Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

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.     

Ruthenium(II)–Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells

Ru^II-arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new Ru^II-arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes ( 2 a , b and 5 ) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC₅₀=39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity.     

Methylmercury Causes Neurodegeneration and Downregulation of Myelin Basic Protein in the Spinal Cord of Offspring Rats after Maternal Exposure

Methylmercury (MeHg) is one of the most dangerous toxic pollutants spread throughout the earth. Chronic MeHg intoxication by contaminated food ingestion is the most common threat to human health, including impairment to the developing fetus. The present study aims at investigating the effects of maternal exposure to MeHg during gestation and lactation on the spinal cord of offspring. Pregnant rats received oral doses of MeHg (40 μg/kg/day) over a period of 42 days (21 gestation and 21 lactation). Control animals received the vehicle only. Total mercury concentration was measured in blood samples from offspring collected at the 41st postnatal day. Counting of motor neurons and immunoreactivity for myelin basic protein (MBP) were assessed in the spinal cords in both control and MeHg-intoxicated animals. Our results showed that MeHg promoted an increase in blood Hg levels. In addition, it caused a reduction in the number of spinal cord motor neurons as well as decreased MBP immunoreactivity in the cervical, thoracic and lumbar segments. Our present findings suggest that MeHg intoxication during rat pregnancy and lactation is associated with a pattern of motor neuron degeneration and downregulation of myelin basic protein in different segments of a developing spinal cord. Further studies are needed to establish the effect of MeHg intoxication in both young and adult rats.     

Human Intestinal Dendritic Cells in Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a serious, costly, and persistent health problem with an estimated prevalence in Western countries around 0.5% of the general population; its socioeconomic impact is comparable with that for chronic diseases such as diabetes. Conventional treatment involves escalating drug regimens with concomitant side effects followed, in some cases, by surgical interventions, which are often multiple, mainly in Crohn's disease. The goal of finding a targeted gut‐specific immunotherapy for IBD patients is therefore an important unmet need. However, to achieve this goal we first must understand how dendritic cells (DC), the most potent antigen present cells of the immune system, control the immune tolerance in the gastrointestinal tract and how their properties are altered in those patients suffering from IBD. In this review, we summarize the current available information regarding human intestinal DC subsets composition, phenotype, and function in the human gastrointestinal tract describing how, in the IBD mucosa, DC display pro‐inflammatory properties, which drive disease progression. A better understanding of the mechanisms inducing DC abnormal profile in IBD may provide us with novel tools to perform tissue specific immunomodulation.     

Impact of intervention strategies on Listeria contamination patterns in crawfish processing plants: a longitudinal study

Two ready-to-eat crawfish processing plants were monitored for 2 years to study the impact of Listeria control strategies, including employee training and targeted sanitation procedures, on Listeria contamination. Environmental, raw material, and finished product samples were collected weekly during the main processing months (April to June) and tested for Listeria spp. and Listeria monocytogenes. Before implementation of control strategies (year 1), the two processing plants showed Listeria spp. prevalences of 29.5% (n = 78) in raw, whole crawfish, 5.2% (n = 155) in the processing plant environment, and 0% (n = 78) in finished products. In year 2, after plant-specific Listeria control strategies were implemented, Listeria spp. prevalence increased in raw crawfish (57.5%, n = 101), in the processing plant environment (10.8%, n = 204), and in the finished product (1.0%, n = 102). Statistical analysis showed a significant increase in Listeria spp. prevalence (P < 0.0001) and a borderline nonsignificant increase in L. monocytogenes prevalence (P = 0.097) on raw material in year 2. Borderline nonsignificant increases were also observed for Listeria spp. prevalence in environmental samples (P = 0.082). Our data showed that Listeria spp. prevalence in raw crawfish can vary significantly among seasons. However, the increased contamination prevalence for raw materials only resulted in a limited Listeria prevalence increase for the processing plant environment with extremely low levels of finished product contamination. Heat treatment of raw materials combined with Listeria control strategies to prevent cross-contamination thus appears to be effective in achieving low levels of finished product contamination, even with Listeria spp. prevalences for raw crawfish of more than 50%.     

Interferon-β Activity Is Affected by S100B Protein

Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca²⁺-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in numerous oncological and neurological diseases. The use of chemical crosslinking, intrinsic fluorescence, and surface plasmon resonance spectroscopy revealed IFN-β binding to Ca²⁺-loaded dimeric and monomeric forms of the S100B protein. Calcium depletion blocks the S100B–IFN-β interaction. S100B monomerization increases its affinity to IFN-β by 2.7 orders of magnitude (equilibrium dissociation constant of the complex reaches 47 pM). Crystal violet assay demonstrated that combined application of IFN-β and S100B (5–25 nM) eliminates their inhibitory effects on MCF-7 cell viability. Bioinformatics analysis showed that the direct modulation of IFN-β activity by the S100B protein described here could be relevant to progression of multiple oncological and neurological diseases.     

In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model

Recent biotechnological applications in the field of clinical oncology led to the identification of new biomarkers as molecular targets of cancer, and to broad developments in the field of personalized medicine. Aptamers are oligonucleotides (ssDNA or RNA) that are selected to specifically recognize a molecular target with high affinity and specificity. Based on this, new horizons for their use as molecular imaging probes are being explored. The objective of this work was to evaluate the Sgc8-c aptamer conjugated with Alexa Fluor 647 fluorophore as an imaging probe in a colon tumor xenograft mouse model, with potential application in molecular imaging. In this study, the LS174T cell line was used to induce colorectal adenocarcinoma in nude mice. After confirmation of PTK7 overexpression by immunohistochemistry, in vivo studies were performed. Pharmacokinetic, in vivo and ex vivo biodistribution imaging, and a competition assay were evaluated by fluorescence imaging. In vivo visualization of the probe in the tumors was assessed two hours after aptamer probe administration, exhibiting excellent tumor-to-background ratios in biodistribution studies and high specificity in the competition test. Our results demonstrated the functionality of Scg8-c as an imaging probe for colon cancer, with potential clinical applications.     

Numerical Analysis on a Latent Thermal Energy Storage System with Phase Change Materials and Aluminum Foam

Abstract

A latent heat thermal energy storage system with phase change material (PCM) is numerically studied. To enhance the heat transfer inside the system, a highly conductive metal foam is employed with ceramic nanoparticles. The latter method of enhancement leads to a new class of material called Nano-PCM. The system under investigation is a 70-L tank filled up with pure PCM or Nano-PCM and several pipes are situated where the heat transfer fluid (HTF) flows. The pipe surfaces are assumed at constant temperature above the PCM melting temperature to simulate the heat transfer from the HTF. The enthalpy-porosity theory is applied to simulate the PCM phase change, while the porous media formulation is assumed to describe the metal foam behavior. The nano-PCM is modeled with single-phase model where the properties are the weighted-average between the fluid base and the nanoparticles. The simulations are accomplished for charging-discharging process at different porosities and nanoparticle concentration. The results are given in term of average melting fraction evolution, average temperature as function of time, average stored energy. The metal foam significantly improves the heat transfer between PCM and HTF respect to the addition of nanoparticles, reducing the charging and discharging time more than one order of magnitude.