Microgravity inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression in macrophage cells

Objective and design

Microgravity environments in space can cause major abnormalities in human physiology, including decreased immunity. The underlying mechanisms of microgravity-induced inflammatory defects in macrophages are unclear.

Material or subjects

RAW264.7 cells and primary mouse macrophages were used in the present study. Lipopolysaccharide (LPS)-induced cytokine expression in mouse macrophages was detected under either simulated microgravity or 1g control.

Methods

Freshly isolated primary mouse macrophages and RAW264.7 cells were cultured in a standard simulated microgravity situation using a rotary cell culture system (RCCS-1) and 1g control conditions. The cytokine expression was determined by real-time PCR and ELISA assays. Western blots were used to investigate the related intracellular signals.

Results

LPS-induced tumor necrosis factor-α (TNF-α) expression, but not interleukin-1β expression, in mouse macrophages was significantly suppressed under simulated microgravity. The molecular mechanism studies showed that LPS-induced intracellular signal transduction including phosphorylation of IKK and JNK and nuclear translocation of NF-κB in macrophages was identical under normal gravity and simulated microgravity. Furthermore, TNF-α mRNA stability did not decrease under simulated microgravity. Finally, we found that heat shock factor-1 (HSF1), a known repressor of TNF-α promoter, was markedly activated under simulated microgravity.

Conclusions

Short-term treatment with microgravity caused significantly decreased TNF-α production. Microgravity-activated HSF1 may contribute to the decreased TNF-α expression in macrophages directly caused by microgravity, while the LPS-induced NF-κB pathway is resistant to microgravity.     

Synthesis and biological evaluation of quinoxaline derivatives as tubulin polymerization inhibitors that elevate intracellular ROS and triggers apoptosis via mitochondrial pathway

A series of novel quinoxaline derivatives were synthesized and evaluated for their antiproliferative activity in three human cancer cell lines. Compound 12 exhibited the most potent antiproliferative activity with IC₅₀ in the range of 0.19–0.51 μM. The compound inhibited tubulin polymerization and disrupted the microtubule network, leading to G2/M phase arrest. Furthermore, compound 12 induced ROS production and malfunction of mitochondrial membrane potential. Compound 12 led to cancer cells apoptosis in a dose‐dependent manner. Western blot analysis showed that compound 12 induced up‐regulation of p21 and affected the expression of cell cycle‐related proteins. The binding mode was also probed by molecular docking.     

Expression of miR-1304 in patients with esophageal carcinoma and risk factors for recurrence

BACKGROUND Esophageal carcinoma is a malignant gastrointestinal tumor with a very poor prognosis.MicroRNA(miR)-1304 is a newly discovered non-coding RNA,which shows differential expression in other cancers,and its clinical value in esophageal carcinoma remains unclear.AIM To explore the expression of miR-1304 in patients with esophageal carcinoma and its clinical value.METHODS The expression of miR-1304 in patients with esophageal carcinoma was analyzed based on the data on miR in esophageal carcinoma downloaded from The Cancer Genome Atlas database.Quantitative real-time polymerase chain reaction was adopted to determine the expression of miR-1304 in the tissues and serum of patients.The clinical diagnostic value of miR-1304 and independent factors for recurrence and prognosis of esophageal carcinoma were then analyzed.The potential target genes of miR-1304 were predicted,and then analyzed based on gene ontology,Kyoto Encyclopedia of Genes,and Genomes,and protein-protein interaction.RESULTS The expression of miR-1304 in the tissues and serum of patients with esophageal carcinoma increased,and was also increased according to the database.Patients with high expression of miR-1304 suffered increased rates of tumor≥3 cm,low differentiation and stage II+III.miR-1304 had a diagnostic value in identifying esophageal carcinoma,tumor size,differentiation and TNM stage.Tumor size,differentiation,TNM stage,and miR-1304 were independent risk factors for recurrence of esophageal carcinoma,and they had certain predictive and diagnostic value for the recurrence of esophageal carcinoma.Seventy-eight patients showed a 3-year survival rate of 38.46%,and patients with high expression of miR-1304 had a relatively lower survival rate.Multivariate analysis revealed that tumor size,differentiation,recurrence and miR-1304 were independent factors for the prognosis of patients.MiRTarBase,miRDB,and Targetscan predicted 20 target genes in total.Gene ontology enrichment analysis found 18 functions with aP<0.05,and Kyoto Encyclopedia of Genes,and Genomes analysis found 11 signal pathways with aP<0.05.String analysis of protein co-expression found 269 relationship pairs,of which co-expression with epidermal growth factor was the most common.CONCLUSION miR-1304 can be used as a potential indicator for the diagnosis and recurrence of esophageal carcinoma and for survival of patients with this disease.     

