The SAGA complex is an important player in the regulation of eukaryotic gene transcription. The interaction of SAGA with the TREX-2 mRNA nuclear export complex makes it possible to efficiently transcribe and export mRNA at loci of actively transcribed genes near nuclear pores. However, it remains unclear whether TREX-2 is involved in anchoring the SAGA complex to the nuclear pore. In this work, we investigated the effect of knockdown of the TREX-2 complex subunits, ENY2 and Xmas-2, on the localization of the SAGA catalytic subunit, histone acetyltransferase Gcn5, in Drosophila melanogaster. The effect of knockdown on the distribution of Sgf11, a component of the SAGA deubiquitinating module, and an mRNP particle component, was also studied. We demonstrated that knockdown of ENY2 and Xmas-2 does not affect the localization of Gcn5 and Sgf11 in proximity to the nuclear pore. Therefore, TREX-2 is not required for the association of SAGA with the nuclear pore. Meanwhile, knockdown of ENY2 and Xmas-2 results in nuclear accumulation of Sgf11, suggesting that TREX-2 is involved in the localization of the SAGA-independent fraction of Sgf11 that participates in mRNA export within the mRNP particle.
Tag proteins, widespread among prokaryotes, are DNA glycosylases that participate in the repair of alkylated DNA excising 3-methyladenine. Among eukaryotes, Tag homologs are found only in plants, but they have not yet been characterized. Here, we report the first study of a plant Tag homolog, BvTAG1 from sugar beet (Beta vulgaris). Unlike bacterial Tags, BvTAG1 lacks activity towards alkylated DNA, which can be explained by the mutation of the critical catalytic Glu residue to Ser. At the same time, BvTAG1 exhibits a high affinity for undamaged DNA, mediated by a long N-terminal tail characteristic of all plant Tag homologs. This binding further increases in the presence of free 3-methyladenine. Our results suggest that plant Tag homologs may be required for regulating the plant response to genotoxic stress, rather than for DNA repair.
The aim to evaluate the effectiveness of long-term therapy with Russian rituximab (RTX) biosimilar in Sjögren's disease (SjD) in real-life clinical practice. MATERIALS AND METHODS : The retrospective study included 53 patients with SjD (Russian 2001 criteria and ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) 2016 criteria), observed at the Nasonova Research Institute of Rheumatology from 2017 to 2024 and receiving long-term RTX therapy (Russian biosimilar Acellbia®, BIOCAD). The signs of clinical and laboratory activity of the disease, stomatological and ophthalmological tests, as well as the incidence of new systemic manifestations and lymphomas were assessed dynamically. RESULTS : The median duration of RTX therapy was 27 [19; 55] months, and the median total dose was 4 [3.5; 5.5] g. Before the therapy, 13 (25%) patients had recurrent parotitis, which was relieved in all patients during the therapy. Persistent enlargement of the salivary glands was observed in 10 (20.4%) patients, in 9 of them it was relieved. A significant increase in stimulated saliva flow was found (from 1.5 [0.5; 3] to 2.4 [1.4; 3.5] mL; p = 0.002), an increase in salivation was found in 51% of patients, stabilization in 28.6%, and deterioration in 20.4%. When assessing the ultrasound dynamics of the salivary glands, the size of hypoechoic avascular lesions significantly decreased (from 1.8 [1.3; 2.3] to 1.3 [1.1; 1.5] mm; p<0.001), and according to the ultrasound activity index, stabilization was noted in 67.4% of patients, improvement in 27.9%, and deterioration in 4.7% of patients. When assessing the dynamics of sialography, the size of cavities significantly decreased (from 1.5 [1.5; 2.5] to 1.0 [0; 1.5] mm; p < 0.001), and according to the assessment of sialographic stages, stabilization was noted in 67.5% of patients, improvement in 32.5% of patients, and deterioration was not noted in any