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Iskalni niz: "ključne besede" (metabolism) .

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1.
Metabolic rates of groundwater species as a function of body mass and temperature
Tiziana Di Lorenzo, Nataša Mori, Tatjana Simčič, 2024, pregledni znanstveni članek

Povzetek: Research on the metabolic physiology of groundwater species, particularly regarding oxygen consumption rates (OCR), has made significant advancement, revealing valuable insights into the adaptations of exclusively groundwater-dwelling (stygobitic) species. However, a comprehensive understanding of how these metabolic rates scale with body mass and respond to temperature changes remains elusive. This study aims to bridge this gap by reviewing published data on OCR across a variety of groundwater organisms to elucidate patterns of metabolic rates in relation to body size and temperature. We employed a combination of literature review and quantitative analyses, focusing on the allometric scaling of OCR with body weight and the effect of temperature on metabolic rates. Our findings indicate that OCR scales with body weight in an allometric pattern, with an inter-species slope of 0.80, suggesting non-isometric scaling. Furthermore, our analysis showed that stygobitic species’ metabolic rates are less responsive to warming than those of non-stygobitic species at low to moderate temperatures. However, at higher temperatures, metabolic rates in stygobitic species decline faster than in non-stygobitic taxa, highlighting a potential vulnerability to global climate change. This study contributes to our understanding of the metabolic strategies of groundwater species, underscoring the need for further research to fully grasp the eco-evolutionary implications of these findings for groundwater conservation.
Ključne besede: allometry, Arrhenius equation, ectotherms, metabolism, oxygen consumption rate, respiration, stygobiont
Objavljeno v DiRROS: 13.09.2024; Ogledov: 45; Prenosov: 44
.pdf Celotno besedilo (1,63 MB)
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2.
Energy metabolism in IDH1 wild-type and IDH1-mutated glioblastoma stem cells : a novel target for therapy?
Cornelis J. F. van Noorden, Vashendriya V. V. Hira, Amber J. van Dijck, Metka Novak, Barbara Breznik, Remco J. Molenaar, 2021, pregledni znanstveni članek

Povzetek: Cancer is a redox disease. Low levels of reactive oxygen species (ROS) are beneficial for cells and have anti-cancer effects. ROS are produced in the mitochondria during ATP production by oxidative phosphorylation (OXPHOS). In the present review, we describe ATP production in primary brain tumors, glioblastoma, in relation to ROS production. Differentiated glioblastoma cells mainly use glycolysis for ATP production (aerobic glycolysis) without ROS production, whereas glioblastoma stem cells (GSCs) in hypoxic periarteriolar niches use OXPHOS for ATP and ROS production, which is modest because of the hypoxia and quiescence of GSCs. In a significant proportion of glioblastoma, isocitrate dehydrogenase 1 (IDH1) is mutated, causing metabolic rewiring, and all cancer cells use OXPHOS for ATP and ROS production. Systemic therapeutic inhibition of glycolysis is not an option as clinical trials have shown ineffectiveness or unwanted side effects. We argue that systemic therapeutic inhibition of OXPHOS is not an option either because the anti-cancer effects of ROS production in healthy cells is inhibited as well. Therefore, we advocate to remove GSCs out of their hypoxic niches by the inhibition of their binding to niches to enable their differentiation and thus increase their sensitivity to radiotherapy and/or chemotherapy.
Ključne besede: glioblastoma stem cells, IDH1-mutation, energy metabolism
Objavljeno v DiRROS: 05.08.2024; Ogledov: 218; Prenosov: 200
.pdf Celotno besedilo (3,87 MB)
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3.
Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy
Bahar Yetkin-Arik, Arnoud W. Kastelein, Ingeborg Klaassen, Charlotte H. J. R. Jansen, Yani P. Latul, Miloš Vittori, Aydan Biri, Korhan Kahraman, Arjan W. Griffioen, Frederic Amant, Christianne A. R. Lok, Reinier O. Schlingemann, Cornelis J. F. van Noorden, 2021, pregledni znanstveni članek

