Predatory and biocontrol potency of Bdellovibrio bacteriovorus toward phytopathogenic strains of Pantoea sp. and Xanthomonas campestris in the presence of exo-biopolymers: in vitro and in vivo assessments.

Bdellovibrios are predatory bacteria that invade other live Gram-negative bacterial cells for growth and reproduction. They have recently been considered as potential living antibiotics and biocontrol agents. In this study, the predatory activity and biocontrol potency of Bdellovibrio bacteriovorus strain SOIR-1 against Pantoea sp. strain BCCS and Xanthomonas campestris, two exo-biopolymer-producing phytopathogens, was evaluated. Plaque formation assays and lysis analysis in the broth co-cultures were used for the in vitro evaluation of bacteriolytic activity of strain SOIR-1. The in vivo biocontrol potential of strain SOIR-1 was evaluated by pathogenicity tests on the onion bulbs and potato tuber slices. The phytopathogens were also recovered from the infected plant tissues and confirmed using biochemical tests and PCR-based 16S rRNA gene sequence analysis. Typical bdellovibrios plaques were developed on the lawn cultures of Pantoea sp. BCCS and X. campestris. The killing rate of strain SOIR-1 toward Pantoea sp. BCCS and X. campestris was 84.3% and 76.3%, respectively. Exo-biopolymers attenuated the predation efficiency of strain SOIR-1 up to 10.2-18.2% (Pantoea sp. BCCS) and 12.2-17.3% (X. campestris). The strain SOIR-1 significantly reduced rotting symptoms in the onion bulbs caused by Pantoea sp. BCCS (69.0%) and potato tuber slices caused by X. campestris (73.1%). Although more field assessments are necessary, strain SOIR-1 has the preliminary potential as a biocontrol agent against phytopathogenic Pantoea sp. BCCS and X. campestris, especially in postharvest storage. Due to the particular physicochemical properties of evaluated exo-biopolymers, they can be used in the designing encapsulation systems for delivery of bdellovibrios.

Investigations of antiproliferative and antioxidant activity of ß-lactam morpholino-1,3,5-triazine hybrids.

This article reports for the first time the synthesis of some novel ß-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a-c, 9a-c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-ß-lactams 8a-l, 10a-f and 12a-c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC50 < 5 µM) against SW 1116 cells, comparable to that of doxorubicin (IC50 = 6.9 µM). An evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 7b, 9a, 9b and 9c have strong free radical scavenging activity. UV absorption titration studies reveal that 7b, 8l, 8g and 8f interact strongly with calf-thymus DNA (CT-DNA) in the order of 8l > 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and ß-lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.

Structural characterization of polysaccharide-coated iron oxide nanoparticles produced by Staphylococcus warneri, isolated from a thermal spring.

The biocompatible-coated iron oxide nanoparticles (IONs) have attracted a great interest because of their various applications in biological science and medicine. In most cases, the toxic effect of naked iron oxide nanoparticles is completely cleared by adding a biocompatible coating, such as polysaccharides, polyethylene glycol (PEG), or biosynthesis of biocompatible-coated IONs using microorganisms such as bacteria. In the present study, polysaccharide-coated iron oxide nanoparticles were produced by a strain of Staphylococcus warneri isolated from a thermal spring. For identification of the isolated bacterium, 16S rRNA gene sequencing was done. Characterization of the nanoparticles was performed for the first time, using transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), X-ray crystallography (XRD), Fourier-transform infrared (FTIR) spectroscopy, vibrating sample magnetometer (VSM), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results indicated that the spherical iron oxide nanoparticles were coated by a polysaccharide (13.6%), which provided a large negative charge of -91 mV and very low saturation magnetization of around 0.28 emu/g. The result of MTT assay on MOLT-4 cell lines showed that the percentage of viability was between 95.6% and 68.9% in the 10-100 µM of nanoparticle concentrations with a high IC 50 value, which makes it appropriate for biomedical applications such as cancer therapy.

Physicochemical and biological characteristics of the nanostructured polysaccharide-iron hydrogel produced by microorganism Klebsiella oxytoca.

