Potential of photodynamic therapy using polycationic photosensitizers in the treatment of lung cancer patients with SARS-CoV-2 infection and bacterial complications: Our recent experience.

The problem of treating cancer patients with lung cancer has become more difficult due to the SARS-CoV-2 viral infection and concomitant bacterial lesions. The analysis shows that the photodynamic effect of long-wavelength polycationic photosensitizers suppresses the tumor process (including the destruction of cancer stem cells), SARS-CoV-2 coronavirus infection, Gram-positive and Gram-negative bacteria, including those that can cause pneumonia. Therefore, the photodynamic approach using such photosensitizers is promising for the development of an effective treatment method for patients with lung cancer, including those with SARS-CoV-2 infection and bacterial complications.

ATP and Formyl Peptides Facilitate Chemoattractant Leukotriene-B4 Synthesis and Drive Calcium Fluxes, Which May Contribute to Neutrophil Swarming at Sites of Cell Damage and Pathogens Invasion.

Here, we demonstrate that human neutrophil interaction with the bacterium fuels leukotriene B4 synthesis induced by the chemoattractant fMLP. In this work, we found that extracellular ATP (eATP), the amount of which increases sharply during tissue damage, can effectively regulate fMLP-induced leukotriene B4 synthesis. The vector of influence strongly depends on the particular stage of sequential stimulation of neutrophils by bacteria and on the stage at which fMLP purinergic signaling occurs.

Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria ; the way to manipulate neutrophil swarming.

Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with .

Photodynamic inactivation of bacteria: Why it is not enough to excite a photosensitizer.

Background: The development of multidrug resistance (MDR) in infectious agents is one of the most serious global problems facing humanity. Antimicrobial photodynamic therapy (APDT) shows encouraging results in the fight against MDR pathogens, including those in biofilms.

Methods: Photosensitizers (PS), monocationic methylene blue, polycationic and polyanionic derivatives of phthalocyanines, electroneutral and polycationic derivatives of bacteriochlorin were used to study photodynamic inactivation of Gram-positive and Gram-negative planktonic bacteria and biofilms under LED irradiation.

Serratia marcescens DUF1471-Containing Protein SrfN Is Needed for Adaptation to Acid and Oxidative Stresses.

Bacteria can quickly adapt to constantly changing environments through a number of mechanisms, including secretion of secondary metabolites, peptides, and proteins. Serratia marcescens, an emerging pathogen with growing clinical importance due to its intrinsic resistance to several classes of antibiotics, can cause an array of infections in immunocompromised individuals. To better control the spread of S.

Biofilm matrix proteome of clinical strain of P. aeruginosa isolated from bronchoalveolar lavage of patient in intensive care unit.

Extracellular matrix plays a pivotal role in biofilm biology and proposed as a potential target for therapeutics development. As matrix is responsible for some extracellular functions and influence bacterial cytotoxicity against eukaryotic cells, it must have unique protein composition. P.

On the possibility of photodynamic inactivation of tracheobronchial tree pathogenic microbiota using methylene blue (in vitro study).

Background: The treatment of patients after mechanical ventilation of lungs suffering from a multi-species infection of the tracheobronchial tree can be complicated.. The situation is aggravated in patients with post-intubation tracheal stenosis, where infection plays a leading pathogenetic role in damage to the tracheal wall.

Gram-Negative Bacteria Boost Leukotriene Synthesis Induced by Chemoattractant fMLP to Stimulate Neutrophil Swarming.

Leukotriene synthesis in neutrophils is critical for host survival during infection. In particular, leukotriene B (LTB) is a powerful neutrophil chemoattractant that plays a crucial role in neutrophil swarming. In this work, we demonstrated that preincubation of human neutrophils with strongly stimulated LTB production induced by the bacterial chemoattractant, peptide N-formyl-L-methionyl-L-leucyl-l-phenylalanine (fMLP), while the reverse sequence of additions was ineffective.

Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides.

