Transthyretin (TTR) aggregation via misfolding of a mutant or wild-type protein leads to systemic or partial amyloidosis (ATTR). Here, we utilized variable biophysical assays to characterize two distinct aggregation pathways for mTTR (a synthesized monomer TTR incapable of association into a tetramer) at pH 4.3 and also pH 7.4 with agitation, referred to as mTTR aggregation and fibrillation, respectively. The findings suggest that early-stage conformational changes termed monomer activation here determine the aggregation pathway, resulting in developing either amorphous aggregates or well-organized fibrils. Less packed partially unfolded monomers consisting of more nonregular secondary structures that were rapidly produced via a mildly acidic condition form amorphous aggregates. Meanwhile, more hydrophobic and packed monomers consisting of rearranged β sheets and increased helical content developed well-organized fibrils. Conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with leucine and glutamine (L-SPIONs and G-SPIONs in order) via a trimethoxysilane linker provided the chance to study the effect of hydrophobic/hydrophilic surfaces on mTTR aggregation. The results indicated a powerful inhibitory effect of hydrophobic L-SPIONs on both mTTR aggregation and fibrillation. Monomer depletion was introduced as the governing mechanism for inhibiting mTTR aggregation, while a chaperone-like property of L-SPIONs by maintaining an mTTR native structure and adsorbing oligomers suppressed the progression of further fibril formation.

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Background: There is a growing demand for mass production of shikalkin (a natural pigment consisted of shikonin and alkannin) due to its increasing applications in cosmetics, pharmaceutical and nutrition industries. The root of Iranian Arnebia euchroma produces shikalkin. The promising capability of this plant for shikalkin production has already been demonstrated in cell culture studies. Objectives: Elicitation effect of Rhizoctonia solani (R. solani) in comparison with the effects of Cu 2+ , methyl jasmonate (MJ), and salicylic acid (SA) on the shikalkin production was investigated in A. euchroma callus. Materials and Methods:The calli from different origins (leaf, collar and root) were proliferated on a modified LinsmaierSkoog (mLS) medium and were subsequently transferred onto the pigment production medium containing various amounts of the desirable elicitor. Observations were quantified and the pigment production was precisely measured spectrophotometrically. Results: Pigment biosynthesis was induced on White medium containing IAA (1 μM) and kinetin (10 μM) in dark at 25°C. Use of R. solani increased the pigment production by 7 fold greater than normal White medium. Cu 2+ only doubled the shikalkin production. MJ and SA showed enhancing effects comparable to that of Cu 2+ . Discussions: It is assumed that upon binding of the polysaccharides of the fungal cells to the plant cell surface, a cascade of signaling is initiated that led to expression of genes involving in the biosynthesis of shikalkin.