Pretreatment with water kefir reduces the development of acidified ethanol-induced gastric ulcers

Abstract To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.

Association of advanced oxidation protein products in seminal plasma with teratospermia and outcome parameters of fertilization / 南方医科大学学报

OBJECTIVE@#To study the association of the level of advanced oxidation protein products (AOPPs) in seminal plasma with teratospermia and the outcome parameters of fertilization (IVF).@*METHODS@#We conducted a cross-sectional study among 272 male patients receiving assisted reproduction treatment in the Center for Reproductive Medicine of our hospital between October, 2018 and March, 2019. The levels of seminal AOPPs and reactive oxygen species (ROS), demographic data, sperm parameters and IVF outcome parameters were analyzed for all the patients. According to the percentage of sperms with normal morphology, the patients were divided before IVF into teratozoospermia group and normal sperm morphology group, and those in teratozoospermia group were further divided into 3 subgroups with mild, moderate and severe teratozoospermia. The patients were also divided on the day oocyte retrieval into 2 groups with fertilizing rates lower (group Ⅰ) and higher (group Ⅱ) than the median rate.@*RESULTS@#We found a significant negative correlation of seminal AOPP level before treatment with the percentage of normal sperm morphology (=0.003) and seminal ROS level (=0.013). The seminal levels of AOPPs (= 0.027) and ROS (=0.036) were significantly elevated in patients with teratospermia, and seminal AOPP level was significantly higher in severe teratospermia group than in mild (=0.019) and moderate (=0.015) teratospermia groups. The seminal levels of AOPPs (=0.003) and ROS (=0.017) on the day of oocyte retrieval were negatively correlated with the fertilization rate in IVF cycles, and the levels of AOPPs (=0.049) and ROS (=0.036) were significantly higher in group Ⅰ than in group Ⅱ.@*CONCLUSIONS@#An elevated level of seminal AOPPs may indicate an increased risk of severe teratospermia and a lower fertilization rate in IVF.

Metabolic syndrome components are associated with oxidative stress in overweight and obese patients

ABSTRACT Objective: The aim of this study is to evaluate the influence of the body mass index (BMI) and the metabolic syndrome (MetS) parameters on oxidative and nitrosative stress in overweight and obese subjects. Subjects and methods: Individuals were divided into three groups: the control group (G1, n = 131) with a BMI between 20 and 24.9 kg/m2, the overweight group (G2, n = 120) with a BMI between 25 and 29.9 kg/m2 and the obese group (G3, n = 79) with a BMI ≥ 30 kg/m2. Results: G3 presented higher advanced oxidation protein products (AOPPs) in relation to G1 and G2 (p = 0.001 and p = 0.011, respectively) whereas G2 and G3 had lower levels of nitric oxide (NO) (p = 0.009 and p = 0.048, respectively) compared to G1. Adjusted for the presence of MetS to evaluate its influence, the levels of AOPPs did not differ between the groups, whereas NO remained significantly lower. Data adjusted by the BMI showed that subjects with higher triacylglycerol levels had higher AOPPs (p = 0.001) and decreased total radical-trapping antioxidant parameter/uric Acid (p = 0.036). Subjects with lower high-density lipoprotein (HDL) levels and patients with higher blood pressure showed increased AOPPs (p = 0.001 and p = 0.034, respectively) and lower NO levels (p = 0.017 and p = 0.043, respectively). Subjects who presented insulin resistance had higher AOPPs (p = 0.024). Conclusions: Nitrosative stress was related to BMI, and protein oxidation and nitrosative stress were related to metabolic changes and hypertension. MetS components were essential participants in oxidative and nitrosative stress in overweight and obese subjects.

