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Effect of crocin on antioxidant gene expression, fibrinolytic parameters, redox status and blood biochemistry in nicotinamide-streptozotocin-induced diabetic rats. 藏红花素对烟酰胺-链脲霉素诱导的糖尿病大鼠抗氧化基因表达、纤溶参数、氧化还原状态及血液生化的影响。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2020-03-02 eCollection Date: 2020-12-01 DOI: 10.1186/s40709-020-00114-5
Ioannis Margaritis, Katerina Angelopoulou, Sophia Lavrentiadou, Ilias C Mavrovouniotis, Maria Tsantarliotou, Ioannis Taitzoglou, Alexandros Theodoridis, Aristidis Veskoukis, Efthalia Kerasioti, Dimitrios Kouretas, Ioannis Zervos

Background: Diabetes is regarded as an epidemiological threat for the twenty-first century. Phytochemicals with known pharmaceutical properties have gained interest in the field of alleviating secondary complications of diseases. Such a substance is crocin, a basic constituent of saffron (Crocus sativus). The present study aimed at examining the beneficial effects of per os crocin administration on the antioxidant status, blood biochemical profile, hepatic gene expression and plasminogen activator inhibitor-1 activity (PAI-1) in the liver, kidney and plasma (an important marker of pre-diabetic status and major factor of thrombosis in diabetes) of healthy rats, as well as of rats with nicotinamide-streptozotocin-induced diabetes.

Results: Diabetes disrupted the oxidation-antioxidation balance, while crocin improved the antioxidant state in the liver by significantly affecting SOD1 gene expression and/or by restoring SOD and total antioxidant capacity (TAC) levels. In the kidney, crocin improved hydrogen peroxide decomposing activity and TAC. In blood, hepatic transaminases ALT and AST decreased significantly, while there was a trend of decrease regarding blood urea nitrogen (BUN) levels. The expression of PAI-1 gene was affected in the liver by the dose of 50 mg kg-1.

Conclusions: Crocin treatment contributed in restoring some parameters after diabetes induction, primarily by affecting significantly hepatic transaminases ALT and AST, SOD1 and PAI-1 gene expression and nephric H2O2 decomposing activity. In conclusion, crocin did contribute to the alleviation of some complications of diabetes.

背景:糖尿病被认为是21世纪的流行病学威胁。具有已知药物特性的植物化学物质在减轻疾病继发性并发症方面引起了人们的兴趣。这种物质是藏红花(Crocus sativus)的基本成分藏红花素。本研究旨在探讨西红花素给药对健康大鼠和烟酰胺-链脲霉素诱导的糖尿病大鼠的抗氧化状态、血液生化特征、肝脏基因表达和血浆纤溶酶原激活物抑制剂-1活性(PAI-1)(糖尿病前期状态的重要标志和糖尿病血栓形成的主要因素)的有益影响。结果:糖尿病破坏了氧化-抗氧化平衡,而藏红花素通过显著影响SOD1基因表达和/或通过恢复SOD和总抗氧化能力(TAC)水平改善了肝脏的抗氧化状态。在肾脏中,藏红花素提高过氧化氢分解活性和TAC。血中肝转氨酶ALT、AST显著降低,血尿素氮(BUN)有降低趋势。50 mg kg-1剂量对PAI-1基因在肝脏中的表达有影响。结论:藏红花素治疗有助于恢复糖尿病诱导后的一些参数,主要是通过显著影响肝转氨酶ALT和AST、SOD1和PAI-1基因表达和肾脏H2O2分解活性。总之,藏红花素确实有助于减轻糖尿病的一些并发症。
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引用次数: 16
Editorial Announcement. 编辑公告。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2020-02-19 eCollection Date: 2020-12-01 DOI: 10.1186/s40709-020-00113-6
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引用次数: 0
Histologic evaluation of femoral nerve demyelinating and axonal neuropathy in Wistar rats due to alendronate intake: a randomised study. 阿仑膦酸钠摄入引起Wistar大鼠股骨神经脱髓鞘和轴突神经病变的组织学评价:一项随机研究。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2020-02-18 eCollection Date: 2020-12-01 DOI: 10.1186/s40709-020-0112-z
Papamitsou Theodora, Papakoulas Apostolos, Papaliagkas Vasileios, Karachrysafi Sofia, Dietrich Eva-Maria, Sioga Antonia

