Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.     

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.     

PDGF/PDGFR: A Possible Molecular Target in Scleroderma Fibrosis

Systemic sclerosis (SSc) is a clinically heterogeneous disorder of the connective tissue characterized by vascular alterations, immune/inflammatory manifestations, and organ fibrosis. SSc pathogenesis is complex and still poorly understood. Therefore, effective therapies are lacking and remain nonspecific and limited to disease symptoms. In the last few years, many molecular and cellular mediators of SSc fibrosis have been described, providing new potential options for targeted therapies. In this review: (i) we focused on the PDGF/PDGFR pathway as key signaling molecules in the development of tissue fibrosis; (ii) we highlighted the possible role of stimulatory anti-PDGFRα autoantibodies in the pathogenesis of SSc; (iii) we reported the most promising PDGF/PDGFR targeting therapies.     

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

Microgravity impairs tissue organization and critical pathways involved in the cell–microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization.     

Where Are We with RPE Replacement Therapy? A Translational Review from the Ophthalmologist Perspective

The retinal pigmented epithelium (RPE) plays a pivotal role in retinal homeostasis. It is therefore an interesting target to fill the unmet medical need of different retinal diseases, including age-related macular degeneration and Stargardt disease. RPE replacement therapy may use different cellular sources: induced pluripotent stem cells or embryonic stem cells. Cells can be transferred as suspension on a patch with different surgical approaches. Results are promising although based on very limited samples. In this review, we summarize the current progress of RPE replacement and provide a comparative assessment of different published approaches which may become standard of care in the future.     

Inactivation of Staphylococcus aureus by the synergistic action of charged and reactive plasma particles

In this paper, a low-pressure capacitively coupled plasma discharge sustained in an argonoxygen mixture was studied in order to evaluate its properties in terms of inactivation of Staphylococcus aureus. The plasma parameters as electron temperature and plasma density were measured by the Langmuir probe (N_e ≈ 10¹⁵ m⁻³, T_e ≈ 1.5 eV), while the neutral atom density was in the range of 10²¹ m⁻³. In the plasma phase, oxygen radicals were taken as reference of the reactive species with antimicrobial activity, and oxygen spectral lines, over a range of plasma process parameters, were investigated by the optical emission spectroscopy. Optimal plasma conditions were found, and a count reduction of 4 log in a few minutes of the bacterium proves the potentiality of an industrial grade plasma reactor as a sterilization agent.     

Prevention of steel corrosion in concrete exposed to seawater with submerged sacrificial anodes

This paper presents the results of a study of the effectiveness of submerged sacrificial anodes in preventing the onset of pitting corrosion in the emerged part of marine piles. Experimental tests were carried out on reinforced concrete columns with steel embedded both in chloride free concrete and chloride contaminated concrete in order to compare the effects of sacrificial anodes on passive steel and on corroding steel. Results have shown, at least under the present testing conditions, that sacrificial anodes may be more effective in preventing corrosion initiation (i.e. in providing cathodic prevention) than in controlling ongoing pitting corrosion (i.e. in guaranteeing cathodic protection). Monitoring criteria for this type of prevention are also discussed.     

Precursor gas chemistry determines the crystallinity of carbon nanotubes synthesized at low temperature

Despite significant progress in carbon nanotube (CNT) synthesis by thermal chemical vapor deposition (CVD), the factors determining the structure of the resulting carbon filaments and other graphitic nanocarbons are not well understood. Here, we demonstrate that gas chemistry influences the crystal structure of carbon filaments grown at low temperatures (500 °C). Using thermal CVD, we decoupled the thermal treatment of the gaseous precursors (C₂H₄/H₂/Ar) and the substrate-supported catalyst. Varying the preheating temperature of the feedstock gas, we observed a striking transition between amorphous carbon nanofibers (CNFs) and crystalline CNTs. These results were confirmed using both a hot-wall CVD system and a cold-wall CVD reactor. Analysis of the exhaust gases (by ex situ gas chromatography) showed increasing concentrations of specific volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) that correlated with the structural transition observed (characterized using high-resolution transmission electron microscopy). This suggests that the crystallinity of carbon filaments may be controlled by the presence of specific gas phase precursor molecules (e.g., VOCs and PAHs). Thus, direct delivery of these molecules in the CVD process may enable selective CNF or CNT formation at low substrate temperatures. The inherent scalability of this approach could impact many promising applications, especially in the electronics industry.     

Oxidative and carbonaceous patterning of Si surface in an organic media by scanning probe lithography

A simple top-down fabrication technique that involves scanning probe lithography on Si is presented. The writing procedure consists of a chemically selective patterning in mesitylene. Operating in an organic media is possible to perform local oxidation or solvent decomposition during the same pass by tuning the applied bias. The layer deposited with a positively biased tip with sub-100-nm lateral resolution consists of nanocrystalline graphite, as verified by Raman spectroscopy. The oxide pattern obtained in opposite polarization is later used as a mask for dry etching, showing a remarkable selectivity in SF₆ plasma, to produce Si nanofeatured molds.