Synthesis of Codon-optimized Human Interleukin-18 Gene by Combination of Chemical and Enzymatic Method

According to the amino acid sequence and codon preference of E. coli, the human interleukin-18（IL-18） gene was optimized to avoid the rare codons. The total length of the synthesized gene is 571 bp; 18 oligonucleotides, DNA fragments were designed and synthesized by the phosphoramidite four-step chemical method. The whole DNA sequence was synthesized by a one-step total gene synthesis method, and then inserted in pUC18 vector. Five positive clones identified by blue-white colony screening were sent to Shanghai Sangon Biological Engineering Technology and Service Co., Ltd. for sequencing. The sequencing result shows that one clone contained the complete correct gene in all the five positive clones.

Analysis of the Role of D-Dimer,Interleukin-6,and Interleukin-18 in Differential Diagnosis of Pediatric Refractory Mycoplasma pneumoniae Pneumonia

Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.

卵巢癌血清CCL18、HK10水平变化及与肿瘤恶性生物学行为的关系

目的探讨卵巢癌血清趋化因子18(CCL18)、人激肽释放酶10(HK10)水平变化及与肿瘤恶性生物学行为的关系。方法选取2018年1月至2023年4月河北省沧州中西医结合医院收治的100例卵巢癌患者作为研究组,50例良性卵巢肿瘤患者作为对照组,50名健康志愿者作为健康组。比较三组血清CCL18、HK10水平,研究组不同肿瘤恶性生物学行为患者血清CCL18、HK10水平,研究组不同化疗灵敏度患者化疗前和化疗3、6个周期后血清CCL18、HK10水平变化值,分析化疗前后血清CCL18、HK10水平变化值与化疗灵敏度的关系及对化疗灵敏度的预测价值。结果研究组血清CCL18、HK10水平均高于对照组、健康组(P<0.05)。研究组不同国际妇产科联盟(FIGO)分期、淋巴结转移、肌层浸润程度血清CCL18和HK10水平、不同分化程度血清HK10水平比较,差异具有统计学意义(P<0.05)。研究组化疗不灵敏患者CCL18△1(△1为化疗3个周期后与化疗前变化值的绝对值)、HK10△1均低于化疗灵敏患者(P<0.05)。CCL18△1、HK10△1联合检测的曲线下面积(AUC)显著高于单一指标(P<0.05)。结论卵巢癌血清CCL18、HK10水平升高与肿瘤恶性生物学行为关系密切,且其变化值能够辅助临床预测化疗灵敏度,两者联合检测具有较高的化疗灵敏度预测价值。

Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma

AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.

Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity

To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biological expression of rhIL-18 was tested by RT-PCR and ELISA method;nude mice were injected with Bcap37 cell with or without the hIL-18 gene.The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3±4.5pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth.These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine;the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity.The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.

普萘洛尔对人脐静脉内皮细胞生物学行为及SOX18、MMP-7、VEGFA表达的影响

目的探讨普萘洛尔对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)增殖、凋亡、迁移及成管能力,以及对性别决定区Y框18(sex determining region Y-box 18,SOX18)、基质金属蛋白酶-7(matrix metalloproteinase-7,MMP-7)和血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)表达的影响。方法以不同浓度的普萘洛尔处理HUVEC,采用CCK-8法检测细胞活力,选出最佳浓度及时间。实验分为对照组,普萘洛尔不同浓度(50、100、150μmol/L)组,采用流式细胞术、细胞划痕实验和成管实验观察HUVEC凋亡、迁移和管腔形成情况,Western blot和实时荧光定量PCR法检测SOX18、MMP-7、VEGFA蛋白及mRNA表达水平。结果与对照组相比,普萘洛尔不同浓度组细胞凋亡率升高(P<0.05),且随药物浓度增加显著升高(P<0.05);普萘洛尔不同浓度组伤口愈合率降低,成管节点数和成管总长度减少,SOX18、MMP-7、VEGFA蛋白及mRNA表达下调(P<0.05)。结论普萘洛尔可抑制HUVEC的增殖、迁移、成管能力并促进细胞凋亡,降低SOX18、MMP-7和VEGFA表达水平。

