ABSTRACT
Extracellular vesicles or exosomes are membrane encapsulated biological nanometric particles secreted virtually by all types of cells throughout the animal kingdom. They carry a cargo of active molecules to proximal and distal cells of the body as mechanism of physiological communication, to maintain natural homeostasis as well as pathological responses. Exosomes carry a tremendous potential for liquid biopsy and therapeutic applications. Thus, there is a global demand for simple and robust exosome isolation methods amenable to point-of-care diagnosis and quality control of therapeutic exosome manufacturing. This can be achieved by molecular profiling of the exosomes for use with specific sets of molecular-markers for diagnosis and quality control. Liquid biopsy is undoubtedly the most promising diagnosis process to advance "personalized medicine." Currently, liquid biopsy is based on circulating cancer cells, cell free-DNA, or exosomes. Exosomes potentially provide promise for early-stage diagnostic possibility; in order to facilitate superior diagnosis and isolation of exosomes, a novel platform is developed to detect and capture them, based on localized surface plasmon resonance (LSPR) of gold nanoislands, through strong affinity between exosomes and peptide called Venceremin or Vn96. Physical modeling, based on the characteristics of the gold nanoislands and the bioentities involved in the sensing, is also developed to determine the detection capability of the platform, which is optimized experimentally at each stage. Preliminary results and modeling present a relationship between the plasmonic shift and the concentration of exosomes and, essentially, indicate possibilities for label-free early diagnosis.
ABSTRACT
UNLABELLED: Assessment of antibacterial as well as antiherpes virus activity of sulfonoquinovosyldiacylglyceride (SQDG), a glycolipid, isolated from the leaves of Azadirachta indica has been described. Antimicrobial activity was evaluated against Gram-positive, Gram-negative bacteria and herpes simplex virus. SQDG showed significant inhibitory activity against Salmonella typhi and two isolates of Shigella dysenteriae with MIC values 32 µg ml(-1) , while three isolates of Salm. typhi, Escherichia coli and Vibrio cholerae were inhibited at 64 µg ml(-1) and have shown zone diameter ranging from 6.2 to 12.3 mm. The growth kinetics study of SQDG on Salm. typhi and Sh. dysenteriae revealed that the growths were completely inhibited at their MIC values within 24 h of exposure. Interestingly, SQDG inhibits herpes simplex virus (HSV) type 1 and 2 with the EC50 of 9.1 and 8.5 µg ml(-1) , compared with acyclovir (2.2 and 2.8 µg ml(-1) against HSV-1 and HSV-2). The selectivity index (SI) was found to be 12.4 against HSV-1 and 13.41 with HSV-2. Furthermore, the expression of proinflammatory cytokines of HSV-infected and SQDG-treated macrophages using ELISA kit revealed that SQDG significantly downregulated the production of TNF-α, IL-1ß, IL-12 and IL-6. SIGNIFICANCE AND IMPACT OF THE STUDY: The water-soluble metabolite sulfonoquinovosyldiacylglyceride (SQDG) isolated from Azadirachta indica (Neem) possess significant antibacterial as well as anti-HSV activity. The efficacies as well as the solubility factor of SQDG substantiate a greater attention for its use as phytotherapeutic drug for controlling microbial infections as most consumers have better acceptance of phytomedicines than synthetic drugs.