A new biomarker for the early diagnosis of ovarian torsion: SCUBE-1 / 대한생식의학회지

OBJECTIVE: Prompt diagnosis and management are essential for saving the adnexal organs from infarction in cases of ovarian torsion (OT). This study aimed to determine the diagnostic significance of signal peptide, complement C1r/C1s, Uegf, and Bmp1 (CUB), and epidermal growth factor-like domain-containing protein-1 (SCUBE-1) levels in cases of OT, an emergent ischemic condition, and the relationship of SCUBE-1 with oxidative stress parameters. METHODS: This prospective study was conducted among 15 OT patients and 20 age- and gravidity-matched healthy women. SCUBE-1 serum concentrations were determined by using enzyme-linked immunosorbent assays. In addition, oxidative stress was evaluated by measuring the serum levels of advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), and glutathione (GSH). RESULTS: The SCUBE-1 titers were significantly higher in the patients with OT than in the controls (p=0.008). In addition, serum FRAP and GSH levels were significantly lower in the OT patients than in the controls (p 0.05). Furthermore, there were no correlations between SCUBE-1 levels and age, gravidity, parity, cyst size, and AOPP, FRAP, or GSH levels (p>0.05). CONCLUSION: We believe that SCUBE-1 may be a promising biomarker for the early diagnosis of OT.

Antioxidant properties of the carotenoid extracts of three Deinococcus­Thermus phylum bacteria, Meiothermus sp. strains RP and TP and Thermus sp. strain YY from Paniphala hot spring, India

BACKGROUND:The purpose of the study was to extract carotenoids from thermophilic bacteria which show efficient antioxidant and protein oxidation inhibition properties, characterize and identify those isolates, extract the carotenoids in different solvents, quantify the carotenoids and perform concentration-dependent and solvent-dependent quantitative assays validated and analysed by appropriate statistical tests. METHODS: Three pigment-forming thermophilic strains were isolated from water sample of Paniphala hot spring, India, and tentatively identified by 16S ribosomal DNA (rDNA) homology. Different concentrations of the carotenoid extracts (100, 80, 40 and 20µg) in three solvents, methanol, DMSO and water, were used to determine the antioxidant activity through five methods: the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay, the ABTS (2,2-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid)) assay, the hydrogen peroxide assay, TOC (total antioxidant capacity) assay and inhibition of protein oxidation assay. Statistical analysis of mean, standard deviation, ANOVA and Pearson correlationcoefficient was performed in Microsoft Excel statistical package.Results:The isolates were tentatively identified as Meiothermussp. strain RP, Meiothermussp. strain TP and Thermusstrain YY.Meiothermussp. formed red coloured pigment, where as Thermussp. formed yellow coloured pigment. Allof the extracts showed positive results in DPPH assay, ABTS assay and hydrogen peroxide radical scavenging assaywith best results obtained when the extracts were dissolved in water. Total antioxidant capacity assay was also highin all the extracts. Protein oxidation inhibition activity was only seen in extracts of strain YY. One-way ANOVA(analysis of variance) clearly showed that choice of solvent influenced the antioxidant capacity of all of the extracts. CONCLUSIONS: Newer and efficient antioxidative compounds are constantly being searched for, and the carotenoid extracts of RP, TP and YY have been shown to catalyze various types of antioxidative reactions, including proteinoxidation inhibition by YY. Thus, all these extracts have huge potential to be industrially and pharmaceutically useful.

The effects of supplemental melatonin administration on the healing of bone defects in streptozotocin-induced diabetic rats

ABSTRACT Diabetes mellitus (DM) causes an increased production of free radicals that can impair bone healing. Melatonin is a hormone secreted mainly by the pineal gland, which participates in the neutralization process of free radicals. Objective The aim of this study was to investigate histologic and biochemical effects of supplemental melatonin administration on bone healing and antioxidant defense mechanism in diabetic rats. Material and Methods Eighty-six Sprague-Dawley male rats were used in this study. Diabetes mellitus was induced by intraperitoneal (i.p.) administration of 65 mg/kg streptozotocin (STZ). Surgical bone defects were prepared in the tibia of each animal. Diabetic animals and those in control groups were treated either with daily melatonin (250 μg/animal/day/i.p.) diluted in ethanol, only ethanol, or sterile saline solution. Rats were humanely killed at the 10th and 30th postoperative days. Plasma levels of Advanced Oxidation Protein Products (AOPP), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) were measured. The number of osteoblasts, blood vessels and the area of new mineralized tissue formation were calculated in histologic sections. Results At the 10th day, DM+MEL (rats receiving both STZ and melatonin) group had significantly higher number of osteoblasts and blood vessels as well as larger new mineralized tissue surfaces (p<0.05 for each) when compared with DM group. At the 30th day, DM group treated with melatonin had significantly lower levels of AOPP and MDA than those of DM group (p<0.05). Conclusion Melatonin administration in STZ induced diabetic rats reduced oxidative stress related biomarkers and showed beneficial effects on bone healing at short term.

