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Abstract: Nowadays, there is an urgent need to discover and develop long-term and effective antimicrobial and biofilm-inhibiting compounds. Employing combination therapies using novel drug delivery systems and also natural antimicrobial substances is a promising strategy in this field. Nanoparticles (NPs)-based materials have become well appreciated in recent times due to their function as antimicrobial agents or carriers for promoting the bioavailability and effectiveness of antibiotics. Flavonoids belong to the promising groups of bioactive compounds abundantly found in fruits, vegetables, spices, and medicinal plants with strong antimicrobial features. Flavonoids and NPs have the potential to work as alternatives to the conventional antimicrobial agents, when used alone as well as in combination. Different classes of flavonoid NPs may be particularly advantageous in treating microbial infections. The most important antimicrobial mechanisms of flavonoid NPs include oxidative stress induction, non-oxidative mechanisms, and metal ion release. However, the efficacy of flavonoid NPs against pathogens and drug-resistant pathogens changes according to their physicochemical characteristics as well as the particular structure of microbial cell wall and enzymatic composition. In this review, we provide an outlook on the antimicrobial mechanism of flavonoid-based NPs and the crucial factors involved in it.

Background: Hepatocellular carcinoma (HCC) is a prevalent and life-threatening tumor with high morbidity and mortality. Proper prediction and prognosis are incredibly stressed to diagnose HCC and increase patient survival. Objectives: This research aims to evaluate gene expression levels of pre-differentiated transcripts for those suffering from chronic hepatitis B (CHB) and HCC. Methods: To examine the previously analyzed peripheral blood mononuclear cells (PBMCs) transcriptomic array data, we selected seven differentially expressed genes (DEGs) in normal versus CHB and CHB versus HCC (CD44, SP3, USP8, E2F2, UFM1, IFN regulative factor binding protein 2 (IRF2BP2), and T-cell intracellular antigen 1 (TIA1)). The study included individuals with treatment-naïve CHB (n = 30) and primary HCC (n = 25) and healthy controls (n = 15). Subsequently, the expression of genes was assayed using qRT-PCR. A phylogenetic evaluation was performed using direct sequencing of HBsAg. Results: In HCC patients, 60% (n = 15) were HBeAg-positive. HBeAg was negative in all CHB patients, but all were anti-HBe-positive. The hepatitis B virus (HBV) load of HCC patients was more than that of CHB subjects. All patients were of the Iranian race and HBV D genotype. The expression of five transcriptional markers (CD44, SP3, USP8, E2F2, and UFM1) was higher in HCC patients than in CHB and healthy subjects, which was similar to the initial microarray data analysis. Conclusions: Transcriptional signatures may be related to the pathogenesis of HCC and used as diagnostic biological markers for the initial monitoring and prediction of HCC.

The escalating prevalence of coronavirus disease 2019 (COVID-19) worldwide, with an increased rate of morbidity and mortality, highlights an urgent need to develop more effective therapeutic interventions. Despite the authorized treatment against COVID-19 by the European Union (EU), the safety and effectiveness of this therapeutic strategy for a wide variety of patients have remained a significant challenge. In this respect, micronutrients such as vitamins and minerals, as essential factors, can be considered for improving the function of the immune system and accelerating the treatment procedure. Dietary supplements can attenuate vascular and inflammatory manifestations related to infectious diseases in large part due to their anti-inflammatory and antioxidant properties. Recently, it has been revealed that poor nutritional status may be one of the notable risk factors in severe COVID-19 infections. In the current review, we focus on the micronutrient therapy of COVID-19 patients and provide a comprehensive insight into the essential vitamins/minerals and their role in controlling the severity of the COVID-19 infection. We also discuss the recent advancements, challenges, negative and positive outcomes in relevance to this approach.

Introduction: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (p=0.014) and 4.9% vs. 23.9% (p=

