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ADAM33 is a zinc-dependent metalloprotease of the ADAM family, which plays a vital biological role as an activator of Th2 cytokines and growth factors. Moreover, this protein is crucial for the normal development of the lung in the fetus two months after gestation leading to determining lung functions all over life. In this regard, mutations in ADAM33 have been linked with asthma risk factors. Consequently, identifying ADAM33 pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) can be very important in asthma treatment. In the present study, 1055 nsSNPs of human ADAM33 were analyzed using biocomputational software, 31 of which were found to be detrimental mutations. Precise structural and stability analysis revealed D219V, C669G, and C606S as the most destabilizing SNPs. Furthermore, MD simulations disclosed higher overall fluctuation and alteration in intramolecular interactions compared with the wild-type structure. Overall, the results suggest D219V, C669G, and C606S detrimental mutations as a starting point for further case-control studies on the ADAM33 protein as well as an essential source for future targeted mechanisms.

The wound is a break in the integrity of the skin produced by injury, illness, or operation. Wound healing is an essential dynamic biological/physiological process that occurs in response to tissue damage. The huge health, economic, and social effects of wounds on patients and societies necessitate the research to find novel potential therapeutic agents in order to promote wound healing. Postbiotics, the newest member of the biotics family, are valuable functional bioactive substances produced by probiotics through their metabolic activity, which have several beneficial properties, including immunomodulatory, anti-inflammatory, antimicrobial, and angiogenesis characteristics, resulting in acceleration of wound healing. In the current study, three topical cold cream formulations containing postbiotics obtained from Lactobacillus fermentum, Lactobacillus reuteri, or Bacillus subtilis sp. natto probiotic strains were prepared. The effectiveness and wound healing activity of the developed postbiotics cold cream formulations were investigated compared to cold cream without postbiotics and no treatment via wound closure investigation, hydroxyproline content assay, and histological assessment in 25 Sprague Dawley rats divided into five groups. Interestingly, analysis of the results revealed that all three formulations containing postbiotics significantly accelerated the wound healing process. However, in general, the Bacillus subtilis natto cold cream manifested a better wound healing property. The pleasing wound healing characteristics of the topical postbiotics cold creams through the in vivo experiment suggest that formulations containing postbiotics can be considered as a promising nominee for wound healing approaches.

Wound healing is a physiological reaction to tissue injuries which plays a crucial role in replacing the destroyed tissues. Probiotics produce valuable compounds that possess antibacterial and anti-inflammatory activities, immunomodulatory effects, and angiogenesis traits leading to the promotion of wound healing. Chitosan nanostructures have versatile properties making them quickly produced into gels, scaffolds, nanoparticles, beads, and sponge structures that can be incorporated into wound healing processes. In the current study, three formulations from nanogel consisting of probiotic supernatant (Lactobacillus reuteri, Lactobacillus fermentum, and Bacillus subtilis sp. natto)-loaded chitosan nanogels were prepared from the culture of corresponding cultures. The chitosan nanogels were previously characterized by Zetasizer, FTIR, and TEM. The prepared formulations' effectiveness and dressing activity were assessed by evaluating wound closure and histological trials in Sprague-Dawley rats. The results indicated that all probiotic lysate formulations have advantages over the wound healing process. However, Bacillus subtilis natto has a better wound healing quality, which is well known in pathology examination. The favorable effects of probiotic lysate nanogels, including the reasonable wound closing rate, good wound appearance, and satisfactory histological observation via in vivo examination, suggest it as a promising nominee for wound healing purposes.

Wound healing is a physiological reaction to tissue injuries which plays a crucial role in replacing the destroyed tissues. Probiotics produce valuable compounds that possess antibacterial and anti-inflammatory activities, immunomodulatory effects, and angiogenesis traits leading to the promotion of wound healing. Chitosan nanostructures have versatile properties making them quickly produced into gels, scaffolds, nanoparticles, beads, and sponge structures that can be incorporated into wound healing processes. In the current study, three formulations from nanogel consisting of probiotic supernatant (Lactobacillus reuteri, Lactobacillus fermentum, and Bacillus subtilis sp. natto)-loaded chitosan nanogels were prepared from the culture of corresponding cultures. The chitosan nanogels were previously characterized by Zetasizer, FTIR, and TEM. The prepared formulations’ effectiveness and dressing activity were assessed by evaluating wound closure and histological trials in Sprague-Dawley rats. The results indicated that all probiotic lysate formulations have advantages over the wound healing process. However, Bacillus subtilis natto has a better wound healing quality, which is well known in pathology examination. The favorable effects of probiotic lysate nanogels, including the reasonable wound closing rate, good wound appearance, and satisfactory histological observation via in vivo examination, suggest it as a promising nominee for wound healing purposes.

Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility. They also resemble pathogens in terms of their size. Their multivalency allows an orderly repetitive display of antigens on their surface, which induces a stronger immune response than single immunogens. In vaccine design, SAPN self-adjuvanticity is regarded an outstanding advantage, since the use of toxic adjuvants is no longer required. SAPNs are usually composed of helical or β-sheet secondary structures and are tailored from natural peptides or de novo structures. Flexibility in subunit selection opens the door to a wide variety of molecules with different characteristics. SAPN engineering is an emerging area, and more novel structures are expected to be generated in the future, particularly with the rapid progress in related computational tools. The aim of this review is to provide a state-of-the-art overview of self-assembled peptide nanoparticles and their use in vaccine design in recent studies. Additionally, principles for their design and the application of computational approaches to vaccine design are summarized.

A novel lipopolymer based system was designed and characterized for cellular delivery of anti-VEGF siRNA in SKBR-3 breast tumor cell line. Polyamidoamine (PAMAM) dendrimers of low generations (G1, G2 and G3) were incorporated into polyethylene glycol (PEG)-stabilized liposomes by following the consecutive steps: (a) synthesis of the cholesterol conjugates (40% molar ratio of cholesterol to primary amines of PAMAM), (b) incorporation of the conjugates in liposome by lipid mixing and (c) microencapsulation of the siRNA using the ethanol drop method. The cholesterol conjugates of PAMAM dendrimers (G1-Chol40%, G2-Chol40% and G3-Chol40%) formed self assembly with low CMC values (

In this data article, carboxyfluorescein-loaded liposomes were prepared and purified from free carboxyfluorescein using gel filtration chromatography in the first part. In the next part, following preparation of anti-VEGF siRNA loaded liposomes incorporating hydrophobically modified G2 PAMAM dendrimer (G2-Chol40%) (Golkar et al., 2016) [1], the cell growth inhibition induced by the formulations (siRNA/Metafectene complexes and siRNA loaded liposomes incorporating hydrophobic G2) was evaluated at two exposure times through MTT assay in a breast cancer cell (SKBR-3) and compared by two-way ANOVA. Keywords: Anti-VEGF siRNA, Cell growth inhibition, Polyamidoaminedendrimer, Liposome

The current study deals with the production of l -methioninase from newly isolated bacterium Alcaligenes spp. via submerged fermentation. The statistical methods of one factor at a time (OFAT) and response surface methodology were used to optimize the nutritional and cultivation factors for the production of l -methioninase by Alcaligenes sp MT-B. The regression models depicted considerably high R2 values of 0.87% for l -methioninase activities, signifying that they are suitable for forecasting associations between lactose, yeast extract, pH and temperature. In accordance with the model, the optimum condition for l -methioninase production were yeast extract 0.2%; lactose 0.75%, pH 6 and temperature 34.6 °C. These forecasted conditions were confirmed by validation trials. In the optimized condition Alcaligenes sp MT-B produced l -methioninase with the activity of 13.06 U/ml which is 1.4 times superior to that produced in initial fermentation condition. Hence, this statistical technique enabled fast identification and combination of key medium factors for Alcaligenes sp MT-B, resulted in the high l -methioninase production.

A new class of cell penetrating peptides (CPPs) named peptide amphiphile was designed to improve the intracellular uptake and the antitumor activity of epirubicin (EPR). Various amphiphilic CPPs were synthesized by solid phase peptide synthesis method and were chemically conjugated to EPR. Their corresponding nanoparticles (CPPs-E4 and CPPs-E8) were prepared via non-covalent binding of the peptides and polyanions. Cytotoxicity and anti-proliferative activity were evaluated by MTT assay. Cellular uptake was examined by flow cytometry and fluorescence microscopy. The CPPs exhibited slight cytotoxicity. Binding of polyglutamate to CPPs (CPPs-E4 and CPPs-E8 nanoparticles) decreased their cytotoxicity. CPPs-E8 nanoparticles showed lower cytotoxicity than CPPs-E4 nanoparticles. Cellular uptake of K3W4K3-E8, K2W4K2-E8 and W3K4W3-E8 reached 100% with no difference between each of the mentioned CPPs and its nanoparticles at 50 µM. The anti-proliferative activity of EPR was enhanced following conjugation to peptides and nanoparticles at 25 µM. CPPs-EPR-E4 and CPPs-E8-EPR nanoparticles displayed higher anti-proliferative activity than CPPs-EPR at 25 µM. CPPs-E8-EPR nanoparticles showed higher anti-proliferative activity than CPPs-E4-EPR. K3W4K3-E8-EPR nanoparticles exhibited the highest anti-proliferative activity at 25 µM. The synthesized peptide nanoparticles are proposed as suitable carriers for improving the intracellular delivery of EPR into tumor cells with low cytotoxicity and high antitumor activity.

Stealth liposomes encapsulating oligonucleotides are considered as promising non-viral gene delivery carriers; however, general preparation procedures are not capable to encapsulate nucleic acids (NAs) efficiently. In this study, the lyophobic complexes of deoxythymidine20 oligonucleotide (dT20) and DOTAP were used instead of free dT20 for nano-encapsulation process by reverse phase evaporation method. Regarding the various factors that can potentially affect the liposome characteristics, Taguchi design was applied to analyze the simultaneous effects of factors comprising PEG-lipid (%), dT20/total lipid molar ratio, cholesterol (Chol%) and organic-to-aqueous phase ratio (o/w) at three levels. The response variables, hydrodynamic diameter, loading efficiency (LE%) and capacity (LC%), were studied by dynamic light scattering and ethidium bromide exclusion assay, respectively. The optimum condition described by minimum particle size as well as high LE% and LC% was obtained at 5% PEG-lipid, dT20/total lipid of 7, 20% Chol and o/w of 3 with an average size of 84 nm, LE% = 83.4% and LC% = 11.6%. Moreover, stability assessments in presence of heparin sulfate revealed the noticeable resistance, unlike DOTAP/dT20 lipoplexes, to premature release of NA. Transmission electron microscopy confirmed formation of discrete and circular vesicles encapsulating dT20.

Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and 1H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (

Context: Anti-HER2 immunoliposomes are promising nanotechnology based systems for active targeting of breast tumors, which depends on the amount of incorporated antibody. Objective/Aim: In this work, we investigated the possible effect of lipid composition on the incorporation of trastuzumab-PEG-PE micelles into nanoliposomes and on their subsequent specific cellular targeting. Materials and methods: Trastuzumab (anti-HER2 monoclonal antibody) was monothiolated and conjugated to maleimide-PEG-PE micelles. Liposomes of different lipid compositions were prepared by the thin layer hydration. Trastuzumab-PEG-PE micelles were incorporated into the liposomes by the post-insertion method. The percentage of lipid mixing was determined based on fluorescence resonance energy transfer. Cellular binding and uptake of rhodamine-labeled immunoliposomes were studied in SKBR-3 (HER2+++) and MCF-7 (HER2+) cells. Also, antitumor cell activity of the immunoliposomes was compared to free trastuzumab and the liposomes. Results: The lipid mixing of trastuzumab-PEG-PE micelles depended on the liposome composition. The immunoliposomes containing DPPC, cholesterol and PEG-PE showed prominent lipid mixing. The lipid mixing was consistent with the cell binding results which showed an efficient and specific binding of the immunoliposomes to SKBR-3 cells. Antitumor cell activity of the immunoliposomes in SKBR-3, unlike MCF-7 cells, depended on the content of trastuzumab. Discussion: Cholesterol and PEG-PE in the liposome composition are prerequisites for a successful lipid mixing due to their ability to facilitate fusion. The higher lipid mixing results in higher antibody incorporation and consequently higher targeted cell binding. Conclusions: The lipid mixing depends on the liposome composition, which reflects targeted cell binding of the immunoliposomes.