@article{MTMT:34541583,
	title = {Emerging Lipid Targets in Glioblastoma},
	url = {https://m2.mtmt.hu/api/publication/34541583},
	author = {Darwish, Ammar and Pammer, Milán and Gallyas, Ferenc and Vigh, László and Balogi, Zsolt and Juhász, Kata},
	doi = {10.3390/cancers16020397},
	journal-iso = {CANCERS},
	journal = {CANCERS},
	volume = {16},
	unique-id = {34541583},
	abstract = {GBM accounts for most of the fatal brain cancer cases, making it one of the deadliest tumor types. GBM is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- and radiotherapy. In order to improve therapeutic efficiency, considerable efforts have been made to target various features of GBM. One of the targetable features of GBM is the rewired lipid metabolism that contributes to the tumor's aggressive growth and penetration into the surrounding brain tissue. Lipid reprogramming allows GBM to acquire survival, proliferation, and invasion benefits as well as supportive modulation of the tumor microenvironment. Several attempts have been made to find novel therapeutic approaches by exploiting the lipid metabolic reprogramming in GBM. In recent studies, various components of de novo lipogenesis, fatty acid oxidation, lipid uptake, and prostaglandin synthesis have been considered promising targets in GBM. Emerging data also suggest a significant role hence therapeutic potential of the endocannabinoid metabolic pathway in GBM. Here we review the lipid-related GBM characteristics in detail and highlight specific targets with their potential therapeutic use in novel antitumor approaches.},
	keywords = {GBM; lipid therapy; tumor hallmarks; tumor lipid},
	year = {2024},
	eissn = {2072-6694},
	orcid-numbers = {Gallyas, Ferenc/0000-0002-1906-4333}
}

@article{MTMT:34108329,
	title = {The Crystal Structure of the Hsp90-LA1011 Complex and the Mechanism by Which LA1011 May Improve the Prognosis of Alzheimer's Disease},
	url = {https://m2.mtmt.hu/api/publication/34108329},
	author = {Roe, S. Mark and Török, Zsolt and McGown, Andrew and Horváth, Ibolya and Spencer, John and Pazmany, Tamas and Vigh, László and Prodromou, Chrisostomos},
	doi = {10.3390/biom13071051},
	journal-iso = {BIOMOLECULES},
	journal = {BIOMOLECULES},
	volume = {13},
	unique-id = {34108329},
	issn = {2218-273X},
	abstract = {Functional changes in chaperone systems play a major role in the decline of cognition and contribute to neurological pathologies, such as Alzheimer's disease (AD). While such a decline may occur naturally with age or with stress or trauma, the mechanisms involved have remained elusive. The current models suggest that amyloid-& beta; (A & beta;) plaque formation leads to the hyperphosphorylation of tau by a Hsp90-dependent process that triggers tau neurofibrillary tangle formation and neurotoxicity. Several co-chaperones of Hsp90 can influence the phosphorylation of tau, including FKBP51, FKBP52 and PP5. In particular, elevated levels of FKBP51 occur with age and stress and are further elevated in AD. Recently, the dihydropyridine LA1011 was shown to reduce tau pathology and amyloid plaque formation in transgenic AD mice, probably through its interaction with Hsp90, although the precise mode of action is currently unknown. Here, we present a co-crystal structure of LA1011 in complex with a fragment of Hsp90. We show that LA1011 can disrupt the binding of FKBP51, which might help to rebalance the Hsp90-FKBP51 chaperone machinery and provide a favourable prognosis towards AD. However, without direct evidence, we cannot completely rule out effects on other Hsp90-co-chaprone complexes and the mechanisms they are involved in, including effects on Hsp90 client proteins. Nonetheless, it is highly significant that LA1011 showed promise in our previous AD mouse models, as AD is generally a disease affecting older patients, where slowing of disease progression could result in AD no longer being life limiting. The clinical value of LA1011 and its possible derivatives thereof remains to be seen.},
	keywords = {DEPHOSPHORYLATION; MODEL; TAU; Alzheimer's disease; A-BETA; HSP90; HSP90; chaperone; Co-chaperone; Amyloid hypothesis; FKBP51; FKBP52; Cochaperone; immunopilin; LA1011; TAU FORMS},
	year = {2023},
	eissn = {2218-273X},
	orcid-numbers = {McGown, Andrew/0000-0002-2187-3850}
}