Inflammatory cytokines and oxidative stress markers in the inhibition of osteoarthritis by curcumin / 浙江大学学报·医学版

To observe the influence of matrix metalloproteinases-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), CD47, L-selectin and advanced oxidation proteinproducts (AOPP) in osteoarthritis and the intervention of curcumin.A total of 20 male C57BL/6 mice (10.05-15.00 g) were randomly divided into control group, OA group, Cur25 group and Cur50 group (intraperitoneal injected 25 μmol/L or 50 μmol/L of curcumin everyday after modeling). After 4 weeks treatment, we observed the morphological changes of the gross specimen by immunohistochemical method, and observed the ultrastructure of cartilage tissue under electron microscope. The expression of MMP-2, MCP-1 and CD47 were detected by western blotting, and L-selectin and AOPP were detected by ELISA and spectrophotometer, respectively.In the cartilage tissue morphology, the chondrocytes of OA group showed obvious change, while Cur25 and Cur50 groups maintained the good cartilage cell membrane intact. Compared with control group, the expressions of MMP-2, MCP-1, L-selectin and AOPP in OA group, Cur25 group and Cur50 group were increased (all<0.05), while CD47 levels were decreased (all<0.05). Compared with OA group, the expressions of MMP-2, MCP-1, L-selectin and AOPP in Cur25 group and Cur50 group were decreased (all<0.05), while CD47 levels were increased (all<0.05), and such changes were more significant in Cur50 group (all<0.05).The MMP-2, MCP-1, CD47, L-selectin and AOPP are closely associated with the pathology course of OA. Curcumin has protection effect on cartilage, which can relieve joint cartilage degeneration, reduce cartilage inflammation and increase the metabolic activity of chondrocytes.

Arctiin ameliorates advanced oxidation protein product-induced epithelial-to- mesenchymal transition in HK-2 cells by inhibiting endoplasmic reticulum stress / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of arctiin on advanced oxidation protein product (AOPP)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells and explore the mechanisms underlying this effect.</p><p><b>METHODS</b>Human proximal tubular cells (HK-2 cells) were treated with bovine serum albumin (BSA) or AOPPs in the presence or absence of arctiin. The expressions of E-cadherin, vimentin, and GRP78 at the protein and mRNA levels in the cells were examined using Western blotting and quantitative real-time PCR. The level of reactive oxygen species (ROS) was measured by flow cytometry with DCFH-DA as the fluorescent probe.</p><p><b>RESULTS</b>Compared with BSA-treated cells, the cells treated with AOPPs showed decreased expression of epithelial cell marker E-cadherin and overexpression of mesenchymal marker vimentin and endoplasmic reticulum stress marker GRP78 with an increased ROS level. These changes induced by AOPPs were partly inhibited by arctiin.</p><p><b>CONCLUSION</b>Arctiin can ameliorate AOPP-induced EMT in tubular cells by inhibiting endoplasmic reticulum stress, and oxidative stress response may participate in this process.</p>

Sirtuin 1 gene rs2273773 C >T single nucleotide polymorphism and protein oxidation markers in asthmatic patients

Background: Sirtuin-1 [SIRT-1], a protein has been found to protect the cells against oxidative stress due to its deacetylase activity. In this investigation, we aimed to study SIRT-1 gene rs2273773 C >T single nucleotide polymorphism and markers of serum protein oxidation [protein carbonyl and sulfhydryl groups] in asthmatic patients

Subjects and methods: 120 asthmatic patients and 120 healthy controls were genotyped for SIRT- 1 gene rs2273773 C > T SNP using polymerase chain reaction - confronting two pair primer method [PCR-CTPP]. Serum protein carbonyl and sulfhydryl groups were measured using colorimetric methods

