Depression and Anxiety Among COVID-19 Patients Admitted to a "Red Zone" Intensive Care Unit: Do the Factors of Self-Awareness of Somatic Health, Anxiety, and Depression Contribute to the Course of Sars-Cov-2 Infection?

BACKGROUND: The prevalence of depressive disorders in the general population increased significantly during the COVID-19 pandemic. The aim of this study is to examine the relationship between history of anxiety and depressive disorders and COVID-19 outcome, hospitalization and severity of anxiety and depression, and whether such relationships are explicable by direct impact of the disease. SUBJECTS AND METHODS: We conducted a questionnaire survey among 98 inpatients in the Department of Infectious Diseases of the Clinics of Samara State Medical University. The self-report questionnaire consisted of 120 items, including socio-demographic characteristics of participants, State-Trait Anxiety Inventory, and the Center for Epidemiologic Studies Depression Scale, with items reflecting subjective feelings about the COVID-19 pandemic. We used one-factor analysis of variance to compare between groups for those indicators that conformed to a normal distribution, and the chi-square test (χ2) or Fisher's exact test to analyze group differences in the distribution of categorical variables was used. RESULTS: The mean (SD) total score on the STAI anxiety scale among hospitalized patients (51 (10.1)) significantly exceeded that of the COMET-G control group (44.9 (11.7) (H=22.8, p<0.001). There was a similar difference in the severity of depression as measured by the CES-D scale (23.4 (12.6) versus 18.0 (11.8), H=15.2 and p<0.001). In contrast to the general population, there were no statistically significant differences in anxiety and depression severity in the matched samples 52 subjects fulfilling the criteria of age, gender, and general perception of health condition. CONCLUSIONS: Anxiety and depression scores among ICU (red zone) inpatients significantly exceeded the scores observed in the COMET-G general population group. Our study did not confirm expected relationship between symptoms of anxiety and depression (based on questionnaire response) and the risk of severe course of COVID-19 (e.g. hospitalization) in matched samples, but proved that the factor of self-awareness of health state may be related to the COVID-19 course severity. Future research would benefit from clinical interview of inpatients and follow-up monitoring of affective disorders to specify whether anxiety and particular type of depression (e.g., anxious) are selectively related to the severity of COVID-19 course and risks of affective disorders persistence after somatic recovery. The accumulation of mental disorders with age, and the bidirectional association of mood disorders and infectious diseases should be considered when assessing the risk factors.

Constituent composition of the essential oils from some species of the genus Saussurea DC.

The genus Saussurea DC is well known for its rich chemical composition and wide range of biological activities. Although content and biological effects of major chemical components are thoroughly studied, the composition and concentrations of minor constituents, such as essential oils, still remains unclear. In total, 62 different chemical compounds have been identified in the essential oils from S. controversa, S. latifolia, S. parviflora and S. salicifolia using a gas chromatography-mass spectrometry method. The essential oils include 1-5% of linalool, 2-7% of eudesmol and oxygen-containing sesquiterpenoids: 7-25% of caryophyllene oxide, 4-5% of spathulenol, 4-6% of humulene-6.7-oxide. The presence of sesquiterpenoids can be considered as a chemotaxonomic feature of the studied species of Saussurea DC. The essential oils can be candidates for new anti-inflammatory, analgesic and anti-tumor drugs due to relatively high concentration of caryophyllene oxide.

Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo.

