Deep Immunophenotyping of Circulating T and B Cells in Relapsing Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a complex systemic inflammatory disorder, categorized as an 'IL-1 driven' inflammasomapathy. Despite this, the interaction between T and B cells remains poorly understood. We conducted a study, enrolling 7 patients with relapsing AOSD and 15 healthy control subjects, utilizing deep flow cytometry analysis to examine peripheral blood T- and B-cell subsets. T-cell and B-cell subsets were significantly altered in patients with AOSD. Within CD4+ T cells, Th2 cells were decreased. Additionally, Th17 cell and follicular Th cell subsets were altered within CD45RA-CD62L+ and CD45RA-CD62L- Th cells in patients with AOSD compared to healthy controls. We identified changes in CD8+ T cell maturation and 'polarization' in AOSD patients, with an elevated presence of the TEMRA CD8+ T cell subset. Furthermore, the percentage of Tc1 cells was decreased, while the frequency of CCR6-CXCR3- Tc2 cells was elevated. Finally, we determined that the frequency of CD5+CD27- B cells was dramatically decreased in patients with AOSD compared to healthy controls. Further investigations on a large group of patients with AOSD are required to evaluate these adaptive immunity cells in the disease pathogenesis.

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation of the cardiovascular system and regeneration processes. In recent years, more and more facts have been accumulating that demonstrate a close relationship between arginine metabolic pathways and immune responses. This opens new opportunities for the development of original ways to treat diseases associated with suppressed or increased activity of the immune system. In this review, we analyze the literature describing the role of arginine metabolism in the immunopathogenesis of a wide range of diseases, and discuss arginine-dependent processes as a possible target for therapeutic approaches.

COVID-19 Heart Lesions in Children: Clinical, Diagnostic and Immunological Changes.

In the beginning of COVID-19, the proportion of confirmed cases in the pediatric population was relatively small and there was an opinion that children often had a mild or asymptomatic course of infection. Our understanding of the immune response, diagnosis and treatment of COVID-19 is highly oriented towards the adult population. At the same time, despite the fact that COVID-19 in children usually occurs in a mild form, there is an incomplete understanding of the course as an acute infection and its subsequent manifestations such as Long-COVID-19 or Post-COVID-19, PASC in the pediatric population, correlations with comorbidities and immunological changes. In mild COVID-19 in childhood, some authors explain the absence of population decreasing T and B lymphocytes. Regardless of the patient's condition, they can have the second phase, related to the exacerbation of inflammation in the heart tissue even if the viral infection was completely eliminated-post infectious myocarditis. Mechanism of myocardial dysfunction development in MIS-C are not fully understood. It is known that various immunocompetent cells, including both resident inflammatory cells of peripheral tissues (for example macrophages, dendritic cells, resident memory T-lymphocytes and so on) and also circulating in the peripheral blood immune cells play an important role in the immunopathogenesis of myocarditis. It is expected that hyperproduction of interferons and the enhanced cytokine response of T cells 1 and 2 types contribute to dysfunction of the myocardium. However, the role of Th1 in the pathogenesis of myocarditis remains highly controversial. At the same time, the clinical manifestations and mechanisms of damage, including the heart, both against the background and after COVID-19, in children differ from adults. Further studies are needed to evaluate whether transient or persistent cardiac complications are associated with long-term adverse cardiac events.

Emission and Migration of Nanoscale Particles during Osseointegration and Disintegration of Dental Implants in the Clinic and Experiment and the Influence on Cytokine Production.

