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Prostate cancer is one of the most frequently diagnosed cancers. In this study, a prostate cancer-specific aptamer, Wy5a, was conjugated to polyethylenimine (PEI) with a polyethylene ...glycol (PEG) linker for prostate cancer-specific gene delivery. PEI-PEG-AS1411 was synthesized as a non-specific control. PEI-PEG-Wy5a formed complexes with plasmid DNA in a spherical form with a diameter of 70nm and a positive surface-charge. In transfection assays, PEI-PEG-Wy5a had higher gene delivery efficiency to PC-3 prostate cancer cells than did PEI-PEG or PEI-PEG-AS1411, but not in other types of cells. The results suggest that PEI-PEG-Wy5a may be useful for prostate cancer-specific gene delivery.
Simultaneous visualization of numerous proteins in cells and tissues is fundamental for understanding their diversity and dynamics and to address the heterogeneity of human diseases. Despite the many ...advantages of multiplex analysis, current methods typically rely upon immunohistochemistry, which can only be used to detect a few proteins. The exceptional optical properties of nanoparticles (NPs) have improved multiplex imaging in cells and tissues. Here, we review recent advances in multiplex imaging-based molecular diagnosis using antibody-conjugated NPs (immuno-NPs). With the aim of furthering development, we anticipate that NP-based multiplex imaging techniques will complement classical immunohistochemistry methods and provide insight into the biological diversity of cells and tissues.
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade the extracellular matrix (ECM) and regulate the extracellular microenvironment. Despite the significant role that MMP ...activity plays in cell-cell and cell-ECM interactions, migration, and differentiation, analyses of MMPs in vitro and in vivo have relied upon their abundance using conventional immunoassays, rather than their enzymatic activities. To resolve this issue, diverse nanoprobes have emerged and proven useful as effective activity-based detection tools. Here, we review the recent advances in luminescent nanoprobes and their applications in in vitro diagnosis and in vivo imaging of MMP activity. Nanoprobes with the purpose of sensing MMP activity consist of recognition and detection units, which include MMP-specific substrates and luminescent (fluorescent or bioluminescent) nanoparticles, respectively. With further research into improvement of the optical performance, it is anticipated that luminescent nanoprobes will have great potential for the study of the functional roles of proteases in cancer biology and nanomedicine.
Tubulysins are a group of bioactive secondary metabolites from myxobacteria exhibiting strong anticancer activity against various cancer cell lines. In this study, we describe the identification of ...putative tubulysin biosynthetic gene clusters (tubA~tubF) in the genome sequences of two tubulysin-producing myxobacterial strains, Archangium gephyra MEHO_002 and MEHO_004. The inactivation of the putative tubulysin biosynthetic genes resulted in a tubulysin-production defect. The DNA sequences of the A. gephyra MEHO_002 and MEHO_004 tubulysin biosynthetic genes were 97% identical, and the amino acid sequences of the encoded proteins shared a similarity of 97−100%. The nucleotide sequences of the tubulysin biosynthetic gene clusters in MEHO_002 and MEHO_004 were 86% identical to that in Cystobacter sp. SBCb004 known as a tubulysin-producing myxobacterium, and the organization of the clusters was identical except for the lack of a tubZ gene in the clusters in MEHO_002 and MEHO_004. The amino acid sequences of the proteins encoded by each gene were 88-97% similar to those encoded by SBCb004, and the domain compositions of the proteins were also identical. KCI Citation Count: 0
Tubulysins are a group of secondary metabolites produced by myxobacteria that inhibit the function of the eukayotic cytoskeleton. We developed a pair of PCR primers that specifically amplified ...tubulysin biosynthetic genes. Using these primers, eight out of the eighty-one strains of myxobacteria belonging to the Cystobacteraceae family that harbored putative tubulysin biosynthetic genes were screened through PCR analysis. The selected strains included two Archangium gephyra, two Stigmatella sp., two Vitiosangium cumulatum, and two unidentified myxobacteria. LC-MS analysis of the culture extracts from the selected strains revealed that A. gephyra KYC4066 produced putative tubulysin A and B. KCI Citation Count: 1
The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) ...(PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.
Acteoside, an active phenylethanoid glycoside, has been used traditionally as an anti-inflammatory agent. The molecular mechanism by which acteoside reduces inflammation was investigated in ...lipopolysaccharide (LPS)-induced Raw264.7 cells and in a mouse model of cecal ligation and puncture (CLP)-induced sepsis.
In vitro
, acteoside inhibits high mobility group box 1 (HMGB1) release and iNOS/NO production and induces heme oxygenase-1 (HO-1) expression in a concentration-dependent manner, while HO-1 siRNA antagonizes the inhibition of HMGB1 and NO. The effect of acteoside is inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and Nfr2 siRNA, indicating that acteoside induces HO-1
via
p38 MAPK and NF-E2-related factor 2 (Nrf2).
In vivo
, acteoside increases survival and decreases serum and lung HMGB1 levels in CLP-induced sepsis. Overall, these results that acteoside reduces HMGB1 release and may be beneficial for the treatment of sepsis.
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