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Nanoparticles (NPs) can modulate protein aggregation and fibril formation in the context of amyloid diseases. Understanding the mechanism of this action remains a critical next step in developing nanomedicines for the treatment or prevention of Parkinson's disease. α-Synuclein (α-Syn) can undergo interactions of different strength with nanoparticles, and these interactions can be prevented by the presence of a protein corona (PC) acquired during the exposure of NPs to serum proteins. Here, we develop a method to attach the PC irreversibly to the NPs, which enables us to study in detail the interaction of α-Syn and polyethylenimine-coated carboxyl-modified polystyrene NPs (PsNPs-PEI) and the role of the dynamics of the interactions. Analysis of the kinetics of fibril formation reveals that the NPs surface promotes the primary nucleation step of amyloid fibril formation without significantly affecting the elongation and fragmentation steps or the final equilibrium. Furthermore, the results show that even though α-Syn can access the surface of NPs that are precoated with a PC, due to the dynamic nature of the PC proteins, the PC nevertheless reduces the acceleratoring effect of the NPs. This effect is likely to be caused by reducing the overall amount of weakly interacting α-Syn molecules on the NP surface and the access of further α-Syn required for fibril elongation. Our experimental approach provides microscopic insight into how serum proteins can modulate the complex interplay between NPs and amyloid proteins.

Functional amyloids are highly organized protein/peptide structures that inter alia promote biofilm formation in different bacteria. One such example is provided by a family of 20-45 residue-long peptides called phenol-soluble modulins (PSMs) from Staphylococcus aureus. External components such as eukaryotic host proteins, which alter self-assembly of bacterial amyloids, can affect the biofilm matrix. Here, we studied the effect of the highly prevalent human plasma protein fibrinogen (Fg) on fibrillation of PSMs. Fg inhibits or suppresses fibrillation of most PSMs tested (PSMα1, PSMβ1, and PSMβ2) except for PSMα3, whose already rapid aggregation is accelerated even further by Fg but leads to amorphous β-rich aggregates rather than fibrils. Fg also induces PSMβ2 to form amorphous aggregates and diverts PSMα1 into off-pathway oligomers which consist of both Fg and PSMα1 and cannot seed fibrillation. Peptide arrays showed that Fg bound to the N-terminus of PSMα1, while it bound to the entire length of PSMα3 (except the C terminus) and to the C-termini of PSMβ1 and PSMβ2. The latter peptides are all positively charged, while Fg is negatively charged at physiological pH. The positive charges complement Fg's net negative charge of -7.6 at pH 7.4. Fg's ability to inhibit PSM fibrillation reveals a potential host-defense mechanism to prevent bacterial biofilm growth and infections in the human body.

Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it is a challenging undertaking and typically relies on recombinant proteins and site-specific conjugations. The scope and utility of this nature-inspired methodology would be broadened tremendously by the advent of facile, scalable techniques in glycosylation, which are currently missing. In this work, we investigated a one-pot aqueous protocol to achieve indiscriminate, surface-wide glycosylation of the surface accessible amines (lysines and/or N-terminus). We reveal that this approach afforded minimal if any change in the protein activity and recognition events in biochemical and cell culture assays, but at the same time provided a significant benefit of stabilizing proteins against aggregation and fibrillation - as demonstrated on serum proteins (albumins and immunoglobulin G, IgG), an enzyme (uricase), and proteins involved in neurodegenerative disease (α-synuclein) and diabetes (insulin). Most importantly, this highly advantageous result was achieved via a one-pot aqueous protocol performed on native proteins, bypassing the use of complex chemical methodologies and recombinant proteins.

In this paper, we propose a new field effect (FE) sensor for fast detection of glycated albumin (GA) based on thiol modified aptamer (TMA). A p-type Si/ (100 nm) SiO2 wafer was used, where the SiO2 layer acts as the gate insulator. This gate insulator is then decorated with a layer of randomly oriented ZnO nanorods, coated with 40 nm of Au to act as binding sites for the TMA. We have shown that the addition of GA significantly reduces the conductivity of the p-type Si channel, which can be used to determine the GA concentration in the test solution. The ZnO/Au/TMA/GA layer can induce negative charges in the Si channel underneath the gate insulator, which is followed by the depletion of the positively charged carriers of the Si, decreasing the conductivity. Accordingly, the charge carriers in the Si channel show a steady decline with increasing GA concentration. We have shown that this decrease in conductivity can be further tuned by varying the gate voltage. The sensor presented here can be used as a fast and reliable sensor for determination of GA.

Aggregation of the 140-residue protein α-synuclein (αSN) is a key factor in the etiology of Parkinson’s disease. Although the intensely anionic C-terminal domain (CTD) of αSN does not form part of the amyloid core region or affect membrane binding ability, truncation or reduction of charges in the CTD promotes fibrillation through as yet unknown mechanisms. Here, we study stepwise truncated CTDs and identify a threshold region around residue 121; constructs shorter than this dramatically increase their fibrillation tendency. Remarkably, these effects persist even when as little as 10% of the truncated variant is mixed with the full-length protein. Increased fibrillation can be explained by a substantial increase in self-replication, most likely via fragmentation. Paradoxically, truncation also suppresses toxic oligomer formation, and oligomers that can be formed by chemical modification show reduced membrane affinity and cytotoxicity. These remarkable changes correlate to the loss of negative electrostatic potential in the CTD and highlight a double-edged electrostatic safety guard.

Herein, an electrochemical label-free biosensor designed for the detection of glycated albumin (GA) using reduced graphene oxide/Au nanoparticles (RGO/AuNPs) modified by anti-GA aptamer. For fast and simple modification of the electrode, the aptamer chain was thiolated. Transition electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) techniques were used to the characterization of synthesized materials. Structural analysis of nanomaterials shows that graphene sheets were synthesized very fine by average thickness of 2.5 nm and Au nanoparticles distributed on the surface of graphene sheets uniformly. Cyclic voltammetry (CV) square wave voltammetry (SWV) and impedance spectroscopy (EIS) were used to electrochemical study of the decorated electrode. Electrochemical studies described the potential of fabricated rGO/AuNPs-aptamer electrode to selectively determine GA properly in buffer solution at the range of 2–10 μg mL−1 by the detection limit of 0.07 μg. mL−1 for GA.

The interaction of reducing sugars with proteins leads to the formation of advanced glycation end products (AGE) and reactive oxidative species (ROS). ROS peroxidise free or membrane included unsaturated fatty acids, leading to generate reactive aldehydes as advanced lipid peroxidation end products (ALE). Aldehydes from lipid peroxidation (LPO) react with proteins to cause alteration of protein structure to exacerbate complication of diseases. Here we studied serum albumin glycation in the presence and absence of liposomes as a bio-membrane model to investigate protein structural changes using various techniques including intrinsic and extrinsic fluorescence spectroscopies and electron microscopy analysis. Accordingly, serum albumin glycation and fibrillation were accelerated and intensified in the presence of liposomes through a hypothesized glycation-peroxidation loop (GPL). Together, our results shed light on the necessity of reconsidering diabetic protein glycation to make it close to physiological conditions mimicry, more importantly, proteins structural change due to diabetic glycation is intensified in the proximity of cell membranes which probably potentiates programmed cell death distinct from apoptosis.

Ethnopharmacological relevance Complementary and alternative medicine has been increasingly used to treat chronic illnesses, such as diabetes mellitus. However, various limitations in terms of their application and efficacies exist. Furthermore, there is still much to be done to discover the right herbal medicine for diabetes. Aim of the study This paper aims to evaluate previous herbal studies on the management of diabetes mellitus, to address their strengths and weaknesses and propose a general framework for future studies. Approach and methods Data sources such as PubMed, ScienceDirect, Scopus, SpringerLink, and Wiley were searched, limited to Iran, using 36 search terms such as herbal, traditional, medicine, and phytopharmacy in combination with diabetes and related complications. Reviewed articles were evaluated regarding the use of botanical nomenclature and included information on (1) identity of plants and plant parts used, (2) the processing procedure, and (3) the extraction process. The main outcomes were extracted and then surveyed in terms of the efficacies of herbs in the management of diabetes mellitus. Then a comparative study was performed between Iranian and non-Iranian studies with respect to herbs best studied in Iran. Results Of the 82 herbs studied in Iran, only six herbs were endemic and 19 were studied in detail. Although most of the reviewed herbs were found to decrease the level of blood glucose (BG) and/or glycated hemoglobin (HbA1C) in both Iranian and non-Iranian studies, information on their pharmacological mechanisms is scarce. However, the level of HbA1C was measured in a limited number of clinical trials or animal studies. Available information on both short- and long-term use of studied herbs on diabetes related complications and functions of involved organs as well as comorbid depression and/or simultaneous changes in lifesyle is also insufficient. Furthermore, little or no information on their phytochemical, toxicological, and herb–drug interaction properties is available. It is worth noting that the efficacy of the reviewed herbs has been studied scarcely in both humans and animals regarding both Iranian and non-Iranian studies. A significant number of reviewed articles failed to cite the scientific name of herbs and include information on the processing procedure and the extraction process. Conclusions Treatment of diabetes mellitus as a multifactorial disease using herbal medicines requires a comprehensive approach. In order to discover the right herbal medicine for the management of diabetes many other important factors than the levels of BG, HbA1C and insulin should be considered. According to our criteria, all the reviewed herbs suffered from inadequate investigation in human, animal and in vitro models in this respect, whereas they are worth investigating further. However, more research on endemic plants and the traditional history of herbal medicine is warranted. In our opinion, the pharmacological, toxicological, and phytochemical information should be obtained before clinical trials. Furthermore, information such as botanical scientific nomenclature, side effects, and toxicity will improve the quality and validity of publications in herbal research. In particular, designing a database covering all valid information about herbs and/or diseases will decrease unnecessary costs and increase the efficiency of research.

The use of herbal medicine has been faced with a huge welcome by patients and scientists, as well as drug industries. It seems that reducing the time of research, economizing investments with better safety, and conducting high-quality botanical research are essential and indispensable. This study aimed to introduce the first reciprocal herb-disease encyclopedia and to recount some of the salient points of herbal research based on Iranian studies. A search limited to Iran was conducted using 36 search terms in the data banks Pubmed, Scopus, ScienceDirect, Wiley, and SpringerLink up to the end of 2012. Data including the investigated disease(s) and common and scientific names of the investigated herbs were extracted from the titles and abstracts of 1310 articles. Investigated subjects and diseases have been categorized in 18 groups: cancer, cardiovascular, cellular-molecular, embryology, endocrinology, genito-urology, gastrointestinal, gynecology, immunology, infectious, metabolism, mucocutaneous, musculoskeletal, neuroscience, ophthalmology, renal, reproductive, and respiratory topics. Herbs including Crocus sativus L., Allium sativum L., and Zataria multiflora Boiss from totally 560 studied herbs were the most studied ones. Only 69 of 560 studied (12.5%) herbs were endemic to Iran. Due to the vast majority of information available for herbs and diseases, an herb-disease encyclopedia comes to the help of herbal researchers and enthusiasts to find that which herb is useful or recommended for which kind(s) of health problems, and/or for the management, pretreatment or treatment of a specific disease or disorders.