通用流感疫苗研究进展

流感是一种对人类危害极大的传染病,接种疫苗被认为是预防流感的最有效手段。目前所用的流感疫苗主要是根据现行流行株的减毒或灭活病毒疫苗及基于流感血凝素和神经氨酸酶设计的重组蛋白质疫苗。但流感病毒变异大,易逃逸机体免疫监视,有效的疫苗须不断分离新流行株和不断更新疫苗免疫原。为解决这一问题,很多科学家一直在研究基于病毒高度保守性蛋白质、能够预防所有流感病毒毒株、可诱导持久保护性免疫的通用流感疫苗。我们对基于基质蛋白M2、核蛋白等的通用流感疫苗做一简要综述。     

含禽流感病毒M2e 氨基端抗原表位的重组传染性法氏囊病毒VP2 蛋白的免疫原性鉴定

【目的】构建传染性法氏囊病毒VP2蛋白展示禽流感M2e抗原表位的重组蛋白,研发预防H5或H9亚型禽流感和传染性法氏囊的基因工程疫苗。【方法】根据现有禽流感疫苗株M2e的氨基端12个氨基酸多肽序列(nM2e)序列,结合GenBank中H5和H9亚型禽流感病毒nM2e的比对结果,确定nM2e序列。用融合PCR分别将1拷贝H5或H9的nM2e序列插入IBD B87株VP2基因的PBC区,获得VP2BCnM2e重组基因。将重组基因克隆至杆状病毒表达系统,转染Sf9细胞进行表达。经间接免疫荧光和Western blotting检测Sf9细胞表达重组基因后,扩繁重组病毒,制备疫苗,间隔4周对非免鸡作2次重复免疫,用间接ELISA和鸡胚成纤维细胞中的病毒血清中和试验检测血清中VP2和nM2e的抗体效价。【结果】成功构建含H5或H9 nM2e的VP2BCnM2e重组基因,该重组基因在Sf9细胞中得到表达。经免疫鸡,两重组蛋白均能激发针对VP2和nM2e的抗体,VP2BCnM2eH5组抗体效价高于VP2BCnM2eH9组。【结论】两重组蛋白均具有免疫原性,VP2BCnM2eH5免疫原性更佳。     

鸟巢蕨孢子繁殖技术研究

研究了鸟巢蕨孢子无菌播种和常规播种两种繁殖方法。结果表明,鸟巢蕨无菌播种中孢子萌发率最高可达66.7%,原叶体在固体培养基上培养不能诱导出孢子体,而需经过振荡培养后才能诱导出孢子体;常规播种法更容易诱导出孢子体,每盆播0.02 g孢子时,每克孢子可产生孢子体4 000株以上,比无菌播种操作简便,成本低。因此,孢子常规播种法更适合于鸟巢蕨规模化生产。     

猪圆环病毒2型新疆株全基因组的滚环扩增与序列分析

滚环扩增技术是一种体外恒温DNA扩增方法,特异性好,敏感性强,已广泛应用于微生物学领域。首先采用鉴别PCR对来自新疆某地区的5份猪病料进行猪圆环病毒2型的检测,接着对检出的2份猪圆环病毒2型阳性DNA样品进行滚环扩增。滚环扩增产物经单一限制性内切酶(SacⅡ)酶切及琼脂糖凝胶电泳鉴定,结果显示2份样品都出现了猪圆环病毒2型基因组大小的条带。对目的条带进行回收、克隆与测序,结果表明2株新疆株猪圆环病毒2型的全基因组大小皆为1768bp。遗传进化分析显示2株的基因型为PCV2a和PCV2e。     

