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Catanionic nanovesicles are attractive as a novel class of delivery vehicle because they can increase the stability, adsorption, and cellular uptake of a broad range of drugs. These hybrid lipid nanocarriers consist of solid and liquid lipids, which are biocompatible and biodegradable. Since liquid lipid is added to the nanocarrier, the lipids are present in a crystalline defect or amorphous structure state. As a result, hybrid lipid nanocarriers have a higher drug loading capability and suffer less drug leakage during preparation and storage compared to the pure lipid nanocarriers. Catanionic nanovesicles have been shown to increase stability, adsorption, cellular uptake, apoptosis induction, tumor cell cytotoxicity, and antitumorigenic effect, making it a highly desirable vehicle for drug delivery. For example, the anticancer compound curcumin (CC) have shown great promise to cure cancers such as lung cancer, breast cancer, stomach cancer, and colon cancer. However, like many potential antitumor drugs, CC on its own has poor water solubility, easy photodegradation, chemical instability, low bioavailability, rapid metabolism, and fast systematic clearance, which severely limits its clinical applications. In this chapter, we demonstrate the use of catanionic nanovesicles to improve the bioavailability and efficacy of CC for anticancer applications. This technique can be easily adapted for delivery and evaluation of other bioactive compounds.The assessment of the efficient binding between a nucleic acid and its associated nanoparticle is crucial for gene delivery. Emerging from the extensive search for versatile gene carriers, are complexes formed between nucleic acids and nonviral nanocarriers that promise to be viable alternatives to the predominantly viral-based gene delivery vehicles. However, much is still to be known about the exact structure and physico-chemical properties of such nanocomplexes. This chapter will concentrate on cationic lipid, polymer, and functionalized metal nanoparticles and their interaction with nucleic acids by direct conjugation or electrostatic interaction. Methods commonly employed to evaluate the nature and extent of nucleic acid interactions with cationic nanocarriers, such a nucleic acid binding, nuclease protection, and dye displacement assays will be described. In addition, the ultrastructural morphology, size, and zeta potential of these nanocomplexes, which are crucial for their cellular uptake and intracellular trafficking, will be assessed using electron microscopy, fluorescent detection, and nanoparticle tracking analysis (NTA). These assays have the ability to visualize and quantify the interaction and can also be used to complement each other, in addition to providing confirmation of the formation of the relevant nanocomplexes.Visual analysis of the gene delivery process when using invasive bacteria as a vector has been conventionally performed using standard light and fluorescence microscopy. These microscopes can provide basic information on the invasiveness of the bacterial vector including the ability of the vector to successfully adhere to the cell membrane. Standard microscopy techniques however fall short when finer details including membrane attachment as well as internalization into the cytoplasm are desired. High-resolution visual analysis of bacteria-mediated gene delivery can allow accurate measurement of the adherence and internalization capabilities of engineered vectors. Here, we describe the use of scanning electron microscopy (SEM) to directly quantify vectors when they are external to the cell wall, and confocal microscopy to evaluate the vectors when they have internalized into the cytoplasm. By performing the invasion procedure on microscope coverslips, cells can be easily prepared for analysis using electron or confocal microscopes. Imaging the invasion complexes in high resolution can provide important insights into the behavior of bacterial vectors including E. coli, Listeria, and Salmonella when invading their target cells to deliver DNA and other molecules.Gene delivery using invasive bacteria as vectors is a robust method that is feasible for plasmid and artificial chromosome DNA construct delivery to human cells presenting β1 integrin receptors. This technique is relatively underutilized owing to the inefficiency of gene transfer to targeted cell populations. Bacterial vectors must successfully adhere to the cell membrane, internalize into the cytoplasm, undergo lysis, and deliver DNA to the nucleus. There are limited studies on the use of exogenous reagents to improve the efficiency of bacteria-mediated gene delivery to mammalian cells. In this chapter, we describe how cationic lipids, conventionally used for DNA and protein transfection, as well as antimicrobial compounds, can be used to synergistically enhance the adherence of invasive bacterial vectors to the cell membrane and improve their predisposition to internalize into the cytoplasm to deliver DNA. Using simple combinatorial methods, functional DNA transfer can be improved by up to four-fold of invaded cell populations. These methods are easy to perform and are likely to be applicable for other bacterial vectors including Listeria and Salmonella.Bactofection, a bacterial-mediated form of genetic transfer, is highlighted as an alternative mechanism for gene therapy. A key advantage of this system for immune-reactivity purposes stems from the nature of the bacterial host capable of initiating an immune response by attracting recognition and cellular uptake by antigen-presenting cells (APCs). The approach is also a suitable technique to deliver larger genetic constructs more efficiently as it can transfer plasmids of varying sizes into target mammalian cells. Given these advantages, bacterial vectors are being studied as potential carriers for the delivery of plasmid DNA into target cells to enable expression of heterologous proteins. The bacteria used for bactofection are generally nonpathogenic; however, concerns arise due to the use of a biological agent. To overcome such concerns, enhanced bacterial degradation has been engineered as an attenuation and safety feature for bactofection vectors. In particular, the ΦX174 lysis E (LyE) gene can be repurposed to both minimize bacterial survival within mammalian hosts while also improving overall gene delivery. More specifically, an engineered bacterial vector carrying the LyE gene showed improved gene delivery and safety profiles when tested with murine RAW264.7 macrophage APCs. This chapter outlines steps taken to engineer E. coli for LyE expression as a safer and more effective genetic antigen delivery bactofection vehicle in the context of vaccine utility.
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with
Lu-labeled PSMA ligands has achieved remarkable results in advanced disease stages of metastatic castration-resistant prostate cancer (mCRPC). However, not all patients benefit from this therapy. Different treatment responses could be explained by tumor heterogeneity triggered by progression and the number of prior treatments. PSMA-negative lesions can be missed on PSMA ligand PET/CT, which subsequently results in an underestimation of tumor burden. Conversely, high FDG uptake may also be an indicator of tumor aggressiveness and thus a poor prognostic marker for response to RLT and overall survival (OS). The aim of this analysis was to investigate the prognostic value of combined PSMA ligand PET/CT and [
F]fluorodeoxyglucose (FDG) PET/CT for outcome prediction in patients undergoing RLT.
This bicentric analysis included 54 patients with mCRPC who underwent both FDG and PSMA ligand PET/CT imaging before RLT. In all patientMA- lesions should be excluded from PSMA RLT.
In an attempt to identify biomarkers that can reliably predict long-term outcomes to immunotherapy in metastatic melanoma, we investigated the prognostic role of [
F]FDG PET/CT, performed at baseline and early during the course of anti-PD-1 treatment.
Twenty-five patients with stage IV melanoma, scheduled for treatment with PD-1 inhibitors, were enrolled in the study (pembrolizumab, n = 8 patients; nivolumab, n = 4 patients; nivolumab/ipilimumab, 13 patients). [
F]FDG PET/CT was performed before the start of treatment (baseline PET/CT) and after the initial two cycles of PD-1 blockade administration (interim PET/CT). Seventeen patients underwent also a third PET/CT scan after administration of four cycles of treatment. Evaluation of patients' response by means of PET/CT was performed after application of the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria and the PET Response Evaluation Criteria for IMmunoTherapy (PERCIMT). Response to treatment was classified into 4 catapplication of the recently proposed PERCIMT criteria is significantly correlated with PFS. This highlights the potential ability of [18F]FDG PET/CT for early stratification of response to anti-PD-1 agents, a finding with possible significant clinical and financial implications. Further studies including larger numbers of patients are necessary to validate these results.
Continuous external negative pressure (CENP) during positive pressure ventilation can recruit dependent lung regions. We hypothesised that CENP applied regionally to the thorax or the abdomen only, increases the caudal end-expiratory transpulmonary pressure depending on positive end-expiratory pressure (PEEP) in lung-injured pigs. Eight pigs were anesthetised and mechanically ventilated in the supine position. Pressure sensors were placed in the left pleural space, and a lung injury was induced by saline lung lavages. A CENP shell was placed at the abdomen and thorax (randomised order), and animals were ventilated with PEEP 15, 7 and zero cmH
O (15 min each). On each PEEP level, CENP of - 40, - 30, - 20, - 10 and 0 cmH
O was applied (3 min each). Respiratory and haemodynamic variables were recorded. EGFR activation Electrical impedance tomography allowed assessment of centre of ventilation.
Compared to positive pressure ventilation alone, the caudal transpulmonary pressure was significantly increased by CENP of ≤ 20 cmranspulmonary pressure. This lead to a shift of lung aeration towards dependent zones as well as improved respiratory mechanics and oxygenation, especially when CENP was applied to the abdomen as compared to the thorax. CENP values ≤ 20 cmH
O impaired the haemodynamics.
In this lung injury model in pigs, CENP increased the end-expiratory caudal transpulmonary pressure. This lead to a shift of lung aeration towards dependent zones as well as improved respiratory mechanics and oxygenation, especially when CENP was applied to the abdomen as compared to the thorax. CENP values ≤ 20 cmH2O impaired the haemodynamics.
Diabetic neuropathy is one of the most common complications of diabetes, which leads to amputation and significant disability in patients. Studies conducted in this field show different prevalences and inconsistencies in the country. This study attempts to determine the overall prevalence of neuropathy in patients with type2diabetes in Iran with ameta-analysis.
The present study was conducted using a meta-analysis method from January 2000 to December 2018. The papers related to the study subject were obtained from searching Scopus, ScienceDirect, Magiran, Barakat Knowledge Network, SID, Medline (PubMed), and Google Scholar databases. The heterogeneity of studies was examined using I
index and the data were analyzed using the software Comprehensive Meta-Analysis (version3, Biostat, Englewood, NJ, USA).
The results of the systematic review showed regional differences in the prevalence of neuropathy in Iran. According to the meta-analysis and review of 10studies and 2992individuals between the ages of 5years and 86years, the overall prevalence of neuropathy in type2 diabetes patients in Iran was 56.
My Website: https://www.selleckchem.com/EGFR(HER).html
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