RESUMEN

Chromatography is a technique of separation based on adsorption and/or interaction of target molecules with stationary phases. Herein, we report the design and fabrication of BTDA@SiO2 core-shell microspheres as a new class of stationary phase and demonstrate its impressive performance for chromatographic separations. The silica microspheres of BTDA@SiO2 were synthesized by in situ method with 1,3,5-benzenetricarboxaldehyde and 3,5-diaminobenzoic to separate peptides and proteins on high-performance liquid chromatography. The BTDA@SiO2 core-shell structure has a high specific surface area and retention factor of 4.27 and 8.31 for anionic and cationic peptides, respectively. The separation factor and resolution were high as well. A typical chromatogram illustrated nearly baseline resolution of the two peptides in less than 3 min. The BTDA@SiO2 was also highly stable in the pH range of 1 to 14. Furthermore, the prepared BTDA@SiO2 core-shell material not only be used for chromatographic separation but also as heavy metal removal from water. Using a BTDA@SiO2, we also achieved a lysozyme enrichment with a maximum saturated adsorption capacity reaching 714 mg/g. In summary, BTDA@SiO2 has great application prospects and significance in separation and purification systems.

Asunto(s)

Metales Pesados , Microesferas , Muramidasa , Dióxido de Silicio , Dióxido de Silicio/química , Muramidasa/química , Muramidasa/aislamiento & purificación , Cromatografía por Intercambio Iónico/métodos , Metales Pesados/química , Metales Pesados/aislamiento & purificación , Adsorción , Cromatografía Líquida de Alta Presión , Tamaño de la Partícula , Propiedades de Superficie , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación

RESUMEN

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

RESUMEN

Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need. It is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are presented. Conventional techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA, and tissue dis-tribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information, while methods for characterization of antibody's interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under development. Recent progress in detecting therapeutic antibodies, in particular, the development of methods suitable for illustrating the molecular dynamics, is described here.

RESUMEN

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs' transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.