Plant-derived pharmaceuticals for the developing world

Plant-produced vaccines and therapeutic agents offer enormous potential for providing relief to developing countries by reducing the incidence of infant mortality caused by infectious diseases. Vaccines derived from plants have been demonstrated to effectively elicit an immune response. Biopharmaceuticals produced in plants are inexpensive to produce, require fewer expensive purification steps, and can be stored at ambient temperatures for prolonged periods of time. As a result, plant-produced biopharmaceuticals have the potential to be more accessible to the rural poor. This review describes current progress with respect to plant-produced biopharmaceuticals, with a particular emphasis on those that target developing countries. Specific emphasis is given to recent research on the production of plant-produced vaccines toward human immunodeficiency virus, malaria, tuberculosis, hepatitis B virus, Ebola virus, human papillomavirus, rabies virus and common diarrheal diseases. Production platforms used to express vaccines in plants, including nuclear and chloroplast transformation, and the use of viral expression vectors, are described in this review. The review concludes by outlining the next steps for plant-produced vaccines to achieve their goal of providing safe, efficacious and inexpensive vaccines to the developing world.     

香菇多糖注射液对直肠癌根治术后患者纤维蛋白水平及免疫功能的影响

目的:研究香菇多糖注射液对直肠癌根治术后患者纤维蛋白水平及免疫功能的影响。方法:将2010年5月-2014年10月期间在我院接受直肠癌根治术的患者随机分为两组,观察组术后接受香菇多糖联合FOLFOX-4化疗,对照组术后接受FOLFOX-4化疗,观察两组患者化疗过程中的不良反应,测定化疗前后纤维蛋白水平及免疫功能指标。结果:观察组患者在化疗过程中消化道反应、肝功能损伤、骨髓抑制、周围神经毒性、口腔黏膜损伤、脱发的发生率均显著低于对照组(P0.05);化疗后,对照组患者外周血中CD3~+CD4~+CD8~-细胞、CD3~+CD4~-CD8~+细胞、CD19~+细胞、CD3~-CD56~+细胞的含量以及血清Ig M、Ig A、Ig G、FIB的含量显著低于化疗前(P0.05),观察组患者外周血中CD3~+CD4~+CD8~-细胞、CD3~+CD4~-CD8~+细胞、CD19~+细胞、CD3~-CD56~+细胞的含量以及血清Ig M、Ig A、Ig G的含量与化疗前无显著性差异(P0.05),血清FIB含量显著低于化疗前(P0.05);观察组患者化疗后外周血中CD3~+CD4~+CD8~-细胞、CD3~+CD4~-CD8~+细胞、CD19~+细胞、CD3~-CD56~+细胞的含量以及血清Ig M、Ig A、Ig G、FIB的含量显著高于对照组(P0.05),血清FIB含量显著低于对照组(P0.05)。结论:香菇多糖注射液辅助治疗能够减轻直肠癌根治术后FOLFOX-4化疗的毒副作用、改善免疫功能。     

15 例重症药疹患者临床特征及激素联合免疫球蛋白的疗效分析

目的:探讨15例重症药疹患者的临床特点及采用激素联合免疫球蛋白治疗改病的临床效果。方法:回顾性分析2012年12月至2014年12月在我院就诊的15例重症药疹患者的临床资料,患者采用激素联合免疫球蛋白进行治疗,观察患者的发病类型、致敏药物及疗效,分析血常规、肝功能、肾功能指标与与预后的关系。结果:15例患者中,中毒表皮坏死松解8例,占53.33%,药疹重型4例,占26.67%,中毒表皮坏死松解并支气管炎患者、史蒂文斯并支气管肺炎患者及重症药疹并重症肝炎患者各1例,占6.67%。致敏药物主要是中药、卡马西平、柳氮磺吡啶、头孢他啶、布洛芬、青霉素、别嘌呤醇、感冒药。治疗总有效率86.67%。白细胞、中性比、总胆红素(TBIL)、谷丙转氨酶、胆碱酯酶、胱抑素、肌酐(Cr)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)与重症药疹患者治愈预后有关(P0.05)。结论:重症药疹以中毒表皮坏死松解患者为主,对不同致敏药物引起的重症药疹患者应进行区别治疗,重症药疹患者的预后与患者内脏受累程度密切相关,临床采用激素联合丙种球蛋白持续治疗,可提高治愈率,改善患者临床症状及预后,     