Povzetek: Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers. We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment.
Ključne besede: angiogenesis, anti-angiogenic therapy, endothelial cells, endothelial cell metabolism, gynecological cancer, non-tip cells, tip cells, tumor microenvironment, vascular disrupting agents
Objavljeno v DiRROS: 05.08.2024; Ogledov: 177; Prenosov: 157
.pdf Celotno besedilo (5,60 MB)
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4.
Metabolic potential, respiration rate and their relationship in offspring of different sizes of marble trout (Salmo marmoratus Cuvier)
Anton Brancelj, Tatjana Simčič, Dušan Jesenšek, 2015, izvirni znanstveni članek

Povzetek: The size and composition of fish eggs are related to female’s characteristics, such as age, size and individual conditions, and they have an impact on the properties of offspring that are important for their fitness. Electron transport system (ETS) activity and respiration rate (R) of early life history stages (i.e. non-fertilized eggs, eggs at eyed stage and larvae with yolk sac) of 13 females of marble trout (Salmo marmoratus) were measured separately in order to determine their metabolic properties in relation to size. The results showed that larger females produced larger eggs in higher numbers. Growth experiments on the survival of offspring of a single female revealed that the survival rate of early embryos was higher for smaller eggs during the earliest stages, but ultimately the percentage of surviving larvae did not correlate with egg size. The ETS activities and respiration rates of non-fertilized eggs, eyed eggs and larvae differed significantly between 13 females. Both parameters increased with increasing dry mass of the early life history stages, but the increase of respiration rate was greater than that of ETS activity. The lower ETS/R ratios in larger individuals therefore indicate that their energy metabolism was less adaptable to environmental changes than that of smaller ones. Larger egg size could be an advantage under favourable conditions, whereas smaller size could be optimal under stressing circumstances in which the higher metabolic potential enables production of the energy required for metabolism. This is first report on the relationship between ETS activity and respiration rate of the early life history stages in salmonids.
Ključne besede: Salmo marmoratus, fitness, metabolism, ETS activity, ETS/R ratio, fishes
Objavljeno v DiRROS: 29.07.2024; Ogledov: 203; Prenosov: 121
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5.
MitomiRs: their roles in mitochondria and importance in cancer cell metabolism
Andrej Renčelj, Nada Gvozdenović, Maja Čemažar, 2021, pregledni znanstveni članek

Povzetek: Background. MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in almost all biological path- ways. They regulate post-transcriptional gene expression by binding to the 3%untranslated region (3%UTR) of messenger RNAs (mRNAs). MitomiRs are miRNAs of nuclear or mitochondrial origin that are localized in mitochondria and have a crucial role in regulation of mitochondrial function and metabolism. In eukaryotes, mitochondria are the major sites of oxidative metabolism of sugars, lipids, amino acids, and other bio-macromolecules. They are also the main sites of adenosine triphosphate (ATP) production. Conclusions. In the review, we discuss the role of mitomiRs in mitochondria and introduce currently well studied mito- miRs, their target genes and functions. We also discuss their role in cancer initiation and progression through the regu- lation of mRNA expression in mitochondria. MitomiRs directly target key molecules such as transporters or enzymes in cell metabolism and regulate several oncogenic signaling pathways. They also play an important role in the Warburg effect, which is vital for cancer cells to maintain their proliferative potential. In addition, we discuss how they indirectly upregulate hexokinase 2 (HK2), an enzyme involved in glucose phosphorylation, and thus may affect energy metabo- lism in breast cancer cells. In tumor tissues such as breast cancer and head and neck tumors, the expression of one of the mitomiRs (miR-210) correlates with hypoxia gene signatures, suggesting a direct link between mitomiR expression and hypoxia in cancer. The miR-17/92 cluster has been shown to act as a key factor in metabolic reprogramming of tumors by regulating glycolytic and mitochondrial metabolism. This cluster is deregulated in B-cell lymphomas, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, and T-cell lymphomas, and is particularly overexpressed in several other cancers. Based on the current knowledge, we can conclude that there is a large number of miRNAs present in mitochondria, termed mitomiR, and that they are important regulators of mitochondrial function. Therefore, mitomiRs are important players in the metabolism of cancer cells, which need to be further investigated in order to develop a potential new therapies for cancer.
Ključne besede: microRNAs, mitomiR, mitochondria, cancer cell metabolism
Objavljeno v DiRROS: 22.07.2024; Ogledov: 216; Prenosov: 86
.pdf Celotno besedilo (736,13 KB)

