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Background:The selective delivery of drugs to their targets prevents their possible side effects; hence, the development of selective transport systems is considered extremely promising. In the present study, we aimed to develop a drug delivery system for targeting bacteria. Methods: Functionalization of apoferritin with wheat germ agglutinin (WGA), as a bacteria-recognizing lectin, was conducted. Afterwards, the complex was loaded with ampicillin. The affinity of the conjugate to Gram-positive bacteria, Bacillus subtilis, was evaluated by anisotropic silver nanoparticles conjugated with this complex, and its interaction with the bacteria was also assessed. Results: The drug-delivery capabilities of the composite were evaluated. Results from the disk diffusion assay revealed that its bactericidal activity is 10-fold greater compared to free antibiotics. The effectiveness of the bactericidal effects of ampicillin-loaded ferritin was also confirmed in whole blood. Conclusion. Lectin-conjugated and ampicillin-loaded apoferritin can be considered as effective drug delivery systems for targeting bacteria.

Introduction: The incidence of brucellosis in Armenia in 2010 was twice as high as in other countries of the Caucasian region and has almost doubled over the last three decades. This study aimed to investigate factors associated with acute or chronic forms of presentation of human brucellosis. Methodology: Retrospective study using data from medical records of 455 patients hospitalized for the first time at the Nork Republican Infectious Disease Referral Hospital in Yerevan, Armenia between the years 2006 and 2016. We undertook descriptive analysis of cases, compared acute and chronic cases, and identified factors associated with acute and chronic cases using regression. Results: The majority of brucellosis cases had acute case presentation (73.0%), were males (70.3%), between the ages of 20-60 years (66.2%) and unemployed (89.9%). About two-thirds of cases reported a history of consumption of raw unpasteurized milk. The multivariate analysis revealed that factors associated with the form of brucellosis were age, symptom duration preadmission, fever, antibody titer, and hospitalization outcomes. Conclusion: This study revealed that brucellosis is unevenly distributed across different age groups, as well as regions of Armenia. Affected individuals did not seek medical attention after the onset of the symptoms for about 2 months. Therefore, the targeted educational campaigns could be of crucial importance to prevent the disease in humans, contribute to its early diagnosis and treatment.

The selective delivery of drugs to their targets prevents their possible side effects; hence, the development of selective transport systems is considered extremely promising. In the present study, we aimed to develop a drug delivery system for targeting bacteria. Functionalization of apoferritin with wheat germ agglutinin (WGA), as a bacteria-recognizing lectin, was conducted. Afterwards, the complex was loaded with ampicillin. The affinity of the conjugate to Gram-positive bacteria, Bacillus subtilis, was evaluated by anisotropic silver nanoparticles conjugated with this complex, and its interaction with the bacteria was also assessed. The drug-delivery capabilities of the composite were evaluated. Results from the disk diffusion assay revealed that its bactericidal activity is 10-fold greater compared to free antibiotics. The effectiveness of the bactericidal effects of ampicillin-loaded ferritin was also confirmed in whole blood. Lectin-conjugated and ampicillin-loaded apoferritin can be considered as effective drug delivery systems for targeting bacteria.

The short lifespan of polymorphonuclear neutrophils (PMNs) in vitro poses challenges, as their limited viability restricts functional assays and experimental manipulations. The HL-60 cell line serves as a valuable model for neutrophil-like differentiation, yet the functional relevance of ATRA- and DMSO-induced differentiation remains incompletely understood. In the present study, we aimed to characterize the differentiation potential of all-trans retinoic acid (ATRA) and dimethyl sulfoxide (DMSO) on HL-60 cells and compare their functionality with primary PMNs. Besides that, we performed profound immunophenotypes of the cells with multicolor cytometry, and evaluated their antitumor capabilities. Our findings indicate that both differentiation conditions yield cells resembling immature neutrophils, exhibiting promyelocyte-like morphology, lacking key maturity markers. However, ATRA-differentiated cells exhibit a more mature phenotype, with higher expression of C/EBPα and reduced proliferation rates, indicating advanced differentiation. Functionally, ATRA-dHL-60 cells displayed limited immune responses, showing minimal phagocytic activity, low ROS production, and a reduced response to LPS. In contrast, DMSO-dHL-60 cells, despite their less mature phenotype, showed enhanced NET formation, and tumor-promoting potential. Additionally, DMSO-dHL-60 cells demonstrated superior adhesion and migration abilities, likely due to increased expression of CD18 and CD31. Overall, different differentiation conditions shape the functional specialization of HL-60 cells, with ATRA promoting a more neutrophil-like maturation and moderate activation, while DMSO results in a more immature phenotype with enhanced NET formation. These distinct properties suggest that ATRA-dHL-60 cells may better model neutrophils in chronic inflammation, whereas DMSO-dHL-60 cells could be more suitable for studying NETosis-driven autoimmune, thrombotic disorders and cancer.

