A novel instrumentation circuit for electrochemical measurements.

In this paper, a novel signal processing circuit which can be used for the measurement of H(+) ion and urea concentration is presented. A potentiometric method is used to detect the concentrations of H(+) ions and urea by using H(+) ion-selective electrodes and urea electrodes, respectively. The experimental data shows that this measuring structure has a linear pH response for the concentration range within pH 2 and 12, and the dynamic range for urea concentration measurement is in the range of 0.25 to 64 mg/dL. The designed instrumentation circuit possesses a calibration function and it can be applied to different sensing electrodes for electrochemical analysis. It possesses the advantageous properties of being multi-purpose, easy calibration and low cost.

Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on antimetastasis in human prostate cancer DU-145 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, wound-healing assay, and Boyden chamber assay. Data also showed acacetin could inhibit the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels. Next, acacetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, the treatment with acacetin to DU145 cells also leads to a dose-dependent inhibition on the binding ability of NF-kappaB and activator protein-1 (AP-1). Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to DU145 cells could cause reduced expressions of MMP-2, MMP-9, and u-PA. These results showed acacetin could inhibit the invasion and migration abilities of DU145 cells by reducing MMP-2, MMP-9, and u-PA expressions through suppressing p38 MAPK signaling pathway and inhibiting NF-kappaB- or AP-1-binding activity. These findings proved acacetin might be offered further application as an antimetastatic agent.

Risk factors for and progression of myopia in young Taiwanese men.

UNLABELLED: Abstract Purpose: To investigate the association between potential risk factors for myopia and its progression in young adult Taiwanese men. METHODS: A survey of male military conscripts (aged 18-24 years) was conducted from February 2010 to March 2011 in Taiwan. Participants underwent comprehensive eye examinations, including measurements of axial length and corneal radius by optical biometry and non-cycloplegic autorefraction. Participants also provided self-reported progression of myopia and information regarding potential risk factors, including age, parental myopia, educational level, close work, outdoor activities, and urbanization. RESULTS: Of 5145 eligible participants, 5048 (98.11%) provided refraction and questionnaire data; 2316 (45.88%) of the 5048 also had biometric measurements. The prevalence of myopia was 86.1% in this group, with a mean refractive error of -3.66 diopters (D). Of the 5048 participants, 1376 (27.3%) had experienced progression of their myopia during the past year. There were trends for a higher prevalence of myopia among older participants (p = 0.014), those with a history of parental myopia (p < 0.001), higher levels of education (p = 0.001), increased time spent reading (p < 0.001), less time outdoors (p = 0.003), and higher levels of urbanization (p = 0.010). However, only parental myopia, close work, and higher urbanization levels were significantly associated with self-reported progression of myopia. CONCLUSION: Older age, parental myopia, higher educational level, close work, fewer outdoor activities, and higher urbanization level were associated with the prevalence of myopia in Taiwanese men.

Antihypertensive action of allantoin in animals.

The agonists of imidazoline I-1 receptors (I-1R) are widely used to lower blood pressure. It has been indicated that guanidinium derivatives show an ability to activate imidazoline receptors. Also, allantoin has a chemical stricture similar to guanidinium derivatives. Thus, it is of special interest to characterize the effect of allantoin on I-1R. In conscious male spontaneous hypertensive rats (SHRs), mean blood pressure (MBP) was recorded using the tail-cuff method. Furthermore, the hemodynamic analyses in catheterized rats were applied to measure the actions of allantoin in vivo. Allantoin decreased blood pressures in SHRs at 30 minutes, as the most effective time. Also, this antihypertensive action was shown in a dose-dependent manner from SHRs treated with allantoin. Moreover, in anesthetized rats, allantoin inhibited cardiac contractility and heart rate as showing in hemodynamic dP/dt max significantly. Also, the peripheral blood flow was markedly increased by allantoin. Both actions were diminished by efaroxan at the dose sufficient to block I-1R. Thus, we suggest that allantoin, as I-1R agonist, has the potential to develop as a new therapeutic agent for hypertension in the future.

Characterization of imidazoline receptors in blood vessels for the development of antihypertensive agents.

It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP) channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.

The role of IL-7 in renal proximal tubule epithelial cells fibrosis.

