Spectroscopic investigation into the design of solid-acid catalysts for the low temperature dehydration of ethanol.

The increased demand for bulk hydrocarbons necessitates research into increasingly sustainable, energy-efficient catalytic processes. Owing to intricately designed structure-property correlations, SAPO-34 has become established as a promising material for the low temperature ethanol dehydration to produce ethylene. However, further optimization of this process requires a precise knowledge of the reaction mechanism at a molecular level. In order to achieve this a range of spectroscopic characterization techniques are required to probe both the interaction with the active site, and also the wider role of the framework. To this end we employ a combination of in situ infra-red and neutron scattering techniques to elucidate the influence of the surface ethoxy species in the activation of both diethyl ether and ethanol, towards the improved formation of ethylene at low temperatures. The combined conclusions of these studies is that the formation of ethylene is the rate determining step, which is of fundamental importance towards the development of this process and the introduction of bio-ethanol as a viable feedstock for ethylene production.

Anti-inflammatory effect and mechanism of action of ellagic acid-3,3',4-trimethoxy-4'-O-α-L-rhamnopyranoside isolated from Hopea parviflora in lipopolysaccharide-stimulated RAW 264.7 macrophages.

Phytochemical investigation of the stem bark of Hopea parviflora resulted in the isolation of 9 compounds; which includes friedelin (1), friedelin-3ß-ol (2), (-)-ampelopsin A (3), (-)-ɛ-viniferin (4), (-)-hopeaphenol (5), vaticaphenol A (6), 2,4,8-trihydroxyphenanthrene-2-O-glucoside (7), ellagic acid-3,3',4-trimethoxy-4'-O-α-L-rhamnopyranoside (8) and ß-sitosterol-ß-D-glucoside (9). Among them, compounds 1, 2, 6, 7, 8 and 9 are isolated for the first time from this species. Further, we evaluated the anti-inflammatory activity of compounds 4, 5, 6, 7 and 8. In this study, compound 8 inhibited the activity of proinflammatory mediators like NO, TNF-α, IL-6, 5-LOX and COX-2, also promoted the action of anti-inflammatory mediator like IL-10 via inhibition of the NF-κB pathway in LPS-stimulated RAW 264.7 macrophages.

Influence of oxygen partial pressure on the composition and orientation of strontium-doped lead zirconate titanate thin films.

The influence of oxygen partial pressure during the deposition of piezoelectric strontium-doped lead zirconate titanate thin films is reported. The thin films have been deposited by RF magnetron sputtering in an atmosphere of high purity argon and oxygen (in the ratio of 9:1), on platinum-coated silicon substrates (heated to 650 degrees C). The influence of oxygen partial pressure is studied to understand the manner in which the stoichiometry of the thin films is modified, and to understand the influence of stoichiometry on the perovskite orientation. This article reports on the results obtained from films deposited at oxygen partial pressures of 1-5 mTorr. The thin films have been studied using a combination of X-ray photoelectron spectroscopy (XPS), glancing angle X-ray diffraction (GA-XRD), and atomic force microscopy (AFM). XPS analysis highlights the marked influence of variations in oxygen pressure during sputtering, observed by variations in oxygen concentration in the thin films, and in some cases by the undesirable decrease in lead concentration in the thin films. GA-XRD is used to study the relative variations in perovskite peak intensities, and has been used to determine the deposition conditions to attain the optimal combination of stoichiometry and orientation. AFM scans show the marked influence of the oxygen partial pressure on the film morphology.

