A comprehensive review of advanced focused ultrasound (FUS) microbubbles-mediated treatment of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration, memory loss, and cognitive impairment leading to dementia and death. The blood-brain barrier (BBB) prevents the delivery of drugs into the brain, which can limit their therapeutic potential in the treatment of AD. Therefore, there is a need to develop new approaches to bypass the BBB for appropriate treatment of AD. Recently, focused ultrasound (FUS) has been shown to disrupt the BBB, allowing therapeutic agents to penetrate the brain. In addition, microbubbles (MBs) as lipophilic carriers can penetrate across the BBB and deliver the active drug into the brain tissue. Therefore, combined with FUS, the drug-encapsulated MBs can pass through the ultrasound-disrupted zone of the BBB and diffuse into the brain tissue. This review provides clear and concise statements on the recent advances of the various FUS-mediated MBs-based carriers developed for delivering AD-related drugs. In addition, the sonogenetics-based FUS/MBs approaches for the treatment of AD are highlighted. The future perspectives and challenges of ultrasound-based MBs drug delivery in AD are then discussed.

Preparation and in vitro evaluation of cell adhesion and long-term proliferation of stem cells cultured on silibinin co-embedded PLGA/Collagen electrospun composite nanofibers.

The present research aims to evaluate the efficacy of Silibinin-loaded mesoporous silica nanoparticles (Sil@MSNs) immobilized into polylactic-co-glycolic acid/Collagen (PLGA/Col) nanofibers on the in vitro proliferation of adipose-derived stem cells (ASCs) and cellular senescence. Here, the fabricated electrospun PLGA/Col composite scaffolds were coated with Sil@MSNs and their physicochemical properties were examined by FTIR, FE-SEM, and TGA. The growth, viability and proliferation of ASCs were investigated using various biological assays including PicoGreen, MTT, and RT-PCR after 21 days. The proliferation and adhesion of ASCs were supported by the biological and mechanical characteristics of the Sil@MSNs PLGA/Col composite scaffolds, according to FE- SEM. PicoGreen and cytotoxicity analysis showed an increase in the rate of proliferation and metabolic activity of hADSCs after 14 and 21 days, confirming the initial and controlled release of Sil from nanofibers. Gene expression analysis further confirmed the increased expression of stemness markers as well as hTERT and telomerase in ASCs seeded on Sil@MSNs PLGA/Col nanofibers compared to the control group. Ultimately, the findings of the present study introduced Sil@MSNs PLGA/Col composite scaffolds as an efficient platform for long-term proliferation of ASCs in tissue engineering.

The recent insight in the release of anticancer drug loaded into PLGA microspheres.

Cancer is a series of diseases leading to a high rate of death worldwide. Microspheres display specific characteristics that make them appropriate for a variety of biomedical purposes such as cancer therapy. Newly, microspheres have the potentials to be used as controlled drug release carriers. Recently, PLGA-based microspheres have attracted exceptional attention relating to effective drug delivery systems (DDS) because of their distinctive properties for a simple preparation, biodegradability, and high capability of drug loading which might be increased drug delivery. In this line, the mechanisms of controlled drug release and parameters that influence the release features of loaded agents from PLGA-based microspheres should be mentioned. The current review is focused on the new development of the release features of anticancer drugs, which are loaded into PLGA-based microspheres. Consequently, future perspective and challenges of anticancer drug release from PLGA-based microspheres are mentioned concisely.

The recent advancements in the early detection of cancer biomarkers by DNAzyme-assisted aptasensors.

Clinical diagnostics rely heavily on the detection and quantification of cancer biomarkers. The rapid detection of cancer-specific biomarkers is of great importance in the early diagnosis of cancers and plays a crucial role in the subsequent treatments. There are several different detection techniques available today for detecting cancer biomarkers. Because of target-related conformational alterations, high stability, and target variety, aptamers have received considerable interest as a biosensing system component. To date, several sensitivity-enhancement strategies have been used with a broad spectrum of nanomaterials and nanoparticles (NPs) to improve the limit and sensitivity of analyte detection in the construction of innovative aptasensors. The present article aims to outline the research developments on the potential of DNAzymes-based aptasensors for cancer biomarker detection.

Protective effect of miR-34c antagomir against STZ-induced memory impairment by targeting mTOR and PSD-95 in the hippocampus of rats.