Mimicking bacterial DNA, synthetic CpG-containing oligodeoxyribonucleotides (CpG-ODNs) have a powerful immunomodulatory potential. Their practical application is mainly associated with the production of vaccines, where they are used as adjuvants, as well as in local antimicrobial therapy. CpG-ODNs act on a wide variety of immune cells, including neutrophilic granulocytes.

Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils.

Neutrophil-mediated innate host defense mechanisms include pathogen elimination through bacterial phagocytosis, which activates the 5-lipoxygenase (5-LOX) product synthesis. Here, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs), which mimic the receptor-recognized sites of bacterial (CpG-ODNs) and genomic (G-rich ODNs) DNAs released from the inflammatory area, on the neutrophil functions after cell stimulation with . A possible mechanism for ODN recognition by Toll-like receptor 9 (TLR9) and RAGE receptor has been proposed.

In Vitro Destruction of Pathogenic Bacterial Biofilms by Bactericidal Metallic Nanoparticles via Laser-Induced Forward Transfer.

A novel, successful method of bactericidal treatment of pathogenic bacterial biofilms in vitro by laser-induced forward transfer of metallic nanoparticles from a polyethylene terephthalate polymeric substrate was suggested. Transferred nanoparticles were characterized by scanning and transmission electron microscopy, energy-dispersive X-ray and Raman spectroscopy. The antibacterial modality of the method was tested on Gram-positive () and Gram-negative () bacterial biofilms in vitro, revealing their complete destruction.

Integrated into Environmental Biofilm Survives Winter with Support of Bacterial Community.

species are common in tropical and subtropical zones in environmental samples according to numerous studies. Here, we describe an environmental case of resident in biofilms associated with spp. roots in Moscow region, Russia (warm-summer humid continental climate zone).

Polarization-Sensitive Surface-Enhanced In Situ Photoluminescence Spectroscopy of Bacteria on Gold Nanospikes.

We report the possibility of a time-resolved bacterial live/dead dynamics observation with the use of plasmonic nanospikes. Sharp nanospikes, fabricated on a 500-nm thick gold film by laser ablation with the use of 1030-nm femtosecond pulses, were tested as potential elements for antibacterial surfaces and plasmonic luminescence sensors. bacteria were stained by a live/dead viability kit, with the dead microorganisms acquiring the red colour, caused by the penetration of the luminescent dye propidium iodide through the damaged cell membrane.

Proteomic Analysis of Human Serum from Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is an important public health problem in the world. The aim of our research was to identify novel potential serum biomarkers of renal injury. ELISA assay showed that cytokines and chemokines IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGFb, G-CSF, GM-CSF, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-1bb, RANTES, TNF-α and VEGF were significantly higher (R > 0.

The Potential of Telomeric G-quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils.

Human neutrophils are the first line of defense against bacterial and viral infections. They eliminate pathogens through phagocytosis, which activate the 5-lipoxygenase (5-LOX) pathway resulting in synthesis of leukotrienes. Using HPLC analysis, flow cytometry, and other biochemical methods, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs) able to fold into G-quadruplex structures on the main functions of neutrophils.

Surface-Enhanced IR-Absorption Microscopy of Bacteria on Bactericidal Nanostructured Si Surfaces.

Surface-enhanced IR absorption (SEIRA) microscopy was used to reveal main chemical and physical interactions between bacteria and different laser-nanostructured bactericidal Si surfaces via simultaneous chemical enhancement of the corresponding IR-absorption in the intact functional chemical groups. A cleaner, less passivated surface of Si nanoripples, laser-patterned in water, exhibits much stronger enhancement of SEIRA signals compared to the bare Si wafer, the surface coating of oxidized Si nanoparticles and oxidized/carbonized Si (nano) ripples, laser-patterned in air and water. Additional very strong bands emerge in the SEIRA spectra on the clean Si nanoripples, indicating the potential chemical modifications in the bacterial membrane and nucleic acids during the bactericidal effect.

Synthetic CpG oligonucleotides as potential modulators of neutrophil survival in PAMP-associated inhibition of apoptosis.

