Hemin acts as CD36 ligand to activate down-stream signalling to disturb immune responses and cytokine secretion from macrophages.

Inflammatory responses to hemin are believed to play an important role in tissue damage and cerebral malaria pathology. Macrophage exposed to hemin exhibits modulation of non-opsonic phagocytosis of aged RBCs, ability to kill bacteria and secretion of cytokines. Immuno-fluorescence study indicates translocation and sequestration of CD36 within the intracellular storage in the hemin treated macrophages. It in-turn modulates the global cytokine secretion from macrophages. CD36 has strong affinity for hemin with a dissociation constant of 1.26±0.24 µM. CD36 has hemin bio-phoric environment involving R292, D372 and Q382. The mutation in biophoric residues significantly reduced the affinity towards hemin. Hemin stimulated MG63 cells (transfected with CD36) showed several folds increment in cytokines TNFα, MCP-1, RANTES and CCL1 and CD36-hemin interaction is crucial for aberrant cytokine secretion. CD-36: Hemin interaction is driving down-stream signalling and subsequent recruitment of adaptor proteins to the cytosolic domain of CD36. Immunoprecipitation of membrane bound CD36 gives Lyn kinase as potential adaptor protein down-stream to CD36: hemin signalling. Interestingly, disruption of Lyn kinase abolishes the hemin mediated dysregulation of immune responses. In summary, hemin-CD36-Lyn kinase signalling axis could be a contribution factor to severe malaria pathology and prognosis.

Multiple function fluorescein probe performs metal chelation, disaggregation, and modulation of aggregated Aß and Aß-Cu complex.

An exceptional probe comprising indole-3-carboxaldehyde fluorescein hydrazone (FI) performs multiple tasks, namely, disaggregating amyloid ß (Aß) aggregates in different biomarker environments such as cerebrospinal fluid (CSF), Aß1-40 fibrils, ß-amyloid lysozyme aggregates (LA), and U87 MG human astrocyte cells. Additionally, the probe FI binds with Cu(2+) ions selectively, disrupts the Aß aggregates that vary from few nanometers to micrometers, and prevents their reaggregation, thereby performing disaggregation and modulation of amyloid-ß in the presence as well as absence of Cu(2+) ion. The excellent selectivity of probe FI for Cu(2+) was effectively utilized to modulate the assembly of metal-induced Aß aggregates by metal chelation with the "turn-on" fluorescence via spirolactam ring opening of FI as well as the metal-free Aß fibrils by noncovalent interactions. These results confirm that FI has exceptional ability to perform multifaceted tasks such as metal chelation in intracellular conditions using Aß lysozyme aggregates in cellular environments by the disruption of ß-sheet rich Aß fibrils into disaggregated forms. Subsequently, it was confirmed that FI had the ability to cross the blood-brain barrier and it also modulated the metal induced Aß fibrils in cellular environments by "turn-on" fluorescence, which are the most vital properties of a probe or a therapeutic agent. Furthermore, the morphology changes were examined by atomic force microscopy (AFM), polarizable optical microscopy (POM), fluorescence microscopy, and dynamic light scattering (DLS) studies. These results provide very valuable clues on the Aß (CSF Aß fibrils, Aß1-40 fibrils, ß-amyloid lysozyme aggregates) disaggregation behavior via in vitro studies, which constitute the first insights into intracellular disaggregation of Aß by "turn-on" method thereby influencing amyloidogenesis.

An anionic conjugated polymer as a multi-action sensor for the sensitive detection of Cu(2+) and PPi, real-time ALP assaying and cell imaging.

A Cu(2+) ensemble polyfluorene derivative, poly[5,5'-(((9H-fluorene-9,9-diyl)bis(hexane-6,1-diyl))bis(oxy))diisophthalate] sodium salt (PFT), displays unprecedented selectivity for PPi (LOD = 2.26 ppb) in aqueous solution as well as in random urine samples at physiological pH vis-a-vis monitoring ALP activity. Furthermore, intracellular imaging of Cu(2+) and PPi in mouse macrophage (J774A.1) and human breast cancer cells (MDA-MB231) was achieved to confirm the viability of PFT in biological systems.