Presence of CRISPR CAS-Like Sequences as a Proposed Mechanism for Horizontal Genetic Exchanges between Trichomonas vaginalis and Its Associated Virus: A Comparative Genomic Analysis with the First Report of a Putative CRISPR CAS Structures in Eukaryotic Cells.

Introduction: Trichomonas vaginalis genome is among the largest genome size and coding capacities. Combinations of gene duplications, transposon, repeated sequences, and lateral gene transfers (LGTs) have contributed to the unexpected large genomic size and diversity. This study is aimed at investigating genomic exchange and seeking for presence of the CRISPR CAS system as one of the possible mechanisms for some level of genetic exchange. Material and Methods. In this comparative analysis, 398 publicly available Trichomonas vaginalis complete genomes were investigated for the presence of CRISPR CAS. Spacer sequences were also analyzed for their origin using BLAST. Results: We identified a CRISPR CAS (Cas3). CRISPR spacers are highly similar to transposable genetic elements such as viruses of protozoan parasites, especially megavirals, some transposons, and, interestingly, papillomavirus and HIV-1 in a few cases. Discussion. There is a striking similarity between the prokaryotes/Archaean CRISPR and what we find as eukaryotic CRISPR. About 5-10% of the 398 T. vaginalis possess a CRISPR structure. Conclusion: According to sequences and their organization, we assume that these repeated sequences and spacer, along with their mentioned features, could be the eukaryotic homolog of prokaryotes and Archaean CRISPR systems and may involve in a process similar to the CRISPR function.

Latent Toxoplasmosis among Breast Cancer Patients in Jahrom, South of Iran.

Objective: Reactivation of latent toxoplasmosis is the main cause of severe infection among immunocompromised patients, including patients with cancer. Hence, this study is aimed at screening the status of Toxoplasma gondii infection among breast cancer patients by serological and molecular methods and determining their associated risk factors in Jahrom County, Fars Province, south of Iran. Methods: One hundred and seven women with breast cancer (aged 34 to 80 years) were screened for anti-T. gondii antibodies (IgG and IgM) during 2019-2020. A questionnaire regarding demographic factors was filled out by participants. Molecular detection was performed by polymerase chain reaction (PCR) using the primer pair targeting the repetitive element (RE) gene of T. gondii. The risk factors and demographic data were analyzed by SPSS software (ver. 20, Chicago, IL, USA) using the Chi-squared test. Results: Anti-T. gondii IgG was detected in 45.8% (49/107) of the patients, which indicates latent infection, but anti-T. gondii IgM and PCR were negative in all samples. Demographic factors revealed a statistically significant increased T. gondii seropositivity among nonmenopause cancer patients (P < 0.0005), patients without previous breast cancer (P = 0.0001), and human epidermal growth factor receptor 2- (HER2-) negative patients (P = 0.00002). As such, patients with a history of previous abortions and who were at stages II, III, and IIII of cancer had higher seropositivity rates than patients without a history of previous abortions or who were at stage I cancer, but the statistical analysis was not significant. We did not find a statistically significant association between T. gondii seropositivity and other risk factors of toxoplasmosis (e.g., education level, type of water source, washing raw fruits and vegetables, consumption of raw or undercooked meat, and contact with soil, cats, and domestic animal). Conclusion: A high seroprevalence rate of latent T. gondii infection was detected among patients with breast cancer; hence, these patients may be at high risk for reactivation of latent infection. Screening of T. gondii infection is recommended to detect active infection among patients with malignancies.

Association of gastric inhibitory polypeptide receptor (GIPR) gene polymorphism with type 2 diabetes mellitus in iranian patients.

INTRODUCTION: Gastric inhibitory polypeptide receptor (GIPR) encodes a G-protein coupled receptor for gastric inhibitory polypeptide (GIP), which was demonstrated to stimulate insulin secretion. Relation of GIPR gene variation to impaired insulin response has been suggested in previous studies. However, little information is available regarding GIPR polymorphisms and type 2 diabetes mellitus (T2DM). Hence, the aim of the study was to investigate single nucleotide polymorphisms (SNPs) in the promoter and coding regions of GIPR in Iranian T2DM patients. MATERIALS AND METHODS: Two hundred subjects including 100 healthy and 100 T2DM patients were recruited in the study. Genotypes and allele frequency of rs34125392, rs4380143 and rs1800437 in the promoter, 5' UTR and coding region of GIPR were investigated by RFLP-PCR and Nested-PCR. RESULTS: Our finding indicated that rs34125392 genotype distribution was statistically different between T2DM and healthy groups (P = 0.043). In addition, distribution of T/- + -/- versus TT was significantly different between the both groups (P = 0.021). Moreover, rs34125392 T/- genotype increased the risk of T2DM (OR = 2.68, 95%CI = 1.203-5.653, P = 0.015). However, allele frequency and genotype distributions of rs4380143 and rs1800437 were not statistically different between the groups (P > 0.05). Multivariate analysis showed that the tested polymorphisms had no effect on biochemical variables. CONCLUSION: We concluded that GIPR gene polymorphism is associated with T2DM. In addition; rs34125392 heterozygote genotype may increase the risk of T2DM. More studies with large sample size in other populations are recommended to show the ethnical relation of these polymorphisms to T2DM.

