The role of C/EBP-α expression in human liver and liver fibrosis and its relationship with autophagy

Aim: To investigate the expression of CCAAT enhancer binding protein-α (C/EBP-α) in normal human liver and liver fibrosis and its probable association with autophagy. Methods: Double label immunohistochemistry was used to detect the location of C/EBP-α in hepatocytes and hepatic stellate cells (HSCs). The expression of C/EBP-α, Atg5, and Atg6 was also evaluated by immunohistochemistry in paraffin sections of human liver. HSC-T6 cells were treated with rapamycin and 3-methyladenine (3MA) to induce or inhibit autophagy, and the expression of C/EBP-α protein was detected by Western blotting. Results: Double label immunohistochemistry showed that C/EBP-α was predominantly located in hepatocytes and that its expression was significantly decreased in fibrosis compared with normal liver. Atg5 expression was increased in fibrosis but was located primarily in liver septa and peri-vascular areas, which was consistent with the distribution of HSCs. In contrast, Atg6 was not expressed in normal or fibrotic liver. Treatment of HSC-T6 cells in culture with rapamycin or 3MA decreased or increased C/EBP-α expression, respectively, as shown by Western blotting. Conclusion: C/EBP-α was primarily expressed in hepatocytes in normal liver, but its expression decreased significantly in liver fibrosis. Autophagy might play a role in liver fibrosis through its association with C/EBP-α, but this hypothesis warrants further investigation.     

Correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma

Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman’s rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma.     

Assessment of the Safety and Efficacy of an Attenuated Live Vaccine Based on Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

The safety and efficacy of the JXA1-R vaccine, an attenuated strain of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), were examined using an intramuscular challenge model in piglets. The JXA1-R vaccine was obtained by passing HP-PRRSV JXA1 through Marc-145 cells (82nd passage). Genomic sequence comparisons showed that strain JXA1-R and its parental strain, JXA1, differ by 47 amino acids, and most of these differences are scattered throughout the PRRSV genome. Four-week-old PRRSV-free piglets were inoculated intramuscularly with JXA1-R vaccine (10^3.0, 10^4.0, 10^5.0, 10^6.0, and 10^7.0 50% tissue culture infective doses [TCID₅₀]/ml for groups 1 to 5, respectively) and then challenged intramuscularly with the 5th passage virus of JXA1 virus (JXA1-F5, 3 ml × 10^4.5 TCID₅₀/ml) 28 days after inoculation. The humoral immune response, swine growth, clinical signs, and differential organ lesions were monitored. The results showed that all vaccinated piglets had a perceptible humoral immune response to vaccination after day 7, which then promptly increased, almost reaching the maximum sample/positive (S/P) ratio value at 28 days postimmunization. Viremia detection indicated that the viral replication levels of the challenge virus in the immunized groups (immunization doses ≥10^4.0/ml) were significantly lower than that of the virus-challenged unvaccinated control group. Piglets in groups 2 to 5 were effectively protected against lethal HP-PRRSV infection and did not show any obvious changes in body temperature or clinical signs of disease at any point during the experiment. However, two of five piglets in group 1 showed mild pathological lesions and transitory high fever. These results suggest that JXA1-R (TCID₅₀/ml ≥10^4.0) is sufficiently attenuated and can provide effective protection against the lethal wild-type HP-PRRSV.     

内镜下射频消融术治疗胃低级别上皮内瘤变的临床研究

目的通过临床大样本研究,进一步明确内镜下射频消融术(RFA)治疗胃低级别上皮内瘤变(LGIN)的有效性及安全性。 方法回顾性选择2014年10月至2019年12月经解放军总医院消化内镜中心术前筛查的175例患者证实为胃LGIN的255例病变纳入研究,并进行内镜下RFA,关注其围手术期并发症发生情况,术后采用Wong-Baker面部表情量表进行疼痛评分,并追踪其复查随访结果。 结果255例病变均成功完成内镜下RFA,术中无明显并发症发生;术后3个月、6个月、1年、2年、3年的治愈率分别为91.3%、90.8%、89.4%、88.2%、86.5%,术后腹痛为主要并发症。 结论内镜下RFA是治疗胃LGIN的一种安全有效、操作简便、可门诊治疗的新方法,具有良好的临床应用前景。     

白细胞介素27在结核性胸腔积液和恶性胸腔积液鉴别诊断中的价值

目的研究胸腔积液中白细胞介素27(IL-27)浓度对于结核性胸腔积液(TPE)和恶性胸腔积液(MPE)的鉴别诊断价值.方法纳入2015~2018年收住北京朝阳医院诊断为TPE或MPE的患者,通过酶联免疫吸附法测定胸腔积液及血浆中IL-27浓度.通过受试者工作特征曲线获取胸腔积液中IL-27的浓度、胸腔积液与血浆IL-27浓度的差值和比值的诊断价值.结果143例患者中TPE组78例,MPE组65例.TPE患者中胸腔积液IL-27浓度显著高于MPE患者,胸腔积液IL-27诊断TPE的诊断界值为499.71 ng/L,敏感度为93.6%,特异度为95.4%,曲线下面积为0.952(95%CI:0.913~0.991),Z统计分析显示,胸腔积液与血浆IL-27浓度差值和比值的诊断价值不高于胸腔积液IL-27浓度.结论胸腔积液IL-27浓度是鉴别TPE和MPE的理想生物标志物.     

Branched polyethyleneimine-assisted 3-carboxybenzoboroxole improved Wulff-type boronic acid functionalized magnetic nanoparticles for the specific capture of cis-diol-containing flavonoids under neutral conditions

Flavonoids have shown a variety of biological activities such as antimicrobial, antibacterial, antifungal, antiviral, antiinflammatory, antitumor, antiatherogenic, and antihyperglycemic activities. A lot of important flavonoids contain cis-diols such as rutin (Ru), quercetin (Qu), luteolin (Lu), myricetin (Myr) and baicalein (Ba) and so on. It is necessary to establish a simple, low-cost and efficient purification method for cis-diol-containing flavonoids from plant extracts. Boronate affinity materials are able to reversibly bind the cis-diols via boronic acids by forming a five- or six-membered boronic cyclic ester in aqueous media. However, conventional boronate affinity materials have to be used in alkaline media, which can lead to the oxidation of cis-diols in compounds. In this study, the polyethyleneimine (PEI)-assisted 3-carboxybenzoboroxole-functionalized magnetic nanoparticles (MNPs) were prepared to achieve efficient capture of cis-diol-containing flavonoids under neutral conditions. Branched PEI was applied as a scaffold to amplify the number of boronic acid moieties, while 3-carboxybenzoboroxole, exhibiting high affinity and excellent water solubility toward flavonoids, was used as an affinity ligand. The prepared boronate affinity MNPs exhibited high binding capacity and fast binding kinetics (equilibrium in 3 min) under neutral conditions. In addition, the obtained boronate affinity MNPs exhibited high binding affinity (K_d ≈ 10⁻⁴ M), low binding pH (pH ≥ 6.0) and tolerance of the interference to abundant sugars.

Flavonoids have shown a variety of biological activities such as antimicrobial, antibacterial, antifungal, antiviral, antiinflammatory, antitumor, antiatherogenic, and antihyperglycemic activities.