, OVA-Gal could alter the structure and abundance of gut microbiota at phylum, family, and genus levels and restore the abundance of bacteria associated with allergenicity, such as Barnesiella, Christensenellaceae_R-7_group, and Collinsela, thereby reducing allergic reactions. These results indicate that OVA-Gal glycation can reduce the IgE binding capacity of OVA and change the structure of human intestinal microbiota. Therefore, Gal glycation may be a potential method to reduce protein allergenicity.

Extraction optimization and identification of four advanced glycation-end products inhibitors from lotus leaves and interaction mechanism analysis.

Previous research indicated lotus leaves extract could effectively inhibit advanced glycation end-products (AGEs) formation, but the optimal extraction condition, bio-active compounds and interaction mechanism remain unclear. The current study was designed to optimize the extraction parameters of AGEs inhibitors from lotus leaves by bio-activity-guided approach. The bio-active compounds were enriched and identified, the interaction mechanisms of inhibitors with ovalbumin (OVA) were investigated by fluorescence spectroscopy and molecular docking. The optimum extraction parameters were solid-liquid ratio of 1:30, ethanol concentration of 70 %, ultrasonic time of 40 min, temperature of 50 °C, and power of 400 W. Isoquercitrin, hyperoside, astragalin, and trifolin were identified from the 80 % ethanol fraction of lotus leaves (80HY). Hyperoside and isoquercitrin were dominant AGEs inhibitors and accounted for 55.97 % of 80HY. Isoquercitrin, hyperoside, trifolin interacted with OVA via the same mechanism, hyperoside exhibited the strongest affinity, trifolin caused the most conformational changes.

The mechanism of low-level arsenic exposure-induced hypertension: Inhibition of the activity of the angiotensin-converting enzyme 2.

It is now well-established that arsenic exposure induces hypertension in humans. Although arsenic-induced hypertension is reported in many epidemiological studies, the underlying molecular mechanism of arsenic-induced hypertension is not fully characterized. In the human body, blood pressure is primarily regulated by a well-known physiological system known as the renin-angiotensin system (RAS). Hence, we explored the potential molecular mechanisms of arsenic-induced hypertension by investigating the regulatory roles of the RAS. Adult C57BL/6JJcl male mice were divided into four groups according to the concentration of arsenic in drinking water (0, 8, 80, and 800 ppb) provided for 8 weeks. Arsenic significantly raised blood pressure in arsenic-exposed mice compared to the control group, and significantly raised plasma MDA and Ang II and reduced Ang (1-7) levels. RT-PCR results showed that arsenic significantly downregulated ACE2 and MasR in mice aortas. In vitro studies of endothelial HUVEC cells treated with arsenic showed increased level of MDA and Ang II and lower levels of Ang (1-7), compared with the control. Arsenic significantly downregulated ACE2 and MasR expression, as well as those of Sp1 and SIRT1; transcriptional activators of ACE2, in HUVECs. Arsenic also upregulated markers of endothelial dysfunction (MCP-1, ICAM-1) and inflammatory cytokines (IL-6, TNF-α) in HUVECs. Our findings suggest that arsenic-induced hypertension is mediated, at least in part, by oxidative stress-mediated inhibition of ACE2 as well as by suppressing the vasoprotective axes of RAS, in addition to the activation of the classical axis.

Co-60 gamma irradiation induced ovalbumin-glucose glycation and allergenicity reduction revealed by high-resolution mass spectrometry and ELISA assay.

Ovalbumin (OVA)-glucose mixture was treated with Co-60 irradiation at 0-25 kGy, and effects of irradiation on the glycation and allergenicity of OVA were investigated. Irradiation induced glycation between OVA and glucose, reflected in the significant increase of glycation sites from 3 to 14. Interestingly, OVA irradiated at 25 kGy had three new glycated peptides (568.782+, 739.382+ and 509.752+). The degree of substitution per peptide molecule (DSP) of glycated peptides exhibited different trends with increasing irradiation dose. Particularly, glycated peptides 17-26, 55-60, 263-267 and 368-375 showed markedly decreased DSP values after irradiation at 20 and 25 kGy, which could be caused by the generation of Maillard reaction products (MRPs). MS/MS spectra suggested that neutral loss occurred in glycated arginine, whose structure was similar to MRPs. The IgG- and IgE-binding abilities of OVA significantly decreased with increasing irradiation dose, indicating that the protein allergenicity was reduced.