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1.
Neuroreport ; 34(14): 713-719, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37556589

ABSTRACT

Paclitaxel is an extensively used chemotherapy antitumor drug and paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common side effect. Rapamycin, originally used as an adjuvant drug for chemotherapy, has recently been found to possess potential neuroprotective activities. Our purposes of this study are to verify the effect of rapamycin on PIPN, which contributes to a new target for PIPN treatment. Mice were given paclitaxel or rapamycin with different injection methods. Paw withdrawal threshold was tested at different time points for mechanical sensitivity assessment. Administration of paclitaxel, both 2 mg/kg and 5 mg/kg, could induce mechanical hypersensitivity. 0.01 mg intrathecal injection of rapamycin showed the best effect on attenuate the mechanical hyperalgesia of PIPN. Intrathecal injection of only rapamycin would not induce the mechanical hyperalgesia while when rapamycin and paclitaxel were used together the mechanical hyperalgesia induced by paclitaxel could be attenuated. Paclitaxel could induce mechanical hyperalgesia in mice and rapamycin could attenuate such mechanical hyperalgesia of PIPN.


Subject(s)
Antineoplastic Agents , Peripheral Nervous System Diseases , Mice , Animals , Paclitaxel/toxicity , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Sirolimus/pharmacology , Sirolimus/therapeutic use , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/drug therapy , Antineoplastic Agents/therapeutic use
2.
Neurochem Res ; 47(2): 315-326, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34498160

ABSTRACT

The effects of general anesthetics on the developing brain have aroused much attention in recent years. Sevoflurane, a commonly used inhalation anesthetic especially in pediatric anesthesia, can induce developmental neurotoxicity. In this study, the differentially expressed mRNAs in the hippocampus of newborn rats exposed to 3% sevoflurane for 6 h were detected by RNA-Sequencing. Those data indicated that the mRNA of Klotho was increased after exposure to sevoflurane. Moreover, the protein expression of Klotho was assayed by Western Blot. Besides over-expression and under-expression of Klotho protein, we also detected changes of cell proliferation, ROS, JC-1, and Bcl-2/Bax ratio in PC12 cells exposed to sevoflurane. After exposure to 3% sevoflurane, the expression of Klotho protein increased in the hippocampus of neonatal rats. In PC12 cells, exposure to sevoflurane could increase cellular ROS level, reduce mitochondrial membrane potential and Bcl-2/Bax ratio. While overexpression of Klotho alleviated the above changes, knockdown of Klotho aggravated the injury of sevoflurane. Klotho protein could reduce oxidative stress and mitochondrial injury induced by sevoflurane in the neuron.


Subject(s)
Anesthetics, Inhalation , Methyl Ethers , Anesthetics, Inhalation/toxicity , Animals , Animals, Newborn , Apoptosis , Hippocampus/metabolism , Humans , Methyl Ethers/toxicity , Neurons/metabolism , Rats , Sevoflurane/toxicity
3.
Cell Transplant ; 29: 963689720903691, 2020.
Article in English | MEDLINE | ID: mdl-32364405

ABSTRACT

During the process of human islet isolation a cascade of stressful events are triggered and negatively influence islet yield, viability, and function, including the production of proinflammatory cytokines and activation of apoptosis. Carbon monoxide-releasing molecule 2 (CORM-2) is a donor of carbon monoxide (CO) and can release CO spontaneously. Accumulating studies suggest that CORM-2 exerts cytoprotective and anti-inflammatory properties. However, the effect of CORM-2 on islet isolation is still unclear. In this study, we found that CORM-2 pretreatment significantly decreased the expression of critical inflammatory genes, including tissue factor, intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2, C-X-C motif chemokine 10, Toll-like receptor 4, interleukin-1ß, interleukin-6, and tumor necrosis factor-α (TNF-α). The isolated islets of the CORM-2 pretreatment group showed reduced apoptotic rate, improved viability, and higher glucose-stimulated insulin secretion, and functional gene expression in comparison to control group. Importantly, CORM-2 pretreatment prevented the impairment caused by TNF-α, evidenced by the improved glucose-stimulated index and transplantation outcomes. The present study demonstrated the anti-inflammatory property of CORM-2 during human islet isolation, and we suggest that CORM-2 pretreatment is an appealing treatment to mitigate inflammation-mediated islet dysfunction during isolation and culture ex vivo and to preserve long-term islet survival and function.


Subject(s)
Inflammation/drug therapy , Organometallic Compounds/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Flow Cytometry , Glucose Tolerance Test , Humans , Immunohistochemistry , Inflammation/metabolism , Intercellular Adhesion Molecule-1/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Islets of Langerhans Transplantation , Male , Mice, Inbred BALB C , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
4.
Int J Biol Macromol ; 132: 1155-1162, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30981769

ABSTRACT

In the present study, in order to improve the properties of nanostarch-based nanocomposite film for food packaging, a type of nanocomposite film based on corn nanostarch (CNS) as the matrix and modified cellulose nanocrystals (modified-CNCs) as the reinforcement was prepared using a solution casting method. The cellulose nanocrystals (CNCs) were modified by a two-step method in which they were initially crosslinked with citric acid, and subsequently amidated with chitosan. Then, a type of CNS/modified-CNCs nanocomposite film with different content levels of modified-CNC were prepared and characterized using Fourier Transform Infrared spectroscopy (FTIR); X-ray Photoelectron Spectroscopy (XPS); X-Ray Diffraction (XRD); Differential Scanning Calorimetry (DSC); and Scanning Electron Microscopy (SEM). It was observed that when compared with the pure CNS film, the 8.0 wt% modified-CNCs loaded nanostarch-based nanocomposite film had displayed a 230.0% increase in tensile strength. And the moisture absorption ability had decreased by 25.6%; water vapor permeability had decreased by 87.4%; and the water contact angle value had increased by 18.1%. Also the results of this experimental study had revealed that the CNS/modified-CNCs nanocomposite film had displayed better antimicrobial activities against E. coli and S. aureus bacteria when compared with the pure CNS film.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cellulose/chemistry , Nanocomposites/chemistry , Nanoparticles/chemistry , Escherichia coli/drug effects , Food Packaging , Permeability , Staphylococcus aureus/drug effects , Steam , Tensile Strength
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