ABSTRACT
BACKGROUND:Periprosthetic osteolysis is the most common long-term complication of total joint arthroplasty.Many studies suggest that the inflammasome may play an important role during the osteolysis.Melatonin is a rhythm-regulated hormone secreted by the pineal gland with many functions including anti-inflammatory,anti-oxidation,and antitumor,but its effects on osteolysis and inflammasome have yet to be explored. OBJECTIVE:To explore the effect of melatonin on the osteolysis induced by wear particles and the role of melatonin on the activation of NLRP3 inflammasome. METHODS:(1)In vivo test:Fifteen C57BL/6 mice were randomly divided into sham operation group,osteolysis group and melatonin group by random number table method,with 5 mice in each group.The osteolysis model of the osteolysis group and the melatonin group was established by injecting cobalt-chromium-molybdenum(CoCrMo)particles into the sagittal suture of the skull.After injection,the melatonin group was intraperitoneally injected with 50 mg/(kg·d)of melatonin for 14 consecutive days.After drug intervention,the mouse calvarium was collected for micro-CT analysis to observe the micro-structural changes around the sagittal suture.(2)In vitro test:Mouse bone marrow-derived macrophages and THP-1 cells(which had been induced to differentiate into macrophages)were taken and divided into seven groups:normal group,lipopolysaccharide group,lipopolysaccharide+CoCrMo group and melatonin 0.5,1,1.5,2 mmol/L groups(lipopolysaccharide and CoCrMo were added to the melatonin intervention groups).After the intervention for 6 hours,the expression of related proteins(NLRP3,Caspase-1,interleukin-1β,and gasdermin D,gasdermin D-N terminal)in the inflammasome of cell lysate or cell culture supernatant was detected by western blot assay.Cytotoxicity and cell death were observed through lactate dehydrogenase release and live-dead fluorescence staining. RESULTS AND CONCLUSION:(1)In vivo test:Micro-CT scanning 3D reconstruction images showed that the bone mass around the sagittal suture of the skull of mice in the osteolysis group was significantly reduced,and the bone tissue structure was severely damaged.Compared with the osteolysis group,the bone mass around the sagittal suture of the skull in the melatonin group was significantly increased,and the destruction of tissue structure was reduced.(2)In vitro test:For mouse bone marrow-derived macrophages,lipopolysaccharide significantly up-regulated NLRP3 protein expression in cell lysate,and melatonin intervention could reduce NLRP3 protein expression in a dose-dependent manner.CoCrMo particles significantly up-regulated the protein expressions of the gasdermin D-N terminal in cell lysate and Caspase-1 and interleukin-1β in the supernatant of cell culture,while melatonin intervention could reduce the expression of these proteins in a dose-dependent manner.For THP-1 cells,the protein expressions of Caspase-1 and interleukin-1β in the supernatant of cell culture were significantly up-regulated by CoCrMo particles,and the expression of these proteins was decreased dose-dependent by melatonin intervention.Lactate dehydrogenase release and live-dead fluorescence staining showed that CoCrMo particles significantly increased the release of lactate dehydrogenase and cell death in the supernatant of mouse bone marrow-derived macrophage culture,and melatonin intervention could reduce the release of lactate dehydrogenase and cell death.(3)The results show that melatonin can inhibit particle-induced inflammasome activation and pyroptosis to suppress periprosthetic osteolysis.
ABSTRACT
Psoriasis-2 (PSORS2) is caused by the heterozygous mutation of the caspase recruitment domain 14 (CARD14) gene on chromosome 17q25. To evaluate the contribution of CARD14 variants in psoriasis of the Chinese Han population, we performed deep sequencing of the CARD14 gene in 372 Chinese Han patients with psoriasis. The exonic nucleotide variants were confirmed by Sanger sequencing in the affected individuals and 1114 controls. In 27 patients with psoriasis, we identified 15 variations, including three novel variants: c.381C[G (p.Cys127Trp), c.712A[G (p.Met238Val) and c.2260_2261delinsGG (p.Gln754Gly). These findings could enrich and update the Human Gene Mutation Database of CARD14 variants for psoriasis.