patient. When assessing the lacrimal glands function, a significant increase in lacrimation was found according to the stimulated Schirmer's test (from 6 [3.75; 12] to 8 [5; 15] mm; p = 0.005); an increase in lacrimation was noted in 38% of patients, stabilization in 40.6%, and a decrease in 21.4%. When assessing the tear break-up time, a tendency towards its increase was noted, but statistically insignificant (from 5 [3.75; 9.25] to 5.5 [4; 9] sec; p = 0.35). Corneal epitheliopathy during the therapy was relieved in 44% and persisted in 56% of patients; worsening of corneal epitheliopathy during the treatment was observed in a few patients, while no cases of ulcer formation or perforation of the cornea were recorded. During the therapy, a significant decrease in the levels of erythrocyte sedimentation rate, gamma globulins, IgG, IgA, IgM, rheumatoid factor, an increase in the C3 complement level, and the elimination of monoclonal gammopathy were observed, while the dynamics of the C4 complement level and cryoglobulinemia were multidirectional. The median duration of B lymphocyte depletion was 5 [4; 6] months, constant depletion could be maintained only in 59.6% of patients. During the therapy, the SjD systemic activity index (ESSDAI, EULAR Sjögren's Syndrome Disease Activity Index) significantly decreased (from 5 [2; 8] to 1 [0; 3] points; p<0.001), and minimal clinically important improvement of this index was achieved in 66.6% of patients. During the observation, one patient developed a new skin lesion (lupus chilblain); no other new systemic manifestations or lymphomas were registered. CONCLUSIONS : According to our retrospective study conducted in real-life clinical practice, long-term therapy with Russian RTX biosimilar in most cases (60-80%) led to stabilization or improvement of SjD manifestations. RTX can be used to treat not only systemic but also glandular manifestations of the disease. Given the lack of an optimal response to RTX therapy in a number of SjD patients, it is necessary to study the effectiveness of drugs that lead to a deeper depletion of B lymphocytes.
Trans-splicing is a rare variant of the splicing process, wherein exons are joined between different pre-mRNAs. This mechanism enables the formation of a broad spectrum of mRNAs encoded by a single locus. The most prominent example in Drosophila melanogaster is the mod(mdg4) locus, where trans-splicing results in the production of more than 30 mRNAs encoding protein isoforms with distinct C-terminal domains. Previous studies have demonstrated that sequences in the 5'-region of the fourth intron of the mod(mdg4) locus play a pivotal role in initiating trans-splicing. In the present study, we show that the integration of MS2 repeats, which form a stable secondary RNA structure, into the sequence of the fourth intron completely suppressed trans-splicing. Conversely, the insertion of MS2 repeats immediately upstream of the intron only marginally reduced the efficiency of this process. Modifications of the sequences of the fourth intron that induce the formation of an additional stem loop in the pre-mRNA also negatively impacted trans-splicing. These findings underscore the significant role of RNA secondary structures in regulating trans-splicing.
CAG repeats in the first exon of the ATXN2 gene play a key role in the development of a number of neurodegenerative diseases. Understanding the mechanisms underlying CAG tract expansions and the factors influencing them could lead to the development of new methods for the prevention and treatment of these diseases. It was established that a single D/H substitution of a hydrogen bond in the CAG tract increases its stability, thereby reducing the likelihood of formation of secondary structures that interfere with the reading of genetic information from the glutamine-coding region. CAA interruptions in the CAG tract in specific locations can have a similar, but weaker, stabilizing effect.
The design of prodrugs for nucleoside antiviral agents is the primary approach to achieving target profiles not only in terms of safety but also efficacy. We have proposed a new chemotype of inhibitors of tick-borne encephalitis virus (TBEV) reproduction among N6-substituted adenosine derivatives, characterized by the presence of a hydrophobic aromatic substituent at the N6 position of adenine and benzoic acid residues attached via ester bonds to the ribofuranose scaffold. The compounds inhibited TBEV reproduction at micromolar concentrations only in their benzoylated form, while exhibiting no detectable cytotoxicity regardless of the substitution on the ribofuranose moiety. Our study demonstrates that modifying nucleoside analogs with hydrophobic groups can yield compounds with improved antiviral activity, and the identified compounds may subsequently serve as prototypes for the development of new antiviral drugs against epidemiologically significant pathogenic RNA viruses affecting humans.
Polypeptide modular nanotransporters (MNTs) were engineered as a targeted delivery platform for prostate cancer cells. The constructs integrate a ligand module to facilitate specific cellular binding and internalization, and a nuclear localization signal (NLS) to enable subsequent nuclear translocation. Two distinct ligand modules were utilized: (a) a nanobody targeting prostate-specific membrane antigen (anti-PSMA) and (b) a gastrin-releasing peptide (GRP) fragment targeting the GRP receptor (GRPR). It was shown that all modules within MNT-antiPSMA and MNT-GRP retained their functional properties. The MNT-antiPSMA construct demonstrated the capacity to accumulate specifically in the nuclei of prostate cancer cells with both low and high PSMA expression. Conversely, MNT-GRP exhibited selective nuclear entry exclusively in cells characterized by high GRPR expression.
The patterns of radiation adaptive response (RAR) induction and transgenerational genomic instability in mice following exposure to carbon ions (12C) with a linear energy transfer (LET) of ~39 keV/μm and to X‑rays with a LET of ~2 keV/μm at a dose of 10 cGy were studied. Low doses of 12C, as well as X‑rays, induce RAR, the magnitude of which depends on the quality of the challenge radiation. In the first- and second- generation offspring of males irradiated 12C at a dose of 10 cGy, an increased spontaneous level of cytogenetic damage and the absence of RAR in the first generation were detected, in contrast to the offspring of males after irradiation with X‑rays.
-Background Interleukin (IL)-6 plays an important role in the pathogenesis of comorbid rheumatoid arthritis (RA) depression. IL-6 inhibitors used to treat patients with RA may also have an antidepressant effect. - of this study is to evaluate the effectiveness of 24-week IL-6 inhibitor therapy with olokizumab (OKZ) in combination with or without psychopharmacotherapy (PPT) in patients with moderate to high RA activity. - A total of 125 patients with RA were included, 102 (81.6%) of them were women. The average age of the patients was 48.5 ± 12.6 years; the majority of the patients (86.4%) had high RA activity and had shown ineffectiveness with stable 12-week therapy using conventional synthetic disease modifying antirheumatic drugs (csDMARDs). Additionally, 34 (27.2%) patients had shown inefficiency with one or more biological DMARDs. According to the International Classification of Diseases, 10th revision (ICD-10), a psychiatrist diagnosed varying severity of depression (chronic or recurrent) in all patients during a semi-structured interview. At week 0, all patients were randomized using sequential numbers in a 2:2:1 ratio into one of three groups: in group 1, patients received csDMARDs + OKZ 64 mg subcutaneously once every 4 weeks (q4w) (n = 49); in group 2, patients received csDMARDs + OKZ 64 mg subcutaneously q4w along with PPT (n = 51); in group 3, patients received csDMARDs + PPT (n = 25). The study duration was 24 weeks. The severity of depression was assessed using the PHQ-9 (Patient Health Questionnaire 9) and MADRS (Montgomery-Asberg Depression Rating Scale) scales, and anxiety was assessed using the HAM-A (Hamilton Anxiety Rating Scale) scale. Projective experimental psychological techniques were also used. - After 12 and 24 weeks of therapy, a significant decrease in the severity of depression and anxiety was observed in all patients' groups. However, the differences between the final and initial values of the scales filled in by a psychiatrist were statistically significantly greater (p < 0.001) in the groups of patients receiving PPT: in group 2 (ΔMADRS24-0 = -20.2 ± 6.57; ΔHAM-A24-0 = -13.2 ± 5.68) and group 3 (ΔMADRS24-0 = -17.8 ± 4.73; ΔHAM-A24-0 = -13.4 ± 4.41), compared with the group 1 (ΔMADRS24-0 = -5.42 ± 7.14; ΔHAM-A24-0 = -4.58 ± 6.80). There were no significant differences between the groups according to the PHQ-9 depression questionnaire (in group 1, ΔPHQ-924-0 = -4.89 ± 4.87; in group 2, ΔPHQ-924-0 = -6.73 ± 4.97; in group 3, ΔPHQ-924-0 = -7.26 ± 5.58, respectively), despite a greater decrease in the severity of depression observed in the groups with PPT. According to a semi-structured interview with a psychiatrist and in accordance with the criteria of ICD-10 the proportion of patients without depression 24 weeks after the start of therapy was significantly higher in the groups receiving PPT: 84.3% in group 2, 100% in group 3, and 16.3% in group 1. - n patients with moderate/high RA activity and comorbid depression, OKZ without PPT can lead to a decrease in the severity of depression or, less often, to a complete regression of depressive symptoms, mainly in patients with minor depression. OKZ therapy without PPT also reduces the severity of anxiety, but does not eliminate it completely. The combination of OKZ and PPT is optimal for achieving complete regression of depression and anxiety in this category of RA patients.
In the previous study [1], we showed an increased risk of malignant neoplasms in carriers of the minor allele rs1052133*G of the hOGG1 gene who were affected by chronic radiation exposure at a wide range of doses (up to 3507 mGy to the red bone marrow at the Techa River (Southern Urals). The objective of the present study was to assess the contribution of radiation factor to the risk of malignant neoplasm development in persons chronically exposed at the Techa River. For this purpose, we analyzed the background level of genetically determined risk in the general population of unexposed people on the basis of meta-analysis of the world literature data on the search for the association of rs1052133 of the hOGG1 gene with the risk of malignant neoplasm development. At the final stage, the results of the meta-analysis were compared with data on exposed people. The study found that unexposed and exposed carriers of the rs1052133*G allele had a comparable increased risk of developing malignant neoplasms, odds ratio OR = 1.20; 95% confidence interval [1.06-1.35], p = 0.01 and odds ratio OR = 1.38; 95% confidence interval [1.05-1.83], p = 0.023, respectively.
The aim of the study was to analyze the effectiveness and tolerability of subcutaneous methotrexate (sc MTX) (METHORTRIT; sc ROMPHARM Company) in RA patients with high disease activity with rapid dose escalation, to assess their quality of life (QOL) in real clinical practice. -The study included 105 patients, mostly women, with a reliable diagnosis of RA with high disease activity (DAS28 ≥ 5.1) aged 18 years and older and ineffectiveness of previous oral MT therapy for at least 6 months or who had not received MT. sc MTX therapy was started at a dose of 15 mg /weekly. During the first month of therapy, a rapid escalation of the scMTX dose of 2.5 mg/week was performed once a week until the dose of 22.5 mg/week was reached; then, with insufficient response, the dose of sc MTX could be increased to 25 mg/week. The evaluation of the effectiveness of therapy, functional status, and QOL was carried out after 4-12-18-24 weeks. -After a rapid escalation of the sc MTX dose during the first month of the study, at all stages of follow-up, a rapid decrease in disease activity was noted for all standard indices (DAS28 from 5.8 ± 0.75 to 2.93 ± 1.05; CDAI from 30.13 ± 8.33 to 7.08 ± 6.07; SDAI from 32.78 ± 9.64 to 7.48 ± 6.53) and the activity index, which was evaluated by the patients themselves (RAPID-3 from 16.18 ± 4.6 to 5.56 ± 4.66), p ≤ 0.05. The number of patients with high disease activity according to DAS28 decreased by 2 times by the 4th week of therapy (to 46.2%), after 12 weeks they remained 13.3%, and by 24 weeks high activity remained only in 4.4% of patients. There was a marked decrease in pain from 65.6 ± 13.07 to 20.5 ± 17.1 mm in VAS (p < 0.001), which contributed to an improvement in the functional state: the HAQ index decreased on average from 1.47 ± 0.65 to 0.64 ± 052 points. Population indices of functional status (HAQ ≤ 0.5) by the 24th week of therapy were observed in 48.9% of patients. A decrease in the level of fatigue (from 6.25 ± 7.04 to 1.81 ± 1.71 cm according to VAS, p < 0.001) was accompanied by a decrease in anxiety (from 7.47 ± 4.03 to 2.36 ± 2.72, p < 0.001) and depression (from 7.77 ± 3.84 to 2.50 ± 2.56, p < 0.001), as well as improved sleep. By the 24th week of the study, 45% of patients had population-based indices of QOL according to the EQ-5D index. Glucocorticoids (GC) were completely eliminated in 2/3 of the patients. Patients who did not receive GC had lower disease activity by 24 weeks in all indices: DAS 28 (2.7 ± 0.1 and 3.4± 0.2, respectively), CDAI (6.0 ± 0.3 and 10.2 ± 0.1), SDAI (6.4 ± 0.2 and 10.9 ± 0.3), p < 0.05. Patients receiving and not receiving GC had the same number of adverse reactions (p > 0.05); however, the number of infections in patients receiving GC was significantly higher (9.5%-0.0, respectively, p = 0.009). The need for nonsteroidal anti-inflammatory drugs (NSAIDs) at the beginning of the study was in 93.2% of patients on average 21.1 days per month; after 24 weeks, the need for NSAIDs was in 54.4% of patients on average 3.8 days per month. In general, the safety profile of MTX was acceptable. -With high RA activity, the tactics of starting therapy with sc MTX at a dose of 15 mg per week and a rapid escalation of its dose of 2.5 mg weekly to 22.5-25 mg/week, allows achieving therapy goals by 3 months in 17.8% of patients, and by 6 months in 64.5%, to quickly improve the QOL, reduce the level of pain, reduce the dose of GC by 3 months of therapy or completely cancel them, and reduce the need for NSAIDs by 7 times with an acceptable level of therapy safety.
Ferroptosis is considered a promising strategy for inducing the death of tumor cells. However, the effectiveness of known ferroptosis inducers, such as erastin, is in some cases limited, which stimulates the search for new combined application strategies. In this study, the combined effect of erastin and docosahexaenoic acid (DHA) on prostate cancer cells was examined over time. It was shown that the combination of these agents is more toxic compared to their separate use for all tumor cells considered. At the same time, known ferroptosis inhibitors, ferrostatin-1 and deferoxamine, effectively prevented cell death, indicating the specificity of the mechanism of action. Transcriptomic analysis of cell lines differing in sensitivity to the combination revealed activation of antioxidant systems in more resistant cells (in particular, pronounced expression of the NQO1 and GCLM genes responsible for the reduction of quinones to hydroquinones and the synthesis of glutathione, respectively). The obtained results indicate the high synergistic potential of the erastin-DHA combination for ferroptosis induction and open new possibilities for the development of combined approaches to the therapy of resistant tumors.
The genotypic variability of the SARS-CoV-2 virus is extremely high, and the emergence of new strains raises concerns about their possible high virulence and ability to bypass responses of the body's immune system induced by previous infection or vaccination. Therefore, one of the main tasks is to study the pathogenesis of various variants of the virus using experimental animal biomodels of SARS-CoV-2 to quickly find methods and approaches to fighting new viruses. The study was performed on humanized mice of the C57BL/6-Tgtn line. Mice were infected intranasally at different doses with three variants of the SARS-CoV-2 virus. We showed that humanized hACE2 mice, when infected with all three variants of the SARS-CoV-2 virus, showed typical pathological changes in lung consistency comparable to those found in COVID-19 in humans. At a dose of 4 log plaque-forming unit (PFU), all variants showed 100% mortality. In a comparative assessment of different variants of the SARS-CoV-2 virus in hACE2 humanized mouse model, it was found that the Delta variant leads to more severe damage compared to Wuhan or Omicron.
For the first time, the composition and fatty acid content of Artemia spp. cysts from three hypersaline lakes in Southern Siberia were analyzed. The fatty acid composition of decapsulated Artemia cysts varied significantly between the studied water bodies. It was found that the cyst profiles from Lakes Cheder and Dus-Khol corresponded to a "marine" type, while those from Lake Tus corresponded to a "freshwater" type. An assessment of the biochemical value, including the content of eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, the ratio of n-3/n-6 fatty acids, as well as hatching rates (hatching efficiency up to 135 thousand specimens/g, the proportion of hatched nauplii up to 85%), allowed us to recommend cysts from Lake Cheder as a promising source for the production of live feed for aquaculture.
Boron Neutron Capture Therapy (BNCT) is one of the innovative methods for treating oncological diseases. Its selectivity is based on the targeted delivery of the boron-10 isotope to tumor cells, followed by neutron irradiation, the 10B(n, α)7Li reaction occurs with a local release of 2.79 MeV of energy. Budding boron delivery agents are nanoscale systems. This study evaluated in vitro cytotoxicity, accumulation, and retention of elemental boron nanoparticles, synthesized by laser ablation and laser fragmentation, in U87 and BT474 tumor cells and BJ-5ta fibroblasts. It was shown that both types of nanoparticles exhibit low cytotoxicity at therapeutically relevant concentrations. Boron accumulation was maximal after 24 h of incubation and was significantly higher in tumor cells, especially in the BT474 cell line, compared to fibroblasts. The obtained data indicate the promise of these nanoparticles as boron delivery agents for BNCT.
The study proposes an experimental approach to determining the rates of individual stages of a reaction catalyzed by bacterial luciferase, based on the tryptophan fluorescence of the protein and the stopped-flow technique. The relationship between the fluorescence intensity of tryptophan residues in luciferase and the presence of substrates and reaction products in the active site of the enzyme is substantiated. The non-steady-state kinetics of bioluminescence in the reaction of two bacterial luciferases with aliphatic aldehydes of different chain lengths, as well as the kinetics of enzyme fluorescence intensity during the reaction, were analyzed. The obtained results confirmed the relationship between the rate of the two kinetic stages of enzyme luminescence and the processes of flavin substrate binding and enzyme activity recovery after the catalytic act.
of the study is to evaluate the efficacy, safety, and immunogenicity of divozilimab (DIV), anti-CD20 monoclonal antibody, in patients with systemic sclerosis (SS). . Patients with SS according to ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) 2013 criteria with modified Rodnan skin score (mRSS) ≥10 and ≤20 and forced vital capacity (FVC) ≥40% from the due took part in the study. Infusions of DIV 250 mg were administered on weeks 0 and 2, and DIV 500 mg on week 24 with the subsequent use in open mode, starting from week 48. This publication presents data obtained for 48 weeks of trial (before the DIV infusion at week 48). Primary endpoint was the change in the mRSS from baseline to week 48. The dynamic of FVC was estimated as the secondary endpoint. The safety evaluation included the frequency and profile of adverse events and adverse reactions (ARs). Immunogenicity was assessed by detection of binding and neutralizing anti-drug antibodies on weeks 2, 24, and 48. : The patients (151) were randomized into two groups: DIV (n = 76) and placebo (n = 75). The most were female; the median duration of the disease was about 3-4 years. The initial value of the mRSS was 14 and 13 points in DIV and Placebo groups, respectively. The change of mRSS from baseline to week 48 was -5.8 ± 1.1 points in DIV group and -2.7 ± 1.0 points in placebo group (adjusted mean difference (AMD) with 95% confidence interval -3.1 (-4.5; -1.7); p < 0.0001). The lung function was stable in patients treated with DIV. A comparable safety profile of DIV and placebo was demonstrated. The most frequent ARs were infusion reactions and a decrease in the number of lymphocytes. There were no severe and serious ARs in DIV group. All infusion reactions were mild and moderate. 5.3% (4/76) patients in DIV group had binding antibodies without neutralizing activity. : Divozilimab has demonstrated a significant decrease in severity of skin fibrosis, a positive effect on the respiratory function, and a favorable safety profile, which allows it to be considered as a promising therapeutic option for SS.
