Developmental Temporal Patterns and Molecular Network Features in the Transcriptome of Rat Spinal Cord

The molecular network features of spinal cord development that are integral to tissue engineering remain poorly understood in placental mammals,especially in terms of their relationships with vital biological processes such as regeneration.Here,using a large-scale temporal transcriptomic analysis of rat spinal cord from the embryonic stage to adulthood,we show that fluctuating RNA expression levels reflect highly active transcriptional regulation,which may initiate spinal cord patterning.We also demonstrate that microRNAs(miRNAs)and transcriptional factors exhibit a mosaic profile based on their expression patterns,while differential alternative splicing events reveal that alternative splicing may be a driving force for the development of the node of Ranvier.Our study also supports the existence of a negative correlation between innate immunity and intrinsic growth capacity.Epigenetic modifications appear to perform their respective regulatory functions at different stages of development,while guanine nucleotidebinding protein(G protein)-coupled receptors(including olfactory receptors(ORs))may perform pleiotropic roles in axonal growth.This study provides a valuable resource for investigating spinal cord development and complements the increasing number of single-cell datasets.These findings also provide a genetic basis for the development of novel tissue engineering strategies.

Tβ4 reverses glial polarization and cognitive impairment via negative regulation of NF-κB signaling axis in APP/PSI mice

Tβ4 plays an important role in the control of actin polymerization in eukaryotic cells.While its effect in multiple organs and diseases has being widely investigated,lttle is known about its influence on Alzheimer's disease and the possible mechanisms.Thus,we aimed to evaluate the effects and mechanisms of T94 on glial polarization and cognitive performance in APP/PS1 transgenic mice.Morris water maze test were conducted to assess memory in APP/PS1 mice.Thioflavin S staining,IHC/IF,ELISA,and immunoblotting were performed to explore Aβaccumulation,glial polarization and TLR4/NF-rB axis.We demonstrated that over expression of T94 alone alleviated Aβaccumulation of APP/PS1 mice,reversed microglia and astrocyte polarization and cognitive behavior performance.In addition,Tβ4 could downregulate both TLR4/MyD88/NF-xB p65 and p52 dependent inflammatory pathway.While combination drug of TLR4 antagonist or NF-rB p65 inhibitor exerted no further effects.

Increased MAD2L2 expression predicts poor clinical outcome in Colon Adenocarcinoma

Background:Colon adenocarcinoma(COAD)is the second leading cause of cancer death worldwide thus,identification of COAD biomarkers is critical.Mitotic Arrest Deficient 2 Like 2(MAD2L2)is a key factor in mammalian DNA damage repair and is highly expressed in many malignant tumors.This is a comprehensive study of MAD2L2 expression,its diagnostic value,prognostic analysis,potential biological function,and impact on the immune system of patients with COAD.Methods:Gene expression,clinical relevance,prognostic analysis,diagnostic value,GO/KEGG cluster analysis,data obtained from TCGA,and bioinformatics statistical analysis were performed using the R package.Immune responses to MAD2L2 expression in COAD were analyzed using TIMER.The expression of MAD2L2 in HCT116 cells induced by the inflammatory factor TNF-αwas detected using Western blot.Results:Our results underscore the clinical diagnostic value and potential biological significance of MAD2L2 in patients with COAD.A high level of MAD2L2 expression has been found in COAD and correlated with tumor status and colon polyps.ROC curve analysis showed that MAD2L2 expression has high diagnostic value in COAD.Analysis of immune infiltration results showed that MAD2L2 expression was positively correlated with neutrophil levels.The western blot results demonstrated that MAD2L2 was dose-dependently present with TNF-α.GO/KEGG revealed that MAD2L2 overexpressed and coexpressed genes were mostly involved in biological functions,including hypoxia response,response to reduced oxygen levels,mitochondrial translation elongation,and other processes.Conclusion:MAD2L2 as a new COAD biomarker contributes to our understanding of how alterations in gene expression and the immunological environment contribute to the development of colon cancer.Following further investigation,MAD2L2 may prove to be a viable target factor for clinical diagnosis and therapy of COAD.

罗汉果对雄性小鼠骨髓微核和精子形态的影响

背景:对罗汉果的遗传毒性进行研究,可为其安全使用提供实验依据。目的:观察罗汉果水提液对雄性小鼠骨髓细胞微核率和附睾精子畸形率的影响,了解其是否有遗传毒性。方法:按罗汉果水提液最大使用剂量(3g/mL)和最大灌胃容量(20mL/kg)灌胃小鼠,观察罗汉果水提液的急性毒性。将雄性昆明小鼠随机分为5组,分别灌胃给予30,15,7.5g/kg的罗汉果水煎液、蒸馏水,连续5d;或腹腔注射40mg/kg环磷酰胺。于灌胃第5天,采用骨髓嗜多染红细胞微核试验计算小鼠的骨髓微核率。于首次灌胃后第35天,观察小鼠精子畸形率。结果与结论:罗汉果水提液对昆明小鼠的经口急性毒性最大耐受剂量大于120g/kg。罗汉果水提液30,15,7.5g/kg灌胃后,小鼠的骨髓微核率、精子畸形率与正常小鼠无差异(P>0.05),均明显低于环磷酰胺诱发的骨髓微核率和精子畸形率(P<0.05)。说明罗汉果水提液对成年雄性小鼠无明显遗传毒性。

The β-amyloid protein induces S100β expression in rat hippocampus through a mechanism that involves IL-1

Objective To explore the effect of β-amyloid protein (Aβ) on S100β expression in rat hippocampus and its mechanisms. Methods At 7 days after bilateral stereotaxis injection of different dose of fibrillar Aβ 25-35 and interluekin-1 receptor antagonist (IL-1ra) into the rat CA1 region, the learning and memory abilities of rats were tested with passive avoidance task. Amyloid deposition was detected by using Congo red staining technique. Nissl staining and immunohistochemical techniques were used to analyze the number of neurons, and GFAP and the S100β expression in hippocampal CA1 region , respectively. Results After fibrillar Aβ injection, the step-through latency of rats was significantly shortened compared to that of the control group. The GFAP positive astrocytes were found surrounding amyloid deposition. Neuronal loss occurred in the pyramidal cell layer of CA1 region. The number of S100β positive cells in Aβ-treated group was significantly increased compared with that in the control group. After IL-1ra injection, the number of S100β positive cells was significantly decreased. Conclusion Intrahippocampal injection of Aβ 25-35 could cause similar pathologic changes of Alzheimer's disease. Aβ 25-35 was capable of up-regulating S100β expression in a dose-dependent manner. The injection of IL-1ra could attenuate the effect of Aβ on S100β expression.