Caspase-2 Short Isoform Interacts with Membrane-Associated Cytoskeleton Proteins to Inhibit Apoptosis

Caspase-2 (casp-2) is the most conserved caspase across species, and is one of the initiator caspases activated by various stimuli. The casp-2 gene produces several alternative splicing isoforms. It is believed that the long isoform, casp-2L, promotes apoptosis, whereas the short isoform, casp-2S, inhibits apoptosis. The actual effect of casp-2S on apoptosis is still controversial, however, and the underlying mechanism for casp-2S-mediated apoptosis inhibition is unclear. Here, we analyzed the effects of casp-2S on DNA damage induced apoptosis through “gain-of-function” and “loss-of-function” strategies in ovarian cancer cell lines. We clearly demonstrated that the over-expression of casp-2S inhibited, and the knockdown of casp-2S promoted, the cisplatin-induced apoptosis of ovarian cancer cells. To explore the mechanism by which casp-2S mediates apoptosis inhibition, we analyzed the proteins which interact with casp-2S in cells by using immunoprecipitation (IP) and mass spectrometry. We have identified two cytoskeleton proteins, Fodrin and α-Actinin 4, which interact with FLAG-tagged casp-2S in HeLa cells and confirmed this interaction through reciprocal IP. We further demonstrated that casp-2S (i) is responsible for inhibiting DNA damage-induced cytoplasmic Fodrin cleavage independent of cellular p53 status, and (ii) prevents cisplatin-induced membrane blebbing. Taken together, our data suggests that casp-2S affects cellular apoptosis through its interaction with membrane-associated cytoskeletal Fodrin protein.     

重组人IL6／2融合蛋白对6.5Gy照射小鼠造血功能恢复的影响

观察了ｈＦＰＩＬ６／２对６．５Ｇｙγ线照射ＮＩＨ小鼠第１０天造血功能恢复的影响。结果表明：照射小鼠连续４ｄ给予ｈＦＰＩＬ６／２２５０μｇ·ｋｇ－１·ｄ－１,其脾重、ＣＦＵ－８、骨髓有核细胞数及ＣＭ－ＣＦＵ分别比对照组增加５９．０％、２７８．５％、５７．９％和１３８．２％,统计学处理均有显著差异;对此四项指标的改善也明显优于２５μｇ组。另外,２５０μｇ剂量组小鼠外周血象３０ｄ的动态观察结果表明,ｈＦＰＩＬ６／２不但能明显提高红细胞和血红蛋白的最低值,而且能使血小板的恢复提前。提示ｈＦＰＩＬ６／２在促进血小板生成和促进红系造血方面可能具有良好的应用前景。     

1,5-diamino-2-pentyne is both a substrate and inactivator of plant copper amine oxidases.

1,5-diamino-2-pentyne (DAPY) was found to be a weak substrate of grass pea (Lathyrus sativus, GPAO) and sainfoin (Onobrychis viciifolia, OVAO) amine oxidases. Prolonged incubations, however, resulted in irreversible inhibition of both enzymes. For GPAO and OVAO, rates of inactivation of 0.1-0.3 min(-1) were determined, the apparent KI values (half-maximal inactivation) were of the order of 10(-5) m. DAPY was found to be a mechanism-based inhibitor of the enzymes because the substrate cadaverine significantly prevented irreversible inhibition. The N1-methyl and N5-methyl analogs of DAPY were tested with GPAO and were weaker inactivators (especially the N5-methyl) than DAPY. Prolonged incubations of GPAO or OVAO with DAPY resulted in the appearance of a yellow-brown chromophore (lambda(max) = 310-325 nm depending on the working buffer). Excitation at 310 nm was associated with emitted fluorescence with a maximum at 445 nm, suggestive of extended conjugation. After dialysis, the color intensity was substantially decreased, indicating the formation of a low molecular mass secondary product of turnover. The compound provided positive reactions with ninhydrin, 2-aminobenzaldehyde and Kovacs' reagents, suggesting the presence of an amino group and a nitrogen-containing heterocyclic structure. The secondary product was separated chromatographically and was found not to irreversibly inhibit GPAO. MS indicated an exact molecular mass (177.14 Da) and molecular formula (C10H15N3). Electrospray ionization- and MALDI-MS/MS analyses yielded fragment mass patterns consistent with the structure of a dihydropyridine derivative of DAPY. Finally, N-(2,3-dihydropyridinyl)-1,5-diamino-2-pentyne was identified by means of 1H- and 13C-NMR experiments. This structure suggests a lysine modification chemistry that could be responsible for the observed inactivation.     

