Novel uncharged triazole salicylaldoxime derivatives as potential acetylcholinesterase reactivators: comprehensive computational study, synthesis and in vitro evaluation.

The present study aims to design and synthesise novel uncharged aldoximes and explore their reactivation abilities, structures, descriptors, and mechanisms of action, as well as assessing the interactions and stabilities in the active site of paraoxon-inhibited acetylcholinesterase enzyme using computational studies and in vitro assay. The comprehensive computational studies including quantum chemical, molecular dynamics simulations and molecular docking were conducted on paraoxon-inhibited human acetylcholinesterase to investigate the reactivation ability of the novel aldoximes and compare them with pralidoxime as a reactivator model molecule.

Design and development of novel magnetic Lentinan/PVA nanocomposite for removal of diazinon, malathion, and diclofenac contaminants.

Increasing population growth and rapid expansion of the industrialization of the world society have caused severe environmental pollution to the planet. This study was carried out in order to investigate the synthesis of biopolymeric texture nano adsorbent based on the Lentinan (LENT), Poly Vinyl Alcohol (PVA) and Iron Oxide nanoparticles for the removal of environmental pollutants. The spherical structural morphology of Fe3O4@LENT/PVA nanocomposite has been determined by FE-SEM analyses. According to the obtained results from FTIR analyses, all absorption bands of the Fe3O4, LENT, and PVA, had been existed in nanocomposite and approved the successful formation of it. From EDS analysis, it has been revealed that 57.21 wt% Fe, 17.56 wt% C and 25.23 wt% O. Also, the XRD pattern of the nanocomposite, approved the presence of polymeric and magnetic parts with card no. JCPDS, 01-075-0033. The BET analysis has defined specific surface area (47 m2/g) and total pore volume (0.15 cm3/g). Moreover, high heterogeneity and structural stability of the fabricated Fe3O4@LENT/PVA nanocomposite have been proven by TGA. Besides, VSM analysis measured great magnetic property of the nanocomposite (48 emu/g). Also, the Fe3O4@LENT/PVA nanocomposite potential for effective removal of malathion (MA), Diazinon (DA), and Diclofenac (DF) from watery solution has studied by an experiment based on the efficacy of adsorbent dosage, pH, and temperature. The adsorption kinetics of three pollutants had investigated using pseudo-first-order (PFO), pseudo-second-order (PSO) and intra-particle diffusion (IPD) velocity equations, the results showed that the kinetics followed PSO velocity equations. Also, the Langmuir, Freundlich, Dubbin-Radushkevich (D-R) and Temkin isotherm models had investigated, and the adsorption isotherm was adopted from the Langmuir model. The results demonstrated that in the presence of Fe3O4@LENT/PVA nanocomposite, at the optimal conditions (contact time = 180 min, pH = 5, nanocomposite dosage = 0.20 g/L and temperature of 298 K) the maximum adsorption capacity of MA, DF, and DA were 101.57, 153.28, and 102.75 mg/g, respectively. The antibacterial features of the Fe3O4@LENT/PVA nanocomposite, had evaluated by Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria, but the result did not show any antibacterial activity.

The Caucasian Whortleberry Extract/Myrtle Essential Oil Loaded Active Films: Physicochemical Properties and Effects on Quality Parameters of Wrapped Turkey Breast Meat.

In this research work, the effects of myrtle essential oil (MEO) and Caucasian whortleberry extract (CWE) as natural additives were investigated on mechanical, physico-mechanical and antimicrobial properties of gellan/polyvinyl alcohol (G/PVA) film. Then, optimal blend active films were used for the wrapping of turkey breast meat stored at low temperature (4 ± 1 °C) for 15 days and chemical and sensory properties of wrapped meats were evaluated. The addition of MEO and CWE decreased tensile strength and increased the strain at the break of the films (p ≤ 0.05). Additionally, with increasing the amount of MEO and CWE, the permeability to water vapor (WVP) and the moisture content (MC) of the films decreased (p ≤ 0.05). MIC test showed that MEO and CWE were effective against S. aureus, E. coli, S. typhimurium, and P. fluorescens. at the concentrations of 5-6 and 15-17 mg/mL, respectively. Different microbiological, chemical, and sensory tests indicated that active films significantly enhanced the shelf life of turkey breast meat (p ≤ 0.05). Therefore, based on our finding in this study, the use of these active and biodegradable packagings can be effective and useful for protecting the microbial and sensory quality of turkey breast meat.

Magnetic UiO-66 functionalized with 4,4'-diamino-2,2'-stilbenedisulfonic as a highly recoverable acid catalyst for the synthesis of 4H-chromenes in green solvent.

According to 4H-chromenes importance, we synthesized a novel magnetic UiO-66 functionalized with 4,4'-diamino-2,2'-stilbenedisulfonic as an efficient and reusable solid acid catalyst for synthesizing 4H-chromene skeletons via a one-pot three components reaction in a green solvent. The structure of the synthesized catalyst was confirmed by various techniques including FT-IR, XRD, BET, TGA, TEM, EDX, and SEM, and also the product yields were obtained in 83-96% of yields for all the reactions and under mild conditions. The reported procedure presents an environmentally friendly approach for synthesizing a significant number of 4H-chromene derivatives. Correspondingly, MOF-based catalyst makes it easy to separate from reaction media and reuse in the next runs.

Synthesis, Cytotoxicity Evaluation, and Antifungal Activity of Novel Nitroglycerin Derivatives against Clinical Candida albicans Isolates.

BACKGROUND: Candida albicans remains the main cause of candidiasis in most clinical settings. Available drugs for candidiasis treatment have many side effects. In this work, novel nitroglycerin derivatives were synthesized and their cytotoxic and antifungal effects evaluated against fluconazole susceptible and resistant clinical C. albicans isolates. METHODS: This experimental study was performed in Tehran University of Medical Sciences and Baqiatallah University of Medical Sciences, Tehran, Iran between Feb to Dec 2019. The in vitro activities of two novel nitroglycerin derivatives (1b and 2b) against 25 clinical fluconazole-susceptible and resistant C. albicans isolates and four standard C. albicans strains were determined according to CLSI reference M27-A3 documents. The cytotoxicity of chemical compounds was investigated near the SNL76/7 cells by colorimetric assay. Real-time PCRs were performed to evaluate the alterations in the regulation of ERG11 and CDR1 genes under nitroglycerin derivatives-treated and untreated conditions. RESULTS: The derivatives 1b and 2b exhibited potent antifungal activity against C. albicans isolates; MICs and MFCs varied from 18 µg/ml to 72 µg/ml and 36 µg/ml to 144 µg/ml, respectively. The cell viability evaluation demonstrated that both chemical compounds are safe within 24h. The nitroglycerin derivatives were able to reduce the transcription level of CDR1 and ERG11 genes in all susceptible and resistant C. albicans isolates. CONCLUSION: Considering the potential and efficacy of these compounds against clinical C. albicans isolates, the complementary in vivo and clinical trials should be investigated.

Enhanced antimicrobial treatment by a clay-based drug nanocarrier conjugated to a guanidine-rich cell penetrating peptide.

In this study, a novel and efficient drug delivery system is proposed for the enhancement of antimicrobial properties of antibiotic medications such as vancomycin (VCM) and levofloxacin (OFX). The architecture of the designed drug carrier is based on halloysite nanotubes (HNTs) with a rolled-laminate shape, suitable for the encapsulation of drug and further release. In order to make them capable for magnetic direction to the target tissue, the exterior surface of the tubes is composed of iron oxide nanoparticles (Fe3O4 NPs), via an in situ process. The main role in the antimicrobial activity enhancement is played by a cell-penetrating peptide (CPP) sequence synthesized in the solid phase, which contains three arginine-tryptophan blocks plus a cysteine as the terminal amino acid (C(WR)3). The drug content values for the prepared nanocargoes named as VCM@Fe3O4/HNT-C(WR)3 and OFX@Fe3O4/HNT-C(WR)3, have been estimated at ca. 10 wt% and 12 wt%, respectively. Also, the drug release investigations have shown that above 90% of the encapsulated drug is released in acetate buffer (pH = 4.6), during a 90 minutes process. Confocal microscopy has corroborated good adhesion and co-localization of the particles and the stained living cells. Moreover, in vitro antimicrobial assessments (optical density, zone of inhibition, and minimum inhibitory concentration) have revealed that the bacterial cell growth rate is significantly inhibited by suggested nanocargoes, in comparison with the individual drugs in the same dosage. Hence, administration of the presented nanocargoes is recommended for the clinical treatment of the infected target organ.

A fluorescence Nano-biosensors immobilization on Iron (MNPs) and gold (AuNPs) nanoparticles for detection of Shigella spp.

The highly sensitive and specificity detection are very important in diagnosis of foodborne pathogens and prevention of spread diseases. Therefore, in the present study, a highly sensitive fluorescence Nano-biosensors was designed for detection of Shigella species. For achieved this purpose, DNA probes and gold nanoparticles (AuNPs) were designed and synthesized, respectively. Then, two DNA probes as signal reporter were immobilized on surface of AuNPs. On the other hand, Iron nanoparticles (MNPs) were synthesized and modified with SMCC (Sulfosuccinimidyl 4-Nmaleimidomethyl cyclohexane-1- carboxylate). The 3th DNA probe was immobilized on surface of MNPs for separation of target DNA. The MNP-DNA probe and DNA probe-AuNP-fluorescence DNA probe were added to target DNA. The MNP- DNA probe-target DNA-DNA probe-AuNP-fluorescence DNA probe complex was isolated by a magnet. The fluorescence DNA probe was released on surface of AuNPs and the fluorescence intensity was read by fluorescence spectrophotometry. Sensitivity and specificity of designed Nano-biosensor was determined. The results showed that the fluorescence intensity was increased with increasing of target DNA concentration. Linear related between target DNA and fluorescence intensity was observed in 2.3 × 102 up to 2.3 × 107 CFU mL-1. The linear equation and regression were Y = 1.8 X + 23.4 and R2 0.9953. Limit of detection (LOD) were determined 90 CFUmL-1. The specificity of Nano-biosensor in present of other bacteria was confirmed.

Precise, direct, and rapid detection of Shigella Spa gene by a novel unmodified AuNPs-based optical genosensing system.

Early detection of infectious bacteria is a necessity for combating infectious diseases. Due to low infectious dose of Shigella, rapid and sensitive detection is needed. Compared to the presented genes, Spa gene can be introduced as a novel sequence for all species of Shigella detection. Herein, the possibility of Spa genes for detection of four species of Shigella was investigated for the first time by AuNPs-based optical genosensing system. In this method, AuNP-DNA probes were hybridized with Spa gene sequence. When the complementary target is present, it prevents the aggregation of the complex under acid environment and the solution remains red whereas in the absence of the specific sequence, it turns to purple. Therefore, visual detection is possible with bare eye. The comparison of this Optical DNA biosensor and PCR-based method showed that the proposed method is simple, cost-effective, rapid operation, with high or comparable detection limit of (LOD and LOQ: 8.14 and 26.6 ng mLl-1, respectively), without need of any expensive techniques, and equipments compared to the conventional methods. In conclusion, the described method may develop into a platform that could be utilized for detection of various bacterial species with high accuracy and prompt screening of samples.

Recent biomedical applications of gold nanoparticles: A review.

Recent advances in nanotechnology are as a result of the development of engineered nanoparticles. Efficiently, metallic nanoparticles have been widely exploited for biomedical application and among them, gold nanoparticles (AuNPs) are highly remarkable. Consequent upon their significant nature, spherical and gold nanorods (Au NRs) nanoparticles attract extreme attention. Their intrinsic features such as optical, electronic, physicochemical and, surface plasmon resonance (SPR); which can be altered by changing the characterizations of particles such as shape, size, aspect ratio, or environment; ease of synthesis and functionalization properties have resulted to various applications in different fields of biomedicine such as sensing, targeted drug delivery, imaging, photothermal and photodynamic therapy as well as the modulation of two or three applications. This article reviewed the popular AuNPs synthesis methods and mentioned their established applications in various demands, especially in biological sensing.

Clinical application of ultrasound for preparation of (99m)Tc-sestamibi complex.

OBJECTIVE: The main aim of this investigation is the clinical application of ultrasound irradiation technique as an alternative method to reconstitute sestamibi kits in comparison of water boiling bath method. METHODS: The 740-3700 MBq (20-100 mCi) (99m)Tc-MIBI (sestamibi) complex samples were prepared due to ultrasound irradiation technique or boiled water bath method as a standard method. Twenty patients (8 men and 12 women; age range 30-72, median 52.45 years) have been referred to Golestan hospital for myocardial perfusion imaging (MPI). The subjects have been divided randomly into group A (3 men, 7 women, age range 36-67, median 51.7 years) and group B (5 men, 5 women, age range 30-72, median 50.3 years), respectively. The (99m)Tc-MIBI radiopharmaceuticals have been prepared by Ultrasound irradiation technique administrated to group A and (99m)Tc-MIBI complex samples due to the boiled water bath technique administrated to the other group. For all patients, the 2-day stress/rest MPI protocol was performed. RESULTS: The radio-HPLC and TLC studies have indicated that the (99m)Tc-MIBI complex samples with good yields could be prepared successfully due to new developed technique. The scintigraphy imaging studies have demonstrated that the (99m)Tc-sestamibi prepared due to the above-mentioned modalities shows very identical biodistribution in the heart, thyroid, lung, liver, gallbladder, kidneys, stomach, large intestine and bladder of the subjects. Any unexpected accumulation of radiotracer samples have not been observed in our approach. CONCLUSIONS: The ultrasound irradiation technique is convenient and sufficient method to prepare (99m)Tc-sestamibi. It can be recommended as an alternative method to reconstitute sestamibi kits particularly in emergency situations to reduce potentially medical risk by avoiding any delay in acute therapy for myocardial infarction.