The Anti-tumor Nano-drug Carrier System Modified by theNuclear Localization Signal Peptide / 中国生物化学与分子生物学报

Nano-drug carrier systems, as the controllable and targeting tool to deliver drugs, can effectively improve the drug bioavailability, enhance their therapeutic outcomes and reduce side effects, mainly through protecting drugs from rapid enzymatic degradation and blood clearance and ensuring them to be delivered to the targeting sites. The nano-drug carrier system owns broad application prospects in the biomedical field and attracts increasing attention in both functional materials and anti-tumor research. Recently, functional surface modification with functional biomolecules to improve the biocompatibility and drug bioactivity is a hot topic in nano medicine research. The nucleus is the main site of action for manyanti-tumor substances. And nuclear localization signal (NLS) peptides, as a type of functional peptides with nuclear-targeting activity, can penetrate through biological membranes and target the nucleus and is considered to be a universal tool for constructing nano-drug carrier systems. The use of NLS peptides to construct a functionalized nano-drug carrier system with nuclear targeting ability has important application values in the field of anti-tumor therapy. Although the synthesis process of nuclear-targeted functionalized nano-drug carrier system has been developed, due to the high preparation cost and complex synthesis process, there is still a long research process in the successful translation of nuclear-targeted nanocarriers from the experimental stage to the clinical stage. This review mainly focuses on the composition and construction of the nuclear-targeted functionalized nano-drug carrier system, analyzes its nuclear entry methods and conditions, and prospects the development of the anti-tumor nano-drug carrier system in the future based on the current challenges.

"An apoptotic ""Eat Me"" signal: phosphatidylserine exposure" / 中国生化药物杂志

Phosphatidylserine (PS) is a phospholipid that is abundant in eukaryotic plasma membranes,has crucial biological functions.Under cell apoptosis, cells can not generate enough ATP for energy and the concentration of cytoplasmic Ca 2 +increases, resulting in PS eversion.Apoptosis and the clearance of apoptotic cells are essential processes in animal development and homeostasis.For apoptotic cells to be cleared, they must display aneat me signal, most likely PS exposure, which prompts phagocytes to engulf the cells.PS is exposed by the action of scramblase on the cell's surface in biological processes such as apoptosis and platelet activation.Once exposed to the cell surface, PS acts as an eat me signal on dead cells, and creates a scaffold for blood-clotting factors on activated platelets.The molecular identities of the flippase and scramblase that work at plasma membranes have long eluded researchers.Indeed, their identity as well as the mechanism of the PS exposure to the cell surface has only recently been revealed.We describe how PS is exposed in activated platelets and in apoptotic cells, and discuss the clearance of apoptotic cells.

Advancesinstudiesofanti-cancerliposomeswithitspreparationandtargeting / 中国生化药物杂志

In recent years, with the rapid development of antitumor targeted drug therapy, the preparation of antitumor liposomes and its targeting research have attracted attention of scholars. Anti-tumor targeted drug treatment requires the drug to reach the tumor site has a relatively high concentration and longer retention time, the tumor cells have a strong cytotoxic activity, while normal cells no significant side effects.The drug has an in vivo distribution and specificity for the target fine action.The preparation methods of liposomes include film dispersion method,reverse evaporation method,ethanol injection method,supercritical reverse phase evaporation method and freeze-drying method. Antitumor targeting liposomes can be divided into active targeting liposomes and passive targeting liposomes. Targeted liposomes can specifically target tumor cells by recognizing specific targets in the tumor tissue,thus enriching tumor cells and killing tumor cells. In this paper,the preparation of anti-tumor liposomes and the progress of its targeting,for future study and application of liposomes provide a reference.

Construction of cationic anticancer peptide Temporin-1 CEa liposomes and evaluation of anti-breast cancer activity in vitro / 中国生化药物杂志

Objective To constract and evaluate the cationic anticancer peptide Temporin-1CEa liposomes and evaluate anti-breast cancer activity in vitro.Methods The polyethylene glycol (PEG)-modified liposomes containing Temporin-1CEa, one recently discovered cationic anticancer peptide ( CAP) , were constructed by using reverse-phase evaporation method.The encapsulation efficiency, particle size and Zeta potential of the Temporin-1CEa-containing liposomes (Temporin-1CEa-LIP) were characterized.In addition, that had the furhter evaluated of the stability and specific toxicity against human breast cancer MCF-7 cells in vitro.Results The data suggested that the PEG-modified liposomes served a promising drug delivery system for CAPs, those indicated by the encapsulation efficiency was (55.57 ±1.56)%, the particle size was (105.3 ±1.37) nm and the Zeta potential was ( -16.17 ±0.964) mV.Moreover, the in vitro test also indicated that Temporin-1CEa-LIP exerted good stability in serum, and it could be efficiently uptaken by MCF-7 cells.Most importantly, after 24h exposure, Temporin-1CEa-LIP showed toxicity against MCF-7 cells, as potent as Temporin-1CEa. Conclusion The results demonstrates that the PEG-modified liposome is a good drug-delivery system and Temporin-1CEa-LIP could serve as potential anti-tumor candidate for cancer therapy.