Isolation and characterization of resveratrol oligomers from the stem bark of Hopea ponga (Dennst.) Mabb. And their antidiabetic effect by modulation of digestive enzymes, protein glycation and glucose uptake in L6 myocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Hopea ponga (Dennst.) Mabb. Is used in traditional herbal formulations for diabetes complications. The aim of this study is to evaluate the antidiabetic effect of extracts and compounds from H. ponga. MATERIALS AND METHODS: Silica gel column chromatography was performed to identify various chemical components of the plant extract. Different extracts of H. ponga and isolated compounds were screened for their antidiabetic effect by modulation of digestive enzymes and protein glycation. The effect of glucose uptake by the compounds and the pathways through which the compounds mediate the glucose uptake potential were confirmed by fluorescent microscopy, flow cytometry and western blot analysis. RESULTS: Acetone and ethanol extracts of the stem bark of Hopea ponga (Dennst.) Mabb. Afforded six resveratrol oligomers namely, E-resveratrol (1), (-)-ε-viniferin (2), (-)-α-viniferin (3), trihydroxyphenanthrene glucoside (THPG) (4), vaticaphenol A (5), (-)-hopeaphenol (6), along with four phytosterols. The structures were determined on the basis of spectroscopic analyses including nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HRMS) data. Compounds 1-5 and 7-10 were tested for their α-glucosidase, α-amylase and glycation inhibitiory activities. All the resveratrol oligomers (1-5) showed prominent α-glucosidase inhibition with IC50 values, 12.56 ±â€¯1.00, 23.98 ±â€¯1.11, 7.17 ±â€¯1.10, 31.74 ±â€¯0.42 and 16.95 ±â€¯0.39 µM, respectively. Molecular docking studies also supported the observed α-glucosidase inhibition. Compound 3 displayed IC50 values of 4.85 ±â€¯0.06 and 27.10 ±â€¯0.04 µM in α-amylase and glycation inhibitory assays activity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the compounds 3 and 4 were found to be less toxic at a concentration of 100 µM (<10%) and 25 µM (<20%), respectively. The effect of glucose uptake performed by 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in L6 myoblast were measured by fluorescent microscopy and flow cytometry. The compounds 3 and 4 showed 2-NBDG uptake of 49.6% and 38.8% respectively. By examining the molecular pathway through which the compounds elicit their glucose uptake potential, it was observed that both the compounds mainly act via AMPK pathway. CONCLUSION: This is the first report on the isolation of compounds from H. ponga. Altogether, the results of this study reveal the antidiabetic effects of H. ponga extracts and isolated compounds promoting traditional use of this plant in the treatment of diabetes.

Antifibrotic action of Cu/Zn SOD is mediated by TGF-beta1 repression and phenotypic reversion of myofibroblasts.

Skin fibrosis is characterized by the proliferation and accumulation of activated fibroblasts called myofibroblasts. They exhibit specific cytoskeletal differentiation, overexpress the fibrogenic cytokine TGF-beta1, synthesize excess extracellular matrix compounds and exhibit a depleted antioxidant metabolism. Recently, SOD was successfully used as an antifibrotic agent in vivo, thus challenging the postulate of established fibrosis irreversibility. We postulated that myofibroblasts could be a direct target for this therapeutic effect. To test this hypothesis, we used three-dimensional co-culture models of skin, in which specific phenotypes of normal fibroblasts versus myofibroblasts are retained. These 3-D models were treated with liposomal and carrier-free Cu/Zn SOD, and examined for their effects on cell number, cell death, and phenotypic differentiation. The results show that SOD did not induce myofibroblast cell death, whereas it significantly reduced TGF-beta1 expression, thus demonstrating that SOD might be proposed as a potent antagonist of this major fibrogenic growth factor. We also found that SOD significantly lowered the levels of the myofibroblast marker alpha-sm actin, of beta-actin, and of the extracellular matrix components alpha1(I) collagen and tenascin-C. In conclusion, our results suggest that SOD antifibrotic action occurred in vitro through the reversion of myofibroblasts into normal fibroblasts.

Histopathological and cellular studies of a case of cutaneous radiation syndrome after accidental chronic exposure to a cesium source.

This study was designed for the histopathological, cellular and biochemical characterization of a skin lesion removed surgically from a young male several months after accidental exposure to cesium-137, with an emphasis on expression of transforming growth factor beta1 (TGFB1) and tumor necrosis factor alpha (TNFA) and the occurrence of apoptosis. Under a hypertrophic epidermis, a highly inhomogeneous inflammatory dermis was observed, together with fibroblastic proliferation in necrotic areas. Immunostaining revealed overexpression of TGFB1 and TNFA inside the keratinocytes of the hypertrophic epidermis as well as in the cytoplasm of the fibroblasts and connective tissue of the mixed fibrotic and necrotic dermis. Inside this dermis, the TUNEL assay revealed areas containing numerous apoptotic fibroblasts next to areas of normal viable cells. Overexpression of TGFB1 was found in the conditioned medium and cellular fractions of both hypertrophic keratinocytes and fibrotic fibroblasts. This overexpression lasted for at least three passages in tissue culture. The present observations were consistent with the central role of TGFB1 in the determination of chronic radiation-induced damage to the skin and a significant involvement of TNFA. In addition, programmed cell death appeared to take place during the remodeling of the mixed fibrotic and necrotic tissue.

