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Bioactive potential of apigenin derivative apigenin-7- -glucoside related to its antifungal activity on spp. and cytotoxic effect on colon cancer cells was studied and compared with bioactive potential of apigenin. Antifungal activity was tested on 14 different isolates of spp. using membrane permeability assay, measuring inhibition of reactive oxidative species and inhibition of CYP51 enzyme. Cytotoxic potential of apigenin-7- -glucoside was tested on colon cancer HCT116 cells by measuring cell viability, apoptosis rate and apoptosis- and colon cancer-related gene expression. Obtained results indicated considerable antifungal activity of apigenin-7- -glucoside towards all isolates. Breakdown of plasma membrane was achieved upon treatment with apigenin-7- -glucoside for shorter period of time then with apigenin. Reduction of intra- and extracellular reactive oxidative species was achieved with minimum inhibitory concentrations of both compounds, suggesting that reactive oxidative species inhibition could be a mechanism of antifungal action. None of the compounds exhibited binding affinity to CYP51 protein. Besides, apigenin-7- -glucoside was more effective compared to apigenin in reduction of cell's viability and induction of cell death of HCT116 cells. Treatment with both compounds resulted in chromatin condensation, apoptotic bodies formation and apoptotic genes expression in HCT116 cells, but the apigenin-7- -glucoside required a lower concentration to achieve the same effect. Compounds apigenin-7- -glucoside and apigenin displayed prominent antifungal potential and cytotoxic effect on HCT116 cells. However, our results showed that apigenin-7- -glucoside has more potent activity compared to apigenin in all assays that we used.

In this paper we present results for reduced ionization coefficients ( α / N, N —gas density) obtained from the breakdown voltage and emission profile measurements in low-pressure dc discharges in two freons: 1,1,1,2-tetrafluoroethane (R134a) with the chemical formula CH2F–CF3 and 2,3,3,3-tetrafluoropropene (HFO1234yf) with the chemical formula CH2=CFCF3. Our results for α / N are determined from the axial emission profiles in low-current Townsend discharge and lay in the intervals of reduced electric fields E / N ( E —electric field, N —gas density), from 2.7 to 5.9 kTd for R134a and from 5 to 23 kTd for HFO1234yf. We also provide a comparison of our experimental results with those from the available literature. Graphical abstract

Repression of retrotransposition is crucial for the successful fitness of a mammalian organism. The domesticated transposon protein L1TD1, derived from LINE-1 (L1) ORF1p, is an RNA-binding protein that is expressed only in some cancers and early embryogenesis. In human embryonic stem cells, it is found to be essential for maintaining pluripotency. In cancer, L1TD1 expression is highly correlative with malignancy progression and as such considered a potential prognostic factor for tumors. However, its molecular role in cancer remains largely unknown. Our findings reveal that DNA hypomethylation induces the expression of L1TD1 in HAP1 human tumor cells. L1TD1 depletion significantly modulates both the proteome and transcriptome and thereby reduces cell viability. Notably, L1TD1 associates with L1 transcripts and interacts with L1 ORF1p protein, thereby facilitating L1 retrotransposition. Our data suggest that L1TD1 collaborates with its ancestral L1 ORF1p as an RNA chaperone, ensuring the efficient retrotransposition of L1 retrotransposons, rather than directly impacting the abundance of L1TD1 targets. In this way, L1TD1 might have an important role not only during early development but also in tumorigenesis.

Organic production, as a sustainable food production system, is designed to implement all agroecological principles that enable the preservation of human and animal health, environmental protection, and positive impact on society and the ecosystem while achieving significant economic benefits. Demand for organic food products is constantly growing, and the land area under organic production is continuously increasing. The problem in this sector is that producers of organic products face many administrative and systemic obstacles that prevent the faster development of this sector. On the other hand, consumers do not have complete confidence in the current mechanisms of control of organic production, so in the sale on the food markets and in the rest of the market, fake and unverified organic products can be found. Based on sensor data from the production field, this paper presents the SAFE platform as a solution for the described problem. The data necessary for producers to carry out the certification process are harmonized with the current legislation for organic food production. The SAFE platform uses blockchain technology to secure data consistency and history since it makes it impossible to change data history. The results of a survey about the SAFE platform are presented. The proposed solution stimulates the development and improvement of agricultural production by organic production methods, accompanied by increasing capacity in organic production.