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

非酒精性脂肪性肝病病人血清长链非编码RNA人类白细胞抗原复合体18水平与氧化应激指标、肝纤维化程度的相关性

目的 探究非酒精性脂肪性肝病(NAFLD)病人血清长链非编码RNA人类白细胞抗原复合体18(lncRNA HCG18)与氧化应激指标及肝纤维化程度的相关性。方法 以儋州市人民医院2020年11月至2022年3月收治的92例NAFLD病人为NAFLD组,另选取同期健康体检志愿者90例为对照组。根据NAFLD肝纤维化(NFS)评分将NAFLD组病人分为排除晚期纤维化组(30例)、中间状态组(46例)、晚期纤维化组(16例)。采用实时荧光定量PCR(qRT-PCR)法检测血清lncRNA HCG18表达水平;酶联免疫吸附测定(ELISA)检测氧化应激指标水平;Pearson相关性分析NAFLD病人血清lncRNA HCG18与氧化应激指标的关系;Spearman相关性分析NAFLD病人血清lncRNA HCG18与NFS评分的关系。采用受试者操作特征(ROC)曲线分析血清lncRNA HCG18对NAFLD的诊断价值。结果 NAFLD组lncRNA HCG18(1.37±0.29比1.01±0.24)、丙二醛[(6.96±2.13)μmol/L比(4.17±1.04)μmol/L]水平明显高于对照组(P<0.001),谷胱甘肽过氧化物酶(GSH-Px)[(72.39±11.26)U/mL比(98.25±13.92)U/mL]、超氧化物歧化酶(SOD)[(68.36±10.65)U/mL比(92.84±12.89)U/mL]水平明显低于对照组(t=9.11、11.19、13.79、13.98,P<0.001)。排除晚期纤维化组、中间状态组、晚期纤维化组lncRNA HCG18(1.20±0.25比1.39±0.30比1.65±0.35)、丙二醛[(5.64±1.88)μmol/L比(7.12±2.16)μmol/L比(8.99±2.51)μmol/L]水平依次显著升高(F=12.36、13.06,P<0.001),GSH-Px[(81.56±13.58)U/mL比(71.74±10.52)U/mL比(57.06±9.05)U/mL]、SOD[(81.45±12.52)U/mL比(66.52±10.25)U/mL比(49.13±8.29)U/mL]水平依次显著降低(F=24.27、48.42,P<0.001)。Pearson相关性分析显示,NAFLD组血清lncRNA HCG18水平与丙二醛呈正相关(r=0.59,P<0.001),与GSH-Px、SOD均呈负相关(r=-0.57、-0.62,P<0.001);Spearman相关性分析显示NAFLD组血清lncRNA HCG18水平与NFS评分呈正相关(r=0.69,P<0.001)。血清lncRNA HCG18诊断NAFLD的ROC曲线下面积(AUC)为0.85。结论 NAFLD病人血清lncRNA HCG18显著升高,与氧化应激指标及肝纤维化程度存在一定的相关性。

