Nitin K. Puri

Increased HO-1 Levels Ameliorate Fatty Liver Development Through a Reduction of Heme and Recruitment of FGF21

Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose, and liver lipids. Our hypothesis is that HO‐1 overexpression ameliorates fatty liver development.

Label-free detection of cardiac troponin-I using gold nanoparticles functionalized single-walled carbon nanotubes based chemiresistive biosensor

We report a specific and ultrasensitive, label-free chemiresistive biosensor based on mercaptopropionic acid capped gold nanoparticles (GNP) functionalized single walled carbon nanotube (SWNT) hybrid for the detection of cardiac specific biomarker troponin-I (cTnI). GNPs were attached to SWNTs through a molecular linker 1-pyrenemethylamine. The highly specific cTnI antibody was covalently immobilized on GNPs through capping agent using carbodiimide coupling reaction. The cTnI interaction to its corresponding antibody was studied with respect to changes in conductance in SWNTs channel, and a detailed field-effect transistor characteristic was delineated. The device exhibited a linear response to cTnI from 0.01 to 10 ng ml−1.

Enhanced ferroelectric photovoltaic response of BiFeO3/BaTiO3 multilayered structure

The present work is based on the photovoltaic properties of multilayered structure of Bismuth ferrite (BFO) and Barium titanate (BTO) thin films prepared by pulsed laser deposition technique on platinum coated silicon substrate. The multilayered structure possesses enhanced ferroelectric properties and shows a remarkable increase in photocurrent (from 1.56 × 10−7 A to 6.96 × 10−5 A) upon illumination with laser light of wavelength 405 nm at an intensity of 160 mW/cm2. The values of short circuit photocurrent and open circuit voltage were found to be 0.3184 mA/cm2 and −1.25 V, respectively, with a light-to-electricity conversion efficiency of 0.067%. A relatively high efficiency calculated at 405 nm for the developed multilayered BFO/BTO structure highlights its practical application in ferroelectric photovoltaics.

PPARδ binding to heme oxygenase 1 promoter prevents angiotensin II-induced adipocyte dysfunction in Goldblatt hypertensive rats

Objective:Renin–angiotensin system (RAS) regulates adipogenic response with adipocyte hypertrophy by increasing oxidative stress. Recent studies have shown the role of peroxisome proliferator-activated receptor-δ (PPARδ) agonist in attenuation of angiotensin II-induced oxidative stress. The aim of this study was to explore a potential mechanistic link between PPARδ and the cytoprotective enzyme heme oxygenase-1 (HO-1) and to elucidate the contribution of HO-1 to the adipocyte regulatory effects of PPARδ agonism in an animal model of enhanced RAS, the Goldblatt 2 kidney 1 clip (2K1C) model.Method:We first established a direct stimulatory effect of the PPARδ agonist (GW 501516) on the HO-1 gene by demonstrating increased luciferase activity in COS-7 cells transfected with a luciferase-HO-1 promoter construct. Sprague-Dawley rats were divided into four groups: sham-operated animals, 2K1C rats and 2K1C rats treated with GW 501516, in the absence or presence of the HO activity inhibitor, stannous mesoporphyrin (SnMP).Results:2K1C animals had increased visceral adiposity, adipocyte hypertrophy, increased inflammatory cytokines, increased circulatory and adipose tisssue levels of renin and Ang II along with increased adipose tissue gp91 phox expression (P<0.05) when compared with sham-operated animals. Treatment with GW 501516 increased adipose tissue HO-1 and adiponectin levels (P<0.01) along with enhancement of Wnt10b and β-catenin expression. HO-1 induction was accompanied by the decreased expression of Wnt5b, mesoderm specific transcript (mest) and C/EBPα levels and an increased number of small adipocytes (P<0.05). These effects of GW501516 were reversed in 2K1C animals exposed to SnMP (P<0.05).Conclusion:Taken together, our study demonstrates, for the first time, that increased levels of Ang II contribute towards adipose tissue dysregulation, which is abated by PPARδ-mediated upregulation of the heme-HO system. These findings highlight the pivotal role and symbiotic relationship of HO-1, adiponectin and PPARδ in the regulation of metabolic homeostasis in adipose tissues.

DEVELOPMENT OF REGIONAL PIXE FACILITY AT PANJAB UNIVERSITY CYCLOTRON, CHANDIGARH (INDIA)

A description of modifications in the variable energy cyclotron (VEC) Chandigarh along with the installation of Proton Induced X-ray Emission (PIXE) setup is presented. A new main magnet power supply of 400A/125V out put with ±10 ppm stability and a new stabilized solid state power supply for RF oscillator has improved the beam characteristics substantially. A new chamber has been designed to cater for Proton Induced Gamma Emission (PIGE) and Rutherford Back Scattering (RBS) along with PIXE measurements. The HPGe x-ray detector, the Ge(Li) γ-ray detector and a silicon surface barrier (SSB) detector can be mounted simultaneously in the chamber for this purpose. A Turbo-Molecular vacuum pump is provided to produce a clean vacuum of the order of 10-8 mbar in the PIXE chamber. A remotely controlled stepper motor is provided to move the wheel having 12/24-position target holder. Beam size optimization along with the minimization of background has been done with the help of graphite collimators, thus making the setup suitable for practical applications. Preliminary experiments for the PIXE analysis of aerosol, gunshot residues and kidney stone samples are presented.

HO-1 Induction Improves The Type-1 Cardiorenal Syndrome in Mice With Impaired Angiotensin II–Induced Lymphocyte Activation

Type-1 cardiorenal syndrome, characterized by acute kidney dysfunction secondary to cardiac failure and renal arteriolar vasoconstriction, is mediated by the renin–angiotensin–aldosterone axis and sympathetic nervous system activation. Previous reports indicate that angiotensin II modulates immune function and causes recruitment and activation of T-lymphocytes. The goal of this study was to evaluate the effects of postischemic heart failure on renal morphology and circulation and the beneficial effects of heme oxygenase-1 (HO-1) induction in T-lymphocyte–suppressed severe combined immune deficiency (SCID) mice. Mice were divided into 4 groups: sham, myocardial infarction (MI), MI treated with an HO-1 inducer, cobalt protoporphyrin, and with or without stannous mesoporphyrin, an inhibitor of HO activity. Heart and kidney function were studied 30 days after surgery. Fractional area change was reduced 30 days after surgery in both the C57 and SCID MI–groups as compared with their respective controls (P<0.01). Renal Pulsatility Index and renal injury were increased in C57 and SCID MI–groups compared with the sham group. HO-1 induction improved renal vasoconstriction as well as ameliorated renal injury in both the SCID and C57 MI–groups (P<0.01). However, improvement was more evident in SCID mice. In addition, our results showed that plasma creatinine, angiotensin II, and renin were significantly increased in the C57 and SCID MI–groups as compared with their respective controls. HO-1 induction decreased these parameters in both MI groups. Stannous mesoporphyrin reversed the beneficial effect of cobalt protoporphyrin in both mouse strains. The study demonstrates that T-lymphocyte suppression facilitated the HO-1–dependent improvement in the attenuation of type-1 cardiorenal syndrome.

Existence of a Strong Correlation of Biomarkers and miRNA in Females with Metabolic Syndrome and Obesity in a Population of West Virginia

Objectives: Metabolic syndrome causes complications like cardiovascular disease and type 2 diabetes mellitus (T2DM). As metabolic syndrome develops, altered levels of cytokines and microRNAs (miRNA) are measurable in the circulation. We aimed to construct a panel detecting abnormal levels of cytokines and miRNAs in patients at risk for metabolic syndrome. Methods: Participants included 54 patients from a Family Medicine Clinic at Marshall University School of Medicine, in groups of: Control, Obese, and Metabolic Syndrome (MetS). Results: Serum levels of leptin, adiponectin, leptin: adiponectin ratio, IL-6, six miRNAs (320a, 197-3p, 23-3p, 221-3p, 27a-3p, and 130a-3p), were measured. Among the three groups, leptin, and leptin: adiponectin ratio, and IL-6 levels were highest in MetS, and levels in Obese were greater than Control (p>0.05). Adiponectin levels were lower in Obese compared to Control, but lowest in MetS (p<0.05). MiRNAs levels were lowest in MetS, and levels in Obese were lower than Control (p>0.05). Conclusion: Our results support the clinical application of biomarkers in diagnosing early stage MetS, which will enable attenuation of disease progression before onset of irreversible complications. Since West Virginians are high-risk for developing MetS, our biomarker panel could reduce the disease burden on our population.

