Pancreatic ductal adenocarcinoma (PDAC) has limited effective therapeutic strategies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and may affect tumor cell fitness via the mevalonate pathway, mitochondrial function, and redox homeostasis. We systematically compared seven statins in patient-derived PDAC cell lines and related viability effects to mitochondrial, redox, cell-cycle, apoptotic, and metabolic responses. Statins were tested in three PDAC cell lines (PDAC-1/2/3) using MTT assays (5-20 µM; 24-120 h). Based on MTT responses, mechanistic profiling was performed after 72 h at 20 µM concentration using lipophilic statins, including apoptosis (Annexin V/7-AAD), cell-cycle distribution, mitochondrial membrane potential (Δψm), intracellular ROS, and 1H-NMR quantification of intracellular and extracellular metabolites. Statins reduced viability in a concentration- and time-dependent manner, with lipophilic statins more active than hydrophilic. PDAC-1 was highly sensitive, PDAC-3 intermediate, and PDAC-2 comparatively resistant. PDAC-1 and PDAC-3 showed G0/G1 accumulation, Δψm depolarization, reactive oxygen species (ROS) elevation, and Annexin V-positive apoptosis, whereas PDAC-2 (high basal ROS) showed ROS reduction and limited apoptosis despite Δψm loss. Metabolomics indicated reduced glucose and amino-acid utilization and lactate secretion while preserving line-specific metabolic fingerprints. PDAC cell lines display marked inter-tumoral heterogeneity in statin responses, supporting evaluation of statins as chemosensitizing adjuvants in functionally guided PDAC treatment strategies.

Anew in vitromodel for modeling Duchenne muscular dystrophy, derived from pediatric patient with a unique mutation in DMD gene is introduced. Peripheral blood was used as asource for primary cells (mononuclear cells) and subsequently reprogrammed into induced pluripotent stem cells with synthetic Sendai vector. Reprogrammed iPS cells showed the expression of pluripotency factors and the ability to differentiateinto all three germ layers.

Background:Cancer remains a major global health challenge, necessitating innovative prevention and treatment approaches. Certain plants, adapted to specific environments, may exhibit bioactive properties with potential anticancer applications. Hypothesis:Seaberry (Hippophae rhamnoides L.) fruit peels may exert anticancer effects in breast carcinoma (BC) models through the additive or synergistic actions of their unique secondary metabolites. Methods:H. rhamnoides fruit peel extracts were analyzed using the LC-DAD-MS and LC-DAD techniques to profile the content of carotenoids and flavonoids, respectively. The preclinical study evaluated seaberry fruit peel extracts in BC models: (1) a syngeneic 4T1 mouse breast adenocarcinoma model (triple-negative), (2) a rat model of chemically induced mammary carcinogenesis, and (3) in vitro studies with MCF-7 (hormone receptor-positive) and MDA-MB-231 (triple-negative) BC cell lines. Results:LC-DAD-MS and LC-DAD analyses identified dominant metabolites, including isorhamnetin, quercetin glycosides, kaempferol glycosides, catechin, zeaxanthin, and lutein. In the 4T1 mouse model, seaberry treatment resulted in a significant, dose-dependent reduction in tumor volume (43% and 48% compared to controls) and a decrease in the mitotic activity index. Serum cytokine analysis showed dose-dependent reductions in IL-6, IL-10, and TNF-α. In the rat chemopreventive model, high-dose seaberry improved cancer prognosis by reducing the ratio of poorly differentiated tumors and increasing caspase-3 and Bax expression while decreasing Ki-67 and malondialdehyde levels. Both treatment doses elevated the Bax/Bcl-2 ratio and reduced the expression of cancer stem cell markers CD44, EpCam, and VEGF compared to controls. Epigenetic analyses revealed histone modifications (H4K16ac, H4K20me3) and altered methylation of tumor-suppressor genes (PITX2, RASSF1, PTEN, TIMP3). Microarray analysis (758 miRNAs) identified beneficial changes in nine oncogenic/tumor-suppressive miRNAs, including miR-10a-5p, miR-322-5p, miR-450a-5p, miR-142-5p, miR-148b-3p, miR-1839-3p, miR-18a-5p, miR-1949, and miR-347. In vitro, ethanolic seaberry extract conferred partial resistance to cisplatin-induced cytotoxicity in MCF-7 and MDA-MB-231 cells at IC50 concentrations. Conclusion:This study of H. rhamnoides in rodent BC models shows promising data but requires rigorous, long-term validation. Integrating plant-based nutraceuticals into oncology necessitates precise cancer-type profiling and patient stratification for effective personalized treatments.