We studied the effects of a synthetic CpG oligonucleotide (CpG ODN2006) on polymorphonuclear leukocyte (PMNL, neutrophil) survival and oxidant status. CpG ODN2006 showed a dose-dependent effect on the apoptosis of resting neutrophils. Without affecting the viability of resting cells, low concentrations of CpG ODN2006 interfered with Salmonella typhimurium-mediated viability prolongation and increased neutrophil apoptosis to control levels.

Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5)-Furanone Derivative against .

causes various infectious diseases, from skin impetigo to life-threatening bacteremia and sepsis, thus appearing an important target for antimicrobial therapeutics. In turn, the rapid development of antibiotic resistance and biofilm formation makes it extremely robust against treatment. Here, we unravel the molecular mechanism of the antimicrobial activity of the recently unveiled consisting of three pharmacophores: chlorinated 2(5)-furanone, sulfone, and -menthol moieties.

Nitric Oxide in Life and Death of Neutrophils.

Background: Nitric Oxide (NO) is a key signalling molecule that has an important role in inflammation. It can be secreted by endothelial cells, neutrophils, and other cells, and once in circulation, NO plays important roles in regulating various neutrophil cellular activities and fate.

Objective: To describe neutrophil cellular responses influenced by NO and its concomitant compound peroxynitrite and signalling mechanisms for neutrophil apoptosis.

G-quadruplex-forming oligodeoxyribonucleotides activate leukotriene synthesis in human neutrophils.

Human polymorphonuclear leukocytes (PMNLs, neutrophils) play a major role in the immune response to bacterial and fungal infections and eliminate pathogens through phagocytosis. During phagocytosis of microorganisms, the 5-lipoxygenase (5-LOX) pathway is activated resulting in generation of leukotrienes, which mediate host defense. In this study, a library of oligodeoxyribonucleotides (ODNs) with varying numbers of human telomeric repeats (d(TTAGGG)) and their analogues with phosphorothioate internucleotide linkages and single-nucleotide substitutions was designed.

Ribonuclease from Acts as an Antiviral Agent against Negative- and Positive-Sense Single Stranded Human Respiratory RNA Viruses.

ribonuclease (binase) was shown to be a promising antiviral agent in animal models and cell cultures. However, the mode of its antiviral action remains unknown. To assess the binase effect on intracellular viral RNA we have selected single stranded negative- and positive-sense RNA viruses, influenza virus, and rhinovirus, respectively, which annually cause respiratory illnesses and are characterized by high contagious nature, mutation rate, and antigen variability.

Ceruloplasmin-derived peptide is the strongest regulator of oxidative stress and leukotriene synthesis in neutrophils.

Ceruloplasmin, an acute-phase protein, can affect the activity of leukocytes through its various enzymatic activities and protein-protein interactions (with lactoferrin, myeloperoxidase, eosinophil peroxidase, serprocidins, and 5-lipoxygenase (5-LOX), among others). However, the molecular mechanisms of ceruloplasmin activity are not clearly understood. In this study, we tested the ability of two synthetic peptides, RPYLKVFNPR (883-892) (P1) and RRPYLKVFNPRR (882-893) (P2), corresponding to the indicated fragments of the ceruloplasmin sequence, to affect neutrophil activation.

Biofilm Regulating Operon and Its Distribution in Bacterial Genomes.

Biofilm formation by spp. is a principal cause of lung chronic infections in cystic fibrosis patients. A "lacking biofilm production" (LBP) strain GIMC4587:Bct370-19 has been obtained by insertion modification of clinical strain with plasposon mutagenesis.

Effects of phosphodiester and phosphorothioate ODN2216 on leukotriene synthesis in human neutrophils and neutrophil apoptosis.

Polymorphonuclear leukocytes (PMNLs, neutrophils) play a major role in the initiation and resolution of the inflammatory response, and neutrophil apoptosis is a critical step in resolving inflammation. We examined the effects of oligodeoxynucleotide (ODN) species with different numbers of phosphodiester and phosphorothioate bonds on leukotriene synthesis in PMNLs and on neutrophil apoptosis. Our modifications were based on the well-known ODN2216 molecule (Krug et al.