After long times of ongoing research, still there is no appropriate cure for Alzheimer's disease (AD). Recently, epigenetic alterations, particularly miRNA, have gotten attention in AD research. Among various miRNA, miR-34c has been addressed to be elevated in the brain of AD patients, however, its exact role and downstream mechanisms have not been elucidated yet. This study aimed to investigate the therapeutic potential of miR-34c antagomir on cognitive dysfunction induced by streptozocin (STZ), considering postsynaptic density protein 95 (PSD-95) and mammalian target of rapamycin expression (mTOR). Forty rats were cannulated intraventricularly under deep anesthesia using stereotaxic apparatus and divided into five groups: saline + saline, STZ + saline, STZ + miR-34c antagomir, STZ + lipofectamine, and STZ + scrambled, and received the related treatments for two weeks. At the end of the treatments, spatial memory and locomotor activity were assessed by Morris water maze (MWM), and open fields, respectively. Finally, PSD-95 and mTOR levels were measured by quantitative real-time PCR (qPCR) and western blotting on hippocampal samples. Results showed that miR-34c antagomir markedly ameliorated spatial learning and memory deficits induced by STZ, and significantly enhanced PSD-95 and mTOR levels in the hippocampus. In conclusion, miR-34c antagomir may be considered as a promising novel therapeutic target for AD patients.

Analysis of carbapenemases genes of carbapenem-resistant Klebsiella pneumoniae isolated from Tehran heart center.

Background and Objectives: Emerging of carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the major concerns among healthcare systems. This study aimed to investigate the antibiotic susceptibility pattern and carbapenemase genes of carbapenemase-producing K. pneumoniae isolates obtained from Iranian hospitalized patients. Materials and Methods: This study was performed on 71 CRKP strains isolated from different clinical specimens collected in Tehran Heart Center (Tehran, Iran). A Modified Hodge test (MHT) was done for the detection of carbapenemase-producing K. pneumoniae. The presence of bla KPC, bla VIM, bla IMP, bla NDM, and bla OXA-48 -type carbapenemases was evaluated by the PCR method. Results: We identified 8.82% (71/805) of K. pneumoniae isolates as CRKP by MHT test. The antibiotic susceptibility indicated that all isolates were resistant to imipenem, meropenem, cefotaxime, ceftazidime, cefepime, ceftriaxone, cephalothin, ciprofloxacin, and augmentin, and then mostly resistant to aztreonam, cefoxitin, gentamicin, and trimethoprim/sulfamethoxazole with 98.6%, 98.6%, 97.2%, and 94.4%, respectively. The lowest resistance was related to amikacin with 46.5% (33/71 isolates). The level of imipenem MIC for all carbapenem-resistant isolates was estimated ≥32 µg/mL. Among positive isolates for carbapenemase genes, the most frequent gene was bla OXA-48. It was found in 48 (67.6%) isolates followed by bla VIM in 28 (39.4%) isolates. bla IMP, bla NDM, and bla KPC genes were identified in 19 (26.8%), 13 (18.3%) and 5 (7.0%) isolates, respectively. These genes were not detected in nine isolates. Conclusion: The relatively high frequency of some carbapenemase genes suggests major concern about the emergence of isolates containing carbapenem resistance genes as a potential health threat.

Recent progress in the early detection of cancer based on CD44 biomarker; nano-biosensing approaches.

CD44 is a cell matrix adhesion molecule overexpressed on the cell surfaces of the major cancers. CD44 as a cancer-related biomarker has an essential role in the invasion and metastasis of cancer. The detection and quantification of CD44 can provide essential information useful for clinical cancer diagnosis. In this regard, biosensors with sensitive and specific properties, give prominence to the development of CD44 detection platforms. To date, various aptamer-based sensitive-enhancers together with nanoparticles (NPs) have been combined into the biosensors systems to provide an innovative biosensing method (aptasensors/nano-aptasensors) with substantially improved detection limit. This review article discusses the recent advances in the field of biosensors, nanobiosensors, and aptasensors for the quantitative determination of CD44 and the detection of CD44-expressing cancer cells.

Self-assembly of an aptamer-decorated chimeric peptide nanocarrier for targeted cancer gene delivery.

In this study, we developed a peptide-based non-viral carrier decorated with aptamer to overcome the specific gene delivery barriers. The carrier (KLN/Apt) was designed to contain multiple functional segments, including 1) two tandem repeating units of low molecular weight protamine (LMWP) to condense DNA into stable nanosize particles and protect it from enzymatic digestion, 2) AS1411 aptamer as targeting moiety to target nucleolin and promote carrier internalization, 3) a synthetic pH-sensitive fusogenic peptide (KALA) for disrupting endosomal membranes and enhancing cytosol escape of the nanoparticles, and 4) a nuclear localization signal (NLS) for active cytoplasmic trafficking and nuclear delivery of DNA. The obtained results revealed the developed carrier capacity in terms of specific cell targeting, overcoming cellular gene delivery barriers, and mediating efficient gene transfection. The KLN/pDNA/aptamer nanoparticles offer remarkable potential for the conceptual design and formation of promising multi-functionalized carriers towards the most demanding therapeutic applications.