Results: SIRT-1 gene rs2273773 C> T SNP genotyping revealed that the TT genotype was significantly higher in the patients compared to the controls [P < 0.05], while there were no significant differences regarding the genotypes TC and CC between the patients and the controls [P> 0.05]. T allele was significantly higher in the patients compared to the controls [P =0.017]. The distribution of the genotypes didn't differ among the atopic and the non-atopic asthmatic patients, also no difference was found in the genotype distribution according to the severity of asthma [P >0.05]. Serum protein carbonyl group concentration was significantly higher in the patients compared to the controls [P < 0. 001], while serum protein sulfhydryl group content decreased significantly in the patients compared to the controls [P < 0.0001]. No differences in markers of protein oxidation according to SIRT-1 gene rs2273773 C > T genotype were found

Conclusion:SIRT-1 gene rs2273773 C> T SNP was associated with asthma but not with protein oxidation markers in Egyptian population

Evaluation of Advanced Oxidation Protein Products, Prooxidant-Antioxidant Balance, and Total Antioxidant Capacity in Untreated Vitiligo Patients

BACKGROUND: Vitiligo is a chronic, common disease of unknown etiology, and oxidative stress is suggested to have a role in its etiopathogenesis. OBJECTIVE: Advanced oxidation protein products (AOPPs), prooxidant-antioxidant balance (PAB), and ferric-reducing antioxidant power (FRAP) were evaluated regarding their role in the pathogenesis of vitiligo as well as their relationship with clinical presentation and disease severity, and these parameters were compared with those of healthy controls. METHODS: The study included 53 patients with vitiligo and 20 healthy volunteers as the control group. AOPP level, PAB, and FRAP were determined by colorimetric methods. RESULTS: PAB and FRAP level were significantly higher in patients with vitiligo than in healthy controls (p<0.001). The AOPP levels in vitiligo patients were not statistically significantly higher than those in healthy controls. The Vitiligo Area Scoring Index positively correlated with disease duration (r(s): 0.531, p<0.001). CONCLUSION: To the best of our knowledge, this is the first report of AOPP and PAB status in vitiligo. PAB may be used as an indicator for oxidative stress in the etiopathogenesis of vitiligo. Our results show that these parameters may play a major role in the melanocyte damage observed in vitiligo. Further studies are required to confirm the mechanisms underlying this effect.

Shenkang pill down-regulates AOPP-induced expression of inflammatory factor MCP-1 via a p38MAPK/NF-κB-dependent mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of the serum of rats fed with Shenkang pill in regulating monocyte chemoattractant protein 1 (MCP-1) expression induced by advanced oxidation protein products (AOPP) in mouse podocyte clone 5 (MPC5) and explore the underlying mechanism.</p><p><b>METHODS</b>MPC5 cultured in vitro were incubated for different time lengths in the presence of different concentrations of serum of rats medicated with Shenkang pill, and the cell proliferation was assessed using MTT assay. In MPC5 treated with AOPP prior to exposure to the rat serum, the changes in the protein expressions of p38MAPK and IκBα were examined with Western blotting, NF-κB p65 nuclear translocation was analyzed with immunofluorescence assay, and MCP-1 expression in the supernatant was determined using ELISA kits.</p><p><b>RESULTS</b>The medicated rat serum time- and concentration-dependently promoted the proliferation of MPC5, with the optimal serum concentration of 5% and incubation time of 24 h. AOPP significantly increased MCP-1 expression in the cell supernatant in a time-and concentration-dependent manner; pretreatment with SB203580 (a p38 inhibitor) or parthenolide (a NF-κB inhibitor) significantly decreased MCP-1 expression, and treatment with the medicated serum significantly decreased AOPP-induced MCP-1 expression. AOPP concentration-dependently increased the protein expression of P-p38 but decreased that of IκBα. Both the medicated serum and SB203580 increased IκBα protein in AOPP-induced cells, but the effect was more obvious with the medicated serum. The medicated serum also decreased NF-κB p65 nuclear translocation in AOPP-induced MPC5.</p><p><b>CONCLUSION</b>Shenkang pill-medicated serum can decrease AOPP-induced expression of MPC-1 in MPC5 by regulating p38MAPK/NF-κB to mediate its anti-inflammatory effect. This finding provides a new theoretical basis for the application of Shenkang pill to treat diabetic nephropathy.</p>

