[Study on the correlation between the arc height of cervical endplate and osteophyte in posterior margin of intervertebral space].

OBJECTIVE: To study the correlation and clinical value of the arc height of upper and lower endplates, the height of intervertebral space and osteophyte of posterior edge of intervertebral space in patients with cervical spondylosis. METHODS: A total of 108 patients with cervical spondylosis who underwent cervical spondylosis surgery from September 2017 to September 2018 were included in the study. Including 48 males with an average age of 52 years (30 to 72) and 60 females with an average age of 54 years (37 to 79). Among them, C2,3 of 6 cases, C3,4 of 15 cases, C4,5 of 32 cases, C5,6 of 42 cases, C6,7 of 13 cases. X-ray films of cervical spine were taken before and after operation. The images were accessed by PACS (Picture Archiving and Communication Systems) system. The lower and upper endplate arc heights (L1, L2), intervertebral space height (L3), and posterior osteophyte width (L4) were measured. Spearman was used to analyze the correlation between them. RESULTS: L1 was negatively correlated with L4 (r=-0.34, P<0.05), L3 was negatively correlated with L4 (r=-0.36, P<0.05). L1 was positively correlated with L3 (r=0.38, P<0.05), L2 was positively correlated with L3 (r=0.48, P<0.05). There was no significant difference between L 1 and L2 (P>0.05), L2 and L4 (P>0.05). CONCLUSION: The arc height of the lower endplate is negatively correlated with the width of osteophyte in the posterior margin of the intervertebral space. The cervical degeneration degree can be determined by measuring the arc height of the lower endplate, which has guiding significance for the early prevention and treatment of cervical spondylosis.

Duration of electrochemical deposition affects the morphology of hydroxyapatite coatings on 3D-printed titanium scaffold as well as the functions of adhered MC3T3-E1 cells.

BACKGROUND: The use of 3D-printed scaffolds in repairing bone defects remains unexplored. We aimed to determine whether the duration of electrochemical deposition (ECD) affects the properties of hydroxyapatite (HA) coatings on 3D-printed titanium (TI) scaffolds as well as the corresponding phenotype of MC3T3-E1 cells seeded on these surfaces. METHODS: Five groups of HA-coated TI scaffolds were produced using different durations of ECD (0, 5, 10, 20, and 30 min) and examined under scanning electron microscopy (SEM). MC3T3-E1 cell adhesion to the HA-coated scaffolds and subsequent proliferation and viability were assessed using SEM, DAPI staining, EdU staining, and Alamar Blue assay, respectively. MC3T3-E1 cell expression of osteogenic genes was analyzed by fluorescence RT-PCR. RESULTS: On SEM, longer ECD durations resulted in more compact HA crystals of differing morphology coated onto the TI scaffolds. MC3T3-E1 cell adhesion differed among the five groups (p < 0.05), with the largest number of cells adhered to the scaffolds prepared with 30 min of ECD, followed by the group prepared with 20 min of ECD. However, the ECD duration of 20 min was associated with the highest cell viability and proliferation rate (both p < 0.05) as well as the highest mRNA expression levels of alkaline phosphatase, collagen I, osteocalcin and runt-related transcription factor 2 among the five groups (p < 0.05). CONCLUSIONS: In the fabrication of HA-coated 3D printed TI scaffolds, an ECD duration of 20 min resulted in scaffolds that best promoted MC3T3-E1 cell viability, proliferation and osteogenic gene expression.

Selective targeting p53WT lung cancer cells harboring homozygous p53 Arg72 by an inhibitor of CypA / 中国药理学与毒理学杂志

OBJECTIVE To explored the potential of pharmacological stabilization and reactivation of p53 for targeted cancer therapies. METHODS The cytotoxicity of a potent Cyclophilin A (CypA) inhibitor HL001 was tasted against a panel of cancer cell lines. The genotypes and activation of p53 were compared with the cytotoxicity profile of HL001. Two-dimensional (2D) PAGE analysis was performed to investigate differentially expressed proteins that involves in the anti-proliferation effects of HL001. Pull-down and Co-IP were used to confirmed the new identified PPI between CypA and G3BP1 and orthotopic animal model of lung cancer was used to tested the anti- tumor activity of HL001 in vivo. RESULTS We identify a novel CypA small molecule inhibitor HL001 that induces non-small cell lung cancer (NSCLC) cell cycle arrest and apoptosis via restoring p53 expression. We find that HL001 stabilizes p53 through inhibiting the MDM2-mediated p53 ubiquitination. Further mechanistic studies reveal that the downregulation of G3BP1 and the induction of reactive oxygen species and DNA damage by HL001 contribute to p53 stabilization. Surprisingly, HL001 selectively suppresses tumor growth in p53 wildtype NSCLC harboring Arg72 homozygous alleles (p53- 72R) through disrupting interaction between MDM2 and p53-72R in a CypA dependent manner. Moreover, combining HL001 with cisplatin synergistically enhance tumor regression in orthotopic NSCLC mouse model. CONCLUSION Pharma?cologic inhibition of CypA offers a potential therapeutic strategy via specific activation of p53-72R in NSCLC.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis / 中国药理学与毒理学杂志

OBJECTIVE Leukotriene B4 (LTB4) biosynthesis and subsequently neutrophilic inflam?mation may provide a potential strategy for the treatment of acute lung injury (ALI) or idiopathic pulmonary fibrosis (IPF). To provide a potential strategy for the treatment of ALI or IPF, we identified potent inhibi?tors of Leukotriene A4 hydrolase (LTA4H), a key enzyme in the biosynthesis of LTB4. METHODS In this study, we identified two known histone deacetylase (HDAC) inhibitors, suberanilohydroxamic acid (SAHA) and its analogue 4-(dimethylamino)-N-〔7-(hydroxyamino)-7-oxoheptyl〕benzamide (M344), as effective inhibitors of LTA4H using enzymatic assay, thermofluor assay, and X- ray crystallographic investigation. We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay. A murine experimental model of ALI was induced by lipopolysaccharide(LPS) inhalation. Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA. We next examined mRNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using qRT- PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA. We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin (BLM)-induced IPF model. RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H, signif?icantly decrease LTB4 levels in neutrophil, and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose. CONCLUSION Collectively, SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Synthesis and biological activities of novel artemisinin derivatives as cysteine protease falcipain-2 inhibitors.

A series of novel artemisinin derivatives were synthesized from artemisinin and different anilines. All compounds were obtained as ß-isomers. The target compounds were evaluated for inhibition activity against Plasmodium falciparum falcipain-2 in vitro, and most of them exhibited potent inhibition in the low micromolar range and proved to be new types of falcipain-2 inhibitors.