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Ključne besede: Campylobacter jejuni, luxS, intercellular signaling, transcriptome, proteome, metabolism, stress response
Objavljeno v DiRROS: 12.07.2024; Ogledov: 56; Prenosov: 31
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Povzetek: Malignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known. Materials and methods The immunoassay and MTT assay were used to assess the concentration of secreted VEGF and cell viability after bevacizumab exposure. Metabolomic studies on cells were performed using high resolution magic angle spinning spectroscopy (HRMAS). Results mIDH1-U87 cells secreted VEGF (13 ng/mL). Regardless, bevacizumab had no cytotoxic effect, even after a 72h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (polyunsaturated fatty acids [PUFA], glycerophosphocholine, and phosphocholine). Conclusions In mIDH1-U87 cells, changes in glutamine group metabolites and lipids were identified as metabolic markers of bevacizumab treatment. These data support the possibility of a functional tricarboxylic acid cycle that runs in reductive manner, as a probable mechanism of action of bevacizumab in IDH1 mutated gliomas and propose a new target pathway for effective treatment of malignant gliomas.
Ključne besede: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer, idh1 mutation, malignant glioma, bevacizumab, metabolic fingerprint
Objavljeno v DiRROS: 11.06.2024; Ogledov: 80; Prenosov: 37
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Povzetek: The pedunculate oak (Quercus robur L.) is economically and ecologically one of the most significant tree species in Serbia, however, little is known about the influence of the riverbed distance and its water supply on ecophysiological responses of this species. Given the limited information on the light-response curve of photosynthesis for oaks in southwest Srem, Serbia, the aim of this paper is to enhance understanding of their ecophysiological responses in this context. Maximum assimilation rate (Amax), the quantum yield (Ф), and light compensation point (LCP) were compared in adult trees situated along the transect from the river: (1) close to the river, (2) intermediate, (3) farthest from the river, and (4) forest reserve (second closest), with the first three transects being managed forests and the last one being an unmanaged forest reserve. The measurements were conducted in July during the first evidence of drought. The highest Amax rates were measured in all light intensities on the site closest to the river and the smallest on the site that was most distant to the water source. The most efficient were trees close to the river and the ones in the forest reserve. No significant difference between compensation points was confirmed for the studied groups of trees, although the forest reserve trees showed slightly higher values. The results demonstrated clear response between transects, which followed the distance from the riverbed. Pedunculate oak's reliance on groundwater is in tight relation with ecophysiological processes in trees; groundwater depletion may threaten its survival in areas distant from the river.
Ključne besede: Quercus robur L., floodplain forest, drought, light-response curves, transects
Objavljeno v DiRROS: 05.06.2024; Ogledov: 1105; Prenosov: 83
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Povzetek: Predicting global change mitigations based on environmental variables, like temperature and water availability, although yielding insightful hypothesis still lacks the integration of environmental responses. Physiological limits should be assessed to obtain a complete representation of a species’ fundamental niche. Detailed ecophysiological studies on the response of trees along the latitudinal gradient are rare. They could shed light on the behaviour under different light intensities and other studied traits. The forests of the Dinaric Mountains and the Carpathians represent the largest contiguous forest complexes in south-eastern Europe. In uneven-aged Carpathian (8 plots) and Dinaric Mountain (11 plots) forests, net assimilation (Amax) and maximum quantum yield (Φ) were measured for beech and fir in three predefined light intensity categories according to the indirect site factor (ISF%) obtained by the analysis of hemispherical photographs in managed and old growth forests, all located above 800 m a.s.l. The measurements were carried out under fixed environmental conditions in each light category per plot for three consecutive years. Data from the last 50-year average period from the CRU TS 4.01 dataset were used for the comparison between Amax, Φ, and climate. The highest Φ for beech were observed in the central part of the Dinaric Mountains and in the south westernmost and northwesternmost part of the Carpathians for both beech and fir, while they were highest for fir in the Dinaric Mountains in the northwesternmost part of the study area. The Φ-value of beech decreased in both complexes with increasing mean annual temperature and was highest in the open landscape. For fir in the Carpathians, Φ decreased with increasing mean annual temperature, while in the Dinaric Mountains it increased with higher temperature and showed a more scattered response compared to the Carpathians. Short-term ecophysiological responses of beech and fir were consistent to long-term radial growth observations observed on same locations. The results may provide a basis and an indication of the future response of two tree species in their biogeographical range to climate change in terms of competitiveness, existence and consequently forest management decisions.
Ključne besede: silver fir, beech, light response, Carpathian Mountains, Dinaric Mountains, temperature, precipitation
Objavljeno v DiRROS: 08.05.2024; Ogledov: 188; Prenosov: 400
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Povzetek: Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies.
Ključne besede: electrochemotherapy, cisplatin, immune response
Objavljeno v DiRROS: 21.03.2024; Ogledov: 270; Prenosov: 168
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