Anticonvulsant drugs such as pregabalin (PGB) and lacosamide (LCM), exhibit potent analgesic effects in diabetic neuropathy; however, their possible role/mechanisms in paclitaxel (PTX)-induced ...peripheral neuropathy have not been elucidated, which is the aim of the present study. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i. p) on days 0, 2, 4 and 6. Forty eight hours after the last dose of PTX, rats were treated orally with 30 mg/kg/day of either PGB or LCM for 21 days. Both therapies improved thermal hyperalgesia and cold allodynia induced by PTX. Interestingly, LCM therapy showed no motor impairment that was observed upon using PGB, as demonstrated using rotarod test. Treatment with PGB or LCM restored the sciatic nerve content of the depleted total antioxidant capacity (TAC) and nerve growth factor (NGF), and lessened the elevated contents of nuclear factor kappa B p65 (NF-kB p65), tumor necrosis factor-α (TNF-α), and active caspase-3. On the molecular level, the drugs reduced the protein expression of Notch1 receptor, phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK), and the trajectory interleukin-6/phosphorylated janus kinase 2/phosphorylated signal transducer and activator of transcription 3 (IL-6/p-JAK2/p-STAT3). Therefore, the current study demonstrated a pivotal role for LCM in the management of PTX-induced peripheral neuropathy similar to PGB, but without motor adverse effects via the inhibition of oxidative stress, inflammation and apoptosis, as well as IL-6/JAK/STAT pathway and Notch1 receptor over-expression.
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•PTX evoked peripheral neuropathy, thermal hyperalgesia and cold allodynia.•PTX induced neuronal oxidative stress, inflammation and apoptosis.•PTX activated Notch 1 receptor and JAK2/STAT3 signal pathway.•PGB and LCM treatments alleviated neuropathy induced by PTX.•LCM shows similar efficacy to PGB but with no motor impairment.
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•PTX caused neuronal oxidative stress, inflammation and apoptosis.•PTX activated Notch 1 receptor and JAK/STAT signal pathway.•PGB and/or BM-MSCs treatments alleviated peripheral ...neuropathy evoked by PTX.•BM-MSCs with PGB improved motor dysfunction induced by PGB therapy alone.•BM-MSCs with PGB provided an additional benefit compared to PGB therapy alone.
Peripheral neuropathy is a common adverse effect observed during the use of paclitaxel (PTX) as chemotherapy. The present investigation was directed to estimate the modulatory effect of bone marrow derived mesenchymal stem cells (BM-MSCs) on pregabalin (PGB) treatment in PTX-induced peripheral neuropathy. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i.p) 4 times every other day. Rats were then treated with PGB (30 mg/kg/day, p.o.) for 21 days with or without a single intravenous administration of BM-MSCs. At the end of experiment, behavioral and motor abnormalities were assessed. Animals were then sacrificed for measurement of total antioxidant capacity (TAC), nerve growth factor (NGF), nuclear factor kappa B p65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and active caspase-3 in the sciatic nerve. Moreover, protein expressions of Notch1 receptor, phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK) were estimated. Finally, histological examinations were performed to assess severity of sciatic nerve damage and for estimation of BM-MSCs homing. Combined PGB/BM-MSCs therapy provided an additional improvement toward reducing PTX-induced oxidative stress, neuro-inflammation, and apoptotic markers. Interestingly, BM-MSCs therapy effectively prevented motor impairment observed by PGB treatment. Combined therapy also induced a significant increase in cell homing and prevented PTX-induced sciatic nerve damage in histological examination. The present study highlights a significant role for BM-MSCs in enhancing treatment potential of PGB and reducing its motor side effects when used as therapy in the management of peripheral neuropathy.
Workshop summary: Kaons@CERN 2023 Anzivino, G.; Cuendis, Sergio Arguedas; Bernard, V. ...
The European physical journal. C, Particles and fields,
04/2024, Letnik:
84, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Kaon physics is at a turning point – while the rare-kaon experiments NA62 and KOTO are in full swing, the end of their lifetime is approaching and the future experimental landscape needs to be ...defined. With HIKE, KOTO-II and LHCb-Phase-II on the table and under scrutiny, it is a very good moment in time to take stock and contemplate about the opportunities these experiments and theoretical developments provide for particle physics in the coming decade and beyond. This paper provides a compact summary of talks and discussions from the Kaons@CERN 2023 workshop, held in September 2023 at CERN.
Prospects for observation at CERN in NA62 Hahn, F; Aliberti, R; Ambrosino, F ...
Journal of physics. Conference series,
07/2015, Letnik:
631, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The rare decays are excellent processes to probe the Standard Model and indirectly search for new physics complementary to the direct LHC searches. The NA62 experiment at CERN SPS aims to collect and ...analyse O(1013) kaon decays before the CERN long-shutdown 2 (in 2018). This will allow to measure the branching ratio to a level of 10% accuracy. The experimental apparatus has been commissioned during a first run in autumn 2014.
Gynandroblastoma is an extremely rare sex cord-stromal ovarian tumor. Only thirty cases have been published in the literature up to now. Clinical investigations include virilism associated with ...menstrual irregularity, or amenorrhea. The surgical treatment is salpingo-oophorectomy and lymphadenectomy if malignant spread is suspected.
Le gynandroblastome est une tumeur rare de l'ovaire, dont seule une trentaine de cas est répertoriée dans la littérature. C'est une tumeur mixte, composée de cellules de la granulosa et de cellules ...de Sertoli. Ses manifestations cliniques peuvent être endocriniennes, avec un tableau d'hirsutisme et de virilisation associé ou non à des troubles du cycle menstruel. Le traitement repose sur une annexectomie première, qui peut être complétée par une chirurgie radicale, en fonction de l'âge ou au moindre signe macroscopique de malignité.
Gynandroblastoma is an extremely rare sex cord-stromal ovarian tumor. Only thirty cases have been published in the literature up to now. Clinical investigations include virilism associated with menstrual irregularity, or amenorrhea. The surgical treatment is salpingo-oophorectomy and lymphadenectomy if malignant spread is suspected.
The Experimental Cavern North 3 (ECN3) is an underground experimental cavern on the CERN Prévessin site. ECN3 currently hosts the NA62 experiment, with a physics programme devoted to rare kaon decays ...and searches of hidden particles approved until Long Shutdown 3 (LS3). Several options are proposed on the longer term in order to make best use of the worldwide unique potential of the high-intensity/high-energy proton beam extracted from the Super Proton Synchrotron (SPS) in ECN3. The current status of their study by the CERN Physics Beyond Colliders (PBC) Study Group is presented, including considerations on beam requirements and upgrades, detector R&D and construction, schedules and cost, as well as physics potential within the CERN and worldwide landscape.
Kaon physics is at a turning point -- while the rare-kaon experiments NA62 and KOTO are in full swing, the end of their lifetime is approaching and the future experimental landscape needs to be ...defined. With HIKE, KOTO-II and LHCb-Phase-II on the table and under scrutiny, it is a very good moment in time to take stock and contemplate about the opportunities these experiments and theoretical developments provide for particle physics in the coming decade and beyond. This paper provides a compact summary of talks and discussions from the Kaons@CERN 2023 workshop.
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