Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7) and normal (MCF10A) cell lines. Antitumor effect was established by МТТ cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay) and analysis of morphological cell changes (Fluorescence microscopy). The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 μg/ml). Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration.The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential

STK11 gene mutations among patients with sporadic breast cancer

Germline mutations affecting STK11 (LRG_319) are profoundly studied in relation to Peutz-Jeghers syndrome, predisposing to the development of various cancers at multiple sites. Though somatic mutations in STK11 are found to be present in several cancers, limited data on its involvement in sporadic breast cancer are available. The present study aims to evaluate the frequency and spectrum of genetic alterations in STK11 in a group of Bulgarian patients with sporadic breast cancer. A total of 73 tumor and 22 corresponding blood specimens derived from the patients, and 10 blood samples from clinically healthy controls were analyzed. High Resolution Melting analysis followed by Sanger sequencing and bioinformatic prediction tools were utilized. Seven patients (9.58%) harbored STK11 alterations, only two (2.74%) of which are exonic: one nonsense c.322A>T; p.K108X (deleterious) and one missense c.440G>A; p.Arg147His (of unknown significance). Two intronic variants were also observed: c.290+36G>T and c. *16+18C>A (novel). To our knowledge the results represent the first data indicating presence of STK11 alterations in patients with sporadic breast cancer. The limited number of the detected deleterious mutations indicates that mutational inactivation of the gene is a rare event and probably plays a minor role in sporadic breast carcinogenesis

Newly Synthesized Lignin Microparticles as Bioinspired Oral Drug-Delivery Vehicles: Flavonoid-Carrier Potential and In Vitro Radical-Scavenging Activity

The aim of the present study was to synthesize lignin microparticles, to evaluate their physicochemical, spectral, morphological and structural characteristics, to examine their encapsulation and in vitro release potential and behaviour towards the flavonoid morin in simulated physiological medium and to assess the in vitro radical-scavenging potential of the morin-loaded lignin microcarrier systems. The physicochemical, structural and morphological characteristics of alkali lignin, lignin particles (LP) and morin-encapsulated lignin microparticles (LMP) were determined based on particle size distribution, SEM, UV/Vis spectrophotometric, FTIR and potentiometric titration analyses. The encapsulation efficiency of LMP was 98.1%. The FTIR analyses proved that morin was successfully encapsulated in the LP without unexpected chemical reactions between the flavonoid and the heteropolymer. The in vitro release performance of the microcarrier system was successfully mathematically described by Korsmeyer–Peppas and the sigmoidal models outlining the general role of diffusion during the initial stages of the in vitro release process in simulated gastric fluid (SGF), and the predominant contribution of biopolymer relaxation and erosion was determined in simulated intestinal medium (SIF). The higher radical-scavenging potential of LMP, as compared to that of LP, was proven via DPPH and ABTS assays. The synthesis of lignin microcarriers not only provides a facile approach for the utilization of the heteropolymer but also determines its potential for the design of drug-delivery matrices

Antiviral, Cytotoxic and Antioxidant Effects of Tanacetum Vulgare L. Crude Extract In Vitro