Advanced oxidation protein products induce epithelial-to-mesenchymal transition in cultured human proximal tubular epithelial cells via oxidative stress / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of advanced oxidation protein products (AOPP) on epithelial-to-mesenchymal transition (EMT) in cultured human proximal tubular epithelial cells (HK-2) and explore the mechanism.</p><p><b>METHODS</b>HK-2 cells treated with 50, 100, 200, and 400 µg/ml AOPP or 50 µg/m bovine serum albumin (BSA) for 24 h, or with 200 µg/ml AOPP for 0.5, 1, 3, 6, 12, and 24 h were examined for the protein expression of α-SMA and E-cadherin. In cells pretreated with diphenyleneiodonium (DPI) or cytoplasmic superoxide dismutase (C-SOD), the effects of 50 µg/ml BSA and 200 µg/ml AOPP were assessed on the expressions of α-SMA and E-cadherin, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, catalase (CAT) activity, and glutathione peroxidase (GSH-px) activity.</p><p><b>RESULTS</b>AOPP treatment up-regulated α-SMA expression and down-regulated E-cadherin expression in a dose- and time-dependent fashion. AOPP exposure of the cells resulted in increased MDA level and lowered activities of SOD, CAT and GSH-PX. DPI and C-SOD partially attenuated the effects of AOPP on α-SMA, E-cadherin, MDA, SOD, CAT and GSH-px.</p><p><b>CONCLUSION</b>AOPP can induce EMT in cultured HK-2 cells via oxidative stress, and this effect can be attenuated by inhibiting the activation of NADPH oxidase and using antioxidants to delay the progression of renal interstitial fibrosis.</p>

Effects of Angiotensin-Converting Enzyme Polymorphism on Soluble Receptor for Advanced Glycation End-Products in Maintenance Hemodialysis Patients / 대한내과학회지

BACKGROUND/AIMS: Advanced glycation end-products (AGEs) exert various toxic effects through the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) is a naturally occurring inhibitor of AGE-RAGE. Recent studies have suggested that inhibition of angiotensin-converting enzyme (ACE) reduces the accumulation of AGEs in diabetes partly by increasing the production and secretion of sRAGE into the plasma. This report describes the relationship between sRAGE and ACE polymorphism in maintenance hemodialysis patients. METHODS: The levels of sRAGE and advanced oxidation protein products (AOPPs) were assessed by enzyme-linked immunosorbent assay (ELISA), and ACE polymorphism was detected by PCR amplification. RESULTS: The distributions of ACE genotypes in 105 hemodialysis patients were as follows: II, 56 (35.9%); ID, 29 (18.6%); and DD, 20 (12.8%). According to the ACE genotypes, the study group consisted of II (n = 56) and ID + DD group (n = 49). sRAGE was correlated with age (r = -0.24; p = 0.013). There were significant differences in sRAGE, AOPP, age, duration of dialysis, C-reactive protein, or 24-h urine volume between two genotype groups. There were no significant differences in sRAGE levels, even though the effect of age was treated as a covariate. CONCLUSIONS: Our findings suggested that sRAGE may be affected only by age, and not by ACE polymorphism in maintenance hemodialysis patients.

Effects of Angiotensin-Converting Enzyme Polymorphism on Soluble Receptor for Advanced Glycation End-Products in Maintenance Hemodialysis Patients / 대한내과학회지

