TY - JOUR AU - Horváth, Ádám AU - Steib, Anita AU - Nehr-Majoros, Andrea Kinga AU - Kántás, Boglárka AU - Király, Ágnes AU - Racskó, Márk AU - Tóth, Balázs István AU - Szánti-Pintér, Eszter AU - Kudová, Eva AU - Skodáné Földes, Rita AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 9 PG - 13 SN - 1661-6596 DO - 10.3390/ijms25094637 UR - https://m2.mtmt.hu/api/publication/34824919 ID - 34824919 AB - The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions. LA - English DB - MTMT ER - TY - JOUR AU - Hudhud, Lina AU - Kovács-Rozmer, Katalin AU - Kecskés, Angéla AU - Pohóczky, Krisztina AU - Bencze, Noémi AU - Buzás, Krisztina AU - Szőke, Éva AU - Helyes, Zsuzsanna TI - Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 7 PG - 13 SN - 1661-6596 DO - 10.3390/ijms25073760 UR - https://m2.mtmt.hu/api/publication/34797924 ID - 34797924 N1 - * Megosztott szerzőség AB - Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive 45Ca2+ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant 45Ca2+ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate 45Ca2+ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC50 values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives. LA - English DB - MTMT ER - TY - JOUR AU - Tarjányi, Vera AU - Ménes, Ákos AU - Hamid, Leila AU - Kurucz, Andrea AU - Priksz, Dániel AU - Varga, Balázs AU - Gesztelyi, Rudolf AU - Kiss, Rita AU - Horváth, Ádám István AU - Szentes, Nikolett AU - Helyes, Zsuzsanna AU - Szilvássy, Zoltán AU - Bombicz, Mariann TI - Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis : Effects on Disease Progression and Inflammatory Biomarkers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 6 PG - 16 SN - 1661-6596 DO - 10.3390/ijms25063292 UR - https://m2.mtmt.hu/api/publication/34763932 ID - 34763932 N1 - Funding Agency and Grant Number: European Union; State of Hungary; University of Debrecen [GINOP-2.3.4-15-2016-00002]; Hungarian Research Network (Chronic Pain Research Group); National Research, Development and Innovation Office (PharmaLab) [RRF-2.3.1-21-2022-00015, TKP2021-EGA-13, OTKA-K 134214]; National Research, Development and Innovation Fund of Hungary [TKP2021-EGA-13, TKP2021-EGA-16]; European Union and the European Regional Development Fund; National Research, Development and Innovation Fund of Hungary under the TKP2021-EGA funding scheme [TKP2021-EGA-18] Funding text: The present research was supported by the European Union, the State of Hungary, and the University of Debrecen under grant number GINOP-2.3.4-15-2016-00002 (V.T., D.P., R.G., Z.H., B.V., A.K., R.K., Z.S., M.B.), the Hungarian Research Network (Chronic Pain Research Group; Z.H.), National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015; Z.H.), TKP2021-EGA-13 (Z.H.), and OTKA-K 134214 (Z.H.). Projects no. TKP2021-EGA-13 and TKP2021-EGA-16 have been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the EGA 13 and EGA 16 funding schemes. The project is co-financed by the European Union and the European Regional Development Fund. Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme. AB - Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund's adjuvant (CFA)-induced chronic arthritis rat model and to identify new biomarkers with clinical utility. CFA was injected into the plantar surface of one hind paw and the root of the tail on day 0, and the tail root injection was repeated on day 1. Flu vaccination was performed on day 1 or 7. Paw volume was measured by plethysmometry, mechanonociceptive threshold by dynamic plantar aesthesiometry, neutrophil myeloperoxidase (MPO) activity, and vascular leakage using in vivo optical imaging throughout the 21-day experiment. Inflammatory markers were