Introduction: Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of Tanacetum vulgare L. against viral strains of three taxonomic groups, including agents that cause socially significant diseases in humans for which antiviral chemotherapy is indicated, namely coxsackievirus B1 (family Picornaviridae), herpes simplex virus type 1 (family Herpesviridae) and influenza A virus (family Orthomyxoviridae). Aim: The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant Tanacetum vulgare L. against some important human viruses for which antiviral chemotherapy is needed and to characterize extract for its antioxidant activity in vitro. Materials and methods: The crude aqueous ethanolic extract from aerial parts of Tanacetum vulgare L. contained flavonoids determined as apigenin, coumarins determined as aesculin, tannic compounds determined as tannin, and others. Antiviral activity of ethanolic extract from herbaceous plant Tanacetum vulgare L. against coxsackievirus B1, influenza A and herpes simplex virus type 1 was evaluated by viral yield reduction technique. The total antioxidant activity was determined by measuring the capacity of the sample to inhibit the generation of thiobarbituric acid reactive substances (TBARS). Results: The results show that the extract has the lowest toxicity on the MDBK cell line and similar cytotoxicity in Hep-2, whereas in the MDCK cells it has more than twice the highest toxicity. Testing the antiviral activity of Tanacetum vulgare L. extract revealed a slight inhibition of replication of HSV-1 with a selective index of 7.07 and IAV/H3N2 (SI = 3.69) but no specific antiviral effect against CVB1 replication was found. The evaluation of the antioxidant activity showed great antioxidant activity of the ethanolic extract from T. vulgare – 26 mmol/l for the applied 20 mg/ml extract. Conclusion: The crude extract from aerial parts of the medicinal plant Tanacetum vulgare L. demonstrated low cytotoxicity in Hep-2, MDBK and moderate cytotoxic effects in MDCK cells. It exerted significant antiviral activity against HSV-1 as determined by the recorded inhibition of viral replication, the blockage of virus entry - absorption stage and direct virucidal effects on extracellular virions. The observed effect when testing Tanacetum’s extract on influenza A H3N2 virus infection in vitro was milder, which probably resulted from the interference with the cellular pathways involved in the replication cycle. The presence of virucidal and adsorption-suppressing activity but the absence of viral replication inhibitory effects against CBV-1 suggests a possible interaction of the extract’s components with viral capsid proteins or related cell receptors

Rhamnolipid Biosurfactants—Possible Natural Anticancer Agents and Autophagy Inhibitors

Background/Aim: A number of biologically active substances were proved as an alternative to conventional anticancer medicines. The aim of the study is in vitro investigation of the anticancer activity of mono- and di-Rhamnolipids (RL-1 and RL-2) against human breast cancer. Additionally, the combination with Cisplatin was analyzed. Materials and Methods: Breast cell lines (MCF-10A, MCF-7 and MDA-MB-231) were treated with RLs and in combination with Cisplatin. The viability was analyzed using MTT assay, and investigation of autophagy was performed via acridine orange staining. Results: In contrast to the healthy cells, both tested cancer lines exhibited sensitivity to RLs treatment. This effect was accompanied by an influence on the autophagy-related acidic formation process. Only for the triple-negative breast cancer cell line (MDA-MB-231) the synergistic effect of the combined treatment (10 µM Cisplatin and 1 µg/mL RL-2) was observed. Conclusion: Based on studies on the reorganization of membrane models in the presence of RL and the data about a higher amount of lipid rafts in cancer cell membranes than in non-tumorigenic, we suggest a possible mechanism of membrane remodelling by formation of endosomes. Shortly, in order to have a synergistic effect, it is necessary to have Cisplatin andRL-2 as RL2 is a molecule inducingpositive membrane curvature

IMPROVING THE COMPETITIVENES OF TRAINING IN CONTROL AND ANALYSIS THROUGH INTERACTIVE MODELS

Съвременното развитие на информационните технологии оказва съществе- но влияние върху начините за преподаване, обучение и комуникация. В процеса на глобализация на висшето образование, образователните институции се стремят да утвърждават своите позиции, за да са конкурентоспособни. Този процес неизменно е съпътстван от използване на нови форми и средства за обучение. В разработката е извършено изследване на съвременните методи за преподаване чрез внедряване на дигитални платформи. Проучени са изискванията на практиката за ключовите компетенции, които трябва да притежават специалистите по контрол и анализ. Представени са етапите на конструиране, апробиране и усъвършенстване на уеббазираната интерактивна платформа Moodle. The development of modern information technologies has a significant impact on teaching, learning and communication. Within the process of globalization of higher education, educational institutions strive to improve their positions in the global educational environment in order to remain competitive. This process invariably includes implementation of new educational forms and methods. The current study reviews the modern teaching methods based on learning management systems. It includes an analysis of the key competences required from the specialists in the field of control and analysis and presents the stages of development, approbation and enhancement of the web-based learning management system Moodle