Aibika Flower Flavonoid Extract Exhibits Antiulcer Activity in a Murine Model of Ethanol-Induced Acute Gastric Injury.

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1ß, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.

Neuroprotective Effect of Abelmoschus manihot Flower Extracts against the H2O2-Induced Cytotoxicity, Oxidative Stress and Inflammation in PC12 Cells.

The progression of neurodegenerative diseases is associated with oxidative stress and inflammatory responses. Abelmoschus manihot L. flower (AMf) has been shown to possess excellent antioxidant and anti-inflammatory activities. This study investigated the protective effect of ethanolic extract (AME), water extract (AMW) and supercritical extract (AMS) of AMf on PC12 neuronal cells under hydrogen peroxide (H2O2) stimulation. This study also explored the molecular mechanism underlying the protective effect of AME, which was the best among the three extracts. The experimental results showed that even at a concentration of 500 µg/mL, neither AME nor AMW showed toxic effects on PC12 cells, while AMS caused about 10% cell death. AME has the most protective effect on apoptosis of PC12 cells stimulated with 0.5 mM H2O2. This is evident by the finding when PC12 cells were treated with 500 µg/mL AME; the viability was restored from 58.7% to 80.6% in the Treatment mode (p < 0.001) and from 59.1% to 98.1% in the Prevention mode (p < 0.001). Under the stimulation of H2O2, AME significantly up-regulated the expression of antioxidant enzymes, such as catalase, glutathione peroxidase and superoxide dismutase; promoted the production of the intracellular antioxidant; reduced glutathione; and reduced ROS generation in PC12 cells. When the acute inflammation was induced under the H2O2 stimulation, AME significantly down-regulated the pro-inflammatory cytokines and mediators (e.g., TNF-α, IL-1ß, IL-6, COX-2 and iNOS). AME pretreatment could also greatly promote the production of nucleotide excision repair (NER)-related proteins, which were down-regulated by H2O2. This finding indicates that AME could repair DNA damage caused by oxidative stress. Results from this study demonstrate that AME has the potential to delay the onset and progression of oxidative stress-induced neurodegenerative diseases.

Sigesbeckia orientalis Extract Ameliorates the Experimental Diabetic Nephropathy by Downregulating the Inflammatory and Oxidative Stress Signaling Pathways.

Diabetes in children and its complications are on the rise globally, which is accompanied by increasing in diabetes-related complications. Oxidative stress and inflammation induced by elevated blood sugar in diabetic patients are considered risk factors associated with the development of diabetes complications, including chronic kidney disease and its later development to end-stage renal disease. Microvascular changes within the kidneys of DM patients often lead to chronic kidney disease, which aggravates the illness. Sigesbeckia orientalis extract (SOE), reported to have strong antioxidative and excellent anti-inflammatory activities, is used in the modern practice of traditional Chinese medicine. Kidneys from three groups of control mice (CTR), mice with streptozotocin (STZ)-induced diabetes (DM), and mice with STZ-induced DM treated with SOE (DMRx) were excised for morphological analyses and immunohistochemical assessments. Only mice in the DM group exhibited significantly lower body weight, but higher blood sugar was present. The results revealed more obvious renal injury in the DM group than in the other groups, which appeared as greater glomerular damage and tubular injury, sores, and plenty of connective tissues within the mesangium. Not only did the DM group have a higher level of cytokine, tumor necrosis factor, and the oxidative stress marker, 8-hydroxyguanosine expression, but also factors of the nuclear factor pathway and biomarkers of microvascular status had changed. Disturbances to the kidneys in DMRx mice were attenuated compared to the DM group. We concluded that SOE is an effective medicine, with antioxidative and anti-inflammatory abilities, to protect against or attenuate diabetic nephropathy from inflammatory disturbances by oxidative stress and to cure vessel damage in a hyperglycemic situation.

Suppressive Effects of Siegesbeckia orientalis Ethanolic Extract on Proliferation and Migration of Hepatocellular Carcinoma Cells through Promoting Oxidative Stress, Apoptosis and Inflammatory Responses.