Objective: MicroRNAs (miRNAs) expression has deregulated in several cancer types including breast cancer (BC). The present study aims at investigating the role, mechanism, clinical value of let-7d and miR-185 in BC, and the possible correlation these miRNAs with Rab25. Materials and Methods: Tumor samples as well adjacent normal tissues (ANT) were acquired from fresh surgical specimens from 110 patients and the expression levels of let-7d, miR-185, Rab25, and snail were evaluated using real-time PCR. The immunohistochemical (IHC) process and western blot were done to detect the level of Rab25 and Snail protein expression in BC samples. Results: By comparing miRNAs expression profiles in clinical tissues of 110 patients using real-time PCR, let-7d, and miR-185 expression were dramatically downregulated in BC tissues (P < 0.05). Tumor size, stage, and lymph node metastasis were significantly related to miRNAs expression. Based on qRT-PCR and bioinformatics database analyses, we also recognized Rab25 as a possible target of miR-185 and let-7d. Rab25 expression was enhanced in BC cells and associated inversely with the expression level of mentioned miRNAs. qRT-PCR, immunohistochemistry, and western blot studies verified that Rab25 upregulation increased the levels of the snail, that key transcription factor of epithelial-mesenchymal transition (EMT). Conclusion: These findings demonstrated that let-7d and miR-185 inhibited EMT by targeting Rab25 expression in BC. Therefore, targeting the let-7d and miR-185/Rab25 interaction may offer new therapeutic opportunities for treating BC patients.

Objective: MiR-140 and miR-196a were known to be correlated with cancer diagnosis and prognosis. The current study aimed at the analysis of miR-140 and miR-196a expression patterns and their clinical significance for breast cancer (BC) patients. Methods: Differentially expressed miR-140 and miR-196a were examined via quantitative PCR in 110 cases of BC and their adjacent non-tumor (ANT) tissues. Results: The results indicated that miR-140 and miR-196a, respectively, notably decreased and increased expression in BC samples in comparison with ANT (p

Abstract: Infection of the central nervous system (CNS) is a global healthcare concern with high rates of death and disease. CNS infections mainly include meningitis, encephalitis, and brain abscesses. Bacteria, viruses, fungi, protozoa, and parasites are the most common causes of neuroinfections. There are many types of medications used in the treatment of CNS infections, but drug delivery through the blood-brain barrier (BBB) is a major challenge to overcome. The BBB is a specialized multicellular barrier separating the neural tissue from the peripheral blood circulation. Unique characteristics of the BBB allow it to tightly control the movement of ions and molecules. Thus, there is a critical need to deal with these conditions with the aim of improving novel antimicrobial agents. Researchers are still struggling to find effective drugs to treat CNS infections. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem because NPs can be tailored to facilitate drug transport across the BBB. NPs are colloidal systems with a size range of 1-1000 nm, which can be used to encapsulate therapeutics, improve drug transport across the BBB, and target specific brain areas in CNS infections. A wide variety of NPs has been displayed for the CNS delivery of therapeutics, especially when their surfaces are coated with targeting moieties. This study aimed to review the available literature on the application of NPs in CNS infections.

Background: Leprosy is still a global health problem, especially in developing countries are important, and Iran is an endemic area for leprosy in the Middle East. Leprosy is a disease caused by the intracellular bacterium Mycobacterium leprae, is a chronic infectious disease of humans that causes inflammatory lesions in the skin and peripheral nerves with the granuloma. Numerous studies, the important role of host genetics in susceptibility to leprosy are confirmed. CTLA4 gene is one of the four exons. Polymorphisms have been identified in the CTLA4 gene with susceptibility to a wide range of autoimmune and infectious diseases dependent on T cells are connected. The aim of this study was to investigate the relationship between polymorphisms of CTLA-4 +49 A / G and susceptibility to leprosy and its impact on the type and severity of disease. Methods: In this study, 157 treated leprosy patients living in nursing homes in Tabriz Baba Baghi and 185 healthy human subjects were enrolled as controls. First blood samples (8-10 ml) of patients Gene polymorphism CTLA-4 +49 A / G were determined, and then the genotype frequencies in two groups were compared. In addition, for each patient clinical forms of the disease, the performance, age at onset, duration of illness, symptoms, age, sex and relationship between genotypes and allele polymorphism review was studied. Results: The average age was 11.90 ± 65.87 years and the highest prevalence of leprosy at the age of 16 to 30 years old. The most common side effects of organ failure, neurological diseases, leprosy protests eye and ear, nose and throat incidence was 33%. Conclusion: Gene CTLA-4 (+49 A / G) showed that the frequency of AA greater was than the other two types.

