Targeted drug delivery to the thrombus by fusing streptokinase with a fibrin-binding peptide (CREKA): an in silico study.

Aim: Streptokinase has poor selectivity and provokes the immune response. In this study, we used in silico studies to design a fusion protein to achieve targeted delivery to the thrombus. Materials & methods: Streptokinase was analyzed computationally for mapping. The fusion protein modeling and quality assessment were carried out on several servers. The enzymatic activity and the stability of the fusion protein and its complex with plasminogen were assessed through molecular docking analysis and molecular dynamics simulation respectively. Results: Physicochemical properties analysis, protein quality assessments, protein-protein docking and molecular dynamics simulations predicted that the designed fusion protein is functionally active. Conclusion: Our results showed that this fusion protein might be a prospective candidate as a novel thrombolytic agent with better selectivity.

[Box: see text].

Exploring the Effects of Various Capping Agents on Zinc Sulfide Quantum Dot Characteristics and In-vitro Fate.

The choice of capping agents used during the synthesis process of quantum dots (QDs) can significantly influence their fate and fundamental properties. Hence, choosing an appropriate capping agent is a critical step in both synthesis and biomedical application of QDs. In this research, ZnS QDs were synthesized via chemical precipitation process and three commonly employed capping agents, namely mercaptoethanol (ME), mercaptoacetic acid (MAA), and cysteamine (CA), were used to stabilize the QDs. This study was aimed to examine how these capping agents impact the physicochemical and optical characteristics of ZnS QDs, as well as their interactions with biological systems. The findings revealed that the capping agents had considerable effects on the behavior and properties of ZnS QDs. MAA-QD exhibited superior crystal lattice, smaller size, and significant quantum yield (QY). In contrast, CA-QDs demonstrated the lowest QY and the highest tendency for aggregation. ME-QDs exhibited intermediate characteristics, along with an acceptable level of cytotoxicity, rapid uptake by cells, and efficient escape from lysosomes. Consequently, it is advisable to select capping agents in accordance with the specific objectives of the research.

Early Diagnosis of Alzheimer's Disease with Blood Test; Tempting but Challenging.

The increasing prevalence of Alzheimer's disease (AD) has led to a health crisis. According to official statistics, more than 55 million people globally have AD or other types of dementia, making it the sixth leading cause of death. It is still difficult to diagnose AD and there is no definitive diagnosis yet; post-mortem autopsy is still the only definite method. Moreover, clinical manifestations occur very late in the course of disease progression; therefore, profound irreversible changes have already occurred when the disease manifests. Studies have shown that in the preclinical stage of AD, changes in some biomarkers are measurable prior to any neurological damage or other symptoms. Hence, creating a reliable, fast, and affordable method capable of detecting AD in early stage has attracted the most attention. Seeking clinically applicable, inexpensive, less invasive, and much more easily accessible biomarkers for early diagnosis of AD, blood-based biomarkers (BBBs) seem to be an ideal option. This review is an inclusive report of BBBs that have been shown to be altered in the course of AD progression. The aim of this report is to provide comprehensive insight into the research status of early detection of AD based on BBBs.

Antimicrobial safety considerations in critically ill patients: part II: focused on anti-microbial toxicities.

INTRODUCTION: Antibiotic prescription is a challenging issue in critical care settings. Different pharmacokinetic and pharmacodynamic properties, polypharmacy, drug interactions, and high incidence of multidrug-resistant microorganisms in this population can influence the selection, safety, and efficacy of prescribed antibiotics. AREAS COVERED: In the current article we searched PubMed, Scopus and Google Scholar for neurotoxicities, hematologic toxicity and fluid stewardship in intensive care units. EXPERT OPINION: Critically ill patients who receive antimicrobial agents should be monitored for neurological, hematologic toxicities especially seizure, thrombocytopenia, and clostridioides infections. Other toxicities including QTc prolongation, electrolyte disturbances, liver enzyme elevation, and infusion-related reactions were being considered. Other changes, including fluid overload, hypoalbuminemia, augmented renal clearance, increased cardiac outputs in septic shock, and acute kidney injury, may influence treatment efficiency and patient outcome.

Antimicrobial safety considerations in critically ill patients: part I: focused on acute kidney injury.

INTRODUCTION: Antibiotic prescription is a challenging issue in critical care settings. Different pharmacokinetic and pharmacodynamic properties, polypharmacy, drug interactions, and high incidence of multidrug-resistant microorganisms in this population can influence the selection, safety, and efficacy of prescribed antibiotics. AREAS COVERED: In the current article, we searched PubMed, Scopus, and Google Scholar for estimating renal function in acute kidney injury, nephrotoxicity of commonly used antibiotics, and nephrotoxin stewardship in intensive care units. EXPERT OPINION: Early estimation of kidney function with an accurate method may be helpful to optimize antimicrobial treatment in critically ill patients. Different antibiotic dosing regimens may be required for patients with acute kidney injury. In many low-resource settings, therapeutic drug monitoring is not available for antibiotics. Acute kidney injury may influence treatment effectiveness and patient outcome.

