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Doklady Biochemistry and Biophysics
Journal Prestige (SJR): 0.257  Citation Impact (citeScore): 1 Number of Followers: 1  Hybrid journal (It can contain Open Access articles)ISSN (Print) 1607-6729 - ISSN (Online) 1608-3091 Published by Springer-Verlag  [2468 journals]
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- Intracellular Gemcitabine Monophosphate Levels Predict Chemotherapy
Efficacy in Gemcitabine-Treated Patients with Bladder Cancer-
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Abstract: Gemcitabine monophosphate (dFdCMP), one of the intracellular forms of phosphorylated gemcitabine, determines its antitumor activity. A pharmaco-molecular model for determining relative gemcitabine monophosphate level based on the assessment of the activity of ENT1 and ENT2 channels as well as dCK and CDA enzymes in tumor tissue was developed. Relative gemcitabine monophosphate level is a more relevant predictive factor of gemcitabine resistance of bladder cancer as compared with the expression of individual markers related to dFdCMP formation.
PubDate: 2023-09-29
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- Synthetic Peptide Fragments of the Wtx Toxin Reduce Blood Pressure in Rats
under General Anesthesia-
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Abstract: Previously, it was shown that the non-conventional toxin WTX from the venom of the cobra Naja kaouthia, when administered intravenously, caused a decrease in blood pressure (BP) and an increase in heart rate (HR) in rats [13]. To identify the site of the toxin molecule responsible for these effects, we studied the influence of synthetic peptide fragments of the WTX on BP and HR in normotensive male Sprague–Dawley rats under general anesthesia induced by Telazol and Xylazine. It was found that peptides corresponding to the WTX central polypeptide loop, stabilized by a disulfide bond, at intravenous injection at concentrations from 0.1 to 1.0 mg/mL caused a dose-dependent decrease in BP, with the HR increasing only in the first 5–10 min after administration. Thus, WTX fragments corresponding to the central polypeptide loop reproduce the decrease in blood pressure caused by the toxin.
PubDate: 2023-09-12
DOI: 10.1134/S1607672923700497
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- The Role of 20-Hydroxyecdysone in the Control of Carbohydrate Levels in
Drosophila melanogaster under Short-Term Heat Stress-
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Abstract: It is known that 20-hydroxyecdysone is one of the most important hormonal regulators of development, reproduction and adaptation to unfavorable conditions in insects. Here, we show for the first time that exogenous 20-hydroxyecdysone increases the content of two main insect carbohydrates, trehalose and glucose, in Drosophila melanogaster females both in normal conditions and under short-term heat stress. It is found that the levels of both trehalose and glucose increase after 39 min of heat exposure and return to their original levels after 1.5 h. A scheme of hormonal regulation of carbohydrate content under heat stress, involving 20-hydroxyecdysone, juvenile hormone, and dopamine, is suggested.
PubDate: 2023-08-01
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- Spectral Analysis of Heart Rate Variability Based on the
Hilbert–Huang Method-
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Abstract: Analysis of heart rate variability (HRV) is widely used for noninvasive assessment of the state of the regulation systems of the heart. The aim of this study was to evaluate the capabilities of the Hilbert–Huang method for calculating spectral parameters of HRV in comparison with the commonly used Fourier analysis. Fourier analysis allows estimation of averaged spectral amplitudes and power of HRV oscillations in fixed frequency intervals, which are associated with the activity of sympathetic, parasympathetic, and humoral regulation systems. Using the Hilbert–Huang method, we revealed four spectral components, described by Gaussian functions, in which HRV oscillations are concentrated, and showed the absence of fixed boundaries between them. The obtained energy quantitative characteristics of the spectral components of heart rhythm oscillations can serve as the basis for diagnostic methods of heart rhythm regulation, supplementing the commonly used ones.
PubDate: 2023-08-01
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- Approbation of a New Model of Secondary Damage after Traumatic Brain
Injury Based on Reprogrammed Rat Embryo Fibroblasts-
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Abstract: The paper presents a new model of secondary injuries after traumatic brain injury. The model is based on the cultivation of rat embryonic fibroblasts reprogrammed to a neuronal phenotype in the presence of cerebrospinal fluid from injured rats. The presented model was used to test the therapeutic effect of inducers of the synthesis of chaperones from the classes of pyrrolylazines and indolylazines, which have neuroprotective properties.
PubDate: 2023-08-01
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- Pharmacogenetic Analysis of the Interaction of the Low-Molecular-Weight
BDNF Mimetic Dipeptide GSB-106 with TRK Receptors-
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Abstract: Using TrkA or TrkB receptor gene knockout HT-22 cells, the selectivity of the interaction of the low-molecular-weight dipeptide BDNF mimetic GSB-106 (hexamethylenediamide bis(N-monosuccinyl-L-seryl-L-lysine)) with TrkB receptors was shown.
PubDate: 2023-08-01
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- Contributing Factors of Diabetes Mellitus among Patients with Gout
(Results of the Long-Term Prospective Study)-
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Abstract: It is assumed that the risk of developing type 2 diabetes mellitus (T2DM) in patients with gout is influenced by both generally accepted risk factors and factors related to gout. The aim of the study was to evaluate the impact of various risk factors for T2DM in patients with gout. A total of 444 patients (49 women, 395 men) ≥18 years old with gout and without DM were included. The duration of observation was 5.66 [2.69; 7.64] years. To identify the factors associated with the risk of developing T2DM, multivariate logistic regression was used, which included sex; T2DM in relatives; insufficient physical activity; unbalanced diet; age ≥ 45 years; ≥4 attacks per year; presence of tophi; BMI ≥30 kg/m2; allopurinol, febuxostat, glucocorticoids, diuretics, metformin, colchicine; GFR < 60 mL/min/1.73 m2; serum uric acid level (sUA) ≥ 420 µmol/L and ≥ 480 µmol/L. T2DM developed in 108 (24.3%) patients. According to the multivariate model, the presence of ≥4 attacks of arthritis per year increased the risk of T2DM (OR = 5.23; 95% CI: 2.98–9.19; p = 0.0001); presence of tophi (OR = 2.61; 95% CI: 1.50–4.54; p = 0.001); sUA ≥ 480 µmol/L (OR = 2.26; 95% CI: 1.02–5.00; p = 0.144); diuretics (OR = 2.35; 95% CI: 1.19–4.64; p = 0.014). Febuxostat (OR = 0.31; 95% CI: 0.11–0.84; p = 0.022) and metformin (OR = 0.49; 95% CI: 0.21–1.16; p = 0.107) reduced the risk of developing T2DM. Risk of T2DM in patients with gout is associated with high incidence of arthritis attacks, MK ≥ 480 μmol/L, hypertension, diuretic use, and febuxostat and metformin reduces risk.
PubDate: 2023-08-01
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- Comparative Pharmacoeconomic Effectiveness of Interleukin-17 Inhibitors
for the Treatment of Ankylosing Spondylitis-
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Abstract: The objective of this study was to compare the clinical efficacy and cost-effectiveness of IL-17 inhibitors (SEC, IXE, NTK) in the treatment of adult patients with ankylosing spondylitis (AS) in the healthcare system of the Russian Federation. Materials and methods. The study is a sub-analysis of a previously published systematic review and network meta-analysis of the comparative efficacy of biologics in adult patients with AS in the Russian Federation. NNT values were calculated for BASDAI 50 and ASAS 20/40 after 16 weeks of therapy for all studied drugs. CpR was estimated for each biologic after 16 weeks and one year of therapy. Additionally, we carried out an assessment of the financial burden of the most cost-effective strategies for the treatment of AS. The use of NTK is characterized by an average of no more than three patients needed to treat to achieve one ASAS 20/40 or BASDAI 50 response, while on IXE and SEC no more than 4–5 patients need to be treated, depending on the estimated effectiveness criterion. According to CpR estimate, NTK is the most cost-effective IL-17 inhibitor for the treatment of AS, both after 16 weeks and after one year of therapy. The obtained results make it possible to compare the effectiveness of IL-17 inhibitors from a clinical and economic points of view and can be used both in decision making on treatment strategies for individual patients and at the population level when deciding on the reimbursement of drugs.
