The impact of concurrent training and antioxidant supplementation on the factors associated with the ocular lens opacity in diabetic rats.

The current study was aimed to investigate the protective effect of vitamins C and E (VCE) supplementation, exercise, and their concurrent application against cataract incidence in the diabetic rats. The obtained results indicated that different supplementation and training treatments were capable to preserve the lens transparency in the diabetic rats. Also, upon applying different supplementation and training treatments, the level of glutathione (GSH) and activity of antioxidant enzymes in the diabetic rats was preserved approximately close to their control levels. In addition, different treatments were capable to maintain the structural integrity of the lens proteins in diabetic rats. Moreover, VCE supplementation, exercise and their simultaneous application prevented lens crystallins of diabetic rats against fibrillation and formation of the increased oligomeric sizes. The results of this study signify the importance of antioxidant supplementation and exercise in reducing the detrimental effects of hyperglycemia on the eye lenses.

Single-chain antibody-decorated Au nanocages@liposomal layer nanoprobes for targeted SERS imaging and remote-controlled photothermal therapy of melanoma cancer cells.

The development of theranostic platforms combining surface-enhanced Raman spectroscopy (SERS) imaging with NIR-stimulated photothermal therapy (PTT) is of utmost importance for the precise diagnosis and selective treatment of cancers, especially in superficial solid tumors. For this purpose, a versatile theranostic nanoprobe of liposomal layer-coated Au nanocages (AuNCs) was decorated with an anti-MUC18 single-chain antibody (scFv). 4-mercapto benzoic acid (p-MBA)-labeled AuNCs (p-AuNCs) were coated by a liposomal layer (p-AuNCs@lip), followed by conjugating anti-MUC18 scFv via post-insertion method to form immuno-liposomal layer-coated AuNCs (p-AuNCs@scFv-lip). Physicochemical characterizations of the p-AuNCs@scFv-lip were investigated by transmission electron microscopy (TEM) and UV-vis and Raman spectroscopy. Furthermore, the targeting ability and theranostic efficiency of the nanoprobe were evaluated for specific diagnosis and treatment of cancerous melanoma cells by flow cytometry, SERS mapping, and live/dead assay. The formation of lipid layer on p-AuNCs surface was confirmed by TEM imaging. After decorating the liposomal layer with scFv, a relevant red shift was observed in the UV-vis spectrum. Moreover, p-AuNCs@lip presented characteristic peaks in the Raman spectrum, which exhibited only a minor change after scFv conjugation (p-AuNCs@scFv-lip). Interestingly, the cellular uptake of AuNCs@scFv-lip by A375 cell line (MUC18+) showed a 24-fold enhancement compared with SKBR3 cells (MUC18-). AuNCs@scFv-lip specifically identified A375 cells from SKBR cells via SERS mapping and effectively killed A375 cells through the PTT mechanism. Taken together, this theranostic platform can provide a promising tool for both in situ diagnosis and remote-controlled thermal ablation of cancer cells.

Isolation of Cysteine-Rich Peptides from Citrullus colocynthis.

The plant Citrullus colocynthis, a member of the squash (Cucurbitaceae) family, has a long history in traditional medicine. Based on the ancient knowledge about the healing properties of herbal preparations, plant-derived small molecules, e.g., salicylic acid, or quinine, have been integral to modern drug discovery. Additionally, many plant families, such as Cucurbitaceae, are known as a rich source for cysteine-rich peptides, which are gaining importance as valuable pharmaceuticals. In this study, we characterized the C. colocynthis peptidome using chemical modification of cysteine residues, and mass shift analysis via matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. We identified the presence of at least 23 cysteine-rich peptides in this plant, and eight novel peptides, named citcol-1 to -8, with a molecular weight between ~3650 and 4160 Da, were purified using reversed-phase high performance liquid chromatography (HPLC), and their amino acid sequences were determined by de novo assignment of b- and y-ion series of proteolytic peptide fragments. In silico analysis of citcol peptides revealed a high sequence similarity to trypsin inhibitor peptides from Cucumis sativus, Momordica cochinchinensis, Momordica macrophylla and Momordica sphaeroidea. Using genome/transcriptome mining it was possible to identify precursor sequences of this peptide family in related Cucurbitaceae species that cluster into trypsin inhibitor and antimicrobial peptides. Based on our analysis, the presence or absence of a crucial Arg/Lys residue at the putative P1 position may be used to classify these common cysteine-rich peptides by functional properties. Despite sequence homology and the common classification into the inhibitor cysteine knot family, these peptides appear to have diverse and additional bioactivities yet to be revealed.

Protective role of antioxidant compounds against peroxynitrite-mediated modification of R54C mutant αA-crystallin.

As a highly potent reactive oxygen and nitrogen species, peroxynitrite (PON) has endogenous production in the eye ball and contributes to a variety of ocular disorders. In the current study the structural characteristics, chaperone-like activity and conformational stability of R54C mutant αA-crystallin (αA-Cry) were studied upon modification with PON and in the presence of three antioxidant compounds such as ascorbic acid (ASA), glutathione (GSH) and N-acetylcysteine (NAC) using gel electrophoresis and different spectroscopy methods. The results of both fluorescence analysis and gel electrophoresis suggested that PON modification leads to dityrosine-mediated intermolecular cross-linking of this cataractogenic mutant protein. Also, the propensity of R54C mutant αA-Cry for disulfide cross-linking was increased upon PON modification. In addition, the PON-modified protein indicated structural alteration, reduced chemical stability and different pattern of proteolysis. Upon modification with PON, mutant αA-Cry displayed a significant increase in the chaperone-like activity against aggregation of γ-crystallin and insulin. In addition, different antioxidant compounds indicated a prominent role in neutralizing the PON damaging effects on structural integrity and stability of this protein. The results of this study may highlight the importance of antioxidant-rich foods or potent antioxidant supplements in protection of lens crystallins against PON-mediated structural damages and cataract development.

The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study).

Increasing evidences implicate impairment of axonal integrity in mechanisms underlying neurodegenerative disorders. Beta-boswellic acid (BBA) is the major component of Boswellia serrata gum. This resin has long been used in Ayurveda (India's traditional medicine) to prevent amnesia. In this study, the effect of BBA was examined on neurites outgrowth and branching as well as on polymerization dynamics of tubulin. The morphometric parameters (axonal length and neuritis branching) were examined microscopically after treating the hippocampal cells with BBA. Also the assembly process of tubulin was assessed using UV/V is spectrophotometer through following of absorbance at 350 nm. The results revealed that BBA could significantly enhance neurite outgrowth, branching, and tubulin polymerization dynamics. The obtained results suggest that enhancing effect of BBA on microtubule polymerization kinetics might be the origin of increasing axonal outgrowth and branching.