Previous studies have demonstrated that Siegesbeckia orientalis (SO) has a suppressive effect on the growth and migration of endometrial and cervical cancer cells. The present study examined the effect of SO ethanolic extract (SOE) on the proliferation and migration of hepatocellular carcinoma (HCC) and examined the effects of SOE on non-cancerous cells using HaCaT keratinocytes as a model. The SOE effectively inhibited the proliferation of Hepa1-6 (IC50 = 282.4 µg/mL) and HepG2 (IC50 = 344.3 µg/mL) hepatoma cells, whereas it has less cytotoxic effect on HaCaT cells (IC50 = 892.4 µg/mL). The SOE treatment increased the generation of ROS in HCC, but decreased the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. In contrast, it reduced intracellular ROS formation and upregulated the expression of the related antioxidant enzymes in the H2O2-stimulated HaCaT cells. The SOE intervention also down-regulated the anti-apoptotic Bcl-2 and the migration-related proteins including matrix metalloproteinases (MMPs) and ß-catenin in the HCC, suggesting that SOE could promote HCC apoptosis and inhibit HCC migration. On the contrary, it reduced apoptosis and promoted the migration of the keratinocytes. Additionally, the SOE treatment significantly up-regulated the pro-inflammatory cytokines, including TNF-α, IL-6 and IL-1ß, in Hepa1-6 and HepG2 cells. Conversely, it significantly decreased the expression of these cytokines in the H2O2-induced HaCaT cells. These findings indicated that SOE treatment can delay the progression of HCC by increasing oxidative stress, promoting inflammatory response, inducing cancer cell apoptosis and inhibiting their migration. It also has protective effects from pro-oxidant H2O2 in non-cancerous cells. Therefore, SOE may provide a potential treatment for liver cancer.

Effects of Abelmoschus manihot Flower Extract on Enhancing Sexual Arousal and Reproductive Performance in Zebrafish.

The flower of Abelmoschus manihot L. is mainly used for the treatment of chronic kidney diseases, and has been reported to have bioactivities such as antioxidant, anti-inflammatory, antiviral, and antidepressant activities. This study used wild-type adult zebrafish as an animal model to elucidate the potential bioactivity of A. manihot flower ethanol extract (AME) in enhancing their sexual and reproductive functions. Zebrafish were fed AME twice a day at doses of 0.2%, 1%, and 10% for 28 days, and were then given the normal feed for an additional 14 days. The hormone 17-ß estradiol was used as the positive control. Sexual behavioral parameters such as the number of times males chased female fish, the production of fertilized eggs, and the hatching rate of the fertilized eggs were recorded at days 0.33, 7, 14, 21, 28, and 42. The expression levels of sex-related genes­including lhcgr, ar, cyp19a1a, and cyp19a1b­were also examined. The results showed that the chasing number, fertilized egg production, and hatching rate were all increased with the increase in the AME treatment dose and treatment time. After feeding with 1% and 10% AME for 28 days, the chasing number in the treated group as compared to the control group increased by 1.52 times and 1.64 times, respectively; the yield of fertilized eggs increased by 1.59 times and 2.31 times, respectively; and the hatching rate increased by 1.26 times and 1.69 times, respectively. All three parameters exhibited strong linear correlations with one another (p < 0.001). The expression of all four genes was also upregulated with increasing AME dose and treatment duration. When feeding with 0.2%, 1%, and 10% AME for 28 days, the four sex-related genes were upregulated at ranges of 1.79−2.08-fold, 2.74−3.73-fold, and 3.30−4.66-fold, respectively. Furthermore, the effect of AME was persistent, as the promotion effect continued after the treatment was stopped for at least two weeks. The present findings suggest that AME can enhance the endocrine system and may improve libido and reproductive performance in zebrafish.

Association of plasma fatty acid-binding protein 3 with estimated glomerular filtration rate in patients with type 2 diabetes mellitus.

Background: Fatty acid-binding protein 3 (FABP3) located in renal mesangial and distal tubular cells, and had been shown to be a sensitive marker of renal injury, potentially be a mediator in pathogenesis of chronic kidney disease (CKD). Our previous study revealed that plasma FABP1 and FABP2 were independently associated with CKD, however, little is known about the relationship between plasma FABP3 level and CKD. The aim of this study was therefore to evaluate the plasma levels of FABP3 at different stages of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 334 subjects with T2DM who enrolled in a disease management program were included in this study and stratified according to eGFR. Plasma FABP3 concentrations were measured by an enzyme-linked immunosorbent assay. Results: FABP3 levels increased in parallel with the eGFR level. Increasing concentrations of FABP3 were independently and significantly associated with eGFR stage G2-G4. Age- and sex-adjusted FABP3 levels were positively associated with uric acid, urinary albumin-to-creatinine ratio, FABP1, FABP2, and fatty liver index, but negatively associated with eGFR and hemoglobin. Conclusion: Our results indicate that circulating FABP3 in patients with T2DM is associated with eGFR, which suggests that increased plasma FABP3 may be involved in the pathogenesis of CKD.

