N-Glycoside of Indolo[2,3-]pyrrolo[3,4-]carbazole LCS1269 Exerts Anti-Glioblastoma Effects by G2 Cell Cycle Arrest and CDK1 Activity Modulation: Molecular Docking Studies, Biological Investigations, and ADMET Prediction.

Indolo[2,3-]pyrrolo[3,4-]carbazole scaffold is successfully used as an efficient structural motif for the design and development of different antitumor agents. In this study, we investigated the anti-glioblastoma therapeutic potential of glycosylated indolocarbazole analog LCS1269 utilizing in vitro, in vivo, and in silico approaches. Cell viability was estimated by an MTT assay.

Corrigendum: Patients with microscopic colitis have altered levels of inhibitory and stimulatory biomarkers in colon biopsies and sera compared to non-inflamed controls.

[This corrects the article DOI: 10.3389/fmed.2021.

Strength and Electrical Properties of Cementitious Composite with Integrated Carbon Nanotubes.

The main objective of this work was to study the effects of carbon nanotubes (CNTs) on the strength and electrical properties of cement mortar. Molecular dynamic simulations (MDSs) were carried out to determine the mechanical and electrical properties of a cementitious composite and its associated mechanisms. To model the atomic structure of a calcium silicate hydrate (C-S-H) gel, tobermorite 11Å was chosen.

A novel glycosylated indolocarbazole derivative LCS1269 effectively inhibits growth of human cancer cells in vitro and in vivo through driving of both apoptosis and senescence by inducing of DNA damage and modulating of AKT/mTOR/S6K and ERK pathways.

In recent decades, indolocarbazole glycosides containing sugar moieties have attracted attention due to their diverse anti-tumor activities. In the present study, a series of new indolo [2,3-a]pyrrolo [3,4-c]carbazole derivatives were synthesized for the first time. First of all, we have shown that compound 6e (LCS1269) had the most pronounced effect on inhibiting tumor growth in the transferable solid and non-solid murine tumors as compared with other synthesized indolocarbazole derivatives.

Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls.

Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients. To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.

Inhibition of FGF2-Mediated Signaling in GIST-Promising Approach for Overcoming Resistance to Imatinib.

Inhibition of KIT-signaling is a major molecular target for gastrointestinal stromal tumor (GIST) therapy, and imatinib mesylate (IM) is known as the most effective first-line treatment option for patients with advanced, unresectable, and/or metastatic GISTs. We show here for the first time that the inhibition of KIT-signaling in GISTs induces profound changes in the cellular secretome, leading to the release of multiple chemokines, including FGF-2. IM increased migration, invasion, and colony formation of IM-resistant GISTs in an FGF2-dependent manner, whereas the use of blocking anti-FGF2 antibodies or BGJ398, a selective FGFR inhibitor, abolished these effects, thus suggesting that the activation of FGF2-mediated signaling could serve as a compensatory mechanism of KIT-signaling inhibited in GISTs.

[Features of the Structure and Expression of NPM and NCL Genes in Cutaneous Melanoma].

Malignant cutaneous melanoma (CM) is an extremely aggressive cancer characterized by a high level of metastatic activity and unfavorable prognosis due to a high incidence of relapses, as well as resistance to standard chemotherapy. Cutaneous melanoma accounts for 80% of deaths from malignant skin tumors. Nucleolin/C23 and nucleophosmin/B23, which constitute altogether ~70% of the nucleolus volume, are promising targets for molecular therapy of melanoma.

[ Spectrum of oncogene mutations is different in melanoma subtypes].

Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma.

Pathomorphological analysis of internal endometriosis.

We performed clinical and morphological examination of 59 women with internal endometriosis (adenomyosis). Women were found to develop adenomyosis more frequently in the perimenopausal period (in their 40s) after repeated abortions and diagnostic surgical procedures. In 90% patients, adenomyosis was associated with the formation of multiple leyomyomatous nodules; glandular hyperplasia of the endometrium and fibrocystic transformation or fibrous degeneration of the ovaries were found in 60 and 100% cases.

[Pathomorphism of tuberculous pleurisy in elderly and senile individuals].

