Seroepidemiological study on coinfection of toxoplasmosis and active tuberculosis in Northern Iran: a case control study.

Coinfection of tuberculosis (TB) and human parasitic infections is common in developing countries. There is little information about the prevalence of Toxoplasma gondii (T. gondii) infection among TB patients in Iran. In this case-control study, anti-toxoplasma antibodies were measured by ELISA method in 100 patients with active tuberculosis and 100 healthy individuals who were matched in terms of sex, age, and place of residence. Anti-T. gondii IgG antibodies were diagnosed in 62% of TB patients (95% CI 53-71%) and 70% of control subjects (95% CI 62-78%). Anti-T. gondii IgM antibodies were found in 1% of both TB patients and control group. The seroprevalence of T. gondii infection was not significantly different between TB patients and healthy individuals (P > 0.05). None of the assessed sociodemographic and behavioral factors was recognized as a risk factor for toxoplasmosis in TB infected patients. Moreover, the level of anti-T. gondii IgG antibodies concentration in TB patients was significantly higher than in control subjects and revealed skewness towards humoral immune response in TB patients. Coinfection of toxoplasmosis and tuberculosis was prevalent but T. gondii infection was independent of active TB in this co-endemic area.

Breast cancer immunotherapy: a comprehensive review.

Cancer remains a major health problem despite numerous new medical interventions that have been introduced in recent years. One of the major choices for cancer therapy is so-called adoptive cell therapy (ACT). ACT can be performed using both innate immune cells, including dendritic cells (DCs), natural killer (NK) cells, and γδ T cells and acquired immune T cells. It has become possible to utilize these cells in both their native and modified states in clinical studies. Because of considerable success in cancer treatment, ACT now plays a role in advanced therapy protocols. Genetic engineering of autologous and allogeneic immune cells (T lymphocytes, NK cells, macrophages, etc.) with chimeric antigen receptors (CAR) is a powerful new tool to target specific antigens on cancer cells. The Food and Drug Administration (FDA) in the US has approved certain CAR-T cells for hematologic malignancies and it is hoped that their use can be extended to incorporate a variety of cells, in particular NK cells. However, the ACT method has some limitations, such as the risk of rejection in allogeneic engrafts. Accordingly, numerous efforts are being made to eliminate or minimize this and other complications. In the present review, we have developed a guide to breast cancer (BC) therapy from conventional therapy, through to cell-based approaches, in particular novel technologies including CAR with emphasis on NK cells as a new and safer candidate in this field as well as the more recent aptamer technology, which can play a major role in BC immunotherapy.

Seroprevalence of Hepatitis C Virus among Prisoners in Lakan Prison, North of Iran, Is There Still a Concern?

BACKGROUND: Hepatitis C is a major cause of liver failure and liver transplantation. The known risk factors of this disease include blood transfusion, injection drug use, high risk sexual behaviors, tattoos, and use of shared blades and syringes. Due to the higher risk of viral hepatitis among people in prison, this study was done to find the seroprevalence of hepatitis C virus (HCV) and associated risk factors in Lakan Prison in Rasht. METHODS: Prisoners in Lakan Prison underwent a cross-sectional study in 2018. A questionnaire containing demographic information and risk factors was distributed to the inmates and they were asked complete them. High-risk individuals were selected and a blood sample was taken and tested. Data were collected and analyzed by SPSS18 software. RESULTS: Out of 2215 prisoners, 1238 people had at least one risk factor, of whom 408 individuals were selected by random sampling. One hundred inmates were positive for anti-HCV antibody, yielding a prevalence of 24.5% (95% CI: 20.4%-28.7%) of whom 42.6% were people who injected drugs and 4 cases were found positive for the hepatitis B surface antigen, yielding a 1% prevalence (95% CI, 0.2%-2%.). A history of injecting drug use (OR 4.28, 95% CI: 2.55-7.17), and previous history of imprisonment (OR 2.94, 95% CI: 1.34-6.53) had association with HCV infection. CONCLUSION: The present study shows that hepatitis C is prevalent in prisons and preventive and screening programs should be implemented with necessary training for inmates.

Serological Evaluation of Toxoplasmosis and Related Risk Factors Among HIV+/AIDS Patients in Northern Iran.