Glossogyne tenuifolia Extract Increases Nitric Oxide Production in Human Umbilical Vein Endothelial Cells.

The vascular nitric oxide (NO) system has a protective effect in atherosclerosis. NO is generated from the conversion of L-arginine to L-citrulline by the enzymatic action of endothelial NO synthase (eNOS). Compounds with the effect of enhancing eNOS expression are considered to be candidates for the prevention of atherosclerosis. In this study, extracts from the aerial, root, and whole plant of Glossogyne tenuifolia (GT) were obtained with ethanol, n-hexane, ethyl acetate (EA), and methanol extraction, respectively. The effects of these GT extracts on the synthesis of NO and the expression of eNOS in human umbilical vein endothelial cells (HUVECs) were investigated. NO production was determined as nitrite by colorimetry, following the Griess reaction. The treatment of HUVECs with EA extract from the root of GT and n-hexane, methanol, and ethanol extract from the aerial, root, and whole plant of GT increased NO production in a dose-dependent manner. When at a dose of 160 µg/mL, NO production increased from 0.9 to 18.4-fold. Among these extracts, the methanol extract from the root of GT (R/M GTE) exhibited the most potent effect on NO production (increased by 18.4-fold). Furthermore, using Western blot and RT-PCR analysis, treatment of HUVECs with the R/M GTE increased both eNOS protein and mRNA expression. In addition, Western blot analysis revealed that the R/M GTE increased eNOS phosphorylation at serine1177 as early as 15 min after treatment. The chemical composition for the main ingredients was also performed by HPLC analysis. In conclusion, the present study demonstrated that GT extracts increased NO production in HUVECs and that the R/M GTE increased NO production via increasing eNOS expression and activation by phosphorylation of eNOS at serine1177.

Elevated plasma level of neutrophil gelatinase-associated lipocalin (NGAL) in patients with breast cancer.

Background: Neutrophil gelatinase­associated lipocalin (NGAL), also known as lipocalin 2, siderocalin, 24p3 or uterocalin, plays a key role in inflammation and in different types of cancer. In this study, we investigated whether plasma NGAL levels were altered in patients with breast cancer. The relationship between plasma NGAL levels and pretreatment hematologic profile was also explored. Methods: Plasma NGAL concentrations were measured using ELISA in breast cancer patients and control subjects. A total of 75 patients with breast cancer and 65 age- and body mass index-matched control subjects were studied. All of the study subjects were female. Results: Plasma NGAL level was found to be elevated in the patients with breast cancer compared to the control subjects (94.3 ng/mL (interquartile range 39.3-207.6) vs. 55.0 ng/mL (interquartile range 25.8-124.7), p = 0.007). Multiple logistic regression analysis revealed that NGAL was independently associated with breast cancer, even after adjusting for known biomarkers. Furthermore, NGAL level was elevated in the breast cancer patients who were negative progesterone receptor status, had a histologic grade ≥ 2, clinical stage III, and pathologic stage T2+T3+T4. In addition, NGAL level was significantly correlated with white blood cell (WBC) count, monocyte count, neutrophil count, and platelet count (all p < 0.01). Moreover, WBC count, neutrophil count, monocyte count, lymphocyte count, platelet count, and NGAL level gradually increased as the stage progressed. Conclusions: Increased plasma NGAL levels were associated with breast cancer independently of risk factors, and were correlated with inflammatory biomarkers. These results suggest that NGAL may act through inflammatory reactions to play an important role in the pathogenesis of breast cancer.

Glossogyne tenuifolia Attenuates Proliferation and Migration of Vascular Smooth Muscle Cells.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the pathogenesis of various vascular diseases, such as atherosclerosis and restenosis. Among the mediators of VSMC during atherosclerosis development, platelet-derived growth factor (PDGF)-BB is a potent mitogen for VSMCs and greatly contributes to the intimal accumulation of VSMCs. Glossogyne tenuifolia (GT, Xiang-Ru) is a traditional antipyretic and hepatoprotective herb from Penghu Island, Taiwan. This study evaluated the inhibitory effect of GT ethanol extract (GTE) and GT water extract (GTW) on proliferative and migratory activities in PDGF-BB-induced VSMCs. The experimental results demonstrated that GTE significantly inhibited the PDGF-BB-stimulated VSMC proliferation and migration, as shown by MTT, wound healing, and Boyden chamber assays. GTE was found to have a much more potent inhibitory activity than GTW. Based on the Western blot analysis, GTE significantly blocked the PDGF-BB-induced phosphorylation of NF-κB and mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK), p38, and JNK, in VSMCs. In addition, GTE retarded the PDGF-BB-mediated migration through the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression in VSMCs. Three main ingredients of GT-chlorogenic acid, luteolin-7-glucoside, and luteolin-all showed significant anti-proliferative effects on PDGF-BB-induced VSMCs. As a whole, our findings indicated that GTE has the potential to be a therapeutic agent to prevent or treat restenosis or atherosclerosis.

Antrodia cinnamomea Extraction Waste Supplementation Promotes Thermal Stress Tolerance and Tissue Regeneration Ability of Zebrafish.

Antrodia cinnamomea (AC) has been shown to have anti-inflammatory, anti-tumor, and immunomodulation activities. It is estimated that hundreds of metric tons of AC extraction waste (ACEW) are produced per year in Taiwan. This study aims to assess the feasibility of applying ACEW as feed supplement in the aquaculture industry. ACEW significantly inhibited the growth of microorganisms in the water tank, by around 39.4% reduction on the fifth day with feed supplemented of 10% ACEW. The feed conversion efficiency of zebrafish with 10% ACEW supplementation for 30 days was 1.22-fold compared to that of the control. ACEW dramatically improved the tolerances of zebrafish under the heat and cold stresses. When at water temperature extremes of 38 °C or 11 °C, compared to the 100% mortality rate in the control group, the 10% ACEW diet group still had 91.7% and 83.3% survival rates, respectively. In a caudal fin amputation test, the fin recovery of zebrafish was increased from 68.4% to 93% with 10% ACEW diet after 3-week regeneration. ACEW effectively down-regulated the gene expression of TNF-α, IL-1ß, IL-6, and IL-10, and up-regulated the gene expression of IL-4/13A. Additionally, the supplement of ACEW in the feed can maintain and prevent the fish's body weight from dropping too much under enteritis. Taken together, ACEW has beneficial potential in aquaculture.

Elevated Plasma Adiponectin Levels Are Associated with Abnormal Corrected QT Interval in Patients with Stable Angina.

Low-circulating levels of adiponectin (ADPN) are associated with obesity, diabetes mellitus, and coronary artery disease. On the contrary, some studies have demonstrated a link between relatively high levels of plasma ADPN and heart failure, atrial fibrillation, and adverse outcome. However, little is known about the relationship between ADPN level and prolonged QT interval. The aim of this study was to investigate the association between plasma ADPN levels and prolonged QT interval in patients with stable angina.In this retrospective study, because the diverse disease severity and condition of the study population may have affected the results, we chose individuals with stable angina. Plasma ADPN concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient.We enrolled 479 stable-angina patients. Patients with an abnormal corrected QT (QTc) interval had higher median plasma ADPN levels than those with normal QTc intervals. Age- and sex-adjusted ADPN levels were positively associated with heart rate, QTc interval, left ventricular mass index, and creatinine but negatively associated with left ventricular ejection fraction, waist circumference, current smoking, total cholesterol, triglycerides, low-density lipoprotein cholesterol, albumin, and estimated glomerular filtration rate. A multiple logistic regression analysis revealed ADPN as an independent association factor for abnormal QTc interval. Increasing concentrations of sex-specific ADPN were independently and significantly associated with abnormal QTc interval, even after full adjustment of known biomarkers.Our results indicate that ADPN may play a role in the pathogenesis of abnormal QTc interval in patients with stable angina.

The Arrhythmogenic Effect of Protein-Bound Uremic Toxin p-Cresylsulfate: An In Vitro Study.