The pathomorphism of tuberculous exudative pleurisy in elderly and senile individuals has been investigated in the past 30 years. Comparison of clinical, X-ray, laboratory, morphological, and immunological data in patients of the first (1978-1987) and second (1998-2007) periods has revealed the signs characteristic of the negative pathomorphism of the disease: progressive latency of tuberculous pleurisy and a lower Mantoux reaction, a lower detection rate for epithelioid giant-cell granulomas in the patients' biopsy specimens, a higher rate of pleural tuberculous inflammation, an increased frequency of comorbidity, a higher drug resistance rate in Mycobacterium tuberculosis, and decreased therapeutic efficiency. In this connection, elderly and senile persons with pleural effusion should be examined in a tuberculosis dispensary, with the bacteriological and morphological verification of the diagnosis being made.

[The specific features of immunity and immunological responsiveness in elderly and senile patients with tuberculous pleurisy].

The paper gives the results of immunological and clinical studies made in 162 elderly and senile patients with tuberculous exudative pleurisy and a control group of 162 tuberculous pleurisy aged 20-40 years. The elderly and senile patients were found to have more significant immunological responsiveness impairments, suppressed T-cell immunity, and inhibited pleural granulomatous reactions than in the young patients. These alterations substantially worsen the course and outcome of the disease and require im munological correction.

[Tuberculous pleurisy in elderly and senile persons: its clinical picture and diagnosis].

The timeliness of detection and clinical manifestations were analyzed in 132 patients aged 60 to 92 years who had tuberculous exudative pleurisy (TEP). In this age group, TEP was encountered twice more frequently seen than in young patients, concurrent with active pulmonary tuberculosis, and, in 33% of cases, attended by bacterial isolation. The obliterated picture, a mild response to the Mantoux test, X-ray features, and significant comordibity make the diagnosis difficult.

[The possibility of the retroviruses participation in human breast neoplasm induction].

The existence of retrovirus related to murine mammary tumor virus (MMTV) and specifically associated with mammary carcinoma has been suggested long ago. This review covers some papers published in the 70-80ies until now, containing evidence for this suggestion. In spite of a lack of direct proof of virus existence this problem still remains to be solved.

[Effect of 5-azacytidine on expression of DNA sequences homologous to ENV gene of murine mammary tumor virus in normal human lymphocytes].

Expression of DNA sequences, related to MMTV env gene, in peripheral blood lymphocytes, which was strictly specific for human mammary carcinoma, has been previously reported. These sequences (homologous to env gene site coding for MMTV gp52 envelope antigen) expressed in T cells can play the key role in virus infection transmission and propagation. In order to elucidate the possible routes of env MMTV-homologous sequences expression, we tried to induced it in donot T lymphocytes by various methods: hormone and virus treatment (related genome "saving" at the expense of the added virus envelope), T cell culturing with conA, interferon-2, and 5-azacytidine.

[An antigen related to the mouse mammary cancer virus env gene product, detected in human lymphocytes, is associated with human breast cancer].

Expression of DNA sequences homologous to sequences of env gene of mouse mammary tumor virus (MMTV) in the lymphocytes of patients with breast cancer and in subjects at a high risk of breast cancer has been reported. Antigen analogous to envelope protein gp52, product of MMTV env gene, is detected in T lymphocytes of virtually all patients with breast cancer and extremely rarely in T cells of controls, where its expression is confined to B cells. For explaining such unexpected results, we studied the molecular basis of this antigen synthesis.

[Correlation between expression of antigen immunologically related to gp52 MMTV and transcription of homologous ENV MMTV DNA sequences in peripheral blood lymphocytes from breast cancer patients].

Previously we reported that HMCAg related to gp52, env product of MMTV, was a specific marker of human breast cancer (BC). This antigen was expressed not only in BC tissue and patients' sera, but in peripheral T- and B-cells. HMCAg was found in 21.

Dialect-I, species-specific repeated DNA sequence from barley, Hordeum vulgare.

Dialect-1, species-specific repetitive DNA sequence of barley Hordeum vulgare, was cloned and analysed by Southern blot and in situ hybridization. Dialect-1 is dispersed through all barley chromosomes with copy number 5,000 per genome. Two DNA fragments related to Dialect-1 were revealed in λ phage library, subcloned and mapped.