Glioblastoma (GBM) is the most common and highly lethal type of brain tumor, with poor survival despite advances in understanding its complexity. After current standard therapeutic treatment, ...including tumor resection, radiotherapy and concomitant chemotherapy with temozolomide, the median overall survival of patients with this type of tumor is less than 15 months. Thus, there is an urgent need for new insights into GBM molecular characteristics and progress in targeted therapy in order to improve clinical outcomes. The literature data revealed that a number of different signaling pathways are dysregulated in GBM. In this review, we intended to summarize and discuss current literature data and therapeutic modalities focused on targeting dysregulated signaling pathways in GBM. A better understanding of opportunities for targeting signaling pathways that influences malignant behavior of GBM cells might open the way for the development of novel GBM-targeted therapies.
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.
This study explored the chemical profile of the aerial parts of Ononis spinosa and further investigated its biological activities. Chemical profiling of the extract revealed the presence of 63 ...different compounds: phenolic acids, flavonoid glycosides and aglycones, isoflavonoid glycosides and aglycones, and other related compounds. Our results revealed that the extract was active against 8 strains of free floating bacteria. It showed anti-biofilm potential against Staphylococcus aureus and was able to supress the production of staphyloxanthin in S. aureus at sub-minimal inhibitory concentrations. Its antioxidant activity was evaluated by using several assays (phosphomolybdenum, DPPH, ABTS, CUPRAC, FRAP, and metal chelating assay), which showed that the extract exhibited a dose dependent activity. Inhibition of AChE, BChE, amylase, glucosidase and tyrosinase was achieved by the extract, demonstrating its anti-enzymatic activity. The antiproliferative potential of the extract towards human cancer cell lines (HepG2, MCF-7, SiHa and A172) was determined by using the crystal violet assay. Ki67, a marker of proliferation was downregulated in the A172 glioblastoma cell line.
Summary
Background
Non‐albicans Candida spp. are an emerging cause of hospital‐acquired bloodstream infections, associated with high mortality due to the challenges in diagnosis and delayed ...treatment.
Objectives
We aimed to investigate a cluster of healthcare‐associated invasive candidiasis caused by C tropicalis and review the literature of healthcare‐associated outbreaks or clusters caused by C tropicalis.
Methods
An investigation was performed to determine clinical presentation, treatment outcomes and the factors contributing to C tropicalis candidemia occurrence. We searched the Medline database via PubMed and Ovid using the keywords of “Candida tropicalis” combined with “outbreak” or “clustering” or “clusters,” and we limited the search to studies conducted from January 1989 to January 2019.
Results
We report two related cases of C tropicalis candidemia among patients with AML following a period of neutropenia, who had erythematous skin rash as a first manifesting sign of candidiasis. C tropicalis was isolated from blood and skin cultures of both patients, which were identical by pulsed‐field gel electrophoresis typing. Our systematic review of outbreaks caused by C tropicalis suggests that (a) most reported outbreaks have occurred in neonatal and adult ICUs; (b) patients who receive total parenteral therapy, antibiotics and those who have indwelling catheters and recent surgery are at high risk of infection; and (c) environmental and healthcare personnel surveillance suggest that cross‐contamination is a major risk factor.
Conclusion
Control of nosocomial outbreaks caused by C tropicalis should include better infection control measures, education of healthcare professionals especially working in adult and neonatal intensive care and haematology units.
•Novel ferrocenes which contain six-membered cyclic ureas ring were synthesized.•Detailed spectroscopic and electrochemical characterization were provided.•In vitro antioxidant, antibacterial and ...antifungal activity have been done.
A small library of ferrocenes that contain six-membered cyclic ureas ring were smoothly synthesized, in moderate to good yields. The purity of >95% and structural characterization for obtained compounds have been established by standard spectroscopic methods, as well as elemental analysis. The electrochemical properties of the prepared compounds have been provided using cyclic voltammetry. Seventeen ferrocene-containing tetrahydropyrimidin-2(1H)-ones were screened for in vitro antioxidant, antibacterial, and antifungal activity. The antioxidant activity of synthesized compounds was determined using two methods: ABTS radical cation and DPPH radical scavenging activities. The antimicrobial potential was evaluated in vitro employing three bacterial strains and three fungal strains. The synthesized compounds showed significantly lower antimicrobial activity compared with commercial antimicrobial compounds, while some of the synthesized ferrocenyl derivatives possess strong ABTS·+ scavenging activity.
Display omitted .
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.
Display omitted
•Nepetalactone and dehydronepetalactone are the main iridoids of N. rtanjensis.•Developmental regulation of nepetalactone biosynthesis occurs in leaves.•Regulation at transcriptional ...level implies a significant role of putative NrIS.•Nepetalactone content in leaves is determined by its biosynthesis and conversion rate.•Biosynthesis and accumulation of nepetalactone is localized in glandular trichomes.
Nepetalactones are accumulated as the main secondary metabolites in the majority of Nepeta species; however, their biosynthetic pathway remains to a great extent unknown, as well as their relationship to the overall physiology of these plants. Nepetalactones most certainly arise through general iridoid biosynthetic pathway leading to nepetalactol, a common precursor of all plant-derived iridoids that is formed in a reaction catalysed by iridoid synthase (IS, EC 1.3.1.99). In this paper, we aimed to localize the sites of nepetalactone biosynthesis and accumulation by comparatively analysing the nepetalactones content and the expression of putative iridoid synthase (NrIS) in leaves of Nepeta rtanjensis Diklić & Milojević, a trans,cis-nepetalactone and dehydronepetalactone rich species. Another aim was to give an insight into the developmental regulation of nepetalactone biosynthesis in leaves of cultivated N. rtanjensis plants. Knowledge on the spatial-, and developmental- regulation of nepetalactone metabolism could greatly benefit potential growers by enabling them to adequately plan and manage plant cultivation, harvesting, and handling and thus increase yield of bioactive compounds.
