Biochemistry of exosomes and their theranostic potential in human diseases.

Exosomes are classified as special extracellular vesicles in the eukaryotic system having diameters ranging from 30 to 120 nm. These vesicles carry various endogenous molecules including DNA, mRNA, microRNA, circular RNA, and proteins, crucial for numerous metabolic reactions and can be proposed as therapeutic or diagnostic targets for several disorders. The donor exosomes release their content to recipient cells and further establish the significant intercellular communication showing biological effects by triggering environmental alterations. Exosomes derived from mesenchymal and dendritic cells have demonstrated their therapeutic potential against organ injury. Yet, various intricacies are involved in exosomal transport and its inclusion in cancer and other disease pathogenesis needs to be explored. The exosomes represent profound potential as diagnostic biomarkers and therapeutic carriers in various pathophysiological conditions such as neurodegenerative diseases, chronic cancers, infectious diseases, female reproductive diseases and cardiovascular diseases. In the current study, we demonstrate the advancements in the implication of exosomes as one of the irrefutable prognostic biological targets in human health and diseases.

A significantly non-toxic novel Cobalt(III) Schiff base complex induces apoptosis via G2-M cell cycle arrest in human breast cancer cell line MCF-7.

AIMS: Metal complexes have ignited considerable interest in the field of chemotherapy after the serendipitous discovery of cisplatin but the severe toxicity of these platinum-based drugs compelled researchers to search for newer, more effective lesser toxic anticancer drugs. MATERIALS AND METHODS: Structural analysis is done by different physicochemical techniques including X-ray single crystallography. Toxicity study has been done in normal Swiss albino mice. MTT assay assessed cell viability. Apoptosis, cell cycle arrest, and cell proliferation were assessed by FACS using Annexin V-PI, PI, and CFSE staining respectively. Western blot quantifies protein expression. While cell migration was studied by wound healing assay. KEY FINDINGS: One-pot synthesis of a novel mononuclear cobalt(III)-Schiff base complex (1) (>99 % purity) and its complete characterization have been done. Cell viability assay showed that 1 (IC50 = 16.81 ± 1.33 µM) exhibits cytotoxicity at much lower concentration in comparison to oxaliplatin (IC50 = 31.4 ± 0.69 µM) against MCF-7 cells for 24 h of therapy without being overly toxic to human PBMCs (IC50 ≥ 60 µM). Additional in vitro studies demonstrated that 1 induces apoptosis via G2-M cell cycle arrest and reduces cell proliferation as well as cell migration in MCF-7 cells. In vivo subacute toxicity (28 days) and systemic chronic toxicity (40 days) studies were carried out in normal Swiss albino mice showed 1 is significantly nontoxic to the host. SIGNIFICANCE: The readily synthesizable, significantly nontoxic cobalt complex with appreciable anticancer activity implies that it might be an effective chemotherapeutic agent for new-age anti-tumor medication.