PURPOSE: Toxoplasma gondii is an important opportunistic intracellular protozoan parasite that can cause severe sequelae and even death in immunodeficient patients. This study aimed to evaluate the seroprevalence and risk factors of toxoplasmosis among HIV+/AIDS patients of the study area. METHODS: A cross-sectional study was carried out on 121 registered HIV+/AIDS patients of behavioral diseases consultation center (BDCC) in Guilan province, north of Iran. Anti-Toxoplasma IgG and IgM antibodies were measured by ELISA technique in the serum samples. IgG avidity was measured for IgG- plus IgM-positive cases. Also, the relationship between T. gondii infection and related demographic and clinical characteristics were investigated. RESULTS: Anti-T. gondii IgG and IgM antibodies were detected in 60.3 and 4.9% of patients, respectively. One case of acute toxoplasmosis (0.83%) was detected using an IgG avidity test. A significant correlation was observed between toxoplasmosis with age and marital status in these patients. The mean CD4+count of HIV+/AIDS patients was 549 ± 27 cells/µl. Viral load in 69.7% of the HIV patients was less than1000 copies/ml. CONCLUSION: None of the T. gondii IgM-positive HIV patients received anti-Toxoplasma prophylaxis. This finding highlights the importance of T. gondii infection surveillance in HIV patients. Regarding the high prevalence of toxoplasmosis in the study population, educational efforts are recommended to prevent reactivation or acquiring primary infection and developing severe cases of toxoplasmosis in immunocompromised HIV+/AIDS patients.

Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled- trials.

BACKGROUND/OBJECTIVE: Systemic inflammation and oxidative stress (OS) are associated with breast cancer. CoQ10 as an adjuvant treatment with conventional anti-cancer chemotherapy has been demonstrated to help in the inflammatory process and OS. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to evaluate the efficacy of CoQ10 supplementation on levels of inflammatory markers, OS parameters, and matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) in patients with breast cancer. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, Scopus, Google Scholar, and Embase, up to December 2020 to identify eligible RCTs evaluating the effect of CoQ10 supplementation on OS biomarkers, inflammatory cytokines, and MMPs/TIMPs. From 827 potential reports, 5 eligible studies consisting of 9 trials were finally included in the current meta-analysis. Quality assessment and heterogeneity tests of the selected trials were performed using the PRISMA checklist protocol and the I2 statistic, respectively. Fixed and random-effects models were assessed based on the heterogeneity tests, and pooled data were determined as the standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Our meta-analysis of the pooled findings for inflammatory biomarkers of OS and MMPs showed that CoQ10 supplementation (100 mg/day for 45-90 days) significantly decreased the levels of VEGF [SMD: - 1.88, 95% CI: (- 2. 62 to - 1.13); I2 = 93.1%, p < 0.001], IL-8 [SMD: - 2.24, 95% CI: (- 2.68 to - 1.8); I2 = 79.6%, p = 0.001], MMP-2 [SMD: - 1.49, 95% CI: (- 1.85 to - 1.14); I2 = 76.3%, p = 0.005] and MMP-9 [SMD: - 1.58, 95% CI: (- 1.97 to - 1.19); I2 = 79.6%, p = 0.002], but no significant difference was observed between CoQ10 supplementation and control group on TNF-α [SMD: - 2.30, 95% CI: (- 2.50 to - 2.11); I2 = 21.8%, p = 0.280], IL-6 [SMD: - 1.56, 95% CI: (- 1.73 to - 1.39); I2 = 0.0%, p = 0.683], IL-1ß [SMD: - 3.34, 95% CI: (- 3.58 to - 3.11); I2 = 0.0%, p = 0.561], catalase (CAT) [SMD: 1.40, 95% CI: (1.15 to 1.65); I2 = 0.0%, p = 0.598], superoxide dismutase (SOD) [SMD: 2.42, 95% CI: (2.12 to 2.71); I2 = 0.0%, p = 0.986], glutathione peroxidase (GPx) [SMD: 2.80, 95% CI: (2.49 to 3.11); I2 = 0.0%, p = 0.543]], glutathione (GSH) [SMD: 4.71, 95% CI: (4.26 to 5.16); I2 = 6.1%, p = 0.302] and thiobarbituric acid reactive substances (TBARS) [SMD: - 3.20, 95% CI: (- 3.53 to - 2.86); I2 = 29.7%, p = 0.233]. CONCLUSION: Overall, the findings showed that CoQ10 supplementation reduced some of the important markers of inflammation and MMPs in patients with breast cancer. However, further studies with controlled trials for other types of cancer are needed to better understand and confirm the effect of CoQ10 on tumor therapy.

Tympanosclerosis and atherosclerosis plaques: a comparative analytical study on some new microbiological and immunohistochemical aspects.

