Bacteria and fungi of the lung: allies or enemies?

Moving from the earlier periods in which the lungs were believed to represent sterile environments, our knowledge on the lung microbiota has dramatically increased, from the first descriptions of the microbial communities inhabiting the healthy lungs and the definition of the ecological rules that regulate its composition, to the identification of the changes that occur in pathological conditions. Despite the limitations of lung as a microbiome reservoir due to the low microbial biomass and abundance, defining its microbial composition and function in the upper and lower airways may help understanding the impact on local homeostasis and its disruption in lung diseases. In particular, the understanding of the metabolic and immune significance of microbes, their presence or lack thereof, in health and disease states could be valuable in development of novel druggable targets in disease treatments.

Overexpression of Glyoxalase 2 in Human Breast Cancer Cells: Implications for Cell Proliferation and Doxorubicin Resistance.

Glyoxalase 2 (Glo2) is an enzyme of the glyoxalase system whose pathway parallels glycolysis and which aims to remove methylglyoxal (MGO). This study analyzed the possible additional roles of the Glo2 enzyme in breast cancer (MCF7) and non-cancer (HDF) cell lines, investigating its presence at the nuclear level and its potential involvement in cell proliferation and chemotherapy resistance. The results revealed that Glo2 is overexpressed in cancer cells, and its expression is higher during the proliferative (S and G2/M) phases of the cell cycle.

Protective Effect of Indole-3-Aldehyde in Murine COVID-19-Associated Pulmonary Aspergillosis.

is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication.

Alginate microparticles containing silver@hydroxyapatite functionalized calcium carbonate composites.

This paper focuses on the preparation and characterization of antibacterial alginate microparticles containing silver@hydroxyapatite functionalized calcium carbonate composites for tissue engineering. Microparticles were prepared by cross-linking a silver@composite sodium alginate dispersion with CaCl. This method showed a very good silver efficiency loading and the presence of silver chloride nanoparticles was detected.

Amniotic fluid stem cell-derived extracellular vesicles educate type 2 conventional dendritic cells to rescue autoimmune disorders in a multiple sclerosis mouse model.

Dendritic cells (DCs) are essential orchestrators of immune responses and represent potential targets for immunomodulation in autoimmune diseases. Human amniotic fluid secretome is abundant in immunoregulatory factors, with extracellular vesicles (EVs) being a significant component. However, the impact of these EVs on dendritic cells subsets remain unexplored.

Unity Is Strength: The Mutual Alliance between CFTR and SLC26A6 as Therapeutic Opportunity in Cystic Fibrosis.

Patients with cystic fibrosis (PwCF) have recently experienced an unprecedented breakthrough with the adoption of modulator therapy in clinical practice. This remarkable achievement has led to the reconsideration of disease management as the increased life expectancy has gradually shifted the attention over a spectrum of extra-pulmonary manifestations that become prevalent in the aging population. It comes to be that complementary approaches that target patient co-morbidities are needed for the optimal clinical management of PwCF.

SARS-CoV-2 Infection is Associated with Age- and Gender-Specific Changes in the Nasopharyngeal Microbiome.

Background: The recent Coronavirus Disease 2019 (COVID-19) pandemic has dramatically exposed our gap in understanding the pathogenesis of airborne infections. Within such a context, it is increasingly clear that the nasal cavity represents a critical checkpoint not only in the initial colonization phase but also in shaping any infectious . This is particularly relevant to COVID-19 in that the nasal cavity is characterized by high-level expression of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) receptor, Angiotensin-Converting Enzyme 2 (ACE2), all along the respiratory tract.

Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein-energy malnutrition in predementia aged people: study protocol for Choko-Age.

Objective: Protein-energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly.

Glutathionyl Hemoglobin and Its Emerging Role as a Clinical Biomarker of Chronic Oxidative Stress.

Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin (HbSSG), increase in several human pathological conditions. The scope of the present review is to provide knowledge about how hemoglobin is subjected to S-glutathionylation and how this modification affects its functionality. The different diseases that showed increased levels of HbSSG and the methods used for its quantification in clinical investigations will be also outlined.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein S1 Induces Methylglyoxal-Derived Hydroimidazolone/Receptor for Advanced Glycation End Products (MG-H1/RAGE) Activation to Promote Inflammation in Human Bronchial BEAS-2B Cells.

The pathogenesis of coronavirus disease 2019 (COVID-19) is associated with a hyperinflammatory response. The mechanisms of SARS-CoV-2-induced inflammation are scantly known. Methylglyoxal (MG) is a glycolysis-derived byproduct endowed with a potent glycating action, leading to the formation of advanced glycation end products (AGEs), the main one being MG-H1.

Bridging of host-microbiota tryptophan partitioning by the serotonin pathway in fungal pneumonia.

The aromatic amino acid L-tryptophan (Trp) is essentially metabolized along the host and microbial pathways. While much is known about the role played by downstream metabolites of each pathways in intestinal homeostasis, their role in lung immune homeostasis is underappreciated. Here we have examined the role played by the Trp hydroxylase/5-hydroxytryptamine (5-HT) pathway in calibrating host and microbial Trp metabolism during Aspergillus fumigatus pneumonia.

Ketorolac Loaded Poly(lactic-co-glycolic acid) Coating of AZ31 in the Treatment of Bone Fracture Pain.

