Getasew Shitaye

Correction for ‘The protein corona at the nano-bio interface: the need for standardized methodology and opportunities for neurodegenerative disease intervention’ by Getasew Shitaye et al. , RSC Adv. , 2026, 16 , 27424–27452, https://doi.org/10.1039/D6RA01255H.

This review analyzes the protein corona at the nano-bio interface and proposes a standardized methodological framework. We explore how nanoparticles can accelerate or inhibit neurodegenerative pathology, turning the PC into a functional tool.

Type 2 diabetes mellitus (T2DM) can be traditionally treated by edible and medicinal species rich in flavonoids and triterpenoids known for their metabolic benefits. Cucumis prophetarum L. has shown antioxidant and antidiabetic properties in decoction extracts. Since solvent polarity strongly influences the extraction of secondary metabolites, this study investigated the hydroalcoholic extracts of C. prophetarum L. to explore their chemical composition and insulin-sensitizing potential. Hydroalcoholic extracts from the leaf, stem, and root of C. prophetarum L. were analyzed by UV-Vis spectroscopy, ATR-FTIR, and UHPLC-ESI-QqTOF–MS/MS to profile their secondary metabolites. The insulin-sensitizing potential of each extract was assessed using an in vitro model of palmitic-acid-induced insulin resistance in L6 skeletal muscle cells, followed by Western blot analysis of key insulin-signaling proteins. Flavonoid glycosides such as apigenin-C,O-dihexoside, apigenin-malonylhexoside, and luteolin-C,O-dihexoside were abundant in leaf and stem extracts, while cucurbitacins predominated in the root. MTT assay confirmed that hydroalcoholic stem and root extracts of C. prophetarum L. were non-cytotoxic to L6 myotubes, whereas the leaf extract reduced viability only at higher concentrations. Oil Red O staining revealed a pronounced decrease in lipid accumulation following stem and root extract treatment. Consistently, the stem extract enhanced insulin signaling through the activation of the IRS-1/PI3K/Akt pathway, while the root extract primarily modulated the AMPK–mTOR pathway. Importantly, both extracts promoted GLUT4 translocation to the plasma membrane, highlighting their complementary mechanisms in restoring insulin sensitivity. Hydroalcoholic extracts of C. prophetarum L. alleviate insulin resistance through multiple molecular mechanisms, with bioactivity and composition differing markedly from previously reported in the decoctions, which highlight a promising source of insulin-sensitizing phytochemicals and underscore the importance of solvent selection in maximizing therapeutic potential.

Models designed to study protein/metal ion interaction are helpful to provide insights into the rules of metal ion selectivity. In this context, the prokaryotic zinc finger family Ros/MucR offers an example of several naturally occurring homologues binding a structural zinc ion with coordination spheres characterized by different amino acid arrays. In particular, Ros87, the zinc binding domain of the protein Ros from A. tumefaciens, binds Zn(II) with a classical Cys ₂ His ₂ coordination sphere, but most of its homologues show a substitution of the second cysteine by an aspartate. In this study, the binding properties to Zn(II), Co(II) and Cd(II) of the protein Ros87‐C27D, Ros87 mutant with a CysAspHis ₂ coordination sphere, are investigated by means of UV–vis, CD and NMR spectroscopies. Dissociation constants, structural effects and the resulting mechanisms of folding are compared with the wild‐type protein bearing the classical Cys ₂ His ₂ coordination sphere. CysAspHis ₂ coordination sphere induces a two‐state mechanism of folding in the presence of all three different metals, while, differently in the case of Ros87 complexed to Zn(II) or Co(II), the presence of the second cysteine in the coordination sphere leads to the formation of a stable metal binding folding intermediate. Our study underlines how the interplay between the different metal ions and the coordinating amino acid sets is determinant in defining the different Kds and the folding pathway of a given protein.

Long COVID, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), refers to a range of persistent health effects associated with SARS-CoV-2 infection. Long COVID is a complex, multisystem disorder that can affect nearly every organ system and is strongly linked with the incidence of diabetes and other chronic conditions. Increasing evidence also connects persistent SARS-CoV-2 infection with the development of new-onset diabetes and other metabolic disorders. In this review, we assess the current evidence and discuss the incidence of new-onset diabetes, along with the pathobiological mechanisms by which SARS-CoV-2 may contribute to the progression of both new-onset type 1 and type 2 diabetes mellitus (T1DM and T2DM). We summarize the latest understanding of the molecular and cellular mechanisms underlying SARS-CoV-2–associated new-onset diabetes. Potential mechanisms include direct damage to pancreatic β-cells, inflammation, insulin resistance, and autoimmune responses. Dysregulation of the ACE2/renin–angiotensin system (RAS) pathway has been linked to multiple inter-organ pathologies, and increased inflammatory cytokines together with dysregulation of interferon regulatory factors (IRFs)—such as overexpression of IRF1—appear to represent key mechanistic links to widespread tissue damage and metabolic alterations. Moreover, the presence of viral RNA or viral RNA fragments may directly damage pancreatic islets, contributing to insulin resistance and β-cell dysfunction that, in turn, may promote the development of new-onset diabetes. In light of these findings, this review further examines evidence supporting the persistence of SARS-CoV-2 RNA in PASC reservoir tissues, including the pancreas, and its potential association with the development of new-onset diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and impaired beta-cell secretory function. Since existing treatments often present side effects based on different mechanisms, alternative therapeutic options are needed. In this scenario, the present study first evaluates the cytotoxicity of decoctions from the leaves, stems, and roots of Cucumis prophetarum L. on HepG2 and L6C5 cells. The extracts were chemically investigated by UV–Vis and ATR-FTIR spectroscopic techniques and by ultra high-performance chromatographic techniques, coupled with high-resolution mass spectrometry. Briefly, decoctions from the leaves and stems were mainly composed of apigenin C-glycosides, while the root decoction was rich in raffinose and cucumegastigmane II. To evaluate the insulin-sensitizing properties of the extracts in insulin-resistant L6 myoblasts, an evaluation by Western blot analysis of the proteins in the insulin signaling pathway was then performed. Particularly, key proteins of insulin signaling were investigated, i.e., insulin receptor substrate (IRS-1), protein kinase B (PKB/AKT), and glycogen synthase kinase-3 (GSK-3β), which have gained considerable attention from scientists for the treatment of diabetes. Under all conditions tested, the three decoctions showed low cytotoxicity. The stem and root decoction (300 μg/mL) resulted in a significant increase in the levels of p-IRS-1 (Tyr612), GSK3β (Ser9), and p-AMPK (Thr172) compared to those of the palmitic acid-treated group, and the leaf decoction resulted an increase in the level of p-IRS-1 (Tyr612) and p-AMPK (Thr172) and a decrease in p-GSK3β (Ser9) compared to the levels for the palmitic acid-treated group. The root decoction also reduced the level of p-mToR (Ser2448). Overall, the acquired data demonstrate the effect of reducing insulin resistance induced by the investigated decoctions, opening new scenarios for the evaluation of these effects aimed at counteracting diabetes and related diseases in animal models.

Persistence and degradation are important factors in determining the safe use of such synthetic products, and numerous studies have been addressed to develop pesticide remediation methods aimed at ameliorating these features. In this frame, the use of different cyclodextrins (CDs) molecules has attracted considerable attention due to their well-known non-toxic nature, limited environmental impact, and capability to reduce the environmental and health risks of pesticides. CDs appear to be a valuable tool for the elimination of pesticides from polluted areas as well as for better pesticide formulations that positively influence their hydrolysis or degradation. The present work investigates the interaction between β-cyclodextrins and three commonly used pesticides (i.e., chlorpropham, monuron, and propanil) both in solution and in the solid state by means of UV-Vis, FT-IR, and X-ray powder diffractometry. We show that such interactions result in all three cases in the formation of inclusion complexes with a 1:1 stoichiometry and binding constants (K_b) of 369.9 M⁻¹ for chlorpropham, 292.3 M⁻¹ for monuron, and 298.3 M⁻¹ for propanil. We also report the energy-minimized structures in silico for each complex. Our data expand and complement the available literature data in indicating CDs as a low-cost and very effective tool capable of modulating the properties that determine the environmental fate of pesticides.