Effects of curcumin on sarcoplasmic reticulum Ca2+-ATPase in rabbits with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of curcumin on sarcoplasmic reticulum Ca2+-ATPase in heart failure rabbits.</p><p><b>METHODS</b>Rabbit heart failure model was made with aortic regurgitation and abdominal aorta constriction and 40 rabbits were randomly divided into 4 groups including: (1) heart failure treated with curcumin; (2) heart failure treated with placebo; (3) healthy control treated with curcumin and (4) healthy control treated with placebo. All rabbits were administrated with curcumin capsules or placebo capsules 100 mg x kg(-1) x d(-1), respectively. All groups were sacrificed after eight weeks. Myocardial ultrastructural organization was detected by transmission electron microscope. RT-PCR and Western blot were used to measure the expression of sarcoplasmic reticulum Ca2+-ATPase in mRNA and protein levels, respectively. Malachite green colorimetric assay was used to evaluate the activity of sarcoplasmic reticulum Ca2+-ATPase.</p><p><b>RESULTS</b>All detected parameters were similar between control curcumin group and control placebo group. Compared with the control groups (Groups 3 and 4), the heart/body weight ratio was significantly increased in the heart failure-curcumin group (Group 1) and the heart failure-placebo group (Group 2, all P < 0.05), but the ratio was significantly lower in heart failure-curcumin group than in heart failure-placebo group (P < 0.05). The degree of heart failure was decreased by curcumin. Activity and mRNA and protein expression for sarcoplasmic reticulum Ca2+-ATPase were significantly reduced in the heart failure-placebo group and which could be significantly attenuated by curcumin (all P < 0.05).</p><p><b>CONCLUSION</b>Curcumin could improve cardiac function via upregulating the expression of sarcoplasmic reticulum Ca2+-ATPase in this model.</p>

IL-1beta Acts in Synergy with Endogenous IL-1beta in A375-S2 Human Melanoma Cell Apoptosis Through Mitochondrial Pathway

Interleukin-1beta (IL-1beta) is a pivotal proinflammatory cytokine. To investigate the mechanism of IL-1beta-induced cell death in human malignant melanoma A375-S2 cells, MTT assay, photomicroscopical observation, DNA agarose gel electrophoresis, radioimmunoassay and Western blot analysis were carried out. IL-1beta did not only induce nuclear condensation and DNA fragmentation, but also increased degradation of two substrates of caspase-3, poly ADP-ribose polymerase (PARP) and inhibitor of caspase-activated DNase (ICAD). Simultaneously, release of precursor of IL-1beta (pro-IL-1beta) and endogenous IL-1beta production were involved in the apoptotic process. IL-1beta enhanced the ratio of Bax/Bcl-2 and Bax/Bcl-xL expression and up-regulated apoptosis inducing factor (AIF) expression, which required the activation of downstream caspases. These results suggest that IL-1beta induces endogenous IL-1beta production, enhances cleavage of caspase downstream substrates and promotes mitochondria mediated apoptosis in A375-S2 cells.

Effect of protein kinase C on human melanoma A375-S2 cell death induced by evodiamine / 药学学报

<p><b>AIM</b>To study the role of PKC in evodiamine-induced A375-S2 cell death.</p><p><b>METHODS</b>Ratio of apoptosis induced by evodiamine was determined by TUNEL assay. MTT assay was carried out to assess cytotoxic effect of evodiamine. The influence on expression of ERK, phospho-ERK and Bcl-2 was detected by Western blotting analysis.</p><p><b>RESULTS</b>TUNEL assay indicated that apoptosis was the type of A375-S2 cell death induced by evodiamine treatment for 24 h. Both staurosporine (inhibitor of PKC) and PD98059 (inhibitor of ERK) cooperated with evodiamine to further induce A375-S2 cell death. Evodiamine inhibited PKC activity, down-regulated the expression of ERK, phospho-ERK and Bcl-2, and staurosporine was capable of augmenting these effects induced by evodiamine.</p><p><b>CONCLUSION</b>PKC lies upstream and exhibits regulatory effect on ERK and Bcl-2 in evodiamine-induced cell death.</p>

Human interleukin-1? induces A375-S2 human melanoma apoptosis through caspase pathway / 中国病理生理杂志

AIM: To study the molecular biological mechanism and signal transduction pathway of interleukin-1? (IL-1?)-induced apoptosis in A375-S2 melanoma cells. METHODS: Photomicrocropy showed typical apoptotic changes. The cytotoxic effect of IL-1? in vitro and influences of caspases in this effect were measured by MTT assay. The cytotoxicity of cells was assessed by LDH-based assay. Degradation of DNA was detected by agarose gel electrophoresis. RESULTS: The inhibitory effect of IL-1? on A375-S2 cell growth was in a dose and time-dependent manner, and cell death rate reached more than 90% at 72 h after treatment with 10~(-9)mol/L IL-1?. The inhibitors of caspase-family, -1, -3, -8, -9, and -10, partially blocked cell death at early stage. LDH assay showed that major IL-1?-induced cell death was apoptosis, and in a dose and time-dependent manner. Typical apoptotic DNA ladder was observed in agarose gel electrophoresis. CONCLUSION: IL-1? induced apoptosis in melanoma A375-S2 cells by activating caspase pathway. [

Effect of processing on antitussive, antiasthmatic and diuretic activities of Morrus alba L / 中成药

AIM: To investigate the antitussive and antiasthmatic activities and diuretic activity of Morrus alba L. before and after being processed. METHODS: The antitussive and antiasthmatic activities in vivo (hypersensitivity) and in vitro (functional experiments) of Morrus alba L. before and after being processed were investigated. The diuretic activity of Morrus alba L. before and after being processed also were studied on rat and rabbit models. RESULTS: The processed Morrus alba L. could inhibite histamine-induced airway hypersensitivity. It's diuretic activity was lower but its antitussive activity was better. CONCLUSION: These results indicate that there are some differentes between Morrus alba L. before and after being processed in antitussive, antiasthmatic and diuretic activities. The diuretic activity of crude Morrus alba L. is superior to the processed Morrus alba L. But its antitussive and antiasthmatic activities are inferior to the processed Morrus alba L.