Increased renal ANP synthesis, but decreased or unchanged cardiac ANP synthesis in water-deprived and salt-restricted rats

Increased renal ANP synthesis, but decreased or unchanged cardiac ANP synthesis in water-deprived and salt-restricted rats.BackgroundExperiments were performed to examine the effect of water deprivation and salt restriction on ANP synthesis in the kidneys and hearts of normal rats.MethodsA 4-day water deprivation (WD) and 7-day salt restriction (SR; 0.01% NaCl) were performed in 12 and 14 rats, respectively. Atrial natriuretic peptide (ANP) mRNA expression in the kidney was assessed with reverse transcription-polymerase chain reaction coupled with Southern blot hybridization, while the ANP mRNA in the hearts was measured by Northern blot hybridization. ANP and angiotensin II concentrations in the extracted plasma were measured by radioimmunoassay. The molecular form of renal ANP-like protein was characterized by reverse phase—high-performance liquid chromatography (RP-HPLC).ResultsRenal outer and inner medullary ANP mRNA showed a respective 11-fold and ninefold increase in WD rats, and an eightfold and fivefold increase in SR rats as compared to corresponding control groups. Inversely, cardiac atrial ANP mRNA and plasma ANP were decreased in WD rats, whereas they did not change in the SR group. Plasma angiotensin II concentration increased in conjunction with the decrease of urine sodium excretion in both groups. RP-HPLC analysis revealed a 45% extraction of ANP in the WD rat kidneys, whereas only 3% ANP in the control kidneys migrated in a molecular form similar to cardiac atrial proANP.ConclusionsOur results demonstrate that water deprivation and salt restriction markedly enhance renal ANP mRNA, whereas water deprivation suppresses cardiac atrial ANP mRNA and plasma ANP concentrations. The current study indicates that renal ANP and cardiac atrial ANP appear to be two distinct systems regulated by different mechanisms and possibly exhibiting different intra-renal paracrine and systemic endocrine functions

Effect of membrane fusion protein AdeT1 on the antimicrobial resistance of Escherichia coli

Acinetobacter baumannii is a prevalent pathogen that can rapidly acquire resistance to antibiotics. Indeed, multidrug-resistant A. baumannii is a major cause of hospital-acquired infections and has been recognised by the World Health Organization as one of the most threatening bacteria to our society. Resistance-nodulation-division (RND) type multidrug efflux pumps have been demonstrated to convey antibiotic resistance to a wide range of pathogens and are the primary resistance mechanism employed by A. baumannii. A component of an RND pump in A. baumannii, AdeT1, was previously demonstrated to enhance the antimicrobial resistance of Escherichia coli. Here, we report the results of experiments which demonstrate that wild-type AdeT1 does not confer antimicrobial resistance in E. coli, highlighting the importance of verifying protein production when determining minimum inhibitory concentrations (MICs) especially by broth dilution. Nevertheless, using an agar-based MIC assay, we found that propionylation of Lys280 on AdeT1 renders E. coli cells more resistant to erythromycin

Identification of a New Peptide for Fibrosarcoma Tumor Targeting and Imaging In Vivo

A 12-mer amino acid peptide SATTHYRLQAAN, denominated TK4, was isolated from a phage-display library with fibrosarcoma tumor-binding activity. In vivo biodistribution analysis of TK4-displaying phage showed a significant increased phage titer in implanted tumor up to 10-fold in comparison with normal tissues after systemic administration in mouse. Competition assay confirmed that the binding of TK4-phage to tumor cells depends on the TK4 peptide. Intravenous injection of 131I-labeled synthetic TK4 peptide in mice showed a tumor retention of 3.3% and 2.7% ID/g at 1- and 4-hour postinjection, respectively. Tumor-to-muscle ratio was 1.1, 5.7, and 3.2 at 1-, 4-, and 24-hour, respectively, and tumors were imaged on a digital γ-camera at 4-hour postinjection. The present data suggest that TK4 holds promise as a lead structure for tumor targeting, and it could be further applied in the development of diagnostic or therapeutic agent

Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma.