determined by Western blot and histopathology. CFA-induced swelling, an increase in MPO activity, plasma extravasation in the tibiotarsal joint. Mechanical hyperalgesia of the hind paw was observed 3 days after the injection, which gradually decreased. Co-administration of the flu vaccine on day 7 but not on day 1 resulted in significantly increased heme oxygenase 1 (HO-1) expression. The influenza vaccination appears to have a limited impact on the progression and severity of the inflammatory response and associated pain. Nevertheless, delayed vaccination could alter the disease activity, as indicated by the findings from assessments of edema and inflammatory biomarkers. HO-1 may serve as a potential marker for the severity of inflammation, particularly in the case of delayed vaccination. However, further investigation is needed to fully understand the regulation and role of HO-1, a task that falls outside the scope of the current study. LA - English DB - MTMT ER - TY - JOUR AU - Shpachynskyi, Oleksandr AU - Kiss, Tamás AU - Helyes, Zsuzsanna AU - Kopchak, Andrii TI - Maxillary Bone Microstructure After Lateral Sinus Flour Augmentation with Deproteinized Bovine Bone Material in Severe Alveolar Bone Atrophy: Comparative Micro-CT Study JF - JOURNAL OF MAXILLOFACIAL AND ORAL SURGERY J2 - JOURNAL OF MAXILLOFACIAL AND ORAL SURGERY PY - 2024 SN - 0972-8279 DO - 10.1007/s12663-024-02113-8 UR - https://m2.mtmt.hu/api/publication/34749536 ID - 34749536 N1 - Funding Agency and Grant Number: Fondo Nacional de Innovacin y Desarrollo Cientfico-Tecnolgico [TKP2021-NVA-07, TKP2021-EGA-13]; National Research, Development and Innovation Fund of Hungary [TKP2021-NVA, TKP2021-EGA] Funding text: The project No. TKP2021-NVA-07 and TKP2021-EGA-13 have been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-NVA and TKP2021-EGA funding schemes. LA - English DB - MTMT ER - TY - JOUR AU - Nehr-Majoros, Andrea Kinga AU - Erostyák, János AU - Fenyvesi, Éva AU - Szabó-Meleg, Edina AU - Szőcs, Levente AU - Sétáló, György (ifj.) AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Cyclodextrin derivatives decrease Transient Receptor Potential vanilloid 1 and Ankyrin 1 ion channel activation via altering the surrounding membrane microenvironment by cholesterol depletion JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 12 PY - 2024 PG - 13 SN - 2296-634X DO - 10.3389/fcell.2024.1334130 UR - https://m2.mtmt.hu/api/publication/34689825 ID - 34689825 AB - Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) are nonselective cation channels expressed in primary sensory neurons and several other non-neuronal structures such as immune cells, keratinocytes, and vascular smooth muscle cells. They play important roles in nociception, pain processing and their chanellopathies are associated with the development of several pathological conditions. They are located in cholesterol- and sphingolipid-rich membrane lipid raft regions serving as platforms to modulate their activations. We demonstrated earlier that disruption of these lipid rafts leads to decreased TRP channel activation and exerts analgesic effects. Cyclodextrins are macrocyclic molecules able to form host-guest complexes with cholesterol and deplete it from the membrane lipid rafts. The aim of this study was to investigate 8 structurally different (methylated and non-methylated) CD derivatives on cell viability, mitochondrial membrane potential, membrane composition and activation abilities of the TRPV1 and TRPA1 channels. We showed that non-methylated derivatives have preferable safety profiles compared to methylated ones. Furthermore, methylated derivatives reduced mitochondrial membrane