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Ultraviolet radiation (UVR) has been recognized as a potential trigger for the transformation of benign melanocytic nevi into melanoma. However, the mechanisms governing the formation and progression of melanocytic nevi remain poorly understood. This lack of understanding is partly due to the difficulty in isolating and culturing nevus tissues in vitro, resulting in a dearth of robust ex vivo models for nevi. Therefore, the establishment of a reliable melanocytic nevus model is imperative. Such a model is essential for elucidating nevus pathogenesis and facilitating the development of effective therapeutic interventions. Therefore, we have sought to establish an ex vivo nevus explant model to study UVR stimulation. And the structural integrity and tissue activity of the ex vivo nevi explant model was evaluated. We then observed melanogenesis and proliferation activity of the explants after UVR stimulation. There was less blister formation after Day 3 in nevi explants under our modified medium conditions. The nevi explant was able to maintain almost the same morphological structure and tissue activity as in vivo tissue within 24 h. Following UVR stimulation, we observed increased melanogenesis and proliferation activity in nevi explants. Nevi explants could serve as an ex vivo model for UVR‐induced nevi stimulation research. [ABSTRACT FROM AUTHOR]

Activation of Gonadotropin-Releasing Hormone type II Receptors (GnRHR-II) exhibits antiproliferative activity. GnRHR-II is not only expressed exclusively in the pituitary, but also in a variety of tumors. To date, the clinical relevance of GnRHR-II in ovarian tumors is unclear. In addition, there is a lack of literature addressing GnRHR-II in ovarian tumors, especially rare types. This study was conducted to investigare the correlation between GnRHR-II expression with clinicopathology and proliferative activity of rare ovarian tumors. The purpose of this study was an analytic observational study with a cross-sectional design that utilized 18 ovarian tumor samples on tissue microarray (TMA). The expression of GnRHR-II and Ki67 was assessed using immunohistochemical staining (IHC) and observed using the IHC profiler plugin ImageJ software to obtain thei r respective H-scores. The data was analyzed using independent t-test, ANOVA, Pearson's test, and Fisher's exact test based on data types. The value of p<0.05 was considered statistically significant. GnRHR-II is expressed in various forms in ovarian tumors, including extrapituitary expression. GnRHR-II expression was highest in the sex cord stromal tumor (SCST) group, 110.30 ± 23.89 (p<0.0001). In addition, there was also a significant difference between GnRHR-II expression with age (p<0.001) and the primary tumor (p<0.05), but not with tumor type (p=0.101). There is a correlation between GnRHR-II expression and proliferative activity (r=-0.043, p=0.866). Elevated GnRHR-II expression is significantly correlation with SCST, individuals over 40 years of age, and tumors confined to the ovary and it is correlates with lower proliferative activity, although this correlation is very weak. [ABSTRACT FROM AUTHOR]

Unlike somatotroph tumors, the data on correlates of tumor granulation patterns in functional TPIT lineage pituitary neuroendocrine tumors (corticotroph tumors) have been less uniformly documented in most clinical series. This study evaluated characteristics of 41 well-characterized functional corticotroph tumors consisting of 28 densely granulated corticotroph tumors (DGCTs) and 13 sparsely granulated corticotroph tumors (SGCTs) with respect to preoperative clinical and radiological findings, tumor proliferative activity (including mitotic count and Ki-67 labeling index), and postoperative early biochemical remission rates. The median (interquartile range (IQR)) tumor size was significantly larger in the SGCT group [16.00 (16.00) mm in SGCT vs 8.5 (9.75) mm in DGCT, p = 0.049]. T2-weighted signal intensity and T2 intensity (quantitative) did not yield statistical significance based on tumor granulation; however, the T2 intensity-to-white matter ratio was significantly higher in SGCTs (p = 0.049). The median (IQR) Ki-67 labeling index was 2.00% (IQR 1.00%) in the DGCT group and 4.00% (IQR 7.00%) in the SGCT group (p = 0.043). The mitotic count per 2 mm2 was higher in the SGCT group (p = 0.001). In the multivariate analysis, the sparse granulation pattern (SGCT) remained an independent predictor of a lower probability of early biochemical remission irrespective of the tumor size and proliferative activity (p = 0.012). The current study further supports the impact of tumor granulation pattern as a biologic variable and warrants the detailed histological subtyping of functional corticotroph tumors as indicated in the WHO classification of pituitary neuroendocrine tumors. More importantly, the assessment of the quantitative T2 intensity-to-white matter ratio may serve as a preoperative radiological harbinger of SGCTs. [ABSTRACT FROM AUTHOR]

Activation of Gonadotropin-Releasing Hormone type II Receptors (GnRHR-II) exhibits antiproliferative activity. GnRHR-II is not only expressed exclusively in the pituitary, but also in a variety of tumors. To date, the clinical relevance of GnRHR-II in ovarian tumors is unclear. In addition, there is a lack of literature addressing GnRHR-II in ovarian tumors, especially rare types. This study was conducted to investigare the correlation between GnRHR-II expression with clinicopathology and proliferative activity of rare ovarian tumors. The purpose of this study was an analytic observational study with a cross-sectional design that utilized 18 ovarian tumor samples on tissue microarray (TMA). The expression of GnRHR-II and Ki67 was assessed using immunohistochemical staining (IHC) and observed using the IHC profiler plugin ImageJ software to obtain their respective H-scores. The data was analyzed using independent t-test, ANOVA, Pearson's test, and Fisher's exact test based on data types. The value of p

Background: The folate metabolism pathway plays an integral part in DNA synthesis, methylation, and repair. Methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase (MTHFD1) are both enzymes that are involved in this pathway, and the single nucleotide polymorphisms (SNPs) in genes coding for them have modulatory effects on DNA expression. This study aimed to investigate the relationship between MTHFR C677T (rs1801133) and MTHFD1 G1958A (rs2236225) polymorphisms and the risk of developing breast cancer in Georgian women. Methods: A case-control study was performed examining the MTHFR C677T and MTHFD1 G1958A SNP in breast cancer–confirmed cases and healthy matched controls. Real time-polymerase chain reaction (PCR) was used to genotype SNPs. The case individuals' pathology reports were obtained following surgeries for cancer characteristic data. Statistical analysis was performed to investigate the significance of the acquired data. Results: Statistical analysis of MTHFR C677T SNP revealed that the CT genotype increased the risk of breast cancer by 2.17 folds in the over-dominant model. Statistical analysis of MTHFD1 G1958A SNP showed that the GA genotype increased the risk of breast cancer by 4.12 folds in the codominant model and 2.41 folds in the over-dominant model. No statistically significant link was found between genotypes and lymph node status, however, patients with the CT genotype had higher percentages of proliferative activity. Conclusions: Breast cancer seems to have a statistically significant association with the CT genotype in MTHFR C677T and the GA genotype in MTHFD1 G1958A in Georgian women. [ABSTRACT FROM AUTHOR]

