Comparison of Autografts and Biodegradable 3D-Printed Composite Scaffolds with Osteoconductive Properties for Tissue Regeneration in Bone Tuberculosis.

Tuberculosis remains one of the major health problems worldwide. Besides the lungs, tuberculosis affects other organs, including bones and joints. In the case of bone tuberculosis, current treatment protocols include necrectomy in combination with conventional anti-tuberculosis therapy, followed by reconstruction of the resulting bone defects. In this study, we compared autografting and implantation with a biodegradable composite scaffold for bone-defect regeneration in a tuberculosis rabbit model. Porous three-dimensional composite materials were prepared by 3D printing and consisted of poly(ε-caprolactone) filled with nanocrystalline cellulose modified with poly(glutamic acid). In addition, rabbit mesenchymal stem cells were adhered to the surface of the composite scaffolds. The developed tuberculosis model was verified by immunological subcutaneous test, real-time polymerase chain reaction, biochemical markers and histomorphological study. Infected animals were randomly divided into three groups, representing the infection control and two experimental groups subjected to necrectomy, anti-tuberculosis treatment, and plastic surgery using autografts or 3D-composite scaffolds. The lifetime observation of the experimental animals and analysis of various biochemical markers at different time periods allowed the comparison of the state of the animals between the groups. Micro-computed tomography and histomorphological analysis enabled the evaluation of osteogenesis, inflammation and cellular changes between the groups, respectively.

Diabetic Nephropathy: Significance of Determining Oxidative Stress and Opportunities for Antioxidant Therapies.

Diabetes mellitus (DM) belongs to the category of socially significant diseases with epidemic rates of increases in prevalence. Diabetic nephropathy (DN) is a specific kind of kidney damage that occurs in 40% of patients with DM and is considered a serious complication of DM. Most modern methods for treatments aimed at slowing down the progression of DN have side effects and do not produce unambiguous positive results in the long term. This fact has encouraged researchers to search for additional or alternative treatment methods. Hyperglycemia has a negative effect on renal structures due to a number of factors, including the activation of the polyol and hexosamine glucose metabolism pathways, the activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, the accumulation of advanced glycation end products and increases in the insulin resistance and endothelial dysfunction of tissues. The above mechanisms cause the development of oxidative stress (OS) reactions and mitochondrial dysfunction, which in turn contribute to the development and progression of DN. Modern antioxidant therapies for DN involve various phytochemicals (food antioxidants, resveratrol, curcumin, alpha-lipoic acid preparations, etc.), which are widely used not only for the treatment of diabetes but also other systemic diseases. It has also been suggested that therapeutic approaches that target the source of reactive oxygen species in DN may have certain advantages in terms of nephroprotection from OS. This review describes the significance of studies on OS biomarkers in the pathogenesis of DN and analyzes various approaches to reducing the intensity of OS in the prevention and treatment of DN.

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia.

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30−300 mg/day and albumin/creatinine ratio 3−30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

Sleep Apnea and Serum Serotonin Level Pre- and Post-PAP Therapy: A Preliminary Study.

INTRODUCTION: The high prevalence of obstructive sleep apnea (OSA), which impairs quality of life for numerous patients and leads to various OSA complications, has contributed to the continued interest in this disorder. The role of serotonin (5-HT) in many physiological processes, studies on its connection with the circadian system, and relationship to changes in sleep architecture are insufficient to assess the interaction of this neurotransmitter with nocturnal hypoxia. The aim of this study was to determine changes in sleep patterns and serum serotonin levels before and after positive airway pressure (PAP) therapy in patients with OSA. METHODS: The study involved 30 OSA patients (27 men and 3 women) who were treated with PAP for 3 months. Polysomnography using the GRASS TELEFACTOR (USA) and blood collection were conducted before and after PAP courses. Determination of serum serotonin was performed by high-performance liquid chromatography (HPLC). PAP therapy was performed using an automatic Prisma 20A (Germany) continuous positive airway pressure (CPAP) device. RESULTS: The use of PAP for 3 months revealed a significant improvement as measured by sleep data and serotonin levels (before: apnea index [AI] 17.2 eV/h, after: 2.4 eV/h p = 0.001; SpO2 < 90% - 45.7 min vs. 6.2 min p = 0.001; serotonin 20.3 ng/mL vs. 26.03 ng/mL p = 0.036]. CONCLUSION: Our results demonstrate an improvement in sleep patterns. There was an increase in serum serotonin levels in OSA patients following PAP therapy, which could be an effect of intermittent hypoxia decline, and could be used as criteria for the effectiveness of PAP and an improvement in sleep quality.

The Effect of Plant Growth Compensation by Adding Silicon-Containing Fertilizer under Light Stress Conditions.

The effects of different spectral compositions of light-emitting diode (LED) sources and fertilizer containing biologically active silicon (Si) in the nutrient solution on morphological and physiological plant response were studied. Qualitative indicators and the productivity of plants of a red-leaved and a green-leaved lettuce were estimated. Lettuce was grown applying low-volume hydroponics in closed artificial agroecosystems. The positive effect of Si fertilizer used as a microadditive in the nutrient solution on the freshly harvested biomass was established on the thirtieth day of vegetation under LEDs. Increase in productivity of the red-leaved lettuce for freshly harvested biomass was 26.6%, while for the green-leaved lettuce no loss of dry matter was observed. However, being grown under sodium lamps, a negative impact of Si fertilizer on productivity of both types of plants was observed: the amount of harvested biomass decreased by 22.6% and 30.3% for the green- and red-leaved lettuces, respectively. The effect of using Si fertilizer dramatically changed during the total growing period: up to the fifteenth day of cultivation, a sharp inhibition of the growth of both types of lettuce was observed; then, by the thirtieth day of LED lighting, Si fertilizer showed a stress-protective effect and had a positive influence on the plants. However, by the period of ripening there was no effect of using the fertilizer. Therefore, we can conclude that the use of Si fertilizers is preferable only when LED irradiation is applied throughout the active plant growth period.

Inflammatory Cell Infiltration of Adrenals in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originated in November-December 2019 in Wuhan, China, and has rapidly spread around the world causing severe health and socioeconomical damage to the entire civilization. The key feature of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is upper respiratory tract infection, which may be complicated by bilateral pneumonia. Angiotensin converting enzyme 2 (ACE2) has been identified as a key host factor, required for virus entry into cells. Interestingly, ACE2 is expressed not only in the respiratory system, but also in the other organs and systems including adrenal glands. Here we provide the first description of the pathomorphological changes in adrenal glands in patients with severe COVID-19 characterized by perivascular infiltration of CD3+ and CD8+ T-lymphocytes. Due to the central role of the adrenals in the stress response of the organism, this finding is of potential clinical relevance, because infection with the SARS-CoV-2 virus might critically impair adrenal function under pathophysiological conditions.

CLOCK 3111TT Genotype Is Associated with Increased Total Cholesterol and Low-Density Lipoprotein Levels in Menopausal Women with a Body Mass Index of at Least 25 kg/m2.

Lipid profile comparative analysis was performed to reveal the interdependence of lipids with Circadian locomoter output cycles protein kaput (CLOCK) 3111T/C gene polymorphism in menopausal women with/without a body mass index (BMI) of ≥25 kg/m2. Methods: A total of 193 female volunteers aged 45 to 60 years were divided into two groups: Those with BMI < 25 kg/m2 (control) and those with BMI ≥ 25 kg/m2. Each group was then divided into two subgroups: Those with the CLOCK TT-genotype and those with the CLOCK TC-, CC-genotypes. Lipid metabolism parameters were determined by the enzymatic method. Single-nucleotide polymorphisms (SNPs) were detected via polymerase chain reaction-restriction fragment length polymorphism technology. Results: There were no differences in CLOCK 3111T/C genotypes or allele frequency between the control and main groups. In addition, there were no differences in lipid profile parameters between women of the control group and different CLOCK 3111T/C genotypes. The total cholesterol (p = 0.041) and low-density lipoprotein cholesterol (p = 0.036) levels were higher in the subgroup of women with a BMI ≥ 25 kg/m2 and CLOCK TT-genotype as compared to the subgroup with a BMI ≥ 25 kg/m2 and minor allele 3111C. Conclusions: SNP 3111T/C of the CLOCK gene is not associated with BMI however, data suggest that the minor allele of the CLOCK 3111T/C gene polymorphism may have a protective role in atherogenic lipid levels in women with a BMI greater than or equal to 25 kg/m2.

PGlu-Modified Nanocrystalline Cellulose Improves Mechanical Properties, Biocompatibility, and Mineralization of Polyester-Based Composites.

The development of biocompatible composite materials is in high demand in many fields such as biomedicine, bioengineering, and biotechnology. In this study, two series of poly (D,L-lactide) and poly (ε-caprolactone)-based films filled with neat and modified with poly (glutamic acid) (PGlu) nanocrystalline cellulose (NCC) were prepared. An analysis of scanning electron and atomic force microscopies' results shows that the modification of NCC with poly (glutamic acid) favored the better distribution of the nanofiller in the polymer matrix. Investigating the ability of the developed materials to attract and retain calcium ions led to the conclusion that composites containing NCC modified with PGlu induced better mineralization from model solutions than composites containing neat NCC. Moreover, compared to unmodified NCC, functionalization with PGlu improved the mechanical properties of composite films. The subcutaneous implantation of these composite materials into the backs of rats and the further histological investigation of neighboring tissues revealed the better biocompatibility of polyester materials filled with NCC-PGlu.

Lipid peroxidation depends on the clock 3111T/C gene polymorphism in menopausal women with Insomnia.

A comparative analysis of lipid peroxidation processes and antioxidant defense system in Caucasian menopausal women with/without insomnia depending on the genotype of Clock 3111T/C gene polymorphism was performed. Two hundred and fourteen Caucasian menopausal women divided into control (without insomnia) and main group (with insomnia) were examined. Lipid peroxidation (conjugated dienes, thiobarbituric acid reactants) and antioxidant defense system parameters (?-tocopherol, retinol, reduced and oxidized glutathione, glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase) were determined by spectrofluorophotometer and immunoenzymometric methods. Patients with insomnia carriers of the TT-genotype had a significantly higher thiobarbituric acid reactants level and glutathione peroxidase activity as compared to group with insomnia carriers of the minor 3111C-allele (p < .05). A comparative analysis of the parameters in the women of the main and control groups showed higher conjugated dienes, thiobarbituric acid reactants levels and lower retinol, reduced glutathione levels, glutathione reductase activity in women with insomnia carriers of the TT-genotype (p < .05). The carriers of the minor allele with insomnia had a higher conjugated dienes levels and lower glutathione peroxidase activity as compared to control (p < .05). Thus, lipid peroxidation and antioxidant system parameters in Caucasian menopausal women with insomnia depend on the Clock 3111T/C gene polymorphism.

Association of the melatonin circadian rhythms with clock 3111T/C gene polymorphism in Caucasian and Asian menopausal women with insomnia.

A comparative analysis of melatonin circadian rhythms in Caucasian (incoming population) and Asian (indigenous population) menopausal women with/without sleep disorders depending on the genotype of Clock 3111T/C gene polymorphism was realized.The melatonin level in the saliva was determined four times a day (6:00-7:00, 12:00-13:00, 18:00-19:00, 23:00-00:00 h). The Caucasian women-carriers of the TT-genotype with insomnia as compared to control group-had a higher morning melatonin level and a lower night melatonin level. The Asian women with TT-genotype and insomnia had a lower levels of melatonin as compared to control at daytime, evening and night. A significantly higher melatonin level in the early morning hours was detected in the Caucasian women-carriers of the TT-genotype with insomnia as compared to group womencarriers of the minor 3111C-allele. There were no statistically significant differences in the circadian rhythms of melatonin in the Asian women depending on the genotype of the Clock 3111T/C polymorphism. An assumption with respect to the protective role of the minor allele 3111C in the development of insomnia associated with the displacement of melatonin circadian rhythms in the representatives of the incoming population was made.

Antioxidant status in peri- and postmenopausal women.

Menopause is a risk factor for oxidative stress. The aim of our study is to assess antioxidant system parameters (α-tocopherol, retinol, reduced glutathione, total antioxidant activity) in peri- and postmenopausal women. The antioxidant defense activity by estimation of total antioxidant activity, α-tocopherol, retinol, oxidized and reduced glutathione levels was studied in women of reproductive age (n=37), in perimenopausal (n=41) and postmenopausal women (n=41). In our study we used spectrofluorofotometer methods. Statistical analysis was performed by non-parametric tests with p<0.05 as the level of significance. The results of our study showed the decrease of α-tocopherol and retinol concentrations and the increase of oxidized glutathione level in blood serum both in perimenopausal and postmenopausal women, the total antioxidant activity of blood serum was decreased in postmenopausal women only. The results of our study demonstrate that decrease of antioxidant defense system resources depends on the menopausal phase.