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The description of ultrafast nonadiabatic chemical dynamics during molecular photo-transformations remains challenging because electronic and nuclear configurations impact each other and cannot be treated independently. Here we gain experimental insights, beyond the Born–Oppenheimer approximation, into the light-induced spin-state trapping dynamics of the prototypical [Fe(bpy) 3 ] 2+ compound by time-resolved X-ray absorption spectroscopy at sub-30-femtosecond resolution and high signal-to-noise ratio. The electronic decay from the initial optically excited electronic state towards the high spin state is distinguished from the structural trapping dynamics, which launches a coherent oscillating wave packet (265 fs period), clearly identified as molecular breathing. Throughout the structural trapping, the dispersion of the wave packet along the reaction coordinate reveals details of intramolecular vibronic coupling before a slower vibrational energy dissipation to the solution environment. These findings illustrate how modern time-resolved X-ray absorption spectroscopy can provide key information to unravel dynamic details of photo-functional molecules. Ultrafast nonadiabatic chemical dynamics during molecular photo-transformations remain challenging to describe since electronic/nuclear configurations are coupled. Here the authors use time-resolved X-ray absorption spectroscopy to probe the light-induced spin-state trapping dynamics of [Fe(bpy) 3 ] 2+ beyond the Born-Oppenheimer approximation.

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.

Aging is an agglomerate of biological long-lasting processes that result being inevitable. Main actors in this scenario are both long-term inflammation and oxidative stress. It has been proved that oxidative stress induce alteration in proteins and this fact itself is critically important in the pathophysiological mechanisms leading to diseases typical of aging. Among reactive species, chlorine ones such as hypochlorous acid (HOCl) are cytotoxic oxidants produced by activated neutrophils during chronic inflammation processes. HOCl can also cause damages by reacting with biological molecules. HOCl is generated by myeloperoxidase (MPO) and augmented serum levels of MPO have been described in acute and chronic inflammatory conditions in cardiovascular patients and has been implicated in many inflammatory diseases such as atherosclerosis, neurodegenerative conditions, and some cancers. Due to these data, we decided to conduct an up-to-date review evaluating chlorinative stress effects on every age-related disease linked; potential anti-oxidant countermeasures were also assessed. Results obtained associated HOCl generation to the aging processes and confirmed its connection with diseases like neurodegenerative and cardiovascular pathologies, atherosclerosis and cancer; chlorination was mainly linked to diseases where molecular (protein) alteration constitute the major suspected cause: i.e. inflammation, tissue lesions, DNA damages, apoptosis and oxidative stress itself. According data collected, a healthy lifestyle together with some dietary suggestion and/or the administration of nutracetical antioxidant integrators could balance the effects of chlorinative stress and, in some cases, slow down or prevent the onset of age-releated diseases.

Exposure to cigarette smoke, allergens, viruses, and other environmental contaminants, as well as a detrimental lifestyle, are the main factors supporting elevated levels of airway oxidative stress. Elevated oxidative stress results from an imbalance in reactive oxygen species (ROS) production and efficiency in antioxidant defense systems. Uncontrolled increased oxidative stress amplifies inflammatory processes and tissue damage and alters innate and adaptive immunity, thus compromising airway homeostasis. Oxidative stress events reduce responsiveness to corticosteroids. These events can increase risk of asthma into adolescence and prompt evolution of asthma toward its most severe forms. Development of new therapies aimed to restore oxidant/antioxidant balance and active interventions aimed to improve physical activity and quality/quantity of food are all necessary strategies to prevent asthma onset and avoid in asthmatics evolution toward severe forms of the disease.

In the early 1970s, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and named high-mobility group (HMG) proteins. High-mobility group box 1 (HMGB1) is the most studied HMG protein that detects and coordinates cellular stress response. The biological function of HMGB1 depends on its subcellular localization and expression. It plays a critical role in the nucleus and cytoplasm as DNA chaperone, chromosome gatekeeper, autophagy maintainer, and protector from apoptotic cell death. HMGB1 also functions as an extracellular alarmin acting as a damage-associated molecular pattern molecule (DAMP). Recent findings describe HMGB1 as a sophisticated signal of danger, with a pleiotropic function, which is useful as a clinical biomarker for several disorders. HMGB1 has emerged as a mediator in acute and chronic inflammation. Furthermore, HMGB1 targeting can induce beneficial effects on oxidative stress related diseases. This review focus on HMGB1 redox status, localization, mechanisms of release, binding with receptors, and its activities in different oxidative stress-related chronic diseases. Since a growing number of reports show the key role of HMGB1 in socially relevant pathological conditions, to our knowledge, for the first time, here we analyze the scientific literature, evaluating the number of publications focusing on HMGB1 in humans and animal models, per year, from 2006 to 2021 and the number of records published, yearly, per disease and category (studies on humans and animal models).

