196,075 research outputs found
Biophysical characterization of antimicrobial peptides activity: From in vitro to ex vivo techniques
No full textAntimicrobial peptides (AMPs) are evolutionarily conserved components of the innate immune defense system of many living organisms varying from prokaryotes to eukaryotes, including humans. Due to their broad-spectrum activity and low level of induced resistance, these short aminoacid sequences represent a novel class of potential antimicrobial agents. Besides the development of anti-bacterial drugs, AMPs constitute ideal molecular models for the design of molecules with wide-ranging nanomedical applications, such as anti-tumorigenic agents and pharmacological tools to cure channelopaties. Several techniques are currently used to shed light on the mechanisms of action of AMPs, ranging from the characterization of the interaction between peptides and biomimetic membranes and/or intracellular targets, to the study of AMPs effects on pathogens, living cells and tissues. Comprehensive and multiscale studies are crucial to design new AMPs and to identify molecules that can boost their activity. In this minireview we summarize the most recent achievements in AMP-characterization, with a special emphasis on the integration of biophysical approaches, which can synergistically help to bridge the gap between in vitro and ex vivo investigations
Interpretazione microscopica dell’effetto osmoprotettivo della taurina mediante dinamica
No full textKeratinocytes oxidative damage mechanisms related to airbone particle matter exposure
No full textEpidemiological evidences have correlated airbone particulate matter (PM) to adverse health effects, mainly linking to pulmonary and cardiovascular disease. Nevertheless, only recently, some studies reported detrimental effects of PM on other organs such as skin. In a recent work, we have reported increased oxidative and inflammatory responses in Reconstituted Human Epidermis (RHE) exposed to ambient particles (CAPs) and we also demonstrated the ability of CAPs to penetrate the skin tissue.The present study was aimed to better understand the cellular mechanisms beyond the oxidative changes induced by CAPs (5-10-25. μg/mL) in human immortalized keratinocytes (HaCaT).After 24. h of treatment, CAPs were able to enter the cells leading to a decrease in viability, increased levels of 4-hydroxinonenal products (4-HNE) and IL-1α release. Overall these data, suggest lipid and protein oxidative damage, as well as an increase of inflammatory response after being challenged with CAPs. In addition, 3. h after CAPs exposure we found a significant increase in NF-kB and Nrf2 translocation into the nucleus. In contrast, no differences in gene expression and enzymatic activity of Nrf2 target genes were detected. This last finding could be explained by the ability of CAPs to possibly alter the binding of Nrf2 to the ARE DNA sequence.Fil: Romani, Arianna. Università di Ferrara; ItaliaFil: Cervellati, Carlo. Università di Ferrara; ItaliaFil: Muresan, Ximena M.. Università di Ferrara; ItaliaFil: Belmonte, Giuseppe. Università di Ferrara; ItaliaFil: Pecorelli, Alessandra. North Carolina State University; Estados UnidosFil: Cervellati, Franco. Università di Ferrara; ItaliaFil: Benedusi, Mascia. Università di Ferrara; ItaliaFil: Evelson, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular. Departamento de Patología; ArgentinaFil: Valacchi, Giuseppe. Università di Ferrara; Italia. North Carolina State University; Estados Unido
"Anointed with oil": pentecostalismo e lotte armate sul Delta del Niger, Nigeria
No full textL’obiettivo di questa tesi è di indagare, storicamente ed etnograficamente, il ruolo dei discorsi e delle pratiche pentecostali così come vengono agiti dagli individui nel contesto della violenta crisi petrolifera del Delta del Niger, a partire dal caso della città di Port Harcourt, Nigeria. La tesi ha voluto mostrare, fra le altre cose, come, grazie all’etnografia, sia possibile narrare i conflitti dovuti all’economia del petrolio nigeriana da una prospettiva più vicina a quella della popolazione, per gran parte della quale il petrolio costituisce al contempo una maledizione e una possibile benedizione, a patto, però, di trasformare la nazione in senso pentecostale
The Peroxisome Proliferator-activated Receptor γ (PPARγ) Controls Natural Protective Mechanisms against Lipid Peroxidation in Amyotrophic Lateral Sclerosis
No full textRecent evidence highlights the peroxisome proliferator-activated receptors (PPARs) as critical neuroprotective factors in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). To gain new mechanistic insights into the role of these receptors in the context of ALS, here we investigated how PPAR transcriptional activity varies in hSOD1(G93A) ALS transgenic mice. We demonstrate that PPARγ-driven transcription selectively increases in the spinal cord of symptomatic hSOD1(G93A) mice. This phenomenon correlates with the up-regulation of target genes, such as lipoprotein lipase and glutathione S-transferase α-2, which are implicated in scavenging lipid peroxidation by-products. Such events are associated with enhanced PPARγ immunoreactivity within motor neuronal nuclei. This observation, and the fact that PPARγ displays increased responsiveness in cultured hSOD1(G93A) motor neurons, points to a role for this receptor in neutralizing deleterious lipoperoxidation derivatives within the motor cells. Consistently, in both motor neuron-like cultures and animal models, we report that PPARγ is activated by lipid peroxidation end products, such as 4-hydroxynonenal, whose levels are elevated in the cerebrospinal fluid and spinal cord from ALS patients. We propose that the accumulation of critical concentrations of lipid peroxidation adducts during ALS progression leads to the activation of PPARγ in motor neurons. This in turn triggers self-protective mechanisms that involve the up-regulation of lipid detoxification enzymes, such as lipoprotein lipase and glutathione S-transferase α-2. Our findings indicate that anticipating natural protective reactions by pharmacologically modulating PPARγ transcriptional activity may attenuate neurodegeneration by limiting the damage induced by lipid peroxidation derivatives