Two new nonimmortalized fibroblast-like cell lineages (MSC-DP-1 and MSC-DP-2) isolated from the pulp of milk teeth of two 6-year-old children of different sex were obtained and characterized. The status of mesenchymal stem cells was confirmed by comparative analysis of a number of characteristics of these cells at early and late passages. The long-term cultivation revealed significant interstrain differences in growth characteristics and replicative senescence (RS). The MSC-DP-1 cells were characterized by a later entry into the MS active stage and more active proliferation compared to MSC-DP-2 cells. Karyotypic analysis showed that both lineages at early passages have a normal human diploid karyotype. Late (18th passage) in the stage of active RS, MSC-DP-2 cells retain the normal karyotype. MSC-DP-1 cells, which enter the active RS much later (at the 42nd passage), had an abnormal karyotype with a large the number of clonal and nonclonal chromosomal rearrangements. Both lineages showed a high proportion of cells carrying surface antigens characteristic of human MSCs—CD44, CD73, CD90, CD105, and HLA-ABC—and a low frequency of cells with CD34, CD45, and HLA-DR antigens. Cells of both lineages at an early passage demonstrated the ability to differentiate in the adipogenic, osteogenic, and chondrogenic directions. However, MSC-DP-2 cells showed a weaker differentiation capacity in the adipogenic direction than MSC-DP-1 cells. During RS, adipogenic differentiation in MSC-DP-1 cells is significantly weakened, while in MSC-DP-2 cells it disappeared. The activity of other differentiations did not change during RS. In general, the results obtained confirmed the MSC status of obtained lineages and revealed interlineage differences in the RS. However, the comparison with the previously obtained MSC-DP lineages did not indicate a gendered nature of the observed differences between these cells. Apparently, they are associated with the genetic characteristics of different donors. [ABSTRACT FROM AUTHOR]

Ability of the continuous cell lines to evolve enables generation of new transformed cell cultures with unlimited life potential and different from the original prototypes in the process of sequential cultivation. There are practically no universal mechanisms and methods for new cell line generation. But it was noted that cell immortalization is associated with chromosomal rearrangements (chromatid morphology) and changes in the number of chromosomes. The paper presents the results of the generation of a new Testis Capra hircus(TCh) cell line, suitable for effective replication of dermatotropic and other types of animal viruses, in order to scale up viral material used for the manufacture of the means for animal disease specific prevention and diagnosis. The monolayer TCh cell line was transformed from the continuous YаDK-04 cell line as a result of more than 50 passages in the growth medium supplemented with 10% of lanthanide-treated bovine serum. Use of the bovine serum purified and supplemented with lanthanides during the cultivation of the continuous cell line YаDK-04 led to significant chromosomal rearrangements and contributed to the formation of a stable and productive new TCh cell line, which differed in cytomorphological and karyological characteristics and had unlimited potential for passaging without changing the cell karyotype and morphology. The novel continuous cell line proved to be suitable for effective reproduction of such disease pathogens as lumpy skin disease, sheep pox, peste des petits ruminants agents. These are mainly viruses of dermatotropic origin.

Background Interleukin-10 (IL-10) is a cytokine with a vast variety of functions, but its role in cancer development and progression is not yet clear. It is involved in two of the hallmarks of cancer: vascularization and immune modulation. IL-10 inhibits angiogenesis and hence is antitumorigenic. But it also can suppress the immune system and be tumorigenic.

Vimentin is a stable mesenchymal immunohistochemical marker and is widely recognized as a major marker of mesenchymal tumors. The purpose of the present study was to investigate if the vimentin expression status might serve as a significant predictor of outcomes in patients with invasive breast carcinoma of no special type (IBC‐NST) and to investigate, by comprehensive RNA sequencing analyses, the mechanisms involved in the heightened malignant potential of vimentin‐positive IBC‐NSTs. This study, conducted using the data of 855 patients with IBC‐NST, clearly identified vimentin expression status as a very important independent biological parameter for accurately predicting the outcomes in patients with IBC‐NST. RNA sequence analyses clearly demonstrated significant upregulation of coding RNAs known to be closely associated with cell proliferation or cellular senescence, and significant downregulation of coding RNAs known to be closely associated with transmembrane transport in vimentin‐positive IBC‐NSTs. We conclude that vimentin‐positive IBC‐NSTs show heightened malignant biological characteristics, possibly attributable to the upregulation of RNAs closely associated with proliferative activity and cellular senescence, and downregulation of RNAs closely associated with transmembrane transport in IBC‐NSTs. [ABSTRACT FROM AUTHOR]

The multi-day dynamics of the intensity of 40K decay fluctuations was compared with motor activity of laboratory mice, circulating cortisol in rabbits, and proliferation of fibroblast-like cultured cells L-929. A positive correlation was established between the intensity of decay fluctuations on the one hand, and total daily motor activity in mice and plasma cortisol level in rabbits, on the other hand. In addition, a negative correlation was observed between 40K decay fluctuations and proliferative activity of the cultured cells. Interestingly, these close correlations were observed not only against the background 4-day rhythm, but also in the time when any rhythmicity was absent. Thus, the intensity of 40K decay fluctuations is an indicator of a biotropic environmental factor that augments motor activity and raises the circulating cortisol in animals and down-regulates proliferation of cultured cells. [ABSTRACT FROM AUTHOR]

Propenylbenzenes, including isosafrole, anethole, isoeugenol, and their derivatives, are natural compounds found in essential oils from various plants. Compounds of this group are important and valuable, and are used in the flavour and fragrance industries as well as the pharmaceutical and cosmetic industries. The aim of this study was to develop an efficient process for synthesising oxygenated derivatives of these compounds and evaluate their potential biological activities. In this paper, we propose a two-step chemo-enzymatic method. The first step involves the synthesis of corresponding diols 1b-5b from propenylbenzenes 1a-5a via lipase catalysed epoxidation followed by epoxide hydrolysis. The second step involves the microbial oxidation of a diasteroisomeric mixture of diols 1b-5b to yield the corresponding hydroxy ketones 1c-4c, which in this study was performed on a preparative scale using Dietzia sp. DSM44016, Rhodococcus erythropolis DSM44534, R. erythropolis PCM2150, and Rhodococcus ruber PCM2166. Application of scaled-up processes allowed to obtain hydroxy ketones 1-4c with the following yield range 36-62.5%. The propenylbenzene derivatives thus obtained and the starting compounds were tested for various biological activities, including antimicrobial, antioxidant, haemolytic, and anticancer activities, and their impact on membrane fluidity. Fungistatic activity assay against selected strains of Candida albicans results in MIC50 value varied from 37 to 124 µg/mL for compounds 1a, 3a-c, 4a,b, and 5a,b. The highest antiradical activity was shown by propenylbenzenes 1-5a with a double bond in their structure with EC50 value ranged from 19 to 31 µg/mL. Haemolytic activity assay showed no cytotoxicity of the tested compounds on human RBCs whereas, compounds 2b-4b and 2c-4c affected the fluidity of the RBCs membrane. The tested compounds depending on their concentration showed different antiproliferative activity against HepG2, Caco-2, and MG63. The results indicate the potential utility of these compounds as fungistatics, antioxidants, and proliferation inhibitors of selected cell lines. [ABSTRACT FROM AUTHOR]