The expression profile of putative NrIS1 is highly correlated with trans,cis-nepetalactone and dehydronepetalactone content/ratio in leaves of different developmental stages. The results strongly indicate that developmental regulation of nepetalactone biosynthesis in leaves resides largely at the level of gene expression, and suggest an important role of NrIS1. Young leaves exhibited the most intensive nepetalactone biosynthesis and accumulation, but also its conversion to dehydronepetalactone. Thus, the pattern of NL accumulation in leaves can be explained by both the rate of its biosynthesis and metabolic degradation.
The gene expression patterns of NrIS1 and NrIS2 transcripts in trichomes and abraded leaves revealed trichomes as the main site of their activity. UHPLC/qqqMS profiling of nepetalactones in trichomes and abraded leaves, complemented with Raman spectroscopy and dichloromethane dipping experiment, supported glandular trichome-specific localization of nepetalactone biosynthesis and accumulation.
Glioblastoma (GBM) is the most common, most aggressive and deadliest brain tumor. Recently, remarkable progress has been made towards understanding the cellular and molecular biology of gliomas. GBM ...tumor initiation, progression and relapse as well as resistance to treatments are associated with glioma stem cells (GSCs). GSCs exhibit a high proliferation rate and self-renewal capacity and the ability to differentiate into diverse cell types, generating a range of distinct cell types within the tumor, leading to cellular heterogeneity. GBM tumors may contain different subsets of GSCs, and some of them may adopt a quiescent state that protects them against chemotherapy and radiotherapy. GSCs enriched in recurrent gliomas acquire more aggressive and therapy-resistant properties, making them more malignant, able to rapidly spread. The impact of SOX transcription factors (TFs) on brain tumors has been extensively studied in the last decade. Almost all
genes are expressed in GBM, and their expression levels are associated with patient prognosis and survival. Numerous SOX TFs are involved in the maintenance of the stemness of GSCs or play a role in the initiation of GSC differentiation. The fine-tuning of
gene expression levels controls the balance between cell stemness and differentiation. Therefore, innovative therapies targeting SOX TFs are emerging as promising tools for combatting GBM. Combatting GBM has been a demanding and challenging goal for decades. The current therapeutic strategies have not yet provided a cure for GBM and have only resulted in a slight improvement in patient survival. Novel approaches will require the fine adjustment of multimodal therapeutic strategies that simultaneously target numerous hallmarks of cancer cells to win the battle against GBM.
L. is a plant traditionally used as folk remedy. There are numerous studies regarding chemical constituents and health beneficial properties of Ononidis Radix. The following study was designed to ...investigate chemical composition and antifungal potential of the methanolic extract obtained from the
L. herb. Chemical analyses regarding phenolic compounds of
were performed by liquid chromatography with mass spectrometry (LC-DAD-ESI/MSn). Antifungal activity, antibiofilm properties and antifungal mode of action of the extract were evaluated, as well as cytotoxicity. Chemical analyses revealed the presence of flavonoids, isoflavonoids and phenolic acids in
with kaempherol-
-hexoside-pentoside being the most abundant compound (5.1 mg/g extract). Methanolic extract was active against all of the tested microfungi with
being the most sensitive to the extract inhibitory effect at 0.02 mg/mL; and effectively inhibited biofilms formed by
strains. Minimum fungicidal concentrations of extract rose in the presence of ergosterol and leakage of cellular components was detected. The extract showed no cytotoxicity to human gingival fibroblast (HGF-1) cells. This study significantly contributes to overall knowledge about medicinal potential of
herbal extract and enlightens previously unrevealed properties.
aerial parts seem to be an interesting candidate for the development of antifungal preparations, non-toxic to human cells.
Blackberry cane diseases with the symptoms of necrosis, canker, and wilting are caused by several fungi worldwide. Surveys conducted from 2013 to 2016 in Serbia revealed the occurrence of ...Gnomoniopsis idaeicola, the causal agent of cane canker and wilting, which was found to be distributed in almost half of the surveyed orchards, in three blackberry cultivars, and with disease incidence of up to 80%. Wide distribution and high disease incidence suggest that G. idaeicola has been present in Serbia for some time. Out of 427 samples, a total of 65 G. idaeicola isolates were obtained (isolation rate of 34.19%). Reference isolates, originating from different localities, were conventionally and molecularly identified and characterized. G. idaeicola was detected in single and mixed infections with fungi from genera Paraconiothyrium, Colletotrichum, Diaporthe, Botryosphaeria, Botrytis, Septoria, Neofusicoccum, and Discostroma, and no diagnostically specific symptoms could be related directly to the G. idaeicola infection. In orchards solely infected with G. idaeicola, blackberry plant mortality was up to 40%, and yield loses were estimated at 50%. G. idaeicola isolates included in this study demonstrated intraspecies diversity in morphological, biological, pathogenic, and molecular features, which indicates that population in Serbia may be of different origin. This is the first record of a massive outbreak of G. idaeicola infection, illustrating its capability of harmful influence on blackberry production. This study represents the initial step in studying G. idaeicola as a new blackberry pathogen in Serbia, aiming at developing efficient control measures.
PDF
