Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols.

Green tea polyphenols (GTPs), particularly epigallocatechin-3-gallate, stand out among natural small molecules screened for their ability to target protein aggregates due to their potent anti-amyloidogenic and neuroprotective activities against various disease-related peptides and proteins. However, the clinical applications of GTPs in amyloid-related diseases have been greatly limited by drawbacks such as poor chemical stability and low bioavailability. To address these limitations, this study utilized an Iranian green tea polyphenolic extract as a reducing agent to neutralize silver ions and facilitate the formation of silver nanoparticle capped by GTPs (GTPs-capped AgNPs). The results obtained from this study demonstrate that GTPs-capped AgNPs are more effective than free GTPs at inhibiting amyloid fibrillation and reducing cytotoxicity induced by amyloid fibrils of human insulin and α-synuclein (α-syn). This improved efficacy is attributed to the increased surface/volume ratio of GTPs-capped AgNPs, which can enhance their binding affinity to amyloidogenic species and boosts their antioxidant activity. The mechanism by which GTPs-capped AgNPs inhibit amyloid fibrillation appears to vary depending on the target protein. For structured protein human insulin, GTPs-capped AgNPs hinder fibrillation by constraining the protein in its native-like state. In contrast, GTPs-capped AgNPs modulate fibrillation of intrinsically disordered proteins like α-syn by redirecting the aggregation pathway towards the formation of non-toxic off-pathway oligomers or amorphous aggregates. These findings highlight polyphenol-functionalized nanoparticles as a promising strategy for targeting protein aggregates associated with neurodegenerative diseases.

The urgent need for integrated science to fight COVID-19 pandemic and beyond.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

Plasmonic gold nanoparticles: Optical manipulation, imaging, drug delivery and therapy.

Over the past two decades, the development of plasmonic nanoparticle (NPs), especially gold (Au) NPs, is being pursued more seriously in the medical fields such as imaging, drug delivery, and theranostic systems. However, there is no comprehensive review on the effect of the physical and chemical parameters of AuNPs on their plasmonic properties as well as the use of these unique characteristic in medical activities such as imaging and therapeutics. Therefore, in this literature the surface plasmon resonance (SPR) modeling of AuNPs was accurately captured toward precision medicine. Indeed, we investigated the importance of plasmonic properties of AuNPs in optical manipulation, imaging, drug delivery, and photothermal therapy (PTT) of cancerous cells based on their physicochemical properties. Finally, some challenges regarding the commercialization of AuNPs in future medicine such as, cytotoxicity, lack of standards for medical applications, high cost, and time-consuming process were discussed.

Catalytic activity, structure and stability of proteinase K in the presence of biosynthesized CuO nanoparticles.

Here, CuO nanoparticles were synthesized using Sambucus nigra (elderberry) fruit extract. Further, the binding of proteinase K, as a model enzyme with green synthesized nanoparticles was investigated. The results demonstrated that the structural changes in enzyme were induced by the binding of nanoparticles. These changes were accompanied by the decrease in the Michaelis-Menten constant at 298 K. This means that the enzyme affinity for the substrate was increased. Thermodynamic parameters of protein stability and protein-ligand binding were estimated from the spectroscopic measurements at 298-333 K. Depending on the temperature, CuO nanoparticles showed a dual effect on the thermodynamic stability and binding affinity of enzyme. Nanoparticles increase the stability of the native state of enzyme at room temperature. On the other hand, nanoparticles stabilize the unfolded state of enzyme at 310-333 K. An overall favorable Gibbs energy change was observed for the binding process at 298-333 K. The enzyme-nanoparticle binding is enthalpically driven at room temperature. It was concluded that hydrogen bonding plays a key role in the interaction of enzyme with nanoparticles at 298-310 K. At higher temperatures, the protein-ligand binding is entropically driven. This means that hydrophobic association plays a major role in the proteinase K-CuO binding at 310-333 K.

Biodegradation of asphaltene and petroleum compounds by a highly potent Daedaleopsis sp.