苯甲醛对果蝇视觉联想记忆的阻断

采用飞行模拟系统,以视觉模式为线索、热惩罚为负强化因子,对于在不同发育时期经受苯甲醛处理过的果蝇的视觉飞行定向条件化进行了检验。苯甲醛气味分别作用于果蝇幼虫和成虫阶段,将阻断果蝇成虫建立视觉联想记忆的能力;雌性果蝇在处女期对苯甲醛气味的接触,会阻断其子代建立视觉联想记忆,这种视觉联想记忆的能力可以通过对其子代连续３代的正常饲养而逐渐得到恢复。     

盐酸右美托咪定联合瑞芬太尼在骨科手术中的应用效果及对呼吸功能的影响

本研究考察了盐酸右美托咪定联合瑞芬太尼(观察组,n=68)和丙泊酚联合瑞芬太尼(对照组,n=68)在我院136例骨科手术患者中的应用效果,应用警觉/镇静观察评分(OAA/S)评价患者用药前(T0)、用药10 min后(T1)、用药20 min后(T2)、用药30 min后(T3)和清醒后(T4)的镇静效果,并比较了两组患者在不同时间点的呼吸频率(RR)、血氧饱和度(SpO2)、心率(HR)和平均动脉压(MAP)。研究结果显示,两组患者在T0、T1和T4时间点的OAA/S评分无统计学差异(p>0.05),观察组在T2和T3时间点的OAA/S评分明显小于对照组(p<0.05)。两组患者在T0、T1和T4时间点的RR无统计学差异(p>0.05),观察组在T2和T3时间点时的RR明显大于对照组(p<0.05)。观察组在T2时间点时的SpO2明显大于对照组(p<0.05)。两组患者的SpO2在其他时间段时无明显差异(p>0.05)。两组患者的HR和MAP均未表现出明显差异(p>0.05)。观察组的不良反应发生率为2.94%,明显高于对照组的11.76%(p=0.049)。本研究结论初步表明,与丙泊酚联合瑞芬太尼相比,盐酸右美托咪定联合瑞芬太尼在骨科手术中具有更好的镇静效果,可有效保障患者的呼吸功能,具有良好的血流动力学稳定性和安全性。     

LncRNA MALAT1 mediates doxorubicin resistance of hepatocellular carcinoma by regulating miR-3129-5p/Nova1 axis

Molecular and Cellular Biochemistry - Drug resistance is one of the major challenges for cancer therapies. In recent years, research on disease-related molecular signaling pathways has become the...     

NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation

ObjectivesNLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied.Materials and methodsWe used ligature‐induced periodontitis models of NLRP3 knockout mice (NLRP3^KO) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm‐Cre/Rosa^nTnG mouse to trace the changes of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro.ResultsHere, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3^KO mice compared with WT littermates, by using ligature‐induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm‐Cre/Rosa^nTnG mice to demonstrate that MCC950 decreases the number of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL‐1β activation and osteoclast differentiation in ligature‐induced periodontitis.ConclusionOur findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation.     

Phytochemical Constituents and Biological Activities of Plants from the Genus Cissampelos

Cissampelos is a significant genus comprising of approximately 21 species of the medicinal plants (Menispermaceae). The plants of this genus are used in traditional medicine for the treatment of various ailments such as asthma, arthritis, dysentery, hyperglycemia, cardiopathy, hypertension and other related problems. These plants are rich in bioactive dibenzylisoquinoline and aborphine as well as small amounts of other ingredients. In recent years, the chemical constituents and pharmacological activities of Cissampelos genus have been paid more and more attention due to their diversity. Herein, we compile the chemical constituents and biological activities on this genus, and summarize the ¹³C-NMR data of the main bioactive ingredients. All information comes from scientific databases such as Google Scholar, PubMed, Sci-Finder, ScienceDirect, Web of Science and CNKI. It provides valuable data for the future research and development of Cissampelos genus.