Induction of immune tolerance with heart-thymus composite allotransplantation in rats

Objective To study on the role of thymus transplantation for heart allograft in rats. Methods Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, level of IL-2, IL-4 and its mRNA expression in serum and cardiac grafts were investigated. Results Heart-thymus combined transplantation achieved effect in the prolongation of cardiac graft survival with short-term administration of cyclosporine. Conclusions Vascularized thymus transplantation induced immune tolerance in thymectomized rats.     

壳聚糖季铵盐对小牛胸腺DNA的作用研究

本文采用均相法合成了水溶性壳聚糖季铵盐（HTCC）,利用傅里叶红外（FTIR）光谱及核磁共振氢谱（1H NMR）对其结构进行了表征,结果表明,HTCC为壳聚糖C2位氨基H被季铵盐侧链取代的产物。在p H7.4的生理条件下,以吖啶橙（AO）为荧光探针,采用荧光光谱法、圆二色谱法,并结合小牛胸腺DNA（ct DNA）热变性测定等实验手段,初步探讨了HTCC与ct DNA的相互作用机理,荧光光谱的分析结果表明:HTCC对AO-ct DNA体系有猝灭作用,且符合静态猝灭特征。圆二色谱、热变性曲线分析结果表明:HTCC主要以嵌插的方式与ct DNA结合,使双螺旋结构更紧密。      

COVID-19 hospitalization rates rise exponentially with age,inversely proportional to thymic T-cell production

Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.     

IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells: Possible Epigenetic Implications Mediated by miRNA

Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed to evaluate whether serum IgG from adult AD patients could modulate the thymic maturation of IL-22-producing T cells and CLA+ T cells of non-atopic infants. Given that miRNAs regulate immune response genes, we evaluated whether miRNA expression is also altered in cultured thymocytes. Thymocytes were cultured with purified IgG from AD patients or control conditions (mock, Intravenous-IgG (IVIg), non-atopic IgG, or atopic non-AD IgG). Using flow cytometry analysis, we assessed the expression of CLA and intracellular levels of IL-4, IFN-γ, and IL-22 on double-positive T cells (DP T), CD4 T cells, or CD8 T cells. We also investigated the frequency of IgG isotypes and their direct interaction with the thymic T cells membrane. The miRNA profiles were evaluated by the Illumina small RNA-seq approach. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Increased frequencies of IL-22 and CLA+ producing CD4+ T cells cultured with IgG of AD patients was seen in non-atopic infant thymocytes compared to all control conditions. No alterations were observed in the frequency of IgG isotypes among evaluated IgG pools. Evidence for a direct interaction between IgG and thymic DP T, CD4 T, and CD8 T cells is presented. The small RNA-seq analysis identified ten mature miRNAs that were modulated by AD IgG compared to mock condition (miR-181b-5p, hsa-miR-130b-3p, hsa-miR-26a-5p, hsa-miR-4497, has-miR-146a, hsa-let-7i-5p, hsa-miR-342-3p, has-miR-148a-3p, has-miR-92a and has-miR-4492). The prediction of the targetome of the seven dysregulated miRNAs between AD and mock control revealed 122 putative targets, and functional and pathway enrichment analyses were performed. Our results enhance our understanding of the mechanism by which IgG can collaborate in thymic T cells in the setting of infant AD.     

钌(Ⅱ)配合物光谱性质及对DNA光切割作用

用紫外吸收光谱、荧光光谱和荧光淬灭技术,研究钌(Ⅱ)多吡啶配合物 [Ru(bpy)2(MDBIP)]2+ (bpy为2,2′-联吡啶; MDBIP为3,5-二溴基-咪唑并[4,5-f][1,10]邻菲咯啉)与小牛胸腺DNA的作用.用琼脂糖凝胶电泳法研究配合物对pBR322质粒DNA的光切割作用.结果表明,[Ru(bpy)2(MDBIP)]2+与小牛胸腺DNA可能是以一种弱的部分插入的方式相结合,对pBR322质粒DNA有较好的光切割作用.     

The interaction of sesamol with DNA and cytotoxicity,apoptosis, and localization in HepG2 cells

Sesamol, a nutritional antioxidant phenolic compound present in sesame seed, has a potential therapeutic molecule effect against cancers. In this study, the interaction between sesamol and DNA was investigated by employing ultraviolet/visible (UV/Vis), fluorescence, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR), and molecular modeling. The fluorescence analysis indicated that the fluorescence quenching mechanism of sesamol by calf thymus DNA (ctDNA) occurred through static quenching. The UV/Vis, CD, FT-IR spectra and molecular docking results implied that the primary binding mode was minor groove binding. Furthermore, the intracellular interaction of sesamol with DNA and its bioactivity effect were explored. The cell activity results demonstrated that sesamol induced hepatic cell line (HepG2) death. The acridine orange (AO)/ethidium bromide (EB) staining assay and DNA fragmentation confirmed that sesamol could efficiently induce the apoptosis of HepG2 cells. Moreover, addition of sesamol to HepG2 cells resulted in nuclear localization, as visualized by confocal microscopy.     

胸腺上皮肿瘤的超微结构观察

目的：观察胸腺上皮肿瘤(thymic epithelial tumor,TET)WHO病理分型的超微结构特征。方法：对14例TET采用WHO病理分型,分别观察组织病理学和超微结构的形态学特征。结果：按WHO病理分型诊断胸腺瘤A型1例,AB型3例,B1型1例,B2型4例,B3型3例,C型2例。各型胸腺瘤均具有上皮性肿瘤的结构特点,如：张力原纤维、桥粒等结构;C型胸腺瘤(胸腺癌)异型性很明显,常见肿瘤性坏死,其他类型则有一定程度的异型性。A型胸腺瘤细胞核异染色质丰富,核仁不明显,无异型性;AB型和B1型异型性不明显,细胞核常染色质较均匀,可见小核仁;B2、B3型胸腺瘤异型性较明显,常染色质较丰富,核仁明显,细胞质宽大,有突起。结论：从超微结构特点来看：A型胸腺瘤生长不活跃,AB型和B1型胸腺瘤生长略活跃;B2、B3型胸腺瘤生长较活跃;C型胸腺瘤生长很活跃。     

中功率密度He—Ne激光诱变固体DNA的拉曼光谱分析

中功率密度He—Ne激光照射DNA固体纤维后,在很短的照射时间,激光对DNA磷酸骨架结构和氢键的损伤就达到了最大值,这时不仅有磷酸二酯键的断裂,氢键也发生了断裂;随着照射时间的延长,激光对DNA的损伤程度先是减小,然后再加剧。激光对碱基的影响,先是使碱基谱线强烈减色,随着照射时间的延长,减色效应逐渐减小,然后变为较强的增色效应,再变为减色效应,这也许是激光在损伤碱基后又破坏碱基-碱基间的垂直堆积状况,造成碱基谱线的拉曼增色效应。     

条斑紫菜藻蓝蛋白的分离纯化及其抗衰老作用研究

目的：分离纯化条斑紫菜藻蓝蛋白并对其进行抗衰老作用的研究。方法：以盐析沉淀法和Sephadex G-200凝胶过滤层析纯化条斑紫菜藻蓝蛋白,并对其热稳定性和酸碱稳定性进行研究。采用D-半乳糖致亚急性小鼠衰老模型,研究藻蓝蛋白的抗衰老作用。结果：在常温下,40%饱和度的硫酸铵盐析条件下,紫菜藻蓝蛋白纯度达到最大值1.73;紫菜藻蓝蛋白在30℃时、中性溶液环境时稳定性良好;藻蓝蛋白处理后均能显著提高衰老模型小鼠的胸腺指数、脾脏指数和血清中的SOD活性(P＜0.05,P＜0.01),显著降低血清中的MDA含量(P＜0.05,P＜0.01)。结论：紫菜藻蓝蛋白具有较强的抗衰老作用。     

Cu2+、Co2+和Mg2+对杜鹃素与DNA相互作用的影响

在pH7.4的缓冲溶液中,采用紫外-可见、荧光光谱法和DNA熔点实验并结合荧光探针亚甲基蓝(MB),研究杜鹃素与小牛胸腺DNA的结合模式以及Cu2+、Co2+和Mg2+分别对结合模式的影响。结果表明：杜鹃素主要以嵌插模式与DNA结合。3种金属离子均能不同程度影响杜鹃素的吸收光谱和增强DNA-MB复合物的荧光强度。随着体系中Cu2+浓度的增加,DNA-杜鹃素复合物的结合常数呈现出先减小后增加的趋势,增加Mg2+的用量则使复合物的结合常数影响先增强然后缓慢减弱,而Co2+浓度的增大对复合物的结合常数影响较小。由此得出,Cu2+、Co2+和Mg2+对该DNA-杜鹃素结合的影响分别取决于金属离子与杜鹃素的结合能力以及与DNA的碱基和磷酸基团间的结合程度。