BACKGROUND: p-Cresylsulfate (PCS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease. Previous studies have indicated that serum total PCS levels are significantly increased in the presence of abnormal corrected QT (QTc) intervals, and that they are associated with QTc prolongation. However, the QTc prolongation effect of PCS remains unclear. The current study aimed to investigate the arrhythmogenic effect of PCS using in vitro experiments and computer simulation. METHODS: The arrhythmogenic effect of PCS was evaluated by incubating H9c2 rat ventricular cardiomyocytes in vitro with increasing concentrations of PCS. Electrophysiological studies and mathematical computer simulations were performed. RESULTS: in vitro, the delayed rectifier potassium current (IK ) was significantly decreased in a dose-dependent manner after treatment with PCS. The modulation of PCS on IK was through regulation of the phosphorylation of the major potassium ion channel protein Kv2.1. In computer simulations, the decrease in IK induced by PCS prolonged the action potential duration (APD) and sped up the re-entrant wave, which is known to be a trigger mechanism for lethal ventricular arrhythmias. CONCLUSIONS: PCS significantly downregulated the phosphorylation of the IK channel protein Kv2.1 and IK current activity, which increased the cardiomyocyte APD. This was observed both in vitro and in the computer O'Hara-Rudy dynamic human ventricular model. These findings suggest that PCS may play a key role in the development of cardiac arrhythmias.

Plasma fatty acid-binding protein 4 (FABP4) level is associated with abnormal QTc interval in patients with stable angina and chronic kidney disease.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) (also known as adipocyte FABP or adipocyte P2) is expressed in adipocytes, macrophages, and capillary endothelial cells. Previous studies have shown associations among plasma FABP4, insulin resistance, metabolic syndrome, diabetes mellitus, greater coronary plaque burden, coronary artery disease, heart failure, and mortality. However, little is known about the relationship between FABP4 level and prolonged QT interval. The aim of this study was to investigate whether plasma FABP4 level is associated with a prolonged QT interval by analyzing 12-lead electrocardiograms (ECGs) in patients with stable angina and chronic kidney disease (CKD). METHODS: This study included 397 consecutive patients with stable angina and CKD who were enrolled in a disease management program. Plasma FABP4 concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient. We assessed the relationships between FABP4 levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation. RESULTS: Patients with an abnormal QTc interval had higher median plasma FABP4 levels than those with borderline and normal QTc intervals (15.9 ng/mL vs. 10.2 ng/mL vs. 8.5 ng/mL, respectively, P < 0.0001). Statistically significant associations were observed between plasma FABP4 levels and QTc interval (ß = 0.267, P < 0.0001). Using multivariate and trend analyses, a higher concentration of plasma FABP4 level was independently associated with QTc prolongation in patients with stable angina and CKD. CONCLUSION: In this study, plasma FABP4 levels were significantly higher in the patients with an abnormal QTc interval and were correlated with QTc prolongation. Further studies are required to elucidate whether plasma FABP4 plays a role in the pathogenesis of QTc prolongation.

Bulnesia sarmientoi Supercritical Fluid Extract Exhibits Necroptotic Effects and Anti-Metastatic Activity on Lung Cancer Cells.

Bulnesia sarmientoi (BS) has long been used as an analgesic, wound-healing and anti-inflammatory medicinal plant. The aqueous extract of its bark has been demonstrated to have anti-cancer activity. This study investigated the anti-proliferative and anti-metastatic effects of BS supercritical fluid extract (BSE) on the A549 and H661 lung cancer cell lines. The cytotoxicity on cancer cells was assessed by an MTT assay. After 72 h treatment of A549 and H661 cells, the IC50 values were 18.1 and 24.7 µg/mL, respectively. The cytotoxicity on MRC-5 normal cells was relatively lower (IC50 = 61.1 µg/mL). BSE arrested lung cancer cells at the S and G2/M growth phase. Necrosis of A549 and H661 cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Moreover, the cytotoxic effect of BSE on cancer cells was significantly reverted by Nec-1 pretreatment, and BSE induced TNF-α and RIP-1 expression in the absence of caspase-8 activity. These evidences further support that BSE exhibited necroptotic effects on lung cancer cells. By wound healing and Boyden chamber assays, the inhibitory effects of BSE on the migration and invasion of lung cancer cells were elucidated. Furthermore, the chemical composition of BSE was examined by gas chromatography-mass analysis where ten constituents of BSE were identified. α-Guaiene, (-)-guaiol and ß-caryophyllene are responsible for most of the cytotoxic activity of BSE against these two cancer cell lines. Since BSE possesses significant cytotoxicity and anti-metastatic activity on A549 and H661 cells, it may serve as a potential target for the treatment of lung cancer.