PubDate: 2023-08-01
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- Structure Analysis of the MatA Locus of Sexual Compatibility in the Edible
Mushroom Pleurotus ostreatus-
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Abstract: The edible oyster mushroom Pleurotus ostreatus is one of the most cultivated species worldwide. Morphogenesis associated with the maturation of fruit bodies is controlled by two unlinked loci of sexual compatibility matA and matB with multiple alleles (tetrapolar system of sexual compatibility). Quantitative analysis of the alleles of mating compatibility loci in 17 natural isolates collected in the Moscow region was performed in mon–mon (monokaryons–monokaryon) and di–mon (dikaryon–monokaryon) crossings. Four monokaryotic testers strains which were heteroallelic at both mating type loci were obtained for each of the five natural mushroom isolates by using original technique of sterile spore prints on Petri dishes and mon–mon crossing. Twelve natural isolates were crossed via di-mon mating with the four monokaryotic testers M-38. Genetic analysis of the alleles of sexual compatibility loci in 17 natural isolates revealed multiple alleles at both loci: at least ten alleles at matA locus and eight alleles at matB locus. Structural organization analysis of the matA locus was performed in silico for homokaryotic strains PC9 and PC15 based on the whole-genome sequencing data available at DOE Joint Genome Institute. The matA locus has an extremely divergent structure: there are one copy of the homeodomain gene hd1 and one copy of the hd2 gene in the PC9 strain, whereas the matA locus of the PC15 strain is composed by two copies of hd1.1 and hd1.2 genes (class HD1 homeodomain proteins) and one copy of hd2 gene (class HD2 proteins). Comprehensive analysis of amino acid sequences of HD1 and HD2 homeodomain proteins demonstrated that the proteins have a globular structure with the nuclear localization and contain a variable N-terminus and a more conserved DNA-binding domain with a specific conserved motif WFXNXR in the third ɑ-helix. The results suggest that multiple alleles of the matA locus of sexual compatibility in basidiomycete fungi is achieved due to both different copy number of the coding hd genes within the locus and the variability of the coding gene sequences.
PubDate: 2023-08-01
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- Accumulation of β-Amyloid Leads to a Decrease in Lynx1 and Lypd6B
Expression in the Hippocampus and Increased Expression of Proinflammatory
Cytokines in the Hippocampus and Blood Serum-
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Abstract: Alzheimer’s disease is a rapidly progressive neurodegenerative disease, the development of which is associated with the accumulation of β-amyloid oligomers, dysfunction of the α7-nAChR nicotinic acetylcholine receptor, and activation of inflammation. Previously, we showed that the neuromodulator Lynx1, which belongs to the Ly6/uPAR family, competes with β-amyloid(1–42) for binding to α7-nAChR. In this work, we studied the expression and localization of Ly6/uPAR family proteins in the hippocampus of 2xTg-AD transgenic mice that model AD and demonstrate increased amyloidosis in the brain. Using real-time PCR, we showed a decrease in the expression of the genes encoding Lynx1, Lypd6b, and the postsynaptic marker PSD95, as well as an increase in the expression of the TNFα gene in the hippocampus of 2xTg-AD mice. Histochemical analysis showed that, in the hippocampus of 2xTg-AD mice, Lynx1 does not colocalize with α7-nAChR, which can lead to the development of pathology when the receptor interacts with oligomeric β-amyloid. In addition, in 2xTg-AD mice, activation of systemic inflammation was shown, which manifests itself in a decrease in the serum level of SLURP-1, a Ly6/uPAR family protein capable of regulating inflammatory processes, as well as in an increase in the content of proinflammatory cytokines TNFα and TNFβ. Thus, α7-nAChR dysfunction and maintenance of the inflammatory microenvironment in the brain in Alzheimer’s disease may be associated with a decrease in the expression of Ly6/uPAR family proteins that regulate α7-nAChR activity and inflammation.