Cigarette smoking impairs the lung innate immune response making smokers more susceptible to infections and severe symptoms. Dysregulation of cell death is emerging as a key player in chronic inflammatory conditions. We have recently reported that short exposure of human monocyte-derived macrophages (hMDMs) to cigarette smoke extract (CSE) altered the TLR4-dependent response to lipopolysaccharide (LPS). CSE caused inhibition of the MyD88-dependent inflammatory response and activation of TRIF/caspase-8/caspase-1 pathway leading to Gasdermin D (GSDMD) cleavage and increased cell permeability. Herein, we tested the hypothesis that activation of caspase-8 by CSE increased pro-inflammatory cell death of LPS-stimulated macrophages. To this purpose, we measured apoptotic and pyroptotic markers as well as the expression/release of pro-inflammatory mediators in hMDMs exposed to LPS and CSE, alone or in combination, for 6 and 24 h. We show that LPS/CSE-treated hMDMs, but not cells treated with CSE or LPS alone, underwent lytic cell death (LDH release) and displayed apoptotic features (activation of caspase-8 and -3/7, nuclear condensation, and mitochondrial membrane depolarization). Moreover, the negative regulator of caspase-8, coded by CFLAR gene, was downregulated by CSE. Activation of caspase-3 led to Gasdermin E (GSDME) cleavage. Notably, lytic cell death caused the release of the damage-associated molecular patterns (DAMPs) heat shock protein-60 (HSP60) and S100A8/A9. This was accompanied by an impaired inflammatory response resulting in inhibited and delayed release of IL6 and TNF. Of note, increased cleaved caspase-3, higher levels of GSDME and altered expression of cell death-associated genes were found in alveolar macrophages of smoker subjects compared to non-smoking controls. Overall, our findings show that CSE sensitizes human macrophages to cell death by promoting pyroptotic and apoptotic pathways upon encountering LPS. We propose that while the delayed inflammatory response may result in ineffective defenses against infections, the observed cell death associated with DAMP release may contribute to establish chronic inflammation. CS exposure sensitizes human macrophages to pro-inflammatory cell death. Upon exposure to LPS, CS inhibits the TLR4/MyD88 inflammatory response, downregulating the pro-inflammatory genes TNF and IL6 and the anti-apoptotic gene CFLAR , known to counteract caspase-8 activity. CS enhances caspase-8 activation through TLR4/TRIF, with a partial involvement of RIPK1, resulting on the activation of caspase-1/GSDMD axis leading to increased cell permeability and DAMP release through gasdermin pores [ 19 ]. At later timepoints caspase-3 becomes strongly activated by caspase-8 triggering apoptotic events which are associated with mitochondrial membrane depolarization, gasdermin E cleavage and secondary necrosis with consequent massive DAMP release.

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.

A comprehensive view of cystic fibrosis gene therapy is provided with the review ofSui et al.Cystic fibrosis is caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). Treatment of a mouse model of ALI with this drug showed a decrease of inflammatory cell infiltration and damage in lung tissue, an inhibition of Rac1/LIMK1/ZO-1/occludin signaling pathway. [...]TMP protects the pulmonary microvascular endothelial cell barrier and may have a promising therapeutic role in preventing acute lung injury from sepsis. [...]this Research Topic has highlighted how knowledge on respiratory diseases is constantly growing and how animal models can help the understanding of the pathophysiological aspects of the main respiratory diseases as well as the pre-clinical testing of new therapeutic approaches.

Patients with Chronic Obstructive Pulmonary Disease (COPD) periodically experience acute exacerbation (AECOPD). Carbocysteine represents a valid add on therapy in COPD by exerting antioxidant and anti-inflammatory activities. The in vivo effects of carbocysteine on inflammatory markers are not yet fully understood. The aims of this study were to assess: (i) miR-21, IL-8, soluble Receptor for Advanced Glycation End Products (sRAGE), and fluorescent Advanced Glycation End Products (fAGEs) in control subjects (n = 9), stable (n = 9), and AECOPD patients (n = 24); and (ii) whether carbocysteine modifies these markers and the functional parameters in mild AECOPD patients. Mild AECOPD patients received or not carbocysteine along with background inhalation therapy for 20 days. At the onset and at the end of the observation period, the following parameters were evaluated: FEV1, FEF25–75%, CAT questionnaire; miR-21 by Real Time PCR; IL-8 and sRAGE by ELISA; and fAGEs by spectro-fluorescence method. COPD patients showed higher levels of miR-21, IL-8, fAGEs and lower levels of sRAGE compared to that of controls. miR-21 inversely correlated with FEV1. IL-8 and fAGEs were significantly different in stable and exacerbated COPD patients. Carbocysteine improved symptoms, FEV1 and FEF25–75%, increased sRAGE, and reduced miR-21, IL-8, and fAGEs in mild AECOPD patients. The present study provides compelling evidence that carbocysteine may help to manage mild AECOPD by downregulating some parameters of systemic inflammation.

Biophotons are an ultra-weak emission of photons in the visible energy range from living matter. In this work, we study the emission from germinating seeds using an experimental technique designed to detect light of extremely small intensity. The emission from lentil seeds and single bean was analyzed during the whole germination process in terms of the different spectral components through low pass filters and the different count distributions in the various stages of the germination process. Although the shape of the emission spectrum appears to be very similar in the two samples used in our experiment, our analysis can highlight the differences present in the two cases. In this way, it was possible to correlate the various types of emissions to the degree of development of the seed during germination.