Longitudinal adaptive immune responses following sequential SARS-CoV-2 vaccinations in MS patients on anti-CD20 therapies and sphingosine-1-phosphate receptor modulators.

Background: Adequate response to the SARS-CoV-2 vaccine represents an important treatment goal in caring for patients with multiple sclerosis (MS) during the ongoing COVID-19 pandemic. Previous data so far have demonstrated lower spike-specific IgG responses following two SARS-CoV-2 vaccinations in MS patients treated with sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb) compared to other disease modifying therapies (DMTs). It is unknown whether subsequent vaccinations can augment antibody responses in these patients.

Spinal subpial delivery of AAV9 enables widespread gene silencing and blocks motoneuron degeneration in ALS.

Gene silencing with virally delivered shRNA represents a promising approach for treatment of inherited neurodegenerative disorders. In the present study we develop a subpial technique, which we show in adult animals successfully delivers adeno-associated virus (AAV) throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron disease, including near-complete preservation of spinal α-motoneurons and muscle innervation.

Survival of syngeneic and allogeneic iPSC-derived neural precursors after spinal grafting in minipigs.

The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation.

A novel role of spinal astrocytic connexin 43: mediating morphine antinociceptive tolerance by activation of NMDA receptors and inhibition of glutamate transporter-1 in rats.

Aims: Connexin 43 (Cx43) has been reported to be involved in neuropathic pain, but whether it contributes to morphine antinociceptive tolerance remains unknown. The present study investigated the role of spinal Cx43 in the development of morphine tolerance and its mechanisms in rats.

Methods: Morphine tolerance was induced by intrathecal (i.

Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells.

A number of studies have demonstrated that inflammation plays a role in doxorubicin (DOX)-induced cardiotoxicity. However, the molecular mechanism by which DOX induces cardiac inflammation has yet to be fully elucidated. The present study aimed to investigate the role of the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway in DOX-induced inflammation and cytotoxicity.

Spinal MCP-1 contributes to the development of morphine antinociceptive tolerance in rats.

Background: The chemokine monocyte chemoattractant protein-1 (MCP-1) has been shown to contribute to neuropathic pain. However, whether MCP-1 is involved in the development of morphine antinociceptive tolerance is incompletely understood.

Methods: Morphine antinociceptive tolerance was induced by intrathecal administration of 15 μg of morphine daily for 7 days.

Hydrogen sulfide protects H9c2 cells against doxorubicin-induced cardiotoxicity through inhibition of endoplasmic reticulum stress.

The roles of hydrogen sulfide (H(2)S) and endoplasmic reticulum (ER) stress in doxorubicin (DOX)-induced cardiotoxicity are still unclear. This study aimed to dissect the hypothesis that H(2)S could protect H9c2 cells against DOX-induced cardiotoxicity by inhibiting ER stress. Our results showed that exposure of H9c2 cells to DOX significantly inhibited the expression and activity of cystathionine-γ-lyase (CSE), a synthetase of H(2)S, accompanied by the decreased cell viability and the increased reactive oxygen species (ROS) accumulation.

Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S against chemical hypoxia-induced injury in H9c2 cells.

Hydrogen sulfide (H(2)S) has been shown to exert cardioprotective effects. However, the roles of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in H(2)S-induced cardioprotection have not been completely elucidated. In this study, cobalt chloride (CoCl(2)), a chemical hypoxia mimetic agent, was applied to treat H9c2 cells to establish a chemical hypoxia-induced cardiomyocyte injury model.

Interaction between ROS and p38MAPK contributes to chemical hypoxia-induced injuries in PC12 cells.

The present study investigated whether there is an interaction between reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) during chemical hypoxia-induced injury in PC12 cells. The results of the present study showed that cobalt chloride (CoCl₂), a chemical hypoxia agent, markedly induced ROS generation and phosphorylation of p38MAPK, as well as neuronal injuries. N-acetylcysteine (NAC), a ROS scavenger, blocked CoCl₂-induced phosphorylation of p38MAPK.

Protective effects of early hypoxic post-conditioning in cultured cortical neurons.

Primary Objective: Recent evidence suggests that delayed hypoxic post-conditioning is neuroprotective. The aim of the present study was to test whether early post-conditioning applied immediately after hypoxia could protect cultured neurons from hypoxia/reoxygenation (H/R)-induced injuries.

Methods: Primary cortical neuronal culture depleted of microglia was exposed to H/R.

Heat shock protein 90 mediates cytoprotection by H₂S against chemical hypoxia-induced injury in PC12 cells.

1. Increasing evidence indicates that hydrogen sulphide (H₂S) may serve as an important biological cytoprotective agent. Heat shock protein (Hsp) 90 can attenuate stress-induced injury.

[Reactive oxygen species scavenger protects cardiac cells against injuries induced by chemical hypoxia].

Objective: To investigate the protective effect of reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), against H9c2 cardiomyocytes from injuries induced by chemical hypoxia.

Methods: H9c2 cells were treated with cobalt chloride (CoCl2), a chemical hypoxia-mimetic agent, to establish the chemical hypoxia-induced cardiomyocyte injury model. NAC was added into the cell medium 60 min prior to CoCl2 exposure.

NMDA receptors are involved in upstream of the spinal JNK activation in morphine antinociceptive tolerance.

N-methyl-d-aspartate (NMDA) receptors and c-Jun N-terminal kinase (JNK) have been shown to be involved in morphine antinociceptive tolerance. However, whether chronic morphine-induced activation of the spinal JNK is NMDA receptor-dependent is unknown. The present study investigated the link between the spinal NMDA receptor NR2B subunit and the JNK activation during morphine antinociceptive tolerance in rats.

