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Pseudomonas aeruginosa is an opportunistic human pathogen that can cause life-threatening nosocomial infections. The alarming increase in antibiotic resistance has led to an urgent need for alternative therapeutic approaches, such as phage therapy, which has shown promising results in many studies. In this study, P121, a new lytic Pseudomonas phage, was isolated and characterized. Whole-genome sequencing showed that it has a genome of 73,001 bp that contains 91 predicted coding sequences. No genes involved in virulence or lysogeny were found in the genome, thus making it potentially safe for therapeutic applications. Genomic and phylogenetic analysis indicated that P121 is a member of the genus Litunavirus, family Schitoviridae. The present study provides some basic information for further research on treatment of P. aeruginosa infections.

BACKGROUND: Biological activities of Pistacia atlantica have been investigated for few decades. The fruit oil of the plant has been used for treatment of wounds, inflammation, and other ailments in Traditional Persian Medicine (TPM). OBJECTIVES: The main objectives of this study were to analyze the chemical composition of Pistacia atlantica fruit oil and to study wound healing and anti-inflammatory effects of oil-absorbed bacterial cellulose in an in vivo burn wound model. METHOD: Bacterial cellulose membrane was prepared from Kombucha culture and Fourier-transform infrared was used to characterize the bacterial cellulose. Cold press technique was used to obtain Pistacia atlantica fruit oil and the chemical composition was analyzed by gas chromatography. Bacterial cellulose membrane was impregnated with the Pistacia atlantica fruit oil. Pistacia atlantica hydrogel was prepared using specific Carbopol. Burn wound model was used to evaluate in vivo wound healing and anti-inflammatory effects of the wound dressings containing either silver sulfadiazine as positive control, Pistacia atlantica hydrogel or bacterial cellulose membrane coated with the Pistacia atlantica fruit oil. Blank dressing was used as negative control. RESULTS: FT-IR analysis showed that the structure of the bacterial cellulose corresponded with the standard FT-IR spectrum. The major components of Pistacia atlantica fruit oil constituted linoleic acid (38.1%), oleic acid (36.9%) and stearic acid (3.8%). Histological analysis showed that bacterial cellulose coated with fruit oil significantly decreased the number of neutrophils as a measure of inflammation compared to either negative control or positive control (p

Abstract Aims: Salmonellosis is a critical, common infectious disease afflicting people and animals alike, that is caused by Salmonellabacteria. With bacteria showing resistance to antibiotics, new methods should be introduced to prevent and treat this disease. To that end, bacteriophages are promising choices. Methods and Results: In this study, phage vB_SenS_TUMS_E19 (E19) was isolated from poultry wastewater against Salmonella enteritidis. Phage characteristics, including plaque formation, transmission electron microscopy, structural protein profile, host range, growth curve, pH and temperature stability were determined. The extracted genome was sequenced, and annotated using standard bioinformatics tools. Average Nucleotide Identity (ANI) and phylogeny were used to compare the phage genome with other Salmonella phages. Following morphological analysis, phage E19 turned out to belong to the Siphoviridae family. It worked on various strains of Salmonella but had no effect on bacteria of other genera. The burst size was approximately 156 plaque-forming units per cell (PFU per cell) and phage was stable at different temperatures as well as pH values. The genome of E19 is a linear dsDNA molecule of 42,813 bp whose G+C content stands at 49.8%. Out of 62 detected putative protein-coding genes, only 44 gene products with known functions were found in database searches. Neither tRNA genes nor genes associated with antibiotic resistance, virulence factor, and lysogeny formation were detected in the genome. Conclusion: The E19 showed lytic activity against some Salmonella enterica serovars and Salmonella pullorum. Genome-based studies exhibited the absence of antibiotic resistance and virulence genes, indicating the safety of this phage for environmental and clinical applications. Significance and Impact of the Study: The findings indicate that the lytic polyvalent E19 is an antibacterial agent that could control Salmonella in food samples and helps with Salmonellosis prevention and treatment.

Background: The inhibitory effect of selenium nanoparticles (SeNPs) on cancer cells has been reported in many studies. In this study, the purpose was to compare the in vitro effects of SeNPs and calcium sulfate coated selenium nanoparticles (CaSO4@ SeNPs) on breast cancer cells. Methods: CaSO4@SeNPs and SeNPs were chemically synthesized and characterized with Field Emission Scanning Electron Microscope (FESEM) and energy-dispersive X-ray spectroscopy (EDX). By applying MTT assay, the cytotoxicity effect of both nanomaterials on the 4T1 cancer cells was investigated. Results: While LD50 of SeNPs on 4T1 cancer cells was 80 µg, the LD50 of CaSO4@SeNPs was reported to be only 15 µg. The difference between the inhibition rates obtained for SeNPs and CaSO4@SeNPs was statistically significant (p=0.05). In addition, at higher concentrations (50 µg) of CaSO4@SeNPs, the cytotoxicity was 100% more than SeNPs alone. Conclusion: According to the result of the present work, it can be concluded that de-coration of SeNPs with calcium sulfate leads to an increase in potency by decreasing the effective dose. This effect can be attributed to activation of intrinsic apoptosis signaling and/or pH regulatory properties of CaSO4@SeNPs. However, further studies are still needed to determine the exact corresponding mechanisms of this synergistic effect.

Background Salmonellosis is a critical and common infectious malady between people and animals caused by Salmonella bacteria. With the advent of antibiotic resistance, it is essential for new methods to be replaced to prevent and treat infections. Bacteriophages are promising choices. Methods In this study, phage vB_SenS_TUMS_E4 against Salmonella enteritidis isolate has been separated from poultry wastewater. Determination of phage characteristics, including plaque formation, imaging with transmission electron microscopy, growth curve, structural proteins profile, host range, and pH and temperature parameters. Also, the Phage genome was extracted, sequenced, and annotated, and by utilizing Average Nucleotide Identity and phylogeny was compared with reference Salmonella phages. Results The burst size was large, nearly 287 plaque-forming units per cell (PFU/cell) and elevated stability to many temperatures and pH values. Phage vB_SenS_TUMS_E4 was effective on various clinical and environmental strains of Salmonella but did not affect bacteria of other genera. The morphological analysis indicated that phage vB_SenS_TUMS_E4 belongs to the Siphoviridae family. The genome of vB_SenS_TUMS_E4 is a linear dsDNA molecule of 43,018 bp with a G + C content of 49.7%. It includes 60 protein-coding genes, yet it contains no tRNA genes. Among the 60 detected putative protein-coding genes, just 43 gene products were contained in database searches. No genes associated with antibiotic resistance, virulence factor, and lysogenic were realized in the vB_SenS_TUMS_E4 genome. Conclusion The findings indicate that the high lytic potency vB_SenS_TUMS_E4 polyvalent phage is an antibacterial agent for controlling Salmonella in food production, prevention, and Salmonella treatment.

Introduction: As the COVID-19 pandemic spreads worldwide, reports about the neurological complications of SARS-CoV-2 are excessively increasing. However, there is still insufficient high-throughput data on neuronal cells infected with SARS-CoV-2 to help predict its neural pathogenesis. HCoV-OC43 is another member of the beta coronavirus family that has confirmed neuro-invasive effects and has available neural omics data. This study predicts the critical genes, biological processes, and pathways mediating in SARS-CoV-2 neurological manifestations using a systems biology approach.Method: We retrieved raw data related to SARS-CoV-2 and HCoV-OC43 infections from gene expression omnibus datasets (GSE147507 and GSE13879 respectively). We constructed gene regulatory networks for both infections, detected significant regulatory motifs by FANMOD software, and created their subnetworks. We also constructed PPI networks and identified the MCODE clusters. In the intersection of merged subnetworks of two viruses, the most critical genes were verified in GRN & PPI networks. We drug-repurposed for the selected target genes and performed the functional enrichment analysis using DAVID and String databases.Results: Some of the top KEGG pathway results included NF-kappa B, Toll-like receptor, NOD-like receptor, MAPK, and Neurotrophin signaling pathways. The most essential identified genes included IL6, TNF, HOXA5, POU2F2, ITGB3, STAT1, YY1, E2F6, ESR1, FOXO3, FOXO1, MEF2A, ATF3, ATF4, DDIT3, TCF4, BCL2L2, and BMP4. These genes were also involved in mechanisms of other viral infections of the nervous system. This study repurposes nine medicines with effects on COVID-19 neurological complications. Some of the repurposed drugs were previously registered in clinical trials for COVID-19 treatment.Conclusion: We recommended some identified crucial genes and medications to investigate further their potential role in treating COVID-19 neurological complications.

Regulation of immune responses is among the beneficial effects of probiotic bacteria on human health. In this study, we aim to investigate the effect of normal and heat-shocked Lactobacillus plantarum PTCC 1058 cell lysate on cytokine expression by human PBMCs. The mid-exponential phase L. plantarum (108 CFU/mL) were used to prepare cell lysate. Isolated PBMCs were stimulated with 100 µg/mL of each normal and heat-shocked L. plantarum cell lysate for 72 h. Non-stimulated PBMCs were also evaluated as negative control. The mRNA expression of IL-6, IL-10, IFN-ɣ, TNF-α, and TGF-β genes was determined by quantitative RT-PCR amplification of total RNA extracted from PBMCs. Both types of cell lysate were able to increase pro-inflammatory cytokines and decrease anti-inflammatory cytokines. However, this effect was significantly stronger in heat-shocked cell lysate-treated PBMCs. Moreover, comparison of IFN-ɣ/IL-10, IFN-ɣ/TGF-β, IL-6/IL-10, IL-6/TGF-β, and TNF-α/IL-10 ratios in both conditions demonstrated that in the heat-shocked group, all of the above ratios were significantly higher than normal lysate treatment (p˂0.001), suggesting that heat-shocked probiotics are a potent inducer of the immune system in comparison to intact probiotics. Regarding these results, it may be possible to develop a new postbiotic product for the stimulation of immune responses of cancer patients or individuals who suffer from an immune defect.

Backgrounds and Aims Selenium nanoparticles (SeNPs) have been reported to exhibit an inhibitory effect on cancer cells. In the present study, we aimed to compare the in vitro and in vivo effects of SeNPs and folic acid surface–coated selenium nanoparticles (FA@SeNPs) on breast cancer. Methods FA@SeNPs and SeNPs were chemically synthesized and characterized with different instrumental techniques. The cytotoxicity of both nanomaterials was evaluated against 4T1 cells. In addition, the intravenous administration effect of these nanomaterials (300 μg/week) on the lifespan and tumor size of cancer-bearing mice was investigated. Results Although the SeNPs showed an antiproliferative effect against the cell line, the cytotoxicity of the FA@SeNPs was higher than that of the SeNPs. A low concentration of FA@SeNPs (25 μg/mL corresponding to 8.75 μg/mL of elemental SeNPs) caused approximately 68% cell mortality. In the in vivo study, the nanomaterials decreased the tumor growth rate in cancerous mice in relation to the control group. FA@SeNPs were more effective than SeNPs. Conclusions The combination of SeNPs and FA has a potent antiproliferative effect against 4T1 cells, significantly increases the lifespan, and prevents tumor growth.

Conventional hepatitis B vaccine contains alum but is less effective to induce Th1 response. Selenium nanoparticles and Bacillus Calmette–Guerin were reported as immune modulators. In this study, SeNPs were extracted from Mycobacterium bovis and characterised. SeNPs were mixed with HBs‐Ag and administered to the mice to investigate he immune response pattern. With an addition of Se ions at a sub‐inhibitory concentration to the Sauton medium broth after 24 h, SeNPs were extracted from M. bovis and characterised by Fourier transform infrared spectroscopy, dynamic light scattering, atomic forcemicroscopy, energy dispersive X‐ray spectrum, transmission electron microscopy, and thermogravimetric analysis. Furthermore, female inbred BALB/c mice were injected subcutaneously on the first, 14th, 28th day with 100 and 200 µg doses of that SeNPs supplemented with HBs‐Ag vaccine. Later, the total antibody, isotypes of Immunoglobulin G1, Interlukin 4, and interferon‐γ were measured by enzye‐linked immunosorbent assay. The size of the SeNPs was

Tellurium (Te) is a semimetal rare element in nature. Together with oxygen, sulfur (S), and selenium (Se), Te is considered a member of chalcogen group. Over recent decades, Te applications continued to emerge in different fields including metallurgy, glass industry, electronics, and applied chemical industries. Along these lines, Te has recently attracted research attention in various fields. Though Te exists in biologic organisms such as microbes, yeast, and human body, its importance and role and some of its potential implications have long been ignored. Some promising applications of Te using its inorganic and organic derivatives including novel Te nanostructures are being introduced. Before discovery and straightforward availability of antibiotics, Te had considered and had been used as an antibacterial element. Antilishmaniasis, antiinflammatory, antiatherosclerotic, and immuno-modulating properties of Te have been described for many years, while the innovative applications of Te have started to emerge along with nanotechnological advances over the recent years. Te quantum dots (QDs) and related nanostructures have proposed novel applications in the biological detection systems such as biosensors. In addition, Te nanostructures are used in labeling, imaging, and targeted drug delivery systems and are tested for antibacterial or antifungal properties. In addition, Te nanoparticles show novel lipid-lowering, antioxidant, and free radical scavenging properties. This review presents an overview on the novel forms of Te, their potential applications, as well as related toxicity profiles.

The aim of the present work was to study the ability of a halophilic bacterial laccase to efficient delignification in extreme conditions. Here, a highly stable extracellular laccase showing ligninolytic activity from halophilic Aquisalibacillus elongatus is described. The laccase production was strongly influenced by NaCl and CuSO4 and under optimal conditions reached 4.8UmL-1. The monomeric enzyme of 75kDa was purified by a synthetic affinity column with 68.2% yield and 99.8-fold purification. The enzyme showed some valuable features viz. stability against a wide range of organic solvents, salts, metals, inhibitors, and surfactants and specificity to a wide spectrum of substrates diverse in structure and redox potential. It retained more than 50% of the original activity at 25-75°C and pH 5.0-10.0. Furthermore, the enzyme was found to be effective in the delignification of sugar beet pulp in an ionic liquid that makes it useful for industrial applications.

Summary: Hepatitis B virus (HBV) infection is known as a life-threatening liver infection and leads to chronic liver disease if left untreated. Nevertheless, the prevalence of HBV infection has been reduced by an approved vaccination approach using recombinant Hepatitis B surface Antigen (HBsAg) and Alum, known as the HBV vaccine. Alum can be used as an adjuvant to increase HBsAg immunogenicity as a strong Th2 stimulator. There is a vital need to stimulate Th1 immunity by HBsAg vaccination; however, the present vaccine does not induce a prophylactic immune response in some groups. The main aim of the present study was to induce a Th1 cytokine pattern and stimulate an immune response after HBsAg vaccination. Experimental mice were fed selenium nanoparticles (SeNPs) and were later immunized with 5 μg of Hepatitis B Vaccine. After a period of 30 days, the experimental animals were given two booster doses of SeNPs during their vaccination course. Group one, i.e., the control vaccine group, was only administered the HBsAg vaccine. The two treated groups, Groups 2 and 3, were daily fed different doses of SeNPs (100 μg and 200 μg, respectively) via gavage. Group four was considered the control group and was only given phosphate buffered saline (PBS). Lymphocyte proliferation, IFN-γ and IL-4 levels, total antibody and the isotypes of IgG1, IgG2a, IgG2b, and IgM were measured by Enzyme Linked Immunosorbent Assay (ELISA). The administration of SeNPs and the HBs antigen vaccine affected the lymphocyte proliferation; moreover, the total antibody responses also increased the IFN-γ level and induced a Th1 response. Conclusions: The present study proposed that the administration of SeNPs with a conventional HBs antigen vaccine induces a better immune response with a Th1 bias. Keywords: Selenium nanoparticles, Hepatitis B vaccine, IFN-γ, Th1 immune response

Lipases as significant biocatalysts had been widely employed to catalyze various chemical reactions such as ester hydrolysis, ester synthesis, and transesterification. Improving the activity and thermostability of enzymes is desirable for industrial applications. The lipase of Serratia marcescens belonging to family I.3 lipase has a very important pharmaceutical application in production of chiral precursors. In the present study, to achieve improved lipase activity and thermostability, using computational predictions of protein, four mutant lipases of SML (MutG2P, MutG59P, Mut H279K and MutL613WA614P) were constructed by site-directed mutagenesis. The recombinant mutant proteins were over-expressed in E. coli and purified by affinity chromatography on the Ni-NTA system. Circular dichroism spectroscopy, differential scanning calorimetry and kinetic parameters (Km and kcat) were determined. Our results have shown that the secondary structure of all lipases was approximately similar to one another. The MutG2P and MutG59P were more stable than wild type by approximately 2.3 and 2.9 in T1/2, respectively. The catalytic efficiency (kcat/Km) of MutH279K was enhanced by 2-fold as compared with the wild type (p

In this study, preparation and characterization of polyacrylamide/reduced graphene oxide-Ag (PAM/rGO-Ag) nanocomposites as a new nanocomposite film were investigated. First, PAM/GO nanocomposite was synthesized by in situ polymerization strategy. Afterward, highly stable and uniformly distributed silver nanoparticles (Ag NPs) have been obtained with PAM/GO nanocomposite as nanoreactors via in situ reduction of silver nitrate (AgNO3) using sodium borohydride (NaBH4) as reducing agent. In addition, the prepared PAM/rGO-Ag nanocomposite was thermally annealed in order to achieve high-performance nanocomposite film with antimicrobial activities. The prepared nanocomposite was characterized by XRD, FT-IR, SEM, TEM and TGA. The obtained results demonstrate that the silver nanoparticles were well decorated and dispersed on the graphene oxide nanosheets. In fact, the GO nanosheets and polyacrylamide chains act as a support and stabilize the Ag nanoparticles. Moreover, antimicrobial activities of the films were also examined, and the films containing well-dispersed and stabilized Ag nanoparticles showed outstanding antibacterial activity.

The modification of tumor-associated antigen-based vaccine to elicit a more robust immune response has been addressed in several ways. In the present work, we aimed to investigate the immunomodulatory effect of selenium nanoparticles as an immunoadjuvant in formulation of a tumor-associated antigen-based vaccine in a preventive form. Fortyfive female inbred BALB/c mice five-to-seven weeks old were used and divided into three groups of test and control, each containing fifteen mice. Group one injected by PBS and used as a control. Group two injected by breast tumor cell lysate alone as vaccine. Group three injected by SeNPs with tumor cell lysate as vaccine. All injections were carried out on day fourteen, twentyone and twentyeight of the study. Tumor induction was done at day thirty. Twenty days after tumor induction serum samples were gathered to measure the cytokine assay. Tumor growth and weight of mice as well as delayed type hyper sensitivity (DTH) response were monitored during the study. Results of the present work showed a significant increase in the level of serum IFN-γ, IL-2, IL-12 and decreased TGF-β in SeNPs/vaccine injected mice as well as lower tumor volume, more potent DTH responses and longer survival rate in comparison to control and tumor lysate vaccine. Taken together, it can be deduced from this work that SeNPs can be considered as an adjuvant in vaccine in triggering robust immune response against breast cancer. But further evaluations are still needed to find the best formula for this agent in antitumor vaccines.

Background: Brain tumors can be serious and life-threatening when they are treated effectively. Many therapeutic approaches, such as chemotherapy, radiotherapy, and surgery have been used to treat brain tumors. In this regard, selenium supplements have been reported effective.Methods: Selenium Nanoparticles (SeNPs) were produced in two forms of synthetic and biogenic to evaluate their cytotoxicity on brain glioblastoma cell lines. A-172 cell line was cultured in DMEM medium. The cytotoxicity of the synthetic and biogenic SeNP was assessed by MTT assay. Results: There was a significant difference between the group treated with biogenic and synthetic SeNP compared with non-treated cells after 24, 48, and 72 h. Both biogenic and synthetic SeNP increased Bax gene and decreased Bcl-2 gene expression. Conclusion: It seems that biogenic SeNP was more lethal than its synthetic form. Therefore, it should be considered that the method of NP construction may be an important parameter for its bioactivity.

The lipase of Serratia marcescens (SML), containing 614 amino acid residues and belonging to the lipase family I.3, has an important pharmaceutical application in production of chiral precursors. Similar to other members of this family, the SML consists of the N-catalytic domain (α/β) that contains the active-site residues and the C-terminal domain that includes the two parallel β-roll domains, the first and second β-roll. The repetitive sequences, a nine-residue sequence motif (GGXGXDXUX), in SML are somewhat degenerated as well as not consecutive. The parallel β-roll domains are separated from each other by a 72-residue spacer. The importance of these repetitive sequences has not been fully understood yet. In the present investigation, as an approach, a C-terminally truncated (∼13 kD) SML was generated using a polymerase chain reaction (PCR)-based site-directed mutagenesis method (designated SML-Δ128). Both wild-type and truncated forms of SML were constructed, overexpressed in Escherichia coli without the Lip system and purified by affinity chromatography on the Ni-NTA system. The kinetic parameters and circular dichroism (CD) spectra were determined and compared. The SML-Δ128 showed an approximately 3.7-fold increase in the turnover rate ( k cat ), relative to that of the full-length enzyme. In conclusion, this report demonstrates that the SML could tolerate extensive modification in the C-terminal extreme of the protein, as deletion of the C-terminal region (∼13 kDa), which consists of several tandem repeats of glycine-rich and 49 residues including the signal peptide, significantly increases the catalytic efficiency of the enzyme.

Hypercholesterolemia is an important risk factor contributing to atherosclerosis and coronary heart disease. Lactic acid bacteria have attracted much attention regarding their promising effect on serum cholesterol levels. Tellurium (Te) is a rare element that has also gained considerable interest for its biological effects. There have been some recent in vivo reports on the reduction effect of Te on cholesterol content. In this study, Lactobacillus plantarum PTCC 1058 was employed for the intracellular biosynthesis of Te NPs. The UV-visible spectrum of purified NPs showed a peak at 214 nm related to the surface plasmon resonance of the Te NPs. Transmission electron microscopy showed that spherical nanoparticles without aggregation had the average size of 45.7 nm as determined by the laser scattering method. The energy dispersive X-ray pattern confirmed the presence of Te atoms without any impurities. A significant reduction was observed in group which received L. plantarum with or without Te NPs during propylthiouracil and cholesterol diet in compare with the control group which received just propylthiouracil and cholesterol. The levels of triglycerides also remarkably decrease (p

Background: Tumor associated antigens can be viably used to enhance host immune response. Objectives: The immunomodulatory effect of biogenic selenium nanoparticles (SeNPs) was compared between treated and untreated mice with crude antigens of 4T1 cells. Materials and Methods: Female inbred BALB/c mice (60) were injected by cancinogenic 4T1 cells causing breast cancer. After 10 days, all tumor bearing mice were divided into 4 groups. Group 1 was daily provided oral PBS and injected by the same buffer after tumor induction and was considered as control. Group 2 received only 100 mg/day SeNPs as an oral supplement for 30 days. Group 3 was only injected with 4T1 cells crude antigens with nil supplementation of SeNPs. Group 4 animals were supplemented 100 mg/day SeNPs for 30 days and simultaneously injected with crude antigens of 4T1 cells. All antigens or PBS injections were introduced at 7, 14 and 28 days following tumor induction. Oral PBS and SeNPs supplementation initiated from the first day of tumor induction and continued up to 30 days. During tumor growth, animal weights and survival rates were monitored and at the end of the study the concentrations of different cytokines and DTH responses were measured. Results: Data clearly showed that the levels of cellular immunomodulatory components (granzyme B, IL-12, IFN-g, and IL-2) significantly increased (P < 0.05) in mice treated with both SeNPs and crude antigens of 4T1 cells in comparison to the other groups. In contrast, the levels of TGF-b in these mice decreased. Conclusions: Although SeNPs showed a noticeable boosting effect for the immune response in mice bearing tumor exposed to crude antigens of 4T1 cells, further complementary studies seem to be inevitable.

Background: Resistance of pathogenic fungi to conventionally available antifungal agents has been increasing and has become a serious problem. On the other hand, nanoscience has emerged as a powerful tool capable of developing and designing new antimicrobial drugs. Objectives: The aim of this study was to test minimum inhibitory concentrations (MICs) of silver (Ag-NPs) and selenium (Se-NPs) nanoparticles, both alone and in combination with antifungal agents fluconazole (FLU), itraconazole (ITR), and amphotericin B (AMB) on resistant C. parapsilosis strains. Methods: Eight C. parapsilosis strains resistant to antifungal agents (FLU, ITR, AMB) and the standard strain of C. parapsilosis (ATCC 22019) as a control were used in this study. The standard protocol of antifungal susceptibility testing for yeast was performed by the broth micro-dilution method described in the clinical and laboratory standards institute (CLSI) guidelines, document M 27-S4. Results and Conclusions: MICs of standard and resistant strains were different against nano compounds, both alone and in combination with antifungal drugs. The growth of yeast was inhibited by Ag-NPs at concentrations as low as 2 µg /mL (against FLCR1 and FLCR3) and 0.25 µg /mL (against ITRR2 and AMBR2). Antifungal activity testing of Se-NPs revealed that it can inhibit the growth of yeasts at concentrations as low as 4 µg /mL (against FLCR1 and FLCR3) and 0.5 mg/mL (against ITRR2, ITRR3 and AMBR1). The results demonstrated that Se-NPs had lower activity than Ag-NPs, but both (Se-NPs and Ag-NPs) had higher activity than common antifungal agents. Further in vitro and in vivo studies are required for this.

Resistance to antibiotics in bacteria, is one of the major problems of mankind. Each year, a large number of patients due to infection, lose their lives. One of the main mechanisms of antibiotic resistance is beta-lactamase secretion. This enzyme hydrolyzes the amide bond of a lactam ring in beta-lactam antibiotics. Bacillus licheniformis is a mesophilic gram-positive bacterium, which has a high potential to produce beta-lactamase class A. In this study, the inhibitory effects of some malate analogous were studied by in vitro and in vivo studies. In addition, the effects of inhibitor binding on beta-lactamase were studied using MD simulations. Our results showed that diethyl malate and 1-methyl malate can decrease the MIC value of benzyl penicillin by sixteen and eight-fold, respectively. Data derived from in vitro studies revealed that decrease in MIC values is correlated with beta-lactamase inhibition. Molecular docking studies predicted the binding mode of inhibitors with the beta-lactamase active site. The structural analysis from MD simulations exhibits that binding of citrate and diethyl malate causes earlier equilibrium of beta-lactamase. After binding, the fluctuation of Ser 70 is also decreased. Based on our data, diethyl malate can be used to design the potent inhibitor against beta-lactamase class A.

In this study, we evaluated the antifungal activity of biogenic tellurium nanoparticles (Te NPs) against Candida albicans (ATCC14053). In addition, the effect of these biogenic NPs on squalene monooxygenase activity and the squalene monooxygenase gene (ERG1) expression level was evaluated. Squalene monooxygenase is an important enzyme involved in the synthesis of ergosterol, cholesterol, and phytosterols. Because of the importance of the noted compound, the squalene monooxygenase gene could be considered a good antifungal target. Results showed that biogenic Te NPs had antifungal effect against C. albicans. The minimal fungicidal concentration-minimal inhibitory concentration ratios of the biogenic Te NPs revealed that these NPs exhibited fungicidal effects against the test strain. The results of an enzyme assay using quantitative high-performance liquid chromatography showed squalene accumulation in C. albicans cells because of enzyme inhibition. Real-time PCR analysis showed an increase in the expression of the ERG1 gene in C. albicans cells, which were treated with Te NPs (0.2 mg/mL). It is conclution that Te NPs can inhibit the squalene monooxygenase enzyme, and, as a result, this inhibition phenomenon can cause an increase in the expression level of the ERG1 gene. This is the first report of the anti-Candida effect of biogenic Te NPs and its possible mechanisms.

The present study was designed to evaluate antioxidant and cytotoxic effect of selenium nanoparticles (Se NPs) biosynthesized by a newly isolated marine bacterial strain Bacillus sp. MSh-1. An organic-aqueous partitioning system was applied for purification of the biogenic Se NPs and the purified Se NPs were then investigated for antioxidant activity using DPPH scavenging activity and reducing power assay. Cytotoxic effect of the biogenic Se NPs and selenium dioxide (SeO2) on MCF-7 cell line was assesed by MTT assay. Tranmission electron micrograph (TEM) of the purified Se NPs showed individual and spherical nanostructure in size range of about 80-220nm. The obtained results showed that, at the same concentration of 200μg/mL, Se NPs and SeO2 represented scavenging activity of 23.1±3.4% and 13.2±3.1%, respectively. However, the data obtained from reducing power assay revealed higher electron-donating activity of SeO2 compared to Se NPs. Higher IC50 of the Se NPs (41.5±0.9μg/mL) compared to SeO2 (6.7±0.8μg/mL) confirmed lower cytotoxicity of the biogenic Se NPs on MCF-7 cell line.

Mahdi Shiri,1,2,* Mona Navaei-Nigjeh,1,3,* Maryam Baeeri,1 Mahban Rahimifard,1 Hossein Mahboudi,4 Ahmad Reza Shahverdi,5 Abbas Kebriaeezadeh,1 Mohammad Abdollahi1,6,7 1Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, 2School of Medicine, Artesh University of Medical Sciences, 3Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Biotechnology, Faculty of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, 6Toxicology Interest Group, USERN, 7Endocrinology & Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Diazinon (DZ) is an organophosphorus insecticide that acts as an acetylcholinesterase inhibitor. It is important to note that it can induce oxidative stress, lipid peroxidation, diabetic disorders, and cytotoxicity. Magnesium oxide (MgO) and selenium nanoparticles (Se NPs) showed promising protection against oxidative stress, lipid peroxidation, cytotoxicity, and diabetic disorders. Therefore, this study was conducted to explore the possible protective mechanisms of MgO and Se NPs against DZ-induced cytotoxicity in PaTu cell line. Cytotoxicity of DZ, in the presence or absence of effective doses of MgO and Se NPs, was determined in human pancreatic cancercell line (PaTu cells) after 24 hours of exposure by using mitochondrial activity and mitochondrial membrane potential assays. Then, the insulin, proinsulin, and C-peptide release; caspase-3 and -9 activities; and total thiol molecule levels were assessed. Determination of cell viability, including apoptotic and necrotic cells, was assessed via acridine orange/ethidium bromide double staining. Furthermore, expression of 15 genes associated with cell death/apoptosis in various phenomena was examined after 24 hours of contact with DZ and NPs by using real-time polymerase chain reaction. Compared to the individual cases, the group receiving the combination of MgO and Se NPs showed more beneficial effects in reducing the toxicity of DZ. Cotreatment of PaTu cell lines with MgO and Se NPs counteracts the toxicity of DZ on insulin-producing cells. Keywords: apoptosis, diazinon, human pancreatic cancer cell line, organophosphorus, toxicity

Treponema (T.) denticola is one of the key etiological agents in the development of periodontitis. The major outer sheath protein (Msp) of T. denticola has been shown to mediate pathogenesis and to facilitate adhesion of T. denticola to mucosal surfaces. This study aimed to find short polypeptides in the amino acid sequence of Msp which may be immunogenic and might elicit protective antisera against T. denticola. The complete msp sequence was divided into six fragments and the corresponding genes were cloned and expressed. Antisera against the polypeptides were raised in rabbits and fragment 3 (F3), hereinafter called PerioVax3 was the most potent fragment of the Msp in terms of yielding high titer antiserum. An adhesion assay was done to examine the inhibitory effects of antisera on the attachment of T. denticola to human gingival fibroblasts (HGFs) and human fibronectin. Antiserum against PerioVax3 significantly inhibited attachment of T. denticola to the substratum. Also, antiserum against PerioVax3 inhibited detachment of HGFs upon T. denticola exposure. To begin examining the clinical relevance of this work, blood samples from 12 sever periodontitis patients were collected and the sera were used in western blotting against the recombinant polypeptides. Periodontitis patient antisera exclusively detected PerioVax3 in western blotting. The data suggest that PerioVax3 carries epitopes that may trigger humoral immunity against T. denticola, which may protect against its adhesion functions. The complexity of periodontitis suggests that PerioVax3 may be considered for testing as a component of an experimental multivalent periodontal vaccine in further preclinical and clinical studies.

Organic salts of bismuth are currently used as antimicrobial agents against Helicobacter pylori. This study evaluated the antibacterial effect of elemental bismuth nanoparticles (Bi NPs) using a serial agar dilution method for the first time against different clinical isolates and a standard strain of H. pylori. The Bi NPs were biologically prepared and purified by a recently described method and subjected to further characterization by infrared spectroscopy and anti-H. pylori evaluation. Infrared spectroscopy results showed the presence of carboxyl functional groups on the surface of biogenic Bi NPs. These biogenic nanoparticles showed good antibacterial activity against all tested H. pylori strains. The resulting MICs varied between 60 and 100 μg/ml for clinical isolates of H. pylori and H. pylori (ATCC 26695). The antibacterial effect of bismuth ions was also tested against all test strains. The antimicrobial effect of Bi ions was lower than antimicrobial effect of bismuth in the form of elemental NPs. The effect of Bi NPs on metabolomic footprinting of H. pylori was further evaluated by (1)H NMR spectroscopy. Exposure of H. pylori to an inhibitory concentration of Bi NPs (100 μg/ml) led to release of some metabolites such as acetate, formic acid, glutamate, valine, glycine, and uracil from bacteria into their supernatant. These findings confirm that these nanoparticles interfere with Krebs cycle, nucleotide, and amino acid metabolism and shows anti-H. pylori activity.

An extracellular haloalkaliphilic thermostable α-amylase producing archaeon was isolated from the saltwater Lake Urmia and identified as Halorubrum xinjiangense on the basis of morphological, biochemical, and molecular properties. The enzyme was purified to an electrophoretically homogenous state by 80 % cold ethanol precipitation, followed by affinity chromatography. The concentrated pure amylase was eluted as a single peak on fast protein liquid chromatography. The molecular mass of the purified enzyme was about 60 kDa, with a pI value of 4.5. Maximum amylase activity was at 4 M NaCl or 4.5 M KCl, 70 °C, and pH 8.5. The K m and V max of the enzyme were determined as 3.8 mg ml(-1) and 12.4 U mg(-1), respectively. The pure amylase was stable in the presence of SDS, detergents, and organic solvents. In addition, the enzyme (20 U) hydrolyzed 69 % of the wheat starch after a 2-h incubation at 70 °C in an aqueous/hexadecane two-phase system.