Effect of electric field on liquid chromatographic separation of peptide digests. Combining capillary separation techniques

A system is described which allows operation of a range of capillary based liquid phase separations including capillary electrophoresis, isocratic and gradient capillary electrochromatography, isocratic and gradient capillary liquid chromatography and electrically assisted gradient capillary liquid chromatography. The system was coupled to electrospray ionization mass spectrometry in the electrically assisted capillary liquid chromatography mode to investigate the effect of applied voltage on the selectivity in peptide mapping separations. Analyses were performed on tryptic digests of recombinant human growth hormone and tissue plasminogen activator. The results show a small but useful effect on selectivity that can be used to fine tune specific separations.     

Synthesis of lipid A derivatives and their interactions with polymyxin B and polymyxin B nonapeptide

Lipid A is the causative agent of Gram-negative sepsis, a leading cause of mortality among hospitalized patients. Compounds that bind lipid A can limit its detrimental effects. Polymyxin B, a cationic peptide antibiotic, is one of the simplest molecules capable of selectively binding lipid A and may serve as a model for further development of lipid A binding agents. However, association of polymyxin B with lipid A is not fully understood, primarily due to the low solubility of lipid A in water and inhomogeneity of lipid A preparations. To better understand lipid A-polymyxin B interaction, pure lipid A derivatives were prepared with incrementally varied lipid chain lengths. These compounds proved to be more soluble in water than lipid A, with higher aggregation concentrations. Isothermal titration calorimetric studies of these lipid A derivatives with polymyxin B and polymyxin B nonapeptide indicate that binding stoichiometries (peptide to lipid A derivative) are less than 1 and that affinities of these binding partners correlate with the aggregation states of the lipid A derivatives. These studies also suggest that cooperative ionic interactions dominate association of polymyxin B and polymyxin B nonapeptide with lipid A.     

Luminescent heteronuclear Au(I)5Ag(I)8 complexes of [1,2,3-C6(C6H4R-4)3]3- (R = H, CH3, But) by cyclotrimerization of arylacetylides

Unusual AuI-AgI heterometallic complexes [Au5Ag8(mu-dppm)4{1,2,3-C6(C6H4R-4)3}(CCC6H4R-4)7]3+ (R = H 1, CH3 2, But 3) were isolated by reactions of polymeric silver arylacetylides (AgCCC6H4R-4)n with binuclear gold component [Au2(mu-dppm)2(MeCN)2]2+ (dppm = bis(diphenylphosphino)methane), in which cyclotrimerization of arylacetylide -CCC6H4R-4 affords trianion {1,2,3-C6(C6H4R-4)3}3- with an unprecedented mu5-bonding mode. Compounds 1(SbF6)3-3(SbF6)3 exhibit intense photoluminescence derived from an MLCT (Au5Ag8 --> CCC6H4R-4) transition, mixed with a metal cluster-centered excited states.     

气溶胶前向散射大气能见度测量系统传递系数的标定及校准方法

分析了气溶胶的前向角散射特性,利用标准的大气透射仪标定前向散射大气能见度测量系统的传递系数。当系统结构发生变化时,传递系数也随之改变,为保证系统测量的准确性和简化系统传递系数的标定过程,提出了一种利用标准漫透射板校准系统传递系数的方法。该方法使用了两块具有相同透射系数的漫透射板,使气溶胶粒子团在前向半球上产生漫散射,此时探测器的测量值即为包含了仪器常数的定值。当系统结构改变时,这个测量值相对于原测量值的变化率作为比例系数代入系统传递系数的计算,实现校准。     

N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats

Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1β and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1β and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment.     

Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling

Leukemia is caused by the malignant clonal expansion of hematopoietic stem cells, and in adults, the most common type of leukemia is acute myeloid leukemia (AML). Autophagy inhibitors are often used in preclinical and clinical models in leukemia therapy. However, clinically available autophagy inhibitors and their efficacy are very limited. More effective and safer autophagy inhibitors are urgently needed for leukemia therapy. In a previous study, we showed that ΔA146Ply, a mutant of pneumolysin that lacks hemolytic activity, inhibited autophagy of triple-negative breast cancer cells by activating mannose receptor (MR) and toll-like receptor 4 (TLR4) and that tumor-bearing mice tolerated ΔA146Ply well. Whether this agent affects AML cells expressing TLR4 and MR and the related mechanisms remain to be determined. In this study, we found that ΔA146Ply inhibited autophagy and induced apoptosis in AML cells. A mechanistic study showed that ΔA146Ply inhibited autophagy by activating mammalian target of rapamycin signaling and induced apoptosis by inhibiting autophagy. ΔA146Ply also inhibited autophagy and induced apoptosis in a mouse model of AML. Furthermore, the combination of ΔA146Ply and chloroquine synergistically inhibited autophagy and induced apoptosis in vitro and in vivo. Overall, this study provides an alternative effective autophagy inhibitor that may be used for leukemia therapy.Subject terms: Translational research, Acute myeloid leukaemia     

Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

Drug resistance is still an obstacle in cancer therapy, leading to the failure of tumor treatment. The emergence of tumor drug resistance has always been a main concern of oncologists. Therefore, overcoming tumor drug resistance and looking for new strategies for tumor treatment is a major focus in the field of tumor research. Natural products serve as effective substances against drug resistance because of their diverse chemical structures and pharmacological effects. We reviewed the signaling pathways involved in the development of tumor drug resistance, including Epidermal growth factor receptor (EGFR), Renin-angiotensin system (Ras), Phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), Wnt, Notch, Transforming growth factor-beta (TGF-β), and their specific signaling pathway inhibitors derived from natural products. This can provide new ideas for the prevention of drug resistance in cancer therapy.