Calcium chelidonate [Ca(ChA)(H2O)3]n was obtained by semi-synthesis using natural chelidonic acid. The structure of the molecular complex was determined by X-ray diffraction analysis. The asymmetric unit of [Ca(ChA)(H2O)3]n includes chelidonic acid coordinated through three oxygen atoms, and three water ligands. The oxygen atoms of acid and oxygen atoms of water from each asymmetric unit are also coordinated to the calcium of another one, forming an infinite linear complex. Calcium geometry is close to the trigonal dodecahedron (D2d). The intra-complex hydrogen bonds additionally stabilize the linear species, which are parallel to the axis. In turn the linear species are packed into the 3D structure through mutual intercomplex hydrogen bonds. The osteogenic activity of the semi-synthetic CaChA was studied in vitro on 21-day hAMMSC culture and in vivo in mice using ectopic (subcutaneous) implantation of CaP-coated Ti plates saturated in vitro with syngeneic bone marrow. The enhanced extracellular matrix ECM mineralization in vitro and ectopic bone tissue formation in situ occurred while a water solution of calcium chelidonate at a dose of 10 mg/kg was used. The test substance promotes human adipose-derived multipotent mesenchymal stromal/stem cells (hAMMSCs), as well as mouse MSCs to differentiate into osteoblasts in vitro and in vivo, respectively. Calcium chelidonate is non-toxic and can stimulate osteoinductive processes.

Docking and antibacterial activity of novel nontoxic 5-arylidenepyrimidine-triones as inhibitors of NDM-1 and MetAP-1.

Background: Antibiotic resistance, which occurs through the action of metallo-ß-lactamases (NDM-1), is a serious problem in the treatment of infectious diseases. Therefore, the discovery of new NDM-1 inhibitors and promising antibacterial agents as inhibitors of alternative targets (MetAP-1) is important. Method & results: In this study, a virtual library of 5-arylidene barbituric acids was created and molecular docking was performed for identification of novel possible inhibitors of NDM-1 and MetAP-1. Antibacterial activity (agar well-diffusion assay) and cytotoxicity (alamarBlue assay) of perspective compounds were evaluated. Pharmacokinetic profiles and molecular properties were predicted. Conclusion: We have identified possible novel inhibitors of NDM-1 and MetAP-1 with bacteriostatic activity, most of which are not cytotoxic and have potential excellent drug-likeness properties.

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia.

Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

Comparative In Vitro Evaluation of Antibacterial and Osteogenic Activity of Polysaccharide and Flavonoid Fractions Isolated from the leaves of Saussurea controversa.

The osteogenic, cytotoxic, and antibacterial activities of polysaccharide (PS-SC) and flavonoid (F-SC) fractions isolated from the leaves extract of Saussurea controversa were studied in vitro. F-SC consists of the five quercetin glycosides in the ratio 2:8:10:1:4, which were isolated from the leaves extract of S. controversa and have been characterized previously. PS-SC was first isolated from the leaves extract of S. controversa and has been described. PS-SC consists in 30 compounds is characterized by a high degree of heterogeneity with a heterogeneity index of 19.74. The Mw and Mn of PS-SC were 108.6 and 5.5 kDa, respectively. Structural fragments are represented by galactose, arabinose, xylose, glucose, uronic acids, mannose, and rhamnose in a 10.1:3.3:2.2:2.1:1.7:0.9:0.5 molar ratio. F-SC as compared with PS-SC showed in vitro microbicidal (50 g/L) and better bacteriostatic (6.25 g/L versus 25 g/L of PS-SC) effects against the 24-h growth of Staphylococcus aureus strain 209 P and a 21-day absence of cytotoxicity on human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs). Both fractions (PS-SC>F-SC) at doses of 10-50 mg/L stimulated differentiation of hAMMSCs into secreting osteoblasts accompanied by local mineralization of extracellular matrix. These fractions of S. controversa and especially F-SC, might be promising peroral drugs in the complex treatment of bone fractures and for prophylaxis of their infectious complications.

Chelidonic Acid and Its Derivatives from Saussurea Controversa: Isolation, Structural Elucidation and Influence on the Osteogenic Differentiation of Multipotent Mesenchymal Stromal Cells In Vitro.

4-oxo-4H-pyran-2.6-dicarboxylic acid (chelidonic acid, ChA) in the native state and in the complex with calcium [Ca(ChA)(H2O)3], named saucalchelin (CaChA), was isolated from the extract of Saussurea controversa leaves for the first time for the Asteraceae family. The structure of ChA was determined by NMR, MS and confirmed by X-ray analysis of its monomethyl ester, and CaChA was described by IR, ICP-MS, CHN analysis. The yield of ChA and CaChA was 45 mg/g and 70 mg/g of extract, respectively. The osteogenic activity of ChA, n-monobutyl ester of chelidonic acid, and CaChA has been studied in vitro in a 21-day culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in a standard nutrient medium without osteogenic supplements. CaChA significantly stimulated the growth of cell mass and differentiation of hAMMSCs into osteoblasts with subsequent mineralization of the culture and it may be a promising substance for accelerating bone tissue regeneration and engineering.

Ochrobactrum cytisi IPA7.2 promotes growth of potato microplants and is resistant to abiotic stress.

Bacteria in natural associations with agricultural crops are promising for use in the improvement of clonal micropropagation of plants. We clarified the taxonomic position of Ochrobactrum cytisi strain IPA7.2 and investigated its tolerance for salinity, high temperature, and glyphosate pollution. We also tested the strain's potential to promote the growth of potato (Solanum tuberosum L.) microplants. Using the IPA7.2 draft genome (no. NZ_MOEC00000000), we searched for housekeeping genes and also for the target genes encoding glyphosate tolerance and plant-growth-promoting ability. A multilocus sequence analysis of the gap, rpoB, dnaK, trpE, aroC, and recA housekeeping genes led us to identify isolate IPA7.2 as O. cytisi. The strain tolerated temperatures up to 50 °C and NaCl concentrations up to 3-4%, and it produced 8 µg ml-1 of indole-3-acetic acid. It also tolerated 6 mM glyphosate owing to the presence of type II 5-enolpyruvylshikimate-3-phosphate synthase. Finally, it was able to colonize the roots and tissues of potato microplants, an ability preserved by several generations after subculturing. We identified the development phase of potato microplants that was optimal for inoculation with O. cytisi IPA7.2. Inoculation of in vitro-grown 15-day-old microplants increased the mitotic index of root meristem cells (by 50%), the length of shoots (by 34%), the number of leaves (by 7%), and the number of roots (by 16%). Under ex vitro conditions, the inoculated plants had a greater leaf area (by 77%) and greater shoot and root dry weight (by 84 and 61%, respectively) than did the control plants. We recommend O. cytisi IPA 7.2 for use in the growing of potato microplants to improve the production of elite seed material.

A novel cell transfection platform based on laser optoporation mediated by Au nanostar layers.

The recently developed laser-induced cell transfection mediated by Au nanoparticles is a promising alternative to the well-established lipid-based transfection or to electroporation. Optoporation is based on the laser plasmonic heating of nanoparticles located near the cell membrane. However, the uncontrollable cell damage from intense laser pulses and from random attachment of nanoparticles may be crucial for transfection. We present a novel plasmonic optoporation technique that uses Au nanostar layers immobilized in culture microplate wells. HeLa cells were grown directly on Au nanostar layers, after which they were subjected to continuous-wave 808 nm laser irradiation. An Au monolayer density ~15 µg/cm2 and an absorbed energy of about 15 to 30 J were found to be optimal for optoporation. Propidium iodide molecules were used as model penetrating agent. The transfection efficiency evaluated using fluorescence microscopy for HeLa cells transfected with pGFP under optimized optoporation conditions (95% ± 5%) was similar to the efficiency of TurboFect. The technique's efficiency (295 ± 10 relative light units, RLU), demonstrated by transfecting HeLa cells with the pCMV-GLuc 2 control plasmid, was greater than that obtained by transfection of HeLa cells with the TurboFect agent (220 ± 10 RLU). The cell viability in plasmonic optoporation (92% ± 7%), too, was greater than that in transfection with TurboFect (75% ± 7%).