Association between hippuric acid and left ventricular hypertrophy in maintenance hemodialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end-stage renal disease. Hippuric acid (HA), a harmful uremic toxin, is known to be elevated in patients with uremia, and serum HA levels are associated with neurological symptoms, metabolic acidosis, and accelerated renal damage associated with chronic kidney disease. However, the pathophysiological role of HA in patients with uremia remains unclear. We investigated the association between serum HA levels and echocardiographic measurements in patients undergoing hemodialysis (HD) treatment. METHODS: Eighty consecutive patients treated at a single HD center (44 males, 36 females; mean age 66 y, mean HD duration 6 y) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. RESULTS: Pearson's correlation analysis revealed that serum HA levels were positively correlated with diastolic blood pressure, serum creatinine, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-diastolic diameter, left ventricular end systolic diameter, end systolic left ventricular posterior wall thickness, and left atrium diameter, and negatively correlated with age. Furthermore, the HD patients with LVH had higher median serum HA levels than those without LVH (34.2 vs. 18.1 µg/ml, p = 0.003). Multiple logistic regression analysis revealed that HA was independently associated with LVH even after adjusting for known biomarkers. Moreover, the receiver operator characteristics curve of HA showed that a HA level of >26.9 µg/ml was associated with LVH. CONCLUSIONS: HA was significantly associated with LVH. HA could be a novel biomarker of left ventricular overload, which is closely associated with an increased risk of death in HD patients.

Circulating secreted frizzled-related protein 5 and chronic kidney disease in patients with acute ST-segment elevation myocardial infarction.

Secreted frizzled-related protein-5 (Sfrp5) known as secreted antagonist binds to Wnt protein. It has been shown to be downregulated by histone acetylation and promoter methylation, and to function as a tumor suppressor gene by inducing apoptosis in renal cell cancer cells. However, its relationship with chronic kidney disease (CKD) has not been well studied. Our objective was to investigate the effect of plasma Sfrp5 levels in subjects with and without CKD. Plasma Sfrp5 levels were determined by enzyme-linked immunosorbent assays in 196 consecutive patients with acute ST-segment elevation myocardial infarction (STEMI). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. For the purpose of this study, stage 1 or 2 CKD patients (eGFR ≥ 60 ml/min per 1.73 m2) were classified as not having CKD. With increasing Sfrp5 tertiles, the patients had higher frequencies of hypertension, stage 4 or 5 CKD, and waist-to-hip ratio, incrementally lower eGFRs and serum hemoglobin levels, and higher levels of blood urine nitrogen (BUN), creatinine, and adiponectin. Multivariate logistic regression analysis showed that an increased plasma Sfrp5 level was independently associated with CKD for all subjects (adjusted odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.14; p = 0.011). Sfrp5 was also significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin. When the patients were stratified by age, plasma Sfrp5 level was independently related to CKD for patients >65 years old (adjusted OR, 1.10; 95% CI, 1.00-1.20; p = 0.045), however, the association was not significant for those <65 years old. In addition, Sfrp5 was significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin in patients >65 years old. Our results suggest that Sfrp5 may play a role in the pathogenesis of CKD in acute STEMI patients who are older than 65 years.

Shift work is associated with metabolic syndrome in male steel workers-the role of resistin and WBC count-related metabolic derangements.

AIMS: There is increasing evidence linking a shift work schedule with various adverse health effects. The present study aimed to examine the relationship between shift work and the metabolic syndrome (MetS) in male steel workers, and also the possible mechanism of shift work-related metabolic derangements. METHODS: A total of 1732 men aged 42 ± 8 years were enrolled in this cross-sectional study, including 862 day workers and 870 shift workers. Circulating levels of resistin were measured by ELISA using monoclonal specific antibodies. RESULTS: The shift workers had higher rates of MetS and its components (central obesity, hypertension, and hypertriglyceridemia) than the day workers. In multiple logistic regression analysis, shift work was independently associated with MetS. In further analysis, the shift workers had elevated circulating levels of resistin (13 ± 10 vs. 10 ± 7 ng/mL) and total white blood cell (WBC) count (6.865 ± 1.819 vs. 6.304 ± 1.547 109/L) than the day workers. In addition, both resistin level and total WBC count were significantly associated with shift work, MetS, and its components (body mass index, fasting glucose, triglyceride, and high-density lipoprotein-cholesterol levels), and plasma resistin levels were significantly associated with total WBC count (ß = 0.34, p < 0.0001). CONCLUSION: Shift work was independently associated with MetS in male steel workers. Resistin and WBC count were associated with shift work-related metabolic derangements.

