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Państwowej Szkoły Wyższej w Białej Podlaskiej

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Autorzy: , , , .
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Tytuł pracy w innym języku: MickaelSacharczukoriginal-articleF000.00993999009994.1001422-0067003Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid SystemInternational Journal of Molecular Sciences20241422-00672023/202410.3390/ijms25136978Paszkiewicz, Justynaendogenous opioid systemFINAL_PUBLISHEDCurrently, pharmacotherapy provides successful seizure control in around 70% of patients with epilepsy; however, around 30% of cases are still resistant to available treatment. Therefore, effective anti-epileptic therapy still remains a challenge. In our study, we utilized two mouse lines selected for low (LA) and high (HA) endogenous opioid system activity to investigate the relationship between down- or upregulation of the opioid system and susceptibility to seizures. Pentylenetetrazole (PTZ) is a compound commonly used for kindling of generalized tonic-clonic convulsions in animal models. Our experiments revealed that in the LA mice, PTZ produced seizures of greater intensity and shorter latency than in HA mice. This observation suggests that proper opioid system tone is crucial for preventing the onset of generalized tonic-clonic seizures. Moreover, a combination of an opioid receptor antagonist-naloxone-and a GABA receptor agonist-diazepam (DZP)-facilitates a significant DZP-sparing effect. This is particularly important for the pharmacotherapy of neurological patients, since benzodiazepines display high addiction risk. In conclusion, our study shows a meaningful, protective role of the endogenous opioid system in the prevention of epileptic seizures and that disturbances in that balance may facilitate seizure occurrence.epilepsyseizures : Michel-Edward : Mariusz : Oryginalny artykuł naukowy : publikacja bezkosztowa : 998599140.0000140.000PUNKTACJA KBNPUNKTACJA MINISTERSTWALISTA FILADELFIJSKAIMPACT FACTOR140.000PUNKTACJA UWM : 009859.000 : Q : 003 : Vol. 25 : CC-BY
Charakterystyka formalna:
Język publikacji: 0184AOartykuł oryginalny naukowyPUBLIKACJAPEŁNA PUBLIKACJAAAartykuł w czasopiśmie z IF (wykaz MNiSW)AFILIACJA PODANAENGhttps://www.mdpi.com/1422-0067/25/13/6978100^a1422-0067^bQ^iX^jXY^kQ009159^a003^b003^c2024-07-08, 13:53^d2024-07-08, 13:54^e3023968886^f3023968885^aSusceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System^aInternational Journal of Molecular Sciences^a2024^bVol. 25^cissue 13^darticle number 6978^a1422-0067^a2023/2024^a10.3390/ijms25136978^aPaszkiewicz, Justyna^cy^aendogenous opioid system^aFINAL_PUBLISHED^bCC-BY^cAT_PUBLICATION^eOPEN_JOURNAL^aCurrently, pharmacotherapy provides successful seizure control in around 70% of patients with epilepsy; however, around 30% of cases are still resistant to available treatment. Therefore, effective anti-epileptic therapy still remains a challenge. In our study, we utilized two mouse lines selected for low (LA) and high (HA) endogenous opioid system activity to investigate the relationship between down- or upregulation of the opioid system and susceptibility to seizures. Pentylenetetrazole (PTZ) is a compound commonly used for kindling of generalized tonic-clonic convulsions in animal models. Our experiments revealed that in the LA mice, PTZ produced seizures of greater intensity and shorter latency than in HA mice. This observation suggests that proper opioid system tone is crucial for preventing the onset of generalized tonic-clonic seizures. Moreover, a combination of an opioid receptor antagonist-naloxone-and a GABA receptor agonist-diazepam (DZP)-facilitates a significant DZP-sparing effect. This is particularly important for the pharmacotherapy of neurological patients, since benzodiazepines display high addiction risk. In conclusion, our study shows a meaningful, protective role of the endogenous opioid system in the prevention of epileptic seizures and that disturbances in that balance may facilitate seizure occurrence.^aepilepsy^aseizures
