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Povzetek: Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present study were to analyze morphological and biological alterations in the liver of an autistic mouse model, BTBR T + Itpr3tf/J (BTBR) mice, and to identify therapeutic strategies for alleviating hepatic impairments using melatonin administration. We studied hepatic cytoarchitecture, oxidative stress, inflammation and ferroptosis in BTBR mice and used C57BL6/J mice as healthy control subjects. The mice were divided into four groups and then treated and not treated with melatonin, respectively. BTBR mice showed (a) a retarded development of livers and (b) iron accumulation and elevated oxidative stress and inflammation. We demonstrated that the expression of ferroptosis markers, the transcription factor nuclear factor erythroid-related factor 2 (NFR2), was upregulated, and the Kelch-like ECH-associated protein 1 (KEAP1) was downregulated in BTBR mice. Then, we evaluated the effects of melatonin on the hepatic alterations of BTBR mice; melatonin has a positive effect on liver cytoarchitecture and metabolic functions.
Ključne besede: autism spectrum disorder, liver, oxidative stress, inflammation, ferroptosis
Objavljeno v DiRROS: 07.08.2024; Ogledov: 101; Prenosov: 91
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Povzetek: One of the earliest hallmarks of plant immune response is production of reactive oxygen species (ROS) in different subcellular compartments, which regulate plant immunity. A suitable equilibrium, which is crucial to prevent ROS overaccumulation leading to oxidative stress, is maintained by salicylic acid (SA), a chief regulator of ROS. However, ROS not only act downstream of SA signaling, but are also proposed to be a central component of a self-amplifying loop that regulates SA signaling as well as the interaction balance between different phytohormones. The exact role of this crosstalk, the position where SA interferes with ROS signaling and ROS interferes with SA signaling and the outcome of this regulation, depend on the origin of ROS but also on the pathosystem. The precise spatiotemporal regulation of organelle-specific ROS and SA levels determine the effectiveness of pathogen arrest and is therefore crucial for a successful immune response. However, the regulatory interplay behind still remains poorly understood, as up until now, the role of organelle-specific ROS and SA in hypersensitive response (HR)-conferred resistance has mostly been studied by altering the level of a single component. In order to address these aspects, a sophisticated combination of research methods for monitoring the spatiotemporal dynamics of key players and transcriptional activity in plants is needed and will most probably consist of biosensors and precision transcriptomics.
Ključne besede: plant immune response, reactive oxygen species, ROS, salicylic acid, programmed cell death, biotic stress, biotechnology
Objavljeno v DiRROS: 05.08.2024; Ogledov: 112; Prenosov: 58
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Povzetek: Soil salinity and drought are among the most serious agricultural and environmental problems of today. Therefore, investigations of plant resistance to abiotic stress have received a lot of attention in recent years. In this study, we identified the complete coding sequence of a 3′-phosphoadenosine-5′-phosphatase protein, ApHal2, from the halotolerant yeast Aureobasidium pullulans. Expression of the ApHAL2 gene in a Saccharomyces cerevisiae hal2 mutant complemented the mutant auxotrophy for methionine, and rescued the growth of the hal2 mutant in media with high NaCl concentrations. A 21-amino-acids-long region of the ApHal2 enzyme was inserted into the Arabidopsis thaliana homologue of Hal2, the SAL1 phosphatase. The inserted sequence included the META motif, which has previously been implicated in increased sodium tolerance of the Hal2 homologue from a related fungal species. Transgenic Arabidopsis plants overexpressing this modified SAL1 (mSAL1) showed improved halotolerance and drought tolerance. In a medium with an elevated salt concentration, mSAL1-expressing plants were twice as likely to have roots in a higher length category in comparison with the wild-type Arabidopsis and with plants overexpressing the native SAL1, and had 5% to 10% larger leaf surface area under moderate and severe salt stress, respectively. Similarly, after moderate drought exposure, the mSAL1-expressing plants showed 14% increased dry weight after revitalisation, with no increase in dry weight of the wild-type plants. With severe drought, plants overexpressing native SAL1 had the worst rehydration success, consistent with the recently proposed role of SAL1 in severe drought. This was not observed for plants expressing mSAL1. Therefore, the presence of this fungal META motif sequence is beneficial under conditions of increased salinity and moderate drought, and shows no drawbacks for plant survival under severe drought. This demonstrates that adaptations of extremotolerant fungi should be considered as a valuable resource for improving stress-tolerance in plant breeding in the future.
Ključne besede: soil salinity and drought, plant resistance, abiotic stress
Objavljeno v DiRROS: 02.08.2024; Ogledov: 151; Prenosov: 138
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Povzetek: Stress-tolerant fungi that can thrive under various environmental extremes are highly desirable for their application to biological control, as an alternative to chemicals for pest management. However, in fungi, the mechanisms of stress tolerance might also have roles in mammal opportunism. We tested five species with high biocontrol potential in agriculture (Aureobasidium pullulans, Debayomyces hansenii, Meyerozyma guilliermondii, Metschnikowia fructicola, Rhodotorula mucilaginosa) and two species recognized as emerging opportunistic human pathogens (Exophiala dermatitidis, Aureobasidium melanogenum) for growth under oligotrophic conditions and at 37 °C, and for tolerance to oxidative stress, formation of biofilms, production of hydrolytic enzymes and siderophores, and use of hydrocarbons as sole carbon source. The results show large overlap between traits desirable for biocontrol and traits linked to opportunism (growth under oligotrophic conditions, production of siderophores, high oxidative stress tolerance, and specific enzyme activities). Based on existing knowledge and these data, we suggest that oligotrophism and thermotolerance together with siderophore production at 37 °C, urease activity, melanization, and biofilm production are the main traits that increase the potential for fungi to cause opportunistic infections in mammals. These traits should be carefully considered when assessing safety of potential biocontrol agents.
Ključne besede: opportunistic pathogen, biocontrol agent, virulence, stress tolerance, secretome, CAZy, protease, thermotolerance, oligotrophism, melanin, siderophore, biofilm
Objavljeno v DiRROS: 23.07.2024; Ogledov: 128; Prenosov: 140
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Povzetek: Bisphenol A (BPA) is one of the most commonly used substances in the manufacture ofvarious everyday products. Growing concerns about its hazardous properties, including endocrinedisruption and genotoxicity, have led to its gradual replacement by presumably safer analogues inmanufacturing plastics. The widespread use of BPA and, more recently, its analogues has increasedtheir residues in the environment. However, our knowledge of their toxicological profiles is limitedand their combined effects are unknown. In the present study, we investigated the toxic effectscaused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP andBPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed thatBPA did not reduce cell viability in HepG2 spheroids after 24-h exposure. In contrast, BPAP andBPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC)decreased cell viability in a dose-dependent manner, but the significant difference was only observedfor the combination of BPA/BPC (both at 40μM). After 96-h exposure, none of the BPs studiedaffected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cellviability in a dose-dependent manner that was significant for the combination of 4μM BPA and 4μMBPAP. None of the BPs and their binary mixtures studied affected the surface area and growth ofspheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggeredoxidative stress, as measured by the production of reactive oxygen species and malondialdehyde,at both exposure times. Overall, the results suggest that it is important to study the effects of BPsas single compounds. It is even more important to study the effects of combined exposures, as thecombined effects may differ from those induced by single compounds.
Ključne besede: BP analogues, hepatic in vitro 3D cell model, combined exposure, viability, oxidative stress, toxicology
Objavljeno v DiRROS: 12.07.2024; Ogledov: 493; Prenosov: 136
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