Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract

Guidance cues along the longitudinal axis of the CNS are poorly understood. Wnt proteins attract ascending somatosensory axons to project from the spinal cord to the brain. Here we show that Wnt proteins repel corticospinal tract (CST) axons in the opposite direction. Several Wnt genes were found to be expressed in the mouse spinal cord gray matter, cupping the dorsal funiculus, in an anterior-to-posterior decreasing gradient along the cervical and thoracic cord. Wnts repelled CST axons in collagen gel assays through a conserved high-affinity receptor, Ryk, which is expressed in CST axons. Neonatal spinal cord secretes diffusible repellent(s) in an anterior-posterior graded fashion, with anterior cord being stronger, and the repulsive activity was blocked by antibodies to Ryk (anti-Ryk). Intrathecal injection of anti-Ryk blocked the posterior growth of CST axons. Therefore, Wnt proteins may have a general role in anterior-posterior guidance of multiple classes of axons.     

脊髓损伤后神经修复过程中的细胞微环境北大核心

背景:以往的研究显示单一改变脊髓损伤区域某一基因表达或者某一细胞的状态,对脊髓损伤后功能恢复无显著影响,而大量证据表明调控脊髓损伤后紊乱的细胞微环境是神经功能恢复的关键因素。目的:对脊髓损伤前后细胞微环境的生物学特性,包括多种细胞之间的相互调控以及细胞外组分对损伤神经修复的作用和机制进行综述。方法:由第一作者检索PubMed及Web of Science数据库,英文检索词为“spinal cord injury,glial cell,neuron,immune cell,neural stem cell,extracellular matrix,cytokine,extracellular vesicle,regeneration”。文献检索的时间范围为2000年1月至2021年12月,最终筛选出64篇文献进行分析。结果与结论:①脊髓损伤后,在细胞微环境的细胞组分中,占比最高的胶质细胞间的相互作用,以及与神经元的相互调控作用最为关键。②在脊髓损伤后的细胞外组分中,利用生物相容性良好的水凝胶模仿天然细胞外基质,可有效模拟和重建损伤区域内的细胞微环境,促进轴突伸长。③在脊髓损伤后的细胞外调节因子中,促炎因子如肿瘤坏死因子α和白细胞介素1β等加剧了细胞微环境的炎症反应,应用受体抑制剂或阻断相关通路抑制上述促炎因子的表达是一种有效的治疗方法,同时在脊髓微环境中增加白细胞介素10等抗炎因子的表达,抑制损伤区域炎症发展的研究也陆续出现。④最近被重视起来的细胞外囊泡作为传递信息的载体在细胞微环境中也发挥了重要作用。⑤文章揭示了脊髓损伤后细胞微环境中的包括细胞组分和细胞外组分之间的多组相互调控关系,证实了细胞微环境中各组分之间所发挥的神经修复作用并不是孤立的。     

Wg3h细胞系转染PSV_2-neo质粒前后生长特性及表面超微结构改变的研究

本文对转染PSV_2-neo质粒后的Wg3h细胞系(Wg3h-neo)在长期传代中的生长特性和表面超微结构与母系Wg3h细胞进行了比较研究。结果发现:转染后Wg3h细胞的DNA合成及生长速度明显高于母系Wg3h细胞,生长饱和密度增大。在软琼脂培养中不形成集落,接种在裸鼠不长肿瘤。在扫描电镜下,细胞表面的微绒毛较母系Wg3h细胞丰富。Southern印迹杂交实验证明PSV_2-neo质粒已整合到宿主细胞的基因组中。转染后Wg3h细胞的生长特性和表面超微结构均发生了某些转化特征。     

Molecular mechanisms underlying IFN-{gamma}-mediated tumor growth inhibition induced during tumor growth inhibition induced during tumor immunotherapy with rIL-12

The present studnt Investigates the molecular by which IFN-produced as a result of in vitroIL-12 addministration exertsits anty-tumor,rIL-12 was administered three or five times intomice bearing CDA1M fibrosarcoma, OV-HM ovarian carcinoma orMCH-1-A1 fibosarcoma. This regimen induced complete regressionof CSA1M and OV-HM tumors but only transient growth inhibitionof MCH-1-A1 tumors. The anty-tumor effects of Il-12 were associatatedwith enhanced induction of IFN-becouse these effects were abrogatedby pretreatment of hosts with anti-IFN- antibody.Exposure inin vitro of the three types of tumor cells to rIFN- resultedin moderate to potent inhibition of tumor cell growth.IFNstimulatedthe expression of mRNAs for an inducible type of NO synthasa(INOS)in CSA1M cells and indoleamine 2,3-dioxygenasa (IDO),an enzyme capable of degrading tryptophan, in OV-HM cells ,but induced only marginal levels of these mRNAs in MCH-I-ALcells. In association withiNOS gene expression, INF--stimulatedCSA1M cells produced a large amount of NO which functioned toinhibit their own growth in vitro. Although OV-HM and MCH-1-A1cells did not produce NO, they also exhibited NO susceptibility.Whereasthe tumor masses from IL-12-treated CSA1M-bearing mice inducedhigher levels of INOS (for CSA1M) or IDO and iNOS (for OV-HM)mRNAs,the MCH-1-A1 tumor mass expressed lower levels of iNOS mRNAalone.Moreover, massive infiltration of CD4⁺and CD8⁺ T cellsand Mac-1⁺ cells was seen only in the CSA1M and OV-HM tumors.Thus, these results indicate that IFN- produced after IL-12treatment induces the expression of various genes with potentialto modulate tumor cells and growth by acting directly on tumorecells or stimulating tumor-infiltrating lymphold cells and thatthe effectiveness of IL12 therapy is assoiated with the operation if these mechanisms.     

Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage

The bone morphogenetic proteins (BMPs), TGFβ superfamily members, play diverse roles in embryogenesis, but how the BMPs exert their action is unclear and how different BMP receptors (BMPRs) contribute to this process is not known. Here we demonstrate that the two type I BMPRs, BMPR-IA and BMPR-IB, regulate distinct processes during chick limb development. BmpR-IB expression in the embryonic limb prefigures the future cartilage primordium, and its activity is necessary for the initial steps of chondrogenesis. During later chondrogenesis, BmpR-IA is specifically expressed in prehypertrophic chondrocytes. BMPR-IA regulates chondrocyte differentiation, serving as a downstream mediator of Indian Hedgehog (IHH) function in both a local signaling loop and a longer-range relay system to PTHrP. BMPR-IB also regulates apoptosis: Expression of activated BMPR-IB results in increased cell death, and we showed previously that dominant-negative BMPR-IB inhibits apoptosis. Our studies indicate that in TGFβ signaling systems, different type I receptor isoforms are dedicated to specific functions during embryogenesis.     

Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD

Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrP(C)) converts into its pathogenic isoform (PrP(Sc)). While PrP(C) conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrP(Sc) with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrP(Sc) of fCJD(R148H) were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrP(Sc) had similar characteristics. Furthermore, comparison of fCJD(R148H) with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrP(Sc) features of fCJD(R148H).     

Ⅲ型胶原肾小球病的形态学观察

目的了解Ⅲ型胶原肾小球病的形态学改变,并对Ⅲ型胶原可能的细胞来源进行初步探讨。方法对3例肾活检组织进行光镜、免疫荧光、电镜和Ⅰ、Ⅲ、Ⅳ型胶原及d平滑肌肌动蛋白(α-SMA)的免疫组织化学染色(SP法)观察。结果2例患者临床表现为肾病综合征,其中1例伴高血压,第3例表现为肾功能不全和肾性高血压。3例均无肾病家族史。光镜检查可见肾小球基膜内和系膜区弥漫性过碘酸-希夫反应阳性物质沉积,系膜细胞无明显增生。电镜检查在基膜内疏松层和系膜区可见大量胶原纤维沉积,系膜细胞胞膜下平行排列的束状微丝明显增加。免疫组织化学显示这些胶原纤维为Ⅲ型胶原,Ⅰ型和Ⅳ型胶原阴性,同时系膜区多数系膜细胞α-SMA阳性。结论Ⅲ型胶原肾小球病光镜、电镜及免疫组织化学上都有其特殊的病理改变。肾小球内激活的系膜细胞可能是Ⅲ型胶原的来源。     

肿瘤坏死因子与肾小球系膜细胞的关系

目的研究肾小球系膜细胞的肿瘤坏死因子的自分泌功能,肿瘤坏死因子对肾小球系膜细胞作用的机制。方法利用体外培养的人和大鼠的肾小球系膜细胞,通过逆转录－多聚酶链反应、原位杂交和免疫组化方法,探讨它们之间的关系。结果肾小球系膜细胞既可产生肿瘤坏死因子,又有肿瘤坏死因子受体。结论肾小球系膜细胞是肿瘤坏死因子作用的靶细胞,肿瘤坏死因子通过旁分泌和自分泌两种途径作用于肾小球系膜细胞。     

电化学治疗昆明小鼠肉瘤及其机理分析

研究了电化学治疗昆明小鼠肉瘤的疗效,并分析其机理。在体外将S-180细胞用不同参数的电场处理,研究适合电化学治疗的电场条件。通过复制肉瘤模型,将肉瘤小鼠随机分成4组:对照组、电疗组、化疗组、电化疗组。研究了不同处理组的肿瘤抑瘤率、治愈率以及小鼠的自由基代谢水平。结果电化疗组的抑瘤率、治愈率都显著高于化疗组和电疗组(P<0.05),电化疗组小鼠受到氧自由基的攻击显著降低,免疫力提高。分析机理发现,电化学治疗肿瘤的机理可能至少涉及细胞膜通透性提高、细胞的耐药性降低、机体的免疫力提高三个方面。