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Nr opisu: na^pPaszkiewicz Justyna^rPASZKIEWICZ^sJUSTYNA^u^tZakład Pielęgniarstwa^qPaszkiewicz J^w930593^x0000013936^zPaszkiewicz Justyna^aTeodorowicz
Autorzy: , , , , Patrycja Tomasz Jarosław Olav Gina Mariusz Michel-Edwar Oryginalny artykuł naukowyACZartykuł w czasopiśmie zagranicznym2.800IF 99929970.0000070.000PUNKTACJA KBNPUNKTACJA MINISTERSTWALISTA FILADELFIJSKAIMPACT FACTOR70.000PUNKTACJA UWM 009929.000 Q 003 Vol. 45 CC-BY TeodorowiczKockiHorbańczukMandaSacharczukMickaeloriginal-article996100009996.2001467-3037003Investigation of the Molecular Evolution of Treg Suppresion Mechanisms Indicates a Covergent OriginCurrent Issues in Molecular Biology20231467-30452022/202310.3390/cimb45010042aiFINAL_PUBLISHEDRegulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms' emergence has not been identified. It is not yet known whether Treg suppression mechanisms diverged from a single pathway or converged from several sources. We investigated the evolutionary history of Treg suppression pathways using various phylogenetic analysis tools. To ensure the conservation of function for investigated proteins, we augmented our study using nonhomology-based methods to predict protein functions among various investigated species and mined the literature for experimental evidence of functional convergence. Our results indicate that a minority of Treg suppressor mechanisms could be homologs of ancient conserved pathways. For example, CD73, an enzymatic pathway known to play an essential role in invertebrates, is highly conserved between invertebrates and vertebrates, with no evidence of positive selection (w = 0.48, p-value < 0.00001). Our findings indicate that Tregs utilize homologs of proteins that diverged in early vertebrates. However, our findings do not exclude the possibility of a more evolutionary pattern following the duplication degeneration-complementation (DDC) model. Ancestral sequence reconstruction showed that Treg suppression mechanism proteins do not belong to one family; rather, their emergence seems to follow a convergent evolutionary pattern.evolutionmolecular evolutiontregs, Patrycja Tomasz Jarosław Olav Gina Mariusz Michel-Edwar Oryginalny artykuł naukowyACZartykuł w czasopiśmie zagranicznym2.800IF 99929970.0000070.000PUNKTACJA KBNPUNKTACJA MINISTERSTWALISTA FILADELFIJSKAIMPACT FACTOR70.000PUNKTACJA UWM 009929.000 Q 003 Vol. 45 CC-BY TeodorowiczKockiHorbańczukMandaSacharczukMickaeloriginal-article996100009996.2001467-3037003Investigation of the Molecular Evolution of Treg Suppresion Mechanisms Indicates a Covergent OriginCurrent Issues in Molecular Biology20231467-30452022/202310.3390/cimb45010042aiFINAL_PUBLISHEDRegulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms' emergence has not been identified. It is not yet known whether Treg suppression mechanisms diverged from a single pathway or converged from several sources. We investigated the evolutionary history of Treg suppression pathways using various phylogenetic analysis tools. To ensure the conservation of function for investigated proteins, we augmented our study using nonhomology-based methods to predict protein functions among various investigated species and mined the literature for experimental evidence of functional convergence. Our results indicate that a minority of Treg suppressor mechanisms could be homologs of ancient conserved pathways. For example, CD73, an enzymatic pathway known to play an essential role in invertebrates, is highly conserved between invertebrates and vertebrates, with no evidence of positive selection (w = 0.48, p-value < 0.00001). Our findings indicate that Tregs utilize homologs of proteins that diverged in early vertebrates. However, our findings do not exclude the possibility of a more evolutionary pattern following the duplication degeneration-complementation (DDC) model. Ancestral sequence reconstruction showed that Treg suppression mechanism proteins do not belong to one family; rather, their emergence seems to follow a convergent evolutionary pattern.evolutionmolecular evolutiontregs.
Tytuł czasopisma:
Charakterystyka formalna: Mariusz^u^t^qSacharczuk M^w^x0000026532^zSacharczuk Mariusz^aMickael
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Autorzy: , , , .