人巨细胞病毒感染与乳腺癌关系的研究进展

人巨细胞病毒(human cytomegalovirus,HCMV)是β疱疹病毒家族成员,全世界70%以上人口感染过该病毒。HCMV通常以潜伏感染形式存在于宿主体内,并产生了逃避宿主免疫系统识别和清除等多种能力,可通过表达HCMV基因及蛋白发挥肿瘤调节作用,干扰细胞代谢过程,促进肿瘤的发生和发展。乳腺癌是女性最常见的恶性肿瘤之一,而HCMV在非肿瘤和乳腺癌患者乳腺上皮细胞中的阳性检出率较高,同时有研究表明晚期暴露于HCMV可引起乳腺癌。近期新型抗HCMV药物对乳腺癌靶向治疗的临床有效性也再次提示,HCMV可能与乳腺癌的发生和发展密切相关。本文主要综述了HCMV的致癌潜能及其与乳腺癌发生和发展的潜在关联。     

聚乙二醇干扰素治疗对慢性乙型肝炎患者Th17/Treg的影响

目的:研究聚乙二醇干扰素抗病毒治疗对慢性乙型肝炎(CHB)患者Th17、Treg及Th17/Treg的影响,及Th17/Treg与表面抗原的关系。方法:30例HBe Ag阴性慢性乙型肝炎患者予聚乙二醇干扰素治疗,在治疗前与治疗后24周、48周时,检测外周血Th17、Treg的细胞频数及表面抗原定量,并与20例健康人的Th17、Treg的细胞频数进行比较,分析聚乙二醇干扰素对Th17、Treg的影响。结果:1CHB患者的Th17及Treg细胞频数较健康人的高,但Th17/Treg比例较健康人低。抗病毒治疗后24周时,Th17/Treg比例较治疗前升高,48周时Th17/Treg比例较24周时稍降低(P0.05),48周时与治疗前相比仍升高(P0.05)。2治疗结束时表面抗原阴转病人的Th17/Treg比未阴转病人高。3慢乙肝病人的Th17/Treg与表面抗原定量成负相关(r=-0.388,P0.05)。结论:CHB患者体内存在着Th17/Treg的失衡,干扰素可以调节CHB患者的免疫功能,有望实现表面抗原阴转。     

白介素17 与结直肠癌

结直肠癌是世界范围内的高发癌症,其发病机理尚不明确。大量研究数据表明,基因突变、表观遗传学的改变、饮食习惯以及生活方式等均是结直肠癌发生发展的高危因素。目前,普遍认为慢性炎症在肿瘤的发生发展中起重要作用。白介素17主要由T细胞的亚型Th17细胞分泌产生,能够促进肿瘤相关性炎症,使肿瘤细胞逃避免疫监控。已在胃癌、宫颈癌、食管癌、非小细胞肺癌、肝细胞肝癌、卵巢癌、黑色素瘤、淋巴瘤、乳腺癌、前列腺癌、结直肠癌等多种恶性肿瘤中发现白介素17呈高表达。现有研究表明,白介素17与肠炎和结直肠癌的发生发展密切相关。尽管尚存在争议,多数学者认为白介素17在结直肠癌的发生发展中起促进作用。本文将近年来关于IL-17在结直肠癌的发生发展中的作用以及其与结直肠癌的预后的研究成果进行总结。     