[Radiation-induced superficial fibrosis and TGF-alpha 1]. / Fibrose superficielle radio-induite et TGF-beta 1.

Radiation-induced fibrosis is a late sequela of both therapeutic and accidental irradiations, which has been described in various tissues, including the lung, liver, kidney and skin. This review presents different aspects of superficial radiation-induced fibrosis, such as clinical observations, histological changes, cellular and molecular regulations, and medical management. Recent evidence on the critical role played by TGF-beta 1 in the initiation, development and persistence of fibrosis are discussed, as well as the possibility that this cytokine may constitute a specific target for antifibrotic agents.

Lactate oxidation coupled to energy production in mitochondria like particles from Setaria digitata, a filarial parasite.

In the filarial parasite, Setaria digitata, the mitochondria like particles (MLP) show NAD reduction with sodium lactate. The MLP also reduces dye and ferricyanide with lactate. The ferricyanide reduction by lactate is found to be sensitive to the cytochrome o inhibitor orthohydroxy diphenyl (OHD) and complex I inhibitor rotenone, modulated by ADP (+) and ATP (-) and inhibited by pyruvate and oxaloacetate. MLP shows lactate oxidation sensitive to OHD, rotenone and sodium malonate. Thus, the lactate utilizing complex system, consisting of an NADH generating MLP bound lactate dehydrogenase and a lactate flavocytochrome reductase tightly linked to complex I and cytochrome o, produces ATP in functional association with fumarate reductase complex and other enzyme systems. Hence, this study provides new dimensions to the study of metabolism in filarial parasites.

Quinone dependent NADH dehydrogenation in mitochondria-like particles from Setaria digitata, a filarial parasite.

In the cattle filarial parasite, Setaria digitata, the mitochondria-like particles have been shown to possess site I associated oxidative phosphorylation and rotenone sensitive and insensitive pathways for the dehydrogenation of NADH. Quinone depleted mitochondria-like particles show a loss of activity of these NADH dehydrogenases and also a complete loss of fumarate reductase activity. Reconstitution with quinone restores both NADH linked oxygen uptake and fumarate reductase activity. Thus activities of complex I and fumarate reductase are linked to quinone. Hence an inhibitor at the level of quinone can simultaneously block both aerobic and anaerobic pathways which drive ATP production and may prove useful in the effective control of filariasis.

Quinone analogue irrecoverably paralyses the filarial parasites in vitro.

2,3-Dimethoxy-5-methyl-1,4-benzoquinone (Q0), an analogue of ubiquinone, irreversibly paralyses the adult and microfilariae of the cattle filarial parasite Setaria digitata. The same concentration of Q0 that paralyses the microfilariae of S. digitata also paralyses the microfilariae of the human filarial parasite Wuchereria bancrofti within the same duration. Thus the experiments done in the model S. digitata system can well be extended to the human filarial system. A drug at the level of the quinone-centered energy generating system, perhaps an analogue of quinone like Q0, can inactivate the filarial parasites and may prove to be an effective drug to control filariasis.

Involvement of extracellular signal-regulated kinase module in HIV-mediated CD4 signals controlling activation of nuclear factor-kappa B and AP-1 transcription factors.

Although the molecular mechanisms by which the HIV-1 triggers either T cell activation, anergy, or apoptosis remain poorly understood, it is well established that the interaction of HIV-1 envelope glycoproteins with cell surface CD4 delivers signals to the target cell, resulting in activation of transcription factors such as NF-kappa B and AP-1. In this study, we report the first evidence indicating that kinases MEK-1 (MAP kinase/Erk kinase) and ERK-1 (extracellular signal-regulated kinase) act as intermediates in the cascade of events that regulate NF-kappa B and AP-1 activation upon HIV-1 binding to cell surface CD4. We found that CEM cells transfected with dominant negative forms of MEK-1 or ERK-1 do not display NF-kappa B activation after HIV-1 binding to CD4. In contrast, NF-kappa B activation was observed in these cells after PMA stimulation. Although the different cell lines studied expressed similar amounts of CD4 and p56(lck), HIV-1 replication and HIV-1-induced apoptosis were slightly delayed in cells expressing dominant negative forms of MEK-1 or ERK-1 compared with parental CEM cells and cells expressing a constitutively active mutant form of MEK-1 or wild-type ERK-1. In light of recently published data, we propose that a positive signal initiated following oligomerization of CD4 by the virus is likely to involve a recruitment of active forms of p56(lck), Raf-1, MEK-1, and ERK-1, before AP-1 and NF-kappa B activation.