Biodegradable metal alloys may be successfully used to support bone repair, avoiding second surgery commonly needed when inert metal alloys are used. Combining a biodegradable metal alloy with a suitable pain relief agent could improve patient quality of life. AZ31 alloy was coated using a poly(lactic-co-glycolic) acid (PLGA) polymer loaded with ketorolac tromethamine using the solvent casting method.

Development of a new indole derivative dry powder for inhalation for the treatment of biofilm-associated lung infections.

The aim of this work was to produce an inhalable dry powder formulation of a new anti-biofilm compound (SC38). For this purpose, chitosan was used as a polymeric carrier and l-leucine as a dispersibility enhancer. SC38 was entrapped by spray-drying into previously optimized chitosan microparticles.

Glyoxalase 2: Towards a Broader View of the Second Player of the Glyoxalase System.

Glyoxalase 2 is a mitochondrial and cytoplasmic protein belonging to the metallo-β-lactamase family encoded by the hydroxyacylglutathione hydrolase (HAGH) gene. This enzyme is the second enzyme of the glyoxalase system that is responsible for detoxification of the α-ketothaldehyde methylglyoxal in cells. The two enzymes glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2) form the complete glyoxalase pathway, which utilizes glutathione as cofactor in eukaryotic cells.

The Glyoxalase System Is a Novel Cargo of Amniotic Fluid Stem-Cell-Derived Extracellular Vesicles.

The glyoxalase system is a ubiquitous cellular metabolic pathway whose main physiological role is the removal of methylglyoxal (MG). MG, a glycolysis byproduct formed by the spontaneous degradation of triosephosphates glyceraldehyde-3-phosphate (GA3P) and dihydroxyacetonephosphate (DHAP), is an arginine-directed glycating agent and precursor of the major advanced glycation end product arginine-derived, hydroimidazolone (MG-H1). Extracellular vesicles (EVs) are a heterogeneous family of lipid-bilayer-vesicular structures released by virtually all living cells, involved in cell-to-cell communication, specifically by transporting biomolecules to recipient cells, driving distinct biological responses.

Antioxidant Properties of Cerium Oxide Nanoparticles Prevent Retinal Neovascular Alterations In Vitro and In Vivo.

In this study, we investigated whether cerium oxide nanoparticles (CeO-NPs), a promising antioxidant nanomaterial, may contrast retinal vascular alterations induced by oxidative damage in vitro and in vivo. For the in vivo experiments, the light damage (LD) animal model of Age-Related Macular Degeneration (AMD) was used and the CeO-NPs were intravitreally injected. CeO-NPs significantly decreased vascular endothelial growth factor (VEGF) protein levels, reduced neovascularization in the deep retinal plexus, and inhibited choroidal sprouting into the photoreceptor layer.

Metabolic Shades of S-D-Lactoylglutathione.

S-D-lactoylglutathione (SDL) is an intermediate of the glutathione-dependent metabolism of methylglyoxal (MGO) by glyoxalases. MGO is an electrophilic compound that is inevitably produced in conjunction with glucose breakdown and is essentially metabolized via the glyoxalase route. In the last decades, MGO metabolism and its cytotoxic effects have been under active investigation, while almost nothing is known about SDL.

Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite.

Background: Despite the great success, the therapeutic benefits of immune checkpoint inhibitors (ICIs) in cancer immunotherapy are limited by either various resistance mechanisms or ICI-associated toxic effects including gastrointestinal toxicity. Thus, novel therapeutic strategies that provide manageable side effects to existing ICIs would enhance and expand their therapeutic efficacy and application. Due to its proven role in cancer development and immune regulation, gut microbiome has gained increasing expectation as a potential armamentarium to optimize immunotherapy with ICI.

Effects of Titanium Dioxide Nanoparticles on Porcine Prepubertal Sertoli Cells: An "" Study.

The increasing use of nanomaterials in a variety of industrial, commercial, medical products, and their environmental spreading has raised concerns regarding their potential toxicity on human health. Titanium dioxide nanoparticles (TiO NPs) represent one of the most commonly used nanoparticles. Emerging evidence suggested that exposure to TiO NPs induced reproductive toxicity in male animals.

Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases.

Bone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boosting research to identify additional mechanisms that may be involved in this two-directional talk.

Glyoxalase-1-Dependent Methylglyoxal Depletion Sustains PD-L1 Expression in Metastatic Prostate Cancer Cells: A Novel Mechanism in Cancer Immunosurveillance Escape and a Potential Novel Target to Overcome PD-L1 Blockade Resistance.

Metastatic prostate cancer (mPCa) is a disease for which to date there is not curative therapy. Even the recent and attractive immunotherapeutic approaches targeting PD-L1, an immune checkpoint protein which helps cancer cells to escape from immunosurveillance, have proved ineffective. A better understanding of the molecular mechanisms contributing to keep an immunosuppressive microenvironment associated with tumor progression and refractoriness to PD-L1 inhibitors is urgently needed.

Methylglyoxal-Dependent Glycative Stress Is Prevented by the Natural Antioxidant Oleuropein in Human Dental Pulp Stem Cells through Nrf2/Glo1 Pathway.

Methylglyoxal (MG) is a potent precursor of glycative stress (abnormal accumulation of advanced glycation end products, AGEs), a relevant condition underpinning the etiology of several diseases, including those of the oral cave. At present, synthetic agents able to trap MG are known; however, they have never been approved for clinical use because of their severe side effects. Hence, the search of bioactive natural scavengers remains a sector of strong research interest.