Targeted SPION siderophore conjugate loaded with doxorubicin as a theranostic agent for imaging and treatment of colon carcinoma.

Recently, the siderophores have opened new horizons in nanomedicine. The current study aimed to design a theranostic platform based on superparamagnetic iron oxide nanoparticles-pyoverdine (SPION/PVD) conjugates bound to MUC1 aptamer (MUC1Apt) and loaded with doxorubicin (DOX) as an anti-cancer agent. The SPION/PVD complex was covalently conjugated to MUC1Apt and loaded with DOX to prepare a targeted drug delivery system (SPION/PVD/MUC1Apt/DOX). The investigation of cellular cytotoxicity and uptake of formulations by MTT and flow cytometry in both MUC1 positive (C26) and MUC1 negative (CHO) cell lines revealed that MUC1Apt could improve both cellular uptake and toxicity in the C26 cell line. The evaluation of tumor-targeting activity by in vivo bio-distribution showed that the targeted formulation could enhance tumor inhibitory growth effect and survival rate in C26 tumor-bearing mice. Furthermore, the potential of synthesized SPION/PVD/MUC1Apt/DOX complex as diagnostic agents was investigated by magnetic resonance imaging (MRI) which improved the contrast of tumor site in MRI. Our findings confirm that aptamer-targeted PVD chelated the SPION as a diagnostic agent and loaded with DOX as a chemotherapeutic drug, would be beneficial as a novel theranostic platform.

Biosensing of microcystins in water samples; recent advances.

Safety and quality of water are significant matters for agriculture, animals and human health. Microcystins, as secondary metabolite of cyanobacteria (blue-green algae) and cyclic heptapeptide cyanotoxin, are one of the main marine toxins in continental aquatic ecosystems. More than 100 microcystins have been identified, of which MC-LR is the most important type due to its high toxicity and common detection in the environment. Climate change is an impressive factor with effects on cyanobacterial blooms as source of microcystins. The presence of this cyanotoxin in freshwater, drinking water, water reservoir supplies and food (vegetable, fish and shellfish) has created a common phenomenon in eutrophic freshwater ecosystems worldwide. International public health organizations have categorized microcystins as a kind of neurotoxin and carcinogen. There are several conventional methods for detection of microcystins. The limitations of traditional methods have encouraged the development of innovative methods for detection of microcystins. In recent years, the developed sensor techniques, with advantages, such as accuracy, reproducibility, portability and low cost, have attracted considerable attention. This review compares the well-known of biosensor types for detection of microcystins with a summary of their analytical performance.

Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis. CONCLUSIONS: Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.

Optical and electrochemical-based nano-aptasensing approaches for the detection of circulating tumor cells (CTCs).

More recently, detection of circulating tumor cells (CTCs) has been considered as an appealing prognostic and diagnostic approach for cancer patients. CTCs as a type of tumor-derived cells are secreted by the tumor and released into the blood circulation. Since the migration of CTCs is an early event in cancer progression, patients who still have tumor-free lymph nodes have to be well examined for the CTCs presence in their blood circulation. Nowadays, there is a broad range of detection methods available to identify CTCs. As artificial RNA oligonucleotides or single-stranded DNA with receptor and catalytic characteristics, aptamers have been standing out, owing to their target-induced conformational modifications, elevated stability, and target specificity to be implemented in biosensing techniques. To date, several sensitivity-enhancement methods alongside smart nanomaterials have been used for the creation of new aptasensors to address the limit of detection (LOD), and improve the sensitivity of numerous analyte identification methods. The present review article supports a focused overview of the recent studies in the identification and quantitative determination of CTCs by aptamer-based biosensors and nanobiosensors.

Prognostic and therapeutic significance of circulating tumor cells in patients with lung cancer.

BACKGROUND: Lung cancer is the second most common cancer and the main cause of cancer-related mortality worldwide. In spite of various efforts that have been made to facilitate the early diagnosis of lung cancer, most patients are diagnosed when the disease is already in stage IV, which is generally associated with the occurrence of distant metastases and a poor survival. Moreover, a large proportion of these patients will relapse after treatment, heralding the need for the stratification of lung cancer patients in addition to identifying those who are at a higher risk of relapse and, thus, require alternative and/or additional therapies. Recently, circulating tumor cells (CTCs) have been considered as valuable markers for the early diagnosis, prognosis and risk stratification of cancer patients, and they have been found to be able to predict the survival of patients with various types of cancer, including lung cancer. Additionally, the characterization of CTCs has recently provided fascinating insights into the heterogeneity of tumors, which may be instrumental for the development of novel targeted therapies. CONCLUSIONS: Here we review our current understanding of the significance of CTCs in lung cancer metastasis. We also discuss prominent studies reporting the utility of enumeration and characterization of CTCs in lung cancer patients as prognostic and pharmacodynamic biomarkers for those who are at a higher risk of metastasis and drug resistance.

Electrochemical-based biosensors for detection of Mycobacterium tuberculosis and tuberculosis biomarkers.

Early detection of tuberculosis (TB) reduces the interval between infection and the beginning of treatment. However, commercially available tests cannot discriminate between BCG-vaccinated healthy persons and patients. Also, they are not suitable to be used for immunocompromised persons. In recent years, biosensors have attracted great attention due to their simple utility, accessibility, and real-time outputs. These sensors are increasingly being considered as pioneering tools for point-of-care diagnostics in communities with a high burden of TB and limited accessibility to reference laboratories. Among other types of biosensors, the electrochemical sensors have the advantages of low-cost operation, fast processing, simultaneous multi-analyte analyzing, operating with turbid samples, comparable sensitivity and readily available miniaturization. Electrochemical biosensors are sub-divided into several categories including: amperometric, impedimetric, potentiometric, and conductometric biosensors. The biorecognition element in electrochemical biosensors is usually based on antibodies (immunosensors), DNAs or PNAs (genosensors), and aptamers (aptasensors). In either case, whether an interaction of the antigen-antibody/aptamer or the hybridization of probe with target mycobacterial DNA is detected, a change in the electrical current occurs that is recorded and displayed as a plot. Therefore, impedimetric-based methods evaluate resistance to electron transfer toward an electrode by a Nyquist plot and amperometric/voltammetric-based methods weigh the electrical current by means of cyclic voltammetry, square wave voltammetry, and differential pulse voltammetry. Electrochemical biosensors provide a promising scope for the new era of diagnostics. As a consequence, they can improve detection of Mycobacterium tuberculosis traces even in attomolar scales.

Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review.

Mucin 1 protein (MUC1) is a membrane-associated glycoprotein overexpressed in the majority of human malignancies and considered as a predominant protein biomarker in cancers. Owing to the crucial role of MUC1 in cancer dissemination and metastasis, detection and quantification of this biomarker is of great importance in clinical diagnostics. Today, there exist a wide variety of strategies for the determination of various types of disease biomarkers, especially MUC1. In this regard, aptamers, as artificial single-stranded DNA or RNA oligonucleotides with catalytic and receptor properties, have drawn lots of attention for the development of biosensing platforms. So far, various sensitivity-enhancement techniques in combination with a broad range of smart nanomaterials have integrated into the design of novel aptamer-based biosensors (aptasensors) to improve detection limit and sensitivity of analyte determination. This review article provides a brief classification and description of the research progresses of aptamer-based biosensors and nanobiosensors for the detection and quantitative determination of MUC1 based on optical and electrochemical platforms.

Zinc solubilization characteristics of efficient siderophore-producing soil bacteria.

BACKGROUND AND OBJECTIVES: Iron and zinc are two essential micro-nutrients for plant growth and development. Therefore, isolation of siderophores-producing and zinc-solubilizing rhizobacteria involved in bio-availability of these elements is of great interest. MATERIALS AND METHODS: In this study, soil samples collected from slightly alkaline soil types were screened for high levels of siderophore secretion and zinc solubilization. RESULTS: Among positive colonies, three isolates, named F21A, F37 and F38, were able to secrete siderophore at high levels, ranged between 200 and 300 µM/liter. A close association was observed between siderophore production capability and growth rate as an indicator of active metabolism. Siderophore production was closely correlated with the level of zinc ion released into the medium as well. All three siderophore producing isolates were able to withstand temperature as high as 37°C, high concentration of NaCl (up to 2.5%) and a wide range of initial pH from 6 to 9 while hydrolyzing Zn compounds actively. One of the isolates, F21A, tolerated the presence of 200 mgl-1 of zinc. Biochemical and molecular characteristics are indicative that these isolates are Pseudomonas japonica. As experienced in a greenhouse experiment, inoculation with the F21A and F37 isolates significantly increase the plants height, fresh and dry weight of corn with compared to control. CONCLUSION: These findings demonstrated that the potential of P. japonica strains as plants growth promoting rhizobacteria (PGPR) in iron and zinc deficient soils.

SELEX methods on the road to protein targeting with nucleic acid aptamers.

Systematic evolution of ligand by exponential enrichment (SELEX) is an efficient method used to isolate high-affinity single stranded oligonucleotides from a large random sequence pool. These SELEX-derived oligonucleotides named aptamer, can be selected against a broad spectrum of target molecules including proteins, cells, microorganisms and chemical compounds. Like antibodies, aptamers have a great potential in interacting with and binding to their targets through structural recognition and are therefore called "chemical antibodies". However, aptamers offer advantages over antibodies including smaller size, better tissue penetration, higher thermal stability, lower immunogenicity, easier production, lower cost of synthesis and facilitated conjugation or modification with different functional moieties. Thus, aptamers represent an attractive substitution for protein antibodies in the fields of biomarker discovery, diagnosis, imaging and targeted therapy. Enormous interest in aptamer technology triggered the development of SELEX that has underwent numerous modifications since its introduction in 1990. This review will discuss the recent advances in SELEX methods and their advantages and limitations. Aptamer applications are also briefly outlined in this review.

Nanomaterial-based biosensors and immunosensors for quantitative determination of cardiac troponins.

Cardiovascular diseases (CVDs) are the most frequent mortality cause in many countries. The acute myocardial infraction (AMI) is one of the most common types of CVDs. Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) as predominant cardiac infarction biomarkers considered as "gold standard" for diagnosis of acute myocardial infraction (AMI). The restrictions of traditional methods have encouraged the development of highly sensitive and specific methods for cTnI and cTnT detection. The rapid, early, reliable, and cost-effective diagnosis of CVDs not only helps with patient survival, but also save cost and time to prosperous prognosis. In recent years, the concept of biosensors has opened new horizons in high precision detection. Once combined with nanomaterials, nano-scale biosensors provide powerful analytical platforms for diagnosing of cTnI and cTnT. In this article, after a brief overview of the cardiac troponins, a classification and description of the research progresses of biosensors and immunosensors for the detection and quantitative determination of cardiac troponins based on optical and electrochemical platforms are presented.

Screening and characterization of in-vitro probiotic criteria of Saccharomyces and Kluyveromyces strains.

BACKGROUND AND OBJECTIVES: Probiotics are defined as live micro-organisms conferring a health benefit on the host. Although most probiotics are bacteria, some yeasts such as Saccharomyces and Kluyveromyces, has been found to have effective probiotic properties. The objective of this study was to isolate and identify indigenous Saccharomyces and Kluyveromyces yeast strains and to compare some probiotic characteristics between these two strains in vitro. MATERIALS AND METHODS: Strains were isolated on yeast glucose chloramphenicol agar medium from 205 samples and identified by morphological, physiological and biochemical assays. The effects of different conditions such as pH and temperature on the survival and growth of the isolates were studied. In addition, resistance to acidic pH (1.5, 2, 3 and 5), pepsin and different concentrations of bile salts (1%, 3% and 5%), as well as proteolytic, lipolytic and hemolytic activity of selected isolates were assessed. Finally, the best isolates were selected for investigation of their viability in samples of dairy products. RESULTS: 126 isolates were identified using biochemical and molecular techniques as yeast strains. Five isolates were found to have effective probiotic properties, belonging to Kluyveromyces marxianus (S97, S101 and S106) and Saccharomyces cerevisiae (S28, S34). These isolates were able to grow at 37°C, pH=1.5, withstand to concentration of 5% oxbile and pepsin and exhibit the proteolytic activity. The isolates of K. marxianus showed better viability in dairy (yogurt). CONCLUSION: In the in-vitro comparative experiments, the isolates of K. marxianus showed better probiotic potentials.

Siderophore-based biosensors and nanosensors; new approach on the development of diagnostic systems.

Siderophores are small organic compounds secreted by microorganisms under iron-depleted conditions which enhance the uptake of iron. Siderophores can play vital roles in ecology, agriculture, bioremediation, biosensor, and medicine. In recent years, the concept of siderophore-based biosensing devices has opened new horizons in high precision detection of various metal ions especially the iron, microorganisms, phosphopeptides, antibiotics as well pesticides. Once combined with nanomaterials, nano-scale siderophore systems provide powerful analytical platforms for detection of low concentration of metal ions and numerous pathogens. In this article, a brief overview of general aspects of siderophore is firstly discussed. In addition, a clear and concise review of recent advances of siderophore-based biosensors (siderosensor) and nanosensors are mainly discussed herein. Subsequently, future perspectives and challenges of siderophore-based sensors are discussed briefly.