Prognostic analysis of Behçet’s disease with aortic regurgitation or involvement

BackgroundAortic regurgitation is the most common cardiovascular damage in Chinese patients with Behçet’s disease (BD) and is usually associated with aortic disease. These patients are easily misdiagnosed, and their prognosis is poor, even after surgical treatment. This study aimed to analyse potential factors that can improve the prognosis of BD patients with aortic regurgitation and/or aortic involvement.MethodsTwenty-two patients with diagnosed or suspected BD as well as aortic regurgitation and/or aortic involvement in our hospital from 2012 through 2017 were collected in this study. Their clinical characteristics were listed, and the diagnosis of BD was evaluated by two different criteria sets. The influences of surgical treatment and immunosuppressive therapy (IST) on their prognosis were also explored.ResultsThe diagnostic positive rate of the International Criteria for Behçet’s Disease was higher than that of the International Study Group criteria (kappa value 0.31, p < 0.05), indicating that the diagnostic consistency between the criteria sets was poor. There was no significant difference in survival between patients who had undergone ≤ 1 operation and those with ≥ 2 operations. Aortic valve replacement alone or in combination with aortic root replacement had no significant effect on the incidence of reoperation or death, but IST did significantly reduce this incidence (p < 0.05). However, there was no significant difference in the occurrence of reoperation or death between preoperative and postoperative IST versus postoperative IST only.ConclusionIST significantly improved the prognosis of BD patients with aortic regurgitation and/or aortic involvement.Supplementary InformationThe online version of this article (10.1007/s12471-021-01567-6) contains supplementary material, which is available to authorized users.     

Peptide receptor radionuclide therapy of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): From literature to practice

Well differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are characterized by the overexpression of specific biomarkers, especially somatostatin receptors subtype 2. Somatostatin receptor scintigraphy and currently, positron emission tomography using ⁶⁸Ga-labeled-somatostatin analogs are considered the gold standard for functional imaging of GEP-NETs. They are complementary to CT scan and to MRI, for the staging and restaging of these tumors and are useful to select patients for peptide receptor radionuclide therapy (PRRT), in a theranostic approach. Somatostatin analogues, radiolabeled with the beta-emitting radionuclides lutetium-177 and yttrium-90, have been developed for PRRT of GEP-NETs. The efficacy of this treatment depends on the intensity of uptake on pre-therapeutic scan, the extent of hepatic involvement, and a preserved global health status. Toxicity, mainly hematologic and renal can be reduced by a rigorous selection of patients and co-infusion of amino-acids. PRRT became possible since 2013 in some specialized centers in France, by the way of clinical research programs and temporary authorization from the Agence nationale de sécurité du médicament et des produits de santé to use PRRT. This decision took place after the communication of preliminary results of the NETTER-1 study, which confirmed the efficacy of LUTATHERA^® in the treatment of midgut NETs. A marketing authorization for this radiopharmaceutical is expected in France in 2017. This article reports the main data of the literature on the development of PRRT and its current use in France. It also reviews the indications and the side effects of the treatment, and presents the perspective of optimization of this promising therapeutic approach for the coming years. The other therapeutic options in GEP-NETs are also presented.     

Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision

1. Download high-res image (171KB)
2. Download full-size image

     

Long noncoding RNA MAGI1-IT1 regulates cardiac hypertrophy by modulating miR-302e/DKK1/Wnt/beta-catenin signaling pathway

Cardiac hypertrophy (CH) is an adaptive cardiac response to overload whose decompensation eventually leads to heart failure or sudden death. Recently, accumulating studies have indicated the implication of long noncoding RNAs (lncRNAs) in CH progression. MAGI1-IT1 is a newly-identified lncRNA that is highly associated with CH, while its specific role in CH progression remains masked. In this study, we uncovered that MAGI1-IT1 was distinctly downregulated in angiotensin (Ang) II-induced hypertrophic H9c2 cells. Also, MAGI1-IT1 overexpression in Ang II-treated H9c2 cells strikingly abolished the enlarged surface area and the enhanced levels of hypertrophic markers such as ANP, BNP, and β-MHC. Mechanically, we found MAGI1-IT1 sponged miR-302e which was identified as a hypertrophy-facilitator here, and that miR-302e upregulation countervailed the inhibition of MAGI1-IT1 overexpression on hypertrophic cells. Moreover, it was confirmed that MAGI1-IT1 boosted DKK1 expression by absorbing miR-302e. Subsequently, we also illustrated that MAGI1-IT1 inactivated Wnt/beta-catenin signaling through a DKK1-dependent pathway. Finally, both the DKK1 inhibition and LiCI (Wnt activator) supplement abrogated the hypertrophy-suppressive impact of MAGI1-IT1 on Ang II-simulated hypertrophic H9c2 cells. Jointly, our findings disclosed that MAGI1-IT1 functioned as a negative regulator in CH through inactivating Wnt/beta-catenin pathway via targeting miR-302e/DKK1 axis, revealing a novel road for CH treatment.     

