The immunomodulatory role of probiotics in allergy therapy.

The increased incidence of allergic disorders may be the result of a relative fall in microbial induction in the intestinal immune system during infancy and early childhood. Probiotics have recently been proposed as viable microorganisms for the prevention and treatment of specific allergic diseases. Different mechanisms have been considered for this probiotic property, such as generation of cytokines from activated pro-T-helper type 1 after bacterial contact. However, the effects of its immunomodulatory potential require validation for clinical applications. This review will focus on the currently available data on the benefits of probiotics in allergy disease.

Evaluation of the prevalence of Legionella pneumophila in Iranian clinical samples: A systematic review and meta-analysis.

BACKGROUND: Legionella pneumophila is the main cause for community-acquired pneumonia especially in hospital environments. In this systematic review and meta-analysis, we evaluated the prevalence of L. pneumophila in clinical samples obtained from Iranian patients. METHODS: The studies reporting L. pneumophila prevalence in Iranian clinical samples that were published between January 2000 and July 2016 were recruited. Comprehensive Meta-Analysis Software (version 3.3.070) was used for quantitative data analysis. Because of high heterogeneity between the studies according to the Cochrane Q and I2 statistics, a random-effects model was used for meta-analysis. RESULTS: Sixteen studies encompassing 1956 subjects were included in the meta-analysis. The overall prevalence of L. pneumophila was 9.6% in clinical samples obtained from the Iranian patients. The age spectrum ranged from 6 months to 80 years old. Dyspnea and cough comprised the most common clinical manifestations. In the subgroup analysis, the prevalence of L. pneumophila was higher in studies with sample size ≤100 (12.9%) in comparison with studies with sample size >100 (8.4%). In addition, the prevalence of L. pneumophila was higher in the years 2009-2016 (9.2%) compared with 2000-2008 (0.7%). CONCLUSION: L. pneumophila is a major cause of community- and hospital-acquired pneumonia. It is of pivotal importance to implement sensitive and reliable molecular and culture-based techniques to detect and control this infection in healthcare environments.

Macrophage plasticity, polarization, and function in health and disease.

Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF, and produce pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, IL-12, IL-23, and TNF-α; and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-ß. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation-associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF-α, IL-1ß, IL-12, and IL-23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL-10 and TGF-ß to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti-microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.

Quercetin nano phytosome: as a novel anti-leishmania and anti-malarial natural product.

Leishmaniasis is a vector-borne disease that affects several populations worldwide with the clinical manifestations in skin, mucous membranes, and internal organs and there are not any effective and available vaccines and conventional treatments are highly toxic. Quercetin is a kind of flavonoid with different biological effects including free radical scavenging and anti-microbial activity and this study is aimed to assess the anti-leishmania and anti-malarial effects of quercetin loaded phytosome and quercetin alone. In this experimental study, the in vitro activity of above drugs were measured using microscopically examinations and for evaluation the anti-leishmanial efficacy, the size of lesions were measured. Moreover the cytotoxicity of the treatments was evaluated on WI38 and J774 cell lines. Our results indicated that quercetin loaded phytosome and quercetin alone have acceptable anti-parasitic activity mostly at concentration of 400 µg/ml on both P. falciparium and L. major. The results of cytotoxicity revealed that the mentioned drugs have no effects on human cell lines and also have no hemolytic activity. The drug of choice for the treatment of leishmaniasis, in addition to killing the parasite, should not have a toxic effect on human cells and our results indicated that quercetin can be a valuable candidate for treatment of different kinds of leishmaniasis.

Identification and Characterization of the miRNAs and Cytokines in Response to Leishmania infantum Infection with Different Response to Treatment.

