Bacillus and Streptomyces spp. as hosts for production of industrially relevant enzymes.

The application of enzymes is expanding across diverse industries due to their nontoxic and biodegradable characteristics. Another advantage is their cost-effectiveness, reflected in reduced processing time, water, and energy consumption. Although Gram-positive bacteria, Bacillus, and Streptomyces spp. are successfully used for production of industrially relevant enzymes, they still lag far behind Escherichia coli as hosts for recombinant protein production. Generally, proteins secreted by Bacillus and Streptomyces hosts are released into the culture medium; their native conformation is preserved and easier recovery process enabled. Given the resilience of both hosts in harsh environmental conditions and their spore-forming capability, a deeper understanding and broader use of Bacillus and Streptomyces as expression hosts could significantly enhance the robustness of industrial bioprocesses. This mini-review aims to compare two expression hosts, emphasizing their specific advantages in industrial surroundings such are chemical, detergent, textile, food, animal feed, leather, and paper industries. The homologous sources, heterologous hosts, and molecular tools used for the production of recombinant proteins in these hosts are discussed. The potential to use both hosts as biocatalysts is also evaluated. Undoubtedly, Bacillus and Streptomyces spp. as production hosts possess the potential to take on a more substantial role, providing superior (bio-based) process robustness and flexibility. KEY POINTS: • Bacillus and Streptomyces spp. as robust hosts for enzyme production. • Industrially relevant enzyme groups for production in alternative hosts highlighted. • Molecular biology techniques are enabling easier utilization of both hosts.

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases.

The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.

Crosstalk between SOX Genes and Long Non-Coding RNAs in Glioblastoma.

Glioblastoma (GBM) continues to be the most devastating primary brain malignancy. Despite significant advancements in understanding basic GBM biology and enormous efforts in developing new therapeutic approaches, the prognosis for most GBM patients remains poor with a median survival time of 15 months. Recently, the interplay between the SOX (SRY-related HMG-box) genes and lncRNAs (long non-coding RNAs) has become the focus of GBM research. Both classes of molecules have an aberrant expression in GBM and play essential roles in tumor initiation, progression, therapy resistance, and recurrence. In GBM, SOX and lncRNAs crosstalk through numerous functional axes, some of which are part of the complex transcriptional and epigenetic regulatory mechanisms. This review provides a systematic summary of current literature data on the complex interplay between SOX genes and lncRNAs and represents an effort to underscore the effects of SOX/lncRNA crosstalk on the malignant properties of GBM cells. Furthermore, we highlight the significance of this crosstalk in searching for new biomarkers and therapeutic approaches in GBM treatment.

A Machine-Learning-Based Approach to Prediction of Biogeographic Ancestry within Europe.

Data obtained with the use of massive parallel sequencing (MPS) can be valuable in population genetics studies. In particular, such data harbor the potential for distinguishing samples from different populations, especially from those coming from adjacent populations of common origin. Machine learning (ML) techniques seem to be especially well suited for analyzing large datasets obtained using MPS. The Slavic populations constitute about a third of the population of Europe and inhabit a large area of the continent, while being relatively closely related in population genetics terms. In this proof-of-concept study, various ML techniques were used to classify DNA samples from Slavic and non-Slavic individuals. The primary objective of this study was to empirically evaluate the feasibility of discerning the genetic provenance of individuals of Slavic descent who exhibit genetic similarity, with the overarching goal of categorizing DNA specimens derived from diverse Slavic population representatives. Raw sequencing data were pre-processed, to obtain a 1200 character-long binary vector. A total of three classifiers were used-Random Forest, Support Vector Machine (SVM), and XGBoost. The most-promising results were obtained using SVM with a linear kernel, with 99.9% accuracy and F1-scores of 0.9846-1.000 for all classes.

Streptomyces sp. BV410: Interspecies cross-talk for staurosporine production.

AIMS: Sequencing and genome analysis of two co-isolated streptomycetes, named BV410-1 and BV410-10, and the effect of their co-cultivation on the staurosporine production. METHODS AND RESULTS: Identification of two strains through genome sequencing and their separation using different growth media was conducted. Sequence analysis revealed that the genome of BV410-1 was 9.5 Mb, whilst that of BV410-10 was 7.1 Mb. AntiSMASH analysis identified 28 biosynthetic gene clusters (BGCs) from BV410-1, including that responsible for staurosporine biosynthesis, whilst 20 BGCs were identified from BV410-10. The addition of cell-free supernatant from BV410-10 monoculture to BV410-1 fermentations improved the staurosporine yield from 8.35 mg L-1 up to 15.85 mg L-1 , whilst BV410-10 monoculture ethyl acetate extract did not have the same effect. Also, there was no improvement in staurosporine production when artificial mixed cultures were created using three different BV410-1 and BV410-10 spore ratios. CONCLUSIONS: The growth of BV410-10 was inhibited when the two strains were grown together on agar plates. Culture supernatants of BV410-10 showed potential to stimulate staurosporine production in BV410-1, but overall co-cultivation attempts did not restore the previously reported yield of staurosporine produced by the original mixed isolate. SIGNIFICANCE AND IMPACT OF STUDY: This work confirmed complex relations between streptomycetes in soil that are difficult to recreate under the laboratory conditions. Also, mining of streptomycetes genomes that mainly produce known bioactive compounds could still be the fruitful approach in search for novel bioactive molecules.

Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation.

Synthesis of protulactone A (PLA, 1) and twelve of its analogues have been achieved starting from d-galactose. PLA was isolated in the crystalline state, and its crystal structure was determined utilizing X-ray crystallography, which confirmed the assumed stereochemistry at all stereocenters. All tested compounds displayed antiproliferative activity against a panel of tumour cell lines, and all of them were non-cytotoxic toward the normal cells (MRC-5). Natural product PLA (1) was the most active against the K562 and MCF-7 cell lines (IC50 6.52 and 2.20 µM, respectively). Some of the synthesized derivatives showed very potent cytotoxicity, especially analogues 11, 13 and 15 (IC50 1.08-1.14 µM against MCF-7), and 9 and 14 (IC50 1.29 and 1.64 µM against K562). SAR analysis indicated important structural motifs for antiproliferative activity. Unfortunately, PLA (1), its C-7 epimer (2) and demethylated analogue (3) did not display a significant antimicrobial activity (two Gram-positive and two Gram-negative bacteria and one fungal strain) and they also cannot affect the ability to modulate bacterial communication.

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies.

Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.

Enhanced Antimicrobial Activity of Biocompatible Bacterial Cellulose Films via Dual Synergistic Action of Curcumin and Triangular Silver Nanoplates.

Curcumin and triangular silver nanoplates (TSNP)-incorporated bacterial cellulose (BC) films present an ideal antimicrobial material for biomedical applications as they afford a complete set of requirements, including a broad range of long-lasting potency and superior efficacy antimicrobial activity, combined with low toxicity. Here, BC was produced by Komagataeibacter medellinensis ID13488 strain in the presence of curcumin in the production medium (2 and 10%). TSNP were incorporated in the produced BC/curcumin films using ex situ method (21.34 ppm) and the antimicrobial activity was evaluated against Escherichia coli ATCC95922 and Staphylococcus aureus ATCC25923 bacterial strains. Biological activity of these natural products was assessed in cytotoxicity assay against lung fibroblasts and in vivo using Caenorhabditis elegans and Danio rerio as model organisms. Derived films have shown excellent antimicrobial performance with growth inhibition up to 67% for E. coli and 95% for S. aureus. In a highly positive synergistic interaction, BC films with 10% curcumin and incorporated TSNP have shown reduced toxicity with 80% MRC5 cells survival rate. It was shown that only 100% concentrations of film extracts induce low toxicity effect on model organisms' development. The combined and synergistic advanced anti-infective functionalities of the curcumin and TSNP incorporated in BC have a high potential for development for application within the clinical setting.

Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells.

Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment strategies are still needed. In this paper we have characterized the anticancer potential of coumarin-palladium(II) complex against pancreatic carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being effective at micromolar concentrations (0.5 µM). Treatments induced apoptosis, increased BAX/BCL-2 ratio and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma xenografts resulted in significant reduction in tumor mass, without provoking any adverse toxic effects including hepatotoxicity. Presented results indicate the great potential of the tested compound and the perspective of its further development towards pancreatic cancer therapy.

Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes.

Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical, metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms. Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21 in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1 cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescence-associated ß-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes. Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic strategies based on miRNA manipulation could prevent senescence and may improve the physiological outcome.

Complete mitogenome data for the Serbian population: the contribution to high-quality forensic databases.

Mitochondrial genome (mtDNA) is a valuable resource in resolving various human forensic casework. The usage of variability of complete mtDNA genomes increases their discriminatory power to the maximum and enables ultimate resolution of distinct maternal lineages. However, their wider employment in forensic casework is nowadays limited by the lack of appropriate reference database. In order to fill in the gap in the reference data, which, considering Slavic-speaking populations, currently comprises only mitogenomes of East and West Slavs, we present mitogenome data for 226 Serbians, representatives of South Slavs from the Balkan Peninsula. We found 143 (sub)haplogroups among which West Eurasian ones were dominant. The percentage of unique haplotypes was 85%, and the random match probability was as low as 0.53%. We support previous findings on both high levels of genetic diversity in the Serbian population and patterns of genetic differentiation among this and ten studied European populations. However, our high-resolution data supported more pronounced genetic differentiation among Serbians and two Slavic populations (Russians and Poles) as well as expansion of the Serbian population after the Last Glacial Maximum and during the Migration period (fourth to ninth century A.D.), as inferred from the Bayesian skyline analysis. Phylogenetic analysis of haplotypes found in Serbians contributed towards the improvement of the worldwide mtDNA phylogeny, which is essential for the interpretation of the mtDNA casework.

Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro.

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum LIII near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN.

The Impact of 22q11.2 Microdeletion on Cardiac Surgery Postoperative Outcome.

22q11.2 microdeletion is the most common microdeletion in humans. The purpose of this study was to evaluate postoperative outcome in children with 22q11.2 microdeletion who had undergone complete surgical correction of a congenital heart defect. The study included 34 patients who underwent complete correction of conotruncal heart defects. Of these, 17 patients diagnosed with 22q11.2 microdeletion represent the investigated group. Another 17 patients without 22q11.2 microdeletion represent the control group. Investigated and control groups differ significantly for total length of stay in the hospital (average 37.35 and 14.12 days, respectively); length of postoperative stay in the intensive care unit (average 10.82 and 6.76 days, respectively); sepsis (eight and two patients, respectively); administration of antibiotics (15 and seven patients, respectively); duration of antibiotic therapy (average 17.65 and 14.59 days, respectively); occurrence of hypocalcemia (16 and 0 patients, respectively); and initiation of peroral nutrition during the postoperative course (average 10.29 and 3.88 days, respectively). No difference was found for duration of ventilatory support (average 6.12 and 4.24 days, respectively), administration of total parenteral nutrition, and postoperative mortality rate. The study results suggest that genotype of 22q11.2 microdeletion affects postoperative outcome after cardiac surgery. Possible targets for intervention in postoperative intensive care management are prevention and treatment of systemic infections, monitoring, and treatment of hypocalcemias, rational administration of antibiotics and careful planning of nutrition. Consequently, this could shorten patients' intensive care stay and overall duration of hospitalization.

Mitochondrial super-haplogroup U diversity in Serbians.

BACKGROUND: Available mitochondrial (mtDNA) data demonstrate genetic differentiation among South Slavs inhabiting the Balkan Peninsula. However, their resolution is insufficient to elucidate the female-specific aspects of the genetic history of South Slavs, including the genetic impact of various migrations which were rather common within the Balkans, a region having a turbulent demographic history. AIM: The aim was to thoroughly study complete mitogenomes of Serbians, a population linking westward and eastward South Slavs. SUBJECTS AND METHODS: Forty-six predominantly Serbian super-haplogroup U complete mitogenomes were analysed phylogenetically against ∼4000 available complete mtDNAs of modern and ancient Western Eurasians. RESULTS: Serbians share a number of U mtDNA lineages with Southern, Eastern-Central and North-Western Europeans. Putative Balkan-specific lineages (e.g. U1a1c2, U4c1b1, U5b3j, K1a4l and K1a13a1) and lineages shared among Serbians (South Slavs) and West and East Slavs were detected (e.g. U2e1b1, U2e2a1d, U4a2a, U4a2c, U4a2g1, U4d2b and U5b1a1). CONCLUSION: The exceptional diversity of maternal lineages found in Serbians may be associated with the genetic impact of both autochthonous pre-Slavic Balkan populations whose mtDNA gene pool was affected by migrations of various populations over time (e.g. Bronze Age pastoralists) and Slavic and Germanic newcomers in the early Middle Ages.

Crosstalk between SOXB1 proteins and WNT/ß-catenin signaling in NT2/D1 cells.

During early vertebrate embryogenesis, the expression of SOXB1 proteins is precisely regulated by a number of different mechanisms, including Wnt/ß-catenin signaling. This is essential for controlling the balance between stemness and differentiation in embryonic stem cells. In the present study, we analyzed the molecular mechanism of LiCl action in NT2/D1 cells and examined the crosstalk between SOXB1 proteins and Wnt signaling in this model system. We have shown that LiCl increases ß-catenin level, induces its translocation to the nucleus and consequently up-regulates ß-catenin/Tcf-dependent transcription in NT2/D1 cells. Our results also suggest that LiCl treatment leads to increased expression of SOX2 and SOX3 proteins in NT2/D1 cells through activation of canonical Wnt signaling. Finally, we have detected a negative feedback loop between ß-catenin and SOX2 expression in NT2/D1 cells. Since ß-catenin and SOX2 have been linked to processes of self-renewal and pluripotency, our results have implications for future research on the maintenance of stemness and lineage commitment of embryonic stem cells.

