Serotonin Effects on Expression of the LDL Receptor Family Member LR11 and 7-Ketocholesterol–Induced Apoptosis in Human Vascular Smooth Muscle Cells

We previously confirmed the effect of sarpogrelate hydrochloride (sarpogrelate), 5-hydroxytryptamine (5-HT) 2A receptor antagonist on cardio-ankle vascular index (CAVI) as a marker of systemic arterial stiffness. After 6 months of treatment with sarpogrelate for 35 type 2 diabetic patients, decreased CAVI, indicating the ameliorated arterial stiffness, was observed. Therefore, via 5-HT2A receptor blockade, sarpogrelate might effect as a vasoactive agent, as well as an inhibitor of platelet aggregation. 5-HT is a known mitogen for vascular smooth muscle cells (VSMCs). In addition, the pathogenic change of VSMCs such as dedifferentiation and proliferation/apoptosis represents one of the atherosclerotic changes. On the other hand, LR11, a mosaic LDL receptor family member, may involve in the invasion of VSMCs into neointimal thickening. We therefore investigated an in vitro study to clarify whether 5-HT was concerned to LR11 expression and apoptosis of human VSMCs induced by 7-ketocholesterol (7KCHO), a major oxidation product of cholesterol involved in plaque destabilization. Resultantly, 5-HT accelerated the proliferation of VSMCs, and this effect was suppressed by simultaneous addition of sarpogrelate. Sarpogrelate also attenuated the 5-HT–induced LR11 mRNA expression in VSMCs. Additionally, 5-HT attenuated the 7KCHO-induced apoptosis of VSMCs through caspase-dependent pathway. These results suggest new knowledge on the modification of human VSMCs induced by 5-HT

NADase as a target molecule of in vivo suppression of the toxicity in the invasive M-1 group A Streptococcal isolates

<p>Abstract</p> <p>Background</p> <p>NAD-glycohydrolase (NADase) secreted by M-1 group A streptococcal (GAS) isolates are suspected as one of the virulence factors to cause severe invasive disease including streptococcal toxic shock-like syndrome (STSS). M-1 GAS strains were divided into three groups based on NADase activity: high activity, low activity and no activity in our previous report.</p> <p>Results</p> <p>The representative high activity isolates taken from STSS patients showed higher virulence compared with isolates from the low activity group, when used to infect mice. The knockout mutant of the <it>nga </it>gene, which encodes NADase also showed reduced virulence in a mouse infection study. The cloned <it>nga </it>gene was able to significantly complement the lost virulence. In addition, the solution containing purified recombinant IFS, which is an inhibitor of NADase, partially rescued mice infected with <it>S. pyogenes</it>.</p> <p>Conclusions</p> <p>These results indicate that NADase is important for the virulence of <it>S. pyogenes </it>in vivo and is the potential target to suppress the virulence.</p

Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans.

Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFβ signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity.AW and AVP were supported by FP7 – BetaBAT, BBSRC (BB/J009865/1), the British Heart Foundation (PG/12/53/29714) and MDU MRC. MJ and HB were supported by Japan Health and Labour Sciences Research grant (H22-rinkensui-ippan-001) and Grants-in–aid for Scientific Research from Japanese Ministry of Education, Culture, Sports, Science and Technology (24390231 and 24790907). VP was supported by Wellcome Trust and the Cambridge Overseas Trust. JR was supported by Ministerio de Educación, through “Programa Nacional de Movilidad de Recursos Humanos del Plan Nacional de I-D+i 2008-2011 (Subprograma de Estancias de Movilidad en el Extranjero “José Castillejo” para jóvenes Doctores, ref: JC2011-0248). SV was supported by MRC. WJS was supported by the Austrian Science Fund (FWF P-20218 and P-20455). Animal work was performed at the MDU DMC Core facilities.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms995

Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans

Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFb signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity

Instantaneous Water Purification by Deep Ultraviolet Light in Water Waveguide: <i>Escherichia Coli</i> Bacteria Disinfection