Background: Bisphosphonates (BPs) are forceful inhibitors of osteoclast-mediated bone resorption. Long-term BP use is associated with multiple rare but severe adverse effects. The objective of this study was to investigate the possible effects of BPs in the structure of femoral nerve. Specimens from the femoral nerve of ten female 12-month old Wistar rats were used as control group and ten female 12-month old Wistar rats to which Alendronate (Fosamax, Merck) was administered per os for 13 weeks, were used as research group. Samples were observed under a Transmission Electron Microscope. G ratio measurements and statistical analysis with SPSS program were also performed.

Results: The control group showed no major changes of the nerve's histologic image, with the exception of some spots of thickness of the nerve myelin sheath. The research group showed major morphological changes which varied from partial disorganization or thickening of the myelin to severe myelin thickening and axon strangulation. A statistically significant difference of the G ratio between the two groups was observed.

Conclusions: The reported values (found in literature) for the morphologic measurements of the femoral nerve in Wistar rats are not complying with the ones we found in our study. There was a significant reduction of all three variables (the mean axon like diameter, the myelin thickness, G ratio) studied in the femoral nerve of the research group in contrast to control group. Our study demonstrates a possible correlation between alendronate administration and femoral nerve's function, nevertheless due to the small specimen further research is needed.

背景:双膦酸盐(BPs)是破骨细胞介导的骨吸收的有效抑制剂。长期使用BP与多种罕见但严重的不良反应相关。本研究的目的是探讨bp对股神经结构的可能影响。以10只12月龄雌性Wistar大鼠股骨神经标本为对照组,10只12月龄雌性Wistar大鼠给予阿仑膦酸钠(福善美,默克)治疗13周为研究组。在透射电子显微镜下观察样品。G比测量及SPSS统计分析。结果:对照组除髓鞘部分增厚外,神经组织学图像无明显改变。研究组表现出主要的形态学变化,从髓磷脂部分紊乱或增厚到髓磷脂严重增厚和轴突绞窄。两组间G比值差异有统计学意义。结论:文献报道的Wistar大鼠股神经形态学测量值与我们的研究结果不一致。与对照组相比,研究组股骨神经的三个变量(平均轴突样直径、髓鞘厚度、G比)均显著降低。我们的研究表明阿仑膦酸钠给药与股神经功能之间可能存在相关性,但由于样本较小,需要进一步研究。
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引用次数: 1
Metabolic engineering of Escherichia coli for the utilization of ethanol. 利用乙醇的大肠杆菌代谢工程。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2020-01-21 eCollection Date: 2020-12-01 DOI: 10.1186/s40709-020-0111-0
Yujin Cao, Hui Mu, Jing Guo, Hui Liu, Rubing Zhang, Wei Liu, Mo Xian, Huizhou Liu

Background: The fuel ethanol industry has made tremendous progress in the last decades. Ethanol can be obtained by fermentation using a variety of biomass materials as the feedstocks. However, few studies have been conducted on ethanol utilization by microorganisms. The price of petroleum-derived ethanol, easily made by the hydrolysis of ethylene, is even lower than that of bioethanol. If ethanol can be metabolized by microorganisms to produce value-added chemicals, it will open a new door for the utilization of inexpensive ethanol resources.

Results: We constructed an engineered Escherichia coli strain which could utilize ethanol as the sole carbon source. The alcohol dehydrogenase and aldehyde dehydrogenase from Aspergillus nidulans was introduced into E. coli and the recombinant strain acquired the ability to grow on ethanol. Cell growth continued when ethanol was supplied after glucose starvation and 2.24 g L-1 of ethanol was further consumed during the shake-flasks fermentation process. Then ethanol was further used for the production of mevalonic acid by heterologously expressing its biosynthetic pathway. Deuterium-labeled ethanol-D6 as the feedstock confirmed that mevalonic acid was synthesized from ethanol.

