arash mahboubi

This study was done to achieve a new drug delivery system delivering two different chemotherapy molecules to the target tissue simultaneously.Significance: Co-delivery of chemotherapy medicines provides synergistic effects leading to lowering the dose of administered drugs and side effects.

Doxorubicin (DOX) was introduced to water-soluble hyaluronic acid (Hyal) using 1-amino-3,3-diethoxy-propane (ADEP), as a pH-sensitive linker, to develop a new hydrophobic structure, i.e. Hyal-ADEP-DOX. The conjugates were grafted in three ratios (7.5%, 12.5%, and 20%) to Hyal and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1HNMR). Cannabidiol (CBD) was physically loaded in the core of nano-micelles.

Prepared nano-micelles were analyzed for critical micelle concentration (CMC) particle size stability and drug release before and after loading the CBD. Hyal-ADEP-DOX-12.5 was the optimized ratio and had a mean diameter of 50 nm before loading the CBD and 120 nm after loading (observed by transmission electron microscopy). The release results showed that DOX releases slowly in physiological pH, and CBD has a burst release at acidic pH from Hyal-ADEP-DOX-12.5. These properties altogether make Hyal-ADEP-DOX nano-micelles, as a stimuli-sensitive nano-carrier, a potential candidate for hydrophobic anticancer agents’ co-delivery.

The grafted DOX exhibited pH-sensitive release behavior, i.e. while 22.8% of the drug was released after 24 h at pH 5.5, and 5% was released after 24 h at pH 7.4. Hyal-ADEP-DOX due to its low CMC value, colloidal stability, slow drug release in physiological pH, and burst release in acidic pH Hyal-ADEP-DOX, is an excellent candidate as a carrier to co-deliver hydrophobic therapeutic agents to tumor tissues.

Infectious wounds are one of the issues that significantly burden population lives and finances each year. Even though there have been significant breakthroughs in wound healing dressing, wound infections continue to be an issue. One of the latest techniques is using contemporary dressings containing antimicrobial agents to expedite wound healing and prevent infection. In the present study, the effect of gold nanoparticles (AuNPs) and hydroxypropylmethylcellulose (HPMC) as the main expedient of a hydrogel formulation on the bioactivity of two newly designed antimicrobial peptide (AMPs) was investigated. AuNPs were produced using two methods of chemical and biological synthesis. AuNPs were characterized individually and in the presence of AMPs in a stepwise manner. The antibacterial activity of these combinations against Staphylococcus aureusand Acinetobacter baumaniiwas evaluated. The results demonstrated that the stability of green-synthesized AuNPswas significantly superior to that of chemically synthesized AuNPs in presence of AMPs. In addition, the antibacterial activity of AMPs changed when combined with AuNPs and HPMC compared to its free state. This alteration wasdifferent based on the AMP identity and the combination composition. In the case of AMP1, designed based on regenerating islet-derived protein 3-alpha (REG3A), addition of AuNPs could enhance the antimicrobial activity. However, in the presence of another AMP (designed based on Cathelicidin-2), activity variations did not adopt with a distinct pattern. In general, the best antimicrobial activity was observed on the A. baumaniiwhen a combination of green synthesized AuNPs, AMP derived from Cathelicidin-2 and HPMC was applied. In conclusion, since the inclusion of hydrogel and nanoparticles inthe most combination conditions resulted in the efficacy reduction of AMPs, further efforts in selecting a suitable polymeric component should be made to develop an effective and inexpensive wound dressing formulation for this designed AMP.

Cyanobacteria and microalgae are promising sources of valuable bioactive compounds for nutraceutical and pharmaceutical applications. Proteins and peptides derived from these microorganisms have been shown different biological actions, including antioxidant and antimicrobial activities. In this study, Desmodesmus sp. protein extract was digested using two proteases, including bacterial protease with optimum activity in alkaline conditions and pepsin with optimum activity in acidic pH. The peptide mixtures derived from protease hydrolysis were evaluated by DPPH assay for antioxidant activity and microdilution antimicrobial assay. The results showed that peptides derived from both pepsin and bacterial protease digestions enhanced the antioxidant activity and these samples had between 80-100% antioxidant activities. In addition, pepsin digestion could reduce the MIC against S. aureus and methicillin-resistant S. aureus (MRSA) twofold compared to the initial protein extract before digestion. In conclusion, the peptides derived from enzymatic digestion of Desmodesmus sp. protein extract had promising biological activities that need further studies to identify the most bioactive peptide.