心脏再同步治疗术中测试腔内心电图参数的临床意义

目的 探讨心脏再同步治疗（CRT）术中测定腔内心电图参数,尤其是左心室激动延迟时间是否可以预测心力衰竭患者左心室逆重构发生.方法 2009年1月至2013年1月37例完全性左束支阻滞患者在天津市胸科医院心内科植入CRT,术中测试窦性心律自身传导情况下右心室-左心室导线的激动时间差（△t）,测试右心室导线起搏到左心室导线感知时间（RVp-LV）及左心室导线起搏到右心室导线感知时间（LVp-RV）.随访观察1年,比较术前、术后心脏结构变化,以左心室舒张末期容积减小15％或射血分数提高5％为标准分为CRT应答组和无应答组.结果 左心室逆重构的发生与术中测试腔内心电图△t、RVp-LV、LVp-RV等参数均无明显关系,△t与术前QRS时限有关,RVp-LV、LVp-RV在左心室舒张末期内径（LVEDD） ＞75 mm的患者中长于LVEDD≤75 mm的患者（P＜0.05）.左心室导线植入在左心室基底部、中段、心尖部的患者发生左心室逆重构的比例分别为71.4％、90.4％、12.5％,差异有统计学意义（P＜0.05）,3个部位的△t、RVp-LV、LVp-RV差异无统计学意义.结论 术中测定腔内心电图相关参数不能预测CRT是否应答,左心室导线位置仍是决定CRT疗效的关键因素.     

血清LP-PLA2、S100B、炎性蛋白与ICU老年骨科术后患者谵妄发生及预后的关系分析

目的探究血清脂蛋白相关磷脂酶A2（LP-PLA2）、S100B蛋白（S100B）、C反应蛋白（CRP）与重症加强护理病房（ICU）老年骨科患者术后谵妄（POD）发生及预后的关系。方法选取ICU老年骨科手术患者97例作为研究对象,根据术后48 h是否发生谵妄分为POD患者24例（观察组）,术后未发生谵妄患者73例（对照组）。比较两组血清LP-PLA2、S100B、CRP水平,采用接收者操作特征（ROC）曲线及ROC曲线下面积（AUC）分析血清LP-PLA2、S100B、CRP预测POD发生的截断值、敏感度、特异度,比较观察组治疗前后血清LP-PLA2、S100B、CRP水平及不同血清水平患者临床疗效总评量表（CGI-SI）、谵妄严重程度（DRS）评分,采用Pearson分析血清LP-PLA2、S100B、CRP与CGI-SI、DRS评分的关系。结果观察组出术后恢复室前、术后24 h血清LP-PLA2、S100B、CRP水平高于对照组（P<0.05）;预测POD发生的AUC：术后24 h CRP＞术后24 h LP-PLA2＞出术后恢复室前CRP＞术后24 h S100B＞出术后恢复室前LP-PLA2＞出术后恢复室前S100B（P<0.05）;术后24 h LP-PLA2、S100B、CRP联合预测POD的AUC大于任何单一指标（P<0.05）;观察组治疗后血清LP-PLA2、S100B、CRP水平低于治疗前（P<0.05）;血清LP-PLA2、S100B、CRP高表达者CGI-SI、DRS评分高于低表达者（P<0.05）;血清LP-PLA2、S100B、CRP与CGI-SI、DRS评分呈正相关（P<0.05）。结论ICU老年骨科术后POD患者血清LP-PLA2、S100B、CRP呈高表达,可预测POD的发生风险,并与患者病情、预后有关。     