The emission of nanoscale particles from the surfaces of dental implants leads to the cumulative effect of particle complexes in the bone bed and surrounding soft tissues. Aspects of particle migration with the possibility of their involvement in the development of pathological processes of systemic nature remain unexplored. The aim of this work was to study protein production during the interaction of immunocompetent cells with nanoscale metal particles obtained from the surfaces of dental implants in the supernatants. The ability to migrate nanoscale metal particles with possible involvement in the formation of pathological structures, in particular in the formation of gallstones, was also investigated. The following methods were used: microbiological studies, X-ray microtomography, X-ray fluorescence analysis, flow cytometry, electron microscopy, dynamic light scattering, and multiplex immunofluorescence analysis. For the first time, titanium nanoparticles in gallstones were identified by X-ray fluorescence analysis and electron microscopy with elemental mapping. The multiplex analysis method revealed that the physiological response of the immune system cells, in particular neutrophils, to nanosized metal particles significantly reduced TNF-a production both through direct interaction and through double lipopolysaccharide-induced signaling. For the first time, a significant decrease in TNF-a production was demonstrated when supernatants containing nanoscale metal particles were co-cultured with proinflammatory peritoneal exudate obtained from the peritoneum of the C57Bl/6J inbred mice line for one day.

Cytokine Storm Signature in Patients with Moderate and Severe COVID-19.

Hypercytokinemia, found in SARS-CoV-2 infection, contributes to multiple organ dysfunctions with acute respiratory distress syndrome, shock etc. The aim of this study was to describe cytokine storm signatures in patients with acute COVID-19 and to investigate their influence on severity of the infection. Plasma levels of 47 cytokines were investigated in 73 patients with moderate and severe COVID-19 (41 and 32, respectively) and 11 healthy donors (HD). The most elevated levels comparing patients and the HD were observed for seven pro-inflammatory cytokines (IL-6, IL-8, IL-15, IL-18, IL-27, IFNγ, TNFα), three chemokines (GROα, IP-10, MIG), two anti-inflammatory cytokines (IL-1RA, IL-10), and two growth factors (G-CSF, M-CSF). The patients with severe disease had significantly higher levels of FGF-2/FGF-basic, IL-1ß, and IL-7 compared to the HD. The two groups of patients differed from each other only based on the levels of EGF, eotaxin, and IL-12 p40. Pneumonia lung injury, characterized by computer tomography, positively correlated with levels of EGF, IP-10, MCP-3 levels and negatively with IL-12 p40. Pro-inflammatory factors including IL-6, TNFα, and IP-10 negatively correlated with the frequency of the circulating T-helper17-like cells (Th17-like) and follicular Th cells that are crucial to develop SARS-CoV-2-specific plasma cells and memory B cells. Obtained data on the cytokine levels illustrate their influence on progression and severity of COVID-19.

Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections-Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection.

Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression.

Immunopathological Inflammation in the Evolution of Mucositis and Peri-Implantitis.

The purpose of this study was to provide an immuno-mediated substantiation of the etiopathogenesis of mucositis and peri-implantitis based on the results of experimental, laboratory and clinical studies. The biopsy material was studied to identify impregnated nanoscale and microscale particles in the structure of pathological tissues by using X-ray microtomography and X-ray fluorescence analyses. Electron microscopy with energy-dispersive analysis identified the composition of supernatants containing nanoscale metal particles obtained from the surfaces of dental implants. The parameters of the nanoscale particles were determined by dynamic light scattering. Flow cytometry was used to study the effect of nanoscale particles on the ability to induce the activation and apoptosis of immunocompetent cells depending on the particles' concentrations during cultivation with the monocytic cell line THP-1 with the addition of inductors. An analysis of the laboratory results suggested the presence of dose-dependent activation, as well as early and late apoptosis of the immunocompetent cells. Activation and early and late apoptosis of a monocytic cell line when THP-1 was co-cultured with nanoscale metal particles in supernatants were shown for the first time. When human venous blood plasma was added, both activation and early and late apoptosis had a dose-dependent effect and differed from those of the control groups.

Succinyl Chitosan-Colistin Conjugates as Promising Drug Delivery Systems.

The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3-8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130-318 µg/mg. The size of the obtained particles was 100-200 nm, and the ζ-potential varied from -22 to -28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1-0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20-60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics.

Alterations in B Cell and Follicular T-Helper Cell Subsets in Patients with Acute COVID-19 and COVID-19 Convalescents.

BACKGROUND: Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. METHODS: Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. RESULTS: Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2' and "Bm3+Bm4" was found if compared with HC. During acute COVID-19 CXCR3+CCR6- Tfh1-like cells were decreased and the levels of CXCR3-CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. CONCLUSIONS: Our data indicate that COVID-19 can impact the humoral immunity in the long-term.

Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery.

The development of intravitreal glucocorticoid delivery systems is a current global challenge for the treatment of inflammatory diseases of the posterior segment of the eye. The main advantages of these systems are that they can overcome anatomical and physiological ophthalmic barriers and increase local bioavailability while prolonging and controlling drug release over several months to improve the safety and effectiveness of glucocorticoid therapy. One approach to the development of optimal delivery systems for intravitreal injections is the conjugation of low-molecular-weight drugs with natural polymers to prevent their rapid elimination and provide targeted and controlled release. This study focuses on the development of a procedure for a two-step synthesis of dexamethasone (DEX) conjugates based on the natural polysaccharide chitosan (CS). We first used carbodiimide chemistry to conjugate DEX to CS via a succinyl linker, and we then modified the obtained systems with succinic anhydride to impart a negative ζ-potential to the polymer particle surface. The resulting polysaccharide carriers had a degree of substitution with DEX moieties of 2-4%, a DEX content of 50-85 µg/mg, and a degree of succinylation of 64-68%. The size of the obtained particles was 400-1100 nm, and the ζ-potential was -30 to -33 mV. In vitro release studies at pH 7.4 showed slow hydrolysis of the amide and ester bonds in the synthesized systems, with a total release of 8-10% for both DEX and succinyl dexamethasone (SucDEX) after 1 month. The developed conjugates showed a significant anti-inflammatory effect in TNFα-induced and LPS-induced inflammation models, suppressing CD54 expression in THP-1 cells by 2- and 4-fold, respectively. Thus, these novel succinyl chitosan-dexamethasone (SucCS-DEX) conjugates are promising ophthalmic carriers for intravitreal delivery.

Application of high-sensitivity flow cytometry in combination with low-voltage scanning electron microscopy for characterization of nanosized objects during platelet concentrate storage.

Platelet concentrates are used in clinic for therapy and prophylaxis of conditions associated with platelet deficiency or malfunction. The characteristics of platelet concentrates gradually change during pretransfusion storage, affecting their clinical effectiveness and the risk of adverse transfusion reactions. The presence of platelet-derived membrane vesicles is an important characteristic of platelet concentrates. Due to their functionality, changes in the number and molecular compositions of platelet-derived vesicles have major effects on the clinical properties of platelet preparations. The existence of different subpopulations of membrane vesicles requires analytical methods capable of providing information at the individual vesicle level. Such methods include flow cytometry and electron microscopy. However, conventional flow cytometry has certain limitations, since the diameters of many platelet-derived membrane vesicles are smaller than its detection limit. The use of classical scanning electron microscopy is also limited due to the requirement for coating with a layer of conductive material, which impedes the detection of small extracellular vesicles. Here, a combination of high-sensitivity flow cytometry and low-voltage scanning electron microscopy was used to increase sensitivity and resolution in the detection of nanosized objects present in platelet concentrates during storage. Apheresis platelet concentrates from eight healthy adult donors were investigated on days 2 and 7 of storage. Fractions of nanosized objects were obtained by differential centrifugation. Fluorophore-conjugated antibodies were used to detect marker-positive vesicles derived from platelets (CD41), red blood cells (CD235a), leukocytes (CD45), and endothelial cells (VEGFR2). Near-spherical objects with diameters ranging from 25 to 700 nm were observed by low-voltage scanning electron microscopy in platelet concentrates and its fractions. On day 7 of storage, objects with diameters of less than 100 nm were attached to and clustered near the terminal ends of pseudopod-like projections. High-sensitivity flow cytometry showed that during storage numbers of CD41(pos) vesicles elevated more than fivefold and numbers of marker-negative nanosized objects, which did not carry any of the investigated cell type-specific markers elevated more than twofold. Major changes in both CD41(pos) vesicles and marker-negative nanosized objects abundances were observed for objects with diameters around 100 nm bead equivalents. Overall, these results emphasized the importance of application of high-sensitivity methods for monitoring the characteristics of cell-derived nanosized objects during platelet concentrate storage.

Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection.

Expression of gene of arginine deiminase (AD) allows adaptation of Streptococcus pyogenes to adverse environmental conditions. AD activity can lead to L-arginine deficiency in the host cells' microenvironment. Bioavailability of L-arginine is an important factor regulating the functions of the immune cells in mammals. By introducing a mutation into S pyogenes M46-16, we obtained a strain with inactivated arcA/sagp gene (M49-16 delArcA), deficient in AD. This allowed elucidating the function of AD in pathogenesis of streptococcal infection. The virulence of the parental and mutant strains was examined in a murine model of subcutaneous streptococcal infection. L-arginine concentration in the plasma of mice infected with S pyogenes M49-16 delArcA remained unchanged in course of the entire experiment. At the same time mice infected with S pyogenes M49-16 demonstrated gradual diminution of L-arginine concentration in the blood plasma, which might be due to the activity of streptococcal AD. Mice infected with S pyogenes M49-16 delArcA demonstrated less intensive bacterial growth in the primary foci and less pronounced bacterial dissemination as compared with animals infected with the parental strain S pyogenes M46-16. Similarly, thymus involution, alterations in apoptosis, thymocyte subsets and Treg cells differentiation were less pronounced in mice infected with S pyogenes M49-16 delArcA than in those infected with the parental strain. The results obtained showed that S pyogenes M49-16 delArcA, unable to produce AD, had reduced virulence in comparison with the parental S pyogenes M49-16 strain. AD is an important factor for the realization of the pathogenic potential of streptococci.

Neutrophil activation in response to monomeric myeloperoxidase.

Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also regulate cellular functions via its nonenzymatic effects. Mature active MPO isolated from normal human neutrophils is a 145 kDa homodimer, which consists of 2 identical protomers, connected by a single disulfide bond. By binding to CD11b/CD18 integrin, dimeric MPO induces neutrophil activation and adhesion augmenting leukocyte accumulation at sites of inflammation. This study was performed to compare the potency of dimeric and monomeric MPO to elicit selected neutrophil responses. Monomeric MPO (hemi-MPO) was obtained by treating the dimeric MPO by reductive alkylation. Analysis of the crucial signal transducer, intracellular Ca2+, showed that dimeric MPO induces Ca2+ mobilization from the intracellular calcium stores of neutrophils and influx of extracellular Ca2+ whereas the effect of monomeric MPO on Ca2+ increase in neutrophils was less. It was also shown that monomeric MPO was less efficient than dimeric MPO at inducing actin cytoskeleton reorganization, cell survival, and neutrophil degranulation. Furthermore, we have detected monomeric MPO in the blood plasma of patients with acute inflammation. Our data suggest that the decomposition of dimeric MPO into monomers can serve as a regulatory mechanism that controls MPO-dependent activation of neutrophils and reduces the proinflammatory effects of MPO.

Novel Quinoxaline-2-Carbonitrile-1,4-Dioxide Derivatives Suppress HIF1α Activity and Circumvent MDR in Cancer Cells.

A series of 3-aryl/hetarylquinoxaline-2-carbonitrile-1,4-dioxides was synthesized and evaluated against breast cancer cell lines in normoxia and hypoxia. Selected compounds in this series demonstrated better cytotoxicity and comparable hypoxia selectivity than tirapazamine. In contrast to Dox, quinoxaline-1,4-dioxides showed potent cytotoxicity against different MDR cells. Compound 2g inhibits of cancer cell growth through p53-independent mechanisms. Our results showed that compound 2g sensitized MCF-7 cells to metformin in hypoxia. Treatment with 2g results in the increase of ROS accumulation in cancer cells. Compound 2g can be considered as the lead compound for further anticancer drug design, evaluation, and development of new potent antitumor agents.

Binding of human myeloperoxidase to red blood cells: Molecular targets and biophysical consequences at the plasma membrane level.

Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also bind to cellular surface proteins. We found that band 3 protein and glycophorins A and B were the key MPO-binding targets of human red blood cells (RBCs). The interaction of MPO with RBC proteins was mostly electrostatic in nature because it was inhibited by desialation, exogenic sialic acid, high ionic strength, and extreme pH. In addition, MPO failed to interfere with the lectin-induced agglutination of RBCs, suggesting a minor role of glycan-recognizing mechanisms in MPO binding. Multiple biophysical properties of RBCs were altered in the presence of native (i.e., not hypochlorous acid-damaged) MPO. These changes included transmembrane potential, availability of intracellular Ca(2+), and lipid organization in the plasma membrane. MPO-treated erythrocytes became larger in size, structurally more rigid, and hypersensitive to acidic and osmotic hemolysis. Furthermore, we found a significant correlation between the plasma MPO concentration and RBC rigidity index in type-2 diabetes patients with coronary heart disease. These findings suggest that MPO functions as a mediator of novel regulatory mechanism in microcirculation, indicating the influence of MPO-induced abnormalities on RBC deformability under pathological stress conditions.

A novel strategy for the synthesis of thermally stable and apoptosis-inducing 2,3-dihydroazetes.

A general and concise approach to thermally and hydrolytically stable alkyl 2,3-dihydroazete-2,3-di-/2,2,3-tricarboxylates from alkyl 2-bromoazirine-2-carboxylates or 4-bromo-5-alkoxyisoxazoles is reported. The synthesis involves the formation of 2-azabuta-1,3-diene by the reaction of rhodium carbenoid with isoxazole or azirine followed by cyclization/hydrodebromination cascade. The latter reaction is the first example of the selective hydrodehalogenation of a valence isomer under equilibrium conditions. In vitro cytotoxicity tests on THP-1 cell line revealed that the 2,3-dihydroazetes greatly differ in their ability to induce apoptosis and/or necrosis. To adequately describe and quantitatively assess these properties, the difference between the two areas under the curves of concentration dependency of apoptosis/necrosis induction within the concentration range was used. Trimethyl 4-phenyl-2,3-dihydroazete-2,2,3-tricarboxylate was found to display the maximal apoptotic potential coupled with high cytotoxic and minimal necrotic potential.

Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations.

Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to the pandemic course of asthma and immunologic features. However, there are no unambiguous data on asthma on the background and after COVID-19. There is correlation between various trigger factors that provoke the development of bronchial asthma. It is now obvious that the SARS-CoV-2 virus is one of the provoking factors. COVID-19 has affected the course of asthma. Currently, there is no clear understanding of whether asthma progresses during or after COVID-19 infection. According to the results of some studies, a significant difference was identified between the development of asthma in people after COVID-19. Mild asthma and moderate asthma do not increase the severity of COVID-19 infection. Nevertheless, oral steroid treatment and hospitalization for severe BA were associated with higher COVID-19 severity. The influence of SARS-CoV-2 infection is one of the protective factors. It causes the development of severe bronchial asthma. The accumulated experience with omalizumab in patients with severe asthma during COVID-19, who received omalizumab during the pandemic, has strongly suggested that continued treatment with omalizumab is safe and may help prevent the severe course of COVID-19. Targeted therapy for asthma with the use of omalizumab may also help to reduce severe asthma associated with COVID-19. However, further studies are needed to prove the effect of omalizumab. Data analysis should persist, based on the results of the course of asthma after COVID-19 with varying degrees of severity.

Identificationof potential lung cancer biomarkers by liquid chromatography tandem mass spectrometry-based proteomics analysis of secretomes of two lung cancer cell lines.

A label-free nano-liquid chromatography tandem mass spectrometry proteomics analysis on the conditioned media (CM) of two lung cancer cell lines of different histological backgrounds to identify secreted or membrane-bound proteins as novel lung cancer biomarkers was performed. Five hundred and seventy seven proteins were identified and 38% of them were classified as extracellular or membrane-bound. For the search of potential biomarkers of lung cancer a series of selection criteria were proposed. We detected known or putative lung cancer markers. In addition, 40 novel proteins were identified, whose role as biomarkers of lung cancer should be explored further.