@article{MTMT:33607647,
	title = {Development of a Laser Microdissection-Coupled Quantitative Shotgun Lipidomic Method to Uncover Spatial Heterogeneity},
	url = {https://m2.mtmt.hu/api/publication/33607647},
	author = {Varga-Zsíros, Vanda and Migh, Ede and Marton, Annamária and Kóta, Zoltán and Vizler, Csaba and Tiszlavicz, László and Horváth, Péter and Török, Zsolt and Vigh, László and Balogh, Gábor and Péter, Mária},
	doi = {10.3390/cells12030428},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {12},
	unique-id = {33607647},
	abstract = {Lipid metabolic disturbances are associated with several diseases, such as type 2 diabetes or malignancy. In the last two decades, high-performance mass spectrometry-based lipidomics has emerged as a valuable tool in various fields of biology. However, the evaluation of macroscopic tissue homogenates leaves often undiscovered the differences arising from micron-scale heterogeneity. Therefore, in this work, we developed a novel laser microdissection-coupled shotgun lipidomic platform, which combines quantitative and broad-range lipidome analysis with reasonable spatial resolution. The multistep approach involves the preparation of successive cryosections from tissue samples, cross-referencing of native and stained images, laser microdissection of regions of interest, in situ lipid extraction, and quantitative shotgun lipidomics. We used mouse liver and kidney as well as a 2D cell culture model to validate the novel workflow in terms of extraction efficiency, reproducibility, and linearity of quantification. We established that the limit of dissectible sample area corresponds to about ten cells while maintaining good lipidome coverage. We demonstrate the performance of the method in recognizing tissue heterogeneity on the example of a mouse hippocampus. By providing topological mapping of lipid metabolism, the novel platform might help to uncover region-specific lipidomic alterations in complex samples, including tumors.},
	year = {2023},
	eissn = {2073-4409},
	orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773; Tiszlavicz, László/0000-0003-1134-6587}
}

@article{MTMT:33154711,
	title = {Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D},
	url = {https://m2.mtmt.hu/api/publication/33154711},
	author = {Kőszegi, Balázs and Balogh, Gábor and Berente, Zoltán and Vranesics, Anett and Pollák, Edit and Molnár, László and Takátsy, Anikó and Poór, Viktória and Wahr, Mátyás and Antus, Csenge Petra and Erős, Krisztián and Vigh, László and Gallyas, Ferenc and Péter, Mária and Veres, Balázs},
	doi = {10.3390/ijms231911274},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {33154711},
	issn = {1661-6596},
	abstract = {In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases.},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Molnár, László/0000-0002-0049-9679; Gallyas, Ferenc/0000-0002-1906-4333}
}