The necessity of small water purification equipment has been increasing in recent years as a result of frequent natural disasters. Ultraviolet (UV) radiation treatment is an effective method for the disinfection of bacterial contaminants in water. As an emerging technology, disinfection by deep-ultraviolet light-emitting diodes (DUV-LEDs) is promising. Few studies have used the point-source characteristics of LEDs and have instead replaced mercury vapor lamps with LEDs. Here, we demonstrate the instantaneous purification of contaminated water by combining the point source characteristics of DUV-LEDs with a water waveguide (WW). The principle is based on the WW region acting as an effective DUV disinfector, whereby a high UV dose in a confined WW region can be applied to bacterial contaminants in a short period of time (around one second). We demonstrate the effect of this DUV-LED WW disinfection technique by showing the results of 3-log disinfection levels of water contaminated with Escherichia coli bacteria after a short treatment time. We believe that the combination of the point-source nature of DUV-LED emission, the water-waveguide effect, and a small photovoltaic cell paves the way toward environmentally friendly and emergency preparedness portable water purification equipment that instantaneously supplies clean water just before drinking

Action Spectra of Bacteria and Purification of Pollutant Water at Faucets Using a Water Waveguide Method

Ultraviolet (UV) radiation treatment is an effective method for purifying pollutant water contaminated with bacteria and/or chemicals. As an emerging technology, purification by deep ultraviolet light-emitting diodes (DUV-LEDs) is promising. Few studies have used the point-source characteristics of LEDs and have instead replaced mercury vapor lamps with LEDs. Here, we show our recent progress in the instantaneous purification of contaminated water by combining the point-source characteristics of DUV-LEDs with a water waveguide (WW). Before the demonstration, we determined the efficacy of disinfection as a function of irradiation wavelength (action spectra) by constructing a wavelength tunable DUV light source. We found that, as a function of irradiation wavelength, there is a strong correlation between the dose-based inactivation rate constants and deoxyribonucleic acid (DNA) absorbance. Based on this correlation, the emission wavelength of 265 nm was determined as the most effective wavelength for disinfecting water contaminated with bacteria. Instantaneous 2-log disinfection levels of water contaminated with Escherichia coli O1 or Pseudomonas aeruginosa were demonstrated by using the DUV-LED WW method. We also discuss how far-UVC radiation shorter than 230 nm, which has recently been attracting attention and is known as a safe and effective disinfection wavelength for the human body, cannot give a higher-dose-based inactivation rate constant compared to that of 265 nm irradiation due to the larger absorption coefficient of water with a wavelength shorter than 230 nm

Time-dose reciprocity mechanism for the inactivation of Escherichia coli explained by a stochastic process with two inactivation effects

Abstract There is a great demand for developing and demonstrating novel disinfection technologies for protection against various pathogenic viruses and bacteria. In this context, ultraviolet (UV) irradiation offers an effective and convenient method for the inactivation of pathogenic microorganisms. The quantitative evaluation of the efficacy of UV sterilization relies on the simple time-dose reciprocity law proposed by Bunsen-Roscoe. However, the inactivation rate constants reported in the literature vary widely, even at the same dose and wavelength of irradiation. Thus, it is likely that the physical mechanism of UV inactivation cannot be described by the simple time-dose reciprocity law but requires a secondary inactivation process, which must be identified to clarify the scientific basis. In this paper, we conducted a UV inactivation experiment with Escherichia coli at the same dose but with different irradiances and irradiation durations, varying the irradiance by two to three orders of magnitude. We showed that the efficacy of inactivation obtained by UV-light emitting diode irradiation differs significantly by one order of magnitude at the same dose but different irradiances at a fixed wavelength. To explain this, we constructed a stochastic model introducing a second inactivation rate, such as that due to reactive oxygen species (ROS) that contribute to DNA and/or protein damage, together with the fluence-based UV inactivation rate. By solving the differential equations based on this model, the efficacy of inactivation as a function of the irradiance and irradiation duration under the same UV dose conditions was clearly elucidated. The proposed model clearly shows that at least two inactivation rates are involved in UV inactivation, where the generally used UV inactivation rate does not depend on the irradiance, but the inactivation rate due to ROS does depend on the irradiance. We conclude that the UV inactivation results obtained to date were simply fitted by one inactivation rate that superimposed these two inactivation rates. The effectiveness of long-term UV irradiation at a low irradiance but the same dose provides useful information for future disinfection technologies such as the disinfection of large spaces, for example, hospital rooms using UV light, because it can reduce the radiation dose and its risk to the human body