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Objective To investigate the correlation between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) level and carotid atherosclerotic plaque stability in patients with acute ischemic stroke.Methods The patients with acute ischemic stroke were enrolled consecutively.According to the findings of carotid artery ultrasound,they were divided into either a non-plaque group or a plaque group,and then the plaque group was redivided into a stable plaque subgroup and an unstable plaque subgroup.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of urinary 8-iso-PGF2α.Multivariate logistic regression analysis and Spearman correlation analysis were used to investigate the relationship between 8-iso-PGF2α and carotid artery plaques.Results A total of 150 patients with acute ischemic stroke were enrolled,including 104 had carotid artery plaque (30 were stable plaques and 74 were unstable plaques) and 46 had no carotid artery plaque.The urinary 8-iso-PGF2α level (86.45 ± 6.20 ng/mmol creatinine vs.45.70 ±6.19 ng/mmol creatinine; t =37.136,P=0.001) and intima-media thickness (IMT) (2.89 ± 1.03 mm vs.0.86 ±0.53 mm; t =3.518,P =0.002) in the plaque group were significantly higher than those in the nonplaque group.Multivariate logistic regression analysis showed that urinary 8-iso-PGF2α level (odds ratio [OR] 1.183,95％ confidence interval [CI] 1.087-1.276; P=0.001) and IMT (OR 28.642,95％ CI 8.276-137.231; P =0.001) were the independent risk factors for carotid artery plaque.Pearson correlation analysis showed that there was no significant correlation between urinary 8-iso-PGF2α level and carotid artery IMT (r =0.075,P =0.264).The urinary 8-iso-PGF2α level of the unstable plaque subgroup was significantly higher than that of the stable plaque subgroup (97.30 ± 7.20 ng/mmol creatinine vs.69.17 ±9.25 ng/mmol creatinine; t =16.506,P =0.001).Multivariate logistic regression analysis showed that urinary 8-iso-PGF2α level (OR 4.652,95％ CI 1.732-12.643; P =0.001) was an independent risk factor for unstable plaque.Conelusions The urinary 8-iso-PGF2α level is associated with the existence of carotid atherosclerotie plaque and instability,its increased level is an independent risk factor for carotid plaque instability in patients with ischemic stroke.
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<p><b>OBJECTIVE</b>To disclose the molecular genetic mechanism of type 2 diabetes mellitus and to determine chromosomal location of type 2 diabetes mellitus gene.</p><p><b>METHODS</b>Genome-wide screening and genotyping were conducted in a family of type 2 diabetes mellitus, and linkage analysis by LINKAGE and GENEHUNTER package was used to determine the potential chromosomal location of the family of type 2 diabetes mellitus gene.</p><p><b>RESULTS</b>Evidence of linkage was found at the long arm of chromosome 2. The maximum Lod score is 1.80 and non-parameter Lod score is 5.06.</p><p><b>CONCLUSION</b>The type 2 diabetes mellitus gene of the family is located at 2q.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Age of Onset , Chromosome Mapping , Chromosomes, Human, Pair 2 , Genetics , Diabetes Mellitus, Type 2 , Genetics , Family Health , Genetic Linkage , Genetic Predisposition to Disease , Genetics , Genome, Human , Lod Score , Microsatellite Repeats , PedigreeABSTRACT
Objective To investigate the clinical guiding significance of lymphoscintigraphy with 99mTc-DX for radical lateral lymph node dissection with pelvic autonomic nerve preservation(PANP) in lower rectal cancer.Methods In 67 patients with pathologically proven lower rectal cancer,37MBq/0.8ml 99mTc-DX was injected into submucosa of the rectum through rectal endoscopy.At 0.5h,1h,2h,3h,4h,6h,12h,and 24h after the injection,the patients underwent pelvic and lower abdominal lymphoscintigraphy. The operative method was determined according to the imaging results,and the results of lymphoscintigrams were correlated with postoperative lateral node histologic examination.Results The scintigrams were postive in 37 cases,and all were unilateral.The positive patients underwent PANP.The image results were compared with histological lymph node examination in all patients operated upon for rectal cancer.Histologically,the cases in conformity were 26(70.3 %),false positive in 11 cases(29.7 %),and 2 of 30 false positive patients who demonstrated metastases to lateral node were operated by PANP,while the others underwent only PANP(type Ⅰ) without lateral lymph nodes dissection.The percentage of good sexual function of the two groups of cases after operation was 74.4 % and 71.4 % respentively.The percentages of mild dysuria and good function of urination were both 100 %.Conclusions Lymphoscintigraphy with 99mTC-DX has particular guiding significance in selection of PANP for lower rectal cancer.
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AIM: To explore the influence of processing with fresh-scorpion on element contents in crude scorpion in order to elucidate the processing method. METHODS: Macro-elements Ca,Mg and trace-elements Fe,Cu,Zn and Pb in crude scorpion were determined with emission spectrometric method. RESULTS: Contents of Ca,Mg in live-scorpion group were obviously lower than that in commercial-scorpion(P0.05). CONCLUSION: Processing with live-scorpion has obviously advantage over one with commercial scorpion on element contents.