Breast cancer is a deadly disease with a high prevalence rate among females. Despite several treatments, scientists are still engaged in finding less invasive treatments for this disease. The cellular proliferation rate and cell viability survey are critical to assess the drug’s effect on both normal and malignant cell populations. Indole derivatives are promising candidates for their cytotoxic effect causing on breast cancer cells; however, they are less toxic on normal cells. This study synthesized 23 novel 5-hydroxyindole-3-carboxylic acids and related esters featuring various linear, cyclic, and primary aromatic amines. The MTT assay indicated the cytotoxicity of all acid and ester derivatives against the MCF-7 cells with no significant cytotoxicity on normal human dermal fibroblasts cells. Compound 5d, an ester derivative possessing a 4-methoxy group, was the most potent compound, with a half-maximal effective concentration of 4.7 µM. Compounds 5a, 5d, and 5l bearing ester group in their structure demonstrated cytotoxicity values < 10 µM against the MCF-7 cell line and were safe for advanced screening.

Since several Helicobacter pylori strains have become resistant to metronidazole, new nitroimidazole derivatives based on metronidazole were designed and synthesized with different substituents on imidazole nitrogen. The activity of the synthesized compounds was evaluated against 20 clinically isolated metronidazole-resistant H. pylori strains. Some synthesized compounds were effective against those metronidazole-resistant H. pylori strains. Three compounds exhibited the most potent inhibitory activities (MIC50 = 8 µg/mL and MIC90 = 16 µg/mL).

Breast cancer is the most common cancer among women and only second in terms of cancer-related death in women. Finding new approaches to treat such cancers is critically important anti-cancer peptides (ACPs) offer the possibility of efficient-cancer drugs, and therefore, the development of drug delivery systems using ACPs as a synergism factor is an attractive strategy to address the current drawbacks of cancer therapeutics. This work investigated the cytotoxicity for a series of synthesized compounds based on triazole or ciprofloxacin conjugated peptides against T-47D breast cancerous cells and possible antibacterial effects. Wang resin was used for constructing peptide sequences on a solid support using the method of solid-phase peptide synthesis (spps) with the Fmoc strategy. Cytotoxicity of the synthesized peptide compounds was evaluated by MTT assay. The antimicrobial effect of synthesized peptide compounds was evaluated by agar well diffusion and Broth microdilution method. Most of the peptide compounds showed a cytotoxic effect toward T-47D cells. The antimicrobial effect of the peptide compounds was examined by agar well diffusion test and broth microdilution method. E. coli and S. aureus strains have shown the least amount of resistance. In the end, we suggest a new design based on these compounds and modifications to gain better anti-cancer agents

One of the attractive sources of bioactive compounds is cyanobacteria and in particular, Chlorellavulgaris and Spirulinaplatensis. Enzymatic digestion of the Spirulinaprotein extract can result in bioactive peptides with diverse activities, including antioxidant function. This study aims to produce peptides with antioxidant properties after the enzymatic digestion of Spirulinaplatensisprotein extract using three enzymes: bacterial protease, pepsin, and papain. The protein extract from Spirulina platensiswas subjected to enzyme hydrolysis for 3 hours at 37°C (pH 7.4 for papain and bacterial protease and pH 5 for pepsin). The concentration of peptide fragments was evaluated to determine the yield of protein digestion. In order to measure the level of anti-oxidative potential of the hydrolysates, the DPPH assay was run. The results indicated that the bacterial protease led to the highest concentration of peptide fragments, while the hydrolysate obtained from pepsin digestion showed the most antioxidant activity (80%), mainly the peptides that have molecular weights less than 14 KDa. Consequently, pepsin can be a proper enzyme to produce antioxidant peptides from the protein extract of S. platensis. In conclusion, the results of the study confirmed that the products of enzymatic digestion by different enzymes have distinct features.