Conclusions: This study demonstrated the possibility of using ethanol as the carbon source by engineered E. coli strains. It can serve as the basis for the construction of more robust strains in the future though the catabolic capacity of ethanol should be further improved.

背景:过去几十年来,燃料乙醇行业取得了巨大进步。乙醇可以利用各种生物质材料作为原料,通过发酵获得。然而,有关微生物利用乙醇的研究却很少。通过乙烯水解就能轻松制得的石油衍生乙醇的价格甚至低于生物乙醇。如果乙醇能通过微生物代谢产生增值化学品,将为利用廉价乙醇资源打开一扇新的大门:结果:我们构建了一株可利用乙醇作为唯一碳源的工程大肠杆菌。将黑曲霉中的醇脱氢酶和醛脱氢酶引入大肠杆菌,重组菌株获得了以乙醇为唯一碳源的生长能力。在葡萄糖饥饿后提供乙醇时,细胞继续生长,在摇床发酵过程中进一步消耗了 2.24 g L-1 的乙醇。然后,通过异源表达甲羟戊酸的生物合成途径,乙醇被进一步用于生产甲羟戊酸。氘标记的乙醇-D6作为原料证实了甲羟戊酸是由乙醇合成的:本研究证明了工程大肠杆菌菌株使用乙醇作为碳源的可能性。结论:本研究证明了大肠杆菌工程菌株利用乙醇作为碳源的可能性,为今后构建更强大的菌株奠定了基础,但乙醇的分解能力有待进一步提高。
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引用次数: 0
Implications of salep collection for the conservation of the Elder-flowered orchid (Dactylorhiza sambucina) in Epirus, Greece. 希腊伊庇鲁斯接骨木花兰花(Dactylorhiza sambucina)保存的salep采集意义。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2019-12-30 eCollection Date: 2019-12-01 DOI: 10.1186/s40709-019-0110-1
Martha Charitonidou, Kalliopi Stara, Konstantinos Kougioumoutzis, John M Halley

Background: In Epirus, Greece, orchids have been traditionally harvested for the production of salep, a beverage made from their tubers. Over-collection of orchids for salep is believed to be a growing threat to wild species, yet very little research has concentrated on orchid populations in the wild. Here, we studied the impact of salep collection on population demographic parameters and uniformity of distribution patterns of the Elder-flowered orchid, Dactylorhiza sambucina, the most commonly collected orchid in northern Greece.

Methods: We carried out fieldwork in four meadows where salep harvesting occurs, and conducted interviews in villages close to these sites. Fieldwork focused on the demographic parameters of orchid populations and on the characteristics of their habitat (natural-anthropogenic). We also measured population size and distribution, extent and multi-scale density, comparing distributions to Poisson and fractal models.

Results: According to interviews, salep collection by the local community has decreased, contrary to collection by people outside the community, which is increasing. Interviewees did not believe that orchid abundance was higher in the past; they claim that it can be very variable. None of the participants seemed aware of the legislation to conserve orchids. Demographic parameters did not seem to be strongly dependent on whether it was a harvested and non-harvested sites and population density was greatest in the site of highest collection pressure.

Conclusions: Our findings show that salep collection is still ongoing in Epirus. Our interview results and our population study indicate that current levels of collection are not significantly affecting the abundance of the Elder-flowered orchid in Epirus subalpine meadows. However, the expanding commercial collection could reach levels that threaten the species. There is a need for a longer-term monitoring of these orchid populations, and a more effective modeling of the species' response to different harvesting pressures.

背景:在希腊的伊庇鲁斯,兰花的传统收获是为了生产salep,一种由它们的块茎制成的饮料。为睡眠过度采集兰花被认为是对野生物种日益严重的威胁,但很少有研究集中在野生兰花种群上。本文研究了salep采集对希腊北部最常见的接骨木兰花(Dactylorhiza sambucina)种群人口统计学参数和分布格局均匀性的影响。方法:我们在4个采沙莱草的草地上进行了实地调查,并在这些地点附近的村庄进行了访谈。野外调查的重点是兰花种群的人口学参数及其生境特征(自然-人为)。我们还测量了种群的大小和分布、范围和多尺度密度,并将分布与泊松模型和分形模型进行了比较。结果:根据访谈,当地社区收集的salep减少了,相反,社区外的人收集的salep增加了。受访者不认为过去兰花的丰度更高;他们声称这是非常多变的。与会者似乎都不知道保护兰花的立法。人口统计参数似乎与采伐地和非采伐地没有太大关系,在采伐压力最大的地点,人口密度最大。结论:我们的研究结果表明,伊庇鲁斯的睡眠收集仍在进行中。我们的访谈结果和种群研究表明,目前的采集水平对伊庇鲁斯亚高山草甸接骨木花兰的丰度没有显著影响。然而,不断扩大的商业收集可能会达到威胁物种的水平。有必要对这些兰花种群进行长期监测,并更有效地模拟该物种对不同收获压力的反应。
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引用次数: 14
Saliva proteomics updates in biomedicine. 唾液蛋白质组学在生物医学中的最新进展。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2019-12-12 eCollection Date: 2019-12-01 DOI: 10.1186/s40709-019-0109-7
Katerina R Katsani, Dimitra Sakellari

In the years of personalized (or precision) medicine the 'omics' methodologies in biomedical sciences-genomics, transcriptomics, proteomics and metabolomics-are helping researchers to detect quantifiable biological characteristics, or biomarkers, that will best define the human physiology and pathologies. Proteomics use high throughput and high efficiency approaches with the support of bioinformatic tools in order to identify and quantify the total protein content of cells, tissues or biological fluids. Saliva receives a lot of attention as a rich biological specimen that offers a number of practical and physiological advantages over blood and other biological fluids in monitoring human health. The aim of this review is to present the latest advances in saliva proteomics for biomedicine.

在个性化(或精确)医学的年代,生物医学科学中的“组学”方法——基因组学、转录组学、蛋白质组学和代谢组学——正在帮助研究人员检测可量化的生物特征或生物标志物,这些特征或生物标志物将最好地定义人类生理学和病理学。蛋白质组学在生物信息学工具的支持下,使用高通量和高效率的方法来鉴定和量化细胞、组织或生物液体的总蛋白质含量。唾液作为一种丰富的生物标本,在监测人体健康方面比血液和其他生物液体具有许多实际和生理上的优势,因此受到了广泛的关注。本文就唾液蛋白质组学在生物医学领域的研究进展作一综述。
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引用次数: 30
Comparative analysis of differentially expressed genes between the ovaries from pregnant and nonpregnant goats using RNA-Seq. 利用RNA-Seq技术对怀孕山羊和未怀孕山羊卵巢差异表达基因进行比较分析。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2019-05-06 eCollection Date: 2019-12-01 DOI: 10.1186/s40709-019-0095-9
Qing Quan, Qi Zheng, Yinghui Ling, Fugui Fang, Mingxing Chu, Xiaorong Zhang, Yong Liu, Wenyong Li

Background: A multitude of genes tightly regulate ovarian follicular development and hormone secretion. These complex and coordinated biological processes are altered during pregnancy. In order to further understand the regulatory role of these genes during pregnancy, it is important to screen the differentially expressed genes (DEGs) in the ovaries of pregnant and nonpregnant mammals. To detect the genes associated with the development of pregnancy in goats, DEGs from the ovaries from pregnant and nonpregnant Anhui white goats (pAWGs and nAWGs, respectively) were analyzed using RNA sequencing technology (RNA-Seq).

Results: In this study, 13,676,394 and 13,549,560 clean reads were generated from pAWGs and nAWGs, respectively, and 1724 DEGs were identified between the two libraries. Compared with nAWGs, 1033 genes were upregulated and 691 genes were downregulated in pAWGs, including PGR, PRLR, STAR and CYP19A1, which play important roles in goat reproduction. Gene Ontology analysis showed that the DEGs were enriched for 49 functional GO terms. Kyoto Encyclopedia of Genes and Genomes analysis revealed that 397 DEGs were significantly enriched in 13 pathways, including "cell cycle", "cytokine-cytokine receptor interaction" and "steroid biosynthesis", suggesting that the genes may be associated with cell cycle regulation, follicular development and hormone secretion to regulate the reproduction process. Additionally, quantitative real-time PCR was used to verify the reliability of the RNA-Seq data.

Conclusions: The data obtained in this work enrich the genetic resources of goat and provide a further understanding of the complex molecular regulatory mechanisms occurring during the development of pregnancy and reproduction in goats. The DEGs screened in this study may play an important role in follicular development and hormone secretion and they would provide scientific basis for related research in the future.

背景:多种基因紧密调控着卵巢卵泡发育和激素分泌。这些复杂而协调的生物过程在怀孕期间发生改变。为了进一步了解这些基因在妊娠期间的调控作用,筛选妊娠和非妊娠哺乳动物卵巢中的差异表达基因(deg)是很重要的。为了检测山羊妊娠发育相关基因,采用RNA测序技术(RNA- seq)分析了妊娠和未妊娠安徽白山羊卵巢deg(分别为pAWGs和nAWGs)。结果:在本研究中,分别从pAWGs和nAWGs中产生了13,676,394和13,549,560个clean reads,在两个文库中鉴定出1724个DEGs。与nAWGs相比,pags中有1033个基因表达上调,691个基因表达下调,包括PGR、PRLR、STAR和CYP19A1等在山羊繁殖中起重要作用的基因。基因本体分析显示,这些基因富含49个功能性氧化石墨烯项。京都基因与基因组百科分析显示,397个基因在“细胞周期”、“细胞因子-细胞因子受体相互作用”和“类固醇生物合成”等13条通路上显著富集,提示这些基因可能与细胞周期调控、卵泡发育和激素分泌有关,调节生殖过程。此外,采用实时荧光定量PCR技术验证RNA-Seq数据的可靠性。结论:本研究丰富了山羊的遗传资源,为进一步了解山羊妊娠发育和繁殖过程中复杂的分子调控机制提供了依据。本研究筛选的deg可能在卵泡发育和激素分泌中发挥重要作用,为今后的相关研究提供科学依据。
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引用次数: 11
A systematic simulation-based meta-analytical framework for prediction of physiological biomarkers in alopecia. 一个基于系统模拟的meta分析框架,用于预测脱发的生理生物标志物。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2019-04-04 eCollection Date: 2019-12-01 DOI: 10.1186/s40709-019-0094-x
Syed Aun Muhammad, Nighat Fatima, Rehan Zafar Paracha, Amjad Ali, Jake Y Chen

Background: Alopecia or hair loss is a complex polygenetic and psychologically devastating disease affecting millions of men and women globally. Since the gene annotation and environmental knowledge is limited for alopecia, a systematic analysis for the identification of candidate biomarkers is required that could provide potential therapeutic targets for hair loss therapy.

Results: We designed an interactive framework to perform a meta-analytical study based on differential expression analysis, systems biology, and functional proteomic investigations. We analyzed eight publicly available microarray datasets and found 12 potential candidate biomarkers including three extracellular proteins from the list of differentially expressed genes with a p-value < 0.05. After expression profiling and functional analysis, we studied protein-protein interactions and observed functional associations of source proteins including WIF1, SPON1, LYZ, GPRC5B, PTPRE, ZFP36L2, HBB, PHF15, LMCD1, KRT35 and VAV3 with target proteins including APCDD1, WNT1, WNT3A, SHH, ESRI, TGFB1, and APP. Pathway analysis of these molecules revealed their role in major physiological reactions including protein metabolism, signal transduction, WNT, BMP, EDA, NOTCH and SHH pathways. These pathways regulate hair growth, hair follicle differentiation, pigmentation, and morphogenesis. We studied the regulatory role of β-catenin, Nf-kappa B, cytokines and retinoic acid in the development of hair growth. Therefore, the differential expression of these significant proteins would affect the normal level and could cause aberrations in hair growth.

Conclusion: Our integrative approach helps to prioritize the biomarkers that ultimately lessen the economic burden of experimental studies. It will also be valuable to discover mutants in genomic data in order to increase the identification of new biomarkers for similar problems.

背景:脱发是一种复杂的多基因和心理破坏性疾病,影响着全球数百万男性和女性。由于脱发的基因注释和环境知识有限,因此需要对候选生物标志物进行系统的分析,从而为脱发治疗提供潜在的治疗靶点。结果:我们设计了一个交互式框架来进行基于差异表达分析、系统生物学和功能蛋白质组学研究的meta分析研究。我们分析了8个公开可用的微阵列数据集,发现了12个潜在的候选生物标志物,其中包括来自差异表达基因列表的3个细胞外蛋白,其p值为p值。结论:我们的综合方法有助于优先考虑最终减轻实验研究经济负担的生物标志物。在基因组数据中发现突变体,以增加对类似问题的新生物标记物的识别,也将是有价值的。
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引用次数: 12
Intraspecific morphological variation of the sperm storing organ in two hermaphroditic land snail species. 两种雌雄同体陆地蜗牛精子储存器官的种内形态变异。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2019-01-30 eCollection Date: 2019-12-01 DOI: 10.1186/s40709-019-0093-y
Alexandra Staikou, Evripidis Koemtzopoulos

Background: Postcopulatory sexual selection is very important in species with reproductive strategies that involve multiple mating and prolonged sperm storage. The sperm storage organ has been hypothesized to evolve in response to different levels of sperm competition in several species while population density has been considered as a factor that approximates sperm competition risk and intensity in the field. Apart from population density, local microclimatic conditions may also play a role in determining sperm competition levels in natural populations of land snails by affecting their chances of encountering mates. The goal of this study was to investigate the variation of the structure of the sperm storage organ in the simultaneously hermaphroditic land snails Helix lucorum and Cepaea vindobonensis occurring sympatrically in two sites which differed in habitat humidity. The populations of both species from the two sites, also differed in density and in duration of reproductive period. Multiple samples were taken from each population in order to test for temporal variation.

Results: In both species, the spermatheca consisted of a simple fertilization chamber and a variable number of lateral tubules. The length of the spermatheca showed no temporal or spatial differentiation nor did it show any correlation with snail size. The number of tubules in Helix lucorum ranged from five to sixteen and in Cepaea vindobonensis from one to eight and in both species a significant difference of this trait between the two study sites was detected. In Cepaea vindobonensis, the difference in tubule number led to difference of the total tubule length which reflects sperm storage capacity of the spermatheca but this was not the case with H. lucorum in which no increase in total tubule length was detected.

Conclusions: Intraspecific variation in the spermatheca was observed in both snail species studied. The variation observed was independent of snail size, and reproduction status, while the two species responded differently to higher sperm competition levels.

背景:交配后的性选择对于那些具有多次交配和长时间精子储存的生殖策略的物种来说是非常重要的。精子储存器官已被假设为在不同物种中响应不同水平的精子竞争而进化,而种群密度已被认为是一个近似于精子竞争风险和强度的因素。除了种群密度外,当地的小气候条件也可能通过影响它们遇到配偶的机会来决定自然种群中陆地蜗牛的精子竞争水平。本研究旨在探讨在不同生境湿度条件下同时雌雄同体的钉螺(Helix lucorum和Cepaea vindobonensis)精子储存器官结构的变化。两个地点的种群密度和繁殖期长短也存在差异。从每个人群中抽取多个样本,以检验时间变化。结果:两种动物的精囊均由一个简单的受精腔和数量不定的侧小管组成。精子囊的长度与蜗牛的大小没有明显的时空差异。双螺旋lucorum的小管数量在5到16个之间,而Cepaea vindobonensis的小管数量在1到8个之间,并且在两个研究地点之间检测到这一特征的显著差异。在Cepaea vindobonensis中,小管数量的不同导致总小管长度的不同,总小管长度反映了精子囊的精子储存能力,但在H. lucorum中没有发现总小管长度的增加。结论:两种蜗牛的精子囊均存在种内变异。观察到的变异与蜗牛的大小和繁殖状态无关,而两种物种对更高的精子竞争水平的反应不同。
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引用次数: 2
Immune cell counts and signaling in body fluids of cows vaccinated against Clostridium difficile. 接种艰难梭菌疫苗的奶牛体液中的免疫细胞计数和信号传导。
IF 3.3 3区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2018-12-10 DOI: 10.1186/s40709-018-0092-4
Christiane Schmautz, Nadine Müller, Marlene Auer, Ines Ballweg, Michael W Pfaffl, Heike Kliem