@article{MTMT:32990270,
	title = {Effect of HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) : protocol for a randomised controlled trial},
	url = {https://m2.mtmt.hu/api/publication/32990270},
	author = {Sebők, Judit and Édel, Zsófia and Dembrovszky, Fanni and Borbásné Farkas, Kornélia and Török, Zsolt and Balogh, Gábor and Péter, Mária and Papp, Ildiko and Balogi, Zsolt and Csizmadiáné Nusser, Nóra and Péter, Iván and Hooper, Philip and Geiger, Paige and Erőss, Bálint Mihály and Wittmann, István and Váncsa, Szilárd and Vigh, László and Hegyi, Péter},
	doi = {10.1136/bmjopen-2022-062122},
	journal-iso = {BMJ OPEN},
	journal = {BMJ OPEN},
	volume = {12},
	unique-id = {32990270},
	issn = {2044-6055},
	abstract = {The burden of type 2 diabetes mellitus (T2DM) is increasing worldwide. Heat therapy has been found effective in improving glycaemic control. However, to date, there is a lack of randomised controlled studies investigating the efficacy of heat therapy in T2DM. Therefore, we aim to investigate whether heat therapy with natural thermal mineral water can improve glycaemic control in patients with T2DM.The HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) Study is a single-centre, two-arm randomised controlled trial being conducted at Harkány Thermal Rehabilitation Centre in Hungary. Patients with T2DM will be randomly assigned to group A (bath sessions in 38°C natural thermal mineral water) and group B (baths in thermoneutral water (30°C-32°C)). Both groups will complete a maximum of 5 weekly visits, averaging 50-60 visits over the 12-week study. Each session will last 30 min, with a physical check-up before the bath. At baseline, patients' T2DM status will be investigated thoroughly. Possible microvascular and macrovascular complications of T2DM will be assessed with physical and laboratory examinations. The short form-36 questionnaire will assess the quality of life. Patients will also be evaluated at weeks 4, 8 and 12. The primary endpoint will be the change of glycated haemoglobin from baseline to week 12. An estimated 65 patients will be enrolled per group, with a sample size re-estimation at the enrolment of 50% of the calculated sample size.The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (818-2/2022/EÜIG). Written informed consent is required from all participants. We will disseminate our results to the medical community and will publish our results in peer-reviewed journals.ClinicalTrials.gov, NCT05237219.},
	keywords = {THERAPEUTICS; DIABETES & ENDOCRINOLOGY; general diabetes},
	year = {2022},
	eissn = {2044-6055},
	orcid-numbers = {Dembrovszky, Fanni/0000-0001-6953-3591; Borbásné Farkas, Kornélia/0000-0002-5349-6527; Erőss, Bálint Mihály/0000-0003-3658-8427; Váncsa, Szilárd/0000-0002-9347-8163; Hegyi, Péter/0000-0003-0399-7259}
}

@article{MTMT:32930192,
	title = {The Small Heat Shock Protein, HSPB1, Interacts with and Modulates the Physical Structure of Membranes},
	url = {https://m2.mtmt.hu/api/publication/32930192},
	author = {Csoboz, Bálint and Gombos, Imre and Kóta, Zoltán and Dukic, Barbara and Klement, Éva and Varga-Zsíros, Vanda and Lipinszki, Zoltán and Páli, Tibor and Vigh, László and Török, Zsolt},
	doi = {10.3390/ijms23137317},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {32930192},
	issn = {1661-6596},
	abstract = {Small heat shock proteins (sHSPs) have been demonstrated to interact with lipids and modulate the physical state of membranes across species. Through these interactions, sHSPs contribute to the maintenance of membrane integrity. HSPB1 is a major sHSP in mammals, but its lipid interaction profile has so far been unexplored. In this study, we characterized the interaction between HSPB1 and phospholipids. HSPB1 not only associated with membranes via membrane-form-ing lipids, but also showed a strong affinity towards highly fluid membranes. It participated in the modulation of the physical properties of the interacting membranes by altering rotational and lat-eral lipid mobility. In addition, the in vivo expression of HSPB1 greatly affected the phase behavior of the plasma membrane under membrane fluidizing stress conditions. In light of our current find-ings, we propose a new function for HSPB1 as a membrane chaperone. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.},
	keywords = {membrane fluidity; stress response; lipid-protein interaction; Membrane chaperone; small HSP},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773; Lipinszki, Zoltán/0000-0002-2067-0832; Páli, Tibor/0000-0003-1649-1097}
}

