Doklady Biochemistry and Biophysics最新文献

The direct antitumor effect of bevacizumab (BEV) has long been debated. Evidence of the direct antitumor activities of drugs are mainly obtained from in vitro experiments, which are greatly affected by experimental conditions. In this study, we evaluated the effect of BEV-containing medium renewal on the results of in vitro cytotoxicity experiments in A549 and U251 cancer cells. We observed starkly different results between the experiments with and without BEV-containing medium renewal. Specifically, BEV inhibited the tumor cell growth in the timely replacement with a BEV-containing medium but promoted tumor cell growth without medium renewal. Meanwhile, compared with the control, a significant basic fibroblast growth factor (bFGF) accumulation in the supernatant was observed in the group without medium renewal but none in that with replaced medium. Furthermore, bFGF neutralization partially reversed the pro-proliferative effect of BEV in the medium non-renewed group, while exogenous bFGF attenuated the tumor cell growth inhibition of BEV in the medium-renewed group. Our data explain the controversy over the direct antitumor effect of BEV in different studies from the perspective of the compensatory autocrine cytokines in tumor cells.

Gout is associated with increased risk of cardiovascular disease (CVD) morbidity and mortality. Therefore, an association between coronary heart disease (CHD) and gout deserves careful examination.

. The aim of this study was to determine the prevalence of CHD and factors associated with CHD in patients (pts) with gout.

. The study involved 286 male patients with gout, age 51.2 [42.8; 59.4] years (ys), disease duration 6.2 [3.8; 12.1] ys. All patients underwent standard clinical examination screening traditional risk factors (TRFs) of CVDs. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI).

. CHD was found in 111 out of the 286 pts (38.8%), MI had a history in 29.7%. Compared to individuals with CHD, participants without CHD were older (56.7[52.1; 61.1] vs 46.2[40.6; 53.4] ys), had longer duration of gout (9.3[4.7; 15.1] vs 5.6[3.3; 9.7] ys) (for all p < 0.05). Abdominal obesity (OR, 3.6; 95% CI, 1.2–10.9), family history of CHD (OR, 2.2; 95% CI, 1.3–3.7), disease duration of gout more 10 ys (OR, 2.8; 95% CI, 1.6–4.7), age of gout onset < 35 ys (OR, 5.5; 95% CI, 2.6–11.7), intraosseous tophi (OR, 3.03; 95% CI, 1.8–5.01), nephrolithiasis (OR, 1.7; 95% CI, 1.04–3.04), renal failure (OR, 5.6; 95% CI, 2.7–11.4), serum total cholesterol (TC), (OR, 1.6; 95% CI, 1.0–2.8), serum creatinine (OR, 2.5; 95% CI, 1.2–5.1), increased the risk for CHD in patients with a gout.

. The prevalence of CHD was 38.8% among individuals with gout (one-third of patients had a history of MI 29.7%). Our study showed that both TRFs of CVD and the severity of gout and a history of renal failure contribute to the development of CHD in patients with gout.

Translation inhibition can activate two cell death pathways. The first pathway is activated by translational aberrations, the second by endoplasmic reticulum (ER) stress. In this work, the effect of ribosome-inactivating protein type II (RIP-II) viscumin on M1 macrophages derived from the THP-1 cell line was investigated. The number of modified ribosomes was evaluated by real-time PCR. Transcriptome analysis revealed that viscumin induces the ER stress activated by the PERK sensor.

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.

. The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL).

. Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(–) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691–0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%.

In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(–) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(–) RA group.

. We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(–) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more “erosive” subtype of the disease than ACPA(+) anti-CarP(–) patients. In ACPA(–) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(–) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases.

The aim of the study was to investigate the features of the clinical picture of the disease in patients with ACPA–negative and ACPA-positive variants of rheumatoid arthritis.

The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the ACPA values, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease, and therapy. The nature of the onset and course of the disease and the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices).

The study involved 79 patients with ACPA-negative variant of RA and 79 ACPA-positive patients. The age of patients (Me [IR] (in years)) with the ACPA(–) variant was 52 [39; 62]; with the ACPA(+) variant, 54 [42; 62]; the duration of the disease (in months) was 59 [23; 122] and 48 [17; 84], respectively.

In ACPA(+) patients, a higher disease activity was determined (by the indices DAS 28crp, DAS28esr, SDAI, CDAI), higher values of C-reactive protein and erythrocyte sedimentation rate, and a greater number of painful and swollen joints (p < 0.05).

According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients.

Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(–) (17.7%) patients. Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, whereas a tendency to a higher frequency of neuropathy, sclerites, and episcleritis was revealed in ACPA(–) patients.

. In patients with ACPA(–) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less “bright” course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.

The composition of fatty acids in the muscle tissue of the unique Central Asian carp-like fish, Potanin Altai osman Oreoleuciscus potanini, was studied for the first time. The populations of these fish in the reservoirs of the semiarid zone (Durgun and Taishir) during the period of their formation are considered. It was shown that the content of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in O. potanini corresponds to the median of this value in the order Cypriniformes. It was established that the basis of the food web of the herbivorous form of this species consists of microalgae (diatoms, Euglena and, possibly, chrysophytes), as well as bacteria. At the same time, the levels of bacterial biomarkers, 15-17BCFA and 17:0 were significantly higher in fish in the Durgun reservoir, whereas the level of EPA (diatom biomarker) in O. potanini was higher in the Taishir reservoir. The established higher values of the heavy nitrogen isotope content in the muscles of O. potanini from the Taishir reservoir are most likely associated with the yet unformed benthic communities and with the incomplete diversification of the riverine form of the Potanin Altai osman into lacustrine forms.

Fundamental aspects in the evolution of nematodes parasitizing woody plants are reviewed. (1) Nematode faunal lists of natural refugia are useful to predict the risks of opportunistic pathogens becoming true pathogens in the forest and park communities. (2) Nematode composition in natural refugia gives a chance to identify nematode antagonists of insect vectors of dangerous fungal and nematode infections, which can be potentially used as the biological agents for woody plants’ protection. (3) Dauers in the ancestors of wood-inhabiting nematodes played a role as a survival stage in the detritus decomposition succession, and they later acquired the functions of dispersal and adaptations for transmission using insect vectors. (4) When inspecting wilted trees, it is necessary to use dauers for diagnostics, as sexually mature nematodes may be absent in tree tissues. (5) Plant parasitic nematodes originated from members of the detritus food web and retained a detritivorous phase in the life cycle as a part of the propagative generation. (6) Vectors in the life cycles of plant parasitic nematodes are inherited from the ancestral detritivorous nematode associations, rather than inserted in the dixenic life cycle of the ‘nematode–fungus–plant’ association. (7) Despite the significant difference in the duration of the nematode–tree and nematode–vector phases of the life cycle, the actual parasitic nematode specificity is dual: firstly to the vector and secondly to the natural host plant (as demonstrated in phytotests excluding a vector).

We performed a detailed ultrastructural reconstruction of the “passive” miracidium of Derogenes varicus Muller, 1784 , a species from the Hemiurata group. The miracidium is highly miniaturized and simplified in comparison with the “active” miracidia. For the first time we elucidated the nature of the spines on the surface of the hemiuroid larva: they are derivatives of the epithelial plates. The anterior end of the larva is equipped with three epithelial plates that bear both spines and cilia. The major part of the miracidial surface is formed by the tegument. The nervous and excretory systems of the D. varicus miracidium are extremely reduced. Single undifferentiated cell comprises the germinal material of the miracidium. We discuss the trends of evolution of hemiuroid miracidia that are associated with the transition to passive strategy of infection.

The giant tegument nuclei of the acanthocephalans of the classes Archiacanthocephala and Palaeacanthocephala are fragmented at the final stage of cystacanthus formation in the intermediate host, but remain connected with each other during later life. It can be assumed that the fragments of each giant tegument nucleus are united with each other to form an independent network that ensures the vital activity of the tegument, the volume of which increases many times during the period of intensive growth of the parasite in the definitive host.