ABSTRACT
Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.
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Objective: To investigate the effects of traditional Chinese medicine Xuebijing injection (血必净注射液) on tissue tumor necrosis factor-?(TNF-?) expression and blood coagulation parameters in septic rats.Methods: Wistar rats were subjected to sepsis induced by cecal ligation and puncture(CLP).Ninety-six healthy rats were randomly divided into four groups: normal group,sham operation group,CLP model group,and Xuebijing-treated group.The two latter groups were given respectively intravenous injection of normal saline or Xuebijing injection with the dose of 4 ml/kg at 0.5,12,24,36,48 and 60 hours after the establishment of CLP model.Eight rats were sacrificed at 2,8,24,48 and 72 hours postCLP in the two latter groups.Prothrombin time(PT),activated partial thromboplastin time (APTT),and fibrinogen(Fbg) levels were determined.Tissue TNF-? protein levels in liver and lung tissues were also measured at various intervals.Results: TNF-? protein levels in liver and lung tissues were significantly increased at 2 hours after establishment of CLP model compared with those of the normal group(both P
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BACKGROUND: Nerve root could be directly or indirectly entrapped due to lateral backward prolapse of nucleus pulposus of intervertebral disc, as well as parenchymal inflammatory tumefaction of the soft tissues in nerve root tube. But the factors and their severity related to cervical nerve entrapment at cervical intervertebral foramen and spinal nervous sulcus still need further studies.OBJECTIVE: To investigate the relationship between the occurrence rate of cervical nerve entrapment at cervical intervertebral foramen and spinal nervous sulcus and the severity of cervical syndrome.DESIGN: A single sample study.SETTING: Department of Anatomy, Department of Geriatrics of the Affiliated Hospital, and Department of Teaching Affairs, Chengde Medical College.PARTICIPANTS: The research was conducted in the Department of Anatomy, Chengde Medical College. Totally 120 sides of 60 cadavers(28 males and 32 females) were provided by the Department of Anatomy.METHODS: The outside diameters of cervical intervertebral foramen and spinal nerve root, as well as the width of external opening of spinal nerve sulcus and transverse diameter width of the anterior branch of intra-spinal nerve were measured, and the data were dealt with statistically.MAIN OUTCOME MEASURES: The ratio of transversal diameter of the forepart of cervical nerves to the width of spinal nerve sulcus; the ratio of the peripheral diameter of cervical nerve roots to the size of intervertebral foramen; the occurrence rate where the ratio was ≥ 1.RESULTS: The ratio between cervical nerve root and intervertebral foramen was significantly larger than that between spinal nerve root and spinal nerve sulcus( t = 2.66, P ＜ 0.01 ). The occurrence rate of cervical nerve entrapment at the intervertebral foramen(24.6% ) was higher than that in spinal nerve sulcus(6.3% ), and the difference had a considerable statistical significance(x2 =6.95, P ＜ 0.01).CONCLUSION: It is suggested that the spinal nerve may be entrapped in the cervical intervertebral foramen and the spinal nervous sulcus, and the spinal nerve lesions in the cervical intervertebral foramen was more serious than in the spinal nervous sulcus. Therefore, in clinic, when diagnosing and treating cervical spondylosis, while nerve entrapment at the intervertebral foramen is fully considered, the possibility of nerve entrapment at the spinal nervous sulcus should not be neglected.
ABSTRACT
BACKGROUND: Whether nerve root is involved or not in cervical spondylosis of nerve root type is related not only to stenosis of bone canal and inflammatory disorder and swelling in peripheral soft tissues, but also to the relevant size of external diameter of nerve root.OBJECTIVE: To probe into the anatomical factors of cervical spondylosis of nerve root type with occurrence rate of involved cervical nerve in cervical intervertebral foramen and sulcus of spinal nerve.DESIGN: Single sample observation was designed.SETTING: Department of Anatomy of Chengde Medical College.PARTICIPANTS: Totally 120 sides of 60 adult corpses were employed with formaldehyde fixation (28 cases of male and 32 cases of female).METHODS: Sixty adult corpses were measured with the vernier of 0.02 mm spinal nerve and the transverse diameter of anterior branch (A-diameter) of superoinferior diameter (S - I diameter) of cervical intervertebral foramen and its spinal nerve root. The ratios were calculated between A-diameter cervical nerve and E-diameter of the corresponding sulcus of spinal nerve and between A - P diameter and S - I diameter of spinal nerve root and those of corresponding intervertebral foramen respectively. The rates of occurrence were concluded for those cervical nerves whose A-diameter larger than or equal to E-diameter of sulcus of spinal nerves and for those spinal nerve roots whose rations larger than or equal to those of corresponding intervertebral foramens.cervical nerve in C3-6 larger than or equal to E-diameter of sulcus of spinal nerve roots in C3-6 larger than or equal to those of corresponding intervertebral foramens.RESULTS: Totally 120 sides of 60 corpses were measured (56 cases of male wedge pressure in intervertebral foramen of cervical nerve root for both male and female, of which, that of female was remarkably superior to the male was 6. 3% for wedge pressure of anterior branch of cervical spinal nerve in sulcus in spinal nerve for both male and female, of which, that of male was remarkably superior to the female(8.9%, 3.9%, χ2 = 6.65, P ＜ 0. 01 ).CONCLUSION: The involvement of cervical nerve is related not only to the stenosis of bone canal but also to the injury of peripheral soft tissues. By the ratios between E-diameter of nerve root and intervertebral foramen and between A-diameter of cervical nerve and E-diameter of sulcus of spinal nerve, those ≥ 1 can be obtained directly as the rate of occurrence of nerve compression.