Familial Mediterranean fever (FMF) is caused by pyrin-encoding MEFV gene mutations and characterized by the self-limiting periods of intense inflammation, which are mainly mediated by a massive influx of polymorphonuclear neutrophils (PMNs) into the inflamed sites. Perturbation of actin polymerization by different pathogens was shown to activate the pyrin inflammasome. Our aim was to test whether cytoskeletal dynamics in the absence of pathogens may cause abnormal activation of PMNs from FMF patients. We also aimed to characterize immunophenotypes of circulating neutrophils and their functional activity. Circulating PMNs displayed heterogeneity in terms of cell size, granularity and immunophenotypes. Particularly, PMNs from the patients in acute flares (FMF-A) exhibited a characteristic of aged/activated cells (small cell size and granularity, up-regulated CXCR4), while PMNs form the patients in remission period (FMF-R) displayed mixed fresh/aged cell characteristics (normal cell size and granularity, up-regulated CD11b, CD49d, CXCR4, and CD62L). The findings may suggest that sterile tissue-infiltrated PMNs undergo reverse migration back to bone marrow and may explain why these PMNs do not cause immune-mediated tissue damage. A multidirectional expression of FcγRs on neutrophils during acute flares was also noteworthy: up-regulation of FcγRI and down-regulation of FcγRII/FcγRIII. We also observed spontaneous and fMPL-induced activation of PMNs from the patients after transmigration through inserts as seen by the increased expression of CD11b and intracellular expression of IL-1β. Our study suggests heightened sensitivity of mutated pyrin inflammasome towards cytoskeletal modifications in the absence of pathogens.

Chronic hyperglycemia can contribute to metabolic disorders, disrupting cellular homeostasis and potentially leading to immunological disturbances. As highly adaptable innate immune cells, macrophages can effectively utilize glucose for energy and adjust their activities in response to environmental changes. We hypothesized that hyperglycemia induces distinct effects on M1 and M2 macrophages, thereby promoting their divergent roles in the inflammatory response. For this, we applied an in vitro hyperglycemia model to investigate its impact on M1- and M2-like macrophages differentiated from primary monocytes. M1-like macrophages exhibited diminished capacity to produce reactive oxygen species (ROS), IL-6, TNF-α, as well as reduced antigen presentation and co-stimulatory abilities under long exposure to high glucose. In contrast, M2-like macrophages showed a shift toward M1 polarization, characterized by increased production of ROS and IL-6, upregulation of CD86 and HLA-DR expression, and reduced reparative abilities. We also observed disturbance of endotoxin tolerance evidenced by increased production of TNF-α and diminished phagocytic ability. The results suggest that hyperglycemia disrupts the typical functional dichotomy of M1 and M2 macrophages, which may explain mixed polarization of tissue macrophages in individuals with metabolic syndromes associated with chronic hyperglycemia.

Type 2 diabetes mellitus (T2DM) is a severe health problem worldwide, reaching epidemic levels. High susceptibility to infections of T2DM patients indicates dysregulated immune responses to pathogens. However, innate immune responses, including monocyte functions, in T2DM are poorly investigated. Therefore, in this study we aimed to assess lipopolysaccharide- (LPS-) induced immune responses of circulating monocytes from T2DM patients. The results showed that monocytes from T2DM were hyporesponsive to LPS challenge as reflected by significantly suppressed secretion of TNFα (p<0.01) and expression of CD11b (p<0.001) and TLR4 (p<0.001) compared to those in monocytes from healthy subjects. Furthermore, LPS-induced IL-10 levels were similar in diabetic and healthy supernatants, while expression levels of CD163 were found to be downregulated on monocytes from T2DM (p<0.001) suggesting impaired ability of monocytes to switch their phenotype to anti-inflammatory. Taken together, our results suggest compromised function of monocytes in T2DM, which may explain, at least partly, high incidence of infection in these patients.

Distal occlusion is one of the most common dentoalveolar anomalies and can be the reason for the obstructive sleep apnea (OSA) syndrome development among children. The aim of the study was to investigate the relationship between cephalometric and OSA parameters in the pediatric population. Methods: The cohort study included 39 children with OSA symptoms. Orthodontic examination consisted of a cephalometric analysis of 39 linear and angular variables. Patients underwent a sleep diagnostic study. Statistical analysis was performed using SPSS 19.0.0. Results: Of the general sample, 53.8% were mouth breathers and 46.2% had a mixed type of breathing. Moreover, 30.8% of patients had bruxism. The mean apnea-hypopnea index and oxygen desaturation index were 4.6/h and 3.9/h, respectively. A 1.06 times increase in the SNA index indicated the anterior position of the upper jaw. The MnPLSN° exceeded the norm by 1.3 times, which indicated the posterior position of the lower jaw and vertical type of the growth. An increase in ANSPNSSPT° by 1.1 times indicated an inclination of the upper jaw in the posterior position and a narrowing of the nasal passages. Patients with pediatric OSA had a significantly smaller lower airway space and MPH parameter. Conclusion: Systematic orthodontic monitoring of children with pediatric OSA is important for diagnosis and timely treatment.

Microsecond timescale explicit-solvent atomistic simulations were carried out to investigate how anionic surfactants modulate protein structure and dynamics. We found that lysozyme undergoes near-complete denaturation at the high concentration (> 0.1 M) of sodium pentadecyl sulfonate (SPDS), while only partial denaturation occurs at the concentration slightly below 0.1 M. In large part, protein denaturation is structurally manifested by disappearance of helical segments and loss of tertiary interactions. The computational prediction of the extent of burial of cysteine residues was experimentally validated by measuring the accessibility of the respective sulfhydryl groups. Overall, our work indicates an interesting synergy between electrostatic and hydrophobic contributions to lysozyme’s denaturation process by anionic surfactants. In fact, first disulfide bridges and hydrogen bonds from protein surface to SPDS head groups loosen the protein globule followed by fuller denaturation via insertion of the surfactant’s hydrophobic tails into the protein core.