Alteration of transforming growth factor-beta1 response involves down-regulation of Smad3 signaling in myofibroblasts from skin fibrosis.

Fibrosis is an unregulated tissue repair process whose predominant characteristics are the proliferation of myofibroblasts and an excessive deposition of extracellular matrix. Transforming growth factor (TGF)-beta1 is considered as one of the most fibrogenic cytokines. However, the molecular mechanisms involved in its profibrotic role are not fully understood. Here, we addressed the role of TGF-beta1 on cell proliferation and intracellular signal transduction in a pig model of skin fibrosis induced by gamma-irradiation. Primary myofibroblasts were isolated from the fibrotic tissue and their response to TGF-beta1 was compared to that of normal skin fibroblasts. The present results show that the differentiation of myofibroblasts involves a lack of TGF-beta1 growth inhibition and an impaired TGF-beta1 signaling. Receptor activity and Smad2/4 or Smad3/4 complex formation were similar in both cell types after TGF-beta1 treatment. However, the translocation of Smad3 protein into the nucleus was reduced in myofibroblasts as compared to that in fibroblasts, as well as its binding to target DNA sequences and the activation of the Smad binding elements found in the PAI-1. Interestingly, Smad2 was translocated similarly to the nucleus in both cell types suggesting that this protein may function normally in myofibroblasts. We propose that uncoupling of antiproliferative and profibrotic actions of TGF-beta1 in fibrosis may occur through differential regulation of the activities of Smad2 and Smad3 transcription factors.

Fc-receptor-mediated intracellular delivery of Cu/Zn-superoxide dismutase (SOD1) protects against redox-induced apoptosis through a nitric oxide dependent mechanism.

BACKGROUND: Using specific antibodies against bovine Cu/Zn-superoxide dismutase (EC 1.15.1.1, SOD1) we demonstrated that anti-SOD antibodies (IgG1) are able to promote the intracellular translocation of the antioxidant enzyme. The transduction signalling mediated by IgG1 immune complexes are known to promote a concomitant production of superoxide and nitric oxide leading to the production of peroxynitrites and cell death by apoptosis. The Fc-mediated intracellular delivery of SOD1 thus limited the endogenous production of superoxide. It was thus of interest to confirm that in the absence of superoxide anion, the production of nitric oxide protected cells against apoptosis. Study in greater detail clearly stated that under superoxide anion-free conditions, nitric oxide promoted the cell antioxidant armature and thus protected cells against redox-induced apoptosis. MATERIALS AND METHODS: The murine macrophage cell-lines J774 A1 were preactivated or not with interferon-gamma and were then stimulated by IgG1 immune complexes (IC), free SOD1 or SOD1 IC and superoxide anion, nitric oxide, peroxynitrite, and tumor necrosis factor-alpha (TNF-alpha) production was evaluated. The redox consequences of these activation processes were also evaluated on mitochondrial respiration and apoptosis as well as on the controlled expression of the cellular antioxidant armature. RESULTS: We demonstrated that SOD1 IC induced a Fcgamma receptor (FcgammaR)-dependent intracellular delivery of the antioxidant enzyme in IFN-gamma activated murine macrophages (the J774 AI cell line). The concomitant stimulation of the FcyR and the translocation of the SOD1 in the cytoplasm of IFN-gamma-activated macrophages not only reduced the production of superoxide anion but also induced the expression of the inducible form of nitric oxide synthase (iNOS) and the related NO production. This inducing effect in the absence of superoxide anion production reduced mitochondrial damages and cell death by apoptosis and promoted the intracellular antioxidant armature. CONCLUSIONS: To define the pharmacologic mechanism of action of bovine SOD1, we attempted to identify the second messengers that are induced by SOD1 IC. In this work, we propose that Fc-mediated intracellular delivery of the SOD1 that reduced the production of superoxide anion and of peroxynitrite, promoted a NO-induced protective effect in inducing the antioxidant armature of the cells. Taken together, these data suggested that specific immune responses against antigenic SOD1 could promote the pharmacological properties of the antioxidant enzyme likely via a NO-dependent mechanism.