Erythrocyte membrane-camouflaged mesoporous silica composite nanoparticles for loading and controlled release of the hepatoprotective agent silibinin: A-synthesis and physicochemical characterization.

OBJECTIVES: Milk thistle has long been used in the treatment of liver and biliary disorders. In the present study, to make a long-acting delivery system for silibinin (SBN, a major active constituent of milk thistle seeds with antioxidant and hepatoprotective function), mesoporous silica composite nanoparticles (NC) were synthesized and coated with RBC membrane. METHODS: A modified Stöber method was used for NC synthesis, which was then characterized using FE-SEM, DLS, TEM, FTIR, and EDAX techniques. A suitable lysis buffer was used to prepare RBC-ghost, and sonication was used to coat SBN-loaded NC (SBN-NC). The RBC-ghost coated SBN-NC (SBN-NC-RBCG) was evaluated by SDS-PAGE, Bradford, TEM, EDAX, and DLS methods. SBN release was then compared for the SBN-NC and SBN-NC-RBCG samples. KEY FINDINGS: the RBC membrane proteins were recovered from the coating of SBN-NC-RBCG, and SBN release was sustained over 24 h when compared with the SBN-NC. CONCLUSIONS: Overall, through prolonging circulation in the bloodstream and evading the immune system, the developed system can improve SBN bioavailability in liver inflammation and fibrosis conditions that need further research.

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.

Potential of oligonucleotide- and protein/peptide-based therapeutics in the management of toxicant/stressor-induced diseases.

Exposure to toxicants/stressors has been linked to the development of many human diseases. They could affect various cellular components, such as DNA, proteins, lipids, and non-coding RNAs (ncRNA), thereby triggering various cellular pathways, particularly oxidative stress, inflammatory responses, and apoptosis, which can contribute to pathophysiological states. Accordingly, modulation of these pathways has been the focus of numerous investigations for managing related diseases. The involvement of various ncRNAs, such as small interfering RNA (siRNA), microRNAs (miRNA), and long non-coding RNAs (lncRNA), as well as various proteins and peptides in mediating these pathways, provides many target sites for pharmaceutical intervention. In this regard, various oligonucleotide- and protein/peptide-based therapies have been developed to treat toxicity-induced diseases, which have shown promising results in vitro and in vivo. This comprehensive review provides information about various aspects of toxicity-related diseases including their causing factors, main underlying mechanisms and intermediates, and their roles in pathophysiological states. Particularly, it highlights the principles and mechanisms of oligonucleotide- and protein/peptide-based therapies in the treatment of toxicity-related diseases. Furthermore, various issues of oligonucleotides and proteins/peptides for clinical usage and potential solutions are discussed.

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.

Medicinal Plants for Viral Respiratory Diseases: A Systematic Review on Persian Medicine.

Introduction: Many medicinal plants have been introduced in Persian medicine references for various respiratory disorders. Considering the growing interest in herbal medicines, this review aimed to introduce medicinal herbs recommended by Persian Medicine (PM) references for respiratory diseases and to discuss their activity against respiratory viruses. Methods: The medicinal plants recommended for respiratory disorders were extracted from the main PM textbooks. Subsequently, their activity against respiratory viruses was systematically investigated via queries of scientific databases. Results: Searching PM references for medicinal plants used in the management of respiratory disorders yielded 45 results. Of them, 18 possess antiviral activity against respiratory viruses. There were 29 in vitro studies (including studies on human cell lines) and 5 in vivo studies. Conclusion: This research demonstrated that many of the medicinal plants mentioned for the respiratory diseases in PM have considerable activity against respiratory viruses. However, human studies regarding the reported medicinal plants are scarce.

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.

Cell-penetrating peptide-mediated delivery of therapeutic peptides/proteins to manage the diseases involving oxidative stress, inflammatory response and apoptosis.

OBJECTIVES: Peptides and proteins represent great potential for modulating various cellular processes including oxidative stress, inflammatory response, apoptosis and consequently the treatment of related diseases. However, their therapeutic effects are limited by their inability to cross cellular barriers. Cell-penetrating peptides (CPPs), which can transport cargoes into the cell, could resolve this issue, as would be discussed in this review. KEY FINDINGS: CPPs have been successfully exploited in vitro and in vivo for peptide/protein delivery to treat a wide range of diseases involving oxidative stress, inflammatory processes and apoptosis. Their in vivo applications are still limited due to some fundamental issues of CPPs, including nonspecificity, proteolytic instability, potential toxicity and immunogenicity. SUMMARY: Totally, CPPs could potentially help to manage the diseases involving oxidative stress, inflammatory response and apoptosis by delivering peptides/proteins that could selectively reach proper intracellular targets. More studies to overcome related CPP limitations and confirm the efficacy and safety of this strategy are needed before their clinical usage.

A Study of L-Lysine-Stabilized Iron Oxide Nanoparticles (IONPs) on Microalgae Biofilm Formation of Chlorella vulgaris.

Despite iron-based nanoparticles gaining huge attraction in various field of sciences and technology, their application rises ecological concerns due to lack of studies on their interaction with microbial cells populations and communities, such as biofilms. In this study, Chlorella vulgaris cells were employed as a model of aquatic microalgae to investigate the impacts of L-lysine-coated iron oxide nanoparticles (lys@IONPs) on microalgal growth and biofilm formation. In this regard, C. vulgaris cells were exposed to different concentrations of lys@IONPs and the growth of cells was evaluated by OD600 and biofilm formation was analyzed using crystal violet staining throughout 12 days. It was revealed that low concentration of nanoparticles (< 400 µg/mL) can promote cell growth and biofilm formation. However, higher concentrations have an adverse effect on microalgal communities. It is interesting that microalgal growth and biofilm are concentration- and exposure time-dependent to lys@IONPs. Over long period (~ 12 days) exposure to high concentrations of nanoparticles, cells can adapt with the condition, so growth was raised and biofilm started to develop. Results of the present study could be considered in ecological issues and also bioprocesses using microalgal cells.

Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines.

Viral infections are a great threat to human health. Currently, there are no effective vaccines and antiviral drugs against the majority of viral diseases, suggesting the need to develop novel and effective antiviral agents. Since the intracellular delivery of antiviral agents, particularly the impermeable molecules, such as peptides, proteins, and nucleic acids, are essential to exert their therapeutic effects, using a delivery system is highly required. Among various delivery systems, cell-penetrating peptides (CPPs), a group of short peptides with the unique ability of crossing cell membrane, offer great potential for the intracellular delivery of various biologically active cargoes. The results of numerous in vitro and in vivo studies with CPP conjugates demonstrate their promise as therapeutic agents in various medical fields including antiviral therapy. The CPP-mediated delivery of various antiviral agents including peptides, proteins, nucleic acids, and nanocarriers have been associated with therapeutic efficacy both in vitro and in vivo. This review describes various aspects of viruses including their biology, pathogenesis, and therapy and briefly discusses the concept of CPP and its potential in drug delivery. Particularly, it will highlight a variety of CPP applications in the management of viral infections.

Impact of magnetic immobilization on the cell physiology of green unicellular algae Chlorella vulgaris.

Cell immobilization on the magnetic nanoparticles (MNPs) and magnetic harvesting is a novel approach for microalgal cells separation. To date, the effect of these nanoparticles on microalgal cells was only studied over a short period of time. More studies are hence needed for a better understanding of the magnetic harvesting proposes or environmental concerns relating to long-term exposure to nanoparticles. In this study, the impact of various concentrations of MNPs on the microalgal cells growth and their metabolic status was investigated over 12 days. More than 60% reduction in mitochondrial activity and pigments (chlorophyll a, chlorophyll b, and carotenoids) content occurred during the first 6 days of exposure to ≥50 µg/mL nanoparticles. However, more than 50% growth inhibitory effect was seen at concentrations higher than 400 µg/mL. Exposure to MNPs gradually induced cellular adaptation and after about 6 days of exposure to stress generating concentrations (˂400 µg/mL) of IONs, microalgae could overcome the imposed damages. This work provides a better understanding regarding the environmental impact of MNPs and appropriate concentrations of these particles for future algal cells magnetic immobilization and harvesting.

Structural characterization of polysaccharide-coated iron oxide nanoparticles produced by Staphylococcus warneri, isolated from a thermal spring.

The biocompatible-coated iron oxide nanoparticles (IONs) have attracted a great interest because of their various applications in biological science and medicine. In most cases, the toxic effect of naked iron oxide nanoparticles is completely cleared by adding a biocompatible coating, such as polysaccharides, polyethylene glycol (PEG), or biosynthesis of biocompatible-coated IONs using microorganisms such as bacteria. In the present study, polysaccharide-coated iron oxide nanoparticles were produced by a strain of Staphylococcus warneri isolated from a thermal spring. For identification of the isolated bacterium, 16S rRNA gene sequencing was done. Characterization of the nanoparticles was performed for the first time, using transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), X-ray crystallography (XRD), Fourier-transform infrared (FTIR) spectroscopy, vibrating sample magnetometer (VSM), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results indicated that the spherical iron oxide nanoparticles were coated by a polysaccharide (13.6%), which provided a large negative charge of -91 mV and very low saturation magnetization of around 0.28 emu/g. The result of MTT assay on MOLT-4 cell lines showed that the percentage of viability was between 95.6% and 68.9% in the 10-100 µM of nanoparticle concentrations with a high IC 50 value, which makes it appropriate for biomedical applications such as cancer therapy.

Cinnamon: A systematic review of adverse events.

Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a popular spice for thousands of years around the world. Many studies have shown therapeutic effects of cinnamon including its antimicrobial, antiviral, antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic, gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon and several human reports on adverse events associated with short or long term use of cinnamon, we aimed to systematically review its human reports of adverse event. Databases including Medline, Scopus, Science Direct, Embase, PubMed Central and Google scholar were searched using the key words "cinnamon" or "cinnamomum" for clinical trials, case reports and case series. Also spontaneous reports about adverse effects of cinnamon were collected from five national and international spontaneous reporting schemes. Thirty eight clinical trials were found, five of them reported adverse events. Twenty case reports and seven case series, as well as, spontaneous reports including 160 adverse events were also included. The most frequent adverse events were gastrointestinal disorders and allergic reactions which were self-limiting in the majority of cases. The available data suggests that despite the safety of cinnamon use as a spice and/or flavoring agent, its use may be associated with significant adverse effects in medicinal uses with larger doses or longer duration of use and should be clinically monitored.

Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial.

Our aim is to assess the effect of cinnamon powder capsules on insulin resistance, anthropometric measurements, glucose and lipid profiles, and androgens of women with polycystic ovarian syndrome (PCOS). Out of 80 women that were diagnosed as PCOS by Rotterdam Criteria, 66 were enrolled in this randomized double-blind placebo-controlled clinical trial. All of the PCOS women were taking medroxy progesterone acetate 10 mg/day for the last 10 days of their menstrual cycles. The cases were randomly allocated to 2 groups. The women in the first group were treated by cinnamon powder capsules 1.5 g/day in 3 divided doses for 12 weeks and the second group by similar placebo capsules. Anthropometric measurements, fasting blood sugar, fasting insulin, blood glucose 2 hr after taking 75 g oral glucose, HbA1c, testosterone, dehydroepiandrosterone sulphate, homeostatic model assessment for insulin resistance, triglyceride, and cholesterol (low-density lipoprotein, high-density lipoprotein, and total) before and after the intervention were evaluated and compared as outcome measures. Fasting insulin (p = .024) and homeostatic model assessment for insulin resistance (p = .014) were reduced after 12 weeks in the cinnamon group compared with the placebo. There was also a significant decrease in low-density lipoprotein in cinnamon group (p = .004) as compared with baseline that caused significant difference with placebo (p = .049). However, changes in other outcome measurements did not lead to statistically significant difference with placebo. The present results suggest that complementary supplementation of cinnamon significantly reduced fasting insulin and insulin resistance in women with PCOS.

Characterization of hydrocortisone biometabolites and 18S rRNA gene in Chlamydomonas reinhardtii cultures.

A unicellular microalga, Chlamydomonas reinhardtii, was isolated from rice paddy-field soil and water samples and used in the biotransformation of hydrocortisone (1). This strain has not been previously tested for steroid bioconversion. Fermentation was carried out in BG-11 medium supplemented with 0.05% substrate at 25 degrees C for 14 days of incubation. The products obtained were chromatographically purified and characterized using spectroscopic methods. 11b,17 beta-Dihydroxyandrost-4-en-3-one (2), 11 beta-hydroxyandrost-4-en-3,17-dione (3), 11 beta,17 alpha,20 beta,21-tetrahydroxypregn-4-en-3-one (4) and prednisolone (5) were the main products of the bioconversion. The observed bioreaction features were the side chain degradation of the substrate to give compounds 2 and 3 and the 20-ketone reduction and 1,2-dehydrogenation affording compounds 4 and 5, respectively. A time course study showed the accumulation of product 2 from the second day of the fermentation and of compounds 3, 4 and 5 from the third day. All the metabolites reached their maximum concentration in seven days. Microalgal 18S rRNA gene was also amplified by PCR. PCR products were sequenced to confirm their authenticity as 18S rRNA gene of microalgae. The result of PCR blasted with other sequenced microalgae in NCBI showed 100% homology to the 18S small subunit rRNA of two Chlamydomonas reinhardtii spp.