Background: New treatment options are needed to prevent relapses following failed antibiotic therapies of Clostridium difficile infections (CDI) in humans. The concomitant therapy with an anti-C. difficile IgA containing whey protein concentrate can support the sustainable recovery of CDI patients. For 31 weeks, nine dairy cows were continuously vaccinated with several anti-C. difficile vaccines by certain routes of administration to produce anti-C. difficile IgA enriched milk. The study aimed at finding decisive differences between low responder (LR) and high responder (HR) cows (> 8.0 µg ml-1 total milk C. difficile specific IgA) concerning their immune response to vaccination on cellular and molecular biological levels.

Results: The results of total and differential cell counting (DCC) in blood and milk and the outcomes of the gene expression analysis of selected immune factors were assessed relating to the usage of two vaccine batches for injection (MucoCD-I batch A and B), marking two immunization (IM) periods, and compared to a control group (Ctr). The MucoCD-I batch A caused short-term leukopenia followed by leukocytosis in the blood of LR and HR. The total somatic cell counts in milk were not altered by the treatment. The DCC revealed that the leukocytes of the treated groups were partly impaired by the treatment. The gene expression analysis exposed cumulative and sustainable differences (p < 0.05) between LR and HR for the genes encoding for lactoferrin, CXCL8, IL1β, IL2, IL6, IL12β, IFNγ, CD4 and CD163. The regulation of the epithelial IgA cell receptor PIGR was not impaired by the IM. In contrast to the vaccination with MucoCD-I batch A, the second IM period with MucoCD-I batch B resulted in mitigation and synchronization of the treated groups' immune responses.

Conclusions: The inversely regulated cytokines in the blood and milk cells of the treated groups led to a variously directed, local T cell response resulting in their different production intensities of C. difficile specific IgA in milk.

背景:在人类艰难梭菌感染(CDI)的抗生素治疗失败后,需要新的治疗方案来预防复发。抗C药物的联合治疗。含有艰难梭菌IgA的乳清蛋白浓缩物可以支持CDI患者的可持续康复。在31周的时间里,9头奶牛连续接种了几种抗C疫苗。艰难梭菌疫苗通过某些给药途径产生抗C。富含艰难梭菌IgA的牛奶。该研究旨在发现低反应(LR)和高反应(HR)奶牛之间的决定性差异(> 8.0µg ml-1总乳艰难梭菌特异性IgA),涉及其在细胞和分子生物学水平上对疫苗接种的免疫反应。结果:评估了血液和牛奶中总细胞计数和差异细胞计数(DCC)的结果,以及选定免疫因子的基因表达分析的结果,这些结果与两个注射用疫苗批次(MucCD-I批次A和B)的使用有关,标记了两个免疫期(IM),并与对照组(Ctr)进行了比较。MucCD-I批次A在LR和HR的血液中引起短期白细胞减少,随后出现白细胞增多。牛奶中的体细胞总数没有因该处理而改变。DCC显示,治疗组的白细胞因治疗而部分受损。基因表达分析揭示了累积和持续的差异(p 乳铁蛋白、CXCL8、IL1β、IL2、IL6、IL12β、IFNγ、CD4和CD163。IM对上皮IgA细胞受体PIGR的调节没有受到损害。与用A批MucCD-I疫苗接种相比,用B批MucCD-I疫苗接种的第二个IM期导致治疗组的免疫反应的缓解和同步。结论:治疗组血液和乳细胞中细胞因子的反向调节导致了不同方向的局部T细胞反应,导致它们在乳中产生不同强度的艰难梭菌特异性IgA。
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引用次数: 1
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Journal of Biological Research-Thessaloniki
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