@article{MTMT:32849807,
	title = {Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells.},
	url = {https://m2.mtmt.hu/api/publication/32849807},
	author = {Tiszlavicz, Ádám and Gombos, Imre and Péter, Mária and Hegedűs, Zoltán and Hunya, Ákos and Dukic, Barbara and Nagy, István and Peksel, Begüm and Balogh, Gábor and Horváth, Ibolya and Vigh, László and Török, Zsolt},
	doi = {10.3390/biomedicines10051172},
	journal-iso = {BIOMEDICINES},
	journal = {BIOMEDICINES},
	volume = {10},
	unique-id = {32849807},
	abstract = {Mild stress could help cells to survive more severe environmental or pathophysiological conditions. In the current study, we investigated the cellular mechanisms which contribute to the development of stress tolerance upon a prolonged (0-12 h) fever-like (40 °C) or a moderate (42.5 °C) hyperthermia in mammalian Chinese Hamster Ovary (CHO) cells. Our results indicate that mild heat triggers a distinct, dose-dependent remodeling of the cellular lipidome followed by the expression of heat shock proteins only at higher heat dosages. A significant elevation in the relative concentration of saturated membrane lipid species and specific lysophosphatidylinositol and sphingolipid species suggests prompt membrane microdomain reorganization and an overall membrane rigidification in response to the fluidizing heat in a time-dependent manner. RNAseq experiments reveal that mild heat initiates endoplasmic reticulum stress-related signaling cascades resulting in lipid rearrangement and ultimately in an elevated resistance against membrane fluidization by benzyl alcohol. To protect cells against lethal, protein-denaturing high temperatures, the classical heat shock protein response was required. The different layers of stress response elicited by different heat dosages highlight the capability of cells to utilize multiple tools to gain resistance against or to survive lethal stress conditions.},
	keywords = {MEMBRANE; STRESS; heat shock response; transcriptomics; LIPIDOMICS; Unfolded protein response; Chinese hamster ovary cells; acquired stress tolerance; membrane lipid metabolism},
	year = {2022},
	eissn = {2227-9059},
	orcid-numbers = {Hunya, Ákos/0000-0002-4547-9284}
}

@article{MTMT:32531214,
	title = {Lipids and Trehalose Actively Cooperate in Heat Stress Management of Schizosaccharomyces pombe},
	url = {https://m2.mtmt.hu/api/publication/32531214},
	author = {Péter, Mária and Gudmann, Péter and Kóta, Zoltán and Török, Zsolt and Vigh, László and Glatz, Attila and Balogh, Gábor},
	doi = {10.3390/ijms222413272},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {32531214},
	issn = {1661-6596},
	year = {2021},
	eissn = {1422-0067},
	orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773}
}

@article{MTMT:32515212,
	title = {Nicotinic Amidoxime Derivate BGP-15, Topical Dosage Formulation and Anti-Inflammatory Effect},
	url = {https://m2.mtmt.hu/api/publication/32515212},
	author = {Pető, Ágota and Kósa, Dóra and Haimhoffer, Ádám and Siposné Fehér, Pálma and Ujhelyi, Zoltán and Sinka, Dávid and Fenyvesi, Ferenc and Váradi, Judit and Vecsernyés, Miklós and Gyöngyösi, Alexandra and Lekli, István and Szentesi, Péter and Marton, Annamária and Gombos, Imre and Dukic, Barbara and Vigh, László and Bácskay, Ildikó},
	doi = {10.3390/pharmaceutics13122037},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {13},
	unique-id = {32515212},
	issn = {1999-4923},
	abstract = {BGP-15 is a Hungarian-developed drug candidate with numerous beneficial effects. Its potential anti-inflammatory effect is a common assumption, but it has not been investigated in topical formulations yet. The aim of our study was to formulate 10% BGP-15 creams with different penetration enhancers to ensure good drug delivery, improve bioavailability of the drug and investigate the potential anti-inflammatory effect of BGP-15 creams in vivo. Since the exact mechanism of the effect is still unknown, the antioxidant effect (tested with UVB radiation) and the ability of BGP-15 to decrease macrophage activation were evaluated. Biocompatibility investigations were carried out on HaCaT cells to make sure that the formulations and the selected excipients can be safely used. Dosage form studies were also completed with texture analysis and in vitro release with Franz diffusion chamber apparatus. Our results show that the ointments were able to reduce the extent of local inflammation in mice, but the exact mechanism of the effect remains unknown since BGP-15 did not show any antioxidant effect, nor was it able to decrease LPS-induced macrophage activation. Our results support the hypothesis that BGP-15 has a potential anti-inflammatory effect, even if it is topically applied, but the mechanism of the effect remains unclear and requires further pharmacological studies.},
	keywords = {ANTIOXIDANT; Drug delivery; Ointments; SURFACTANTS; BGP-15; PARP inhibitor; Anti-inflammatory drug; Dosage formulation; Dosage formulation; Nicotinic amidoxime derivate; Nicotinic amidoxime derivate},
	year = {2021},
	eissn = {1999-4923},
	orcid-numbers = {Szentesi, Péter/0000-0003-2621-2282}
}