Objectives: Staphylococcus aureus (S. aureus) is the most prevalent cause of skin infections, especially in colonized individuals. Panton–Valentine leukocidin (PVL) and Arginine catabolic mobile element (ACME) are known as the most common virulence factors of S. aureus. This cross-sectional study was conducted to examine the prevalence of ACME-arcA and PVL genes among S.aureus isolates in the student population. Nasal swab samples were randomly collected from 400 healthy students from Tabriz, Iran. The antibiotic resistance pattern of S.aureus isolates was examined by the disk diffusion method. The presence of ACME-arcA, PVL, and mecA genes was detected by PCR reaction.Results: overall, 15% (60/400) students were nasal carriage of S. aureus and 2.75 % (11/400) were MRSA carriage. The frequency of mecA, ACME-arcA, and PVL genes was 54.54% (36/60), 46.66% (28/60), and 16.66% (10/60) respectively. The prevalence of ACME-arcA and PVL genes was independent of gender (P =0.142, P=0.337, respectively). A notable association was observed between the existence of ACME-arcA gene and the frequency of mecA gene (P PVL was independent on mecA. These findings highlight the necessity of monitoring nasal carriers in a healthy community to prevent subsequent infections.

Coronavirus disease 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 253,381 deaths worldwide since its emergence in late 2019 (updated May 6th, 2020). COVID-19 is caused by a novel emerged coronavirus named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens. In this study, we have targeted spike (S) glycoprotein, as an important surface antigen of SARS-CoV-2, to identify its immunodominant B- and T-cell epitopes. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020). The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531–N711; T717–C877; and V883–E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations. These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in the animal studies.

Inadequate data are available on the global epidemiology of mucormycosis, mainly derived from the evaluation of specific population groups. Rhinocerebral mucormycosis is an invading and fatal mycosis, particularly among diabetic patients. In the present study, patients hospitalised in Imam Reza Hospital in Tabriz, from 2007 to 2017, were evaluated. The hospital information system (HIS) was used to collect the records of the patients. A total of 42 patients with a diagnosis of mucormycosis were included in the study, 40 cases (95%) of which had a diagnosis of the rhinocerebral form. Of these 40 patients, 21 (52.5%) and 19 (47.5%) were male and female, respectively. Seven cases (17.5%) of rhinocerebral mucormycosis were due to dental procedures. The most predisposing factor in the patients was diabetes with 36 (90%) cases. In our study, the role of tooth extraction in patients with uncontrolled diabetes was identified as an important factor. It may show the important role of dentists in preventing of the disease in diabetic patients.

Bacteria have a considerable ability and potential to acquire resistance against antimicrobial agents by acting diverse mechanisms such as target modification or overexpression, multidrug transporter systems, and acquisition of drug hydrolyzing enzymes. Studying the mechanisms of bacterial cell physiology is mandatory for the development of novel strategies to control the antimicrobial resistance phenomenon, as well as for the control of infections in clinics. The SOS response is a cellular DNA repair mechanism that has an essential role in the bacterial biologic process involved in resistance to antibiotics. The activation of the SOS network increases the resistance and tolerance of bacteria to stress and, as a consequence, to antimicrobial agents. Therefore, SOS can be an applicable target for the discovery of new antimicrobial drugs. In the present review, we focus on the central role of SOS response in bacterial resistance mechanisms and its potential as a new target for control of resistant pathogens.

Objectives: Brucellosis is a worldwide zoonotic disease with high morbidity in the absence of treatment. The early diagnosis of brucellosis is efficient to prevent chronic infections. The aim of this study is evaluation of nested PCR efficiency in comparison with conventional methods for diagnosis of human brucellosis. A total of 120 patients with brucellosis symptoms were included in this study. Serological and microbiological tests and nested PCR were used for detection of Brucella bacteria. Results: Based on serological tests, 60.83% (73/120) of individuals were positive for brucellosis which only 8.33% of cases were confirmed by blood culture. Among them, 55% of cases were positive in serum agglutination test (SAT≥1:160) and Coombs (C-SAT≥1:160) tests. Furthermore, 7 negative SAT cases were positive in C-SAT as evidence for chronic brucellosis. Also, 68.18% and 56.06% of SAT positive samples were positive in blood nested PCR and serum nested PCR respectively. The sensitivity of blood nested PCR was more than serum nested PCR, SAT≥1:160 and blood culture (P

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is often the cause of a wide broad of infections ranging from minor skin infections to serious infections such as toxic shock syndrome (TSS) in hospital and community settings. Toxic shock syndrome toxin 1 (TSST-1) superantigen is the main cause of TSS. Objectives: The current study aimed to determine the frequency of MRSA carriage and TSST-1 virulence factor among high school students. Methods: A total of 400 nasal swab samples were randomly collected from male and female students of six different high schools in Tabriz, Iran. After confirmation of S. aureus strains by standard biochemical tests, the antibiotic sensitivity pattern of the isolates was determined by the disk diffusion method. The presence of mecA and TSST-1 genes was examined by PCR. Results: From 400 students, 15% (n = 60) were positive for S. aureus. Antimicrobial susceptibility testing was performed using 12 antibiotic disks. Based on the results, 100% of the isolates were resistant to ampicillin while all of them were sensitive to vancomycin. Moreover, 18.34% of the S. aureus isolates were resistant to cefoxitin and 11.67% were resistant to oxacillin. The presence of the mecA gene was confirmed in 54.54% of the cases. These results indicated oxacillin-susceptible mecA-positive S. aureus (OS-MRSA) colonization among students. Based on the PCR results, only one of the MRSA isolates belonging to a female student was positive for the TSST-1 gene. Conclusions: Our findings highlight the spread of OS-MRSA among the healthy population in Tabriz, Northwest of Iran. Nevertheless, a combination of genetic and phenotypic tests is needed to accurately detect MRSA.

Escalating antibiotic resistance is now a serious menace to global public health. It may be led to the emergence of "postantibiotic age" in which most of infections are untreatable. At present, there is an essential need to explore novel therapeutic strategies as a strong and sustainable pipeline to combat antibiotic-resistant infections. This review focuses on recent advances in this area including therapeutic antibodies, antimicrobial peptides, vaccines, gene therapy, genome editing, and phage therapy for tackling drug-resistant infections.

Aims: To determine the inhibitory effect of oral Lactobacillus against bacterial pathogens and investigate correlation between presence of Lactobacillus strains and health promotion. Method: One hundred saliva samples were collected from oral cavity of domestic dairy consumers and were investigated for the isolation and identification of Lactobacillus strain by conventional culture and sequencing of 16SrRNA. Furthermore, well diffusion assay was performed to determination of antibacterial activity of Lactobacillus strains against bacterial pathogens including Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis and Enterococcus faecium. Finally, association between health condition and isolation of Lactobacillus were investigated and obtained data using questionary form were analysed by chi-square test. Results: Thirty Lactobacillus strains recovered from 100 hundred saliva samples. The most common isolated strain was L. gasseri (n=18) and followed by L. vaginalis (n=3) and L. salivarius (n=3). All Lactobacillus strains demonstrated antibacterial activity against at least one of the investigated pathogens. However, the strongest results were obtained by L. vaginalis against K. pneumonia. The correlation between the presence of thirty Lactobacillus strains and health promotion not found. However, only L. gasseri species has significant positive impact on health in their hosts (P < 0.05). Conclusion: Only some Lactobacillus species have a positive impact on health promotion. Despite of weak activity against the investigated pathogens, L. gasseri has a positive impact on the mental problem (intense anger and depression) of their hosts. Resumen Objetivos: Determinar el efecto inhibidor del Lactobacillus aislado de la cavidad oral contra patógenos bacterianos e investigar la correlación entre la presencia de cepas de Lactobacillus y la promoción de la salud. Método: se recolectaron cien muestras de saliva de la cavidad oral de consumidores de productos lácteos y se investigó el aislamiento e identificación de la cepa de Lactobacillus mediante cultivo convencional y secuenciación de 16SrRNA. Además, se realizó un ensayo de difusión en pocillos para determinar la actividad antibacteriana de las cepas de Lactobacillus contra patógenos bacterianos que incluyen Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis y Enterococcus faecium. Finalmente, se investigó la asociación entre el estado de salud y el aislamiento de Lactobacillus y se obtuvieron los datos utilizando el cuestionario mediante la prueba de chi-cuadrado. Resultados: Se aislaron treinta cepas de Lactobacillus de 100 muestras de saliva. La cepa aislada más común fue L. gasseri (n = 18), seguida por L. vaginalis (n = 3) y L. salivarius (n = 3). Todas las cepas de Lactobacillus demostraron actividad antibacteriana contra al menos uno de los patógenos investigados. Sin embargo, los resultados más fuertes fueron obtenidos por L. vaginalis contra K. pneumonia. No se encontraron correlación entre la presencia de algunas de las treinta cepas de Lactobacillus y la promoción de la salud. Sin embargo, solo la especie L. gasseri tuvo un impacto positivo significativo en la salud de sus hospedadores (P

Background Increasing prevalence of multidrug-resistant (MDR) A. baumannii isolates coupled with survival ability in adverse conditions has made this pathogen a serious threat to global health. A cross-sectional study was conducted to examine biofilm forming genes and antibiotic resistance profiles of A. baumannii clinical isolates in Tabriz, North-west Iran. Methods A total of 100 A. baumannii strains were isolated from hospitalized patients in Tabriz city, northwest of Iran. The isolates were detected through standard microbiological and biochemical tests and blaOXA-51 detection. After the examination of antibiotic resistance profile, the biofilm formation capacity was investigated by a microtitre plate assay. The presence of bap and ompA genes related to biofilm-forming was examined by PCR reaction. Results The highest resistance rate was observed against meropenem (100%), tigecycline (100%), and ceftizoxime (99%), respectively. Analysis for resistance to different antibiotic classes revealed that 100% of the isolates were multidrug-resistant (MDR), and 79% of them were extensively drug-resistant (XDR). Overall, 84% of the isolates were able to produce biofilm that 3.57% (3/84) of them were strongly capable to form a biofilm. All of the strong biofilm-forming A. baumannii isolates were found as XDR. Also, 100% of the isolates had the ompA gene, and 89% of them were positive for the bap gene. Conclusion Our findings revealed a high prevalence of biofilm-forming and biofilm-related genes of bap and ompA in MDR A. baumannii strains in the study region. Based on our results, there is a correlation between the presence of the bap gene and biofilm formation.

Introduction and objectives Methicillin-resistant Staphylococcus (S.) aureus (MRSA) is responsible for clinical infections ranging from minor skin infections to severe infections. Alpha hemolysin (hla) and beta hemolysin (hlb) are the most common virulence factors in S. aureus. The current study was aimed to detect hla and hlb genes in nasal methicillin-resistant S. aureus isolates in the student population. Materials and method A total of 1420 nasal samples were obtained from 23 different high schools in Tabriz city. After confirmation of S. aureus strains by standard biochemical tests, the antibiotic resistance pattern was determined by the disk diffusion method. The presence of mecA, hla, and hlb genes was examined by PCR reaction. Result Of 1420 samples, 14.30% (203 cases) were positive S. aureus. Among them, 18.72% (38/203) of the isolates were MRSA based on disk diffusion. Based on results, more than 90% of the isolates were susceptible to chloramphenicol, ciprofloxacin, and cefazolin, suggesting that these drugs may indicate better function to treat MRSA infections. The existence of mecA, hla, and hlb genes was observed in 56.16%, 88.18%, and 62.07%, respectively. There is a significant relationship between the prevalence of hla and frequency of the macA gene (p = 0.049), while the rate of hlb was independent on mecA. Discussion and conclusion The increasing prevalence of hla/hlb positive S. aureus isolates indicates an essential need to monitor nasal carriers in a healthy community to prevent subsequent infections.

Bacteroides fragilis is a most frequent anaerobic pathogen isolated from human infections, particularly found in the abdominal cavity. Different factors contribute to the pathogenesis and persistence of B. fragilis at infection sites. The knowledge of the virulence factors can provide applicable information for finding alternative options for the antibiotic therapy and treatment of B. fragilis caused infections. Herein, a comprehensive review of the important B. fragilis virulence factors was prepared. In addition to B. fragilis toxin (BFT) and its potential role in the diarrhea and cancer development, some other important virulence factors and characteristics of B. fragilis are described including capsular polysaccharides, iron acquisition, resistance to antimicrobial agents, and survival during the prolonged oxidative stress, quorum sensing, and secretion systems.

Objectives Methicillin resistant Staphylococcus (S.) aureus colonization is one of the main causes of serious infections in hemodialysis patients. This cross-sectional study was performed to examine prevalence of MRSA colonization and evaluation of risk factors in hemodialysis patients. A total of 560 swab samples from nasal, the skin around catheter and throat were collected from 231 hemodialysis patients in Tabriz. The standard biochemical tests were used for identification of S. aureus isolates. Antimicrobial susceptibility profile was determined against 11 antibiotics by the disk diffusion method. Phenotypic test of S. aureus was performed using novobiocin 30 μg/disc, and methicillin sensitivity test was performed by cefoxitin 30 μg/disc. Results Overall, 50.65% (118/231) hemodialysis patients were positive for S. aureus which 34.93% (80/231) of patients were MRSA carriage. The MRSA colonization in patients with a catheter (44.06%) was more than individuals utilizing a fistula (24.57%, p = 0.030). Among sampling sites, the highest MRSA was related to nasal samples (30.70%, p

Objectives During recent years, multidrug-resistant Acinetobacter baumannii strains have become a serious threat to global health. Furthermore, the appearance of new resistant markers, such as New Delhi metallo-β-lactamase (NDM-1) with the ability to hydrolyze a wide range of β-lactams has limited the treatment process. Aim This cross-sectional study was aimed to detect blaOXA-23 and blaNDM-1 carbapenemase genes among A. baumannii clinical isolates in Tabriz, North-west Iran. Methods A total of 100 A. baumannii isolates were collected from Imam Reza Hospital of Tabriz city. Isolates were recognized by standard biochemical tests and molecular detection of blaOXA-51 gene. Antimicrobial susceptibility profile was examined via the disk diffusion method. The presence of blaOXA-23 and blaNDM-1 resistance genes was determined by PCR and sequencing. Results Overall, the highest resistance rate was against ciprofloxacin (95%), aztreonam (90%) and imipenem (82%) whereas the highest susceptibility was detected to gentamicin (65%). The frequency of MDR and XDR strains was 76% and 30%, respectively. All of carbapenem resistant isolates were carrying blaOXA-23 gene and only one of them (1%) was positive for blaNDM-1 resistance gene. Conclusion Our results are indicating a high incidence of blaOXA-23 like gene and the emergence of blaNDM-1 gene as a resistance factor to almost all antibiotics among the carbapenem resistant A. baumannii strains in our study region.

microRNAs (miRNAs), as a group of noncoding RNAs, posttranscriptionally control gene expression by binding to 3'-untranslated region (3'-UTR). Ras-associated binding (Rab) proteins function as molecular switches for regulating vesicular transport, which mainly have oncogenic roles in cancer development and preventing the efficacy of chemotherapies. Increased evidence supported that miRNAs/Rabs interaction have been determined as potential therapeutics for cancer therapy. Nevertheless, instability and cross-targeting of miRNAs are main limitations of using miRNA-based therapeutic. The mutual interplay between Rabs and miRNAs has been poorly understood. In the present review, we focused on the essence and activity of these molecules in cancer pathogenesis. Also, numerous hindrances and potential methods in the expansion of miRNA as an anticancer therapeutics are mentioned.

Pseudomonas aeruginosa is an opportunistic bacterium that causes serious nosocomial infection in immunocompromised patients. The aim of this study was to prepare a fusion protein consisting of exotoxin A (ExoA) and flagellin (Fla) from P. aeruginosa and to evaluate its potential as a vaccine candidate against P. aeruginosa infection. The genes encoding for ExoA and Fla proteins were cloned in-frame and expressed in Escherichia coli. The recombinant ExoA–Fla fusion protein was purified by Ni-NTA affinity chromatography. Mice were immunized subcutaneously with ExoA, Fla, and ExoA–Fla fusion proteins, and the humoral immune response was evaluated by ELISA method. The immunized and control group mice were challenged with a 2× LD50 (7.5 × 107 CFU) of P. aeruginosa for the protection assay. The results indicated that vaccination with Fla, ExoA, and ExoA–Fla fusion proteins produced a significant amount of specific immunoglobulin G antibodies. Immunization of mice with ExoA–Fla fusion protein showed significant protection against intraperitoneal challenge with 7.5 × 107 CFU (2× LD50) P. aeruginosa. Results of this study suggest that recombinant ExoA–Fla fusion protein is a highly immunogenic protective protein showing promise as a vaccine candidate against P. aeruginosa.

The aims of this study were to determine carbapenem resistance mechanisms, molecular epidemiological relationship, clinical impact, and patient outcome of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections. A total of 42 nonduplicated CRPA were recovered from Urmia, Iran. Antimicrobial susceptibility tests were carried out using phenotypic methods. The carbapenem resistance mechanisms such as carbapenemase genes, efflux pump hyperexpression, AmpC overproduction, and OprD gene downregulation were determined by phenotypic and molecular methods. Eighteen metallo-β-lactamase (MBL) producer isolates were found to be sensitive to amikacin. Among the CRPA, 52.3%, 26.1%, 26.1%, and 59.5% were identified as carbapenemase, efflux pump hyperexpression, AmpC overproduction, and reduced expression OprD gene, respectively. Random Amplified Polymorphic DNA analysis yielded 25 distinct profiles. Most MBL-positive isolates were recovered from patients hospitalized in urology and internal wards with urinary tract infections. Most of the strains showed downregulation of porin. The clonal distribution of the strains was related to carbapenem resistance mechanisms (most of MBL producers belong to the same clones) and the same hospital wards where the isolates were collected. The study demonstrates that the main risk factor of MBL-related infections was hospitalization in non-intensive wards. Amikacin was considered a very efficient antibiotic to treatment of MBL-producing CRPA isolates. Our results showed that OprD downregulation and IMP-type MBL are the main carbapenem resistance mechanisms in CRPA isolates from northwest of Iran.

Background: Multidrug resistant (MDR) Acinetobacter baumanii strains have emerged as novel nosocomial pathogens threatening patients’ lives, especially in intensive-care units (ICU). Various types of extended-spectrum β-lactamases (ESBLs) are involved in conferring resistance to β-lactam antibiotics, making their genotypic characterization an essential prerequisite to take proper preventative measures. Objectives: The aim of this study was to determine the antimicrobial susceptibility and prevalence of blaTEM, blaSHV, blaCTX-M, blaOXA-2, and blaOXA-10 genes among A. baumanii isolates obtained from patients in Tabriz city, North-west Iran. Methods: The clinical isolates of A. baumanii were collected from patients hospitalized in the Imam Reza hospital of Tabriz. Antimicrobial susceptibility patterns were determined by the disk diffusion method. The frequency of different ESBLS resistance genes were determined by PCR. Results: Antimicrobial susceptibility testing through the disk diffusion method revealed that the lowest resistance rates were against polymyxin B (16%), colistin (23%), and rifampin (27%); whereas the highest resistance rate was observed against ticarcillin (100%), cefixime (100%), and ceftizoxim (100%). Screening by double disk synergy test showed that 60% of the isolates were ESBL producers. PCR technique on ESBL-positive isolates determined blaSHV gene as the most prevalent (31.6%) and blaOXA-10 as the least prevalent (8.3%) among the studied resistance genes. Conclusions: The high prevalence of resistance genes supported the essential role of ESBLs in antibiotic resistance of A. baumanii.

Background Q fever is an endemic disease in different parts of Iran. This study aimed to investigate the prevalence of acute Q fever disease among at-risk individuals in northwestern Iran. Methodology An etiological study was carried out in 2013 in Tabriz County. A total of 116 individuals who were in contact with livestock and had a nonspecific febrile illness were enrolled in the study. IgG phase II antibodies against Coxiella burnetii were detected using ELISA. Principal findings The prevalence of acute Q fever was 13.8% (95% confidence interval [CI]: 8.0, 21.0%). Headache (87.5%) and fatigue and weakness (81.3%) were the dominant clinical characteristics among patients whit acute Q fever. Acute lower respiratory tract infection and chills were poorly associated with acute Q fever. Furthermore, 32% (95% CI: 24, 41%) of participants had a history of previous exposure to Q fever agent (past infection). Consumption of unpasteurized dairy products was a weak risk factor for previous exposure to C. burnetii. Conclusion This study identified patients with acute Q fever in northwestern of Iran. The evidence from this study and previous studies conducted in different regions of Iran support this fact that Q fever is one of the important endemic zoonotic diseases in Iran and needs due attention by clinical physicians and health care system., Author summary Q fever is a zoonotic contagious disease caused by a bacterium called Coxiella burnetii. It is mostly asymptomatic in livestock and animals. Clinical manifestations of Q fever in humans includes asymptomatic, acute and chronic to fatigue syndrome. The most frequent clinical manifestation of acute Q fever is a flu-like and self-limited illness, and clinical presentations of these patients are highly variable and extensive. Chronic Q fever is accompanied by symptoms such as endocarditis, vasculitis, prosthetic joint arthritis, osteoarticular infection and lymphadenitis. Studies conducted in Iran emphasize that Q fever is an endemic disease in different parts of Iran. Since few studies have been conducted to identify acute Q fever patients with in Iran, the present study set to investigate the prevalence of acute Q fever among at-risk individuals in northwestern Iran. The prevalence of acute Q fever was 14.0% among 116 suspected febrile patients. It was also shown that 32% of the participants had serological evidence of previous infection (past infection) with Q fever. The findings showed that most clinical symptoms in patients with acute Q fever were fever, headache, fatigue and weakness, arthralgia, myalgia, chills, chest pain and dyspnea, respectively.

The prevalence of metallo-β-lactamase (MBL) production among 104 clinical isolates of Pseudomonas aeruginosa from northwest of Iran was investigated by phenotypic and polymerase chain reaction (PCR) methods. Thirty-nine (37.50%) of isolates were MBL positive by double-disk synergy test. Results of PCR revealed that 18 (17.31%) and 6 (5.77%) imipenem nonsusceptible isolates of P. aeruginosa carried bla(VIM) and bla(IMP) genes respectively, while 92.4% (62/67) of isolates contained class 1 integron gene. This is the first report of MBL-producing P. aeruginosa from northwest of Iran.

Summary Background The empirical therapy of urinary tract infections (UTI) relies on the predictability of the agents causing UTI and knowledge of their antimicrobial susceptibility patterns. Methods In a prospective study undertaken over a 14-month period, 5136 samples from patients suspected of having a UTI were analyzed, of which 676 were culture-positive. Isolated bacteria were identified by standard tests, and antibiotic susceptibility was determined by disk diffusion method. Results According to our results, Escherichia coli was the most common etiological agent of UTI (74.6%), followed by Klebsiella spp (11.7%), Staphylococcus saprophyticus (6.4%), and Pseudomonas aeruginosa (2.2%). Analysis of the frequency of isolated bacteria according to the age of the patients revealed that Klebsiella infections are more prevalent in the older age groups (>10 years) and Pseudomonas infections are more prevalent in children and the elderly ( 60 years). Results of antimicrobial susceptibility analysis for E. coli , as the most prevalent cause of UTI, to commonly used antibiotics are as follows: amikacin (97.8%), gentamicin (97%), ciprofloxacin (94%), nitrofurantoin (87.1%), nalidixic acid (93.7%), trimethoprim–sulfamethoxazole (48.2%), cephalexin (76%), and ampicillin (6.9%). Conclusions The results show that the antimicrobial resistance patterns of the causes of UTI are highly variable and continuous surveillance of trends in resistance patterns of uropathogens is important.

Background: Methicillin resistant Staphylococcus aureus strains (MRSA) are important pathogens that cause serious diseases in humans. Throughout the recent years, the spread of these strains has increased in medical environments and society, and has become a serious challenge in health systems. Therefore, it is vital to investigate the various MRSA types to identify the origins of the infections and to control the spread of these infections in hospitals. Objectives: The current study aimed to evaluate the different SCCmec types in MRSA isolates from hospitals of Tabriz, by staphylococcal cassette chromosome mec (SCCmec) typing. Materials and Methods: The present descriptive and retrospective study was performed on 151 selected S. aureus isolates obtained from clinical specimens who were referred to Tabriz university of medical sciences educational-health care centers from April 2005 to September 2012. MRSA isolates were identified by agar disk diffusion and mecA PCR assays. Ultimately, they were typified according to the genetic diversity of the chromosome cassette of SCCmec and ccr regions. Results: Of the 151 isolates, 53 were recognized as MRSA. All of these 53 samples were sensitive to teicoplanin and vancomycin. Antibiotic resistance patterns were as follows: azithromycin 56.6%, ciprofloxacin 28.3%, imipenem 11.3%, meropenem 9.4%, ofloxacin 13.2%, ceftriaxone 66%, cotrimoxazole 49.1%, gentamicin 52.8%, linezolid 11.3%, penicillin 90.6%, and rifampicin 5.7%. The majority of MRSA isolates belonged to SCCmec III (69.8%) followed by SCCmec IVc (7.5%), SCCmec IVa (3.8%), and SCCmec I (1.9%). Other types of SCCmec were not observed in the present study. Moreover, from the 53 MRSA samples, 9 were recognized as non-typable. However, staphylococcal cassette chromosome recombinase (ccr ) genetic complex analysis revealed that among the 53 studied samples, 4 isolates had ccr type 1 pattern, and 11 and 32 isolates had ccr type 2 and ccr type 3 pattern, respectively. Furthermore, 6 isolates were considered as non-typable with ccr -typing. Conclusions: As about 70% of methicillin-resistant isolates belonged to SCCmec III, the present study can conclude that, over an 8-year period, only one dominant and stable clone of MRSA strain was found in Tabriz hospitals. This finding could be a result of incorrect medical orientations, inadequate infection controlling policies, and insufficient preventive approaches.