PURPOSE: Due to the complexity of cytokine and microRNA function in progression and/or suppression of an infection, in this study, we examined miR-3473f, miR-2128, miR-6994-5p, miR-7093-3p, miR-5128, miR-574-5p, miR-7235, IL-2, IL-4, IL-5, IL-10 and IL-13 in patients with VL caused by Leishmania infantum in an in vivo study. METHODS: Sampling was carried out from patient with leishmaniasis and with different responses to treatment during March 2016-January 2020. DNA was extracted and purified using QIAamp Kit. The L. infantum were cultured in DMEM medium and protein content was determined by the Micro BCA Protein Assay Kit. Cytokines were evaluated using a MILLIPLEX MAP Mouse Cytokine/Chemokine Panel I kit. The relative expression of miRNAs was measured in duplicate using automatic thermocycler ABI Prism 7500 sequence detection system (Applied Bio-systems) using the TaqMan MicroRNA Assay kit. RESULTS: The real-time PCR assay revealed that miR-2128, miR-6994-5p, miR-7093-3p, miR-5128, miR-574-5p and miR-7235 were down-regulated and miR-3473 were up-regulated in patients with semi-resistance and resistance parasite strain (P < 0.05). In the current work, cytokine patterns in patients who were slow-to-clear or unable-to-clear L. infantum infection during drug treatment were seen to have decreased protective Th1 cytokines (IL-2, IL-12, TNF-α, and IFN-ɤ, P < 0.001) and increased Th2 cytokines (IL-5, IL-10, and IL-13, P < 0.001). No association was seen with IL-4 in patients with different treatment outcomes. CONCLUSION: Overall, the results of a recent study have shown that cytokines and microRNAs can play a key role in response to treatment, and more comprehensive studies are needed to support this hypothesis.

The Comparison of the IFN-ɤ, TNF-α and IL-10 Cytokines in Healing and Non-healing Cutaneous Leishmaniasis.

BACKGROUND: Leishmaniasis is one of the main vectors borne and neglected tropical parasitic diseases. T cell cytokine responses are highly important in the presentations of disease such as control or progression, and understanding of the host immunological response is valuable in diagnosis, follow-up, and vaccine designs. In the current study, the profile of IFN-ɤ, TNF-α, and IL-10 cytokines was investigated through the ELISA technique in PBMCs isolated from antimony resistance and susceptible patients. METHODS: In this experimental study, 54 patients with healing (n=27) or non-healing (n=27) CL were recruited. Lesion samples were collected to determine the genotype of Leishmania spp. and peripheral blood mononuclear cells (PBMCs) were obtained to evaluate the cytokines profiles using soluble Leishmania antigen (SLA) and phytohaemagglutinin (PHA) mitogen. Cytokines were assessed by the ELISA technique. RESULTS: The IFN-ɤ and TNF-α cytokines were significantly increased in the healing group treated with both SLA antigen and PHA mitogen (P<0.001). The level of IL-10 was significantly increased in non-healing and significantly declined in healing groups (P<0.001). CONCLUSION: The profile of IFN-ɤ, TNF-α, and IL-10 cytokines are crucially associated with the response of treatment.

Assessment of DNA vaccine encoding Toxoplasma gondii microneme complete gene and IL-12 as adjuvant in BALB/c mice.

OBJECTIVES: Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis in humans and animals. Micronemes (MICs) are effective candidates for DNA vaccine. MATERIALS AND METHODS: In this study, we evaluated the immune response of BALB/c mice against MIC3 gene of Toxoplasma gondii and interleukin 12 (IL-12) as DNA vaccine. The MIC3 gene was cloned into the PTZ57R/T vector before sub-cloning in pcDNA3. Recombinant pc-MIC3 was transformed into Escherichia coli (TOP10 strain). The pc-MIC3 plasmid was then transfected into Chinese Hamster Ovary (CHO) cells, and the expression of the MIC3 gene was evaluated by SDS-PAGE and Western blotting. Sixty female BALB/c mice were divided into 6 groups. Each group received 3 intramuscular immunizations on days 0, 21st and 42nd using one of the following stimulants: phosphate-buffered saline, pcDNA3, pCAGGS-IL12, pc-MIC3 (100 µg), pc-MIC3 (50 µg), or combined pCAGGS-IL12 (50 µg) and pc-MIC3 (50 µg). The enzyme-linked immunosorbent assays was applied to evaluate interferon gamma (IFN-γ) and IL-4 cytokines excretion of lymphocytes stimulated with tachyzoites lysate antigen, as well as the total levels of immunoglobulin G (IgG), IgG2a and IgG1 in immunized mice sera. RESULTS: Our results showed that mice challenged with pc-MIC3 (100 µg) had the highest longevity and quantity of immunoglobulin. Moreover, the highest expression level of IFN-γ was found in mice injected with combined pcMIC3 and pCAGGS-IL12 (P<0.05). CONCLUSION: The MIC3 gene can be an efficient DNA vaccine candidate against toxoplasmosis. While, the single-gene vaccine can confer partial protection to mice against toxoplasmosis, the multigene vaccine can significantly enhance immune responses.