Cardiovascular diseases (CVD) are the leading cause of premature death and disability. Hypoxic conditions play a central role in the pathophysiology of all CVD. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor used for diabetes mellitus type II therapy, has demonstrated a beneficial role in improving cardiovascular outcomes for patients with heart failure. Our study aimed to assess the cardioprotective effect of EMPA on primary human cardiomyocytes in a chemically induced hypoxia model. The cardioprotective effect of the SGLT2 inhibitor was evaluated through four individual experiments including: (1) evaluating mitochondrial network integrity, (2) determining cell count, (3) metabolomic profiling, and (4) determining alterations in miRNA expression. After 24 h of EMPA treatment, we observed a significant improvement in mitochondrial network complexity, as evidenced by increased branching (p < 0.05) and a reduced number of rod-shaped mitochondria (p < 0.05) in EMPA-treated cells compared to controls. After cobalt treatment, we didn't observe any protective effect of EMPA in cells affected by cobalt in various biological aspects, including miRNA expression, metabolomics, or viability. Although EMPA treatment was not able to propagate beneficial effects in the presence of cobalt, pretreatment of cells with EMPA indicated a potential cardioprotective effect associated with improving mitochondrial morphology.

Metastatic colorectal cancer is one of the most critical causes of cancer-related dead in patients suffering this type of malignancy. As the liver metastases are found in almost 25-50% of all colorectal cancer patients, there is an urgent need for suitable in vitro and in vivo models. To the best of our knowledge, only a limited number of well-described 2D or 3D organoid/spheroid cell lines originated from human liver metastases was reported for this type of malignancy and submitted to ATCC and other repository centers for general use. Here, we present a novel, well-characterized cell line Coala that was derived directly from liver metastasis of patient with colorectal cancer. Coala cancer cell line was derived by 2D and 3D culture technology and can be, therefore, cultured as standard 2D cell line or as 3D spheroid culture. When transplanted into athymic mice, Coala cell line forms fast growing tumors with histological features similar to original tumor and expressed CDX2, SATB2, and CK20. Whole exome sequencing analysis of Coala cell line showed the presence of pathogenic mutations in C8B, PRKCQ, IRGM, FGFR4, POLR1C, APC and TP53 genes. As verified by antibody array chip analysis, Coala cells express Snail, Pdx-1, FoxA2, and E-cadherin. Our cell line represents a new, well characterized in vitro research tool for cancer research and will be available to researchers in the field via biorepository centers.

