百乐眠胶囊联合艾司西酞普兰片对失眠伴抑郁焦虑患者睡眠质量、不良情绪以及神经递质水平的影响

摘要 目的：探讨百乐眠胶囊联合艾司西酞普兰片对失眠伴抑郁焦虑患者睡眠质量、不良情绪以及神经递质水平的影响。方法：选取2017年7月~2019年12月期间我院收治的失眠伴抑郁焦虑患者117例,将上述患者根据随机数字表法分为对照组（n=58,艾司西酞普兰片治疗）和研究组（n=59,百乐眠胶囊联合艾司西酞普兰片治疗）,比较两组患者睡眠质量、不良情绪、多导睡眠图（PSG）参数、神经递质水平及不良反应。结果：研究组治疗2个月后的临床总有效率为93.22%（55/59）,高于对照组的79.31%（46/58）（P<0.05）。两组治疗2个月后汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）以及匹兹堡睡眠质量指数（PSQI）评分、睡眠潜伏期、P物质（SP）均较治疗前降低,且研究组低于对照组（P<0.05）。两组治疗2个月后睡眠总时间、睡眠效率、神经肽Y（NPY）、5-羟色胺（5-HT）升高,且研究组高于对照组（P<0.05）。治疗期间研究组不良反应发生率较对照组降低（P<0.05）。结论：失眠伴抑郁焦虑患者经百乐眠胶囊联合艾司西酞普兰片治疗后,睡眠质量、不良情绪得到显著改善,同时还可有效改善血清神经递质水平,减少不良反应,临床应用效果确切。     

促凋亡基因Bad在胰腺癌中的调控及靶向治疗研究进展

胰腺癌是一种预后极差的恶性消化道肿瘤,5年生存率小于5%,这与胰腺癌细胞的凋亡异常有着密切的关系。Bad基因是Bcl-2家族中的一种促凋亡基因,被认为可以通过浓度依赖性方式替换Bcl-xL/Bax、Bcl-2/Bax二聚体中的Bax,从而达到促进细胞凋亡、防止胰腺癌的发生。Bad基因在胰腺癌中的调控主要以磷酸化/去磷酸化调控最为常见,研究显示,胰腺癌中Bad表达总量变化不明显,而在Ser112位点上的磷酸化为灭活的pBad112形式表达却明显增多。胰腺癌中过表达的14-3-3sigma、Pim-3、cAMP等均可诱导Bad蛋白磷酸化,而PKC、MAP4K3等可诱导其去磷酸化。同时,针对Bad的靶向治疗在胰腺癌中的应用研究已经有所进展,其中有研究发现人参皂苷Rg3、Cantharidin、Stemonamid等药物均可通过Bad途径促胰腺癌细胞凋亡。对胰腺癌中的Bad的深入研究,有利于了解其与胰腺癌发病机制的关系,为胰腺癌的靶向治疗提供新的方向。     

VEGF, Bcl-2 and Bad regulated by angiopoietin-1 in oleic acid induced acute lung injury

Molecular mechanisms of acute lung injury (ALI) are poorly defined. Our previous study demonstrated that recombinant angiopoietin-1 (Ang1) can protect against oleic acid (OA) induced ALI at an early stage. The purpose of this study was to elucidate whether vascular endothelial growth factor (VEGF), Bcl-2, and Bad, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) play any role in the protective mechanism of recombinant Ang1 in OA-induced ALI. All BALB/C mice were administered a single dose of OA to induce lung injury. Lungs, bronchoalveolar lavage fluid (BALF), and serum were harvested at certain time points. The expression of VEGF, Bcl-2, Bad, PI3K/Akt, and the histological changes in the lung, and the levels of VEGF, IL-6, and IL-10 in serum and BALF were examined. A second cohort of mice was followed for survival for 7 days. We observed increased expression of VEGF in BALF and serum and reduced expression of VEGF in lung tissue. Recombinant Ang1 treatment, however, up-regulated VEGF expression and p-Akt/Akt in lung tissue but down-regulated VEGF expression in BALF and serum. OA led to a decrease of anti-apoptotic marker Bcl-2 and a marked increase of pro-apoptotic marker Bad. Compared with the ALI group, in the recombinant Ang1 treated group, Bcl-2 expression was restored, and Bad expression was clearly attenuated. In addition, recombinant Ang1 attenuated the lung pathological changes and improved the survival of mice. These findings suggest that recombinant Ang1 may be a promising potential treatment for ALI. It seems that VEGF is mediated by PI3K/Akt pathway which is required for Ang1-mediated protection of lung injury. Activation of Akt stimulates expression of Bcl-2 and inhibits the expression of Bad, thus inhibiting the execution of apoptosis.     