A Meta-Analysis of the Prevalence of Class 1 Integron and Correlation with Antibiotic Resistance in Pseudomonas aeruginosa Recovered from Iranian Burn Patients.

The role of integrons has been highlighted in antibiotic resistance among Pseudomonas aeruginosa isolates. Therefore, we here reviewed the prevalence of class 1 integrons and their correlations with antibiotic resistance of P. aeruginosa isolated from Iranian burn patients. This review was conducted according to the guidelines of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). Cross-sectional and cohort studies published from January 1, 2000 until December 31, 2018 were enrolled. Meta-analysis was performed by Comprehensive Meta-Analysis (CMA) software using the random effects model, Cochran's Q, and I2 tests. Publication bias was estimated by Funnel plot and Egger's linear regression test. Nine out of 819 studies met the eligibility criteria. The overall combined prevalence of class 1 integrons in P. aeruginosa isolates was 69% (95% confidence interval [CI]: 50.5-83%). The highest combined resistance was reported against Cloxacillin (87.7%), followed by Carbenicillin (79.1%) and Ceftriaxone (77.3%). The combined prevalence of multidrug-resistant (MDR) isolates was 79.3% (95% CI: 31.1-97%). Also, a significant correlation was noted between the presence of class 1 integrons and antibiotic resistance in 55.5% of the included studies (P < .05). The results showed high prevalence of class 1 integrons, antibiotic resistance, and MDR strains in P. aeruginosa isolated from Iranian burn patients. Also, most of the included studies showed a significant correlation between the presence of class 1 integrons and antibiotic resistance.

Evaluation of Immune Responses Induced by GRA7 and ROP2 Genes by DNA Vaccine Cocktails Against Acute Toxoplasmosis in BALB/c Mice.

BACKGROUND: The severe damages of toxoplasmosis clearly indicate the need for the development of a more effective vaccine. Immunization with plasmid DNA is a promising vaccination technique. Therefore, GRA7 plasmid was prepared to be used as a vaccine. The purpose of this study was evaluation of immunization with cocktail DNA vaccine including plasmids encoding Toxoplasma gondii ROP2 and GRA7 in BALB/c mice. METHODS: In this study, 733 bp of GRA7 gene was cloned in pCDNA3.1 plasmid as an expression vector. The plasmids containing GRA7 and ROP2 genes were administered via IM according to immunized mice three times with a 3 week interval. For lymphocyte proliferation and cytokine assay, splenocytes of immunized mice were cultured for proliferation and cytokine assay. The other mice in each group were inoculated by the parasite and mortality of the mice was evaluated on a daily basis. RESULTS: The cytokine assay results and lymphocyte proliferation response in cocktail DNA vaccines showed that IFN-γ levels were significantly higher than controls (p<0.05), whereas IL-4 expression level in BALB/c mice immunized with cocktail was lower than that in control groups and these results are confirmed by MTT test. Predominance of the levels of IgG2a over IgG1 was observed in sera of the immunized mice. Furthermore, IgG2a values in cocktail DNA vaccines pcGRA7 were significantly higher than control group (p<0.01). In contrast, IgG1 antibodies were similar between the two groups (p>0.5). So, survival time in the immune groups was significantly prolonged in comparison to control ones (p<0.01). CONCLUSION: The immunized mice by DNA vaccine produce higher titration of IFNγ, indicated with Th1 response which is confirmed by high level of IgG2a. These data demonstrate that the cocktail GRA7/ROP2 is a potential vaccine candidate against toxoplasmosis.