Tytuł pracy:
Strony: RadziszewskiFraczekWolińskaPaszkiewiczReligaSacharczukF014101.00993999009994.1001422-0067003The Journey of Cancer Cells to the BrainInternational Journal of Molecular Sciences20231422-00672022/202310.3390/ijms24043854Paszkiewicz, JustynabraineFINAL_PUBLISHEDCancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of signaling pathways participating in migration, infiltration of the blood-brain barrier, interaction with host cells (e.g., neurons, astrocytes), and the immune system. Development of novel therapies offers a glimpse of hope for increasing the diminutive life expectancy currently forecasted for patients suffering from brain metastasis. However, applying these treatment strategies has not been sufficiently effective. Therefore, there is a need for a better , Jakub, Karolina, Renata, Justyna, Piotr, Mariusz, utrzymanie i rozwój potencjału badawczego - art. 365 pkt 2 ustawy, 998599140.0000140.000PUNKTACJA KBNPUNKTACJA MINISTERSTWALISTA FILADELFIJSKAIMPACT FACTOR140.000PUNKTACJA UWM, 009859.000, Q, 003, Challenges and Opportunities, Vol. 24, CC-BY, , , , 017, , , 009999.000, 2023-03-15, 10:29, issue 4, y, AT_PUBLICATION, , , , WNZS0101, , , 009859.000202320232023Journey of Cancer Cells to the Brain Challenges and Opportunities00000450840000000466AOartykuł oryginalny naukowyPUBLIKACJAPEŁNA PUBLIKACJAAAartykuł w czasopiśmie z IF (wykaz MNiSW)AFILIACJA PODANAENGhttps://www.mdpi.com/1422-0067/24/4/3854100, 2024-06-25, 14:23, article number 3854
ISBN: Radziszewski
Charakterystyka formalna:
Język publikacji: arczuk Mariusz^bMariusz^c^d^e^f^g^h^i ^m_^n_^oSacharczuk Mariusz^pSacharczuk Mariusz^rSacharczuk^sMariusz^u^t^qSacharczuk M^w^x0000026532^zSacharczuk MariuszŁazarczyk Marzena Mickael Michel Edward Skiba Dominik Kurzejamska Ewa Ławiński Michał Horbańczuk Jarosław Olav^aF01^butrzymanie i rozwój potencjału badawczego - art. 365 pkt 2 ustawy^a4101.00^11ACZartykuł w czasopiśmie zagranicznym4.900IF^a993999^b998599140.0000140.000PUNKTACJA KBNPUNKTACJA MINISTERSTWALISTA FILADELFIJSKAIMPACT FACTOR140.000PUNKTACJA UWM^a009994.100^b009859.000^c009999.000^d009859.000202320232023Journey of Cancer Cells to the Brain Challenges and Opportunities00000450840000000466AOartykuł oryginalny naukowyPUBLIKACJAPEŁNA PUBLIKACJAAAartykuł w czasopiśmie z IF (wykaz MNiSW)AFILIACJA PODANAENGhttps://www.mdpi.com/1422-0067/24/4/3854100^a1422-0067^bQ^iX^jXY^kQ009159^a003^b003^c2023-03-15, 10:29^d2024-06-25, 14:23^e3127899210^f3024798816^aThe Journey of Cancer Cells to the Brain^bChallenges and Opportunities^aInternational Journal of Molecular Sciences^a2023^bVol. 24^cissue 4^darticle number 3854^a1422-0067^a2022/2023^a10.3390/ijms24043854^aPaszkiewicz, Justyna^cy^abraine^aFINAL_PUBLISHED^bCC-BY^cAT_PUBLICATION^eOPEN_JOURNAL^aCancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of signaling pathways participating in migration, infiltration of the blood-brain barrier, interaction with host cells (e.g., neurons, astrocytes), and the immune system. Development of novel therapies offers a glimpse of hope for increasing the diminutive life expectancy currently forecasted for patients suffering from brain metastasis. However, applying these treatment strategies has not been sufficiently effective. Therefore, there is a need for a better understanding of the metastasis process to uncover novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the diverse processes that they undergo to colonize the brain. These processes include EMT, intravasation, extravasation, and infiltration of the blood-brain barrier, ending up with colonization and angiogenesis. In each phase, we focus on the pathways engaging molecules that potentially could be drug target candidates.^acancer^aimmune cells^ametastasis
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