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Targeting CXCL1 chemokine signaling for treating cisplatin ototoxicity
In this study, we investigated the role of CXCL1, a cytokine which increased in the serum and cochlea by 24 h following cisplatin administration. Adult male Wistar rats treated with cisplatin demonstrated significant hearing loss, assessed by auditory brainstem responses (ABRs), hair cell loss and loss of ribbon synapse. Immunohistochemical studies evaluated the levels of CXCL1 along with increased presence of CD68 and CD45-positive immune cells in cochlea. Increases in CXCL1 was time-dependent in the spiral ganglion neurons and organ of Corti and was associated with progressive increases in CD45, CD68 and IBA1-positive i...
Source: Frontiers in Immunology - March 31, 2023 Category: Allergy & Immunology Source Type: research

Phosphate NIMA-Related Kinase 2-Dependent Epigenetic Pathways in Dorsal Root Ganglion Neurons Mediates Paclitaxel-Induced Neuropathic Pain
CONCLUSIONS: pRSK2/JMJD3/H3K27me3/TRPV1 signaling in the DRG neurons plays as a key regulator for PTX therapeutic approaches.PMID:36753440 | DOI:10.1213/ANE.0000000000006397
Source: Anesthesia and Analgesia - February 8, 2023 Category: Anesthesiology Authors: Ming-Chun Hsieh Cheng-Yuan Lai Wen-Long Cho Li-Ting Lin Chou-Ming Yeh Po-Sheng Yang Jen-Kun Cheng Hsueh-Hsiao Wang Kuan-Hung Lin Siao-Tong Nie Tzer-Bin Lin Hsien-Yu Peng Source Type: research

Identification of lncRNA and mRNA expression profiles in dorsal root ganglion in rats with cancer-induced bone pain
CONCLUSION: LncRNA played important roles in regulation of CIBP or mRNA expression in peripheral neuropathy in CIBP. These alterd mRNAs and lncRNAs might be potential therapeutic targets for the treatment of CIBP.PMID:34364296 | DOI:10.1016/j.bbrc.2021.07.063
Source: Cell Research - August 7, 2021 Category: Cytology Authors: Jinrong Wei Qianshu Dou Futing Ba Guang-Yin Xu Guo-Qin Jiang Source Type: research

CREB Participates in Paclitaxel-Induced Neuropathic Pain Genesis Through Transcriptional Activation of Dnmt3a in Primary Sensory Neurons
AbstractChemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of cyclic AMP response element-binding protein (CREB) in dorsal root ganglion (DRG) neurons. Blocking this increase through DRG microinjection ofCreb siRNA attenuated paclitaxel-induced mechanical, heat, and cold nociceptive...
Source: Neurotherapeutics - October 13, 2020 Category: Neurology Source Type: research

Upregulation of lncRNA-NONRATT021203.2 in the dorsal root ganglion contributes to cancer-induced pain via CXCL9 in rats.
In this study, we found that lncRNA-NONRATT021203.2 was increased in the CIP rats and that lncRNA-NONRATT021203.2-siRNA could relieve hyperalgesia in these rats. For elucidation of the underlying mechanism, we showed that lncRNA-NONRATT021203.2 could target C-X-C motif chemokine ligand 9 (CXCL9), which was increased in the CIP rats, and that CXCL9-siRNA could relieve hyperalgesia. At the same time, silencing lncRNA-NONRATT021203.2 expression decreased the mRNA and protein levels of CXCL9. Immunofluorescence analysis showed that CXCL9 was mainly expressed in the CGRP-positive and IB4-positive DRG neurons. Further research s...
Source: Biochemical and Biophysical Research communications - February 11, 2020 Category: Biochemistry Authors: Sun RM, Wei J, Wang SS, Xu GY, Jiang GQ Tags: Biochem Biophys Res Commun Source Type: research

SOCS and Herpesviruses, With Emphasis on Cytomegalovirus Retinitis
Christine I. Alston1,2 and Richard D. Dix1,2* 1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - April 10, 2019 Category: Allergy & Immunology Source Type: research

The association of neuronal stress with activating transcription factor 3 in dorsal root ganglion of in vivo and in vitro models of bortezomib-induced neuropathy.
This study exhibited important mechanistic insight into how BTZ induces neurotoxicity through the activation of ATF3 resulting in intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress and provided a novel potential therapeutic target by blocking ATF3 signaling. PMID: 30289077 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - October 3, 2018 Category: Cancer & Oncology Authors: Yin Y, Qi X, Qiao Y, Liu H, Yan Z, Li H, Liu Z Tags: Curr Cancer Drug Targets Source Type: research

AKAP150 involved in paclitaxel-induced neuropathic pain via inhibiting CN/NFAT2 pathway and downregulating IL-4
In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or AKAP150flox/flox in rodents alleviated the pain behavior induced by paclitaxel, and partly restored the decreased calcineurin (CN) phosphatase activity after paclitaxel treatment. Paclitaxel decreased the expression of anti-inflammatory cytokine interleukin-4 (IL-4), and intrathecal injections of IL-4 effectively alleviated paclitaxel-induced hypersensitivity and the frequency of dorsal root ganglion (DRG) neurons action potential. The decreased CN enzyme activity, ...
Source: Brain, Behavior, and Immunity - January 11, 2018 Category: Neurology Source Type: research

AKAP150 involved in Paclitaxel-Induced Neuropathic Pain via Inhibiting CN/NFAT2 pathway and downregulating IL-4.
In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or AKAP150(flox/flox) in rodents alleviated the pain behavior induced by paclitaxel, and partly restored the decreased calcineurin (CN) phosphatase activity after paclitaxel treatment. Paclitaxel decreased the expression of anti-inflammatory cytokine interleukin-4 (IL-4), and intrathecal injections of IL-4 effectively alleviated paclitaxel-induced hypersensitivity and the frequency of dorsal root ganglion (DRG) neurons action potential. The decreased CN enzyme activity...
Source: Brain, Behavior, and Immunity - October 19, 2017 Category: Neurology Authors: Nie B, Liu C, Bai X, Chen X, Wu S, Zhang S, Huang Z, Xie M, Xu T, Xin W, Zeng W, Ouyang H Tags: Brain Behav Immun Source Type: research

Inhibition of long non-coding RNA IGF2AS has profound effect on inducing neuronal growth and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion neurons
Conclusions Inhibiting endogenous IGF2AS may promote neuronal growth and protect local-anesthetic induced neurotoxicity in DRG neurons, possibly through complimentary IGF2 upregulation and autocrine activation neurotrophin genes.
Source: Biomedicine and Pharmacotherapy - May 17, 2016 Category: Drugs & Pharmacology Source Type: research

Abstract 4415: Tyrosine phosphorylation is essential for OCT2 function and a target of inhibition by TKIs
Cisplatin and oxaliplatin are among the most widely used anticancer drugs in both children and adults. The clinical use of these agents is associated with dose-limiting damage to kidneys (nephrotoxicity) and peripheral nerves (neurotoxicity). Mechanistic understanding of the underlying etiology remains incomplete and preventive strategies are currently unavailable. We previously reported that cisplatin nephrotoxicity (Filipski et al, CPT 2009) and oxaliplatin neurotoxicity (Sprowl et al, PNAS 2013) are dependent on organic cation transporter-mediated uptake mechanisms and can be reduced by genetic or pharmacological inhibi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Pabla, N., Sprowl, J. A., Ong, S. S., Gibson, A. A., Du, G., Lin, W., Hu, S., Li, L., Chen, T., Sparreboom, A. Tags: Experimental and Molecular Therapeutics Source Type: research