A systematic and complete antibacterial study on well-designed and well-characterized microparticle (micro), nanoparticle (nano), and capped nano ZnO has been carried out in both dark and light conditions with the objective of arriving at the mechanism of the antibacterial activity of ZnO, particularly in the dark. The present systematic study has conclusively proved that reactive oxygen species (ROS) such as (•)OH, (•)O2(-), and H2O2 are significantly produced from aqueous suspension of ZnO even in the dark and are mainly responsible for the activity in the dark up to 17%, rather than Zn(2+) ion leaching as proposed earlier. This work further confirms that surface defects play a major role in the production of ROS both in the presence and absence of light. In the dark, superoxide ((•)O2(-)) radical mediated ROS generation through singly ionized oxygen vacancy is proposed for the first time, and it is confirmed by EPR and scavenger studies. ROS such as (•)O2(-), H2O2, and (•)OH have been estimated by UV-visible spectroscopy using nitro blue tetrazolium (NBT), KMnO4 titrations, and fluorescence spectroscopy, respectively. These are correlated to the antibacterial activity of ZnO in the dark and light. The activity is found to be highest for nano ZnO and least for micro ZnO, with capped ZnO between the two, highlighting the important role of surface defects in generation of ROS. The surface charge density of ZnO in dark and light has been estimated for the first time to the best of our knowledge, and it can influence antibacterial activity. Our work proposes a new mechanism mediated by superoxide species, for antibacterial activity of ZnO especially in the dark.
We have previously demonstrated that macrophages stimulated in the presence of immune complexes produce high levels of IL-10. We now examine the mechanism of IL-10 superinduction. We report that the enhanced production of IL-10 correlates with a rapid and enhanced activation of two MAPKs, ERK and p38. The inhibition of either ERK or p38 prevented IL-10 induction, indicating that both MAPKs were required for IL-10 synthesis. By chromatin immunoprecipitation assay, we demonstrate that activation of ERK leads to the phosphorylation of serine 10 on histone H3 at the il-10 gene, making the promoter more accessible to transcription factors generated in response to p38 activation. Inhibition of ERK activation prevented histone modifications, and decreased the binding of Sp1 and STAT3 to the IL-10 promoter. We conclude that the activation of ERK following FcγR ligation leads to a remodeling of the chromatin at the il-10 locus, making it more accessible to transcription factors. The rapid and transient regulation of transcription factor accessibility to the IL-10 promoter by MAPK activation represents a novel way that the production of this cytokine is regulated.
Background
Pulmonary hypertension (PH) has diverse causes with heterogeneous physiology compelling distinct management. Differentiating patients with primarily elevated pulmonary vascular resistance (PVR) from those with PH predominantly due to elevated left sided filling pressure is critical.
Methods and Results
We reviewed hemodynamics, echocardiography, and clinical data for 108 patients seen at a referral PH clinic with transthoracic echocardiogram and right heart catheterization within 1 year. We derived a simple echocardiographic prediction rule to allow hemodynamic differentiation of PH due to pulmonary vascular disease (PHPVD, defined as pulmonary artery wedge pressure (PAWP) ≤ 15mmHg and PVR >3WU). Age averaged 61.3±14.8 years, μPAWP and PVR were 16.4±7.1mmHg and 6.3±4.0WU respectively, and 52 (48.1%) patients fulfilled PHPVD hemodynamic criteria. The derived prediction rule ranged from −2 to +2 with higher scores suggesting higher probability of PHPVD: +1 point for left atrial AP dimension<3.2cm; +1 for presence of a mid-systolic notch or acceleration time<80msec; −1 for lateral mitral E:e′>10; −1 for left atrial AP dimension>4.2cm. PVR increased stepwise with score (for −2, 0 and +2, μPVR were 2.5, 4.5, and 8.1WU) while the inverse was true for PAWP (corresponding μPAWP were 21.5, 16.5 and 10.4mmHg). Among subjects with complete data, the score had an AUC of 0.921 for PHPVD. A score ≥ 0 had 100% sensitivity and 69.3% positive predictive value for PHPVD, with 62.3% specificity. No patients with a negative score had PHPVD. Patients with a negative score and acceleration time >100msec had normal PVR (μPVR=1.8WU, range=0.7–3.2WU).
Conclusions
We present a simple echocardiographic prediction rule that accurately defines PH hemodynamics facilitates improved screening and focused clinical investigation for PH diagnosis and management.
Background:Coleus forskohlii Willd. is a popular traditional medicine used since ancient times for treatment of heart diseases, abdominal colic and respiratory disorders.Objective:The aim of this study was to characterize the root extract of the medicinal plant Coleus forskohlii.Materials and Methods:Dry roots of C. forskohlii were used to extract Forskolin using toluene as a solvent. Thus, obtained extract of C. forskohlii was standardized to 30% and used for further studies.Results:The physical properties of the extract were analyzed through scanning electron microscopy analysis, while the characterization of root extract through X-ray diffraction (XRD) and element analysis. The morphological feature of the C. forskohlii extract showed a flake like structure and the XRD showed sulfur trioxide (SO3) and trimer of sulfur trioxide (S3 O9). Through element analysis, elements such as carbon, oxygen, magnesium, aluminum, silicon, phosphorous, and sulfur were identified. Carbon showed the highest weight of 75.49% in comparison to all other elements.
Environmental hazard caused due to the release of dyes in effluents is a concern in many countries. Among the various methods to combat this problem, Advanced Oxidation Process, in which semiconductor photocatalysts are used, is considered the most effective one. These materials release Reactive Oxygen Species (ROS) such as hydroxyl radical and superoxide in suspension that degrade the dyes into non-toxic minerals. However, this process requires visible or UV light for activation. Hence, there is a need to develop materials that release ROS, both in the absence and in the presence of light, so that the efficiency of dye removal is enhanced. Towards this objective, we have designed and synthesized a new nanocomposite ZnO2/polypyrrole which releases ROS even in the dark. The ROS released in the dark and in light were estimated by standard methods. It is to be noted that ZnO2 degrades the dye only under UV light but not in dark or in the presence of visible light. We propose the mechanism of dye degradation in dark and light. The synergically coupled nanocomposite of ZnO2/ppy is the first example that degrades dyes in the dark, through advanced oxidation process without employing additional reagents.
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