Petroleum, as the major energy source, is indispensable from our lives. Presence of compounds resistant to degradation can pose risks for human health and environment. Basidiomycetes have been considered as powerful candidates in biodegradation of petroleum compounds via secreting ligninolytic enzymes. In this study a wood-decaying fungus was isolated by significant degradation ability that was identified as Daedaleopsis sp. by morphological and molecular identification methods. According to GC/MS studies, incubation of heavy crude oil with Daedaleopsis sp. resulted in increased amounts of C24 compounds. Degradation of asphaltene, anthracene, and dibenzofuran by the identified fungal strain was determined to evaluate its potential in biodegradation. After 14 days of incubation, Daedaleopsis sp. could degrade 93.7% and 91.2% of anthracene and dibenzofuran, respectively, in pH 5 and 40 °C in optimized medium, as revealed by GC/FID. Notably, analysis of saturates, aromatics, resins, and asphaltenes showed a reduction of 88.7% and 38% in asphaletene and aromatic fractions. Laccase, lignin peroxidase, and manganese peroxidase activities were enhanced from 51.3, 145.2, 214.5 U ml-1 in the absence to 121.5, 231.4, and 352.5 U ml-1 in the presence of heavy crude oil, respectively. This is the first report that Daedaleopsis sp. can degrade asphaltene and dibenzofuran. Moreover, compared to the reported results of asphaltene biodegradation, this strain was the most successful. Thus, Daedaleopsis sp. could be a promising candidate for biotransformation of heavy crude oil and biodegradation of recalcitrant toxic compounds.

Design and fabrication of pectin-coated nanoliposomal delivery systems for a bioactive polyphenolic: Phloridzin.

Nanostructured colloidal delivery systems comprising of pectin-coated nanoliposomes (pectonanoliposomes) were developed as carriers for a bioactive polyphenolic compound (phloridzin). Phloridzin-loaded nanoliposomes were fabricated using a heating-stirring-sonication method, and coated with low methoxyl pectin using an electrostatic deposition approach. Dynamic light scattering, micro-electrophoresis, atomic force microscopy, and UV-Visible spectroscopy were used to investigate the impact of system composition on the size, charge, morphology and stability as well as immobilization, adsorption and encapsulation efficiencies of the pectonanoliposomes. Response surface methodology was used to optimize the composition of the pectonanoliposomes based on particle size and charge characteristics. Linear, quadratic and interaction effects of 1,2-dioleoyl-3-trimethyl ammonium propane/lecithin, phloridzin/lecithin and pectin/liposome ratios significantly influenced the mean hydrodynamic diameter and/or surface charge of pectonanoliposomes. Second-order polynomial regression models were generated for intensity-weighted particle size and zeta potential of the designed carriers. Topographic and phase contrast images showed that pectonanoliposomes exhibited a range of different morphologies. Coating the nanoliposomes with pectin improved their immobilization and encapsulation efficiencies as well as physical storage stability. Cationic pectonanoliposomes were superior to plain systems regarding long-term stability. Our results suggest that pectonanoliposomes may be suitable delivery systems for polyphenolic nutraceuticals, such as phloridizin, in functional food and pharmaceutical applications.

A spectroscopic study on the absorption of carbonic anhydrase onto the nanoporous silica nanoparticle.

Herein, KIT-6 nanoporous silica nanoparticles were used as a solid support for immobilization of bovine carbonic anhydrase, isoform II (BCA II). The zeta potential study revealed that KIT-6 and BCA II provided negative (-13.58±1.95mV) and positive (4.23±0.72mV) charge distribution, respectively. Dynamic light scattering (DLS) analysis also showed that the hydrodynamic radius of KIT-6 is less than 100nm. In addition, the structural studies of free and immobilized BCA II against urea-induced denaturation were investigated by circular dichroism (CD) and fluorescence spectroscopy. CD studies showed that the absorbed BCA II, in comparison with the free enzyme, demonstrated higher stability against rising urea concentration. Fluorescence spectroscopy showed lower values of Stern- Volmer constant (KSV) for immobilized BCA II relative to free enzyme, reflecting the relative enzyme stability of BCA II after immobilization. Melting temperature (Tm) measurement of free and immobilized BCA II showed that immobilized enzyme had a more stable structure (Tm=71.9°C) relative to the free counterpart (Tm=64.7°C). In addition, the immobilized BCA II showed pronounced stability against pH and thermal deactivation. This study may provide new and complementary details regarding the design and development of enzymes in industrial applications.

3D QSAR studies, pharmacophore modeling, and virtual screening of diarylpyrazole-benzenesulfonamide derivatives as a template to obtain new inhibitors, using human carbonic anhydrase II as a model protein.