There is relatively little literature on adjuvant radiotherapy after radical nephroureterectomy with bladder cuff excision (RNU) for patients with upper tract urothelial carcinoma (UTUC). This study was designed to determine the efficacy of adjuvant radiotherapy for patients with pT3N0M0 UTUC. We retrospectively reviewed 198 patients treated with RNU between December 2001 and January 2015. Postoperative radiotherapy was administered in 40 (20.2%) of patients. Patients who received radiotherapy were younger than those that did not (65.2 vs. 70.5 years, p = 0.023). With median follow up of 29.1 months, Kaplan-Meier analysis with the log-rank test demonstrated no significant differences between those omitting vs receiving adjuvant radiotherapy in regards to 2-year rates of overall survival (72.0% vs. 73.4%, p = 0.979), cancer-specific survival (73.2% vs. 75.3%, p = 0.844), and recurrence-free survival (61.2% vs. 66.3%, p = 0.742). However, in multivariable analysis with Cox regression, young age, absence of chronic kidney disease, negative lymphovascular invasion, negative surgical margin, and adjuvant chemotherapy were also associated with better cancer-specific survival. In conclusion, adjuvant radiotherapy did not offer any significant benefit in terms of overall, cancer-specific, and recurrence-free survivals in patients with pT3N0M0 UTUC after RNU. More effective systemic adjuvant chemotherapy is necessary to improve the outcome of these patients

Guard Ring Design to Prevent Edge Breakdown in Double-Diffused Planar InGaAs/InP Avalanche Photodiodes

We report on the design of an attached guard ring (AGR) and a floating guard ring (FGR) in a planar separate absorption, grading, charge, and multiplication In0.53Ga0.47As/InP avalanche photodiode to prevent premature edge breakdowns. The depths of the two Zn diffusions were utilized to manipulate the guard ring structures. Results from TCAD simulation indicate that the optimal AGR diffusion depth is right at the turning point where the breakdown current shifts from the edge of active region to the AGR region. The devices with optimal AGR depth contain significantly higher breakdown voltages than those of devices either with shallower—or without any— AGR. For the FGR design, a series of devices with different spacings between AGR and FGR and different FGR opening widths for diffusion were fabricated and characterized. We show that when the spacing is longer than the critical value, the breakdown voltage can increase ~1.5 V higher than those of the APD devices without FGR. In addition, the wider the FGR opening width, the higher the breakdown voltage. TCAD simulations were also performed to study the effect of FGR, but showed less pronounced improvements, which could be due the discrepancy between the calculated and experimental diffusion profile

Oenothera laciniata Hill Extracts Exhibits Antioxidant Effects and Attenuates Melanogenesis in B16-F10 Cells via Downregulating CREB/MITF/Tyrosinase and Upregulating p-ERK and p-JNK

Oenothera laciniata Hill is a perennial herb traditionally used to alleviate inflammatory complications. This study investigated the antioxidant and anti-melanogenic activities of O. laciniata. The methanolic extract (OLM) of O. laciniata and its different fractions, including ethyl acetate (OLEF), n-butanol (OLBF), and water (OLWF) fractions, were prepared. Antioxidant activities were evaluated by total phenolic content, the radical-scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•), and superoxide anion (O2−•), reducing capacity, and metal chelating ability. OLM and its fractions exhibited potent antioxidant activity in these in vitro assays, with a correlation between radical-scavenging activity and total phenolic content. OLM and its fractions inhibited the mushroom tyrosinase activity superior to the reference control, ascorbic acid. In B16-F10 melanoma cells, OLM and its fractions significantly decreased melanin production and tyrosinase activity. Mechanistic investigations revealed that OLM and its fractions inhibited tyrosinase and TRP-2 expressions via downregulating MITF and phosphorylated CREB and differentially inducing ERK or JNK phosphorylation. Additionally, OLM and its fractions caused no significant cytotoxicity towards B16-F10 or skin fibroblast cells at concentrations used in these cellular assays. These findings demonstrated the potential of O. laciniata extracts as the ideal skin protective agent with dual antioxidant and anti-melanogenic activities

Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma.