@article{MTMT:32509125,
	title = {Heat therapy shows benefit in patients with type 2 diabetes mellitus: a systematic review and meta-analysis},
	url = {https://m2.mtmt.hu/api/publication/32509125},
	author = {Sebők, Judit and Édel, Zsófia and Váncsa, Szilárd and Borbásné Farkas, Kornélia and Kiss, Szabolcs and Erőss, Bálint Mihály and Török, Zsolt and Balogh, Gábor and Balogi, Zsolt and Nagy, Rita and Hooper, Philip L and Geiger, Paige C and Wittmann, István and Vigh, László and Dembrovszky, Fanni and Hegyi, Péter},
	doi = {10.1080/02656736.2021.2003445},
	journal-iso = {INT J HYPERTHER},
	journal = {INTERNATIONAL JOURNAL OF HYPERTHERMIA},
	volume = {38},
	unique-id = {32509125},
	issn = {0265-6736},
	abstract = {Type-2 diabetes mellitus (T2DM) is a common health condition which prevalence increases with age. Besides lifestyle modifications, passive heating could be a promising intervention to improve glycemic control. This study aimed to assess the efficacy of passive heat therapy on glycemic and cardiovascular parameters, and body weight among patients with T2DM.A systematic review and meta-analysis were reported according to PRISMA Statement. We conducted a systematic search in three databases (MEDLINE, Embase, CENTRAL) from inception to 19 August 2021. We included interventional studies reporting on T2DM patients treated with heat therapy. The main outcomes were the changes in pre-and post-treatment cardiometabolic parameters (fasting plasma glucose, glycated plasma hemoglobin, and triglyceride). For these continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Study protocol number: CRD42020221500.Five studies were included in the qualitative and quantitative synthesis, respectively. The results showed a not significant difference in the hemoglobin A1c [WMD -0.549%, 95% CI (-1.262, 0.164), p = 0.131], fasting glucose [WMD -0.290 mmol/l, 95% CI (-0.903, 0.324), p = 0.355]. Triglyceride [WMD 0.035 mmol/l, 95% CI (-0.130, 0.200), p = 0.677] levels were comparable regarding the pre-, and post intervention values.Passive heating can be beneficial for patients with T2DM since the slight improvement in certain cardiometabolic parameters support that. However, further randomized controlled trials with longer intervention and follow-up periods are needed to confirm the beneficial effect of passive heat therapy.},
	keywords = {[Meta-analysis]},
	year = {2021},
	eissn = {1464-5157},
	pages = {1650-1659},
	orcid-numbers = {Váncsa, Szilárd/0000-0002-9347-8163; Borbásné Farkas, Kornélia/0000-0002-5349-6527; Erőss, Bálint Mihály/0000-0003-3658-8427; Nagy, Rita/0000-0002-2663-4912; Dembrovszky, Fanni/0000-0001-6953-3591; Hegyi, Péter/0000-0003-0399-7259}
}