Due to their unique mechanisms of action, antimicrobial peptides (AMPs) are promising candidates to combat different infectious diseases. They usually non-specifically interact with the bacterial cell membrane, create pores in their membrane and increase its permeability which causes the death of pathogens. In the design and development of AMPs, in silicostrategies have been developed to enhance the function and activity of natural peptides. In this study, in silicoapproaches were used to develop a novel AMP with several extra bioactivities. Then, the designed AMP were analyzed through computational methods by in vitroexperiments. Bioinformatics research revealed a 10-amino-acid peptide (LVSARIRCPK) having antibacterial, anti-biofilm, antiviral, antifungal, and anti-inflammatory effects. However, only the antiviral capabilities of the peptide were validated in the experimental analysis of antibacterial, antifungal, and antiviral activities. This data suggests that; while bioinformatics approaches have greatly advanced in recent years, more optimization work has to be done in order to attain high accuracy and minimize mistakes

Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents.

In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed.

Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM’s lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min.

The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-SS-PNIPAM compared to the free drug (DOX).

Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.

Microemulsion-based gels (MBGs) were prepared for transdermal delivery of lidocaine and evaluated for their potential for local anesthesia. Lidocaine solubility wasmeasured in various oils, and phase diagrams were constructed tomap the concentration range of oil, surfactant, cosurfactant, and water for oil-in-water (o/w)microemulsion (ME) domains, employing the water titrationmethod at different surfactant/cosurfactant weight ratios. Refractive index, electrical conductivity, droplet size, zeta potential, pH, viscosity, and stability of fluid o/w MEs were evaluated. Carbomer® 940 was incorporated into the fluid drug-loaded MEs as a gelling agent. Microemulsion-based gels were characterized for spreadability, pH, viscosity, and in-vitro drug release measurements, and based on the results obtained, the best MBGs were selected and subsequently subjected to ex-vivo rat skin permeation anesthetic effect and irritation studies. Data indicated the formation of nano-sized droplets of MEs ranging from 20 - 52 nm with a polydispersity of less than 0.5. In-vitro release and ex-vivo permeation studies on MBGs showed significantly higher drug release and permeation in comparison to the marketed topical gel. Developed MBG formulations demonstrated greater potential for transdermal delivery of lidocaine and advantage over the commercially available gel product, and therefore, they may be considered as potential vehicles for the topical delivery of lidocaine.

 As a widely used therapeutic protein, recombinant human erythropoietin (rhEPO) is currently one of the most effective biopharmaceuticals on the market for the treatment of anemia in patients with chronic renal disease. Increasing in vivo rhEPO half-life and its bioactivity is a significant challenge. It was hypothesized that the application of self-assembly PEGylation retaining activity, named supramolecular (SPRA) technology, could prolong the protein half-life without a significant loss of bioactivity.

 This study aimed to assess the stability of rhEPO during synthetic reactions, including the conjugation with adamantane and the formation of the SPRA complex. To do this, the secondary structure of the protein was also evaluated.

 FTIR, ATR-FTIR, Far-UV-CD, and SDS-PAGE methods were employed. Thermal stability studies of SPRA-rhEPO complex and rhEPO were investigated at 37°C for ten days using a nanodrop spectrophotometer.

 The secondary structure of lyophilized rhEPO, AD-rhEPO, and rhEPO (pH 8) was compared to rhEPO. Results showed that the secondary structure of the protein was unaffected by lyophilization, pH change, and the formation of covalent bonds in conjugation reaction. SPRA-rhEPO complex was also stable for seven days in phosphate buffer (pH 7.4) at 37°C.

 It was concluded that the stability of rhEPO could increase by complexation using SPRA technology.

The emergence of drug resistance to the existing antibacterial and anti-HIV-1 therapeutics has posed an urgent medical need to develop new molecules. We describe in this regard, a series of novel N'-arylidene-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide derivatives with anti-HIV-1 and antibacterial activities were designed and synthesized in this study.

The synthesized compounds were evaluated for the blocking of both the IN ST process and cell-based HIV-1 replication. The synthesized compounds were also examined for in vitro antibacterial activities using the minimum inhibitory concentration (MIC) assay.