PURPOSE: The aim of this study was to compare chemical contents, expression of BMP-8a, and the presence of Mycoplasma and ExoS-ExoU exotoxins producing Pseudomonas aeruginosa in tympanosclerosis (TS) and atherosclerosis (AS) plaques. METHODS: Thirty-six cases with TS and AS plaques (18 each) were selected and examined for chemical, immunohistochemical, and microbial analysis. SPSS ver. 21 and t test analysis were used for comparing the findings, and the level of significance was considered as p < 0.05. RESULTS: TS plaques showed lower carbon, higher calcium, and phosphorous contents compared to AS plaques (p value < 0.05). Chlorine was detected in AS plaques (1.8 w%) which could probably be due to the presence of myeloperoxidase (MPO) in atherosclerotic artery. Contrary to spherical shape of the surface of TS plaques, AS plaques were needle shaped. BMP-8a expression in TS plaques (59.5%) was significantly higher (p value < 0.0001) than AS plaques (20%). Of the 18 TS specimens, 12, 14, and 3 were positive for ExoS, ExoU Pseudomonas aeruginosa, and Mycoplasma genes, respectively, while of the 18 AS specimens, 2, 2, and 3 were positive for ExoS, ExoU Pseudomonas aeruginosa, and Mycoplasma genes, respectively. CONCLUSION: TS plaques are different from AS plaques in terms of elemental components, surface morphology, and BMP-8a expression. Therefore, different calcification process and pathogenesis may be responsible for these two diseases. The results of our study showed that both TS and AS plaques have genetic footprint of Mycoplasma, but the level of calcium concentration-dependent exotoxins genes was found only in TS plaques.

Association study of copy number variation in BMP8A gene with the risk of ankylosing spondylitis in Iranian population.

BACKGROUND: Copy number variation (CNV) of DNA segments has been considered as an important component of genetic variation, affecting the quality and quantity of gene expression. Bone morphogenic protein 8A (BMP8A) has been reported to function in bone formation. With respect to the bone and joint complications in ankylosing spondylitis (AS), this investigation aimed to study the role of BMP8A gene CNV in impressing the gene expression as well as the disease risk. METHODS: A total of 900 individuals, including 450 patients with AS and 450 healthy controls were enrolled. The copy numbers of BMP8A gene were detected by TaqMan real-time polymerase chain reaction (PCR) method. BMP8A messenger RNA (mRNA) transcript level in peripheral blood mononuclear cells (PBMCs) was also measured by SYBR Green real-time gene expression PCR method. RESULTS: No significant association of BMP8A copy number was detected with the risk of AS. BMP8A mRNA expression level was significantly downregulated in patients compared with controls. mRNA expression level of BMP8A in both AS patients with and without syndesmophyte was significantly lower than the healthy control group. There was no correlation between the mRNA expression level of BMP8A and both demographic and clinical data of the patients. CONCLUSIONS: Although BMP8A gene expression was downregulated in patients with AS, its copy number could not affect the transcript level of BMP8A gene in PBMCs and was not associated with susceptibility to AS in Iranian population. BMP8a may take into account as an indicator of bone formation process in AS, but it seems that mechanisms other than CNV may regulate this protein.

Allergic Rhinitis in Adults with Chronic Suppurative Otitis Media.

INTRODUCTION: Chronic suppurative otitis media (CSOM) is considered one of the most common causes of acquired hearing impairment in developing countries. CSOM is a multifactorial persistent inflammatory disease of the middle ear. A distinct pathophysiologic mechanism linking allergic rhinitis (AR) and CSOM remains to evolve. The purpose of this study was to investigate the association between AR and CSOM in adults.This was a case-control study. MATERIALS AND METHODS: The subjects were 62 adults (23 male, 39 female) with established CSOM and 61 healthy controls. CSOM was diagnosed when there was a history of chronic (persisting for at least 3 months) otorrhea, accumulation of mucopurulent exudates in the external auditory canal or middle ear and/or perforated tympanic membrane on otoscopy. All participants were evaluated for the presence of AR by clinical evaluation of allergic symptoms, and underwent a skin-prick test for 23 common regional allergens. Statistical analysis was performed using SPSS version 16. RESULTS: The prevalence of clinical rhinitis (allergic and non-allergic) was significantly higher among the cases compared with controls (62.5% vs. 37.5%, P=0.02). The prevalence of AR (proven by positive skin-prick test) was also significantly higher among affected adults than controls (24.6% and 13.8%, respectively). Adjusting for age, a logistic regression model showed that there was a significant difference between the two groups. Patients with AR and non-AR were at 3.27- (95% CI=1.15-9.29; P=0.036) and 2.57-(95% CI=1.01-6.57; P=0.048) fold increased risk of developing CSOM, respectively, compared with healthy individuals. CONCLUSION: The study showed a higher prevalence of AR in CSOM patients than in controls. It may be valuable to evaluate and control this factor in these patients.