Stress induced enhanced polarization in multilayer BiFeO3/BaTiO3 structure with improved energy storage properties

Present work reports the fabrication of a multilayer (5-layer) structure of BiFeO3(BFO)/BaTiO3(BTO) using spin-coating technique. The crystallographic structure, surface morphology and ferroelectric behavior of multilayer structure in metal-ferroelectric-metal capacitor have been studied. Le-Bail refinement of X-ray diffraction data revealed the formation of polycrystalline pure perovskite phase with induced stress. The values of remnant (Pr) and saturation polarization (Ps) for BFO/BTO multilayer structure are found to be 38.14 μC/cm2 and 71.54 μC/cm2 respectively, which are much higher than the corresponding values reported for bare BFO thin film. A large value of dielectric constant of 187 has been obtained for multilayer structure with a low leakage current density of 1.09 × 10−7 A/cm2 at applied bias of 10 V. The BFO/BTO multilayer structure favors the enhanced energy storage capacity as compared to bare BFO thin film with improved values of energy-density and charge-discharge efficiency as 121 mJ/cm...

Antioxidants Condition Pleiotropic Vascular Responses to Exogenous H2O2: Role of Modulation of Vascular TP Receptors and the Heme Oxygenase System

AIMS Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants. RESULTS Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was obliterated in arteries pretreated with antioxidants, including tempol, pegylated superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting radicals downstream of H(2)O(2), also uncovered vasodilation. INNOVATIONS Redox-dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 μM), thromboxane (TP) synthase (CGS13080-10 μM), and TP receptor antagonist (SQ29548-1 μM). However, H(2)O(2) did not increase vascular thromboxane B(2) release; instead, it sensitized the vasculature to a TP agonist, U46619, an effect reversed by PEG-SOD. Antioxidant-conditioned dilatory response to H(2)O(2) was accompanied by enhanced vascular heme oxygenase (HO)-dependent carbon monoxide generation and was abolished by HO inhibitors or by HO-1 & 2 antisense oligodeoxynucleotides treatment of SD rats. CONCLUSION These results demonstrate that H(2)O(2) has antioxidant-modifiable pleiotropic vascular effects, where constriction and dilation are brought about in the same vascular segment. H(2)O(2)-induced oxidative stress increases vascular TP sensitivity and predisposes these arterial segments to constrictor prostanoids. Conversely, vasodilation is reliant upon HO-derived products whose synthesis is stimulated only in the presence of antioxidants targeting radicals downstream of H(2)O(2).

Effect of insertion of low leakage polar layer on leakage current and multiferroic properties of BiFeO3/BaTiO3 multilayer structure

Polycrystalline BiFeO3 is a well established leaky room temperature multiferroic material. The present work focuses on the realization of high end functionalities such as polarization, low leakage current and high magnetization in a sandwich structure of BaTiO3 and BiFeO3. Interestingly, it was found that the BaTiO3 barrier layer effectively reduces the leakage current which in turn significantly improves the ferroelectric and ferromagnetic properties. The increase in the number of BaTiO3 barrier layers stops the charge carriers for long range mobility. X-ray diffraction (XRD) analysis suggests that an increase in the number of BaTiO3 layers significantly increases the stress modulus in the both the constituent layers along c-axis and tetragonality in the BiFeO3 films which helps in improving the multiferroic properties in multilayered structure. The saturation polarization (Ps) and magnetization (Ms) significantly increased from 18 to 99 μC cm−2 and 28 to 95 emu cm−3 respectively with increase in number of barrier layers from 2 to 6. The BiFeO3/BaTiO3 multilayered structure with enhanced multiferroic properties finds potential application in the tunable devices.