血清DKK1、sRAGE、hCAP-18对急性淋巴细胞白血病患儿的诊断和预后不良的预测价值

目的 探讨血清Dickkopf相关蛋白1(DKK1)、可溶性晚期糖基化终末产物受体(sRAGE)、人类阳离子抗菌蛋白-18(hCAP-18)对急性淋巴细胞白血病患儿的诊断和预后不良的预测价值。方法 选取2020年4月至2022年4月南京鼓楼医院集团宿迁医院收治的84例急性淋巴细胞白血病患儿作为研究组,包括标危28例、中危36例、高危20例。另选取同期在南京鼓楼医院集团宿迁医院体检的84例健康儿童作为对照组。收集所有研究对象的临床资料。采用酶联免疫吸附试验检测所有研究对象血清DKK1、sRAGE、hCAP-18水平。对研究组患儿进行为期1年的随访,并按随访结果分为预后不良组和预后良好组。绘制受试者工作特征(ROC)曲线分析血清DKK1、sRAGE、hCAP-18在急性淋巴细胞白血病患儿诊断和预后不良的预测价值。采用多因素Logistic回归分析影响急性淋巴细胞白血病发生的因素。结果 与对照组相比,研究组患儿白细胞计数(WBC)、DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。与研究组标危患儿相比,中危和高危患儿血清DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05);与中危患儿相比,高危患儿血清DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。血清DKK1、sRAGE、hCAP-18联合诊断急性淋巴细胞白血病的曲线下面积(AUC)显著高于血清DKK1、sRAGE、hCAP-18单独诊断的AUC(Z=2.820,P=0.005;Z=5.170,P<0.001;Z=5.272,P<0.001)。多因素Logistic回归分析结果显示,血清WBC、DKK1、sRAGE、hCAP-18是急性淋巴细胞白血病发生的影响因素(P<0.05)。随访1年后,26例患儿纳入预后不良组,58例患儿纳入预后良好组。与预后良好组相比,预后不良组患儿血清DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。与预后不良组中危患儿相比,高危患儿DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。血清DKK1、sRAGE、hCAP-18联合预测急性淋巴细胞白血病患儿预后不良的AUC明显高于血清DKK1、sRAGE、hCAP-18单独预测的AUC(Z=2.312,P=0.021;Z=3.160,P=0.002;Z=2.926,P=0.003)。结论 急性淋巴细胞白血病患儿血清DKK1高表达,sRAGE、hCAP-18低表达,且三者联合检测对急性淋巴细胞白血病具有一定的诊断和预后预测价值。

血清中Interleukin-18含量的检测对结肠癌预后判断的价值

目的 探讨结肠癌患者血清中白细胞介素 18(IL 18)水平与预后的关系。方法 收集 10 6例结肠癌患者和 60例健康成人的血清 ,采用酶联免疫吸附反应 (ELISA )检测IL 18的水平。结果 1997年 6月及以前的血清 5 9份 ,IL 18的平均含量为3 3 8.46pg/ml ;1997年 6月以后的血清 47份 ,IL 18的平均含量为 3 2 8.85 pg/ml ;2组比较无显著性差异 (P <0 .0 5 ) ;结肠癌组患者血清IL 18的含量 ( 3 46.5 3 pg/ml± 3 1.2 3pg/ml)明显高于正常对照组 ( 2 3 3 .3 2 pg/ml± 2 2 .5 4pg/ml) ,有显著性差异 (P <0 .0 5 ) ;Ⅱ期、Ⅲ期和Ⅳ期患者血清中IL 18水平明显高于对照组 (P <0 .0 5 ) ,血清IL 18≥ 3 46pg/ml组的患者 5年生存率为 5 .3 % ,血清IL 18<3 46pg/ml的患者 5年生存率为 18.6% ;两组比较有显著性差异 (P <0 .0 5 ) ;多因素分析表明 ,血清IL 18含量是判断结肠癌患者预后的独立因素。结论 血清中IL 18含量与结肠癌患者 5年生存率有密切相关。血清中IL

ILTV Glycoprotein B(gB)与鸡Interleukin-18(IL-18)真核双表达载体的构建及表达

将ILTVgB基因和鸡IL-18基因插入到真核双表达载体pIRES中,构建共表达gB和IL-18基因的重组质粒pIRES-gB/IL18和表达gB基因的pIRES-gB质粒。通过脂质体将其转染鸡胚成纤维细胞,利用RT-PCR及间接免疫荧光检测重组质粒在体外的表达。将重组质粒通过腿部肌肉多点注射免疫21日龄雏鸡,应用ELISA和流式细胞仪分别检测免疫鸡的体液免疫及细胞免疫水平。结果显示,pIRES-gB/IL18和pIRES-gB转染细胞中分别含gB/IL-18基因的mRNA和gB基因的mRNA。间接免疫荧光检测表明,pIRES-gB/IL18和pIRES-gB在CEF细胞中有效地转录并表达gB蛋白。pIRES-gB/IL18和pIRES-gB免疫雏鸡后均能促进外周血T淋巴细胞亚群数量和血清中特异性抗体水平的增加,但前者的免疫效果明显优于后者,表明gB基因和鸡IL-18基因均获得了表达,且鸡IL-18能明显增强ILTV DNA疫苗诱发的免疫应答。

人乳头瘤病毒16/18阳性联合阴道镜检查在宫颈细胞学阴性宫颈病变诊断中的应用

目的观察人乳头瘤病毒(HPV)16/18阳性联合阴道镜检查在宫颈细胞学阴性的宫颈病变诊断中的应用。方法选取我院妇科门诊2018年6月至2021年6月收治的宫颈细胞学检测结果为阴性且HPV 16/18阳性结果的患者120例,所有患者均接受阴道镜检查及宫颈活检联合宫颈管搔刮术(ECC),以病理学诊断为标准,分析诊断效果。结果组织病理学结果显示,120例患者中宫颈炎85例(70.8%),宫颈上皮内瘤变(CIN)Ⅰ15例(12.5%),CINⅡ13例(10.8%),CINⅢ5例(4.2%),宫颈癌2例(1.7%)。120例宫颈细胞学检测结果为阴性且HPV 16/18阳性的患者中,HPV 16型感染90例(75.0%),HPV18型感染20例(16.7%),HPV16/18型同时阳性感染10例(8.3%)。90例HPV 16阳性患者中,宫颈炎72例,CIN 8例,CINⅡ6例,CINⅢ3例,宫颈癌1例;20例HPV 18阳性患者中,宫颈炎10例,CINⅠ5例,CINⅡ4例,CINⅢ1例,宫颈癌0例;10例HPV 16/18同时阳性患者中,宫颈炎3例,CINⅠ2例,CINⅡ3例,CINⅢ1例,宫颈癌1例。HPV 16/18 HPV同时阳性患者≥CINⅡ级比例为50.0%,高于HPV16/18单一阳性患者的11.1%和25.0%,差异具有统计学意义(P<0.05)。阴道镜诊断宫颈细胞学阴性、HPV 16/18阳性患者的宫颈病变准确率为95.0%,灵敏度为96.0%,特异度为85.5%。结论对于宫颈细胞学阴性、HPV 16/18阳性患者宜进一步行阴道镜宫颈活检,以减少宫颈高级别鳞状CIN甚至癌变的漏诊。

过表达lncRNA HCG18调控miR-107/CDKN2B轴对甲状腺癌细胞增殖、迁移和侵袭的机制研究

目的探讨长链非编码RNA人类白细胞抗原复合体18(lncRNA HCG18)调控miR-107/周期蛋白依赖激酶抑制因子2B(CDKN2B)轴对甲状腺乳头状癌(PTC)细胞增殖、侵袭、迁移的影响。方法实时荧光定量PCR(qRT-PCR)、Western blot分别检测60例PTC患者癌组织、癌旁组织及人正常甲状腺上皮细胞TEC及人PTC细胞WRO、TPC-1、SW579中HCG18、miR-107、CDKN2B蛋白表达;将WRO细胞分为CK组、si-NC组、si-HCG18组、pcDNA组、pcDNA-HCG18组、pcDNA-HCG18+mimic NC组、pcDNA-HCG18+miR-107 mimic组,qRT-PCR检测各组细胞HCG18、miR-107表达;CCK-8法检测细胞增殖;划痕实验检测细胞迁移;Transwell检测细胞侵袭;Western blot检测CDKN2B、细胞周期素D1(CyclinD1)、基质金属蛋白酶(MMP)-2、MMP-9蛋白表达;双荧光素酶实验验证HCG18和miR-107、miR-107和CDKN2B的关系。结果在PTC组织和PTC细胞中,HCG18、CDKN2B蛋白低表达,miR-107高表达,且在WRO细胞中HCG18、CDKN2B蛋白水平最低,miR-107表达最高(P<0.05),因此,选择WRO细胞进行转染。与si-NC组比较,si-HCG18组HCG18、CDKN2B蛋白表达降低,miR-107表达升高(P<0.05);与pcDNA组比较,pcDNA-HCG18组HCG18、CDKN2B蛋白表达升高,miR-107表达降低(P<0.05);与pcDNA-HCG18+mimic NC组比较,pcDNA-HCG18+miR-107 mimic组HCG18表达变化差异无统计学意义(P>0.05),miR-107表达升高,CDKN2B蛋白表达降低(P<0.05);上调HCG18可抑制WRO细胞增殖、侵袭、迁移及CyclinD1、MMP-2、MMP-9蛋白表达,而下调HCG18则呈相反趋势;过表达miR-107可减弱上调HCG18对WRO细胞增殖、侵袭与迁移的抑制作用;HCG18与miR-107、miR-107与CDKN2B存在靶向调控关系。结论过表达HCG18可能通过海绵化miR-107来上调CDKN2B表达,进而抑制PTC细胞增殖、迁移与侵袭。

Association of polymorphisms of interleukin-18 gene promoter region with chronic hepatitis B in Chinese Han population

AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma

AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS:Serum IL-18,IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (< 105 pg/mL) (4 and 11 mo,respectively,P = 0.015). Multivariate analyses showed that serum IL-18 level,but not IL-6 and IL-12 levels,was a significant and independent prognostic factor of survival. CONCLUSION:These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus,the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.

Plasma interleukin-18 reflects severity of ulcerative colitis

AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.

Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn's disease

AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st,2013.Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis.A metaanalysis was conducted using a random-effects model with STATA 12.0 software.Crude odds ratios(ORs) with95%confidence intervals(95%CI) were calculated.RESULTS:Seven case-control studies,with a total of1930 CD cases and 1930 healthy subjects,met our inclusion criteria.The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238G>C polymorphisms may correlate with an increased risk of CD under five genetic models(all P < 0.05).Furthermore,we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models(C allele vs A allele:OR = 2.03,95%CI:1.20-3.43,P = 0.008;CC vs AA+AC:OR = 2.39,95%CI:1.2-4.43,P = 0.006;CC vs AC:OR = 2.31,95%CI:1.22-4.38,P = 0.010).However,such associations were not found for the IL-18 rs917997 C>T,codon 35 A>C and rs1946519G>T polymorphisms(all P> 0.05).A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD.Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans(all P < 0.05),but not among Caucasians(all P> 0.05).CONCLUSION:This meta-analysis indicated that the IL-18 rs1946518 A> C,rs187238 G>C and rs360718A>C polymorphisms may contribute to susceptibility to CD,especially among Asians and Africans.These polymorphisms are known to reduce IL-18 mRNA and protein levels.

Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients

AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.

Enhancing cellular immune response to HBV M DNA vaccine in mice by codelivery of interleukin-18 recombinant

Objective:To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines.Methods:BALB/c mice were immunized with pCMV-M alone or co-immunized with pcDNA3-18 and pCMV-M and then their sera were collected for analysing anti-HBsAg antibody by ELISA;splenocytes were isolated for detecting specific CTL response and cytokine assay in vitro.Results:The anti-HBs antibody level of mice co-immunized with pcDNA3-18 and pCMV-M was slightly higher than that of mice immunized with pCMV-M alone,but there was not significantly different (P>0.05).Compared with mice injected with pCMV-M, the specific CTL cytotoxity activity of mice immunized with pcDNA3-18 and pCMV-M was significantly enhanced (P<0.05) and the level of IFN-γ in supernatant of splenocytes cultured with HBsAg in vitro was significantly elevated (P<0.05) while the level of IL-4 had no significant difference (P>0.05).Conclusion:The plasmid encoding IL-18 together with HBV M gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response induced in mice, so that IL-18 is a promising immune adjuvant.

Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease

AIM:To investigate the effects of rosiglitazone(RGZ) on expression of interleukin-18(IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease(NAFLD) rats.METHODS:Twenty-eight Sprague-Dawley(SD) rats were randomly divided into control,NAFLD,and RGZ treated NAFLD groups.A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk.The NAFLD animals were treated with RGZ or vehicle for the last 4 wk(week 9-12) and then sacrificed to obtain liver tissues.Histological changes were analyzed with HE,oil red O and Masson's trichrome staining.Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction(RT-PCR) analysis.RESULTS:The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group.Steatosis,inflammation and fibrosis,found in the liver of NAFLD rats,were significantly improved 4 wk after RGZ treatment.The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.CONCLUSION:RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats.The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.