BACKGROUND/AIMS: Advanced glycation end-products (AGEs) exert various toxic effects through the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) is a naturally occurring inhibitor of AGE-RAGE. Recent studies have suggested that inhibition of angiotensin-converting enzyme (ACE) reduces the accumulation of AGEs in diabetes partly by increasing the production and secretion of sRAGE into the plasma. This report describes the relationship between sRAGE and ACE polymorphism in maintenance hemodialysis patients. METHODS: The levels of sRAGE and advanced oxidation protein products (AOPPs) were assessed by enzyme-linked immunosorbent assay (ELISA), and ACE polymorphism was detected by PCR amplification. RESULTS: The distributions of ACE genotypes in 105 hemodialysis patients were as follows: II, 56 (35.9%); ID, 29 (18.6%); and DD, 20 (12.8%). According to the ACE genotypes, the study group consisted of II (n = 56) and ID + DD group (n = 49). sRAGE was correlated with age (r = -0.24; p = 0.013). There were significant differences in sRAGE, AOPP, age, duration of dialysis, C-reactive protein, or 24-h urine volume between two genotype groups. There were no significant differences in sRAGE levels, even though the effect of age was treated as a covariate. CONCLUSIONS: Our findings suggested that sRAGE may be affected only by age, and not by ACE polymorphism in maintenance hemodialysis patients.

Advanced oxidation protein products promote expression of stromal-cell derived factor-1alpha of ECV304 cells through ERK signal pathway / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of advanced oxidation protein products (AOPP) on expressions of stromal cell-derived factor-1alpha (SDF-1alpha) in ECV304 cells and the signal pathway that mediated the effects.</p><p><b>METHODS</b>AOPP-BSA was made from bovine serum albumin (BSA) and sodium hypochlorite. After treated with AOPP-BSA of different concentrations (50, 100, 200 micromol/L), the expressions of SDF-1alpha mRNA in ECV304 cells were measured by reverse transcription-polymerase chain reaction (RT-PCR) and the expressions of SDF-1alpha protein and the levels of phosphorylated extracellular signal-regulated kinase (ERK) in ECV304 cells were analyzed by Western blot. In inhibition test, U0126, the special inhibitor of ERK of different concentrations (0.1, 1, 10 rmol/L) were added into ECV304 cells culture media for 1 hour, then the cells were treated with AOPP-BSA for 24 hours, at last the protein levels in supernatant were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>AOPP-BSA obviously promoted the expressions of SDF-1alpha mRNA and increased the levels of SDF-1beta protein of ECV304 cells in dose-dependent manner (all P < 0.01), after 15 minutes treated with 200 micromol/L AOPP-BSA, the levels of phosphorylated ERK of ECV304 cells increased significantly (P < 0.01). When the ERK pathway was blocked by U0126, the promoting effects of AOPP-BSA on expressions of SDF-la protein in ECV304 cells were significantly inhibited in dose-dependent manner (P < 0.05).</p><p><b>CONCLUSION</b>AOPP induced the expression of SDF-la of ECV304 cells, ERK signal pathway is an important pathway that mediated the effects.</p>

Advanced oxidation protein products inhibit proliferation and differentiation of rat osteoblasts through oxidative stress / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of advanced oxidation protein products (AOPP) on proliferation, differentiation, and oxidative stress in rat osteoblasts.</p><p><b>METHODS</b>The cell proliferation and differentiation of osteoblasts isolated from neonatal SD rat skull were evaluated following treatment with different concentrations (50, 100, 200, and 400 µg/ml) of AOPP using CCK-8 kit and ALP assay kit, respectively. The levels of reactive oxygen species (ROS) in the treated cells were analyzed using 2', 7'-dichlorofluorescin diacetate, and the transcription levels of ALP, collagen I and RAGE were assessed using real-time PCR.</p><p><b>RESULTS</b>Compared with the control group, AOPP-treated osteoblasts showed obviously inhibited proliferation and differentiation with down-regulated expressions of ALP and collagen I and increased ROS production and RAGE expression.</p><p><b>CONCLUSION</b>AOPP can inhibit the proliferation and differentiation of rat osteoblasts partially by up-regulating RAGE and inducing ROS production.</p>

Effect of arctiin on mouse podocyte epithelial-mesenchymal transition induced by advanced oxidation protein products / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of arctiin on mouse podocyte epithelial-mesenchymal transition (EMT) induced by advanced oxidation protein products (AOPP).</p><p><b>METHODS</b>Mouse podocytes were stimulated by 200 µg/ml AOPP for 24 h in the presence of 50, 100, 200, and 400 µmol/L arctiin. The expressions of α-smooth muscle actin, Grp78 and CHOP were detected using Western blotting.</p><p><b>RESULT</b>The expressions of α-SMA, Grp78 and CHOP were inhibited by arctiin, showing a dose-dependent effect within a given range of arctiin concentration.</p><p><b>CONCLUSION</b>AOPP causes endoplasmic reticulum stress to induce EMT of mouse podocytes, and arctiin can decrease EMT by alleviating the stress. This finding sheds light on a new scope of research of renal fibrosis.</p>