Controlled regeneration processes involving tissue growth using the surface and structure of scaffolds, are actively used in tissue engineering. Reactive magnetron sputtering is a versatile surface modification method of both metal and polymer substrates, as the properties of the formed coatings can be modified in a wide range by changing the process parameters. In magnetron sputtering, the working gas and its composition have an influence on the chemical composition and physical characteristics of the obtained coatings. However, there are no studies addressing the influence of the nitrogen/xenon gas mixture ratio in direct current magnetron sputtering on the deposition rate, physicochemical and in vitro properties of surface-modified biocompatible poly-L-lactic acid scaffolds. In this study, the application of mixtures of nitrogen and xenon in various ratios is demonstrated to modify the surface of non-woven poly-L-lactic acid scaffolds by direct current magnetron sputtering of a titanium target. It has been found that the magnetron sputtering parameters chosen do not negatively influence the morphology of the prepared scaffolds, but increase the hydrophilicity. Moreover, quantitative spectroscopic analysis results indicate that the formed coatings are primarily composed of titanium oxide and titanium oxynitride compounds and is dependent on the gas mixture ratio only to a certain extent. Atomic force microscopy investigations of the roughness of the fibers of the electrospun scaffolds and the thickness of the coatings formed on them show that the considerable variations observed in the intrinsic fiber reliefs are due to the formation of a fine layer on the fiber surfaces. The observed decrease in roughness after plasma modification is due to temperature and radiation effects of the plasma. In vitro experiments with human osteosarcoma cells show that the scaffolds investigated here have no cytotoxic effect on these cells. The cells adhere and proliferate well on each of the surface-modified electrospun scaffolds, with stimulation of cell differentiation in the osteogenic direction. [ABSTRACT FROM AUTHOR]

The main advantage of transformed cell lines as compared to primary ones is that they allow generation of the stable material suitable for long-term research and practical use. Therefore, development of new continuous cell cultures from various animal tissues is of great practical importance. Results of examination of transformed cell lines derived from organs of domestic pigs (Sus scrofa L.) for their biological, cytomorphological and karyological features are described in the paper. The said cell cultures are confirmed to be susceptible to various animal viruses. Also, a procedure for preparation of new diploid cell culture from porcine spleen (SSs – Splеen Sus scrofa) is described. Based on the obtained data analysis it was concluded that the epithelial cells derived from trypsinized porcine spleens could be successfully immortalized. All transformed cell lines of porcine origin have similar morphology with predominated epithelium-like forms. Some of them – SPEV, А4 С2 , RSK – tend to adopt a spherical shape in suspension. Such cell lines as PSGK-30 and PPES cell lines form partial multilayer or they are characterized by significant monolayer compaction with pseudosyncytium formation. Only pseudodiploid cell culture (SPEV cell culture) tends to grow in suspension, it also grows in rotating culture flasks. Karyological transformations in different cell cultures stabilized at certain level. Spontaneous increase in chromosome numbers in the main population of transformed cell lines towards triploidy resulted in stabilization of culture properties and increase in proliferation. PSGK-30 cell culture has the highest modal class – 64 chromosomes. Near-diploid cultures (А4 С2 , RSK) demonstrate stable growth properties and are similar to SPEV cell culture in adopting spherical cell forms in medium, monolayer character and cell morphology. PK-15 cell culture having a distinct karyotype under different cultivation conditions while retaining other culture properties is found to be the most adaptive. A new transformed diploid SSs cell culture is developed by long-term incubation, subcultivation (more than 80 passages) and selection at the FGBI “ARRIAH” laboratory; it can remain diploid or may spontaneously become heteroploid-immortalized during further passaging. The cell hyperploidy is very likely to enhance telomerase activity, which in turn stabilizes immortalization and results in proliferative activity increase The cell viability has been maintained so far by regular reseedings (split ratio – 1:2–1:3) performed 1–2 times a week.

The study’s aim was to investigate the S100A4-mediated mechanisms of the regulation of tumor cell proliferation and migration in the human triple-positive breast carcinoma cell line MCF-7 (TPBC) and triple-negative breast carcinoma cell line MDA-MB-231 (TNBC). The proliferative activity of TNBC more than doubled during the incubation in the conditioned medium of TPBC. Extracellular S100A4 dose-dependently decreased the proliferative response of TPBC. TPBC negatively impacted the growth of TNBCs during their co-culturing. TPBC significantly decreased the migration activity of the TNBC cells while the S100A4 intracellular level in the TNBC was also decreasing. The decrease in the S100A4 intracellular level occurred due to the protein’s monomeric form while the contribution of the dimeric form into the overall S100A4 concentration in TNBC cells increased 1.5-2-fold. The S100A4 pathway in the intercellular communication between TNBC and TPBCs also included the dexamethasone-sensitive mechanisms of S100A4 intra- and extracellular pools regulation.

Development of "indirect antioxidants" capable of activating redox-sensitive signaling systems, primarily the Keap1/Nrf2/ARE system, is a promising area of modern pharmacology. Among its chemical inducers is the hydrophilic monosubstituted monophenol sodium 3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonate (TS-13) that we have developed. The aim of this study was to investigate the antiproliferative activity of TS-13 against BT-474 tumor cells in vitro and acute oral toxicity in mice in vivo. The relationship between TS-13 concentration and the proliferative activity of BT-474 human breast ductal carcinoma cells was determined by the MTT test with calculation of IC50. The results were compared with the previously obtained data for the MCF-7 line and compared with the functional properties of cells based on the level of gene expression (in silico GSEA analysis). Acute toxicity in vivo was examined on 50 C57Bl/6y female mice, which had a solution of TS-13 in distilled water administered to them at various doses via an intragastric tube. LD50 obtained experimentally was compared with predicted in silico using the GUSAR web service. The IC50 value of TS-13 for BT-474 cells calculated from the equation of exponential approximation was 59.5 μM, which was 2.2 times less than previously obtained for MCF-7 cells. This may be due to functional differences between BT-474 and MCF-7 cells, as evidenced by the results of GSEA analysis. The LD50 value established in the experiments in vivo was 936 mg/kg body weight of mice. The obtained value satisfactorily corresponds to the predicted in silico (561 mg/kg), although in reality the compound turned out to be somewhat less toxic than could be expected based on its structure. The study of the acute toxicity of the new water-soluble monophenol TS-13 allows it to be assigned to hazard class 4 on the Hodge–Sterner scale (low-toxicity compounds) or to hazard class 3 according to GOST (State Standard) 12.1.007-76 (moderately hazardous substances). [ABSTRACT FROM AUTHOR]

Objective: To observe the morphology and growth pattern of the neural stem cells neural stem cells (NSCs) in hippocampus tissue, and to provide the basis for the extraction and culture of the NSCs. Methods: The NSCs were isolated from hippocampus tissue of the newborn SD rats. The morphology of the NSCs in hippocampus tissue was observed; flow cytometry was used to detect the purities of the NSCs in hippocampus tissue; immunofluorescence method was used to detect the expressions of Nestin and EdU proteins in the NSCs; the proliferative activities of the NSCs were analyzed by cell counting and CCK-8 methods. Results: On the 0 day of culture, the NSCs in hippocampus tissue were suspended in the culture medium with the form of single cells; on the 2nd day of culture, the NSCs in hippocampus tissue suspended in the culture medium and began to gather into the cell clumps with different sizes and irregular shapes; On the 8th day of culture, the neurospheres showed round or oval neurosphere with different sizes, and showed clear boundary without synapse. The purity of the NSCs in hippocampus tissue was 76. 50%－85. 40% On the 8th day of culture, the positive expression of Nestin in the cytoplasm of the NSCs was green, and the positive expression of EdU in the nucleus was red. The neurospheres were composed of the Nestin and EdU co-staining cells. the NSCs were at logarithmic growth period, and the proliferation abilities were high when cultured for 5－11 d. Conclusion: The proliferation ability of the NSCs is high; the purity of the NSCs is high on the 8th day of culture; the proliferation ability of the NSCs is high when cultured for 5－11 d. [ABSTRACT FROM AUTHOR]

THz radiation induces a variety of processes in cells and has attracted the attention of researchers in recent decades. Here, data on the effects of high-intensity terahertz (THz) radiation on human directly reprogrammed neural progenitor cells (drNPCs) and on neuroblastoma cells (SK-N-BE (2)) were obtained for the first time. The results demonstrated that the exposure of non-tumor and tumor cells to broadband (0.1–3 THz) THz pulses with the intensity of 21 GW/cm2 and the electric field strength of 2.8 MV/cm for 30 min induced neither a noticeable genotoxic effect nor a statistically significant change in the proliferative activity and cell differentiation. It was also shown that the combined effect of THz radiation and salinomycin, a promising antitumor agent, on neuroblastoma cells did not enhance the genotoxic effect of this antibiotic. However, further studies involving chemotherapy drugs and other exposure parameters are warranted to introduce this new concept into anti-tumor clinical practice and to enhance the efficacy of the existing approaches. [ABSTRACT FROM AUTHOR]

Recently, human mesenchymal stem cells (hMSc) have attracted a great deal of attention as potential therapeutic agents in the treatment of socially significant diseases. Despite substantial advances in stem-cell therapy, the biological mechanisms of hMSc action after transplantation remain unclear. The use of magnetic resonance imaging (MRI) as a non-invasive method for tracking stem cells in the body is very important for analysing their distribution in tissues and organs, as well as for ensuring control of their lifetime after injection. Herein, detailed experimental data are reported on the biocompatibility towards hMSc of heavily gadolinium-doped cerium oxide nanoparticles (Ce0.8Gd0.2O2−x) synthesised using two synthetic protocols. The relaxivity of the nanoparticles was measured in a magnetic field range from 1 mT to 16.4 T. The relaxivity values (r1 = 11 ± 1.2 mM−1 s−1 and r1 = 7 ± 1.2 mM−1 s−1 in magnetic fields typical of 1.5 and 3 T MRI scanners, respectively) are considerably higher than those of the commercial Omniscan MRI contrast agent. The low toxicity of gadolinium-doped ceria nanoparticles to hMSc enables their use as an effective theranostic tool with improved MRI-contrasting properties. [ABSTRACT FROM AUTHOR]

Background: Peripheral ameloblastoma is an extraosseous variant of ameloblastoma. We report a rare case arising in an extragingival location. Case Presentation: The patient was a 79-year-old man with a firm nodule in the right-side buccal mucosa. Imaging examinations showed a well-demarcated mass in the right masticator space (infratemporal fossa). The diagnosis of ameloblastoma was made from the biopsy specimen. After conservative tumor excision, the patient had no recurrence during the follow-up period of eight and a half years. The Ki-67 labeling index indicated the nonaggressive nature of the tumor. Conclusion: Conservative surgery is applicable to extragingival peripheral ameloblastomas. [ABSTRACT FROM AUTHOR]

In the present study, a series of novel Trp-Pro-Val containing peptides were prepared via solid-phase synthesis, and their structures were cyclized by a disulfide bridge, or modified by adding heterocycles of pyrazine, pyroglutamic acid, and 1,3,4-oxadiazoles to their N-terminus. These peptides were designed to antagonize gonadotropin-releasing hormone (GnRH)-receptor. Based on the detailed in vitro studies, incorporation of disulfide bond (peptide 1), the addition of pyroglutamate at the N-terminus (peptide 2), the addition of pyrazine at the N-terminus (peptide 3), and incorporation of GFRW to the N-terminus (peptide 5) were beneficial for inhibition of proliferation and induction of apoptosis in GnRH receptor-bearing cells including Hela and MCF-7 cell lines, whereas ineffective on Hep-G2 liver cancer and SW-48 colorectal adenocarcinoma cell lines devoiding of GnRH receptor. These results imply that the synthesized peptides 1, 2, 3, and 5 are GnRH antagonists and selective for GnRH receptors on the surface of tumor cells. [ABSTRACT FROM AUTHOR]

Aim To evaluate the relationship between numerical and categorical immunohistochemical score of Ki-67 and human epidermal growth factor of receptor 2 (HER2) with clinicopathological parameters of breast cancer (BC). Methods The study included 311 patients with invasive BC diagnosed at the Department of Pathology, School of Medicine in Sarajevo, Bosnia and Herzegovina, during the period 2015-2019. The expression level of Ki-67 and HER2 was detected by immunohistochemical analysis. Results The expression of Ki-67, as a numerical variable correlated significantly with tumour grade (p=0.025), progesterone receptor (PR) (p=0.034) and categorical score of HER2 (p=0.028). When Ki-67 was categorized into high (>14%) and low (≤14%) level groups, a statistically significant association was found between Ki-67 level groups and HER2 status (categorical and numerical) (p=0.001 and p=0.043, respectively), as well as significant negative linear correlation with PR (p=0.037). The expression of HER2, as a numerical variable, showed a statistically significant correlation with tumour grade (p=0.038), PR (p=0.025) and categorical Ki-67 (p=0.043). Categorical score of HER2 correlated significantly with age (p=0.025), histologic type (p=0.039), tumour grade (p=0.016), estrogen receptor (ER), (p=0.002) progesterone receptor (PR) (p=0.0001), and categorical and numerical value of Ki-67 (p=0.0001 and p=0.0001, respectively). Conclusion The results demonstrated that the categorical immunohistochemical score of HER2 provided a greater association with clinicopathological parameters than numerical score of BC. Furthermore, a slightly better correlation with clinicopathological parameters was shown by the numerical value than by the categorical score of Ki-67 by applying a cut-off value of 14%.

Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.

The dynamics of proliferative activity of the L-929 cell culture of mouse fibroblast-like cells in the phase of logarithmic growth was compared with some heliogeophysical parameters (Ap and ULF indexes of geomagnetic activity, vertical component of the interplanetary magnetic field, and intensity of fluctuations of secondary cosmic radiation estimated by the neutron monitoring near the Earth's surface). Among the considered heliogeophysical parameters, only the magnitude of fluctuations of minute-to-minute changes in the neutron monitor indicator reliably and negatively correlates with the rate of cell culture reproduction. Considering that the amplitude of secondary cosmic fluctuations is about 5%, which is 0.1% of the total ray flux, and proliferative activity varies in the range of 30-50%, the probability of a direct biotrophic effect of this physical factor is extremely low. It seems likely that proliferative activity of L-929 cell culture is directly affected by another environmental factor, the marker of which is the intensity of neutron counting rate fluctuations. [ABSTRACT FROM AUTHOR]

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Summary Introduction. Cellulose nanocrystals (CNCs) as attractive natural materials, have numerous applications in the biomedical field. Their unique biomechanical characteristics, surface chemistry, low cost and sustainable nature make them an engaging alternative to conventional materials and potentiate their use as progressive material. Therefore, it is critical to evaluate the cytocompatibility and immunomodulatory properties of nCNCs, which have not been completely explored. The objective of this study was to examine a dose-dependent effect of native (n)CNCs on cytotoxicity and proliferative activity of human peripheral blood mononuclear cells (PBMNCs) in vitro. Methods. PBMNCs, obtained from the healthy blood donors, were cultivated with nCNCs. Cell viability was analyzed by flow cytometry assay, while proliferative activity was determined by MTT, [3H]-thymidine uptake assay and detection of IL-2 production. Results. The cytotoxicity results suggested that no concentration of nCNCs (50-400 μg/ml) affected necrosis of PBMNCs, whereas apoptosis was induced by the highest concentration of nCNCs compared to control (p

Recently, human mesenchymal stem cells (hMSc) have attracted a great deal of attention as potential therapeutic agents in the treatment of socially significant diseases. Despite substantial advances in stem-cell therapy, the biological mechanisms of hMSc action after transplantation remain unclear. The use of magnetic resonance imaging (MRI) as a non-invasive method for tracking stem cells in the body is very important for analysing their distribution in tissues and organs, as well as for ensuring control of their lifetime after injection. Herein, detailed experimental data are reported on the biocompatibility towards hMSc of heavily gadolinium-doped cerium oxide nanoparticles (Ce0.8Gd0.2O2−x) synthesised using two synthetic protocols. The relaxivity of the nanoparticles was measured in a magnetic field range from 1 mT to 16.4 T. The relaxivity values (r1 = 11 ± 1.2 mM−1 s−1 and r1 = 7 ± 1.2 mM−1 s−1 in magnetic fields typical of 1.5 and 3 T MRI scanners, respectively) are considerably higher than those of the commercial Omniscan MRI contrast agent. The low toxicity of gadolinium-doped ceria nanoparticles to hMSc enables their use as an effective theranostic tool with improved MRI-contrasting properties.

We studied the dynamic of proliferative activity of cultured mouse transformed fibroblast-like L-929 cells in the logarithmic growth phase. During a long period (December 5-23, 2020), we revealed a 4-day rhythm of daily increase in the number of L-929 cells with an amplitude not lower than in a culture of embryonic fibroblast-like cells. Hence, the formation of the 4-day rhythm is not associated with the molecular mechanisms of inhibition of proliferation, which are absent in transformed cells. Daily thawing of samples of one culture over 17 days showed the presence of a 4-day rhythm synchronous between all thawed samples and the control cell culture. As deep freezing leads to the cessation of all life processes in cells, the formation of a 4-day rhythm of proliferative activity of cell culture is determined by an exogenous mechanism. [ABSTRACT FROM AUTHOR]

Functional activity is a basic concept of biology; however, instrumental methods of its determination are absent. The interrelation between bone marrow cell proliferative activity, as one of the functional activity parameters, the content of calcium, copper, and reactive oxygen species (ROS) in the cells, and the electrical conductivity of the cell culture was studied in young and old Wistar rats aged 3 and 20 months. We determined the electrical conductivity of the bone marrow cell cultures and parameters of bone marrow cells (proliferative activity and calcium, copper and ROS content). The bone marrow cells of old intact animals had higher proliferative activity in the primary culture as compared to that of young animals. The content of the 8 main morphological cell types in the young and old animals were similar, while the lymphocyte content was larger in the old animals. Content of ions in the bone marrow cell cultures of old animals as compared with that in young animals varied as follows: Content of calcium was 75 % higher, copper was 5 times lower, and ROS was 2.5 times lower. It was found that the conductivities of the pure culture medium and of that after the cultivation of the bone marrow cells in the nutrient medium were significantly different. It has been suggested that the electrical conductivity of biological media could be used as an integral characteristic of the ionic composition and structural organization of biological media. [ABSTRACT FROM AUTHOR]

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Two new nonimmortalized cell lines, MSC-PL-1 and MSC-PL-2, were established from different placenta regions of the same donor. Analysis of different characteristics was carried out at early (sixth) and late passages. In the course of long-term cultivation, significant interline differences in growth characteristics and replicative senescence were revealed. Karyotypic analysis showed that, at an early passage, both lines have a normal diploid karyotype with an insignificant number of nonclonal chromosomal rearrangements. MSC-PL-2 cells retain their normal karyotype at the late 15th passage. MSC-PL-1 cultured up to passage 14 in addition to nonclonal rearrangements acquired clonal rearrangements, one of which, X, add (X) (p22.3), was common for MSC-PL-1 cells during replicative senescence. Most cells exhibited high expression of CD44, CD73, CD90, and CD105 surface antigens, vimentin, and HLA-ABC and very low expression of CD34, CD45, and HLA-DR antigens. It was shown that these cells at an early passage have the ability to differentiate in the osteogenic, chondrogenic and adipogenic directions. During the replicative senescence, adipogenic differentiation disappears in MSC-Pl-1 cells, while in the MSC-Pl-2 line, it significantly decreased. Reverse transcription polymerase chain reaction analysis showed a correlation between the level of adipogenic differentiation and the transcriptional activity of the glut4 gene. RT-PCR analysis of nse expression showed a low potency of cells of both lines for neuronal differentiation. It is assumed that the main reason for interline differences lies in the physiological characteristics of the organ region from which the cells were derived. [ABSTRACT FROM AUTHOR]

Objectives: to provide a rationale for existing approaches for the evaluation of chemoresistance of ovarian cancer in vitro, to perform a comparative analysis of the methods and to assess the perspectives of their further application.Materials and methods. For the review preparation, we analyzed articles on experimental testing of ovarian cancer resistance to chemotherapeutic agents, available at biomedical literature databases SciVerse Scopus (158), PubMed (323), Web of Science (285), RSCI (64). The review cited 37 recent publications, 12 of them being published over the past three years, and 16 articles being referred as pioneer publications on techniques previously and used today.Results. Peculiarities of the main methods for assessing the resistance and sensitivity of a cancer to various chemotherapeutic drugs using primary cultures of tumor cells obtained from biopsy or surgical material are analyzed. Proliferative and metabolic activities as well as the level of cell death were considered as the main evaluated characteristics of tumor cells. The methodological features of the described methods are discussed, as well as the prospects for their further application.Conclusion. Predictive detection of chemoresistance of ovarian cancer is based on testing the viability of tumor cells in the presence of a chemotherapeutic drug. The results of studies of the key mechanisms of chemoresistance development in tumor cells provide the rationale for improving in vitro testing.

Abstract Background The category of grade 3 neuroendocrine tumor (NET G3) was newly introduced in the 2017 World Health Organization (WHO 2017) classification of neuroendocrine neoplasms of the pancreas. Pancreatic NET G3 shows a carcinoid-like morphology with high proliferative activity and the prognosis is intermediate between NET G2 and neuroendocrine carcinoma. There is no category corresponding to NET G3 in the current WHO 2015 classification of lung tumors. Herein, we report two cases of lung neuroendocrine carcinoma with carcinoid morphology that correspond to NET G3. Case presentation Case 1: An abnormal chest shadow was detected in a 78-year-old female never-smoker during a routine medical examination. She was asymptomatic. The radiological assessment revealed a mass in the peripheral S4 segment of the right lung. She underwent right middle lobectomy for the mass preoperatively diagnosed as non-small cell lung carcinoma. Postoperative histological examination revealed a neuroendocrine tumor with carcinoid morphology and a mitotic count of 15/2 mm2. Case 2: An abnormal chest shadow was detected in a 74-year-old female never-smoker undergoing follow-up for another disease. She was asymptomatic. The radiological assessment revealed a mass in the peripheral S3 segment of the right lung. She underwent right upper lobectomy for the mass suspected to be lung carcinoma. Postoperative histological examination revealed a neuroendocrine tumor with carcinoid morphology with mitotic count of 13/2 mm2. Both of these tumors showed carcinoid morphology but with a mitotic count exceeding 10/2 mm2; thus, we diagnosed them as small cell lung carcinomas according to the current WHO 2015 classification. Conclusions Our tumors occurred in female never-smokers and their histology showed carcinoid morphology without extensive necrosis. Moreover, proliferative abilities of them were extremely low compared to small cell lung carcinoma. The clinical and pathological features of our tumors appeared to be different from those of small cell lung carcinoma. Although there is no category corresponding to NET G3 in the current classification of lung tumors, we consider that our tumors may correspond to NET G3 and identification of this subset is relevant for therapeutic management.

Purpose of the study. Improvement of the results of treatment of patients with arteriovenous forms (AVF) of congenital vascular malformations (CVM) of the extremities based on the development of the classification scheme of CVM and the study of proliferative activity of the pathology. Materials and methods. The clinical data of 155 patients with AVF of CVM of extremities were analyzed in terms of observation from 1 month to 10 years. Patients of sex of men there were 65 (42%), women – 90 (58%), their correlation – 1 : 1,4; the average age was about 25,1 ± 10,4, children's age group – 53 (34%). The division into clinicalanatomical forms (11 groups) was carried out on the basis of the «working» classification scheme «VASC + T». Expression proliferation markers VEGF and KI-67 woos study were performed by immunoperoxidase method with additional hematoxylin staining. Results and discussion. Pathomorphological (66; 45,8%) and immunohistochemical studies (10; 7%) revealed the presence of proliferative activity of angiomatous tissues and degenerative changes in the walls of the vessels both due to developmental defects and disorders of hemodynamics, while the source of progression of the AVF of CVM there are vessels of the microvasculature. Conclusions. The application of the CVM classification scheme and the step-by-step complex treatment approach, depending on the clinical and anatomical AVF of CVM, led to the absence of major postoperative complications. This tactic made it possible to achieve satisfactory long-term results in 136 (94,4%) cases.

Comprehensive study of the biological activity of structural components and metabolites of “beneficial” microorganisms opens the prospects of efficient and rational use of their biotechnological potential in the correction of microecological and related disorders. The study tested proliferative activity and biofilm formation by Bifidobacterium bifidum probiotic strain under the influence of cell-free extracts containing structural components and metabolites of the probiotic strains of B. bifidum and Lactobacillus reuteri. Cell-free extracts were obtained by disintegrating suspensions of probiotic cells by cyclic freezing-thawing, cultivating probiotic microorganisms in their own disintegrates and subsequent filtration of the obtained disintegrates and cultures. The proliferative activity and biofilm formation of the probiotic test culture were studied by spectrophotometric microtiter plate method with 10%vol, 30%vol and 50%vol content of cell-free extracts in the cultivation medium. All investigated extracts showed a significant concentration-dependent stimulatory effect on the proliferative activity of B. bifidum. According to the degree of stimulatory effect on the B. bifidum proliferation, cell-free extracts arranged in ascending order: MLG (filtrate of L. reuteri culture, grown in L. reuteri disintegrate supplemented with 0.8 M glycerol and 0.4 M glucose) < MB (filtrate of В. bifidum culture, grown in В. bifidum disintegrate) < B (filtrate of В. bifidum disintegrate) < ML (filtrate of L. reuteri culture, grown in L. reuteri disintegrate) < L (filtrate of L. reuteri disintegrate). With the same content in the culture medium, filtrates of disintegrates had a more pronounced stimulatory effect than filtrates of cultures grown in their own disintegrates. Cell-free extracts from L. reuteri (L and ML) exerted a more pronounced stimulatory effect than cell-free extracts from B. bifidum. Not all studied cell-free extracts stimulated the biofilm formation by B. bifidum. The effect of cell-free extracts on this process depended on their type and concentration. Extract L had a predominantly inhibitory effect on biofilm formation by B. bifidum. The most pronounced stimulatory effect on biofilm formation by B. bifidum came from extract MLG. ML, B and MB extracts stimulated this process approximately equally. The detection of significant bifidogenic effect of the studied cell-free extracts may contribute to their pharmaceutical applications. Cell-free extracts can be used as metabiotics or prebiotics for increasing the survival of the injected probiotic, facilitating its inoculation in the gastrointestinal tract when used together. The obtained data encourage further careful study of the biochemical composition of cell-free extracts and efforts to clarify the mechanism of their action.

Background: Similar to poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma with high-grade features (PTC HGF) demonstrates increased mitotic activity and/or necrosis; however, PTC HGF is excluded from the World Health Organization (WHO) definition of PDTC based on maintained nuclear features of PTC. Methods: Consecutive tumors that met criteria for PTC HGF, defined as tumors with maintained nuclear features of PTC and mitoses numbering 5 or more per 10 contiguous high-power fields and/or tumor necrosis, and PDTC (defined as per the WHO criteria) were identified. Clinicopathologic characteristics, follow-up data, and targeted next-generation sequencing results were compared between groups. Results: There were 15 PTC HGF and 47 PDTC. PTC HGF was associated with a higher rate of pT4 disease (53% vs. 13%, p = 0.0027) and lymph node metastases (73% vs. 38%, p = 0.049). The disease-specific survival was worse for patients with PTC HGF compared with those with PDTC using Kaplan–Meier estimation (p < 0.001) and was worse in subgroup analysis evaluating patients with widely invasive PDTC (i.e., those with a similar rate of pT4 disease) and PTC HGF (p = 0.040). PTC HGF had a higher BRAFV600E mutation rate (42% vs. 3%; p = 0.003), a trend toward more gene fusions (25% vs. 3%; p = 0.052), and a higher rate of relative gain of 1q (67% vs. 15%; p = 0.002) than PDTC. Conclusions: Our results demonstrate that PTC HGF are important to recognize based on their aggressive behavior. The molecular differences between PTC HGF and PDTC suggest that PTC HGF should be considered a distinct group from PDTC. [ABSTRACT FROM AUTHOR]

Aim To evaluate the relationship between numerical and categorical immunohistochemical score of Ki-67 and human epidermal growth factor of receptor 2 (HER2) with clinicopathological parameters of breast cancer (BC). Methods The study included 311 patients with invasive BC diagnosed at the Department of Pathology, School of Medicine in Sarajevo, Bosnia and Herzegovina, during the period 2015-2019. The expression level of Ki-67 and HER2 was detected by immunohistochemical analysis. Results The expression of Ki-67, as a numerical variable correlated significantly with tumour grade (p=0.025), progesterone receptor (PR) (p=0.034) and categorical score of HER2 (p=0.028). When Ki-67 was categorized into high (>14%) and low (=14%) level groups, a statistically significant association was found between Ki-67 level groups and HER2 status (categorical and numerical) (p=0.001 and p=0.043, respectively), as well as significant negative linear correlation with PR (p=0.037). The expression of HER2, as a numerical variable, showed a statistically significant correlation with tumour grade (p=0.038), PR (p=0.025) and categorical Ki-67 (p=0.043). Categorical score of HER2 correlated significantly with age (p=0.025), histologic type (p=0.039), tumour grade (p=0.016), estrogen receptor (ER), (p=0.002) progesterone receptor (PR) (p=0.0001), and categorical and numerical value of Ki-67 (p=0.0001 and p=0.0001, respectively). Conclusion The results demonstrated that the categorical immunohistochemical score of HER2 provided a greater association with clinicopathological parameters than numerical score of BC. Furthermore, a slightly better correlation with clinicopathological parameters was shown by the numerical value than by the categorical score of Ki-67 by applying a cut-off value of 14%. [ABSTRACT FROM AUTHOR]

A communal disease of the breast is breast cancer which happens mainly in women. Breast cancer is the most common cancer in women in both the developed and less developed world. The potential biological aggressiveness and behavior of breast neoplasm are of prognostic significance in tumor pathology and this can be assessed by measuring the tumor proliferative activity and malignant transformation. One of such markers is AgNOR (Argyrophilic Nuclear Organizer Region). A search of database sites such as PUBMED, Google Scholar, and Web of Science, as well as, other sources of literature available across public libraries was conducted to obtain information related to the topic. This review has presented a critical discussion on histologically assessing the proliferative activity of various grades and types of breast carcinoma using AgNOR expression and its prognostic significance. This exposé is anticipated to enlighten research scientists on specific management and assessing targets of tumors, which may merit prospective research into developing an appropriate mechanism for assessing the proliferative activity of breast cancer to help solve medical issues relating to cancers. [ABSTRACT FROM AUTHOR]

Multi-layer graphene (2–10 layers), also called graphene nanoplatelets (GNPs), is a carbon-based nanomaterial (CBN) type with excellent properties desirable for many biomedical applications. Despite the promising advantages reported of GNPs, nanoscale materials may also present a potential hazard to humans. Therefore, in this study, the in vivo toxicity of these nanomaterials at a wide range of concentrations from 12.5 to 500 µg/mL was evaluated in the Caenorhabditis elegans model for 24 h (acute toxicity) and 72 h (chronic toxicity). Furthermore, their in vitro toxicity (from 0 to 10 µg/mL for 12 and 24 h), proliferative activity at 72 and 96 h, and their effect on the expression of thirteen genes in human keratinocytes HaCaT cells were studied. The physico-chemical and morphological aspects of the GNPs used in this study were analyzed by Raman scattering spectroscopy, electron microscopy, zeta potential as a function of pH, and particle size measurements by dynamic light scattering. The results of this study showed that GNPs showed in vivo non-toxic concentrations of 25 and 12.5 µg/mL for 24 h, and at 12.5 µg/mL for 72 h. Moreover, GNPs present time-dependent cytotoxicity (EC50 of 1.142 µg/mL and 0.760 µg/mL at 12 h and 24 h, respectively) and significant proliferative activity at the non-toxic concentrations of 0.005 and 0.01 μg/mL in the HaCaT cell line. The gene expression study showed that this multi-layer-graphene is capable of up-regulating six of the thirteen genes of human keratinocytes (SOD1, CAT, TGFB1, FN1, CDH1, and FBN), two more genes than other CBNs in their oxidized form such as multi-layer graphene oxide. Therefore, all these results reinforce the promising use of these CBNs in biomedical fields such as wound healing and skin tissue engineering.

Abstract Background Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. Results Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. Conclusions Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.

Проблематика. Культивування культур клiтин на синтетичних покриттях дає можливість отримати комплексну просторово організовану клітинну систему, що підвищує прикріплення клітин і сприяє їх подальшій диференціації, проліферації та формуванню мiжклiтинного матриксу. Тому виникає потреба у вивченні властивостей покриттів, зокрема біосумісності з клітинами, оскільки вони можуть бути використанні для різних біологічних і медичних досліджень. Мета. Завданням наших досліджень є вивчення впливу наноповерхонь, модифікованих AПТЕСом, декстраном, альбуміном та їх композиціями, на проліферативну і метаболічну активність клітин B16F10. Методика реалізації. У дослідженні використовували клітини лінії B16F10, які культивували на живильному середовищі ДМЕМ із додаванням 10 % ЕТС, 1 % пеніциліну та стрептоміцину в атмосфері з вмістом 5 % CO2 при 37 °C упродовж 72 год. Клітини висівали на скельця, модифіковані наношарами у різних комбінаціях: контрольна група – скло; скло/APTES; cкло/APTES/декстран; скло/APTES/альбумін; скло/альбумін; скло/APTES/декстран/альбумін. Вплив покриттів на проліферативний ріст і життєздатність культури оцінювали кожні 24 год культивування. Для визначення активності лактатдегідрогенази кондиційне середовище відбирали на 24, 48 та 72-гу год культивування. Результати. Висока життєздатність та інтенсивність проліферативного росту клітин спостерігались при культивуванні на поверхнях, модифiкованих АПТЕСом, альбуміном, АПТЕС/декстран/альбуміном. Підвищення проліферації клітин B16F10, вирощених на нанопокриттях з альбуміном (P < 0,001) та АПТЕС/декстран/альбуміном (P < 0,001), відзначено на 48 та 72-гу год культивування, на відміну від контролю та інших дослідних груп. При культивуванні на покритті з АПТЕСом кількість клітин зростала, на відміну від клітин на поверхні скелець, тільки на 72-гу год культивування. Висновки. Досліджувані наноповерхні, модифіковані альбуміном і АПТЕС/декстран/альбуміном, покращують життєздатність та проліферацію клітин лінії B16F10 та можуть бути використані як 3D-системи для вирощування клітин різних типів.