6.
Direct regulation of shikimate, early phenylpropanoid, and stilbenoid pathways by subgroup 2 R2R3-MYBs in grapevine
Luis Orduña, Miaomiao Li, David Navarro-Payá, Chen Zhang, A. Santiago, Pablo Romero, Živa Ramšak, Gabriele Magon, Janine Höll, Patrick Merz, Kristina Gruden, Alessandro Vannozzi, Dario Cantu, Jochen Bogs, Darren C. J. Wong, Shao-shan Carol Huang, José Tomás Matus, 2022, izvirni znanstveni članek

Povzetek: The stilbenoid pathway is responsible for the production of resveratrol in grapevine (Vitis vinifera L.). A few transcription factors (TFs) have been identified as regulators of this pathway but the extent of this control has not been deeply studied. Here we show how DNA affinity purification sequencing (DAP-Seq) allows for the genome-wide TF-binding site interrogation in grape. We obtained 5190 and 4443 binding events assigned to 4041 and 3626 genes for MYB14 and MYB15, respectively (approximately 40% of peaks located within −10 kb of transcription start sites). DAP-Seq of MYB14/MYB15 was combined with aggregate gene co-expression networks (GCNs) built from more than 1400 transcriptomic datasets from leaves, fruits, and flowers to narrow down bound genes to a set of high confidence targets. The analysis of MYB14, MYB15, and MYB13, a third uncharacterized member of Subgroup 2 (S2), showed that in addition to the few previously known stilbene synthase (STS) targets, these regulators bind to 30 of 47 STS family genes. Moreover, all three MYBs bind to several PAL, C4H, and 4CL genes, in addition to shikimate pathway genes, the WRKY03 stilbenoid co-regulator and resveratrol-modifying gene candidates among which ROMT2-3 were validated enzymatically. A high proportion of DAP-Seq bound genes were induced in the activated transcriptomes of transient MYB15-overexpressing grapevine leaves, validating our methodological approach for delimiting TF targets. Overall, Subgroup 2 R2R3-MYBs appear to play a key role in binding and directly regulating several primary and secondary metabolic steps leading to an increased flux towards stilbenoid production. The integration of DAP-Seq and reciprocal GCNs offers a rapid framework for gene function characterization using genome-wide approaches in the context of non-model plant species and stands up as a valid first approach for identifying gene regulatory networks of specialized metabolism.
Ključne besede: secondary metabolism, regulatory networks, transcription factors, transcriptional regulation, DNA affinity purification sequencing
Objavljeno v DiRROS: 16.07.2024; Ogledov: 203; Prenosov: 152
.pdf Celotno besedilo (20,80 MB)
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7.
Leafhopper males compensate for unclear directional cues in vibration-mediated mate localization
Jernej Polajnar, Ana Kuhelj, Rok Janža, Nada Žnidaršič, Tatjana Simčič, Meta Virant-Doberlet, 2023, izvirni znanstveni članek

