2,5-Hexanedione induced apoptosis in rat spinal cord neurons and VSC4.1 cells via the proNGF/p75NTR and JNK pathways

Increasing evidence suggests that n-hexane induces nerve injury via neuronal apoptosis induced by its active metabolite 2,5-hexanedione (HD). However, the underlying mechanism remains unknown. Studies have confirmed that pro-nerve growth factor (proNGF), a precursor of mature nerve growth factor (mNGF), might activate apoptotic signaling by binding to p75 neurotrophin receptor (p75NTR) in neurons. Therefore, we studied the mechanism of the proNGF/p75NTR pathway in HD-induced neuronal apoptosis. Sprague–Dawley (SD) rats were injected with 400 mg/kg HD once a day for 5 weeks, and VSC4.1 cells were treated with 10, 20, and 40 mM HD in vitro. Results showed that HD effectively induced neuronal apoptosis. Moreover, it up-regulated proNGF and p75NTR levels, activated c-Jun N-terminal kinase (JNK) and c-Jun, and disrupted the balance between B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Our findings revealed that the proNGF/p75NTR signaling pathway was involved in HD-induced neuronal apoptosis; it can serve as a theoretical basis for further exploration of the neurotoxic mechanisms of HD.     

Can Sophie's Choice Be Adequately Captured by Cold Computation of Minimizing Losses? An fMRI Study of Vital Loss Decisions

The vast majority of decision-making research is performed under the assumption of the value maximizing principle. This principle implies that when making decisions, individuals try to optimize outcomes on the basis of cold mathematical equations. However, decisions are emotion-laden rather than cool and analytic when they tap into life-threatening considerations. Using functional magnetic resonance imaging (fMRI), this study investigated the neural mechanisms underlying vital loss decisions. Participants were asked to make a forced choice between two losses across three conditions: both losses are trivial (trivial-trivial), both losses are vital (vital-vital), or one loss is trivial and the other is vital (vital-trivial). Our results revealed that the amygdala was more active and correlated positively with self-reported negative emotion associated with choice during vital-vital loss decisions, when compared to trivial-trivial loss decisions. The rostral anterior cingulate cortex was also more active and correlated positively with self-reported difficulty of choice during vital-vital loss decisions. Compared to the activity observed during trivial-trivial loss decisions, the orbitofrontal cortex and ventral striatum were more active and correlated positively with self-reported positive emotion of choice during vital-trivial loss decisions. Our findings suggest that vital loss decisions involve emotions and cannot be adequately captured by cold computation of minimizing losses. This research will shed light on how people make vital loss decisions.     

Intrinsic differences in the response of the human lutropin receptor versus the human follitropin receptor to activating mutations

In contrast to the human lutropin receptor (hLHR), very few naturally occurring activating mutations of the structurally related human follitropin receptor (hFSHR) have been identified. The present study was undertaken to determine if one aspect underlying this discrepancy might be a general resistance of the hFSHR to mutation-induced constitutive activity. Five different mutations were introduced into both the hLHR and hFSHR (four based on activating mutations of the hLHR gene, one based on an activating mutation of the hFSHR gene). Our results demonstrate that hFSHR constitutively activating mutants (CAMs) were not as active as hLHR CAMs containing the comparable mutation. Furthermore, although all hFSHR CAMs exhibited strong promiscuous activation by high concentrations of the other glycoprotein hormone receptors, hLHR CAMs showed little or no promiscuous activation. Our in vitro findings are consistent with in vivo observations of known pathophysiological conditions associated with hLHR CAMs, but not hFSHR CAMs, and with promiscuous activation of hFSHR CAMs, but not hLHR CAMs. Computational experiments suggest that the mechanisms through which homologous mutations increase the basal activity of the hLHR and the hFSHR are similar. This is particularly true for the strongest CAMs like L460(3.43)R. Disparate properties of the hLHR versus hFSHR CAMs may, therefore, be due to differences in shape and electrostatics features of the solvent-exposed cytosolic receptor domains involved in the receptor-G protein interface rather than to differences in the nature of local perturbation at the mutation site or in the way local perturbation is transferred to the putative G protein binding domains.     

微载体技术在软骨损伤修复中的应用与展望北大核心CSCD

软骨内部无血管结构、细胞外基质含量高的特点,使软骨组织的自我恢复能力很差。在临床治疗中,轻度的软骨缺损通常采用物理治疗或药物治疗方式,严重者需进行手术治疗。近年来,软骨组织工程技术为治疗软骨缺损提供了新的思路,与传统的手术治疗方式相比,结合软骨组织工程技术进行治疗具有创口小、恢复佳的优点。将微载体技术融入组织工程支架的设计中,可以利用微载体直径小、能够负载多种生长因子的特点,进一步扩展支架功能、促进软骨组织再生。文中首先对微载体技术进行介绍,对近年来微载体的主要制备方式和创新内容进行了概括总结,作为后续介绍的基础内容。然后对应用于软骨修复中的微载体进行了材料和功能上的划分,介绍了不同材料、不同功能微载体的属性特征和在软骨修复方面的具体应用,最后结合该领域发展历程对其今后发展趋势及方向进行展望,并基于笔者团队关于骨软骨一体化层状支架的研究,提出了通过微载体优化层状支架性能的思路,有望制备出更贴合天然软骨结构特征的仿生支架。     

指导学生认识蘑菇的孢子印

蘑菇以其低脂肪高蛋白的品质成为人们日常食用的具有保健功能的上等菜肴,各地农贸市场以及超市均有出售,常见的蘑菇不下20多种,广大学生对此并不陌生。然而学生对蘑菇所产生的用于繁殖的孢子所知甚少,仅听说过孢子,但从未见过。为此,笔者在我系及附中进行生物学课外科技活动辅导时,开展了认识蘑菇孢子印的活动,效果很好。简介如下。     

Down‐regulated HDAC3 elevates microRNA‐495‐3p to restrain epithelial‐mesenchymal transition and oncogenicity of melanoma cells via reducing TRAF5

MicroRNAs (miRNAs) are emerging biomarkers in biological processes and the role of miR‐495‐3p has been identified in melanoma, while the detailed molecular mechanisms remain to be further explored. We aim to explore the effect of histone deacetylase 3 (HDAC3) and miR‐495‐3p on epithelial‐mesenchymal transition (EMT) and oncogenicity of melanoma cells by regulating tumour necrosis factor receptor‐associated factor 5 (TRAF5). Levels of HDAC3, miR‐495‐3p and TRAF5 in melanoma tissues and pigmented nevus tissues were determined, and the predictive roles of HDAC3 and miR‐495‐3p in prognosis of melanoma patients were measured. The melanoma cells were screened and transfected with relative oligonucleotides and plasmids, and the expression of HDAC3, miR‐495‐3p and TRAF5, and phenotypes of melanoma cells were gauged by a series of assays. The relations between HDAC3 and miR‐495‐3p, and between miR‐495‐3p and TRAF5 were confirmed. HDAC3 and TRAF5 were increased while miR‐495‐3p was decreased in melanoma cells and tissues, and the low expression of miR‐495‐3p as well as high expression of HDAC3 indicated a poor prognosis of melanoma patients. Inhibited HDAC3 elevated miR‐495‐3p to suppress EMT and oncogenicity of melanoma cells by reducing TRAF5. HDAC3 particularly bound to miR‐495‐3p and TRAF5 was the target gene of miR‐495‐3p. Our results revealed that down‐regulated HDAC3 elevates miR‐495‐3p to suppress malignant phenotypes of melanoma cells by inhibiting TRAF5, thereby repressing EMT progression of melanoma cells. This study may provide novel targets for melanoma treatment.     

增温对冻土区泥炭沼泽土壤孔隙水甲烷关联微生物和溶解性有机碳的影响

多年冻土区泥炭沼泽土壤孔隙水甲烷关联微生物及底物的研究有助于深入理解气候变化背景下寒区湿地生态系统甲烷循环过程。选取大兴安岭连续多年冻土区柴桦-泥炭藓和狭叶杜香-泥炭藓两种典型植被群落泥炭沼泽,设置开顶箱(Open Top Chamber,OTC)增温实验。于生长季(6月、7月、8月和9月)采集土壤孔隙水样品,对比分析OTC内外土壤孔隙水中产甲烷菌数量、甲烷氧化菌数量及溶解性有机碳(Dissolved Organic Carbon,DOC)浓度的动态变化特征,并探究土壤孔隙水甲烷关联微生物与DOC浓度的关系。结果表明:增温提高了生长季大兴安岭多年冻土区土壤孔隙水中产甲烷菌数量和DOC浓度,而对甲烷氧化菌数量的影响因月份而异。生长季柴桦-泥炭藓和狭叶杜香-泥炭藓泥炭沼泽土壤孔隙水中产甲烷菌数量的平均增加幅度分别为54.52%和44.97%,DOC浓度的平均增加幅度分别为34.16%和28.33%。增温使得生长季柴桦-泥炭藓和狭叶杜香-泥炭藓泥炭沼泽土壤孔隙水中甲烷氧化菌平均数量分别降低了46.20%和31.42%。一元线性回归分析结果表明,土壤孔隙水中DOC浓度可分别解释柴桦-泥炭藓和狭叶杜香-泥炭藓泥炭沼泽土壤孔隙水中产甲烷菌数量变化的29.00%和24.10%(P<0.01),而对两种植被群落下土壤孔隙水中甲烷氧化菌数量的影响并不显著(P>0.05)。     

Cancer targeting gene-viro-therapy for pancreatic cancer using oncolytic adenovirus ZD55-IL-24 in immune-competent mice

Cancer targeting gene-viro-therapy (CTGVT) may prove to be an effective treatment for pancreatic cancer (PC). This study was intended to explore the anti-tumor effect of ZD55-IL-24 (oncolytic adenovirus ZD55 harboring IL-24) on PC in immune-competent mice. The expression of gene harbored by oncolytic adenovirus ZD55 in PC cells was detected by reporter-gene assays. The in vitro anti PC ability of ZD55-IL-24 was tested by MTT, crystal violet staining and apoptosis assays. The in vivo anti PC effect of ZD55-IL-24 was further observed in an immune-competent mice model by detecting anti-tumor immunity and induction of apoptosis. The expression of gene harbored by ZD55 in PC cells was significantly higher than that harbored by the replicated-deficient adenovirus, and the amount of gene expression was time-dependent and dose-dependent. Both ZD55-IL-24 and ZD55 inhibited PC cells growth, but the anti-tumor effect of ZD55-IL-24 was significantly stronger than that of ZD55, and the ability of ZD55-IL-24 in inducing PC apoptosis was significantly stronger than that of ZD55. The tumor-forming rate of group ZD55-IL-24 was the lowest, and the tumor-growing rate was also significantly lower than that of group ZD55 in immune-competent PC models. Moreover, ZD55-IL-24 mediated more anti-cancer immunity effects by induction of stronger T-lymphocytes response to PC cells, higher levels of γ-IFN and IL-6 cytokines. ZD55-IL-24-mediated CTGVT could inhibit PC growth not only by inducing oncolysis and apoptosis but enhancing the anti-cancer immune effects by inducing T cell response to PC and up-regulating γ-IFN and IL-6 cytokine in immune-competent mice. This may serve as a candidate therapeutic approach for the treatment of PC.