Hydrogen sulphide protects H9c2 cells against chemical hypoxia-induced injury.

1. The aim of the present study was to investigate the effect of hydrogen sulphide (H(2)S) on cobalt chloride (CoCl(2))-induced injury in H9c2 embryonic rat cardiac cells. 2.

A novel role of minocycline: attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia.

We have previously demonstrated that activation of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal microglia mediates morphine antinociceptive tolerance. Minocycline, a selective inhibitor of microglia activation, has been reported to attenuate peripheral inflammation-induced hyperalgesia by depressing p38 MAPK in the spinal microglia. The aim of the present study is to explore the effect of intrathecal minocycline on the development of morphine antinociceptive tolerance and p38 activation in the spinal microglia induced by chronic morphine treatment.

Inhibition of neuronal nitric oxide synthase antagonizes morphine antinociceptive tolerance by decreasing activation of p38 MAPK in the spinal microglia.

We have demonstrated that the activation of p38 mitogen-activated protein kinase (MAPK) in the spinal microglia played an essential role in the development of morphine antinociceptive tolerance. The aim of this study was to investigate whether inhibition of neuronal nitric oxide synthase (nNOS) attenuated tolerance to morphine analgesia by modulating p38 activation in the spinal microglia. It was shown that the selective inhibitor of nNOS, 7-NINA (7-Nitroindazole, sodium salt) (25 microg, i.

Inducible nitric oxide synthase and cyclooxgenase-2 mediate protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells.

The induction of inducible nitric oxide synthase (iNOS) in response to different stress is associated with simultaneous induction of cyclooxygenase-2 (COX-2) in various cell types. Both iNOS and COX-2 have been reported to mediate the late phase of cardioprotection induced by different preconditioning. However, whether both iNOS and COX-2 are mediators in the neuroprotection induced by preconditioning with hydrogen peroxide (H(2)O(2)) at low concentration is unknown.

[Inhibition of 8-OH-DPAT on spontaneous unit discharges of 5-hydroxytryptamine inhibitory unit in rat primary somatosensory cortex].

Aim: To investigate the effect of 5-hydroxytryptamine (5-HT) on spontaneous unit discharges of primary somatosensory cortex (SI-SUD) and the role of 5-HT1A receptor in 5-HT inhibitory effect on SI-SUD in rat.

Methods: The SI-SUD was recorded before and during microiontophoresis of 5-HT and 8-OH-DPAT (the selective agonist for 5-HT1A receptor. The changes of mean of interspike interval (MISI) of SI-SUD were analysed and handled with the statistics.

Activation of p38 mitogen-activated protein kinase in spinal microglia mediates morphine antinociceptive tolerance.

Compelling evidence has suggested that spinal glial cells were activated by chronic morphine treatment and involved in the development of morphine tolerance. However, the mechanisms of glial activation were still largely unknown in morphine tolerance. In present study, we investigated the role of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal cord in the development of chronic morphine antinociceptive tolerance.

Hydrogen peroxide preconditioning protects PC12 cells against apoptosis induced by dopamine.

Dopamine (DA), one of the major sources of reactive oxygen species (ROS), is implicated in neuronal death associated with Parkinson's disease (PD). Preconditioning with oxidative stress has been shown to provide cytoprotection similar to ischemic preconditioning (IPC), against cell apoptosis. In this study, using the model neurosecretory cell line, PC12, we investigated whether hydrogen peroxide (H(2)O(2)) at low concentration (10 microM) can protect PC12 cells against apoptosis induced by DA.

Protection of oxidative preconditioning against apoptosis induced by H2O2 in PC12 cells: mechanisms via MMP, ROS, and Bcl-2.

The present study is designed to investigate the effects of preconditioning with different doses of hydrogen peroxide (H2O2) on oxidative stress-induced apoptosis and the changes in mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) level, and expression of Bcl-2 during H2O2 preconditioning in rat pheochromocytoma (PC12) cells. It was shown that (1) H2O2 induced apoptosis in PC12 cells in a dose-dependent manner; (2) the preconditioning with 10 micromol L(-1) or 20 micromol L(-1) H2O2 can significantly protect PC12 cells against apoptosis induced by 50 or 100 micromol L(-1) H2O2, low (5 micromol L(-1)) and higher (30 micromol L(-1)) concentrations of H2O2 had no cytoprotections; (3) high concentration (100 micromol L(-1)) of H2O2 reduced MMP and expression of Bcl-2, and increased ROS level, but these effects were blocked by preconditioning with 10 micromol L(-1) H2O2; (4) the preconditioning with 10 micromol L(-1) H2O2 induced overexpression of Bcl-2. These results suggested that the preconditioning with low dose of H2O2 could protect the oxidative stress-induced PC12 cells apoptosis not only by preventing the reduction of MMP and expression of Bcl-2 as well as increase in ROS level, but also through overexpression of Bcl-2.

Hydrogen peroxide preconditioning protects PC12 cells against apoptosis induced by oxidative stress.

Oxidative stress can induce significant cell death by apoptosis. We explore whether prior exposure to H2O2 (H2O2 preconditioning) protects PC12 cells against the apoptotic consequences of subsequent oxidative damages and what role the ATP-sensitive potassium (K(ATP)) channels play in the preconditioning protection. PC12 cells were preconditioned with 90 min exposure to H2O2 at 10 micromol/L, followed by 24-h recovery and subsequent exposures to different concentrations (20, 30, 50 and 100 micromol/L) of H2O2 for 24 h respectively.