Inhibitory Effects of Siegesbeckia orientalis Extracts on Advanced Glycation End Product Formation and Key Enzymes Related to Metabolic Syndrome.

Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase, pancreatic lipase and angiotensin I-converting enzyme (ACE). This study used an in vitro approach to assess the potential of four extracts of Siegesbeckia orientalis linne on key enzymes relevant to metabolic syndrome. In this research, S. orientailis was firstly extracted by ethanol. The ethanol extract (SE) was then partitioned sequentially with hexane, ethyl acetate and methanol, and these extracts were named SE-Hex, SE-EA and SE-MeOH, respectively. The experimental results showed that SE-EA had the highest total phenolic content (TPC, 76.9 ± 1.8 mg/g) and the total flavonoids content (TFC, 5.3 ± 0.3 mg/g). This extract exhibited the most significant antioxidant activities, including DPPH radical-scavenging capacity (IC50 = 161.8 ± 2.4 µg/mL), ABTS radical-scavenging capacity (IC50 = 13.9 ± 1.5 µg/mL) and reducing power. For anti-glycation activities, SE-EA showed the best results in the inhibition of AGEs, as well as inhibitory activities against α-glucosidase (IC50 = 362.3 ± 9.2 µg/mL) and α-amylase (IC50 = 119.0 ± 17.7 µg/mL). For anti-obesity activities, SE-EA indicated the highest suppression effect on pancreatic lipase (IC50 = 3.67 ± 0.52 mg/mL). Finally, for anti-hypertension activity, SE-EA also demonstrated the strongest inhibitory activity on ACE (IC50 = 626.6 ± 15.0 µg/mL). Close relationships were observed among the parameters of TPC, antioxidant activities, inhibitory activities on α-amylase, α-glucosidase, lipase and ACE (R > 0.9). Moderate correlations were found among the parameters of TFC, antioxidant activities, and suppression of dicarbonyl compounds formation (R = 0.5-0.9). Taken together these in vitro studies reveal the therapeutic potential of SE-EA extract in the prevention and treatment of metabolic disorders.

Glossogyne tenuifolia (Hsiang-ju) extract suppresses T cell activation by inhibiting activation of c-Jun N-terminal kinase.

BACKGROUND: Glossogyne tenuifolia (GT) (Hsiang-ju) is a Chinese herbal medicine previously exhibited an anti-inflammatory activity. This study aimed to investigate the effect of GT ethanol extract (GTE) on T cell-mediated adaptive immunity. METHODS: Human peripheral blood mononuclear cells (PBMCs) and Jurkat T cells were activated by phytohemagglutinin in the presence of various doses (3.13-50 µg/mL) of GTE. The effect of GTE on T cell activation was examined by a proliferation assay of activated PBMCs and the level of the activation marker CD69 on the surface of activated Jurkat T cells. Apoptosis was determined by propidium iodide staining in hypotonic solution. Signaling pathway molecules were assessed by western blotting. RESULTS: Glossogyne tenuifolia ethanol extract was demonstrated to inhibit T cell activation, not only in the proliferation of human PBMCs at the concentrations of 12.5, 25 and 50 µg/mL (P = 0.0118, 0.0030 and 0.0021) but also in the CD69 expression in Jurkat cells, which was not due to the cytotoxicity of GTE. The presence of GTE did not change the activity of nuclear factor kappa-light-chain-enhancer of activated B cells or extracellular signal-regulated kinase upon T cell activation. In addition, GTE significantly reduced activation of c-Jun N-terminal kinase (JNK) (P = 0.0167) and p38 (P = 0.0278). Furthermore, decreased JNK activation mediated the preventive effect of GTE on T cell activation-induced cell death (AICD). CONCLUSION: Glossogyne tenuifolia ethanol extract inhibited T cell activation of Jurkat cells and freshly prepared human PBMCs due to suppression of JNK activity. Furthermore, GTE inhibited AICD by blocking prolonged JNK phosphorylation in activated T cells. Taken together, the anti-inflammatory effects exerted by GTE were mediated via suppression of JNK phosphorylation in T cell activation.

Siegesbeckia orientalis Extract Inhibits TGFß1-Induced Migration and Invasion of Endometrial Cancer Cells.

Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE) on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor ß (TGFß). The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFß1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFß1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors.