Pathogenesis of glucocorticoid-induced osteoporosis based on label-free mass proteomics / 中国骨伤

OBJECTIVE@#To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics.@*METHODS@#Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis.@*RESULTS@#Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway.@*CONCLUSION@#Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.

Mercury species analysis and tissue distribution in rats after continuous administration of Cinnabaris / 中国中药杂志

Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics, and its safety has always been a concern. This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris. In the experiment, 30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium), low-dose Cinnabaris group(0.2 g·kg~(-1)), high-dose Cinnabaris group(2 g·kg~(-1)), pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose), and pseudogerm-free Cinnabaris group(2 g·kg~(-1)). They were orally administered for 30 consecutive days. Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(Ⅱ)], methylmercury(MeHg), and ethylmercury(EtHg) in different tissue, plasma, urine, and feces of rats. The optimal detection conditions and extraction methods were optimized, and the linearity(R~2>0.999 3), precision(RSD<7.0%), and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied, meeting the requirements of analysis. The results of mercury species detection showed that Hg(Ⅱ) was detected in all the tissue of the five experimental groups, and the main accumulating organs were the intestinal tract, stomach, and kidney. MeHg existed at a low concentration in most tissue, and EtHg was not detected in all groups. In addition, pathological examination results showed that hepatocyte vacuolar degeneration, loose cytoplasm, light staining, and mononuclear cell infiltration were observed in the high-dose Cinnabaris group, low-dose Cinnabaris group, and pseudogerm-free Cinnabaris group, with slightly milder lesions in the low-dose Cinnabaris group. Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group, but there was no significant difference between the other groups and the control group. No abnormal changes were found in the brain tissue of rats in each group. This paper studied the different mercury species and tissue distribution in normal and pseudogerm-free rats after continuous administration of Cinnabaris for 30 days and clarified its effects on the tissue structure of the liver, kidney, and brain, which provided supporting evidence for the safety evaluation of Cinnabaris.

Chemical constituents of traditional Chinese materia medica for alleviating renal damage of paracetamol:research advances / 国际药学研究杂志

Paracetamol (acetaminophen, APAP)is one of the commonly used analgesic, antipyretic and anti-inflammatory drugs, but it can cause acute kidney injury(AKI)or even acute renal failure due to blind, large, combined or long-term use. The mechanism reseach on the APAP-induced nephrotoxicity is mainly focused on the formation of metabolic toxic substances, oxidative stress, inflammatory response, mitochondrial dysfunction, endoplasmic reticulum stress(ERS), and changes in glomerular hemody namics. This paper summarizes the toxicity mechanism of APAP-induced AKI(APAP-AKI), and the research progress in the protec tive effect of active ingredients of traditional Chinese materia medicas(TCMM)on APAP-AKI, including polyphenols, flavonoids, quinones, terpenoids, amino acids and other type substances, with an aim to clarify the key mechanisms and signaling pathways of APAP-AKI and to provide reference for the development of drugs for the prevention and treatment of APAP-AKI.

Research Advance of Effective Components of Traditional Chinese Medicine on Alleviating Acetaminophen-Induced Liver Injury / 中国药学杂志

Acetaminophen (APAP) is one of the commonly used analgesic antipyretic anti-inflammatory drugs, which cause drug-induced liver damage and even acute liver failure due to take large amounts of drugs blindly, combination drugs-using or long-term medication. The mechanisms of APAP-induced hepatotoxicity mainly focus on the generation of toxic metabolites, mitochondrial dysfunction, inflammatory response, oxidative stress, the release of damage associated molecular patterns (DAMPs), autophagy, endoplasmic reticulum stress, and microcirculatory dysfunction. This article summarizes the toxic mechanism of drug-induced liver injury induced by APAP, and summarizes the research progress of active ingredients of traditional Chinese medicine on the protective effect of APAP-induced liver injury, including polyphenols, flavonoids, saponins, organic acids, terpenoids, phenylpropanoids compounds, sugars, alkaloids and other compounds, to provide a reference for the development of drugs to prevent and treat APAP-induced liver injury.