Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxic-ischemic (HI) brain injury in the perinatal period causes significant morbidity. Minocycline (MN) is a tetracycline derivative that has reduced brain injury in various animal models of neurodegeneration, including perinatal ischemia. To determine whether MN can modulate the expression of chemokine receptors and interleukin-10 (IL10) in a model of neonatal brain injury, we produced an HI insult to the right cerebral hemisphere (ipsilateral) of the 7-day-old rat (PD7) by right common carotid artery ligation and 2.25 hr of hypoxia in 8% oxygen. MN (45 mg/kg, i.p.) or vehicle (PBS) was injected twice: 2 days and immediately before the HI insult. At 0, 1, 3, and 24 hr and 14 days after HI, total RNA from the ipsilateral and contralateral (exposed to hypoxia only) hemispheres was extracted, reverse transcribed, and amplified with gene-specific primers using a semiquantitative RT-PCR for macrophage inflammatory protein-1alpha), interferon-inducible protein (IP-10), C-C chemokine receptor 5 (CCR5; MIP-1alpha receptor), C-X-C chemokine receptor 3 (CXCR3; IP-10 receptor), and IL10. We found that, in the ipsilateral hemisphere, a significant (P < 0.05) increase in MIP-1alpha, IP-10, CCR5, and CXCR3 mRNA levels was observed. MN treatment decreased mRNA levels for CCR5 and CXCR3. In contrast, the levels of antiinflammatory cytokine IL10 were markedly decreased as a result of HI insult. Treatment with MN, however, had no effect on IL10. We conclude that MN decreased proinflammatory chemokine receptor expression but had little or no influence on the expression of antiinflammatory cytokine IL10. These effects confirm the antiinflammatory effect of MN in neonatal HI brain injury.
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PMID:Minocycline modulates chemokine receptors but not interleukin-10 mRNA expression in hypoxic-ischemic neonatal rat brain. 1754 54

Drug-induced liver injury has become a serious public health problem. Although the mechanism of acetaminophen (APAP)-induced liver injury has been studied for decades it has not been fully elucidated. In-depth study into the mechanisms underlying APAP-induced liver injury may provide useful information for more effective prevention and treatment. In the present study, the role of C-X-C motif chemokine ligand-9 (CXCL9) in APAP-induced liver injury was investigated thus providing a novel direction for the prevention and treatment of drug hepatitis. A total of 20 fasting male patients ingested APAP tablets at Nanjing First Hospital. In addition, wild type (WT) mice were treated with 250 mg/kg APAP or isodose PBS for 1, 3, 6 and 12 h, respectively. Results from reverse-transcription-quantitative polymerase chain reaction analyses demonstrated that CXCL9 mRNA levels were increased in the blood of patients who took APAP in a fasting state and in the livers of APAP-treated WT mice, compared with their respective controls. Hepatocyte apoptosis in the liver tissue of APAP-treated mice decreased following administration of a CXCL9 neutralizing antibody. Caspase-3, caspase-8 and phosphorylated-AKT (S437) were activated in primary hepatocytes isolated from WT mice following CXCL9 treatment. However, no significant differences in expression of caspase-3, caspase-8 and p-AKT (S437) were detected in hepatocytes isolated from C-X-C motif chemokine receptor 3 (CXCR3)-/- mice following CXCL9 treatment. After CXCL9 administration, WT mice exhibited higher serum levels of aspartate transaminase and increased caspase-3 and caspase-8 activity in liver tissue compared with controls. The same trends were not observed in CXCR3-/- mice. In conclusion, CXCL9 regulated APAP-induced liver injury through stimulation of hepatocyte apoptosis via binding to CXCR3. These findings provide a novel prevention and treatment strategy for DILI.
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PMID:CXCL9 regulates acetaminophen-induced liver injury via CXCR3. 3177 48