Genetic predisposition without doubt is one of the risk factors of cancer initiation. It is known that single nucleotide polymorphisms (SNP) of genes that maintain the genome stability, including SNP of DNA repair, may contribute to the initiation of carcinogenesis. Single-nucleotide polymorphisms of genes that support genome stability, including SNP of DNA repair genes, can contribute to cancer initiation. Polymorphism of the excision repair gene OGG1 causes interest of leading scientific groups from various countries. It is assumed that there is relationship between the rs1052133 polymorphism in the gene and predisposition to cancer initiation. The objective of this study was to establish association between rs1052133 polymorphism of base excision repair gene OGG1 and the risk of cancer initiation in people chronically exposed to ionizing radiation. Residents (888 people) of the Techa riverside settlements, chronically exposed to low or medium dose radiation from the Techa River and the East-Urals Radioactive Trace were included in the study. The study allowed researchers to establish that exposed to chronic radiation people, carriers of the rs1052133*G allele, have increased risk of malignant neoplasm initiation: OR = 1.38; 95% CI [1.05-1.83], p = 0.023. The multifactorial synergistic interactions between the dose to the red bone marrow and the rs1052133 polymorphism of the OGG1 gene was found: Testing Balanced Accuracy (TBA) = 0.56; Cross Validation Consistency (CVC) = 10/10; p = 0.01). The study found that the rs1052133 polymorphism may be considered as genetical marker of risk of cancer initiation in people chronically exposed to radiation with doses ranged from 0.74 to 3507.07 mGy (average 523.10 ± 33.89 mGy). It was found that the presence of the rs1052133*G in combination with radiation exposure can modify the risk of solid cancers initiation, as it is indicated by the synergistic relationship between the SNP and the radiation dose.
We previously demonstrated that fragments of the central loop of the non-conventional toxin WTX reduce blood pressure in rats and inhibit certain nicotinic acetylcholine receptor subtypes [10]. In the present study, we examined the effects of hexamethonium and methylicaconitine, which are nicotinic acetylcholine receptor inhibitors, as well as of atropine, a muscarinic acetylcholine receptor inhibitor, on the hypotensive effect of the WTX central loop fragment. For this purpose, these compounds were administered intravenously before the peptide. We found that hexamethonium and methylicaconitine enhanced the fragment's hypotensive effect, while atropine weakened this effect. Only methylicaconitine enhanced the tachycardic effect of the peptide. These data indicate the involvement of both nicotinic and muscarinic acetylcholine receptors in the hemodynamic effects of the WTX central loop fragment.
Aliphatic aldehydes are involved in many important biological processes, but detection of them at low concentrations requires expensive laboratory equipment and labor-intensive analytical methods. Typically, chromatographic and chromatograph mass spectrometric methods are used for this purpose. Therefore, developing a simple method for detecting aldehydes at low concentrations is a pressing scientific and technical challenge. We have demonstrated that a bacterial bioluminescent system can be effectively used for the semiquantitative determination of biogenic aldehydes in vitro at nanomolar concentrations. Furthermore, this system holds promise for detecting biogenic aldehydes in vivo.