Modulation of cutaneous carotenoids content by ozone exposure
No full textOzone (O3) is a harmful air pollutant to which we are constantly exposed. Given its strong oxidizing effects and pervasiveness in the air we breathe, O3 is especially damaging to target organs in the respiratory system (e.g., lungs) and the integumentary apparatus (e.g., skin). Both of these systems act as a barrier and are able to limit the penetration of atmospheric pollutants into the body. In this regard, skin—the largest and main barrier against atmospheric intrusions—offers continuous protection against environmental intrusions. The skin is equipped with several defensive molecules that act as protective intracellular antioxidants against oxidative intrusions, including O3. Among these antioxidants are carotenoids, a family of lipophilic phytonutrients that are abundant in fruits and vegetables. It is well established that carotenoids accumulate in the epidermis layer of the skin, where they confer protection against oxidative intrusions and modulate inflammation, and that there is a direct correlation between skin and serum carotenoids level. The present study aimed to evaluate the variations in carotenoid content present in human skin prior to and after O3 exposure in 141 human subjects. Carotenoids were measured non-invasively using a resonance Raman spectroscopy (RRS)-based photonic device (Pharmanex BioPhotonic Scanner (BPS) Nu Skin Enterprises). In each volunteer, RRS skin carotenoids were determined at baseline and after 15 and 30 min of exposure to O3 0.8 ppm. The data obtained have an indicative value for individual variations in the cutaneous carotenoids, which have been shown to correlate with plasmatic contents. After the first 15 min of O3 exposure, there was a modulation of skin carotenoids, confirming their importance in the maintenance of cutaneous redox homeostasis
Circadian clock and oxidative Stress: functional cross-talk in skin homeostasis
No full textOzone is among the most toxic environmental stressors to which we are continuously exposed. Due to its critical location, skin is one of the most susceptible tissues to oxidative stress damaging effect of ozone. An increasing collection of data suggests a significant role of circadian system in regulation of cellular response to oxidative stress. However, the molecular mechanism linking circadian clock and antioxidant pathway it is not completely understood. Here we investigated a possible protective role of entrained circadian clock to ozone induced damage in keratinocytes, the main cellular component of human epidermis. Our results showed that, clock-synchronized keratinocytes compared to arrhythmic ones exhibited a more efficient antioxidant response, attested by a faster activation of the master antioxidant regulatory factor NRF2. Moreover, analysis of clock gene expression profiles reveals a more rapid induction of the cardinal clock gene Bmal1 in entrained cells. Based on these findings, we suppose that an adequate coordination of circadian system and antioxidant pathway might be essential to maintain homeostasis in the skin. Alteration of metabolic pathways occurred in neurological diseases or in irregular schedule of life activity could negatively influence tissue gene expression programs and associated organ physiology via its effect on the circadian system
Atomic level description of the protecting effect of osmolytes against thermal denaturation of proteins
No full textThe protecting effect of the osmolyte molecule taurine against thermal denaturation of the protein Chimotripsin Inhibitor 2 was modelled using Molecular Dynamics simulations. The protein was simulated in denaturing conditions at different taurine concentrations. Analysis of the molecular details of its behaviour shows that the protective effect of the osmolyte is concentration dependent. Moreover, the influence of taurine on the solvent structure was studied. A concentration dependent ordering effect of taurine on water molecules emerges from solvent structure analysis and is well correlated to the protecting effect observed. Based on these observations an interpretation of the osmoprotective effect is proposed. © 2007 Elsevier B.V. All rights reserved
Circadian clock as possible protective mechanism to pollution induced skin damage
No full textOzone is among the most toxic environmental stressors to which we are continuously exposed. Due to its critical location, skin is one of the most susceptible tissues to oxidative stress damaging effect of ozone. An increasing collection of data suggests a significant role of circadian system in regulation of cellular response to oxidative stress. However, the molecular mechanism linking circadian clock and antioxidant pathway it is not completely understood. Here we investigated a possible protective role of entrained circadian clock to ozone induced damage in keratinocytes, the main cellular component of human epidermis. Our results showed that, clock-synchronized keratinocytes compared to arrhythmic ones exhibited a more efficient antioxidant response, attested by a faster activation of the master antioxidant regulatory factor NRF2. Moreover, analysis of clock gene expression profiles reveals a more rapid induction of the cardinal clock gene Bmal1 in entrained cells. Based on these findings, we suppose that an adequate coordination of circadian system and antioxidant pathway might be essential to maintain homeostasis in the skin. Alteration of metabolic pathways occurred in neurological diseases or in irregular schedule of life activity could negatively influence tissue gene expression programs and associated organ physiology via its effect on the circadian system
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