BACKGROUND:Breast cancer (BC) is the most commonly diagnosed malignancy in women (∼25% of new cases). Plants adapted to specific niches accumulate secondary metabolites with bioactivity, including anticancer effects. OBJECTIVE:The objective of this study was to evaluate the chemopreventive and treatment potential of Vaccinium myrtillus (bilberry) peel-enriched pomace powder in BC models, hypothesizing system-level effects and synergy with standard therapy. METHODS:Chemistry was profiled by liquid chromatography with diode-array detection-mass spectrometry (LC-DAD-MS)/liquid chromatography with diode-array detection (LC-DAD) from 2 extracts: BILHEX (hexane) and BILMeOH (methanol). Biology was tested in the following: 1) 4T1 triple-negative mouse model (treatment); 2) NMU rat mammary carcinogenesis (chemoprevention); and 3) in vitro assays with MCF-7 and MDA-MB-231, including 3D spheroids and cisplatin combinations. RESULTS:BILMeOH was enriched for phenolics; BILHEX for unsaturated triacylglycerols/triterpene acids. Compared with control, bilberry diet reduced 4T1 tumor volume by 51% and 91% (low/high dose; P < 0.05/0.001), lowered mitotic index (P < 0.001), and reduced necrosis:tumor ratio (P < 0.05). In NMU rats, chemoprevention increased cleaved caspase-3 (P < 0.05) and Bax/Bcl-2 (P < 0.001), and decreased Ki-67 (P < 0.05), MDA, and CD133 (P < 0.01). Histone marks shifted (↓H3K4me3 P < 0.05; ↑H4K20me3 P < 0.01; ↑H4K16ac P < 0.001). Promoter methylation was gene-specific (e.g., RASSF1 +12% absolute, P < 0.05); low-baseline loci were treated as low magnitude. miRNA profiling (758 features) identified significant dysregulation (|FC| ≥ 2) of let-7d-5p, let-7i-5p, miR-1224-3p, miR-494-3p, and miR-6216. TGF-β and IL-10 increased (both P < 0.001), IL-6 rose (P < 0.05), indicating selective immunomodulation. Metabolomics showed shifts in lactate (P < 0.05), branched-chain ketoacids (P < 0.05/0.01), and histidine (P < 0.001). In vitro, BILHEX suppressed proliferation, induced G2/M arrest, activated intrinsic apoptosis (cytochrome-c → caspase-9 → caspase-3/7 → PARP), and synergized with cisplatin in 3D spheroids (Bliss). CONCLUSIONS:Bilberry pomace shows multitarget anticancer activity across BC models; translational studies should confirm mechanisms, refine dosing, and explore biomarker-guided use.

Up-to-date data on roles of ATP‑sensitive potassium (KATP) channels indicate their emerging roles in neurodegeneration. The aim of present study was to evaluate the significance of KATP channels on cell viability, calcium dynamics, and mitochondrial morphology with the accent on their intracellular localization. We distinguished between whole-cell KATP effects and specific effects of mitochondrial KATP under both physiological conditions and pathological conditions simulating in vitro Parkinson´s-type neurodegeneration. SH‑SY5Y cells with its high fidelity to dopaminergic neurons were treated for 24 h with the non‑selective KATP opener pinacidil and blocker glibenclamide, or with the mitochondrial KATP opener diazoxide and blocker 5‑hydroxydecanoate (5HD). The effects of modulators were analysed alone or alongside with rotenone, which is widely used as an inducer of Parkinson´s-type neurodegeneration. Intracellular calcium distribution and mitochondrial rebuild pattern was evaluated using the cell segmentation performed by fluorescent confocal microscopy. Although none of the KATP modulators reversed the negative effects of rotenone, significant and selective effects of mitochondrial KATP modulation on calcium homeostasis and mitochondrial morphology were observed. For antagonists, both compounds showed consistent effects, with non-selective glibenclamide exerting stronger effects, particularly in elevating calcium. More distinctive results were obtained for agonists: both reduced calcium concentration; however, pinacidil tended to induce mitochondrial fragmentation, an effect absent in diazoxide-treated cells. Furthermore, strong correlations were identified between calcium levels and several mitochondrial and cell viability parameters.

Based on the potential of DPSCs as the most promising candidates for bone tissue engineering, we comprehensively investigated the time-dependent cellular and molecular changes that occur during their osteodifferentiation. To analyze this area in-depth, we used both cellular and molecular approaches. Morphological changes were monitored using bright-field microscopy, while the production of mineral deposits was quantified spectrophotometrically. The expression of a key mesenchymal stem cell marker, CD90, was assessed via flow cytometry. Finally, protein-level changes in whole cells were examined by fluorescence microscopy. Our results show successful long-term osteodifferentiation of the patient’s DPSCs within 25 days. In differentiated cells, mineralized extracellular matrix production gradually increased; in contrast, the expression of the specific stem cell marker CD90 significantly decreased. We observed dynamic changes in intracellular and extracellular proteins when collagen1 A1 and osteopontin appeared as earlier markers of osteogenesis, while apolipoprotein A2, bone morphogenetic protein 9, dentin sialophosphoprotein, and matrix metalloproteinase 8 were produced mainly in the late stages of this process. A decrease in actin microfilament expression indicated a reduction in cell proliferation, which could be used as another marker of osteogenic initiation. Our results suggest a coordinated process in vitro in which cells synthesize the necessary proteins and matrix components to regulate the growth of hydroxyapatite crystals and form the bone matrix.