Study of Bacterial Infections Among Patients Receiving Kidney Transplant in Mashhad, Iran.

OBJECTIVES: Over the past 2 decades, significant advances have been made in the management of infections after transplant; however, transplant recipients are still at high risk of infectious complications. This study aimed to evaluate the prevalence of bacterial infections and antimicrobial resistance patterns in kidney transplant recipients. MATERIALS AND METHODS: This cross-sectional study included 356 patients who received kidney transplants, regardless of the underlying disease, from 2013 to 2015 at the Montaserieh Transplant Hospital (Mashhad, Iran). Clinical samples collected from patients were sent to the microbiology laboratory for culture processing. Typing of bacteria was conducted, and susceptibility testing was performed according to the Clinical and Laboratory Standards Institute guideline by use the of disk diffusion agar method. Data were then analyzed by SPSS software (SPSS: An IBM Company, IBM Corporation, Armonk, NY, USA) using chi-square test. RESULTS: Among 356 kidney recipients (206 men and 150 women), 115 (32.3%) received transplants from living donors and 241 (67.7%) received transplants from deceased donors. Of 356 total patients, 112 patients (31.5%) had an infection at various times after transplant. The most common gram-negative and gram-positive isolated bacteria were Escherichia coli and coagulase-negative Staphylococcus, with prevalence rates of 66.1% and 48.6%. Most of the isolates were resistant against selected antibiotics. CONCLUSIONS: Because of the high prevalence of infection among transplant patients, infection prevention should receive more attention, and antibiotic susceptibility should be determined before treatment.

Anti-Trichomonas vaginalis activity of nano Micana cordifolia and Metronidazole: an in vitro study.

Trichomonas vaginalis is a flagellate parasite living in the genital tract and it is accounted as a sexually transmitted disease. The clinical symptoms vary from the asymptomatic to the severe form which is usually associated with the irritation, itching and infertility in some severe cases. Many drugs have been applied to treat this disease and Metronidazole is the gold standard for treatment; however, it has also detected that this medicine has many side-effects which it has been motivated the researchers to find an appropriate alternative for this medicine. One of the treatment options is the use of the herbal medicines and natural compounds. Thus, the aim of this study was to compare the in vitro anti-T. vaginalis activity of nano-emulsion of Micana cordifolia and Metronidazole. In this study, T. vaginalis was isolated from the clinical samples and were cultured on a modified Dorsate medium. The nano-emulsion of M. cordifolia was prepared by heating technique. The effect of nano-emulsion of M. cordifolia was separately investigated on the T. vaginalis at the times of 12, 24 and 72 h and the obtained data were analyzed by the Spss 20 using the ANOVA test. The results indicated that the concentration of 100 ppm of nano-emulsion of M. cordifolia at the times of 12, 24 and 72 h has the anti-T. vaginalis activity of 44 ± 1.66, 37 ± 1 and 25 ± 2, respectively. It is also observed that the concentration of 500 ppm of the extract has the best effect and was able to eliminate the 85% of T. vaginalis. Furthermore, the anti-T. vaginalis activity of nano M. cordifolia was observed to be 100% in the concentrations of 1000 ppm. It can be concluded, based on the results, that the nano M. cordifolia has acceptable efficacy on the elimination of T. vaginalis and it can be a suitable alternative for Metronidazole after implementation of complementary tests on laboratory animals and human cells.

Free-living amoebae in the water resources of Iran: a systematic review.