Role of reactive oxygen species in the renal fibrosis / 中华医学杂志(英文版)

Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology. Accumulating evidence indicates that oxidative stress, resulting in generation of reactive oxygen species (ROS), plays a critical role in the initiation and progression of fibrotic diseases. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the predominant enzyme source for ROS generation and is now recognized as a key mediator of cell proliferation and matrix accumulation in renal disease. Multiple stimuli and agonists, such as transforming growth factor β1, tumor necrosis factor, platelet derived growth factor, angiotensin II, hyperglycemia, oxidized low-density lipoprotein and albumin have been shown to alter the activity or expression of the NADPH oxidase and ultimately increase ROS production. ROS directly incites damage to biologically important macromolecules and leads to generation of the so-called advanced oxidation protein products (AOPPs) and advanced glycation end products, which are not only markers of oxidative stress but also cause renal injury. Targeting NADPH oxidase and/or reducing AOPPs production might be a novel strategy for the therapeutic intervention of variety of fibrotic kidney disorders.

Role of oxidative stress and thioredoxin in gastric cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of oxidative stress and the antioxidant protein thioredoxin in the tumorigenesis and progression of gastric cancer.</p><p><b>METHODS</b>The plasma levels of adenosine deaminase (ADA), glutathione peroxidase (GPX), superoxide dismutase (SOD), and advanced oxidation protein products (AOPP) were determined by colorimetry, and the plasma levels of thioredoxin were determined by enzyme-linked immunosorbent assay (ELISA) in 48 gastric cancer patients and 30 healthy subjects. RT-PCR assay was employed to examine the expression levels of thioredoxin mRNA in the tissue samples of the patients.</p><p><b>RESULTS</b>Compared with the healthy controls, patients with gastric cancer had significantly increased plasma levels of ADA and AOPP (P<0.05), decreased plasma GPX level (P<0.05), and similar plasma SOD levels. The plasma levels of thioredoxin were significantly higher in patients with gastric cancer than in the healthy controls (P<0.05). Thioredoxin levels was not associated with gender, age, degree of tumor cell differentiation, invasion depth, or lymph node metastasis (P>0.05), but was correlated to distant tumor metastasis (P<0.05). The expression of Trx mRNA was significantly higher in gastric carcinoma than in normal gastric tissue (P<0.05).</p><p><b>CONCLUSION</b>Gastric cancer patients have high levels of oxidative stress and thioredoxin expression, and the latter is related to distant metastasis of the tumor.</p>

Relation of advanced oxidation protein products with VEGF and TGF-β1 in colon cancer cells exposed to intermittent hypoxia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association of advanced oxidation protein products (AOPP) with oxidative stress in colon cancer cells exposed to intermittent hypoxia (IH).</p><p><b>METHODS</b>Colon cancer SW480 cells were exposed to IH, continuous hypoxia, or normoxia. Enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of AOPP and vascular endothelial growth factor (VEGF), xanthine oxidase assay was used to determine malonaldehyde (MDA) and glutathione peroxidase (GSH-PX), and Western blotting and immunofluorescence assay were performed for detection of transforming growth factor-β(1) (TGF-β(1)) expression.</p><p><b>RESULTS</b>Compared with the normoxia group, the two hypoxia groups showed significantly increased AOPP and MDA levels (P<0.05) and lowered SOD and GSH-PX levels (P<0.05). The concentration of AOPP was positively correlated to MDA, VEGF, and TGF-β(1) levels (P<0.05), but inversely to SOD. No significant correlation was found between AOPP and GSH-PX levels.</p><p><b>CONCLUSION</b>Compared with continuous hypoxia, IH results in more obvious protein oxidation in relation to oxidative stress. The increased expression of VEGF and TGF-β(1) in the context of hypoxia is closely related to AOPP level.</p>