白藜芦醇抑制胃癌细胞株MKN45增殖的机制研究*

目的 通过研究白藜芦醇抑制胃癌MKN45细胞增殖及对丝裂原活化蛋白激酶(MEK)/细胞外信号调节激酶（ERK）信号通路的影响,探讨白藜芦醇抗胃癌的作用机制。方法 体外常规培养胃癌MKN45细胞,将细胞分为对照组、MEK/ERK信号通路抑制剂PD98059组（PD98059组）、白藜芦醇低剂量组（100?μmol/L）、 白藜芦醇高剂量组（400?μmol/L）。各组细胞处理1、2和4?h后,MTT法检测细胞增殖抑制率,Western blotting法检测Ras、Raf、MEK、ERK1/2蛋白的表达,细胞免疫化学法检测Ras、Raf、MEK、ERK1/2蛋白荧光强度的变化。结果 与对照组比较,PD98059组、白藜芦醇低剂量组和白藜芦醇高剂量组细胞在处理1、2和4?h后,细胞增殖受到抑制（P?<0.05）,且呈时间剂量依赖性;PD98059组、白藜芦醇低剂量组和白藜芦醇高剂量组细胞Ras、Raf、MEK和ERK1/2表达下降,差异有统计学意义（P?<0.05）,且白藜芦醇的作用呈剂量依赖性（P?< 0.05）;MEK和ERK1/2蛋白主要定位于细胞质中,且PD98059组、白藜芦醇低剂量组和白藜芦醇高剂量组细胞ERK1/2的荧光强度均减弱。结论 白藜芦醇呈剂量依赖性抑制胃癌细胞株MKN45的增殖,可能与抑制MEK/ERK信号通路,减弱Ras、Raf、MEK和ERK1/2的表达有关。     

胃窦部超声指导下妇科腹腔镜手术患者术前 口服10% 葡萄糖溶液的临床应用

目的 研究在胃窦部超声指导下妇科腹腔镜手术患者术前2 h 口服4 ml/kg、10% 葡萄糖溶液的 临床应用。方法 选取2019 年1 月—2019 年8 月延安大学附属医院拟在全身麻醉下行腹腔镜手术的妇科患 者60 例作为研究对象,根据随机数字表法分为口服糖水组和常规禁饮组,每组30 例。常规禁饮组术前常规 禁食、禁饮8 ～ 12 h ;口服糖水组常规禁食,术前2 h 口服4 ml/kg、10% 葡萄糖溶液。进入手术室后先用超 声测量2 种不同体位下的胃窦部横截面积（CSA）：半卧位为CSA1,右侧卧位为CSA2。应用公式计算胃容量（GV） 及单位体重胃容量（GV/W）。采用视觉模拟评分（VAS）分别在术前30 min 与术前3 h 对所有患者行口渴感、 饥饿感及焦虑感评分,然后将不同时间的评分差值进行比较。记录两组术后首次排气及排便时间。结果 两 组CSA1、CSA2、GV1、GV2、GV1/W 及GV2/W 等胃超声测量数据比较,差异无统计学意义（P >0.05）。两组 术前30 min 与术前3 h 口渴感、饥饿感及焦虑感的VAS 评分差值比较,差异有统计学意义（P <0.05）。与常 规禁饮组比较,口服糖水组术后首次排气时间缩短（P <0.05）。结论 在胃窦部超声指导下妇科腹腔镜手术 患者术前2 h 口服4 ml/kg、10% 葡萄糖溶液安全可行,并且可以改善患者术前的主观不适感,缩短术后首次 排气时间,促进患者胃肠功能早期恢复。     

美罗培南配合免疫球蛋白治疗新生儿败血症的疗效及其对炎症因子的影响

目的?探讨新生儿败血症患儿实施美罗培南配合免疫球蛋白治疗的疗效及炎症水平变化。方法?选取2016年4月—2018年4月海南医学院第二附属医院收治的新生儿败血症患儿100例,以挂号就诊单病案号单、双数为基准,分为研究组和对照组。治疗组采用美罗培南+免疫球蛋白治疗,对照组采用美罗培南治疗,对比两组临床症状改善时间、临床疗效、炎症水平及临床指标。结果?研究组拒奶改善时间、体温改善时间、神经系统症状改善时间、血培养转阴时间及住院时间低于对照组（P?<0.05）,研究组总有效率高于对照组（P?<0.05）,研究组治疗前后白细胞介素-6、白细胞介素-1、高敏感C反应蛋白及肿瘤坏死因子-α的差值高于对照组（P?<0.05）,研究组治疗前后分化抗原3、分化抗原8、免疫球蛋白G及免疫球蛋白M的差值高于对照组（P?<0.05）。结论?新生儿败血症患儿实施美罗培南配合免疫球蛋白治疗的临床疗效显著,可明显改善机体炎症水平,值得借鉴。