Toxoplasma gondii, HBV, and HCV co-infection and their correlation with CD4 cells among Iranian HIV-positive patients.

INTRODUCTION: Human immunodeficiency virus (HIV/AIDS) infected patients have a higher risk of opportunistic infections (OIs) depending on their immunological status, especially CD4 + cell count. Toxoplasma gondii, hepatitis C virus (HCV), and hepatitis B virus (HBV) are important OIs among Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) patients. However, little is known about co-infection of these pathogens among HIV-infected individuals and their correlation with the patient's CD4 + cell count. Hence, this study aimed to investigate the serological and molecular status of T. gondii infection among HIV-infected individuals who had co-infection with HBV and HCV infections. METHODS: A total of 100 HIV/AIDS patients in two cities in the southwest of Iran was tested for T. gondii Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies as well as DNA detection by polymerase chain reaction (PCR) targeting the RE gene. HBV and HCV were detected by hepatitis B surface antigen (HBsAg) test, hepatitis C antibody (HCV Ab) test, and Real-Time PCR. The number of CD4 + cell counts was determined by Flow cytometry. RESULTS: Anti-T. gondii IgG was positive in 22% of the patients, but anti-T. gondii IgM and PCR were negative in all samples. HBV and HCV were positive in 8% and 33% of the patients, respectively. Co-infections were as followed: HIV + HCV (16%), HIV + HCV + T. gondii (11%), HIV + T. gondii (5%), HIV + HBV (1%), HIV + HBV + T. gondii (1%), HIV + HBV + HCV (1%), and HIV + HBV + HCV + T. gondii (5%). A significant decline in CD4 + cell counts was found in such co-infection groups (HIV + T. gondii, HIV + HCV + T. gondii, and HIV + HBV + HCV + T. gondii) compared with the HIV mono-infection group. CONCLUSIONS: Our study showed that co-infections of T. gondii, HCV, and HBV were common among HIV-infected patients and co-infections had a negative correlation with CD4 + cell counts of the patients.

Are Blastocystis hominis and Cryptosporidium spp. playing a positive role in colorectal cancer risk? A systematic review and meta-analysis.

OBJECTIVE: Intestinal protozoa Blastocystis hominis and Cryptosporidium spp. are two influential factors in intestinal complications and malignancies. In present study, we estimated the pooled prevalence and odds ratio (OR) of the two parasites in colorectal cancer (CRC) patients and their possible association with the deadly disease. METHOD: Our systematic search was conducted for published researches between January 1, 2000 and April 30, 2022 by using four international databases include Scopus, PubMed, and Web of Science as well as Google scholar search engine. The random- and fixed-effects models were used to estimate the pooled prevalence, OR, and 95% confidence interval (CI) by comprehensive meta-analysis (V2.2, Bio stat) software. Inclusion and exclusion criteria were applied. RESULTS: Thirteen papers (seven case-control and six cross-sectional studies) for B. hominis/CRC and six papers (two case-control and four cross-sectional studies) for Cryptosporidium spp./CRC were eligible to include in data synthesis. Pooled prevalence of B. hominis and Cryptosporidium spp. in CRC patients was calculated to be 26.8% (95% CI 19.4-35.7%) and 12.7% (95% CI 6.8-22.5%), respectively. Based on case-control studies, significant difference was found between case and controls in both protozoa (B. hominis OR 2.10; 95% CI 1.39-3.18% vs. Cryptosporidium spp. OR 5.06; 95% CI 1.8-13.6%). Considering the Blastocystis subtypes, ST1 (5/6; 83.33% studies) and ST3 (5/6; 83.33% studies) had the highest number of reports in CRC patients. Regarding the Cryptosporidium species, only C. parvum and C. hominis were reported. CONCLUSION: Given the significant prevalence of both parasites in CRC patients and their statistically significant association, there is a need to pay more attention to these two intestinal parasites in under treatment patients.

Testosterone Augments Propagation of Toxoplasma gondii in Glioblastoma Cells In Vitro.

PURPOSE: Toxoplasmosis can induce various hormonal and behavioral alterations in humans and rodents. Previous studies revealed alterations of sex hormones; especially testosterone, in infected humans and rodents, but little is known about the effects of sex hormones on the propagation of T. gondii. Hence, we aimed to investigate whether testosterone and progesterone influence on T. gondii propagation in neural cells. METHODS: The glioblastoma cells (U-87MG) were treated with different concentrations of testosterone and progesterone and the infection was done by tachyzoites of the RH strain of T. gondii. The number of infected cells, viability of T. gondii-infected cells, and parasite burden were measured by direct counting under a light microscope, MTT assay, and quantitative real-time PCR (qPCR), respectively. RESULTS: The results showed that testosterone at concentrations of 100 and 250 nM significantly increased the number of infected cells and parasite burden 24 and 48 h post-treatment compared to untreated controls. Progesterone had no significant effects in the same manner. CONCLUSION: The results indicated that testosterone could augment the propagation of T. gondii in in vitro.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Helminth infections and immunosenescence: The friend of my enemy.

Age-associated alterations of the immune system, which known as "immunosenescence", is characterized by a decline in innate and adaptive immunity, which leading to increased susceptibility to age-associated diseases, such as infectious diseases, rheumatic disease and malignancies. On the other hand, helminth infections are among the most prevalent infections in older individuals, especially in the nursing homes. Most of helminth infections have minor clinical symptoms and usually causing chronic infections without treatment. Nevertheless, chronic helminthiasis alters immune responses somewhat similar to the immunosenescence. Some similarities also exist between helminth infections and immunosenescence: 1) both of them led to declining the immune responses; 2) undernutrition is a consequence of immunosenescence and helminthiasis; 3) vaccine efficacy declines in aging and individuals with helminth infections; 4) increase incidence and prevalence of infectious diseases in the elder individuals and patients with helminth infections; and 5) both of them promote tumorigenesis. Hence, it is probable that helminth infections in the elderly population can intensify the immunosenescence outcomes due to the synergistic immunoregulatory effects of each of them. It would be suggested that, diagnosis, treatment and prevention of helminth infections should be more considered in older individuals. Also, it would be suggested that helminths or their antigens can be used for investigation of immunosenescence because both of them possess some similarities in immune alterations. Taken together, this review offers new insights into the immunology of aging and helminth infections.

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study.

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

Therapeutic Potential of Helminths and Helminth-Derived Antigens for Resolution of Inflammation in Inflammatory Bowel Disease.

Inflammation plays a pivotal role in the pathogenesis of inflammatory bowel disease (IBD), and treatment of IBD mainly targets on inhibition of pro-inflammatory mediators. Helminth-based therapy is a novel strategy for resolution of inflammation in IBD, because helminths have great immunomodulatory properties. Helminth-based therapy may be efficacious as a vaccine for patients with IBD. This article is a highlight on the therapeutic potential of helminths in IBD.

Screening of toxoplasmosis in cancer patients: a concern.

Toxoplasmosis is an opportunistic infectious disease in immunocompromised patients, including cancer patients, whose detection is by molecular and serological methods. A total of 106 blood samples from patients with different types of cancer were evaluated for anti- Toxoplasma gondii IgG and IgM antibodies by the enzyme-linked immunosorbent assay (ELISA) and the parasite DNA by nested polymerase chain reaction (PCR). These were detected in 41.51% (44/106) and 0.94% (1/106), respectively, but T. gondii IgM antibody was not detected at all. These results suggest that the screening of toxoplasmosis should be considered more routinely in cancer patients.

Intestinal parasitic infections in different groups of immunocompromised patients in Kashan and Qom cities, central Iran.

INTRODUCTION: Intestinal parasitic infections (IPIs) are important causes of morbidity and mortality in patients with immunocompromising conditions. OBJECTIVE: The aim of this study was to determine the prevalence of IPIs in different groups of immunocompromised patients, including hemodialysis patients (HD), renal transplant recipients (RTR), cancer and HIV/AIDS patients in comparison with healthy individuals in two central cities of Iran (Kashan and Qom). METHODS: In this case-control study, the stool samples of 135 HD, 50 RTR, 60 cancer patients, 20 HIV/AIDS patients and 120 healthy subjects were tested using direct-smear, formol-ether concentration, Ziehl-Neelsen staining and Agar plate method. RESULTS: The overall infection rate was 11.7% (31/265) in patient groups and 0% (0/120) in the control group. The frequency of parasites was 25% in HIV/AIDS patients, 11.9% (16/135) in HD, 12.0% (6/50) in RTR and 6.7% (4/60) in cancer patients. Blastocystis hominis (4.2%) and Giardia lamblia (3.0%) were the most prevalent parasites in patient groups. The infection rate was significantly higher in male (17.6%) than female (5.4%) patients (p = .002), but no statistically significant association was observed according to the age and educational levels. CONCLUSIONS: This study showed a high prevalence of IPIs in immunocompromised patients. The results of this study suggest that periodic stool examinations for screening of IPIs should be included as a part of routine medical care in these patients.

Pro- and anti-inflammatory cytokines in cutaneous leishmaniasis: a review.

Cutaneous leishmaniasis (CL) is caused by different species of the genus Leishmania. Pro- and anti-inflammatory cytokines play different roles in resistance/susceptibility and the immunopathogenesis of Leishmania infection. The balance and dynamic changes in cytokines may control or predict clinical outcome. T helper 1 (Th1) inflammatory cytokines (especially interferon-γ, tumor necrosis factor-α and interleukin-12) are the crucial factors in the initiation of protective immunity against L. major infection, whereas T helper 2 cytokines including IL-5, IL-4, and IL-13 facilitate the persistence of parasites by downregulating the Th1 immune response. On the other hand, aggravation of inflammatory reactions leads to collateral tissue damage and formation of ulcer. For this reason, immunity system such as T regulatory cells produce regulatory cytokines such as transforming growth factor-ß and IL-10 to inhibit possible injures caused by increased inflammatory responses in infection site. In this article, we review the role of pro- and anti-inflammatory cytokines in the immunoprotection and immunopathology of CL.