Laser irradiation affects the biological identity and cellular uptake of plasmonic nanoparticles.

The biological identity of nanoparticles (NPs) is defined by a protein layer formed on their surface, called protein corona (PC), once they meet the biological milieu. Any change in the PC composition may influence the biological fate of NPs. The PC composition is strongly dependent on several parameters including the physicochemical properties of NPs, and biological and environmental factors. As one of the main features of plasmonic NPs is their capacity to induce local heating by laser irradiation, we hypothesized that laser irradiation may change the biological identity of NPs and therefore alter their biological fate. To test this hypothesis, here we investigated the effects of either simultaneous or sequential laser irradiation on the conformations of a few proteins selected from two main categories of plasma proteins (i.e. human serum albumin and human fibrinogen) on the surfaces of gold nanorods (AuNRs). The outcomes revealed a significant role of laser irradiation on conformational changes of fibrinogen compared to albumin. Moreover, the effects of plasmonic heating - at various times - on the achieved corona composition from interactions of AuNRs and human plasma with various concentrations were monitored. Consequently, the cellular uptake of the corona coated AuNRs was measured in two cell types: malignant (MCF-7) and normal (MCF-10A) breast cell lines. The results demonstrated a substantial reduction in the cellular uptake of AuNRs in response to an increase in the laser irradiation time, especially in MCF-10A. Our results may pave the way for a mechanistic understanding of the biological identity of plasmonic NPs which in turn can help their safe and efficient clinical translations.

Bare surface of gold nanoparticle induces inflammation through unfolding of plasma fibrinogen.

The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids. It is now being increasingly accepted that NPs with particular physiochemical properties have a capacity to induce conformational changes to proteins and therefore influence their biological fates, we hypothesized that the gold NP's metal surface may also be involved in the observed Fg unfolding and inflammatory response. To mechanistically test this hypothesis, we probed the interaction of Fg with gold surfaces using molecular dynamic simulation (MD) and revealed that the gold surface has a capacity to induce Fg conformational changes in favor of inflammation response. As the integrity of coatings at the surface of ultra-small gold NPs are not thorough, we also hypothesized that the ultra-small gold NPs have a capacity to induce unfolding of Fg regardless of the composition and surface charge of their coatings. Using different surface coatings at the surface of ultra-small gold NPs, we validated this hypothesis. Our findings suggest that gold NPs may cause unforeseen inflammatory effects, as their surface coatings may be degraded by physiological activity.

Cell shape affects nanoparticle uptake and toxicity: An overlooked factor at the nanobio interfaces.

HYPOTHESIS: It is now being increasingly accepted that cells in their native tissue show different morphologies than those grown on a culture plate. Culturing cells on the conventional two-dimensional (2D) culture plates does not closely resemble the in vivo three-dimensional (3D) structure of cells which in turn seems to affect cellular function. This is one of the reasons, among many others, that nanoparticles uptake and toxicology data from 2D culture plates and in vivo environments are not correlated with one another. In this study, we offer a novel platform technology for producing more in vivo-like models of in vitro cell culture. EXPERIMENTS: The normal fibroblast cells (HU02) were cultured on "pseudo-3D" substrates, made from cell imprinting approach. The respond of the cells to a model nanoparticle (gold nanorod) were compared in 2D and "pseudo-3D" cultures modes, by cytotoxicological assays. FINDINGS: It is illustrated here that the cells' respond to the exact same type of nanoparticles is majorly dependant in their shape. The use of "pseudo-3D" substrates which could partially mimic the shape of cells in vivo is strongly proposed as a means of better predicting the efficacy of the 2D cell culture plates.

Polyionic complex of single-walled carbon nanotubes and PEG-grafted-hyperbranched polyethyleneimine (PEG-PEI-SWNT) for an improved doxorubicin loading and delivery: development and in vitro characterization.

To take advantages of single-walled carbon nanotubes (SWNTs) for cellular delivery of chemotherapeutic agents (e.g. doxorubicin) in order to decrease general toxicities of doxorubicin (DOX) and to promote the efficacy, we aimed to develop a novel approach to stabilize SWNTs through consequent steps of oxidation and PEG-g-PEI polyionic complexation (PEG-PEI-SWNT). The DOX loading capacity of modified SWNTs was about 900%. Moreover, it showed an enhanced dispersibility in physiologic-stimulated medium. DOX release was prolonged, independent of dilution, and exhibited an acidic pH-stimulated release. Therefore, PEG-PEI-SWNT could be used for cancer chemotherapy in vivo.