Major depressive disorder (MDD) in adolescents is a prevalent psychiatric condition worldwide with severe consequences. Growing evidence shows that microRNAs (miRNAs) regulate many processes hypothesized to be involved in the pathogenesis of MDD including inflammation, suggesting their suitability as biomarkers. Still, more research is needed regarding miRNAs as biomarkers and the role of inflammation in adolescents with MDD. This study applied the NanoString nCounter technology to identify dysregulated miRNAs in plasma from hospitalized female adolescents with MDD compared to healthy controls, as well as before and after antidepressant treatment. A multiplexed immunoassay was also performed to assess the plasma levels of 27 inflammatory proteins. A total of 33 patients and 14 healthy controls were included in the study. miR-1246 and miR-1253 were downregulated in female adolescents with MDD compared to healthy controls, suggesting their potential as diagnostic biomarkers. Additionally, miR-496 was downregulated with treatment, indicating its potential as a prognostic biomarker. Moreover, increased levels of PDGF-BB and IL-7 were seen in adolescents with MDD compared to healthy controls, while IL-9 and MIP-1β levels decreased with antidepressant treatment. Finally, the expression of specific miRNAs were found to correlate with the levels of several inflammatory proteins. In summary, miR-1246, miR-1253, and miR-496 are suggested as potential diagnostic and prognostic biomarkers. Furthermore, this study contributes in more detail to our understanding of miRNAs, inflammation, and MDD in female adolescents.

Background: Colorectal cancer is the third most diagnosed cancer and a leading cause of cancer-related deaths worldwide. Early detection significantly improves patient outcomes, yet many cases are identified only at late stages. The high molecular and genetic heterogeneity of colorectal cancer presents major challenges in accurate diagnosis, prognosis, and therapeutic stratification. Recent advances in gene expression profiling offer new opportunities to discover genes that play a role in colorectal cancer carcinogenesis and may contribute to early diagnosis, prognosis prediction, and the identification of novel therapeutic targets. Methods: This study involved 142 samples: 84 primary tumor samples, 27 liver metastases, and 31 adjacent non-tumor tissues serving as controls. RNA sequencing was performed on a subset of tissues (12 liver metastases and 3 adjacent non-tumor tissues) using a targeted RNA panel covering 395 cancer-related genes. Data processing and differential gene expression analysis were carried out using the DRAGEN RNA and DRAGEN Differential Expression tools. The expression of six genes involved in hypoxia and epithelial-to-mesenchymal transition (EMT) pathways (SLC16A3, ANXA2, P4HA1, SPP1, KRT19, and LGALS3) identified as significantly differentially expressed was validated across the whole cohort via quantitative real-time PCR. The relative expression levels were determined using the ΔΔct method and log2FC, and compared between different groups based on the sample type; clinical parameters; and mutational status of the genes KRAS, PIK3CA, APC, SMAD4, and TP53. Results: Our results suggest that the expression of all the validated genes is significantly altered in metastases compared to non-tumor control samples (p < 0.05). The most pronounced change occurred for the genes P4HA1 and SPP1, whose expression was significantly increased in metastases compared to non-tumor and primary tumor samples, as well as between clinical stages of CRC (p < 0.001). Furthermore, all genes, except for LGALS3, exhibited significantly altered expression between non-tumor samples and samples in stage I of the disease, suggesting that they play a role in the early stages of carcinogenesis (p < 0.05). Additionally, the results suggest the mutational status of the KRAS gene did not significantly affect the expression of any of the validated genes, indicating that these genes are not involved in the carcinogenesis of KRAS-mutated CRC. Conclusions: Based on our results, the genes P4HA1 and SPP1 appear to play a role in the progression and metastasis of colorectal cancer and are candidate genes for further investigation as potential biomarkers in CRC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease. Specific modifications in DNA methylation, histone marks, and non-coding RNAs are emerging as robust predictors of disease progression and patient survival, offering the potential for more precise prognostic tools compared to conventional clinical staging. Moreover, the detection of epigenetic alterations in blood and other non-invasive samples holds promise for earlier diagnosis and improved manage- ment of PDAC.This review comprehensively summarises current epigenetic research in PDAC and identifies persisting challenges. These include the complex nature of epigenetic profiles, tumour hetero- geneity, limited access to early-stage samples, and the need for highly sensitive liquid biopsy technologies. Addressing these challenges requires the standardisation of methodologies, integra- tion of multi-omics data, and leveraging advanced computational tools such as machine learning and artificial intelligence. While resource-intensive, these efforts are essential for unravelling the functional consequences of epigenetic changes and translating this knowledge into clinical appli- cations. By overcoming these hurdles, epigenetic research has the potential to revolutionise the management of PDAC and improve patient outcomes.