PubDate: 2023-08-01
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- Different Clinical Relevance of Anti-Citrullinated Protein Antibodies in
RA Patients-
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Abstract: The objective of the study was to find a potential relationship between ACPAs and disease activity, bone destruction, and ACPA responses to various therapeutic regimens. The study included 232 patients with rheumatoid arthritis (RA); 90 patients had early RA, and 142 patients had an advanced stage of the disease. 77 (85.6%) patients with early RA were highly positive for anti-CCP, and 29 (70.7%) patients were highly positive for anti-MCV. A positive correlation was found between anti-MCV and DAS28 (r = 0.4; p = 0.04). As for advanced RA, 78 (80.4%) patients were high-positive for anti-CCP, and 70 (79.5%) were high-positive for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r = 0.4; p = 0.02), as well as CDAI (r = 0.4; p = 0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0–122.0)) were found in pts highl-positive for anti-MCV (n = 79), compared to low-positive/negative (n = 27) patients (57.0 (31.0–88.0); p < 0.05). Anti-MCV levels dropped significantly in pts on rituximab and tocilizumab therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment. Anti-MCV levels correlated with inflammatory activity and development of bone destruction and decreased in pts on treatment. Anti-CCP was less responsive and showed minor changes during treatment; therefore, its thorough monitoring was not feasible.
PubDate: 2023-08-01
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- Anti-topoisomerase 1 Antibody Level Changes after B Cell Depletion Therapy
in Systemic Sclerosis-
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Abstract: The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANAs) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSs) patients on rituximab (RTX) therapy. The prospective study included 88 patients (73 women) with a mean age of 47 (17–71) years. The mean disease duration was 5.9 ± 4.8 years. The mean follow-up period was more than 2 years (27 (12–42) months). We documented a statistically significant change in skin score, the disease activity index, improvement of pulmonary function and reduction of mean dose of prednisolone after RTX treatment. There was a significant decrease in the number of patients with high levels of ANA and overall decrease of the ANA and anti-Topo 1 levels. A moderate positive statistically significant correlation was found between ANA and anti-Topo 1 (r = 0.403). In the group of patients positive for anti-Topo 1 there were a more pronounced depletion of B lymphocytes, significantly higher increase in forced vital capacity and diffusion capacity, decrease in the disease activity index, compared with patients negative for anti-Topo 1. We observed the decline in the level of ANA and anti-Topo 1 in SSc patients after RTX therapy, and it was correlated by an improvement of the main outcome parameters of the disease. Therefore, anti-Topo 1 positivity could be considered as a predictor of a better response to RTX treatment, especially in SSc patients with hyperproduction of anti-Topo 1.
PubDate: 2023-08-01
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- Growth Induction of Solid Ehrlich Ascitic Carcinoma in Mice after Proton
Irradiation of Tumor Cells Ex Vivo-
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Abstract: This study presents data on the growth rate and frequency of induction of the solid form of Ehrlich’s ascites carcinoma (EAC) in mice in the short and long term after inoculation of ascitic cells irradiated ex vivo with a proton beam in the dose range of 30–150 Gy. It was shown that the growth rate of solid tumors after inoculation of irradiated cells ex vivo coincided with the growth of tumors in the control group. The frequency of tumor induction in mice after inoculation of EAC cells irradiated at a dose of 30 Gy was 80%, 60 Gy—60%, 90 Gy—25%, and 120 Gy—10%; at irradiation at a dose of 150 Gy, no tumors appeared during the entire observation period. Thus, we determined the dose of proton radiation required to eliminate tumor cells and/or signaling factors that can lead to the induction of tumor growth of EAC in mice.
PubDate: 2023-08-01
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- Global Antiphospholipid Syndrome Score (GAPSS) in Patients with Systemic
Lupus Erythematosus-
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Abstract: The Global Antiphospholipid Syndrome Score (GAPSS) is a tool proposed to quantify the risk of clinical manifestations associated with antiphospholipid antibodies (aPL) and certain cardiovascular risk factors. To validate GAPSS in a cohort of patients with systemic lupus erythematosus in Russia. 115 patients with SLE were included in the study, including 51 (44%) patients with systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), 14 (12%) SLE patients with aPL, and 50 (44%) patients with SLE. There was a history of thrombosis in 58 (50%) out of 115 patients; of them, 14 (24%) had arterial thrombosis, 29 (50%) had venous thrombosis, and 15 (26%) had combined thrombosis. Pregnancy against the background of the disease occurred in 43 women included in the study. Of them, 29 (67%) had obstetric pathology. Patients with thrombosis and obstetric pathology had a GAPSS score of 7.17 ± 5.64 versus 4.48 ± 4.55 without these manifestations (p = 0.0003). There was a significant association between GAPSS levels and thrombosis: patients with thrombosis had a GAPSS of 7.31 ± 5.70, those without thrombosis—4.00 ± 4.81 (p = 0.001). GAPPS values were higher in arterial thrombosis compared to venous thrombosis (10.40 ± 25.30 versus 5.82 ± 5.28, p = 0.01). GAPSS levels ≥ 6 and ≥10 were analyzed to select GAPSS values at which a high risk of recurrent thrombosis and/or obstetric pathology could be indicated. All GAPSS levels had a significant association with clinical manifestations of APS. The quality of GAPSS by ROC analysis showed an area under the curve (AUC) for GAPSS of 0.697. GAPSS can be used to assess the risk of recurrence or development of thrombosis and/or obstetric pathology in patients with SLE in the Russian Federation. The GAPSS ≥6 values should be used to stratify patients with SLE into high risk group for recurrence of vascular complications. Further prospective follow-up is needed to confirm the value of GAPSS.
PubDate: 2023-08-01
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- Are the Goals of Therapy Achievable in Patients with Rheumatoid Arthritis
Receiving Upadacitinib in Real Clinical Practice'-
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Abstract: The aim of the study was to evaluate the effectiveness of UPA in RA patients in real clinical practice after 3 and 6 months of therapy. The study included 63 RA patients with high activity of the disease. Activity was assessed according to the DAS28(ESR), DAS28(CRP), SDAI, CDAI; functional ability to HAQ; quality of life to the EQ-5D; disease activity according to the patient’s RAPID-3 index; the level of depression and anxiety to the HADS scale. The effectiveness of therapy was evaluated after 3 (n = 45) and 6 (n = 31) months of UPA therapy. Remission or low activity of the disease by 3 months of therapy was achieved by most patients: remission of 69.8% of patients, low activity of the disease—16.3% of patients. Moderate or high activity persisted in 13.9% of patients. By the 6th month of UPA therapy, the number of remissions reached 90%, low activity 3.3%, moderate activity persisted in 6.7% of patients, high activity of the disease was not in any patient. 20% improvement in function was achieved in 71.8% of patients by the 3rd month of therapy and in 77.8% by the 6th month of treatment; the difference in average HAQ values by the 3rd month of therapy was 0.38 points, by the 6th month—0.58 points. After 3 months of follow—up, 31.1% of patients continued taking GC, by 6 months—24.2%. The dose of GC was reduced from an average of 7.23 to 5.6 mg/s. The percentage of patients requiring NSAIDs decreased from 95.2 to 35.6% and 33.3%, respectively. DMARDs continued to be received by 75.6% of patients by 3 months and 69.7% by 6 months of follow-up. Achieving remission or low activity of the disease in patients with RA receiving UPA in real clinical practice is possible in most patients. A rapid decrease in inflammatory activity is accompanied by a significant improvement in the functional state and quality of life of patients. UPA therapy reduces the need for the use of NSAIDs and reduces the dose of GC in a third of patients.
PubDate: 2023-08-01
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- Antibodies to Domain I β2-Glycoprotein 1 in Patients with
Antiphospholipid Syndrome and Systemic Lupus Erythematosus-
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Abstract: The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of β2-glycoprotein 1 (β2-GP1), IgG anti-β2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-β2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-β2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-β2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-β2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-β2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-β2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-β2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-β2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-β2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-β2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-β2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively).