potential. However, all investigated derivatives influence the ordered cell membrane structure depleting membrane cholesterol and inhibit the TRPV1 agonist capsaicin- and the TRPA1 agonist allyl isothiocyanate-induced Ca 2+− influx. This mechanism of action might provide novel perspectives for the development of peripherally acting analgesics via indirectly decreasing the generation and transmission of nociceptive signals. LA - English DB - MTMT ER - TY - GEN AU - Nehr-Majoros, Andrea Kinga AU - Bencze, Noémi AU - Payrits, Maja AU - Kemény, Ágnes AU - György, Sétáló Jr. AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Analgesic effects of cyclodextrin derivatives via modulation of Transient Receptor Potential Ankyrin 1 ion channel function PY - 2024 UR - https://m2.mtmt.hu/api/publication/34577002 ID - 34577002 LA - English DB - MTMT ER - TY - GEN AU - Payrits, Maja AU - Csekő, Kata AU - Pohóczky, Krisztina AU - Dávid, Ernszt AU - Klaudia, Barabás AU - Nehr-Majoros, Andrea Kinga AU - Bencze, Noémi AU - Nemes, Balázs AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Effect of estradiol on the Transient Receptor Potential Vanilloid 1 and Ankyrin 1 receptors regulated pain responses PY - 2024 UR - https://m2.mtmt.hu/api/publication/34576980 ID - 34576980 LA - English DB - MTMT ER - TY - JOUR AU - Nehr-Majoros, Andrea Kinga AU - Király, Ágnes AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Lipid raft disruption as an opportunity for peripheral analgesia JF - CURRENT OPINION IN PHARMACOLOGY J2 - CURR OPIN PHARMACOL VL - 75 PY - 2024 PG - 11 SN - 1471-4892 DO - 10.1016/j.coph.2024.102432 UR - https://m2.mtmt.hu/api/publication/34561496 ID - 34561496 AB - Chronic pain conditions are unmet medical needs, since the available drugs, opioids, non-steroidal anti-inflammatory/analgesic drugs and adjuvant analgesics do not provide satisfactory therapeutic effect in a great proportion of patients. Therefore, there is an urgent need to find novel targets and novel therapeutic approaches that differ from classical pharmacological receptor antagonism. Most ion channels and receptors involved in pain sensation and processing such as Transient Receptor Potential ion channels, opioid receptors, P2X purinoreceptors and neurokinin 1 receptor are located in the lipid raft regions of the plasma membrane. Targeting the membrane lipid composition and structure by sphingolipid or cholesterol depletion might open future perspectives for the therapy of chronic inflammatory, neuropathic or cancer pain, most importantly acting at the periphery. LA - English DB - MTMT ER - TY - JOUR AU - Gunkl-Tóth, Lilla AU - Sütő, Gábor AU - Kumánovics, Gábor AU - Kun, József AU - Urban, Peter AU - Gyenesei, Attila AU - Kiralyhidi, Panna AU - Schett, Georg AU - Nagy, Gyorgy AU - Helyes, Zsuzsanna TI - Transcriptomic Analysis of Peripheral Blood Mononuclear Cells Reveals Pain and Inflammation Specific Alterations in Difficult-to-treat Rheumatoid Arthritis JF - ARTHRITIS & RHEUMATOLOGY J2 - ARTHRITIS RHEUMATOL VL - 75 PY - 2023 SP - 802 EP - 803 PG - 2 SN - 2326-5191 UR - https://m2.mtmt.hu/api/publication/34787132 ID - 34787132 N1 - Supplement: 9 LA - English DB - MTMT ER - TY - JOUR AU - Hosszú, Ádám AU - Balogh, Dóra Bianka AU - Tóth, Ákos Roland AU - Csekő, Kata AU - Hodrea, Judit AU - Helyes, Zsuzsanna AU - Szabó, Attila AU - Fekete, Andrea TI - Sigma-1 receptor agonist mitigates bleomycin-induced pulmonary fibrosis in mice JF - EUROPEAN RESPIRATORY JOURNAL J2 - EUR RESPIR J VL - 62 PY - 2023 PG - 2 SN - 0903-1936 DO - 10.1183/13993003.congress-2023.PA2364 UR - https://m2.mtmt.hu/api/publication/34521724 ID - 34521724 N1 - Supplement: 67 LA - English DB - MTMT ER -