A 3D-QSAR modeling was performed on a series of diarylpyrazole-benzenesulfonamide derivatives acting as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The compounds were collected from two datasets with the same scaffold, and utilized as a template for a new pharmacophore model to screen the ZINC database of commercially available derivatives. The datasets were divided into training, test, and validation sets. As the first step, comparative molecular field analysis (CoMFA), CoMFA region focusing and comparative molecular similarity indices analysis (CoMSIA) in parallel with docking studies were applied to a set of 41 human (h) CA II inhibitors. The validity and the prediction capacity of the resulting models were evaluated by leave-one-out (LOO) cross-validation approach. The reliability of the model for the prediction of possibly new CA inhibitors was also tested.

ß-lactoglobulin-pectin Nanoparticle-based Oral Drug Delivery System for Potential Treatment of Colon Cancer.

Colon cancer is one of the most common internal malignancies, and conventional chemotherapy is not effective in its treatment. Nanoparticles hold tremendous potential as an effective drug delivery system. The physicochemical properties of ß-lactoglobulin, the main whey protein of cow's milk, such as its stability at low pH, its resistance to gastric protease, and its ability to bind hydrophobic ligands, give it potential for transporting drugs specifically for colon cancer. In the present research, ß-lactoglobulin-pectin nanoparticles were designed to transfer a newly synthesized, anticancer platinum complex (bipyridine ethyl dithiocarbamate Pt(II) nitrate), to the colon. The effects of multiple factors on the size and the colloidal stability of the nanoparticles were studied using dynamic light scattering and scanning electron microscopy techniques. Results showed that the best particle size and highest colloidal stability were obtained in phosphate buffer, pH 4.5, with 0.5 mg/mL ß-lactoglobulin and 0.025-0.05wt% pectin. The drug release profile in simulated gastrointestinal conditions demonstrated that ß-lactoglobulin with a secondary coating is stable in acidic conditions but is able to release its cargo at pH 7. Hence, these nanoparticles have potential to serve as novel and effective vehicles for oral drug delivery preparations.

Probing the biological evaluations of a new designed Pt(II) complex using spectroscopic and theoretical approaches: human hemoglobin as a target.

In recent years, using heavy metal compounds such as platinum as anticancer agent is one of the common ways in chemical therapy. In this study, a new anticancer compound of glycine derivatives of Pt(II) complex (amyl-glycine1, 10-phenanthroline Platinum nitrate) was designed, and the biological effects of this novel compound on the alterations in the function and structure of human hemoglobin (Hb) at different temperatures of 25 and 37°C were assessed by applying various spectroscopic (fluorescence and circular dichroism (CD)) and theoretical methods. Fluorescence data indicated the strong ability of Pt(II) complex to quench the intrinsic fluorescence of Hb. The binding constant, number of binding sites, and thermodynamic parameters at two temperatures were calculated, and the results indicated the major possibility of occurring van der Waals force or hydrogen bond interactions in the Pt(II) complex-Hb interaction. For evaluating the alteration of secondary structure of Hb upon interaction with various concentrations of complex, far-UV CD spectra were used and it was observed that in high dose of complex, significant changes were occurred which is indicative of some side effects in overdosing of this complex. On the other hand, the molecular docking results illustrate that are well in agreement in obtaining data with spectroscopy. Above results suggested that using Pt(II) complex as an anticancer agent, model drug in high-dose usage might cause some disordering in structure and function of Hb as well as improve understanding of the side effects of newly designed metal anticancer drugs undergoing.

The new insight into oral drug delivery system based on metal drugs in colon cancer therapy through ß-lactoglobulin/oxali-palladium nanocapsules.

Many efforts have been made to improve the targeting and potential applications of oral drug delivery systems. In this paper, we have demonstrated and investigated how biopolymer nanocapsules can be used as a novel oral drug delivery system for metal-based drug delivery in colon cancer therapy. In this work, ß-lactoglobulin nanocapsules containing oxali-palladium were chosen to be synthesized and investigated for the use in colon cancer therapy. These nanocapsules were fabricated in three different pHs (3, 4.5 and 7) and investigated both in the presence and absence of low methoxyl pectin. The results obtained from these experiments indicated that the soluble and stable ß-lactoglobulin nanocapsules which contained oxali-palladium had the ability to be formed at a size smaller than 200 nm when in the presence of low methoxyl pectin and at pH 4.5. The in vitro release data indicated that the maximum release occurs at pH 7.0 and 7.5. There lease mechanism demonstrated an anomalous diffusion with a predominant contribution from erosion. Finally, it can be concluded that the ß-LG nanocapsules containing oxali-palladium complexed with low methoxyl pectin can be a very promising candidate for the use in oral drug delivery for colon cancer treatment.