PubDate: 2023-08-01
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- Tripterine Serves a Dual Role in Palmitate-Induced Pancreatic Beta-Cell
Lipotoxicity-
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Abstract: Tripterine (TP, also called celastrol), a pentacyclic triterpene extracted from Tripterygium wilfordii, has beneficial effects on multiple diseases, including obesity and diabetes. However, the effects of TP on β‑cell lipotoxicity have not been fully explored. Here, we found that TP modulated β-cell lipotoxicity in a concentration-dependent and bidirectional manner. At low concentrations, TP potentially protected MIN6 β-cells from palmitate (PA)-induced lipotoxicity. At high concentrations, TP significantly promoted β-cell lipotoxicity, further reinforcing PA-induced cell apoptosis. Furthermore, low-concentration TP inhibited the PA-induced increase in reactive oxygen species (ROS) levels, and its protective effects were abolished by the ROS inducer tert-butyl hydroperoxide. Conversely, high-concentration TP significantly exacerbated the PA-triggered ROS generation, and its enhanced cytotoxicity was partially reversed by the ROS inhibitor N-acetyl-L-cysteine. Thus, TP plays a dual role in β-cell lipotoxicity, suggesting that care should be taken when it is used for obesity and diabetes treatment.
PubDate: 2023-08-01
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- The Effect of the Agonist Cholecystokinin-4 D-GB-115 On the Character of
Motor Activity of Paramecium caudatum-
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Abstract: The study investigated the effect of GABA in various concentrations and D-GB-115 at a concentration of 10–7 M on the behavior of Paramecium caudatum. It was shown that GABA increases motor activity and changes the movement strategy of these protozoans, and the dose–effect relationship is domed, which can be explained by the presence of two types of GABA receptors in the outer membrane of paramecia: GABA-A and GABA-B. The active concentrations of GABA range from 10–3 to 10–13 M. The effect of pharmacological agents interacting with the GABA system on the behavior of ciliates (nembutal and D-GB-115) was studied.
PubDate: 2023-06-01
DOI: 10.1134/S1607672923700175
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- Simulation of Microgravity and Coculturing with Hematopoietic Cells
Oppositely Modulate Wnt Signaling in Mesenchymal Stromal Cells-
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Abstract: The osteogenic potential of mesenchymal stromal cells (MSCs) can determine bone homeostasis and the physical characteristics of bones. Microgravity reduces the ability of these cells to differentiate in osteogenic direction. It has been shown that the addition of hematopoietic stem and progenitor cells (HSPCs) to MSC culture in vitro can have the opposite effect. The aim of this study was to identify transcriptional changes in 84 genes associated with Wnt signaling in MSCs during microgravity simulation and interaction with HSPCs. The results indicate an increase in the non-canonical Wnt signaling activity during coculturing of MSCs and HSPCs, while simulated microgravity enhances the canonical component of this signaling pathway. These changes may underlie the modulation of osteogenic potential of MSCs in hematopoietic niche under microgravity.
PubDate: 2023-06-01
DOI: 10.1134/S1607672923700187
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- Modular Nanotransporters Capable of Binding to SARS-CoV-2 Virus
Nucleocapsid Protein in Target Cells-
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Abstract: On the basis of literature data, an antibody-like molecule, monobody, was selected that is capable of interacting with the nucleocapsid protein (N protein) of the SARS-CoV-2 virus with a high affinity (dissociation constant 6.7 nM). We have previously developed modular nanotransporters (MNTs) to deliver various molecules to a selected compartment of target cells. In this work, a monobody to the N protein of the SARS-CoV-2 virus was inserted in the MNT using genetic engineering methods. In this MNT, a site for the cleavage of the monobody from the MNT in endosomes was also inserted. It was shown by thermophoresis that the cleavage of this monobody from the MNT by the endosomal protease cathepsin B leads to a 12-fold increase in the affinity of the monobody for the N protein. Cellular thermal shift assay showed the ability of the obtained MNT to interact with the N protein in A431 cells transfected with the SARS-CoV-2 N protein fused to the mRuby3 fluorescent protein.
PubDate: 2023-06-01
DOI: 10.1134/S1607672922600233
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