The results revealed the moderate antibacterial activity of the synthesized compounds. Moreover, no significant integrase inhibitory and anti-HIV-1 activities were observed for the synthesized compounds at concentrations < 100 µM.

According to the docking analyses, the orientation of the designed scaffold in the active site of integrase is similar to the other inhibitors of the HIV integrase and can be regarded as an acceptable template for further structural modification to improve potencies.

Illegal and excessive use of veterinary antibiotics as a food additive for growth promotion in livestock can lead to allergic reactions and antibiotic resistance, which is a worldwide concern. A biochip-based semi-quantitative screening method of antimicrobial residues in milk was validated based on Commission Decision 2002/657/EC and the European guideline to validate screening methods for veterinary medicines. This multi-analytical screening method enables to determine of 3 beta-lactams (cefalexin, ampicillin, and cefuroxime) simultaneously. Analysis of 20 blank and 20 spiked milk samples showed that for all 3 antibiotic residues, the positivity threshold T was above cut-off value Fm, and no false-positive results were obtained for all 3 antibiotics. All detection capabilities (CCβ) were below Maximum Residue Level (MRL) authorized by European Commission. 47 UHT cow’s milk samples collected from Tehran province, IR Iran, were screened, and compliance was found in 100% of samples. This study found that the biochip method is valid to determine antibiotic residues in milk samples at the measured validation levels. The method was fast, simple, and able to simultaneous screen three families of beta-lactams from a single milk sample with almost no sample preparation.

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.

Mobilization and engraftment of Hematopoietic Stem Cells (HSCs) are challenging issues in Autologous HSC transplantation (AHSCT) so several attempts such as colony-stimulating factors (CSF) and plerixafor have been used for enhancement of HSCs mobilization and engraftment. In this randomized, double-blind and placebo-controlled study, we evaluated the melatonin’s efficacy and safety, as endogenous CSF inducer, co-administered with Filgrastim in mobilizing and engraftment of HSC. AHSCT patients were randomized to receive either Melatonin or placebo plus filgrastim. Of Fifty-one patients, 26 patients received the melatonin (In mobilization phase 3 mg sublingual twice daily, then 9 mg single dose 30 min before apheresis session and then 3 mg twice daily from +1 until engraftment) and 25 patients received the placebo. The mean number of CD34 cells/kg × 106 in the melatonin group was 6.54 versus 4.22 in the placebo group (p = 0.025). The mean day to neutrophil engraftment in the melatonin group was 11.69 ± 2.093, whereas 12.68 ± 2.42 days in the placebo group (p = 0.021). In this study, the second apheresis session requirement, the use of plerixafor and hospital stay duration, were comparable between the two groups. Considering the result of the study, it could be suggested that melatonin plus Filgrastim can be effectively used in AHSCT patients to enhance the number of peripheral CD34 cells/kg × 106 and decrease the day number of neutrophil engraftment.

This research aimed to evaluate the cytotoxicity, anti-bacterial, anti-fungal and heme polymerization inhibition activities, as well as the detection of the chemical composition of essential oils and measurement of the amount of total phenol and flavonoids of Cousinia harazensis and C. calocephala. In-vitro growth inhibitory effects of methanol extracts on A2780, T-47D, A549 and Hep-G2 cells were evaluated by MTT assay. MIC and MBC/MFC were determined by the agar dilution method. The anti-malarial activity of herbs was assessed with an inhibition test of heme detoxification (ITHD). Total phenol and flavonoids content measured by Folin-Ciocalteu method. The essential oils from two herbs were extracted by hydro-distillation, and GC/MS analyzed their compositions. Cell studies against selected cell lines growth in MTT assay were related to C. harazensis on Hep-G2 with IC50 of 4.521 µg/mL. The MIC of anti-bacterial and anti-fungal effects is related to C. harazensis extract on Staphylococcus epidermidis and Aspergillus fumigatus with 15.62 and 62.5 mg/mL, respectively. Both extracts do not have anti-malarial activity. C. harzensis content was richer in total phenol and flavonoids rather than the other herb. m-benzyl benzyl alcohol (46.7%) and butyl phthalate (14.7%) are the major compounds of C. harazensis; main components of C. calocephala are 3-methyl-tetrahydrofuran (24.6%) and oleic acid (15.4%). In conclusion, C. harazensis with more phenol and flavonoids content showed better results in terms of biological activities.

The most common diagnostic method for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Upper respiratory tract samples, including nasopharyngeal swab (NPS), oropharyngeal swab (OPS), saliva and lower respiratory tract samples such as sputum, are the most widely used specimens for diagnosis of SARS-CoV-2 using RT-qPCR. This study aimed to compare the diagnostic performance of different samples for Coronavirus disease 2019 (COVID-19) detection. It was found that NPS, the reference respiratory specimen for COVID-19 detection, is more sensitive than OPS. However, the application of NPS has many drawbacks, including challenging sampling process and increased risk of transmission to healthcare workers (HCWs). Saliva samples can be collected less invasively and quickly by HCWs with less contact or by own patients, and they can be considered as an alternative to NPS for COVID-19 detection by RT-qPCR. Additionally, sputum, which demonstrates higher viral load can be applied in patients with productive coughs and negative results from NPS. Commonly, after viral RNA purification from patient samples, which is time-consuming and costly, RT-qPCR is performed to diagnose SARS-CoV-2. Herein, different approaches including physical (heat inactivation) and chemical (proteinase K treatment) methods, used in RNA extraction free- direct RT-qPCR, were reviewed. The results of direct RT-qPCR assays were comparable to the results of standard RT-qPCR, while cost and time were saved. However, optimal protocol to decrease cost and processing time, proper transport medium and detection kit should be determined.

Veterinary drugs are extensively and legally consumed to treat and prevent disease in chattels but some are also used illegally as growth-stimulating agents. Inappropriate or intensive use of antibiotics can cause allergic reactions and, above all, antibiotic resistance. A multiclass approach for the screening of antimicrobial substances in milk was validated in consonance with Commission Decision 2002/657/EC and to the European guideline for the validation of screening methods for veterinary medicines. This biochip-based approach enables the simultaneous determination of a total of 13 sulphonamide, dapsone and trimethoprim. For monitoring of antibiotic residues, 53 UHT milk samples collected from Tehran, IR Iran were screened applying this technology. The result showed that for all antibiotic residues, the positivity threshold T was much more than the cut-off value Fm. A false positive rate of less than 5% was found for all antibiotics which are satisfactory. All detection capabilities (CCβ) were well below the Maximum Residue Level (MRL) set by the European Commission (100 µg/kg for the sum of all sulphonamides and 50 µg/kg for trimethoprim in milk). The screening results of 53 milk samples showed that 71.7% of samples were compliant and all positive samples were below the MRL set by European Commission. This study showed that the biochip-based technique is valid to identify and quantify antibiotic residues in milk at the studied validation levels. The method was rapid, easy, safe, and able to screen 13 sulphonamide, dapsone and trimethoprim from a single milk sample simultaneously with no sample preparation procedure (or just one-step centrifugation).

Human exposure to polycyclic aromatic hydrocarbons (PAHs) is known as a carcinogen risk factor. In this study, a gas chromatography-mass spectrometry (GC-MS) technique combined with the QuEChERS extraction method was developed for concurrent analysis of 10 polycyclic aromatic hydrocarbons (PAHs) in Iranian traditional Sangak bread samples. The method was validated by determining different parameters, including; linearity, accuracy, precision, limit of detection (LOD) and limit of quantitation (LOQ). Calibration curves showed a linear relationship in the concentration range of 10-500 ng/g with a coefficient of determination (R2) ranged between 0.994 and 0.999. The obtained mean recoveries were 92-106% with the relative standard deviations (RSDs) in the range of 3-7% with an acceptable precision (RSD < 20%). The Limit of detections (LODs) for different PAHs were between 0.14-0.78 ng/g, while the limit of quantitation (LOQ) was 0.46-2.60 ng/g. Matrix effect studies showed that the analytes concluded signal suppressions or enhancements. Therefore, spiked calibration curves were used for overcoming this issue. The result of Sangak bread samples analysis using the validated method showed that 9 (19.4%) out of 47 Sangak bread samples were contaminated with phenanthrene (PHE) and anthracene (ANT) at the mean level of 10.08 ± 6.38 ng/g which were higher than the permissible limit of European Commission regulatory control value for BaP (1 μg/kg of wet weight) in processed cereal-based foods and baby foods for infants and young children.

Since 1980 after introducing the concept of live cell encapsulation by Lim et al., this technology has received enormous attention. Several studies have been conducted to improve this technique; different polymers, either natural or synthetic, have been used as microcapsules` making materials and different substances as coating layers. Literature review leads us to the conclusion that alginate (Alg) multilayer microcapsules and, in particular, alginate-poly l-lysine (PLL)-alginate (APA) are the most used structures for live cell encapsulation. Although, disadvantages of PLL (e.g., weak mechanical strength and low biocompatibility) made researchers work on other cationic polymers to find an alternative. This review aims to discuss more popularly suggested cationic polymers such as poly l-ornithine (PLO), chitosan, etc. As alternatives for PLL and, more importantly, we want to take a closer look to see which one of these systems are closer to clinical applications.

The aim of this study is to investigate the novel application of a ‎handheld near infra-red spectrophotometer coupled with classification methodologies as a screening approach in detection of adulterated lime juices. For this purpose, a miniaturized near infra-red spectrophotometer (Tellspec®) in the spectral range of 900–1700 nm was used. Three diffuse reflectance spectra of 31 pure lime juices were collected from Jahrom, Iran and 25 adulterated juices were acquired. Principal component analysis was almost able to generate two clusters. Partial least square discriminant analysis and k-nearest neighbors algorithms with different spectral preprocessing techniques were applied as predictive models. In the partial least squares discriminant analysis, the most accurate prediction was obtained with SNV transforming. The generated model was able to classify juices with an accuracy of 88% and the Matthew’s correlation ‎coefficient ‎value of 0.75 in the external validation set. In the k-NN model, the highest accuracy and Matthew’s correlation ‎coefficient in the test set (88% and 0.76, respectively) was obtained with multiplicative signal correction followed by 2nd-order derivative and 5th nearest neighbor. The results of this preliminary study provided promising evidence of the potential of the handheld near infra-red spectrometer and machine learning methods for rapid detection of lime juice adulteration. Since a limited number of the samples were used in the current study, more lime juice samples from a wider range of variability need to be analyzed in order to increase the robustness of the generated models and to confirm the promising results achieved in this study.

Nanosilver particles have the potential to serve as bactericidal agent because of the antimicrobial influences of silver ion. This in vitro study aimed to evaluate the antimicrobial and antibiofilm properties of nanosilver against two dental plaque microorganisms, namely Streptococcus mutans (Sm) and Aggregatibacter actinomycetemcomitans (Aa).

Initially, growth inhibition zone test was performed in brain heart infusion agar medium using Cup-plate method. Subsequently, microdilution method was utilized to determine the Minimal Inhibitory Concentrations (MIC) and Minimal Bactericidal Concentrations (MBC). Furthermore, the kinetics of bacterial death was assessed by the Time-Kill Test in different time points (i.e., 30, 60, and 120 sec, as well as 5 min). In addition, the effect of these microorganisms was investigated on the formation of the bacterial biofilms using the tissue Culture Plate Method (TCP).

The results of the t-test indicated that chlorhexidine (120 μg/ml) and nanosilver (200 μg/ml) had the same antimicrobial effect on S m, whereas chlorhexidine was more effective against Aa (P<0.0001). The MIC and MBC of silver nanoparticles were 3.90 and 3.90 μg/ml for Sm and 6.5 and 13.01 μg/ml for Aa. The kinetics of bacterial death evaluation demonstrated that in both tested bacteria, the antimicrobial agents were able to reduce microorganism populations regarding 6 algorithmic cycles significantly after 30 sec of the contact with the antibacterial agent. The t-test statistical analysis showed no significant difference between nanosilver and chlorhexidine groups regarding the biofilm decreasing percentage for Sm and Aa (P>0.05).

Nanosilver had rapid and significant antibacterial effects against dental plaque microorganisms. It is also very effective in inhibiting biofilm formation in two bacterial species in in vitro condition.

Poly l-lysine (PLL) has been introduced as a strengthening covering layer for alginate microcapsules which are the most convenient way for cell encapsulation. Some disadvantages of PLL such as high price and low biocompatibility have prompted scientists to find better alternatives. Linear poly ethylene imine (LPEI), thanks to its highly similar structure to PLL, could be considered as a proper cost-effective alternative. In this study LPEI and PLL were compared as covering layers of cell-loaded alginate-LPEI-alginate (cALA) and alginate-PLL-alginate (cAPA) microcapsules.

In addition to the physico-mechanical properties, the encapsulation efficiency, cell survival post encapsulation, cell viability, and cellular metabolic activity within the microcapsules were evaluated using trypan blue, live/dead cell staining, and MTT test, respectively.

Physico-mechanical evaluation of the microcapsules revealed that the cell microencapsulation process did not affect their shape, size, and mechanical stability. Although the encapsulation efficiency for cALA and cAPA was not different (P>0.05), cell survival post encapsulation was higher in cALA than in cAPA (P<0.05) which could be the reason for the higher cell viability and also cellular metabolic activity within these microcapsules in comparison to cAPA.

Here, based on these results, ALA could be introduced as a preferable alternative to APA for cell encapsulation.

Melatonin is widely available as over the counter product. Despite promising effects of melatonin supplementation on glycemic control, there is a significant heterogeneity between studies. The current study aimed at determining the effect of melatonin on fasting blood glucose (FBG), insulin resistance/sensitivity indices, glycosylated hemoglobin A1c (HbA1c), and high sensitivity C-reactive protein (hs-CRP) among type 2 diabetes mellitus (T2D) population during 8 weeks in a randomized, triple-blind, placebo-controlled trial. Thirty four subjects with the mean age ± standard deviation of 57.74 ± 8.57 years and 36 subjects with the mean age of 57.61 ± 9.11 years were allocated to 6 mg nightly melatonin and placebo groups, respectively. Melatonin and placebo groups were matched by age, gender, body mass index, and duration of diabetes. Also, there was no significant difference in laboratory findings except for HbA1c, which was lower in the placebo group (7.00±0.89% vs 7.60±1.47%, P=0.042). After trial completion, the increase of serum levels of melatonin was greater in the intervention than the placebo group (3.38±1.33 vs 0.94±1.28 ng/L, P=0.192). Moreover, compared to placebo group, among melatonin users, homeostasis model assessment of insulin resistance (HOMA1-IR) tended to be unfavorable at the end of follow-up [-0.51 (-1.76-0.81) vs. 0.28 (-1.24-1.74), P=0.20]; the similar trend was also shown for insulin sensitivity index (HOMA1-S) [2.33 (-3.59-12.46) vs. -2.33 (-10.61-9.16), P=0.148]. No differences were observed in FBG, HbA1C, and hs-CRP changes between the trial groups. The current study did not support the improving effect of melatonin on glucose homeostasis.

Recently, antimicrobial peptides have been introduced as potent antibiotics with a wide rangeof antimicrobial activities. They have also exhibited other biological activities, including antiinflammatory,growth stimulating, and anti-cancer activities. In this study, an analog of MagaininII was designed and produced as a recombinant fusion protein. The designed sequence contained24 amino acid residues (P24), in which Lys, His, Ser residues were substituted with Arg and also,hydrophobic Phe was replaced with Trp. Recombinant production of P24 in Escherichia coli (E.coli) BL21 using pTYB21, containing chitin binding domain and intein sequence at the N-terminusof the peptide gene, resulted in 1 μg mL-1 product from culture. Chitin column chromatography,followed by online peptide cleavage with thiol reducing agent was applied to purify the peptide.Antimicrobial activity was evaluated using five bacteria strains including Staphylococcus aureus,Enterococcus faecalis, Klebsiella pneumonia, E. coli, and Pseudomonas aeruginosa. DesignedAMP exhibited promising antimicrobial activities with low minimum inhibitory concentration, inthe range of 64-256 μg/mL. P24 showed potent antimicrobial activity preferably against Grampositivebacteria, and more potent than pexiganan as a successful Magainin II analog for topicalinfections. In general, further modification can be applied to improve its therapeutic index.