There is an increasing interest in the nanostructured polysaccharide-iron hydrogel produced by Klebsiella oxytoca. Critical physicochemical and biological characteristics of these nanostructures should be revealed for biomedical applications. Accordingly, an iron reducing strain K. oxytoca, which synthesizes biogenic polysaccharide-iron hydrogel nanoparticles, known as Fe (III)-exopolysaccharide (Fe-EPS) was isolated from a mineral spring. For microbiological identification purpose 16S rRNA sequence analysis and different morphological, physiological, and biochemical characteristics of the isolate were studied. Critical physicochemical and biological characteristics of the produced Fe-EPS were evaluated using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, X-ray crystallography (XRD), vibrating sample magnetometer (VSM). In addition, for the first time, Fe-EPS which synthesized by K. oxytoca was evaluated by dynamic light scattering (DLS), thermo gravimetric analysis (TGA), and cytotoxicity assay. TEM micrographs showed that the biogenic Fe-EPS is composed of ultra-small (about 1.8 nm) iron oxide nanoparticles (IONs) which are trapped in a polysaccharide matrix. The matrix was about 17% (w/w) of Fe-EPS total weight and provided a large negative charge of -71 mV. Interestingly, Fe-EPS showed a growth promotion effect on hepatocarcinoma cell line (Hep-G2) and 36% increase in the percentage of viability was observed by 24 h exposure to 500 µg ml-1 Fe-EPS.

In Silico Analysis of Glutaminase from Different Species of Escherichia and Bacillus.

BACKGROUND: Glutaminase (EC 3.5.1.2) catalyzes the hydrolytic degradation of L-glutamine to L-glutamic acid and has been introduced for cancer therapy in recent years. The present study was an in silico analysis of glutaminase to further elucidate its structure and physicochemical properties. METHODS: Forty glutaminase protein sequences from different species of Escherichia and Bacillus obtained from the UniProt Protein Database were characterized for homology search, physiochemical properties, phylogenetic tree construction, motif, superfamily search, and multiple sequence alignment. RESULTS: The sequence level homology was obtained among different groups of glutaminase enzymes, which belonged to superfamily serine-dependent ß-lactamases and penicillin-binding proteins. The phylogenetic tree constructed indicated 2 main clusters for the glutaminases. The distribution of common ß-lactamase motifs was also observed; however, various non-common motifs were also observed. CONCLUSION: Our results showed that the existence of a conserved motif with a signature amino-acid sequence of ß-lactamases could be considered for the genetic engineering of glutaminases in view of their potential application in cancer therapy. Nonetheless, further research is needed to improve the stability of glutaminases and decrease their immunogenicity in both medical and food industrial applications.

Production of a novel multi-epitope peptide vaccine for cancer immunotherapy in TC-1 tumor-bearing mice.

In our previous research, several bioinformatic strategies were utilized to design an efficient multi-epitope peptide vaccine (MEV) against cancer. The designed vaccine consists of Wilms tumor-1 (WT-1) and human papillomavirus (HPV) E7 cytotoxic T lymphocyte (CTL) epitopes, tetanus toxin fragment C (TTFrC) and HLA-DR epitope (PADRE) helper T lymphocyte (HTL) epitopes and heparin-binding hemagglutinin (HBHA) as an immunostimulatory adjuvant. All segments were fused together by suitable linkers. In the current study, we cloned and expressed the designed MEV in E. coli. We subsequently performed in vivo preventative and therapeutic assays to evaluate antitumor efficacy of the vaccine against the HPV-16 E7-expressing murine tumor cell line TC-1 as a model for cancer immunotherapy. The results showed that in preventive experiments, vaccination with MEV significantly augmented the IgG antibody titer and the percentage of tumor-free mice compared to control groups (PBS and E7). Moreover, in therapeutic experiments, vaccination with MEV led to a reduction in the number of metastatic nodules, lung weights and the ratio of lung weights to body weights compared to other groups. In sum, our epitope vaccine could efficiently induce preventive and therapeutic antitumor immunity in TC-1 tumor bearing mice.