Quantification of the Thyroid Scan (TS) and correlation to Multiparametric Ultrasounds (MPUS): A textbook case of nuclear molecular imaging

For decades, thyroid scintigraphy (TS) has been considered an interesting tool, especially in the field of hyperthyroidism. In recent years, TS has rapidly gained importance since it provides unique molecular information that cannot be obtained by any other modality. In fact, despite a limited 6 mm spatial resolution, it can highlight molecular and histo-functional changes that characterize most thyroid function disorders. However, to become such a powerful molecular image, the TS must be quantified. How much iodine is taken-up characterizes the Uptake (Up), while where iodine distributes characterizes the Spatial Targeting (ST). Methodology, results and limits of the thyroid Uptake are presented, including suppressed tests. Methods to determine the anatomical thyroid volume are revisited with special focus on planar scintigraphy. Recent developments in quantification make the ¹²³I-TS a new molecular imaging procedure. Since ¹²³I targets the sodium iodide symporter (NIS) and tracks the whole organification process, we derived a fundamental linear relationship between the TSH and the precocious (120–240 min) Uptake (p¹²³IUp). This relationship indicates whether the ¹²³I input follows the physiological TSH stimulation or is predictive of a non TSH-suppressible function, whatever the imaging pattern. This allows identification of toxic or compensated (TSH > 0.1 mU/L) Thyroid Functional Autonomy (TFA), even at baseline. Spatial Targeting, measured with the aid of computational algorithms, provides a reproducible Spatial Targeting Index (STI). This allows estimating a functional thyroid volume, that is likely more informative than the anatomical one. Most aspects of TS quantification and the interest to compare the structure (mostly MultiParametric US) and the function (molecular ¹²³I-TS) are presented.     

Mapping suitable great ape habitat in and around the Lobéké National Park,South‐East Cameroon

As a result of extensive data collection efforts over the last 20–30 years, there is quite a good understanding of the large‐scale geographic distribution and range limits of African great apes. However, as human activities increasingly fragment great ape spatial distribution, a better understanding of what constitutes suitable great ape habitat is needed to inform conservation and resource extraction management. Chimpanzees (Pan troglodytes troglodytes) and gorillas (Gorilla gorilla gorilla) inhabit the Lobéké National Park and its surrounding forest management units (FMUs) in South‐East Cameroon. Both park and neighboring forestry concessions require reliable evidence on key factors driving great ape distribution for their management plans, yet this information is largely missing and incomplete. This study aimed at mapping great ape habitat suitability in the area and at identifying the most influential predictors among three predictor categories, including landscape predictors (dense forest, swampy forest, distance to water bodies, and topography), human disturbance predictors (hunting, deforestation, distance to roads, and population density), and bioclimatic predictor (annual precipitation). We found that about 63% of highly to moderately suitable chimpanzee habitat occurred within the Lobéké National Park, while only 8.4% of similar habitat conditions occurred within FMUs. For gorillas, highly and moderately suitable habitats occurred within the Lobéké National Park and its surrounding FMUs (82.6% and 65.5%, respectively). Key determinants of suitable chimpanzee habitat were hunting pressure and dense forest, with species occurrence probability optimal at relatively lower hunting rates and at relatively high‐dense forest areas. Key determinants of suitable gorilla habitat were hunting pressure, dense forests, swampy forests, and slope, with species occurrence probability optimal at relatively high‐dense and swampy forest areas and at areas with mild slopes. Our findings show differential response of the two ape species to forestry activities in the study area, thus aligning with previous studies.