Free-living amoebae (FLA) are a group of protozoa with the capabilities of growth in the environment and invasion to the human body which have been isolated from different water sources. Acanthamoeba, Naegleria, and Balamuthia are the most important FLA. These cause a variety of severe complications of eye and central nervous system. Despite the fact that various studies have demonstrated the prevalence of FLA in different parts of Iran, there is no comprehensive evaluation and conclusion regarding the pollution of various water sources in Iran. This review was carried out to achieve the prevalence pattern of FLA in water resources across Iran to design appropriate health strategies. For this purpose, 8 online databases in English and Persian and also graduate thesis and national parasitology congresses were studied. The key words such as "free living amoebae", "Acanthamoeba", "Naegleria", "Hartmannella", "Balamuthia", "Sappinia", "Vermamoebae", "Valkampfia", "water resources", "water" and "Iran" were used to search articles between 1990 to 2017. From a total of 236 articles found, 38 reliable articles were included in the study. From the total number of investigated studies, the estimated prevalence was obtained as 36% among 2430 samples. Although Acanthamoeba prevalence has been considered as a priority, most kinds of free-living amoebae were found in all kinds of water resources. Due to the lack of free-living amoebae prevalence in more than a quarter of the Iranian provinces, more studies are recommended to achieve a better perspective to make comprehensive decisions to improve the hygiene of water resources.

Immune response of newborn BALB/c mice to Cryptosporidium infection.

Cryptosporidium parvum is a protozoan parasite which causes diarrheal in human and animals worldwide. Infection transmission has reported through oral-fecal by infectious objects through foods and drinks. In this study we explored the immune response pathway in animal model for C. parvum to develop the new treatment way. Oocysts collected from fecal positive for C. parvum and diluted about 1:5 in sucrose solution. New born BALB/c mice (3 days) divided to 2 different groups. Control group hadn't received any oocyst, the test groups received 5 × 10(5) oocysts. 5 mice selected for each control group and 11 mice chosen for each test group. Blood collected from heart bleeds in days of 6, 9, 12 and 16. Protein concentrations determined by bio-photometer. Dot blotting used to find out total antibody concentrations oocyst antigen. Among the test and the control groups, blots appeared in test group which means antibody production, but not any blot observed in the control groups. The non-characteristic proteins in serum were measured by the biophotometer. In this study, we investigated antibody serum production against C. parvum oocysts in new born BALB/c mice. The detected antibody through dot blot technique was our aims which had conjugated to our characteristic antiserum. The recorded numbers for the controls by biophotometer related to the non characteristic proteins in serum. The results of this study can used to produce polyclonal or monoclonal antibodies against cryptosporidiosis.

Relationship Between Low Back Pain With Quality of Life, Depression, Anxiety and Stress Among Emergency Medical Technicians.

BACKGROUND: Musculoskeletal disorders have become increasingly common among healthcare providers. They have become the most common cause of work-related disabilities among nurses. OBJECTIVES: The current cross-sectional study aimed to measure the prevalence of back pains among emergency medical technicians (EMTs), and association of back pain with quality of life, depression, anxiety and stress. MATERIALS AND METHODS: One hundred and eighty registered nurses working as EMTs at the Hamadan Emergency Medical Center were selected by consensus. Data collection tools were Demographic, Perceived Quality-of-Life, Short Form Health Survey (SF-36), and Depression Anxiety Stress Scales (DAS21) and pain scale measurements. RESULTS: Data showed that while 50.7% of the participants had an average awareness of the basic principles of back care, the majority (71.8%) had at least one type of back pain. There were associations between the prevalence of pain and depression (P = 0.049), pain and awareness (P = 0.035), and stress and job satisfaction (P = 0.024). CONCLUSIONS: A large number (about two-thirds) of EMTs had some sort of back pain; it is highly recommended to promote the attitude and motivation of the individuals to take care to prevent back injury and inform them of the principles of back care. Implications for primary prevention and care practice include encouraging EMTs to apply accurate principles of back care.

Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens.

Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies.