Transport of Dietary Anti-Inflammatory Peptide, γ-Glutamyl Valine (γ-EV), across the Intestinal Caco-2 Monolayer

The present study analyzed the transepithelial transport of the dietary anti-inflammatory peptide, γ-glutamyl valine (γ-EV). γ-EV is naturally found in dry edible beans. Our previous study demonstrated the anti-inflammatory potency of γ-EV against vascular inflammation at a concentration of 1mM, and that it can transport with the apparent permeability coefficient (P_app) of 1.56 × 10⁻⁶ ± 0.7 × 10⁻⁶ cm/s across the intestinal Caco-2 cells. The purpose of the current study was to explore whether the permeability of the peptide could be enhanced and to elucidate the mechanism of transport of γ-EV across Caco-2 cells. The initial results indicated that γ-EV was nontoxic to the Caco-2 cells up to 5 mM concentration and could be transported across the intestinal cells intact. During apical-to-basolateral transport, a higher peptide dose (5 mM) significantly (p < 0.01) enhanced the transport rate to 2.5 × 10⁻⁶ ± 0.6 × 10⁻⁶ cm/s. Cytochalasin-D disintegrated the tight-junction proteins of the Caco-2 monolayer and increased the P_app of γ-EV to 4.36 × 10⁻⁶ ± 0.16 × 10⁻⁶ cm/s (p < 0.001), while theaflavin 3′-gallate and Gly-Sar significantly decreased the P_app (p < 0.05), with wortmannin having no effects on the peptide transport, indicating that the transport route of γ-EV could be via both PepT1-mediated and paracellular.     

Pancreatic β Cells Inhibit Glucagon Secretion from α Cells: An In Vitro Demonstration of α–β Cell Interaction

Interactions between endocrine α and β cells are critical to their secretory function in vivo. The interactions are highly regulated, although yet to be fully understood. In this study, we aim to assess the impact of α and β cell co-culture on hormone secretion. Mouse clonal cell lines α-TC6-1 (α cell line) and MIN-6 (β cell line) were cultured independently or in combination in a medium containing 5.5, 11.1, or 25 mM glucose, respectively. After 72 h, hormone release was measured using insulin and glucagon secretion assays, the cell distribution was visualized by inverted microscopy and an immunocytochemistry assay, and changes in gene expressions were assessed using the RT-PCR technique. The co-culture of the two cell lines caused a decrease in glucagon secretion from α-TC1-6 cells, while no effect on insulin secretion from MIN-6 cells was revealed. Both types of cells were randomly scattered throughout the culture flask, unlike in mice islets in vivo where β cells cluster in the core and α cells are localized at the periphery. During the α–β cell co-culture, the gene expression of glucagon (Gcg) decreased significantly. We conclude that islet β cells suppress glucagon secretion from α cells, apparently via direct cell-to-cell contact, of which the molecular mechanism needs further verification.     

α-Viniferin and ε-Viniferin Inhibited TGF-β1-Induced Epithelial-Mesenchymal Transition,Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression

Resveratrol has well-known anticancer properties; however, its oligomers, including α-viniferin, ε-viniferin, and kobophenol A, have not yet been well investigated. This is the first study examining the anti-epithelial-mesenchymal transition (EMT) effects of α-viniferin and ε-viniferin on A549, NCI-H460, NCI-H520, MCF-7, HOS, and U2OS cells. The results showed that α-viniferin and ε-viniferin significantly inhibited EMT, invasion and migration in TGF-β1- or IL-1β-induced non-small cell lung cancer. α-Viniferin and ε-viniferin also reversed TGF-β1-induced reactive oxygen species (ROS), MMP2, vimentin, Zeb1, Snail, p-SMAD2, p-SMAD3, and ABCG2 expression in A549 cells. Furthermore, ε-viniferin was found to significantly inhibit lung metastasis in A549 cell xenograft metastatic mouse models. In view of these findings, α-viniferin and ε-viniferin may play an important role in the prevention of EMT and cancer metastasis in lung cancer.     

Uptake of intact TPGS (d-alpha-tocopheryl polyethylene glycol 1000 succinate) a water-miscible form of vitamin E by human cells in vitro

The mechanism by which TPGS (alpha-tocopheryl succinate esterified to polyethylene glycol 1000 [PEG 1000]) delivers tocopherol (vitamin E) was studied in human fibroblasts and erythrocytes and a human intestinal cell line, Caco-2. The total cellular tocopherol content of saponified samples of fibroblasts or Caco-2 incubated for 4 h with TPGS (4 mumol/L) increased 10-fold without an increase in the free tocopherol content of nonsaponified samples. A 24-h incubation resulted in a free tocopherol content of approximately 20%, suggesting that intracellular hydrolysis of ester bonds had occurred. The increase in total tocopherol content after a 4-h incubation with TPGS was temperature dependent; no change was measurable at 4 degrees C. Addition of metabolic inhibitors during incubation with TPGS at 37 degrees C did not prevent the increase. [14C]TPGS (synthesized from [14C]PEG 1000) was taken up by Caco-2 cells but [14C]PEG 1000 was not. The intracellular total tocopherol (pmol) equaled the [14C]TPGS (pmol), unequivocally demonstrating uptake of the intact TPGS molecule.     

β-Carotene Status Is Associated with Inflammation and Two Components of Metabolic Syndrome in Patients with and without Osteoarthritis

This study was conducted to investigate the β-carotene status in osteoarthritis (OA) patients and examine its relationships with the risk of inflammation and metabolic syndrome. OA patients were stratified by obesity based on body fat percentage (obese OA, n = 44; non-obese OA, n = 56), and sixty-nine subjects without OA or obesity were assigned as a non-obese control group. β-carotene, metabolic parameters, and inflammation status were assessed. Obese OA patients exhibited a significantly higher rate of metabolic syndrome (p = 0.02), abdominal obesity (p < 0.01), and lower β-carotene status (p < 0.01) compared with non-obese OA and non-obese controls. After adjusting for potential confounders, β-carotene status (≥0.8 µM) was significantly inversely correlated with the risk of metabolic syndrome (odds ratio = 0.27, p < 0.01), abdominal obesity (odds ratio = 0.33, p < 0.01), high blood pressure (odds ratio = 0.35, p < 0.01), hyperglycemia (odds ratio = 0.45, p < 0.05), and inflammation (odds ratio = 0.30, p = 0.01). Additionally, subjects who had a high β-carotene status with a low proportion of metabolic syndrome when they had a low-grade inflammatory status (p < 0.01). Obese OA patients suffered from a higher prevalence of metabolic syndrome and lower β-carotene status compared to the non-obese controls. A better β-carotene status (≥0.8 µM) was inversely associated with the risk of metabolic syndrome and inflammation, so we suggest that β-carotene status could be a predictor of the risk of metabolic syndrome and inflammation in patients with and without OA.     

Pancreatic β-Cell Dysfunction Is Associated with Nonalcoholic Fatty Liver Disease

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with decreased insulin sensitivity. However, the association between NAFLD and pancreatic β-cell function is still ambiguous. Here, we assessed whether pancreatic β-cell function is associated with NAFLD. Method: The data of NHANES III from 1988 to 1994 were used. NAFLD was diagnosed when subjects had ultrasonographically hepatic steatosis without other liver diseases. Disposition index (DI) was employed to assess pancreatic β-cell function. A total of 6168 participants were included in this study. Results: NAFLD participants had much higher HOMA2-%B (weighted mean, 124.1; standard error, 1.8) than the non-NAFLD participants (weighted mean, 100.7; standard error, 0.9). However, when evaluating the β-cell function in the context of insulin resistance by using DI index, DI levels were much lower in NAFLD subjects (weighted mean, 79.5; standard error, 1.0) compared to non-NAFLD (weighted mean, 95.0; standard error, 0.8). Multivariate logistic regression analyses showed that DI was inversely associated with NAFLD prevalence. The adjusted OR (95% CI) for quartile 1 versus quartile 4 was 1.81 (1.31–2.50) (p < 0.001 for trend). Moreover, DI was also inversely associated with the presence of moderate to severe hepatic steatosis. The multivariable-adjusted ORs across quartiles of DI were 2.47, 1.44, 0.96 and 1.00 for the presence of moderate to severe hepatic steatosis (p < 0.001 for trend). Conclusions: Pancreatic β-cell function might be a new predictor for the presence of NAFLD, and insufficient compensatory β-cell function is associated with NAFLD.     

Effect of Dietary Glycemic Index on β-Cell Function in Prediabetes: A Randomized Controlled Feeding Study

The glycemic index (GI) reflects the relative ability of carbohydrates to raise blood glucose. We utilized a controlled feeding study to assess the impact of the dietary GI on β-cell function in adults with prediabetes (17F/18M, mean ± SEM: BMI 32.44 ± 0.94 kg/m², age 54.2 ± 1.57 years). Following a 2 week Control diet (GI = 55–58), participants were randomized to either a 4 week low GI (LGI: GI < 35, n = 17) or high GI (HGI: GI > 70, n = 18) diet (55% of energy from carbohydrate/30% fat/15% protein). The data from 4 h meal tolerance tests (MTTs) underwent mathematical modeling to assess insulin sensitivity, insulin secretion and β-cell function. Glucose concentrations during the MTT decreased on the LGI diet (p < 0.001) and trended to increase on the HGI diet (p = 0.14; LGI vs. HGI p < 0.001), with parallel changes in insulin and C-peptide concentrations. Total insulin secretion, adjusted for glucose and insulin sensitivity, increased on the LGI diet (p = 0.002), and trended lower on the HGI diet (p = 0.10; LGI vs. HGI p = 0.001). There was no significant diet effect on insulin sensitivity or other measures of β-cell function. Total insulin clearance increased on the LGI diet (p = 0.01; LGI vs. HGI p < 0.001). We conclude that short-term consumption of an LGI diet reduced glucose exposure and insulin secretion but had no impact on measures of β-cell function.     

Machine Learning and In Vitro Chemical Screening of Potential α-Amylase and α-Glucosidase Inhibitors from Thai Indigenous Plants

Diabetes mellitus is a major predisposing factor for cardiovascular disease and mortality. α-Amylase and α-glucosidase enzymes are the rate-limiting steps for carbohydrate digestion. The inhibition of these two enzymes is clinically used for the treatment of diabetes mellitus. Here, in vitro study and machine learning models were employed for the chemical screening of inhibiting the activity of 31 plant samples on α-amylase and α-glucosidase enzymes. The results showed that the ethanolic twig extract of Pinus kesiya had the highest inhibitory activity against the α-amylase enzyme. The respective ethanolic extract of Croton oblongifolius stem, Parinari anamense twig, and Polyalthia evecta leaf showed high inhibitory activity against the α-glucosidase enzyme. The classification analysis revealed that the α-glucosidase inhibitory activity of Thai indigenous plants was more predictive based on phytochemical constituents, compared with the α-amylase inhibitory activity (1.00 versus 0.97 accuracy score). The correlation loading plot revealed that flavonoids and alkaloids contributed to the α-amylase inhibitory activity, while flavonoids, tannins, and reducing sugars contributed to the α-glucosidase inhibitory activity. In conclusion, the ethanolic extracts of P. kesiya, C. oblongifolius, P. anamense, and P. evecta have the potential for further chemical characterization and the development of anti-diabetic recipes.     

Dose- and Sex-Dependent Changes in Hemoglobin Oxygen Affinity by the Micronutrient 5-Hydroxymethylfurfural and α-Ketoglutaric Acid

5-Hydroxymethylfurfural (5-HMF) is known to increase hemoglobin oxygen affinity (Hb–O₂ affinity) and to induce a left shift of the oxygen dissociation curve (ODC). It is under investigation as a therapeutic agent in sickle cell anemia and in conditions where pulmonary oxygen uptake is deteriorated or limited (e.g., various clinical conditions or altitude exposure). The combination of 5-HMF and α-ketoglutaric acid (αKG) is commercially available as a nutritional supplement. To further elucidate dose effects, ODCs were measured in vitro in venous whole blood samples of 20 healthy volunteers (10 female and 10 male) after the addition of three different doses of 5-HMF, αKG and the combination of both. Linear regression analysis revealed a strong dose-dependent increase in Hb–O₂ affinity for 5-HMF (R² = 0.887; p < 0.001) and the commercially available combination with αKG (R² = 0.882; p < 0.001). αKG alone increased Hb–O₂ affinity as well but to a lower extent. Both the combination (5-HMF + αKG) and 5-HMF alone exerted different P50 and Hill coefficient responses overall and between sexes, with more pronounced effects in females. With increasing Hb–O₂ affinity, the sigmoidal shape of the ODC was better preserved by the combination of 5-HMF and αKG than by 5-HMF alone. Concerning the therapeutic effects of 5-HMF, this study emphasizes the importance of adequate dosing in various physiological and clinical conditions, where a left-shifted ODC might be beneficial. By preserving the sigmoidal shape of the ODC, the combination of 5-HMF and αKG at low (both sexes) and medium (males only) doses might be able to better maintain efficient oxygen transport, particularly by mitigating potentially deteriorated oxygen unloading in the tissue. However, expanding knowledge on the interaction between 5-HMF and Hb–O₂ affinity in vitro necessitates further investigations in vivo to additionally assess pharmacokinetic mechanisms.     

α1-Acid Glycoprotein and Dietary Intake in End-Stage Renal Disease Patients

Management of end-stage renal disease (ESRD) patients requires monitoring each of the components of malnutrition–inflammation–atherosclerosis (MIA) syndrome. Restrictive diet can negatively affect nutritional status and inflammation. An acute-phase protein—α₁-acid glycoprotein (AGP), has been associated with energy metabolism in animal and human studies. The aim of our study was to look for a relationship between serum AGP concentrations, laboratory parameters, and nutrient intake in ESRD patients. The study included 59 patients treated with maintenance hemodialysis. A 24 h recall assessed dietary intake during four non-consecutive days—two days in the post-summer period, and two post-winter. Selected laboratory tests were performed: complete blood count, serum iron, total iron biding capacity (TIBC) and unsaturated iron biding capacity (UIBC), vitamin D, AGP, C-reactive protein (CRP), albumin, prealbumin, and phosphate–calcium metabolism markers (intact parathyroid hormone, calcium, phosphate). Recorded dietary intake was highly deficient. A majority of patients did not meet recommended daily requirements for energy, protein, fiber, iron, magnesium, folate, and vitamin D. AGP correlated positively with CRP (R = 0.66), platelets (R = 0.29), and negatively with iron (R = −0.27) and TIBC (R = −0.30). AGP correlated negatively with the dietary intake of plant protein (R = −0.40), potassium (R = −0.27), copper (R = −0.30), vitamin B₆ (R = −0.27), and folates (R = −0.27), p < 0.05. However, in multiple regression adjusted for confounders, only CRP was significantly associated with AGP. Our results indicate that in hemodialyzed patients, serum AGP is weakly associated with dietary intake of several nutrients, including plant protein.     

New Delhi Metallo-β-Lactamase–Producing Enterobacterales Bacteria,Switzerland, 2019–2020

Carbapenemase-producing Enterobacterales (CPE) bacteria are a critical global health concern; New Delhi metallo-β-lactamase (NDM) enzymes account for >25% of all CPE found in Switzerland. We characterized NDM-positive CPE submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance during a 2-year period (January 2019–December 2020) phenotypically and by using whole-genome sequencing. Most isolates were either Klebsiella pneumoniae (59/141) or Escherichia coli (52/141), and >50% were obtained from screening swabs. Among the 108 sequenced isolates, NDM-1 was the most prevalent variant, occurring in 56 isolates, mostly K. pneumoniae (34/56); the next most prevalent was NDM-5, which occurred in 49 isolates, mostly E. coli (40/49). Fourteen isolates coproduced a second carbapenemase, predominantly an OXA-48-like enzyme, and almost one third of isolates produced a 16S rRNA methylase conferring panresistance to aminoglycosides. We identified successful plasmids and global lineages as major factors contributing to the increasing prevalence of NDMs in Switzerland.     

Vitamin E status of 20- to 59-year-old adults living in the Seoul metropolitan area of South Korea

BACKGROUND/OBJECTIVES

Vitamin E is a fat-soluble vitamin and functions primarily as a lipid antioxidant. Inadequate vitamin E status may increase risk of several chronic diseases. Thus, the objectives of this study were to estimate intake and plasma concentration of each tocopherol and to evaluate vitamin E status of Korean adults.

SUBJECTS/METHODS

Three consecutive 24-h food recalls and fasting blood samples were collected from healthy 20- to 59-y-old adults (33 males and 73 females) living in the Seoul metropolitan area, South Korea. α-, β-, δ-, and γ-tocopherol intakes and plasma concentrations of tocopherols (α-, δ-, and γ-tocopherol) were analyzed by gender.

RESULTS

Dietary vitamin E and total vitamin E intake (dietary plus supplemental vitamin E) was 17.68 ± 14.34 and 19.55 ± 15.78 mg α-tocopherol equivalents, respectively. The mean daily α-tocopherol, and γ-tocopherol intakes were 3.07 ± 2.27 mg and 5.98 ± 3.74 mg, respectively. Intakes of total vitamin E and each tocopherol of males were significantly higher than those of females (P < 0.05). Plasma α-tocopherol concentration was 15.45 ± 10.16 of males and 15.00 ± 4.54 µmol/L of females, respectively. There were no significant differences in plasma tocopherol concentrations by gender (P ≥ 0.05). Plasma α-tocopherol was negatively correlated with γ-tocopherol intake (P < 0.05). Twenty-three percent of the subjects had plasma α-tocopherol concentrations < 12 µmol/L indicating a biochemical deficiency of vitamin E. Approximately 8% and 9% of these participants had plasma α-tocopherol:total lipid ratio less than 1.59 µmol/mmol and plasma α-tocopherol:total cholesterol ratio less than 2.22 µmol/mmol, respectively, which are also indicative of vitamin E deficiency.

CONCLUSIONS

Vitamin E intakes of Korean adults were generally adequate with the Korean Dietary Reference Intakes for vitamin E. However, α-tocopherol intake was lower than that reported in other countries, and 23% of the subjects in the current study were vitamin E deficient based on plasma α-tocopherol concentrations.     

High-Load Resistance Exercise Augments Androgen Receptor–DNA Binding and Wnt/β-Catenin Signaling without Increases in Serum/Muscle Androgens or Androgen Receptor Content

The purpose of this study was (1) to determine the effect of single bouts of volume- and intensity-equated low- (LL) and high-load (HL) full-body resistance exercise (RE) on AR-DNA binding, serum/muscle testosterone and dihydrotestosterone, muscle androgen receptor (AR), and AR-DNA binding; and, (2) to determine the effect of RE on sarcoplasmic and nucleoplasmic β-catenin concentrations in order to determine their impact on mediating AR-DNA binding in the absence/presence of serum/muscle androgen and AR protein. In a cross-over design, 10 resistance-trained males completed volume- and intensity-equated LL and HL full-body RE. Blood and muscle samples were collected at pre-, 3 h-, and 24 h post-exercise. Separate 2 × 3 factorial analyses of variance (ANOVAs) with repeated measures and pairwise comparisons with a Bonferroni adjustment were used to analyze the main effects. No significant differences were observed in muscle AR, testosterone, dihydrotestosterone, or serum total testosterone in either condition (p > 0.05). Serum-free testosterone was significantly decreased 3 h post-exercise and remained significantly less than baseline 24 h post-exercise in both conditions (p < 0.05). In response to HL, AR-DNA binding significantly increased at 3 h post-exercise (p < 0.05), whereas no significant differences were observed at any time in response to LL (p > 0.05). Moreover, sarcoplasmic β-catenin was significantly greater in HL (p < 0.05) without significant changes in nucleoplasmic β-catenin (p > 0.05). In conclusion, increases in AR-DNA binding in response to HL RE indicate AR signaling may be load-dependent. Furthermore, despite the lack of increase in serum and muscle androgens or AR content following HL RE, elevations in AR-DNA binding with elevated sarcoplasmic β-catenin suggests β-catenin may be facilitating this response.     

Protein Digests and Pure Peptides from Chia Seed Prevented Adipogenesis and Inflammation by Inhibiting PPARγ and NF-κB Pathways in 3T3L-1 Adipocytes

The objective was to evaluate the mechanisms of digested total proteins (DTP), albumin, glutelin, and pure peptides from chia seed (Salvia hispanica L.) to prevent adipogenesis and its associated inflammation in 3T3-L1 adipocytes. Preadipocytes (3T3-L1) were treated during differentiation with either DTP or digested albumin or glutelin (1 mg/mL) or pure peptides NSPGPHDVALDQ and RMVLPEYELLYE (100 µM). Differentiated adipocytes also received DTP, digested albumin or glutelin (1 mg/mL), before (prevention) or after (inhibition) induced inflammation by addition of conditioned medium (CM) from inflamed macrophages. All treatments prevented adipogenesis, reducing more than 50% the expression of PPARγ and to a lesser extent lipoprotein lipase (LPL), fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SREBP1), lipase activity and triglycerides. Inflammation induced by CM was reduced mainly during prevention, while DTP decreased expression of NF-κB (−48.4%), inducible nitric oxide synthase (iNOS) (−46.2%) and COX-2 (−64.5%), p < 0.05. Secretions of nitric oxide, PGE2 and TNFα were reduced by all treatments, p < 0.05. DTP reduced expressions of iNOS (−52.1%) and COX-2 (−66.4%). Furthermore, digested samples and pure peptides prevented adipogenesis by modulating PPARγ and additionally, preventing and even inhibiting inflammation in adipocytes by inhibition of PPARγ and NF-κB expression. These results highlight the effectiveness of digested total proteins and peptides from chia seed against adipogenesis complications in vitro.     

Absorption of water-miscible forms of vitamin E in a patient with cholestasis and in thoracic duct-cannulated rats

Oral administration of vitamin E (100 mg tocopherol X kg-1 X day-1) as tocopheryl polyethylene glycol 1000 succinate (TPGS) to a child with congenital hepatic cholestasis (unresponsive to oral administration of dl-alpha-tocopheryl acetate) promoted an increase of tocopherol in plasma and adipose tissue while tocopheryl acetate emulsified with medium chain triglycerides and polysorbate 80 (MCT-E) did not. alpha-Tocopherol absorption, quantitated in thoracic duct-cannulated rats receiving intraduodenal infusions of soybean oil and saline, was similar for TPGS, MCT-E, and dl-alpha-tocopheryl acetate; gamma-tocopherol absorption from soybean oil was not affected by the presence of the supplemental alpha-tocopherol. Following bile duct ligation in one rat, TPGS promoted the absorption of alpha-tocopherol while absorption of gamma-tocopherol from soybean oil was decreased 30 fold, demonstrating that TPGS, which forms a micellar solution, delivers alpha-tocopherol through the unstirred water layer to enterocytes, while free tocopherol (alpha or gamma) absorption requires the presence of bile salts.     

One-Week High-Dose β-Alanine Loading Improves World Tour Cyclists’ Time-Trial Performance

Supplementation with β-alanine is becoming a common practice in high-performance athletes. The purpose of the present study was to investigate the effects of a one-week high-dose β-alanine loading phase employing a sustained-release powder on preserving the time-trial performance capacity of world tour cyclists during overreaching training. Per day, 20 g of sustained-release β-alanine was administered during one week (7 days) of intensive team training camp in a randomised balanced placebo-controlled parallel trial design, with six participants in each β-alanine (BA) or placebo (PLA) group. A 10-min time trial (10′ TT) was carried out to analyse performance and biochemical variables. Anthropometry, paresthesia, and adverse event data were also collected. Power-based relative training load was quantified. Compared to placebo, the BA improved mean power (6.21%, 37.23 W; 95% CI: 3.98–70.48 W, p = 0.046), distance travelled (2.16%, p = 0.046) and total work (4.85%, p = 0.046) without differences in cadence (p = 0.506) or RPE. Lactate (p = 0.036) and anion gap (p = 0.047) were also higher in the BA group, without differences in pH or Bicarbonate. High daily and single doses were well tolerated. One-week high-dose β-alanine loading with a sustained-release powder blend can help attenuate 10′ TT performance losses of world tour cyclists due to intensive training.     

α-Lipoic Acid Inhibits Apoptosis by Suppressing the Loss of Ku Proteins in Helicobacter pylori-Infected Human Gastric Epithelial Cells

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and triggers various stomach diseases. H. pylori induces reactive oxygen species (ROS) production and DNA damage. The heterodimeric Ku70/Ku80 protein plays an essential role in the repair of DNA double-strand breaks (DSB). Oxidative stress stimulate apoptosis and DNA damage that can be repaired by Ku70/80. However, excessive reactive oxygen species (ROS) can cause Ku protein degradation, resulting in DNA fragmentation and apoptosis. α-lipoic acid (α-LA), which is found in organ meats such as liver and heart, spinach, broccoli, and potatoes, quenches free radicals, chelates metal ions, and reduces intracellular DNA damage induced by oxidative stress. Here, we investigated whether H. pylori decreases Ku70/80 and induces apoptosis, and whether α-LA inhibits changes induced by H. pylori. We analyzed ROS, DNA damage markers (γ-H2AX, DNA fragmentation), levels of Ku70/80, Ku–DNA binding activity, Ku80 ubiquitination, apoptosis indices (Bcl-2, Bax, apoptosis-inducing factor (AIF), and caspase-3), and viability in a human gastric epithelial adenocarcinoma cell line (AGS). H. pylori increased ROS, DNA damage markers, Ku80 ubiquitination, and consequently induced apoptosis. It also decreased nuclear Ku70/80 levels and Ku–DNA-binding activity; increased Bax expression, caspase-3 cleavage, and truncated AIF; but decreased Bcl-2 expression. These H. pylori-induced alterations were inhibited by α-LA. The antioxidant N-acetylcysteine and proteasome inhibitor MG-132 suppressed H. pylori-induced cell death and decreased nuclear Ku70/80 levels. The results show that oxidative stress induced Ku70/80 degradation via the ubiquitin–proteasome system, leading to its nuclear loss and apoptosis in H. pylori-infected cells. In conclusion, α-LA inhibited apoptosis induced by H. pylori by reducing ROS levels and suppressing the loss of Ku70/80 proteins in AGS cells.     

Natural Polysaccharide β-Glucan Protects against Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress

Doxorubicin (DOXO) can be used to treat a variety of human tumors, but its clinical application is limited due to severe cardiotoxic side effect. Here, we explore the role of β-glucan in DOXO-induced cardiotoxicity in mice and study its underlying mechanism. When co-administered with DOXO, β-glucan was observed to prevent left ventricular dilation and fibrosis. In fact, DOXO reduces the activity of mitochondrial respiratory chain complex and enhances oxidative stress, which in turn impairs heart function. DOXO decreases the ATP production capacity of the heart and increases the ROS content, while β-glucan can restore the heart capacity and reduce oxidative stress. β-glucan also increases the activity of antioxidant enzymes GSH-PX and SOD, and reduces the level of MDA in the serum. In addition, the mRNAs of cardiac dysfunction marker genes ANP, BNP and Myh7 were significantly increased after DOXO induction, however, they did not increase when combined with β-glucan administration. In conclusion, our results indicate that β-glucan can improve the antioxidant capacity of the heart, thereby serving as a potential therapeutic strategy to prevent DOXO-induced cardiotoxicity.