Gastronomic identity is a crucial segment of sustainable gastronomy and its successful positioning in the tourism market. As such, it calls for the creation of a suitable SusGastroIdentity scale that would identify influential factors. The research investigated the opinions of the employees in catering establishments in two tourist destinations in the Balkans: Fruška Gora Mountain, a tourist area in the Autonomous Province of Vojvodina in Serbia, and Jahorina Mountain, a tourist area in the Republic of Srpska entity in Bosnia and Herzegovina. The study involved 606 participants, 66% of whom work in à la carte restaurants. Of these participants, 68% hold operational roles in hospitality establishments, and 58.3% have over 5 years of experience in the hospitality industry. After conducting a survey using a questionnaire and performing appropriate statistical analysis of the responses, four factors of gastronomic identity and sustainable gastronomy were defined: geographic and cultural characteristics of gastronomy, gastro-tourism events, economic aspects of business operations, and commercial aspects of business operations. The present research has shown that employees in hospitality and tourism perceive geographic and cultural characteristics and the economic aspects of business as the significant factors of gastronomic identity that affect both the sustainability of gastronomy in tourism and the tourist destination itself.

Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with a debilitating impact on quality of life. Here, we review the complex interplay of innate and adaptive immune dysregulation in HS pathogenesis, in the context of microbial dysbiosis, genetic predisposition, cellular dysfunction and epigenetic factors. Hyperactivation of the innate system triggered by follicular occlusion leads to a cascade of activated signaling pathways leading to persistent inflammation as the disease progresses. This immune hyperactivation is further complicated by microbiome dysbiosis, which is associated with dysregulation of inflammasomes and altered expression of host antimicrobial peptides. Keratinocytes, fibroblasts, macrophages, and neutrophils exhibit altered functions, and contribute to the inflammatory cascade and disease chronicity in HS. Epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNAs modulate immune responses and contribute to aberrant cytokine and chemokine expression that drive the persistent inflammatory state in HS pathogenesis. We highlight the need for future research to explore the concept of epigenetic memory in epidermal stem cells and inflammasome activation to gain a better understanding of these mechanisms and pave the way for development of future novel therapeutic targets and strategies to disrupt the persistent chronic inflammation cycle in this debilitating condition.

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.

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.

Although impaired keratinocyte migration is a recognized hallmark of chronic wounds, the molecular mechanisms underpinning impaired cell movement are poorly understood. Here, we demonstrate that both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) exhibit global deregulation of cytoskeletal organization in genomic comparison to normal skin and acute wounds. Interestingly, we found that DFUs and VLUs exhibited downregulation of ArhGAP35, which serves both as an inactivator of RhoA and as a glucocorticoid repressor. Since chronic wounds exhibit elevated levels of cortisol and caveolin-1 (Cav1), we posited that observed elevation of Cav1 expression may contribute to impaired actin-cytoskeletal signaling, manifesting in aberrant keratinocyte migration. We showed that Cav1 indeed antagonizes ArhGAP35, resulting in increased activation of RhoA and diminished activation of Cdc42, which can be rescued by Cav1 disruption. Furthermore, we demonstrate that both inducible keratinocyte specific Cav1 knockout mice, and MβCD treated diabetic mice, exhibit accelerated wound closure. Taken together, our findings provide a previously unreported mechanism by which Cav1-mediated cytoskeletal organization prevents wound closure in patients with chronic wounds.Jozic et al observe deregulated cytoskeleton components and elevated levels of cortisol and caveolin-1 in chronic wounds. They also show that inducible-keratinocyte specific Cav1 knockout or drug-induced cholesterol disruption in diabetic mice leads to accelerated wound closure suggesting a therapeutic approach for diabetic foot ulcers.

Chronic wounds present a major burden to patients, health care professionals, and health care systems worldwide, yet treatment options remain limited and often ineffective. Although initially promising, growth factor-based therapies displayed limited and underwhelming effectiveness largely due to poor bioavailabilbioity and impaired receptor function within the chronic wound microenvironment. Here we demonstrate that chronic wounds exhibit elevated cholesterol synthesis, which disrupts growth factor signaling by sequestering receptors within lipid rafts. To address this, we developed a novel therapy combining growth factors with cyclodextrin in an ECM-mimetic scaffold, enabling localized cholesterol modulation and improved receptor accessibility. We demonstrate that this approach enhances growth factor bioavailability and functionality, creating a regenerative environment. In both human ex vivo and diabetic mouse wound models, this targeted co-delivery strategy significantly improved healing outcomes by stimulating angiogenesis and re-epithelialization, supporting a promising new direction for chronic wound therapy through localized metabolic modulation of the wound niche.