BACKGROUND: Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, interleukin-7 (IL-7) may exert antifibrotic activities in pulmonary fibrosis model. However, the role of IL-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, we hereby elucidate the effects of IL-7 in cultured renal proximal tubular epithelial cells (designated as HK-2) treated under hyperglycemic condition. METHODS: Cells were cultured in high glucose (27.5mM) for 2 days. Different concentration of IL-7 (10, 50, 100 or 200ng/ml) was added in the last 24h of culture. ELISA was used to evaluate the secreted protein such as fibronectin and TGF-ß(1). Western blot was used to examine the EMT marker (including α-smooth muscle actin (α-SMA) and E-cadherin), signal transducer (including Smad Smad2/3 and Smad7) and EMT initiator (e.g. Snail). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin and Snail). RESULTS: We found that IL-7 significantly attenuated high glucose-inhibited cellular growth and high glucose-induced fibrosis. More importantly, high glucose-induced up-regulation of fibronectin, TGF-ß, TGF-ß RII and pSmad2/3 was markedly inhibited by IL-7. On the contrary, high glucose-induced down-regulation of Smad7 was significantly reversed by IL-7 instead. IL-7 markedly inhibited high glucose-induced increase in α-SMA and Snail and decrease in E-cadherin. CONCLUSION: We demonstrate that IL-7 has the potential to inhibit high glucose-induced renal proximal tubular fibrosis partly by modulating Smads and EMT pathway.

Effect of Lactobacillus reuteri GMNL-263 treatment on renal fibrosis in diabetic rats.

Hyperglycemia is the most important factor in the progression of renal fibrosis in diabetic kidney. Prevention and treatment of renal fibrosis may improve diabetic nephropathy. To explore whether probiotic Lactobacillus reuteri GMNL-263 treatment was linked to altered hyperglycemia-mediated renal fibrosis in diabetic kidney, the mechanisms of L. reuteri GMNL-263 treatment responsible for the inhibition of renal fibrosis in streptozotocin (STZ)-induced diabetic rats were examined. Diabetic rats were induced by intraperitoneal injection of STZ (50 mg/kg). Induction of diabetes was confirmed by measurement of the blood glucose using the glucose oxidase method, and hyperglycemic rats with levels >16 mmol/L were used. We found that L. reuteri GMNL-263 treatment caused reduction of glycated hemoglobin and blood glucose levels in STZ-induced diabetic rats for 28 days (all p<0.05). Treatment with L. reuteri GMNL-263 increased body weight but decreased kidney weight in diabetic rats as compared to diabetic control (p<0.05). In diabetic renal cortex, the Janus kinase 2/signal transducers and activators of transcription 1 (but not extracellular signal-regulated kinase/c-Jun N-terminal kinase/p38 mitogen-activated protein kinase) activation was markedly blocked by L. reuteri GMNL-263 treatment. The ability of L. reuteri GMNL-263 treatment to inhibit renal fibrosis was verified by the observation that it significantly decreased protein levels of plasminogen activator inhibitor-1, p21(Waf1/Cip1), α-smooth muscle actin, and fibronectin in diabetic renal cortex. The results obtained in this study indicate that L. reuteri GMNL-263 treatment may protect STZ-induced diabetic rats from hyperglycemia-enhanced renal fibrosis.

Alpha-mangostin suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expressions via alphavbeta3 integrin/FAK/ERK and NF-kappaB signaling pathway in human lung adenocarcinoma A549 cells.

The purpose of this study is to investigate the anti-metastatic effect of alpha-mangostin on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in A549 human lung adenocarcinoma cells. Firstly, alpha-mangostin could inhibit PMA-induced abilities of the adhesion, invasion, and migration. Data also showed alpha-mangostin could inhibit the activation of alphavbeta3 integrin, focal adhesion kinase (FAK), and extracellular signal-regulated kinase1/2 (ERK1/2) involved in the downregulation the enzyme activities, protein and messenger RNA levels of MMP-2 and MMP-9 induced by PMA. Next, alpha-mangostin also strongly inhibited PMA-induced degradation of inhibitor of kappaBalpha (IkappaBalpha) and the nuclear levels of nuclear factor kappa B (NF-kappaB). Also, a dose-dependent inhibition on the binding abilities of NF-kappaB by alpha-mangostin treatment was further observed. Furthermore, reduction of FAK or ERK1/2 phosphorylation by FAK small interfering RNA (FAK siRNA) potentiated the effect of alpha-mangostin. Finally, the transient transfection of ERK siRNA significantly down-regulated the expressions of MMP-2 and MMP-9 concomitantly with a marked inhibition on cell invasion and migration. Presented results indicated alpha-mangostin is a novel, effect, anti-metastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.

Dividable membrane with multi-reaction wells for microarray biochips.

This paper presents a multi-well membrane fabricated using polydimethylsiloxane (PDMS) as a part of a microarray biochip that allows dividable incubation chambers to be provided on a single chip. The conditions of the forming temperature, time, and mixing proportion of the materials were investigated to obtain optimal physical absorption with the surface of the chip substrate. To verify the properties of the multi-well chip, immunoassays were performed by the alpha-1-fetoprotein (AFP) antigen sandwich experiment. The results showed that the detection limit reached to the concentration of 10 ng/ml AFP antigen, and that the dynamic range was 30-3000 ng/ml. Attaining excellent physical absorption helps in avoiding cross-contamination or interference between different samples on the same biochip. The merits of dividable multi-well chips include promoting effective use of surface and multiple-sample experiments.