Experimental design of medium optimization for invertase production by Pichia sp.

The culture medium requirement for invertase production by Pichia sp. was optimized and identified by initial screening method of Plackett-Burman. Furthermore, optimum concentrations of medium components, which were selected by in initial screening by Plackett-Burman, were determined by the Box-Behnken and its representative three-factor response-surface method. The regression models showed significantly high R (2) values of 97% for invertase activities, indicating that they are appropriate for predicting relationships between yeast extract, peptone and sucrose concentration with invertase production. According to the model the optimal concentrations of sucrose, yeast extract and peptone were 40, 5 and 4 g/ml, respectively. These predicted conditions were verified by validation experiments. In the optimized medium Pichia sp. produced invertase with activity of 38.71 U/ml, which is 4 times higher than that produced in original medium. Thus, this statistical approach enabled rapid identification and integration of key medium parameters for Pichia sp. BCCS M1, resulted the high invertase production.

Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.

In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.

Induction of antitumor immunity against cervical cancer by protein HPV-16 E7 in fusion with ricin B chain in tumor-bearing mice.

OBJECTIVE: In immunotherapy of HPV-16-associated cervical cancers, the E7 protein is considered as a prime candidate. However, it is a poor inducer of a cytotoxic T-cell response when used as a singular antigen in protein vaccination. Therefore, to design effective cancer vaccines, the best tumor antigens should be combined with the most effective immunogens or drug delivery tools to achieve positive clinical results. In this study, we fused HPV-16 E7 with the lectin subunit of ricin toxin (RTB) from castor plant as a vaccine adjuvant/carrier. MATERIALS AND METHODS: After reaching the soluble form of the recombinant protein, we designed 2 preventive and inhibition tumor models for investigation of the prevention and rejection of TC-1 cell growth in female C57BL/6 mice, respectively. In each model, mice were immunized with the recombinant protein of E7-RTB or E7 without any adjuvant. RESULTS: We demonstrated that prophylactic immunization of E7-RTB protected mice against challenge from TC-1 cells. Also in the therapeutic model, E7-RTB could inhibit TC-1 tumor growth in the lung. The results were significant compared with the immunization of E7 singularly. CONCLUSIONS: We concluded that immunization with E7-RTB protein without any adjuvant could generate antitumor effects in mice challenged with TC-1 cells. This research verifies the clinical applications and the future prospects for development of HPV-16 E7 therapeutic vaccines fused to immunoadjuvants.

Immune checkpoint molecules in prevention and development of asthma.

Allergic asthma is a respiratory disease initiated by type-2 immune responses characterized by secretion of alarmins, interleukin-4 (IL-4), IL-5, and IL-13, eosinophilic inflammation, and airway hyperresponsiveness (AHR). Immune checkpoints (ICPs) are inhibitory or stimulatory molecules expressed on different immune cells, tumor cells, or other cell types that regulate immune system activation and maintain immune homeostasis. Compelling evidence indicates a key role for ICPs in both the progression and prevention of asthma. There is also evidence of asthma development or exacerbation in some cancer patients receiving ICP therapy. The aim of this review is to provide an updated overview of ICPs and their roles in asthma pathogenesis, and to assess their implications as therapeutic targets in asthma.

Exploring the potential and safety of quantum dots in allergy diagnostics.

Biomedical investigations in nanotherapeutics and nanomedicine have recently intensified in pursuit of new therapies with improved efficacy. Quantum dots (QDs) are promising nanomaterials that possess a wide array of advantageous properties, including electronic properties, optical properties, and engineered biocompatibility under physiological conditions. Due to these characteristics, QDs are mainly used for biomedical labeling and theranostic (therapeutic-diagnostic) agents. QDs can be functionalized with ligands to facilitate their interaction with the immune system, specific IgE, and effector cell receptors. However, undesirable side effects such as hypersensitivity and toxicity may occur, requiring further assessment. This review systematically summarizes the potential uses of QDs in the allergy field. An overview of the definition and development of QDs is provided, along with the applications of QDs in allergy studies, including the detection of allergen-specific IgE (sIgE), food allergens, and sIgE in cellular tests. The potential treatment of allergies with QDs is also described, highlighting the toxicity and biocompatibility of these nanodevices. Finally, we discuss the current findings on the immunotoxicity of QDs. Several favorable points regarding the use of QDs for allergy diagnosis and treatment are noted.

In Silico Evaluation of Nonsynonymous SNPs in Human ADAM33: The Most Common Form of Genetic Association to Asthma Susceptibility.

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.

Computational Elucidation of Phylogenetic, Functional and Structural Features of Methioninase from Pseudomonas, Escherichia, Clostridium and Citrobacter Strains.

BACKGROUND: L-Methioninase (EC 4.4.1.11; MGL) is a pyridoxal phosphate (PLP)-dependent enzyme that is produced by a variety of bacteria, fungi, and plants. L-methioninase, especially from Pseudomonas and Citrobacter sp., is considered as the efficient therapeutic enzyme, particularly in cancers such as glioblastomas, medulloblastoma, and neuroblastoma that are more sensitive to methionine starvation. OBJECTIVE: The low stability is one of the main drawbacks of the enzyme; in this regard, in the current study, different features of the enzyme, including phylogenetic, functional, and structural from Pseudomonas, Escherichia, Clostridium, and Citrobacter strains were evaluated to find the best bacterial L-Methioninase. METHODS: After the initial screening of L-Methioninase sequences from the above-mentioned bacterial strains, the three-dimensional structures of enzymes from Escherichia fergusonii, Pseudomonas fluorescens, and Clostridium homopropionicum were determined through homology modeling via GalaxyTBM server and refined by GalaxyRefine server. RESULTS AND CONCLUSION: Afterwards, PROCHECK, verify 3D, and ERRAT servers were used for verification of the obtained models. Moreover, antigenicity, allergenicity, and physico-chemical analysis of enzymes were also carried out. In order to get insight into the interaction of the enzyme with other proteins, the STRING server was used. The secondary structure of the enzyme is mainly composed of random coils and alpha-helices. However, these outcomes should further be validated by wet-lab investigations.

A Novel Effective Formulation of Bioactive Compounds for Wound Healing: Preparation, In Vivo Characterization, and Comparison of Various Postbiotics Cold Creams in a Rat Model.

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.

Characterization of the first highly predatory Bdellovibrio bacteriovorus from Iran and its potential lytic activity against principal pathogenic Enterobacteriaceae.

OBJECTIVES: Bdellovibrio-and-like organisms (BALOs) are predatory prokaryotes that attack and kill other Gram-negative bacteria for growth and reproduction. This study describes the isolation, identification, biological properties, and bacteriolytic activity of the first Bdellovibrio bacteriovorus with a broad prey range from Iran. MATERIALS AND METHODS: One BALO strain with high predatory potency was isolated from the rhizosphere soil using Enteropathogenic Escherichia coli as prey. It was identified and designated as Bdellovibrio bacteriovorus strain SOIR-1 through plaque assays, transmission electron microscopy (TEM), Bdellovibrio-specific PCRs, and 16S rRNA gene sequence analysis. Biological characterization and analysis of bacteriolytic activity were also performed. RESULTS: TEM and Bdellovibrio-specific PCRs confirmed that the strain SOIR-1 belongs to the genus Bdellovibrio. Analysis of the 16S rRNA gene sequence revealed its close phylogenetic relationship with strains of Bdellovibrio bacteriovorus. The strain SOIR-1 grew within the temperature range of 25-37 °C and the pH range of 6.0-8.0, with the optimal predatory activity at 30 °C and pH 7.4. It had the highest and lowest bacteriolytic activity toward Shigella dysenteriae and Pseudomonas aeruginosa with a killing rate of 89.66% and 74.83%, respectively. CONCLUSION: Considering the hypothesis of bdellovibrios heterogeneity, identification of new isolates contributes to a deeper understanding of their diversity, their ecological roles, and their promising potential as living antibiotics or biocontrol agents. Bdellovibrios with broad bacteriolytic nature has not previously been reported in sufficient detail from Iran. The results of this study showed the great potential of native B. bacteriovorus strain SOIR-1 in the control and treatment of diseases caused by pathogenic Enterobacteriaceae.

Development and In Vivo Characterization of Probiotic Lysate-Treated Chitosan Nanogel as a Novel Biocompatible Formulation for Wound Healing.

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.

Enterobacter sp. Mediated Synthesis of Biocompatible Nanostructured Iron-Polysaccharide Complexes: a Nutritional Supplement for Iron-Deficiency Anemia.

FDA has approved iron oxide nanoparticles (IONs) coated with organic compounds as a safe material with less toxic effects compared with the naked metal ions and nanoparticles. In this study, the biological and physicochemical characteristics of a nanostructured iron-polysaccharide complexes (Nano-IPC) biosynthesized by Enterobacter sp. were evaluated. Furthermore, the serum biochemical parameters, tissue iron level, red blood cell parameters, and organ ferritin of rats were measured for investigating the effect of the Nano-IPCs in comparison with FeSO4 as a supplement for iron deficiency. The biosafety data demonstrated 35% increment of viability in Hep-G2 hepatocarcinoma cell lines when treated with nanoparticles (500 µg/mL) for 24 h. Besides, iron concentration in serum and tissue as well as the expression of ferritin L subunit in animals treated with the Nano-IPCs supplement were meaningfully higher than the FeSO4-supplemented and negative control animals. Moreover, the expression level of ferritin H subunit and biochemical factors remained similar to the negative control animals in the Nano-IPC-supplemented group. These results indicated that Nano-IPCs can be considered as a nontoxic supplement for patients carrying iron-deficiency anemia (IDA).

Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications.

Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their production and storage advantages compared to probiotics, they seem to be fascinating candidates for promoting human health condition as a replacement or in association with probiotics. This review discusses different aspects of prebiotics, including their crucial role in human well-being.

Three-component synthesis of chromeno ß-lactam hybrids for inflammation and cancer screening.

Highly diastereoselective synthesis of chromeno ß-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired ß-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4-hydroxycoumarin in the presence of 1,4-diazabicyclo [2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1D and 2D NMR spectra, X-ray analysis, H-H COSY and H-C HSQC two-dimensional NMR experiments, and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. ß-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. ß-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.

The Inhibition Effect of Lactobacilli Against Growth and Biofilm Formation of Pseudomonas aeruginosa.

The emergence of antibiotic-resistant and food-spoilage microorganisms has renewed efforts to identify safe and natural alternative agents of antibiotics such as probiotics. The aim of this study was the isolation of lactobacilli as potential probiotics from local dairy products with broad antibacterial and anti-biofilm activities against antibiotic-resistant strains of Pseudomonas aeruginosa and determination of their inhibition mechanism. Antibiotic susceptibility and classification of acquired resistance profiles of 80 P. aeruginosa strains were determined based on Centers for Disease Control and Prevention (CDC) new definition as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) followed by antibacterial assessment of lactobacilli against them by different methods. Among the 80 P. aeruginosa strains, 1 (1.3%), 50 (62.5%), and 78 (97.5%) were PDR, XDR, and MDR, respectively, and effective antibiotics against them were fosfomycin and polymyxins. Among 57 isolated lactobacillus strains, two strains which were identified as Lactobacillus fermentum using biochemical and 16S rDNA methods showed broad inhibition/killing and anti-biofilm effects against all P. aeruginosa strains. They formed strong biofilms and had bile salts and low pH tolerance. Although investigation of inhibition mechanism of these strains showed no bacteriocin production, results obtained by high-performance liquid chromatography (HPLC) analysis indicated that their inhibitory effect was the result of production of three main organic acids including lactic acid, acetic acid, and formic acid. Considering the broad activity of these two L. fermentum strains, they can potentially be used in bio-control of drug-resistant strains of P. aeruginosa.