There is relatively little literature on adjuvant radiotherapy after radical nephroureterectomy with bladder cuff excision (RNU) for patients with upper tract urothelial carcinoma (UTUC). This study was designed to determine the efficacy of adjuvant radiotherapy for patients with pT3N0M0 UTUC. We retrospectively reviewed 198 patients treated with RNU between December 2001 and January 2015. Postoperative radiotherapy was administered in 40 (20.2%) of patients. Patients who received radiotherapy were younger than those that did not (65.2 vs. 70.5 years, p = 0.023). With median follow up of 29.1 months, Kaplan-Meier analysis with the log-rank test demonstrated no significant differences between those omitting vs receiving adjuvant radiotherapy in regards to 2-year rates of overall survival (72.0% vs. 73.4%, p = 0.979), cancer-specific survival (73.2% vs. 75.3%, p = 0.844), and recurrence-free survival (61.2% vs. 66.3%, p = 0.742). However, in multivariable analysis with Cox regression, young age, absence of chronic kidney disease, negative lymphovascular invasion, negative surgical margin, and adjuvant chemotherapy were also associated with better cancer-specific survival. In conclusion, adjuvant radiotherapy did not offer any significant benefit in terms of overall, cancer-specific, and recurrence-free survivals in patients with pT3N0M0 UTUC after RNU. More effective systemic adjuvant chemotherapy is necessary to improve the outcome of these patients

Characterization of a Novel Dermal Fibrosis Model Induced by Areca Nut Extract that Mimics Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is an oral potentially malignant disorder and areca quid chewing is the main etiological factor. However, the molecular mechanism underlying OSF remains unclear, partly due to the lack of an appropriate animal model. The present study aimed to establish and characterize an animal model of areca nut extract (ANE)-induced skin fibrosis that mimics OSF. Mice were divided into 4 groups: the control group; the bleomycin group; and the ANE10 and ANE20 groups, which received 10mg/ml and 20mg/ml subcutaneous (SC) injection of ANE, respectively. Skin fibrosis was evaluated by histological analyses. Additionally, the expression levels of the fibrotic marker genes were determined by immunohistochemical staining and immunoblotting. ANE administration significantly increased dermal thickness and collagen deposition compared with the control group. Moreover, ANE induced the expression of the fibrotic marker genes alpha smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) in the skin lesions. The SC injection of ANE successfully induced skin fibrosis, exhibiting characteristics similar to those of OSF. This model may facilitate future studies of the mechanism underlying OSF

Motor Cortical Activity during Observing a Video of Real Hand Movements versus Computer Graphic Hand Movements: An MEG Study

Both action observation (AO) and virtual reality (VR) provide visual stimuli to trigger brain activations during the observation of actions. However, the mechanism of observing video movements performed by a person’s real hand versus that performed by a computer graphic hand remains uncertain. We aimed to investigate the differences in observing the video of real versus computer graphic hand movements on primary motor cortex (M1) activation by magnetoencephalography. Twenty healthy adults completed 3 experimental conditions: the resting state, the video of real hand movements (VRH), and the video of computer graphic hand movements (CGH) conditions with the intermittent electrical stimuli simultaneously applied to the median nerve by an electrical stimulator. The beta oscillatory activity (~20 Hz) in the M1 was collected, lower values indicating greater activations. To compare the beta oscillatory activities among the 3 conditions, the Friedman test with Bonferroni correction (p-value < 0.017 indicating statistical significance) were used. The beta oscillatory activities of the VRH and CGH conditions were significantly lower than that of the resting state condition. No significant difference in the beta oscillatory activity was found between the VRH and CGH conditions. Observing hand movements in a video performed by a real hand and those by a computer graphic hand evoked comparable M1 activations in healthy adults. This study provides some neuroimaging support for the use of AO and VR in rehabilitation, but no differential activations were found