Mitochondrial DNA perspective of Serbian genetic diversity.

Although south-Slavic populations have been studied to date from various aspects, the population of Serbia, occupying the central part of the Balkan Peninsula, is still genetically understudied at least at the level of mitochondrial DNA (mtDNA) variation. We analyzed polymorphisms of the first and the second mtDNA hypervariable segments (HVS-I and HVS-II) and informative coding-region markers in 139 Serbians to shed more light on their mtDNA variability, and used available data on other Slavic and neighboring non-Slavic populations to assess their interrelations in a broader European context. The contemporary Serbian mtDNA profile is consistent with the general European maternal landscape having a substantial proportion of shared haplotypes with eastern, central, and southern European populations. Serbian population was characterized as an important link between easternmost and westernmost south-Slavic populations due to the observed lack of genetic differentiation with all other south-Slavic populations and its geographical positioning within the Balkan Peninsula. An increased heterogeneity of south Slavs, most likely mirroring turbulent demographic events within the Balkan Peninsula over time (i.e., frequent admixture and differential introgression of various gene pools), and a marked geographical stratification of Slavs to south-, east-, and west-Slavic groups, were also found. A phylogeographic analyses of 20 completely sequenced Serbian mitochondrial genomes revealed not only the presence of mtDNA lineages predominantly found within the Slavic gene pool (U4a2a*, U4a2a1, U4a2c, U4a2g, HV10), supporting a common Slavic origin, but also lineages that may have originated within the southern Europe (H5*, H5e1, H5a1v) and the Balkan Peninsula in particular (H6a2b and L2a1k).

The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1.

The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

Speech Sounds Production, Narrative Skills, and Verbal Memory of Children with 22q11.2 Microdeletion.

22q11.2 deletion syndrome (22q11.2DS), the most frequent microdeletion syndrome in humans, is related to a high risk of developing neurodevelopmental disorders. About 95% of patients with 22q11.2DS have speech and language impairments. Global articulation, story generation, and verbal memory tests were applied to compare articulatory characteristics of speech sounds, spontaneous language abilities, and immediate verbal memory between four groups of Serbian-speaking children: patients with 22q11.2DS, children with clinical presentation of 22q11.2DS that do not have the microdeletion, children with non-syndromic congenital heart defects, and their peers with typical speech-sound development. The obtained results showed that children with this microdeletion have impaired articulation skills and expressive language abilities. However, we did not observe weaker receptive language skills and immediate verbal memory compared to healthy controls. Children with 22q11.2DS should be considered a risk category for the development of speech-sound pathology and expressive language abilities. Since speech intelligibility is an instrument of cognition and adequate peer socialization, and language impairment in school-aged children with 22q11DS might be an indicator of increased risk for later psychotic symptoms, patients with 22q11.2 microdeletion should be included in a program of early stimulation of speech-language development immediately after diagnosis is established.

The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes.

Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.

Chemical profiling of Anthriscus cerefolium (L.) Hoffm., biological potential of the herbal extract, molecular modeling and KEGG pathway analysis.

This study was designed to investigate chemical composition and biological activities of the Anthriscus cerefolium methanolic extract. Chemical characterization of the extracts was performed by LC-HRMS/MS analysis. Antimicrobial activities of the extract were investigated on six bacteria and eight fungi while antioxidant activity was assessed by six different assays. Anti-enzymatic activity of the methanolic extract was tested on five enzymes associated with therapy of neurodegenerative diseases and diabetes mellitus type 2. Cytotoxic properties of the extract were tested on human immortalized keratinocytes (HaCaT) and tumor cell lines (SiHa, MCF7, HepG2). Anti-inflammatory activity of the extract was assessed on bacteria mediated inflammation model using HaCaT cell line. Molecular docking studies of enzymes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis were performed. The results showed that the obtained extract was rich in phenolic compounds (a total of seventy-two were identified), with malonyl-1,4-O-dicaffeoylquinic acid and 3,5-O-dicaffeoylquinic acid dominating in the sample. The extract expressed antimicrobial, antioxidant, anti-enzymatic, cytotoxic and anti-inflammatory properties. The identified compounds demonstrated strong binding to the acetylcholinesterase (AChE) and to a lesser extent, to the butyrylcholinesterase (BChE), glucosidase, amylase, and modestly, to tyrosinase. KEGG pathway analysis has shown that the certain phenolic compounds may be related to anti-tumor, anti-inflammatory and anti-microbial activities of the extract. The data obtained suggest that phenolic compounds of the extract and their mixtures should be considered for future research as ingredients in pharmaceutical and nutraceutical formulations.