PESV 对K562 细胞BCR/ABL 融合基因及凋亡调控因子Bcl-2、Bad 表达的影响

目的:探讨PESV对K562细胞BCR/ABL融合基因及凋亡调控因子bcl-2和bad表达的影响.方法:将体外培养K562细胞,经PESV处理不同时间后,流式细胞术检测细胞凋亡率,荧光定量RT-PCR检测BCR/ABL、Bcl-2、Bad mRNA水平变化.结果:与对照组相比,PESV处理后K562细胞,凋亡率增加,BCR/ABL融合基因表达降低,抗凋亡相关基因Bcl-2 mRNA表达降低,促凋亡基因Bad mRNA表达增加.结论:PESV能降低降低K562细胞BCR/ABL融合基因的表达,可能通过调节Bcl-2和Bad表达,抑制K562细胞增殖,促进其凋亡.     

软骨多糖对L1210白血病小鼠生长抑制作用的研究

目的:研究软骨多糖对L1210白血病小鼠的生长抑制作用,并探讨其抑瘤作用机理。方法:建立DBA/2小鼠L1210腹水瘤模型,将小鼠分为对照组、低剂量组、中剂量组和高剂量组进行实验,通过腹腔注射软骨多糖治疗,每天称重并记录小鼠的生存时间,计算生命延长率。于0h、24h、48h、72h抽取治疗组小鼠的腹水瘤细胞进行细胞周期的分析;采用常规HE染色观察细胞形态学变化;应用免疫荧光方法检测BCL-2和BAD蛋白表达变化,以进一步探讨软骨多糖的抑瘤机制。结果:软骨多糖可以明显提高DBA/2小鼠的生存率;细胞形态学观察可见细胞出现细胞浆浓缩、核固缩及凋亡小体等现象;软骨多糖作用后的L1210细胞,其细胞周期被阻遏于Go/G1期,24h-48h凋亡率迅速上升;Bad蛋白的表达水平于给药24h-72h后升高,抗凋亡基因Bcl-2表达下降。结论:软骨多糖可能通过影响肿瘤细胞周期和Bad、Bcl-2蛋白的表达来诱导L1210细胞凋亡,并显著抑制肿瘤细胞的生长,延长DBA/2小鼠的生存时间,是一种新型的抑癌活性物质。     

Regulation of Prostate Cancer Cell Survival by Protein Kinase C? Involves Bad Phosphorylation and Modulation of the TNFα/JNK Pathway

Protein kinase Cϵ (PKCϵ), a diacyglycerol- and phorbol ester-responsive serine-threonine kinase, has been implicated in mitogenic and survival control, and it is markedly overexpressed in human tumors, including in prostate cancer. Although prostate cancer cells undergo apoptosis in response to phorbol ester stimulation via PKCδ-mediated release of death factors, the involvement of PKCϵ in this response is not known. PKCϵ depletion by RNAi or expression of a dominant negative kinase-dead PKCϵ mutant potentiated the apoptotic response of PMA and sensitized LNCaP cells to the death receptor ligand TNFα. On the other hand, overexpression of PKCϵ by adenoviral means protected LNCaP cells against apoptotic stimuli. Interestingly, PKCϵ RNAi depletion significantly enhanced the release of TNFα in response to PMA and greatly potentiated JNK activation by this cytokine. Further mechanistic analysis revealed that PMA fails to promote phosphorylation of Bad in Ser¹¹² in PKCϵ-depleted LNCaP cells, whereas PKCϵ overexpression greatly enhanced Bad phosphorylation. This effect was independent of Akt, ERK, or p90Rsk, well established kinases for Ser¹¹² in Bad. Moreover, expression of a S112A-Bad mutant potentiated PMA-induced apoptosis. Finally, we found that upon activation PKCϵ accumulated in mitochondrial fractions in LNCaP cells and that Bad was a substrate of PKCϵ in vitro. Our results established that PKCϵ modulates survival in prostate cancer cells via multiple pathways.     