In vitro fertilized embryos do not secrete detectable HLA-G on day two.

BACKGROUND: Pregnancy is a successful transplantation. The factors evading rejection of the fetus are poorly understood. Recently an interest has grown, in HLA-G molecules as one of these factors. Since these antigens are mainly expressed on the surface of cytotrophoblasts that are in direct contact with maternal tissues, it has been suggested that these molecules may have a role in induction of immune tolerance in mothers. OBJECTIVE: to find the association of soluble HLA-G (sHLA-G) and the success of pregnancy with intracytoplasmic sperm injection (ICSI) procedure. METHODS: In this study, the supernatant of 287 individually cultured embryos corresponding to 96 women under ICSI procedure were assayed for soluble HLA-G1 and G5 by a sandwich ELISA. RESULTS: Clinical pregnancy successfully occurred in 30 of candidates. No differences in clinical parameters (age, infertility duration, stimulation regimen) were observed between pregnant and nonpregnant women under ICSI procedure. None of the embryo supernatants in either group showed any detectable sHLA-G molecules. CONCLUSION: Our results showed that detectable level of sHLA-G is not produced by day 2 embryos and such a measurement may not provide reliable information for embryo selection and estimation of pregnancy success.

Soluble CD26 and CD30 levels in patients with anthroponotic cutaneous leishmaniasis.

OBJECTIVE: Leishmania tropica is the causative agent of anthroponotic cutaneous leishmaniasis (CL) in Iran. The disease often heals within a year; however, the non-healing forms of disease are also known. The aim of the present study was the determination of the levels of soluble (s) CD26 and CD30 co-stimulatory molecules in sera of L. tropica-infected individuals. The correlations of sCD26 and sCD30 levels with clinical presentation of the disease were assessed. METHODS: The levels of sCD26 and sCD30 were determined by a sandwich enzyme-linked immunosorbent assay in sera from patients with acute and non-healing presentation of disease. RESULTS: The serum level of sCD26 was significantly higher in non-healing patients than in cases with acute CL (P<0.001). There was no significant difference in sCD26 level between patients with acute CL and healthy controls. However, the levels of sCD30 in sera from all L. tropica-infected individuals were higher than controls (P<0.001). A significant difference was also found in sCD30 level between non-healing cases and patients with acute CL (P<0.001). CONCLUSION: These findings suggest sCD30 is more relevant to clinical manifestation of cutaneous leishmaniasis than sCD26. The high sCD26 and sCD30 levels in non-healing patients reflect the presence of mixed Th1- and Th2-type responses in these patients.

Surrogate markers of immunity to Leishmania major in leishmanin skin test negative individuals from an endemic area re-visited.

BACKGROUND: In the screening of vaccine candidates it is important to select candidates that evoke immune responses associated with protection. Valid surrogate markers against human leishmaniasis are still lacking. METHODS: A controlled injection of live Leishmania known as leishmanization, (LZ), was used to evaluate vaccine (alum-precipitated autoclaved Leishmania major with BCG) efficacy and more accurately define surrogate markers of immunity to leishmaniasis in humans. Cellular immune responses to this artificial infection were monitored in the volunteers prior to and 9 months post infection. Comparisons were made between those who developed a lesion after infection and those who did not. RESULTS: In the volunteers monitored there was no significant difference in LST, IFNgamma production, or source of IFNgamma between those who developed a lesion and those who did not after LZ, with the exception that ulcer development was associated with an enhanced number of IFNgamma secreting CD4(+) CD45RA(-) (memory) T cells. DISCUSSION: Ulcer development following LZ was lower than anticipated by a pilot study (47% versus 78%) using the same stabilate several years earlier. While this may be an effect of low viability/virulence of the LZ inocula, alternative explanations are also possible. The IFNgamma responses in the study subjects were significantly lower compared to volunteers with previous history of cutaneous leishmaniasis. The findings raise the possibility that the selection of LST-negative volunteers in an endemic area may bias the study towards potentially non/low L. major-reactive volunteers.