Povzetek: Ambient noise and transmission properties of the substrate pose challenges in vibrational signal-mediated mating behavior of arthropods, because vibrational signal production is energetically demanding. We explored implications of these challenges in the leafhopper Aphrodes makarovi (Insecta: Hemiptera: Cicadellidae) by exposing males to various kinds of vibrational noise on a natural substrate and challenging them to find the source of the female playback. Contrary to expectations, males exposed to noise were at least as efficient as control males on account of similar searching success with less signaling effort, while playing back male–female duets allowed the males to switch to satellite behavior and locate the target without signaling, as expected. We found altered mitochondrial structure in males with high signaling effort that likely indicate early damaging processes at the cellular level in tymbal muscle, but no relation between biochemical markers of oxidative stress and signaling effort. Analysis of signal transmission revealed ambiguous amplitude gradients, which might explain relatively low searching success, but it also indicates the existence of behavioral adaptations to complex vibrational environments. We conclude that the observed searching tactic, emphasizing speed rather than thorough evaluation of directional cues, may compensate for unclear stimuli when the target is near.
Ključne besede: biotremology, vibrational communication, sexual behavior of insects, impact of noise on behavior, metabolism of vibrational production
Objavljeno v DiRROS: 12.07.2024; Ogledov: 180; Prenosov: 197
.pdf Celotno besedilo (2,12 MB)
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8.
9.
Exploring the safety of cannabidiol (CBD) : a comprehensive in vitro evaluation of the genotoxic and mutagenic potential of a CBD isolate and extract from Cannabis sativa L
Alja Štern, Matjaž Novak, Katja Kološa, Jurij Trontelj, Sonja Žabkar, Tjaša Šentjurc, Metka Filipič, Bojana Žegura, 2024, izvirni znanstveni članek

Povzetek: Cannabidiol (CBD), a naturally occurring cyclic terpenoid found in Cannabis sativa L., is renowned for its diverse pharmacological benefits. Marketed as a remedy for various health issues, CBD products are utilized by patients as a supplementary therapy or post-treatment failure, as well as by healthy individuals seeking promised advantages. Despite its widespread use, information regarding potential adverse effects, especially genotoxic properties, is limited. The present study is focused on the mutagenic and genotoxic activity of a CBD isolate (99.4 % CBD content) and CBD-rich Cannabis sativa L extract (63.6 % CBD content) in vitro. Both CBD samples were non-mutagenic, as determined by the AMES test (OECD 471) but exhibited cytotoxicity for HepG2 cells (~IC50 (4 h) 26 µg/ml, ~IC50 (24 h) 6–8 µg/ml, MTT assay). Noncytotoxic concentrations induced upregulation of genes encoding metabolic enzymes involved in CBD metabolism, and CBD oxidative as well as glucuronide metabolites were found in cell culture media, demonstrating the ability of HepG2 cells to metabolize CBD. In this study, the CBD samples were found non-genotoxic. No DNA damage was observed with the comet assay, and no influence on genomic instability was observed with the cytokinesis block micronucleus and the γH2AX and p-H3 assays. Furthermore, no changes in the expression of genes involved in genotoxic stress response were detected in the toxicogenomic analysis, after 4 and 24 h of exposure. Our comprehensive study contributes valuable insights into CBD’s safety profile, paving the way for further exploration of CBD’s therapeutic applications and potential adverse effects.
Ključne besede: cannabidiol, CBD, metabolism, cytotoxicity, genotoxicity, mutagenicity
Objavljeno v DiRROS: 09.07.2024; Ogledov: 195; Prenosov: 181
.pdf Celotno besedilo (4,31 MB)
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10.
New insights in ATP synthesis as therapeutic target in cancer and angiogenic ocular diseases
Cornelis J. F. van Noorden, Bahar Yetkin-Arik, Paola Serrano Martinez, Noëlle Bakker, Mathilda E. van Breest Smallenburg, Reinier O. Schlingemann, Ingeborg Klaassen, Bernarda Majc, Anamarija Habič, Urban Bogataj, Katrin S. Galun, Miloš Vittori, Mateja Erdani-Kreft, Metka Novak, Barbara Breznik, Vashendriya V. V. Hira, 2024, pregledni znanstveni članek

Povzetek: Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production.
Ključne besede: aerobic glycolysis, anaerobic glycolysis, angiogenesis, ATP synthesis, cancer cells, cancer stem cells, endothelial cells, energy metabolism, eye diseases, oxidative phosphorylation, pericytes, retina, Warburg effect
Objavljeno v DiRROS: 18.06.2024; Ogledov: 273; Prenosov: 153
.pdf Celotno besedilo (3,75 MB)
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