Mesenchymal stem cells (MSCs) are an essential tool in cell-based therapies. One of the most crucial factors for efficacy in regenerative medicine is the source of MSCs. Tissue origin has long been suggested as a potential determinant of MSC properties. Human dermal fibroblasts (HDFa) share similar characteristics with MSCs, and the question of whether HDFa are functionally equivalent to MSCs remains debated. The present work used proteomic and phenotypic analyses to compare HDFa, dental pulp stem cells (DPSCs), and adipose-derived mesenchymal stem cells (AD-MSCs). We observed similarities and/or differences in morphology, cell surface markers, differentiation, and proteomic profile. Proteome was profiled by nano liquid chromatography and comprehensively quantified by mass spectrometry. In fact, HDFa and MSCs shared similar surface markers, growth kinetics, and differentiation capacity. Proteomic analysis reproducibly identified and quantified 3,051 proteins, 86 of them were differentially abundant according to strict statistical criteria. We identified a set of proteins that determined signatures for each stem cell origin. Gene Ontology (GO) term enrichment of differentially accumulated proteins, and Gene Set Enrichment Analysis (GSEA) identified signaling pathways characteristic to individual cell types. Particularly, we highlighted signaling pathways involved in cell migration, adhesion, and Wnt signaling as downregulated in HDFa compared to DPSCs. Angiogenesis and vascularization were explicitly associated with AD-MSCs. The tissue repair process requires a well-coordinated integration of complex molecular events, including cell migration and proliferation, extracellular matrix deposition, angiogenesis, and remodeling. We propose that HDFa are an alternative to MSCs, but predict their worse behavior in defect repair models compared to DPSCs. Plausibly, AD-MSCs are more suitable candidates for angiogenesis models compared to DPSCs.

Inward rectifying potassium channels sensitive to ATP levels (KATP) have been the subject of investigation for several decades. Modulators of KATP channels are well-established treatments for metabolic as well as cardiovascular diseases. Experimental studies have also shown the potential of KATP modulation in neurodegenerative disorders. However, to date, data regarding the effects of KATP antagonists/agonists in experiments related to neurodegeneration remain inconsistent. The main source of confusion in evaluating available data seems to be the choice of experimental models. The present study aims to provide a comprehensive understanding of the effects of both opening and blocking KATP channels in two forms of SH-SY5Y cells. Our results offer valuable insights into the significance of metabolic differences between differentiated and non-differentiated SH-SY5Y cells, particularly in the context of glibenclamide and diazoxide effects under normal conditions and during the initiation of pathological events simulating Parkinson's disease in vitro. We emphasize the analysis of mitochondrial functions and changes in mitochondrial network morphology. The heightened protein expression of KATP channels identified in non-differentiated SH-SY5Y cells seems to be a platform for a more significant impact of KATP modulators in this cell type. The efficiency of rotenone treatment in inducing morphological changes in the mitochondrial network depends on the differentiation status of SH-SY5Y cells.