凡纳滨对虾饲料中酵母水解物替代鱼粉适宜比例的研究

试验添加酵母水解物替代不同比例鱼粉, 添加量分别为0(对照组)、2.5%、5.0%、7.5%、10%和12.5%,替代鱼粉的比例分别为0、8%、16%、24%、32%和40%, 通过评估生长性能、消化酶和免疫相关酶活性等指标评价酵母水解物替代鱼粉对凡纳滨对虾健康生长的影响。选择健康凡纳滨对虾[初重(0.630.01) g]随机分为6组, 每组3个重复, 养殖8周。结果表明, Y2.5和Y5.0处理组对虾增重率和特定生长率与Y0相比差异不显著(P0.05), 但是显著高于其余各组(P0.05), Y2.5组饲料系数和Y0组相比差异不显著, 显著低于其余各组(P0.05); Y5.0组肝胰腺糜蛋白酶和Y0组相比差异不显著(P0.05), 显著高于其余各组(P0.05); Y2.5和Y7.5组胰蛋白酶和Y0组相比差异不显著, 但是显著高于其余各组(P0.05); Y2.5组与Y5.0酚氧化酶活性显著高于其余各组(P0.05), Y2.5组与Y7.5组和Y0组总一氧化氮合酶活性显著高于其余各组(P0.05), Y5.0组和Y7.5组血清溶菌酶活性显著高于其余各组(P0.05)。以增重率为判据, 经二次曲线拟合得出, 获得最大增重率时酵母水解物添加量为1.62%, 替代鱼粉比例为5.19%; 酵母水解物替代鱼粉比例达24%时不会对增重率产生显著影响。     

Association between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis

Infection with mosquito-borne West Nile virus (WNV) is usually asymptomatic but can lead to severe WNV encephalitis. The innate cytokine, macrophage migration inhibitory factor (MIF), is elevated in patients with WNV encephalitis and promotes viral neuroinvasion and mortality in animal models. In a case-control study, we examined functional polymorphisms in the MIF locus in a cohort of 454 North American patients with neuroinvasive WNV disease and found patients homozygous for high-expression MIF alleles to be >20-fold (p = 0.008) more likely to have WNV encephalitis. These data indicate that MIF is an important determinant of severity of WNV neuropathogenesis and may be a therapeutic target.     

Host factors associated with serologic inflammatory markers assessed using multiplex assays

Chronic systemic inflammation contributes to the development of adverse health conditions, yet the influence of fixed and modifiable risk factors on many serologic biomarkers of inflammation remains largely unknown. Serum concentrations of twenty-three biomarkers, including C-reactive protein (CRP), cytokines (CXCL11, CXCL8, CXCL10, CCL2, CCL13, CCL4, CCL17, CXCL13, IL-10, IL-12p70, IL-6, TNF-α, IL-2, IFN-γ, IL-1β, GM-CSF, BAFF), and soluble immune receptors (sCD14, sIL-2Rα, sCD27, sgp130, sTNF-R2) were measured longitudinally using multiplexed immunometric assays in 250 HIV-uninfected men followed in the Multicenter AIDS Cohort Study (1984–2009). Generalized gamma regression was used to determine the statistical significance of factors associated with each biomarker. After accounting for age, race, and education, and for analysis of multiple biomarkers, higher concentrations of specific individual biomarkers were significantly (P < 0.002) associated with hypertension, obesity, hepatitis C infection, stimulant use, and diabetes and lower concentrations with hypercholesterolemia. These associations should be taken into account in epidemiological studies of these biomarkers, and may provide potential targets for disease prevention and treatment.     

过敏性紫癜性肾炎肾组织中KIM-1的表达与临床意义

目的:探讨过敏性紫癜性肾炎肾组织中肾损伤分子1(kidney injury molecule 1,KIM-1)的表达与临床意义。方法:选择2015年4月到2018年1月在我院诊治的过敏性紫癜性肾炎患者150例作为研究对象,采用免疫组化法检测患者肾组织中KIM-1表达,采用半定量评分系统进行肾脏病理损害评分,并对二者进行相关性分析。结果:肾炎组织与肾旁组织的KIM-1相对表达量分别为(9.28±1.38)和(2.74±1.30),肾炎组织中KIM-1的表达显著高于肾旁组织(P=0.000);肾炎组织的毛细血管外肾小球活动、系膜增殖、内皮增殖、肾间质炎症、肾小球慢性化、肾小管间质慢性化指数评分均显著高于肾旁组织(P0.05);肾组织KIM-1表达量与肾小球慢性化指数、肾间质炎症指数、肾小管间质慢性化指数均呈显著正相关性(P0.05)。结论:过敏性紫癜性肾炎组织中KIM-1呈高表达,可能作为评估肾脏病理病变程度的参考指标。