Downregulation of hepatoma-derived growth factor activates the Bad-mediated apoptotic pathway in human cancer cells

Hepatoma-derived growth factor (HDGF) is highly expressed in human cancer and its expression is correlated with poor prognosis of cancer. The growth factor is known to stimulate cell growth while the underlying mechanism is however not clear. Transfection with HDGF cDNA stimulated while its specific antisense oligonucleotides repressed the growth of human hepatocellular carcinoma HepG2 cells. Furthermore, knock-down of HDGF by antisense oligos also induced apoptosis in HepG2 cells and in other human cancer cells, e.g. human squamous carcinoma A431 cells. HDGF knock-down was found to induce the expression of the pro-apoptotic protein Bad and also inactivate ERK and Akt, which in turn led to dephosphorylation of Bad at Ser-112, Ser-136, and activation of the intrinsic apoptotic pathway, i.e. depolarization of the mitochondrial membrane, release of mitochondrial cytochrome c, increase in the processing of caspase 9 and 3. As HDGF knock-down not only suppresses the growth but also induces apoptosis in human cancer cells, HDGF may therefore serve as a survival factor for human cancer cells and a potential target for cancer therapy. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Green tea polyphenol (-) -epigallocatechin-3-gallate promotes the rapid protein kinase C- and proteasome-mediated degradation of Bad: implications for neuroprotection

The aim of the present study was to gain a deeper insight into the cell signaling pathways involved in the neuroprotection/neurorescue activity of the major green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG). EGCG (1 micro m) caused an immediate (30 min) down-regulation (approximately 40%) of Bad protein levels, and a more pronounced reduction after 24 h (55%) in the human neuroblastoma cell line SH-SY5Y. Co-treatment with EGCG and the protein synthesis inhibitor cycloheximide prominently shortened Bad half-life, with as little as 30% of the Bad protein content remaining after 2 h, suggesting an effect of EGCG on Bad protein degradation. Accordingly, the proteasome inhibitors MG-132 and lactacystin damped Bad down-regulation by EGCG. The general protein kinase C (PKC) inhibitor GF109203X, or the down-regulation of conventional and novel PKC isoforms, abolished EGCG-induced Bad decline. However, no inhibition was seen with the cell-permeable myristoylated pseudosubstrate inhibitor of the atypical PKCzeta isoform. The enforced expression of Bad for up to 72 h rendered the cells more susceptible to serum deprivation-induced cell death, whereas EGCG treatment significantly improved cell viability (up to 1.6-fold). The present study reveals a novel pathway in the neuroprotective mechanism of the action of EGCG, which involves a rapid PKC-mediated degradation of Bad by the proteasome.     

口臭微生态治疗技术研究进展

口臭是指呼吸时排出挥发性硫化物等臭味气体,主要由口腔微生态失调引起,具体为生理性菌群数目减少,产臭类菌群种类和数目增加。口臭是局部口腔或全身系统不良代谢状况的一种表现,临床可根据口腔异味来诊断疾病,并通过口腔微生态的调整来治疗口臭。本研究从口臭与微生态的关系、口臭主要相关微生物等方面进行分析,综述机械、化学和中医药等方法调整口腔微生态来治疗口臭的进展。     

N-acetylphytosphingosine-induced apoptosis of Jurkat cells is mediated by the conformational change in Bak

N-acetylphytosphingosine (NAPS), a sphingolipid derivative, is one of the well-known signal molecules that mediates various cellular functions, including cell growth, differentiation, and apoptosis. In this study, we demonstrated that NAPS induces apoptosis of Jurkat cells by activating Bak, but not Bax, which are both members of a proapoptotic subfamily of the Bcl-2 proteins. NAPS activated caspase-8 in a FADD-independent manner, but the lack of caspase-8 did not suppress the activation of caspase-3 and -9 and cell death, indicating that caspase-8 activation does not play an important role in NAPS-induced cell death. The overexpression of Bcl-x_L, an anti-apoptotic protein, completely inhibited the activation of the caspases and apoptosis, assuming that NAPS-induced apoptosis was initiated by the mitochondria. The expression levels of pro- and anti-apoptotic Bcl-2 family members were not changed by the NAPS treatment. However, Bad was translocated from the cytosol into the mitochondria, where it bound to Bcl-x_L, and Bak was dissociated from Bcl-x_L and conformationally changed. Taken together, these findings indicate that NAPS induced apoptosis of Jurkat cells in a mitochondria-dependent manner that was controlled by the translocation of Bad and the conformational change in Bak. These authors contributed equally to this paper