ABSTRACT
Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.
ABSTRACT
Aim To explore the pharmacological mechanism and the effects of polysaccharide sulfat(PSS) on cardiovascular diseases induced by type 2 diabetes mellitus(DM) through observing the risk factors.Methods Type 2 diabetic animal model was established by high-sugar and high-fat diets,combined with injection of small amount streptozotocin(STZ 20 mg?kg-1,iv).Adult male wistar rats were divided into five groups: normal control group,model group,polysaccharide sulfate group,metformin group and lovastatin group.They were treated with exact medicne for 8 weeks,but control group and model group were treated with 0.9% Nacl.During this process,FBG and serum lipid concentrations were measured.22 weeks later,the rats were sacrificed.The activity of tissue-type plasminogen activator(t-PA) and plasminogen activator inhibitor type-1(PAI-1) were detected by chemical methods.The aortas were collected for histopathlogical,immunohistochemical and Western blot studies.Results FBG concentrations and serum lipid(TC,TG,LDL) levels decreased in PSS group as compared from those of model group(P
ABSTRACT
To achieve the fusion of cranio-jaw-facial CT and MRI image,the single value decomposition-iterative closest point method based on contour feature and the multiresolution method based on wavelet pyramid were used.The results showed that the fusion was operated easily and promptly,its images were satisfactory and its reliability was good. The fusion of cranio-jaw-facial CT and MRI image was obtained. It suggested that the fusion of cranio-jaw-facial CT and MRI image was feasible in clinical practice. It can provide the image basis helping the analysis of diagnosis and treatment for diseases of the cranio-jaw-facial region with complicated anatomical formation.