Objective: lymph node metastases occur in 90% of cases in patients with gastric adenocarcinoma, and survival is less than 15% in the late stages of disease. Therefore, the purpose of the study was to screening markers for predicting the likelihood of metastases developing in gastric adenocarcinoma. Materials and methods: for the study 47 patients with diagnosis of gastric adenocarcinoma were used (with the localized tumor form T3-4N0M0 (n = 18) and the locally distributed form T3-4N1-3M0 (n = 29)). The copy number variation of 16 genes (APC, AURKA, CCND1, C-MYC, GKN1, HER2, IRX1, MDM2, MET, NFKB, OCT1, P53, PIK3CA, POU5F1B, S6K2 and HV2) was determined by RT-PCR. Immunohistochemical studies were performed on sections of paraffin blocks using monoclonal antibodies to p53, Bcl-2, Ki-67 and Her2. Results: the loss of duplicity of HV2 locus was most frequent CNV in samples of stomach adenocarcinoma, but CNV significant change in the T3-4N0M0 group relative to T3-4N1-3M0 was not detected. A significant increase of CNV in the T3-4N1-3M0 group relative to T3-4N0M0 was found in 2 of 16 loci - NFKB and HER2 in 1.75 and 1.90 times (p

The biologic behavior of the oral lesions can be determined by their active phases of cell division, cells entering the cell cycle and their proliferation. AgNORs (argyrophilic nucleolar organizer regions) staining is the one of the cytochemical technique used to evaluate the cell proliferation of oral lesions. Tumor cells in premalignant and malignant conditions usually exhibits a rise in synthesis of abnormal proteins and proportionately there is a increase in the AgNOR material. The aim of this study was to review the concepts of proliferative activity of cells of malignant and premalignant conditions through the AgNORs staining procedure and thereby proving the usefulness of AgNORs in diagnosing the oral lesions. [ABSTRACT FROM AUTHOR]

We studied daily dynamics of proliferative activity of embryonic fibroblast-like cells in culture during the logarithmic growth phase. Daily increase in cell count in the culture showed a 4-day rhythm that persisted over 3 weeks of culturing. In cultures from different animals, the phase of this rhythm was synchronous and did not depend on the moment of cell isolation. It can be hypothesized that the 4-day biorhythm of proliferative activity of embryonic fibroblast-like cells in culture is determined by external environmental factors, probably of electromagnetic nature. [ABSTRACT FROM AUTHOR]

We studied the effect of algae pigment fucoxanthin on proliferative activity of melanocyte culture from human skin. Fucoxanthin in high concentrations can be cytotoxic, which was confirmed by changes in melanocyte morphology and a decrease in their proliferative activity. [ABSTRACT FROM AUTHOR]

Background: Pathogenic CD4+CD28null cells are characterized by inflammatory cytokine synthesis and tropism to the inflamed tissues. Recent studies showed the involvement of CD28null T cells in a severe clinical outcome of lupus. However, their role in moderately active disease is still unresolved. Methods: We examined the levels of circulating CD4+CD28null cells and CD8+CD28null suppressor T cells. We also compared the CD4+CD28null and CD4+CD28+ T-cell functional properties, including the expression of interferon gamma (IFN-γ) and Ki67 among systemic lupus erythematosus (SLE) patients (n = 20) and healthy controls (n = 20). All the patients were under immunosuppressive treatment and exhibited moderate SLE activity (median SLE Disease Activity Index (SLEDAI) = 6). Results: In patients, we found elevated CD4+CD28null and unchanged levels of suppressor CD8+CD28null T cells. There was no difference between patients and controls in IFN-γ and Ki67-expressing CD4+, CD4+CD28+, and CD4+CD28null T cells, except for higher IFN-γ levels in CD4+CD28+ T cells in SLE. In each studied group, we observed a higher preponderance of IFN-γ- and Ki67-expressing cells among CD4+CD28null T cells and lower levels of IFN-γ in CD4+CD28null T cells compared to the CD28+ subset. Similarly, Ki67 intensity was decreased in healthy CD4+CD28null cells, whereas in patients, comparably high expression was observed in both subsets. IFN-γ intensity in CD4+CD28null T cells correlated with SLEDAI. Conclusion: SLE with a moderately active clinical course is characterized by peripheral blood expansion of CD4+CD28null T cells and a normal abundance of suppressor CD8+CD28null T cells. The demonstration that these pathogenic CD4+ T cells, despite the lack of CD28, maintain the ability to produce pro-inflammatory IFN-γ positively correlated with disease activity as well as relatively high proliferative capacity may suggest their potentially predictive role in SLE flares. [ABSTRACT FROM AUTHOR]

Thymus species has been used for antioxidant, antiseptic, antitussive, carminative, anti-inflammatory and antimicrobial activities as well as tonic and herbal teas. The present study was conducted to evaluate antioxidant, antimicrobial and proliferative properties of ethanol crude extract and fractions of Thymus spathulifolius (Hausskn. and Velen.) herbes. The antioxidant properties of ethanol extracts and fractions of Thymus spathulifolius were investigated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, ferrous chelating activity, total flavonoid and total phenolic content analysis. Antimicrobial activity of the plant extracts were tested using the microdilution method, while proliferative activity were evaluated by MTT assay. Results showed that IC50 of T. spathulifolius extracts that scavenged 50% of the DPPH radical was found to be ranged from 62.39 to 1000 µg/mL. Hexane extract possessed moderate antimicrobial activity towards gram-positive bacteria of S. aureus and fungi of C. albicans. S. aureus was the most sensitive bacteria than other tested microorganisms. The hexane and water extracts exhibited a good proliferative activity with ED50 of 3.28 µg/mL and 2.77 µg/mL, respectively. The antioxidant and antimicrobial activities, together with the ability of proliferation, provide some support for the T.spathulifolius’s traditional use.