同种异体胚胎神经干细胞移植修复脊髓损伤的时效性观察

目的:观察同种异体胚胎神经干细胞移植对脊髓损伤大鼠双后肢运动功能的修复作用,并分析其移植时效性。方法:实验于2003-07/08在大连医科大学分子生物学实验室和大连理工大学环境与生命学院生物医学实验室完成。①取孕14￣16d的大白鼠1只,引颈处死,剖腹,取出胎鼠,钳取大脑皮质及皮质下脑室旁的脑组织,体外培养大鼠胚胎神经干细胞。②将30只成年SD大鼠按随机数字表法分为3组,即损伤对照组、早期移植组和延期移植组,每组10只。3组大鼠均制作脊髓横断损伤模型,造成大鼠下肢瘫痪,早期移植组、延期移植组大鼠分别在伤后3d及3周移植胎鼠脑组织神经干细胞。观察移植后大鼠双后肢的运动功能恢复情况,通过胶质原纤维酸性蛋白及神经元特异性烯醇化酶免疫组化染色法观察各组大鼠的脊髓组织形态学变化,胶质原纤维酸性蛋白是星形胶质细胞特异性标志蛋白,神经元特异性烯醇化酶是神经元特异性蛋白。结果:脊髓损伤建模实验纳入大鼠30只,全部进入结果分析,无脱失。①各组大鼠神经干细胞移植后双后肢的功能恢复情况:早期移植组和延期移植组大鼠双后肢的运动功能均有明显改善,但早期移植组表现尤为显著。早期移植组和延期移植组细胞移植后五六天即可见瘫痪大鼠的后肢肌力开始恢复,二三周后可出现爬行,4周后后肢活动活跃;损伤对照组大鼠的瘫痪肢体无任何恢复。②移植4周后早期移植组大鼠移植区脊髓组织的形态学变化:脊髓移植区肉眼可见有增生的组织充填,镜下有大量新生的细胞,表现为神经元和神经胶质细胞阳性染色(胶质原纤维酸性蛋白( ),神经元特异性烯醇化酶( ))。结论:神经干细胞移植对脊髓横断大鼠运动功能恢复有促进作用,早期移植疗效更好。     

CD79a: a novel marker for B-cell neoplasms in routinely processed tissue samples

The CD79 molecule, comprising two polypeptide chains, mb-1 (CD79a) and B29 (CD79b), is physically associated in the B-cell membrane with immunoglobulin. It transmits a signal after antigen binding and may, therefore, be considered the B cell equivalent of CD3. It appears before the pre-B-cell stage, and the mb-1 (CD79a) chain can still be present at the plasma cell stage. In this report, we describe a new anti-CD79a monoclonal antibody, JCB117, which reacts with human B cells in paraffin embedded tissue sections, including decalcified bone marrow trephines. When tested on a total of 454 paraffin embedded tissue biopsies, gathered from a number of different institutions, it reacted with the great majority (97%) of B-cell neoplasms, covering the full range of B-cell maturation, including 10 of 20 cases of myeloma/plasmacytoma. It is of interest that the antibody labels precursor B-cell acute lymphoblastic leukemia samples, making it the most reliable B-cell marker detectable in paraffin-embedded specimens in this disorder. All neoplasms of T cell or nonlymphoid origin were negative, indicating that antibody JCB117 may be of value to diagnostic histopathologists for the identification of B-cell neoplasms of all maturation stages.     

Overlapping Mechanisms of Action of Brain-Active Bacteria and Bacterial Metabolites in the Pathogenesis of Common Brain Diseases

The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but comparative literature is scarce. To fill this gap, we explored the contribution of the microbiota–gut–brain axis to the pathophysiology of seven brain-related diseases (attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease, major depressive disorder, and bipolar disorder). In this article, we discussed changes in bacterial abundance and the metabolic implications of these changes on disease development and progression. Our central findings indicate that, mechanistically, all seven diseases are associated with a leaky gut, neuroinflammation, and over-activated microglial cells, to which gut-residing bacteria and their metabolites are important contributors. Patients show a pro-inflammatory shift in their colon microbiota, harbouring more Gram-negative bacteria containing immune-triggering lipopolysaccharides (LPS) in their cell walls. In addition, bacteria with pro-inflammatory properties (Alistipes, Eggerthella, Flavonifractor) are found in higher abundances, whereas lower abundances of anti-inflammatory bacteria (Bifidobacterium, Coprococcus, Eucbacterium, Eubacterium rectale, Faecalibacterium, Faecalibacterium prasunitzii, Lactobacillus, Prevotella, Roseburia) are reported, when compared to healthy controls. On the metabolite level, aberrant levels of short-chain fatty acids (SCFAs) are involved in disease pathogenesis and are mostly found in lower quantities. Moreover, bacterial metabolites such as neurotransmitters (acetylcholine, dopamine, noradrenaline, GABA, glutamate, serotonin) or amino acids (phenylalanine, tryptophan) also play an important role. In the future, defined aberrations in the abundance of bacteria strains and altered bacterial metabolite levels could likely be possible markers for disease diagnostics and follow-ups. Moreover, they could help to identify novel treatment options, underlining the necessity for a deeper understanding of the microbiota–gut–brain axis.