P38 mitogen-activated protein kinases (p38 MAPK, p38) consist of 4 subunits: p38α, p38β, p38γ and p38δ. They play a well-recognized role in regulating intracellular signaling transduction in mammalian cells. p38 MAPK induces a variety of intracellular responses associated with neuropathic pain and other chronic pain. Thus, specific targeting p38 MAPK molecule and its signaling pathway represent potential therapeutic strategies for pain management. Based on the understanding of the crystal structure, biological functions and its signaling pathway of p38 MAPK, chemically synthesized p38 MAPK inhibitors have become available. Natural products and biological components may also serve as potential p38 MAPK inhibitors. To this end, we will evaluate their potential for chronic pain management.
6 June 2015 in Current Pharmaceutical Biotechnology
Recombinant adeno-associated virus (rAAV) vector is one of the promising delivery tools for gene therapy. Currently, hundreds of clinical trials are performed but the major barrier for clinical application is the absence of any ideal large scale production technique to obtain sufficient and highly pure rAAV vector. The large scale production technique includes upstream and downstream processing. The upstream processing is a vector package step and the downstream processing is a vector purification step. For large scale downstream processing, the scientists need to recover rAAV from dozens of liters of cell lysate or medium, and a variety of purification strategies have been developed but not comprehensively compared till now. Consequently, this review will evaluate the scalable downstream purification strategies systematically, especially those based on the physicochemical properties of AAV virus, and attempt to find better scalable downstream strategies for rAAV vectors.
11 March 2016 in Journal of Zhejiang University-SCIENCE B
Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. i
In this paper, near-infrared emitting long-persistence luminescent Zn3Ga2Ge2O10:Cr3+ (ZGG) nanoparticles with diameters of 30–100 nm and bright luminescence were prepared by a sol–gel synthesis method. After the surface amination, the nanoparticles were further bioconjugated with breast cancer-specific monoclonal antibody (anti-EpCAM) to form ZGG-EpCAM nanoprobes which can specifically target breast cancer cell lines (MCF7) in vitro. The results of in vitro images show that the luminescence signals from the cells treated with ZGG-EpCAM nanoprobes are stronger than those from cells treated with ZGG-unconjugated antibody, indicating that the prepared ZGG-EpCAM nanoprobes possessed excellent specific recognition capability. Furthermore, due to their long afterglow properties, the imaging could persist more than 1 h. Therefore, these nanoprobes could not only provide a high specificity detection method for cancer cells but also realize the long-time monitoring. Developed near-infrared emitting long-persistence luminescent nanoprobes will be expected to find new perspectives for cell therapy research and diagnosis applications.
Elizabethkingia anophelis, originally discovered from Anopheles mosquito gut, is an emerging pathogen, especially in immunocompromised patients. We isolated two strains of E. anophelis from two separate patients with multiple organ dysfunction syndrome and lower respiratory tract infection. In this paper, we reviewed the status of E. anophelis infection and its antibiotics resistance from reported cases.
Elizabethkingia anophelis 12012‐2 PRCM was isolated from a patient with multiple organ dysfunction syndrome and lower respiratory tract infection in China. Minimum inhibitory concentration (MIC) analysis demonstrated that it was resistant to 20 antibiotics including trimethoprim/sulfamethoxazole and ciprofloxacin, which were effective for the elimination of other Elizabethkingia infections. To investigate multidrug resistance and pathogenicity mechanisms, we analyzed genome features of 12012‐2 PRCM and compared them to the other Elizabethkingia species. The draft genome size was 4.02 Mb with a GC content of 32%, comparable to that of other E. anophelis strains. Phylogenetic analysis showed that E. anophelis 12012‐2 PRCM formed a sister group with E. anophelis 502, distinct from clades formed by other clinical and environmental E. anophelis isolates. E. anophelis 12012‐2 PRCM contained multiple copies of β‐lactamase genes as well as genes predicted to function in antimicrobial efflux. It also contained 92 genes that were potentially involved in virulence, disease, and defense, and were associated with resistance and pathogenicity. Comparative genomic analysis showed high homology among three clinical and two environmental E. anophelis strains having a variety of similar antibiotic resistance and virulence factor genes, and similar genomic structure. Applications of this analysis will contribute to understanding the antibiotic resistance and pathogenic mechanisms of E. anophelis infections, which will assist in the management of infections as it increases in prevalence.