Inflammatory bowel disease (IBD) refers to chronic immune-mediated conditions. Damage to the intestinal barrier is associated with changes in bacterial product levels and the systemic inflammation persistence. The mucosal barrier molecular components, such as I-FABP, mucin 2, TFF2, and TFF3, are involved in maintaining the epithelium integrity and the inflammatory response modulation. However, the diagnostic value of those in IBD is still poorly understood. The single center cross-sectional comparative study aimed to perform a comprehensive comparative assessment of the mucosal barrier serum components in healthy donors and patients with IBD. A total of 20 patients with IBD and 20 healthy donors were enrolled. Serum concentrations of I-FABP, mucin 2, TFF2, and TFF3 were determined by the enzymelinked immunosorbent assay. Statistical analysis was conducted using the Mann–Whitney U-test, the differences were considered significant at p ≤ 0.05. Significant differences were reported for TFF2 and TFF3. In patients with IBD, TFF2 levels were 5 times higher, than in healthy donors, and TFF3 levels were 4.2 times higher. Thus, serum levels of TFF2 and TFF3 are elevated in IBD, which reflects activation of the repair mechanisms and can be considered as an inflammatory activity marker.
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Changes in the ratio of the C-reactive protein (CRP) pentameric (anti-inflammatory) and (monomeric) isoforms during treatment of combined metabolic disorders with glucocorticoids are still poorly understood. The study aimed to assess plasma concentrations of CRP and its isoforms (pentameric and monomeric) in rats with obesity combined with arthrosis. The experiment involved 180 male Wistar rats (n = 180; 8–10 weeks, 200–250 g) randomized into five groups (n = 36). The first one represented the control; obesity and arthrosis were simulated in groups II–V. Groups I and II were administered 1.0 mL of saline; groups III–V were administered 1, 10, 100 ng/mL of dexamethasone daily for 10 days; concentrations of CRP and its isoforms (pentameric and monomeric) were assessed by ELISA on days 3, 5, and 10. Calculation was performed using the Statistica 10.0 software; the data were presented as M ± SD with 95% confidence intervals, with p < 0.05. The increase in CRP levels was reported in group (arthrosis + obesity): by 2.1% on day 3, 26.4% on day 5, 174.5% by day 10 (p < 0.001) relative to the control (group I). Dexamethasone 1 and 10 ng/mL reduced inflammation on day 3 (CRP levels decreased by 7.9% and 26.1%, respectively (p < 0.05)); CRP levels increased by 231.6% and 152.3% by day 10 (p < 0.001). The dose of 100 ng/mL reduced CRP levels by 9.5% on day 5, showing the increase by 149.0% on day 10; p < 0.001. In group II, the mCRP concentration increased by 287.1% by day 10, and in groups III, IV, and V it increased by 360.2%, 270.9%, and 280.6%, respectively (p < 0.001). The nCRP concentration decreased by day 10 in groups II and V (by 25.7% and 18.1%; p < 0.05). No deaths or adverse reactions were reported.  Conclusions: dexamethasone 1 and 10 ng/mL reduces the CRP concentration throughout 3 days, and the dose of 100 ng/mL up to 5 days with the development of resistance and the increase in total and monomeric CRP levels on day 10.
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In earlier experimental studies in vitro the Newcastle disease virus strain NDV/Altai/pigeon/770/2011 demonstrated significant cytolytic properties against various tumor cell lines, including colorectal cancer cells. It also inhibited the growth of various types of tumors in xenograft and syngeneic tumor models. The aim of the present study was to evaluate of the antitumor activity of several forms of NDV-containing drug on experimental adenocarcinoma CT26 and to compare the therapeutic effect with the classical cytostatic agent. Male BALB/c mice were used as model animals. Two experiments were conducted. In the first, intravenous antitumor therapy was started 48 hours after subcutaneous injection of CT26 tumor cells; in the second, therapy was started when the tumor reached a size of 150–400 mm3. A single injections of virus-containing drugs were administered for five days to mice from the experimental groups in each experiment: the unpurified form of the virus-containing drug and two purified forms of the virus-containing drug with the addition of hydroxyethyl starch and glucose. The mice in the control group were untreated. The comparison mice group was injected with cyclophosamide intraperitoneally (twice). According to the oncological parameters, therapy with an unpurified form of a virus-containing drug based on NDV strain proved to be effective, and the therapeutic effect was comparable in all major parameters with the group of animals receiving standard cyclophosphamide therapy.
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Cholelithiasis is a common surgical disorder creating a high burden of the healthcare system. The introduction of minimally invasive technologies justifies the shift towards hospital-replacing models, but the institutional aspects of their use in the metropolis are still poorly understood. The study aimed to assess the role of hospital-replacing technologies in organizing elective surgical care provision to patients with cholelithiasis based on the retrospective analysis data for the years 2016–2025. A retrospective observational study was conducted based on the aggregate data of the Moscow City Health Department. The dynamics and structure of elective cholecystectomy procedures, the development of the short-stay unit (SSU) network, length of hospital stay, and age distribution were analyzed. The number of laparoscopic cholecystectomy procedures increased by 48%, the number of open surgical interventions decreased by 93.4%. The SSU network expanded from 5 to 30 units, the share of surgery due to cholelithiasis performed at the SSU reached 40.2% relative to the year 2016. The SSU stay was associated with the 75.0% bed-day reduction (to one day) and the actual hospital stay reduction by more than 80.0% (to 16.2 ± 7.4 h) compared to the round-the-clock hospital (RCH). Age differences (the share of patients over the age of 70 was 13.3% in the SSU vs. 36.0% in the RCH) support selective routing of patients at lower risk to the SSU. Conclusions: SSU has become an important organizational instrument of elective surgery due cholelithiasis that has ensured a sharp patient treatment time reduction over the preceding 10 years.
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Pulmonary fibrosis is characterized by irreversible remodeling of the lung tissue, with limited treatment options. Selective vitamin D receptor (VDR) agonists are regarded as promising antifibrotic agents, but the dose dependence of their effects in pulmonary fibrosis has been little studied. The aim of the experimental study was to carry out a comparative analysis of the effects of two doses of paricalcitol in experimental aerosol bleomycin-induced pulmonary fibrosis. The experiment was performed on 60 Wistar rats: an intact group (n = 6), a control group with fibrosis modeling (n = 18), and two experimental subgroups with intraperitoneal administration of paricalcitol at doses of 0.1 μg/animal (EG-A; n = 18) and 0.5 μg/animal (EG-B; n = 18) once every 3 days. The animals were withdrawn from the experiment on days 10, 20, and 30, with histopathological analysis and scoring on the modified Ashcroft scale, immunohistochemical study (CD68, CD80, CD163, MMP-9, TGF-β1, p38 MAPK, VDR), and analysis of the relative mRNA expression of IL1β, TNFα, TGF-β1, and SMA-α. Both doses of paricalcitol reduced the severity of the inflammatory and fibrotic changes, but the effect was dose-dependent: on day 30 the Ashcroft score was 5.01 ± 0.45 points in the control, 3.40 ± 0.28 in EG-A (–32.1%), and 2.12 ± 0.25 in EG-B (–57.7%; p < 0.05 compared with EG-A). Paricalcitol limited the early M1 response, reduced the number of CD163+ macrophages, and suppressed the expression of TGF-β1, MMP-9, and p38 MAPK. With the high dose, by day 30 the mRNA levels of IL1β, TNFα, TGF-β1, and SMA-α did not differ from those in the intact group. Thus, the antifibrotic action of paricalcitol is dose-dependent and is most pronounced at the later stages of the experiment.
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Bordetella bronchiseptica is a respiratory pathogen of humans and animals that infects a wide range of hosts. This study aimed to characterize the phylogenetic position and genomic features of 31 laboratory isolates of B. bronchiseptica, 25 of which were obtained from humans and six from animals. The studied isolates were compared with 30 reference genomes of B. bronchiseptica, B. pertussis, and B. parapertussis. The analysis included the determination of average nucleotide identity (ANI), phylogenetic reconstruction based on 120 marker proteins and 42 ribosomal proteins, and the identification of virulence factors, potential antibiotic resistance genes, prophage regions, and antiphage defense systems. A subsample of 20 genomes has also been subjected to pangenomic and metabolic analyses. In the overall dataset, B. pertussis and B. parapertussis formed compact clades, whereas B. bronchiseptica isolates were distributed across several phylogenetic lineages. B. bronchiseptica lines differed in their repertoires of virulence factors, putative antibiotic-resistance determinants, prophages, and antiphage defense systems. In the subsample of 20 genomes, representatives of the classical Bordetella retained the main modules of central metabolism and a substantial proportion of the shared gene clusters. The resulting data demonstrate a pronounced phylogenetic and functional genomic heterogeneity of B. bronchiseptica.
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Peritoneal carcinomatosis in colorectal and gastric cancer is associated with the extremely poor prognosis and the limited standard therapy efficacy, which suggests the need to develop new targeted drugs. The study aimed to assess the long-term outcomes of the efficacy of the RAS-GTPase peptide inhibitor (“Ing-Ras”) intraperitoneally administered by the PIPAC method to patients with stage III–IV gastric and colorectal tumors. A total of 38 patients (21 with colorectal cancer (CRC), 17 with gastric cancer (GC), including with peritoneal carcinomatosis) were included in the prospective open-label nonrandomized multicenter phase I/IIa trial. The long-term outcomes were assessed after 30 months of follow-up. A significant increase in the overall survival parameters was reported for both disease entities: the one- and two-year overall survival was 95.24 and 80.95% for CRC (historical control: 65–85% and 50–65%), 76.47 and 47.06%, respectively, for GC vs. 40–60% and 20–30%; progression and recurrence rates decreased significantly. Thus, the use of “Ing-Ras” makes it possible to increase the survival rate and reduce the recurrence rate relative to the historical control, which justifies conducting phase III trials.
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