Ethnomedicinal records have long mentioned the historical usage of
L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding ...female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of
on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with
extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the
extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.
The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of ...their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.
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
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.
SOX14 is a member of the SOXB2 subgroup of transcription factors implicated in neural development. Although the first SOX14 gene in vertebrates was cloned and characterized more than a decade ago and ...its expression profile during development was revealed in various animal model systems, the role of this gene during neural development is largely unknown. In the present study we analyzed the expression of SOX14 in human NT2/D1 and mouse P19 pluripotent embryonal carcinoma cells. We demonstrated that it is expressed in both cell lines and upregulated during retinoic acid induced neural differentiation. We showed that SOX14 was expressed in both neuronal and non-neuronal differentiated derivatives, as revealed by immunocytochemistry. Since it was previously proposed that increased SOXB2 proteins level interfere with the activity of SOXB1 counteracting partners, we compared expression patterns of SOXB members during retinoic acid induction of embryonal carcinoma cells. We revealed that upregulation of SOX14 expression is accompanied by alterations in the expression patterns of SOXB1 members. In order to analyze the potential cross-talk between them, we generated SOX14 expression construct. The ectopic expression of SOX14 was demonstrated at the mRNA level in NT2/D1, P19 and HeLa cells, while an increased level of SOX14 protein was detected in HeLa cells only. By transient transfection experiments in HeLa cells we showed for the first time that ectopic expression of SOX14 repressed SOX1 expression, whereas no significant effect on SOX2, SOX3 and SOX21 was observed. Data presented here provide an insight into SOX14 expression during in vitro neural differentiation of embryonal carcinoma cells and demonstrate the effect of its ectopic expression on protein levels of SOXB members in HeLa cells. Obtained results contribute to better understanding the role of one of the most conserved SOX proteins.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
L. (lady's mantle) was used for centuries in Europe and Balkan countries for treatments of numerous conditions and diseases of the reproductive system, yet some of the biological activities of lady's ...mantle have been poorly studied and neglected. The present study aimed to estimate the potential of
ethanolic extract from Southeast Serbia to prevent and suppress tumor development in vitro, validated by antioxidant, genoprotective, and cytotoxic properties. A total of 45 compounds were detected by UHPLC-HRMS analysis in
ethanolic extract. Measurement of antioxidant activity revealed the significant potential of the tested extract to scavenge free radicals. In addition, the analysis of micronuclei showed an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes.
extract strongly suppressed the growth of human cell lines derived from different types of tumors (MCF-7, A375, A549, and HCT116). The observed antitumor effect is realized through the blockade of cell division, caspase-dependent apoptosis, and autophagic cell death. Our study has shown that
L. is a valuable source of bioactive compounds able to protect the subcellular structure from damage, thus preventing tumorigenesis as well as suppressing tumor cell growth.
Salvia nemorosa L. is a rich source of bioactive constituents. We have used different solvents to obtain 14 different extracts in order to evaluate solvents impact on S. nemorosa inflorescences ...bioactivities. Firstly, the extraction yield, chemical composition and cytotoxic properties towards HaCaT cell line were elaborated. Afterwards, we have studied the extracts bioactivity in terms of wound healing, antioxidant and antidiabetic potentials as well as antimicrobial and antibiofilm capacities; followed by the determination of the antimicrobial mechanism. The extracts yield ranged from 3.03% to 15.75% and they were dominated by epigallocatechin gallate and rosmarinic acid. The majority of extracts did not possess cytotoxic properties towards human keratinocytes. Butanol was the most appropriate solvent for the improvement of wound healing capacity. Combined extraction with ethanol and water resulted in the highest antioxidant potential of the extracts that could be attributed to the high abundance of detected polyphenols. Extraction with butanol led to the increased inhibition towards enzymes linked to type 2-diabetes and increase in antimicrobial capacities. The extracts have shown antibiofilm potential towards Staphylococcus lugdunensis biofilms with more than 90% inhibition for the most active ones. The selected extract EB7 reduced bacterial ability to adhere to human keratinocytes and provided immunomodulatory action in HaCaT cells exposed to S. lugdunensis. The antibacterial mechanism of action of the same extract was associated with moderate perturbation in the cell membrane integrity and with the reduction in bacterial mitochondrial activity. S. nemorosa inflorescences were abundant sources of bioactive polyphenols and with different extraction solvents their bioactivities were further improved. This study reported for the first time the effects of extraction solvents on various bioactivities of S. nemorosa inflorescences, supporting S. nemorosa role as a natural bioactive therapeutic agent with possible antioxidant, antidiabetic and antimicrobial applications.
•S. nemorosa inflorescences bioactivities are influenced by the extraction solvents.•Extracts exhibited antimicrobial, antioxidant, antidiabetic activities.•Wound healing and cytotoxic properties were shown.•Individual phenolic profile was dependent on the extraction solvents.
Different Schiff base complexes have biological activities that make them suitable for drug design. The biological properties of tetradentate Schiff base copper( ii ) complexed with N , N ...′-bis(acetylacetone)propylenediimine have been studied. The cytotoxic activity towards Caco-2 cells were determined by MTT, Anexin V and PI apoptosis assays. N , N ′-bis(acetylacetone)propylenediimine-copper( ii ) showed the anti-cancer and anti-proliferative properties by inducing apoptosis in Caco-2 cells. A comparison of the cytotoxic activity of this compound with cisplatin shows that it is more effective on the colorectal cancer cell line Caco-2. The binding capacity and interaction of N , N ′-bis(acetylacetone)propylenediimine-copper( ii ) with HSA were systemically investigated by in vitro fluorescence spectroscopy, CD spectroscopy, and in silico molecular docking study. Furthermore, in vitro and in silico interaction studies indicated that the complex binds to HSA through a static quenching mechanism without changes in protein conformation. The calculated number of binding sites was in line with molecular docking studies. The obtained K a value suggests that the compound can be released from the protein in target cells. The tetradentate Schiff base copper( ii ) complex exhibited in vitro biological activities against cancer epithelial cells, which depend on the molecular structure of the complex, causing apoptosis, and the complex can bind to the protein drug carrier in circulation to the target tissue.
This study aimed to analyze the measurement properties of the Health-related quality of life questionnaire for polycystic ovary syndrome (PCOSQ-50) in a sample of Serbian women with polycystic ovary ...syndrome (PCOS). Seventy-six women with PCOS from an endocrinology clinic and 28 healthy women participated between October 2016 and March 2017. The measure was rigorously translated and culturally adapted into Serbian. Psychometric evaluation included descriptive analysis, internal consistency (Cronbach's alpha coefficient), test-retest reliability (intraclass-correlation coefficient - ICC) and construct validity testing. Cronbach's alpha coefficient ranged from 0.67 to 0.96 for domain scales of PCOSQ-50 scores, while the ICCs for test-retest reliability for these domains ranged from 0.66 to 0.89. Women with PCOS had significantly lower scores than healthy women for hirsutism, obesity and menstrual disorders and the total PCOSQ-50 scale score (p ≤ 0.03), but not for the psychosocial and emotional, fertility, sexual function, and coping scales. These results show that the Serbian PCOSQ-50 measure is acceptable and could produce reliable and valid assessments of PCOS-related quality of life for at least four out of seven domains. Considering that validity testing is an iterative process, additional work is needed before the whole measure is used in routine clinical practice.
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.
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