The analysis of volatile organic compounds (VOCs) present in various biological samples holds immense potential for non-invasive disease diagnostics and metabolic profiling. One of the biological fluids that are suitable for use in clinical practice is urine. Given the limited quantity of VOCs in the urine headspace, it's imperative to enhance their extraction into the gaseous phase and prevent any degradation of VOCs during the thawing process. The study aimed to test several key parameters (incubation time, temperature, and thawing) that can influence urine volatilome and monitor selected VOCs for their stability. The analysis in this study was performed using a BreathSpec® (G.A.S., Dortmund, Germany) device consisting of a gas chromatograph (GC) coupled with an ion mobility spectrometer (IMS). Testing three different temperatures and incubation times yielded a low number of VOCs (9 out of 34) that exhibited statistically significant differences. However, examining three thawing conditions revealed no VOCs with statistically significant changes. Thus, we conclude that urine composition remains relatively stable despite exposure to various thermal stresses.

Metabolomics has proven to be a sensitive tool for monitoring biochemical processes in cell culture. It enables multi-analysis, clarifying the correlation between numerous metabolic pathways. Together with other analysis, it thus provides a global view of a cell’s physiological state. A comprehensive analysis of molecular changes is also required in the case of mesenchymal stem cells (MSCs), which currently represent an essential portion of cells used in regenerative medicine. Reproducibility and correct measurement are closely connected to careful metabolite extraction, and sample preparation is always a critical point. Our study aimed to compare the efficiencies of four harvesting and six extraction methods. Several organic reagents (methanol, ethanol, acetonitrile, methanol–chloroform, MTBE) and harvesting approaches (trypsinization vs. scraping) were tested. We used untargeted nuclear magnetic resonance spectroscopy (NMR) to determine the most efficient method for the extraction of metabolites from human adherent cells, specifically human dermal fibroblasts adult (HDFa) and dental pulp stem cells (DPSCs). A comprehensive dataset of 29 identified and quantified metabolites were determined to possess statistically significant differences in the abundances of several metabolites when the cells were detached mechanically to organic solvent compared to when applying enzymes mainly in the classes of amino acids and peptides for both types of cells. Direct scraping to organic solvent is a method that yields higher abundances of determined metabolites. Extraction with the use of different polar reagents, 50% and 80% methanol, or acetonitrile, mostly showed the same quality. For both HDFa and DPSC cells, the MTBE method, methanol–chloroform, and 80% ethanol extractions showed higher extraction efficiency for the most identified and quantified metabolites Thus, preparation procedures provided a cell sample processing protocol that focuses on maximizing extraction yield. Our approach may be useful for large-scale comparative metabolomic studies of human mesenchymal stem cell samples.

IntroductionWithin oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer.HypothesisChokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment.Aims of the study and MethodsBased on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells.ResultsThe dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines.ConclusionThis study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.

Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments.

In recent decades, we have seen significant technical progress in the modern world, leading to the widespread use of telecommunications systems, electrical appliances, and wireless technologies. These devices generate electromagnetic radiation (EMR) and electromagnetic fields (EMF) most often in the extremely low frequency or radio-frequency range. Therefore, they were included in the group of environmental risk factors that affect the human body and health on a daily basis. In this study, we tested the effect of exposure EMF generated by a new prototype wireless charging system on four human cell lines (normal cell lines—HDFa, NHA; tumor cell lines—SH-SY5Y, T98G). We tested different operating parameters of the wireless power transfer (WPT) device (87–207 kHz, 1.01–1.05 kW, 1.3–1.7 mT) at different exposure times (pulsed 6 × 10 min; continuous 1 × 60 min). We observed the effect of EMF on cell morphology and cytoskeletal changes, cell viability and mitotic activity, cytotoxicity, genotoxicity, and oxidative stress. The results of our study did not show any negative effect of the generated EMF on either normal cells or tumor cell lines. However, in order to be able to estimate the risk, further population and epidemiological studies are needed, which would reveal the clinical consequences of EMF impact.