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Recurrent spontaneous abortion (RSA) is one of the major pregnancy-related complications. The roles of different immune cells have been studied in pregnancy complications. The current study aimed to investigate myeloid-derived suppressor cells (MDSCs) in a murine abortion model and introduce a therapeutic approach by using in vitro–generated MDSCs in this model. CBA/J × DBA/2 (abortion prone) and CBA/J × Balb/C (normal pregnancy) mice were used. The frequency of granulocytic MDSCs, monocytic MDSCs, and Tregs was checked in the bone marrow and uteroplacental tissue of mice on three gestational days (gd9.5, gd13.5, and gd17.5) using the flow cytometry approach. MDSCs were generated in vitro from bone marrow-isolated cells using GM-CSF and IL-6 cytokines. Abortion-prone mice were injected intravenously with in vitro–generated MDSCs at gd0.5, and pregnancy outcomes were recorded in treated mice. The frequency of G-MDSCs and M-MDSCs in the bone marrow of abortion-prone mice was decreased at gd9.5 (p = 0.026 and p = 0.05, respectively). In uteroplacental tissue, the frequency of G-MDSCs was significantly lower at gd9.5 and gd13.5 (p = 0.001, p = 0.029, respectively), while M-MDSCs only showed decreased number at gd9.5 (p = 0.05) in abortion-prone mice. Injection of in vitro–generated MDSCs resulted in the increased fetus and placenta weights (p = 0.049 and p = 0.012, respectively) but showed no effect on the number of live fetuses and abortion rate. The reduced frequency of both G-MDSCs and M-MDSCs in the bone marrow and at the feto-maternal interface is associated with pregnancy complications. In vitro–generated MDSCs could be considered as a potential approach to reduce these complications. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is accounted as the most etiologic agent for digestive disorders, in particular, the most important of them i.e. peptic ulcer and gastric cancer. In the recent years, association of vacA genotypes and gastrointestinal disorders has attracted a lot of attention. In present study, we assessed the correlation between vacA genotypes (s1, s2, m1, m2, s1m1, s1m2, s2m1 and s2m2) and development to peptic ulcer in Iranian population. Methods: In our study, first, 24 original articles containing of information of 3328 patients were evaluated. Statistical analysis was done by Comprehensive Meta-Analysis version 2.0 software (Biostat, Englewood, NJ, USA). In this regards, we used from fixed-effects model for analysis of data with low heterogeneity, while for analysis of data with high heterogeneity (I2 statistic index > 25%, Cochrane Q statistic p value < 0.05), random-effects model was used. Results: Abundance of each of s1, s2, m1, m2, s1m1, s1m2, s2m1, and s2m2 was estimated 36.24, 28.32, 42.90 29.86, 27.88, 32.34, 15.70, and 25.94%, respectively. According to the results, the m1, s1, and s1m2 genotypes were among the most prevalent genotypes among the Iranian patients, whereas, s2m1 genotype had the lowest frequency. Conclusions: Overall, 24 articles (total participants = 3328) were included in this comprehensive analysis. H. pylori infection rate were 90.26% in these cases, so that 33.65% of whom had peptic ulcer. Moreover, the abundance of each vacA genotypes including s1, s2, m1, m2, s1m1, s1m2, s2m1, and s2m2 was estimated as 36.24, 28.32, 42.90 29.86, 27.88, 32.34, 15.70, and 25.94% respectively. We demonstrated that there is a significant relationship between infection of stomach with m1, s1m1, and s2m1 genotypes and development to peptic ulcer disease. [ABSTRACT FROM AUTHOR]

• ILC2s increases during normal pregnancy. • ILC2s are less frequent in abortion-prone mice compare to normal pregnancy. • The frequency of Tregs positively correlates with the frequency of ILCs. • Inflammatory ILC2s are the major ILC2s subset in abortion-prone mice. Recurrent spontaneous abortion (RSA) is the most common pregnancy related complication, affecting 1–5 % of pregnancies. Despite hormonal, genetic and anatomical factors that result in abortion, impairment of immune response at the feto-maternal interface during the first trimester of pregnancy is also one of the main causes of RSA. In the present study, we evaluated the frequency of blood and uterine group 2 innate lymphoid cells (ILC2s), their subsets and regulatory T cells (Tregs) in CBA/J × DBA/2 J as an abortion-prone model compared to normal pregnant (NP) mice using immunophenotyping. Results indicated that the percentages of ILC2s were significantly decreased in the AP group compared to the NP group at mid-gestation (P ≤ 0.01). Moreover, the percentages of both blood and uterine nILC2s were increased in NP mice at mid-gestation (P ≤ 0.01, and P ≤ 0.05, respectively), while iILC2s significantly increased in AP mice at mid-gestation (P ≤ 0.01, and P ≤ 0.05, respectively). Tregs were reduced in AP mice at both early and mid-gestation stages (P ≤ 0.01). Overall, our findings suggest that the changes in blood and uterine ILC2s might be associated with abortion in mice. [ABSTRACT FROM AUTHOR]

Dysfunction of regulatory T cells (Tregs) may contribute to certain immune‐related pregnancy complications. Forkhead box protein 3 (FOXP3) is the key transcription factor of Treg. We performed a systematic review and meta‐analysis to evaluate the possible association between FOXP3 polymorphisms −924A/G (rs2232365) and −3279C/A (rs3761548) and immune‐related pregnancy complications. After reviewing 78 fully published studies, 10 studies fulfilled previously defined eligibility criteria and were used for meta‐analysis. Two single nucleotide polymorphisms showed a significant correlation with increased or reduced risk for immune‐related pregnancy complications. For rs3761548, women with allele A were significantly at a higher risk than women carrying allele C (odds ratio = 1.29, 95% confidence interval: 1.20–1.38; p = 0.001). For rs2232365, women with GG or AG genotype were at a higher risk than women with genotype AA, thereby, allele G was significantly associated with a higher risk than allele A. Our meta‐analysis supports the notion that immune‐related pregnancy complications might be linked to genetic variations in the FOXP3 gene. [ABSTRACT FROM AUTHOR]

The complement system exerts crucial functions both in innate immune responses and adaptive humoral immunity. This pivotal system plays a major role dealing with pathogen invasions including protozoan parasites. Different pathogens including parasites have developed sophisticated strategies to defend themselves against complement killing. Some of these strategies include the employment, mimicking or inhibition of host's complement regulatory proteins, leading to complement evasion. Therefore, parasites are proven to use the manipulation of the complement system to assist them during infection and persistence. Herein, we attempt to study the interaction´s mechanisms of some prominent infectious protozoan parasites including Plasmodium, Toxoplasma, Trypanosoma, and Leishmania dealing with the complement system. Moreover, several crucial proteins that are expressed, recruited or hijacked by parasites and are involved in the modulation of the host´s complement system are selected and their role for efficient complement killing or lysis evasion is discussed. In addition, parasite's complement regulatory proteins appear as plausible therapeutic and vaccine targets in protozoan parasitic infections. Accordingly, we also suggest some perspectives and insights useful in guiding future investigations. [ABSTRACT FROM AUTHOR]

Objectives: Hepatitis C virus (HCV) is one of the most global health problems with 2.5% prevalence worldwide. It seems that regulatory T (Treg) cells, which are able to modulate the host immune responses, play a substantial role in the immunopathogenesis of HCV infection. In this study, we evaluated the distribution of Treg cells in HCV-infected patients and its correlation with viral load and clinical manifestations. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 14 newly diagnosed HCV-infected patients and 23 age- and sex-matched healthy subjects, and the frequency of CD4+CD25+CD127−/low Treg cells was determined by flow cytometry. Results: Our results showed that the mean level of CD4+CD25+CD127−/low Treg cells in HCV-infected patients was significantly higher than that in healthy control subjects (8.2 ± 1.48% vs 5.4 ± 0.36%, p <.05). However, there was no statistical correlation between Treg cells frequency and viral load or clinical manifestations. Conclusion: A higher proportion of Treg cells in HCV-infected patients might indicate their critical role in viral persistence and candidate them as a new target of immunotherapy to improve antiviral immunity. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is accounted as the most etiologic agent for digestive disorders, in particular, the most important of them i.e. peptic ulcer and gastric cancer. In the recent years, association of vacA genotypes and gastrointestinal disorders has attracted a lot of attention. In present study, we assessed the correlation between vacA genotypes (s1, s2, m1, m2, s1m1, s1m2, s2m1 and s2m2) and development to peptic ulcer in Iranian population.Methods: In our study, first, 24 original articles containing of information of 3328 patients were evaluated. Statistical analysis was done by Comprehensive Meta-Analysis version 2.0 software (Biostat, Englewood, NJ, USA). In this regards, we used from fixed-effects model for analysis of data with low heterogeneity, while for analysis of data with high heterogeneity (I2 statistic index > 25%, Cochrane Q statistic p value < 0.05), random-effects model was used.Results: Abundance of each of s1, s2, m1, m2, s1m1, s1m2, s2m1, and s2m2 was estimated 36.24, 28.32, 42.90 29.86, 27.88, 32.34, 15.70, and 25.94%, respectively. According to the results, the m1, s1, and s1m2 genotypes were among the most prevalent genotypes among the Iranian patients, whereas, s2m1 genotype had the lowest frequency.Conclusions: Overall, 24 articles (total participants = 3328) were included in this comprehensive analysis. H. pylori infection rate were 90.26% in these cases, so that 33.65% of whom had peptic ulcer. Moreover, the abundance of each vacA genotypes including s1, s2, m1, m2, s1m1, s1m2, s2m1, and s2m2 was estimated as 36.24, 28.32, 42.90 29.86, 27.88, 32.34, 15.70, and 25.94% respectively. We demonstrated that there is a significant relationship between infection of stomach with m1, s1m1, and s2m1 genotypes and development to peptic ulcer disease. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a serious global health issue. Nearly 20% of HCV patients spontaneously clear the virus. While some studies have shown an association of spontaneous clearance (SC) of the virus with interleukin (IL) 28B single-nucleotide polymorphisms (SNPs), others did not show such a relationship. Thus, the purpose of the present study was to investigate the association of IL28B polymorphisms (12979860 SNP) with SC of HCV infection. Upon initial screening of the databases, a total of 545 articles were retrieved, of which 22 studies that met predefined eligibility criteria were entered into the meta-analysis. Odds ratios (ORs) with confidence intervals (95% CI), heterogeneity, publication bias, and sensitivity analysis were assessed. According to the meta-analysis results, a significant association was observed between the rs12979860 SNP and SC of HCV infection. The results indicated that the ORs of SC from hepatitis C virus infection were 2.75 times higher in those with cytokine gene polymorphisms (95% CI, 2.23 to 3.38). Moreover, it was found that the prevalence of rs12979860 CC was 0.33 with 95 CI 0.28-0.38 in genotype 1 and was 0.40 with 95 CI 0.34-0.47 in other genotypes. Our meta-analysis results suggest that IL28B rs12979860 CC is a strong predictor for SC of hepatitis C infection in PEG IFN-a/RBV-treated patients. [ABSTRACT FROM AUTHOR]

Objective Placenta accreta is a pregnancy-related disorder with extreme trophoblast invasion and the adherence of the placenta to the uterine wall. This study aimed to investigate the serum level of transforming growth factor-beta 1 (TGF-β1) and interleukin (IL)-35 in patients with placenta accreta. Methods Thirty-one women with placenta accreta and 57 healthy pregnant women were enrolled. The serum levels of TGF-β1 and IL-35 were measured using the enzyme-linked immunosorbent assay method. Results The serum levels of both TGF-β and IL-35 were significantly higher in the placenta accreta group compared with the group of healthy women (1082.48 pg/mL vs 497.33 pg/mL and 4541.14 pg/mL vs 1306.04 pg/mL; P <.001, respectively). Moreover, the level of TGF-β1 positively correlated with the IL-35 level but other factors such as age, gestations, live births, and abortions did not correlate with IL-35 and TGF-β1 levels. Conclusion The serum levels of IL-35 and TGF-β1 may contribute to the pathogenesis of placenta accreta and could be considered as potential targets in clinical and diagnostic approaches. [ABSTRACT FROM AUTHOR]

The mechanistic (or mammalian) target of rapamycin (mTOR) is considered as a critical regulatory enzyme involved in essential signaling pathways affecting cell growth, cell proliferation, protein translation, regulation of cellular metabolism, and cytoskeletal structure. Also, mTOR signaling has crucial roles in cell homeostasis via processes such as autophagy. Autophagy prevents many pathogen infections and is involved on immunosurveillance and pathogenesis. Immune responses and autophagy are therefore key host responses and both are linked by complex mTOR regulatory mechanisms. In recent years, the mTOR pathway has been highlighted in different diseases such as diabetes, cancer, and infectious and parasitic diseases including leishmaniasis, toxoplasmosis, and malaria. The current review underlines the implications of mTOR signals and intricate networks on pathogen infections and the modulation of this master regulator by parasites. Parasitic infections are able to induce dynamic metabolic reprogramming leading to mTOR alterations in spite of many other ways impacting this regulatory network. Accordingly, the identification of parasite effects and interactions over such a complex modulation might reveal novel information regarding the biology of the abovementioned parasites and might allow the development of therapeutic strategies against parasitic diseases. In this sense, the effects of inhibiting the mTOR pathways are also considered in this context in the light of their potential for the prevention and treatment of parasitic diseases. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia (PE) is the most common pregnancy complication affecting 2-8% of all pregnancies. PE could lead to maternal and prenatal morbidity. Imbalanced cytokine network and altered levels of several inflammatory and antiinflammatory cytokines have been reported in PE. Because of scare information regarding the roles of IL-17 and IL-35 in PE, the current study aimed to investigate the serum level of these cytokines in a group of Iranian women suffering from PE. Methods: Serum samples were collected from 100 pre-eclamptic and 100 healthy pregnant women. Patients and controls were matched for age, ethnicity and body mass index. The level of IL-35 and IL-17 were evaluated by ELISA technique. T test and one-way ANOVA with Tukey Post-Hoc test were used for analysis and p<0.05 were assumed significant. Results: The serum level of IL-35 was increased in pre-eclamptic subjects as compared with healthy pregnant women (p<0.001). There was no significant difference in the serum level of IL-17 between pre-eclamptic and healthy pregnant women (p=0.73). Moreover, the results of the present study also showed that the pregnant women with severe pre-eclampsia had higher level of IL-35 in their sera when compared to those with mild form of the disease (p<0.001). In addition, the serum level of IL-35 was significantly elevated in women with higher proteinuria (p<0.001). Conclusion: Based on the our results, it seems that elevated levels of IL-35 in sera of pre-eclamptic women might work as a marker to evaluate the severity of the preeclampsia. [ABSTRACT FROM AUTHOR]

Vaccination is the most effective way to prevent Hepatitis B (HB) infection. The goal of vaccination is to induce immunological memory. Hence, determining the frequency of memory B-cell (MBC) subsets is an important indicator of vaccine efficacy. This study aimed to evaluate the frequency of different B-cell subpopulations and the expression of PD-1 on B-cell subsets in low responders (LR) and high responders (HR) to HB vaccine. According to our findings, the expression level of PD-1 was significantly higher on atypical MBC (atMBC) than that of naive B cell and classical MBC (cMBC) in LR and HR groups. Moreover, cMBCs had a significant higher PD-1 expression than naive B cells in LR group. No significant differences were found in the frequency of various B-cell subpopulations and the expression level of PD-1 on B-cell subsets between LR and HR groups. We observed a negative correlation between age and HBsAb titer and a positive correlation between age and PD-1 expression level on cMBC in LR group. It can be concluded that inadequate specific memory B-cell response, rather than total memory B-cell deficiency, may be implicated in low responsive rate to HB vaccine in healthy individuals. [ABSTRACT FROM AUTHOR]

• Annexins (ANXs) play different functions in cell biological processes. • ANXs might be expressed on both parasite structure and secretion and in parasite-infected host cells. • The modulation of such proteins can affect the parasite-infections pathogenesis. • Targeting ANXs could be implicated in therapeutic and vaccine trials. Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated proteins might express on both parasite structure and secretion and in parasite-infected host cells. In addition to the characterization of these pivotal proteins, describing their mechanism of action can be also fruitful in recognizing their roles in the pathogenesis of parasitic infections. Accordingly, this study presents the most prominent ANXs thus far identified and their relevant functions in parasites and infected host cells during pathogenesis, especially in the most important intracellular protozoan parasitic infections including leishmaniasis, toxoplasmosis, malaria and trypanosomiasis. The data provided in this study demonstrate that the helminth parasites most probably express and secret ANXs to develop pathogenesis while the modulation of the host-ANXs could be employed as a crucial strategy by intracellular protozoan parasites. Moreover, such data highlight that the use of analogs of both parasite and host ANX peptides (which mimic or regulate ANXs physiological functions through various strategies) might suggest novel therapeutic insights into the treatment of parasitic infections. Furthermore, due to the prominent immunoregulatory activities of ANXs during most parasitic infections and the expression levels of these proteins in some parasitic infected tissues, such multifunctional proteins might be also potentially relevant as vaccine and diagnostic biomarkers. We also suggest some prospects and insights that could be useful and applicable to form the basis of future experimental studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective This systematic review and meta-analysis study was performed to assess the potential association between interleukin-1 beta (IL-1β) single nucleotide polymorphisms (SNPs) (rs1143634 and rs16944) and interleukin-6 (IL-6) SNP (rs1800795) and pre-eclampsia (PE). Methods A comprehensive literature search was conducted in the international search engines and databases, including MEDLINE (via PubMed), Scopus, and Web of Science (ISI) up to 9 March 2021. After retrieving relevant articles, data extraction was performed by four authors independently. Pooled ORs and corresponding 95% CIs were used to evaluate the association between IL-1β and IL-6 polymorphisms and PE risk. Cochran's Q test was used to check heterogeneity, and the I2 index was calculated for measuring the heterogeneity between the estimations of included studies. Results After reviewing fully published studies, 21 studies were included in this study based on the eligibility criteria. Our results showed that rs16944 and rs1143634 of IL-1β were significantly associated with the risk of PE. Regarding rs16944, the minor C allele significantly decreased the risk of PE (C vs. T: OR = 0.79, 95% CI = 0.69–0.90). In contrast, the minor T allele of rs1143634 significantly increased the risk of PE (T vs. C: OR = 1. 28, 95% CI = 1.04–1.58). There was no significant association between IL-6 rs1800795 (C vs. G: OR = 1.04, 95% CI = 0.93–1.16) polymorphism and PE risk. Conclusions In conclusion, this meta-analysis suggests rs1143634 and rs16944 polymorphisms of IL-1β are related to the risk of PE. [ABSTRACT FROM AUTHOR]

Introduction: The frequencies and functions of T stem cell memory (TSCM) subsets vary in autoimmune diseases. We evaluated the frequencies of CD4+ and CD8+ TSCM subsets as well as their PD‐1 expression levels in patients with T1D. Methods: Blood samples were collected from new case (NC) (n = 15), and long‐term (LT) (n = 15) groups and healthy controls (n = 15). Five subsets of T cells including TCM(CD4+/CD8+ CCR7+ CD45RO+ CD95+), TCMhi (CD4+/CD8+ CCR7+ CD45ROhi CD95+), TEM(CD4+/CD8+ CCR7− CD45RO+ CD95+), TSCM(CD4+/CD8+ CCR7+ CD45RO− CD95+), and T naive (CD4+/CD8+ CCR7+ CD45RO− CD95−) were detected by flow‐cytometry. Results: The frequency of CD4+ TSCM was higher in NC patients than LT patients and controls (p <.0001 and p =.0086, respectively). A higher percentage of the CD8+ T naive cells was shown in NC patients as compared with LT and healthy individuals (p =.0003 and p =.0002, respectively). An increased level of PD‐1 expression was observed on the CD4+TCM and TCMhi cells in LT patients as compared with healthy controls (p =.0037 and p =.0145, respectively). Also, the higher PD‐1 expression was observed on the CD8+ TCM and TCMhi in NC and LT patients as compared with controls (p =.0068 and p <.0001; p =.0012 and p =.0012, respectively). Conclusion: Considering TSCMs' capacities to generate all memory and effector T cells, our results may suggest a potential association between the increased frequencies of TSCMs and T1D progression. [ABSTRACT FROM AUTHOR]

Hypothyroidism disturbs redox homeostasis and takes part in cardiovascular system dysfunction. Considering antioxidant and cardio-protective effects of PPAR-γ agonists including pioglitazone (POG) and rosiglitazone (RSG), the present study was aimed to determine the effect of POG or RSG on oxidants and antioxidants indexes in the heart and aorta tissues of Propylthiouracil (PTU)-induced hypothyroid rats. The animals were divided into six groups: (1) Control; (2) propylthiouracil (PTU), (3) PTU-POG 10, (4) PTU-POG 20, (5) PTU-RSG 2, and (6) PTU-RSG 4. Hypothyroidism was induced in rats by giving 0.05% propylthiouracil (PTU) in drinking water for 42 days. The rats of PTU-POG 10 and PTU-POG 20 groups received 10 and 20 mg/kg POG, respectively, besides PTU, and the rats of PTU-RSG 2 and PTU-RSG 4 groups received 2 and 4 mg/kg RSG, respectively, besides PTU. The animals were sacrificed, and the serum of the rats was collected to measure thyroxine level. The heart and aorta tissues were also removed for the measurement of biochemical oxidative stress markers. Hypothyroidism was induced by PTU administration, which was indicated by lower serum thyroxine levels. Hypothyroidism also was accompanied by a decrease of catalase (CAT), superoxide dismutase (SOD) activities, and thiol concentration in the heart and aorta tissues while increased level of malondialdehyde (MDA). Interestingly, administration of POG or RSG dramatically reduced oxidative damage in the heart and aorta, as reflected by a decrease in MDA and increased activities of SOD, CAT, and thiol content. The results of this study showed that administration of POG or RSG decreased oxidative damage in the heart and aorta tissues induced by hypothyroidism in rats. [ABSTRACT FROM AUTHOR]

• miRNAs are important regulators of different cell signaling/responses. • mTOR signaling could be correlated with the pathogenesis of Leishmania. • The crosstalk between miRNAs and mTOR may clarify various aspects of the pathogenicity and biology of Leishmania infections. • Targeting miRNAs that modulate mTOR by small molecules and RNA-based therapeutics could be new treatment options. Micro RNAs (miRNAs), as regulators of gene expression at the post-transcriptional level, can respond to/or interact with cell signaling and affect the pathogenesis of different diseases/infections. The interaction/crosstalk of miRNAs with various cellular signaling networks including mTOR (as a master regulator of signaling relevant to different cellular mechanisms) might lead to the initiation, progression or restriction of certain disease processes. There are numerous studies that have identified the crosstalk between regulatory miRNA expression and the mTOR pathway (or mTOR signaling regulated by miRNAs) in different diseases which has a dual function in pathogenesis. However, the corresponding information in parasitic infections remains scarce. miRNAs have been suggested as specific targets for therapeutic strategies in several disorders such as parasitic infections. Thus, the targeting of miRNAs (as the modulators/regulators of mTOR) by small molecules and RNA-based therapeutics and consequently managing and modulating mTOR signaling and the downstream/related cell signaling/pathways might shed some light on the design of new therapeutic strategies against parasitic diseases, including Leishmaniasis. Accordingly, the present study attempts to highlight the importance of the crosstalk between regulatory miRNAs and mTOR signaling, and to review the relevant insights into parasitic infections by focusing specifically on Leishmania. [Display omitted] [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a pathogenic protozoan parasite belonging to the apicomplexan phylum that infects the nucleated cells of warm-blooded hosts leading to an infectious disease known as toxoplasmosis. Apicomplexan parasites such as T. gondii can display different mechanisms to control or manipulate host cells signaling at different levels altering the host subcellular genome and proteome. Indeed, Toxoplasma is able to modulate host cell responses (especially immune responses) during infection to its advantage through both structural and functional changes in the proteome of different infected cells. Consequently, parasites can transform the invaded cells into a suitable environment for its own replication and the induction of infection. Proteomics as an applicable tool can identify such critical proteins involved in pathogen (Toxoplasma)-host cell interactions and consequently clarify the cellular mechanisms that facilitate the entry of pathogens into host cells, and their replication and transmission, as well as the central mechanisms of host defense against pathogens. Accordingly, the current paper reviews several proteins (identified using proteomic approaches) differentially expressed in the proteome of Toxoplasma-infected host cells (macrophages and human foreskin fibroblasts) and tissues (brain and liver) and highlights their plausible functions in the cellular biology of the infected cells. The identification of such modulated proteins and their related cell impact (cell responses/signaling) can provide further information regarding parasite pathogenesis and biology that might lead to a better understanding of therapeutic strategies and novel drug targets. [ABSTRACT FROM AUTHOR]

Simple Summary: The One Health concept to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. Toxoplasmosis outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. Consequently, the development of effective vaccine and diagnostic strategies is urgent for the elimination of this disease. Proteomics analysis has allowed the identification of key proteins that can be utilized in the development of novel disease diagnostics and vaccines. This work presents relevant proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites. In fact, it brings together the main functionality key proteins from Toxoplasma parasites coming from proteomic approaches that are most likely to be useful in improving the disease management, and critically proposes innovative directions to finally develop promising vaccines and diagnostics tools. Toxoplasma gondii is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts leading to an infectious zoonotic disease known as toxoplasmosis. The infection outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. The One Health approach to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. The presence of drug resistance and side effects, the further improvement of sensitivity and specificity of serodiagnostic tools and the potentiality of vaccine candidates to induce the host immune response are considered as justifiable reasons for the identification of novel targets for the better management of toxoplasmosis. Thus, the identification of new critical proteins in the proteome of Toxoplasma parasites can also be helpful in designing and test more effective drugs, vaccines, and diagnostic tools. Accordingly, in this study we present important proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites that are potential diagnostic or vaccine candidates. The current study might help to understand the complexity of these parasites and provide a possible source of strategies and biomolecules that can be further evaluated in the pathobiology of Toxoplasma parasites and for diagnostics and vaccine trials against this disease. [ABSTRACT FROM AUTHOR]

The current drug treatments against protozoan parasitic diseases including Chagas, malaria, leishmaniasis, and toxoplasmosis represent good examples of drug resistance mechanisms and have shown diverse side effects. Therefore, the identification of novel therapeutic strategies and drug compounds against such life-threatening diseases is urgent. According to the successful usage of selenium (Se) compounds-based therapy against some diseases, this therapeutic strategy has been recently further underlined against these parasitic diseases by targeting different parasite´s essential pathways. On the other hand, due to the important functions played by parasite selenoproteins in their biology (such as modulating the host immune response), they can be also considered as a novel therapeutic strategy by designing specific inhibitors against these important proteins. In addition, the immunomodulatory potentiality of these compounds to trigger T helper type 1 (Th1) cells and cytokine-mediated immune response for the substantial induction of proinflammatory cytokines, thus, Se, selenoproteins, and parasite selenoproteins could be further investigated to find possible vaccine antigens. Herein, we collect and present the results of some studies regarding Se-based therapy against protozoan parasitic diseases and highlight relevant information and some viewpoints that might be insightful to advance toward more effective studies in the future. [ABSTRACT FROM AUTHOR]

• MDSCs are a broad and heterogeneous population with myeloid origin and mostly contribute to immunosuppressive conditions. • MDSCs, especially PMN-MDSCs are highly abundant at feto-maternal interface and in peripheral blood of pregnant women. • Several factors such as sex hormones, trophoblasts, HLA-G, hypoxia, and cytokines play critical roles in MDSCs expansion and activation at feto-maternal interface. • MDSCs are also abundant in fetuses and neonates and contribute to the balance of immune system. Myeloid-derived suppressor cells (MDSCs) have emerged as a new immune regulator at the feto-maternal interface. Although the phenotypes and functions of these cells were primarily studied in pathological conditions such as cancers and infections, new evidence has underscored their beneficial roles in homeostasis and physiological circumstances such as normal pregnancy. In this regard, studies have shown an increased number of MDSCs, particularly granulocytic MDSCs, at the feto-maternal interface. These cells participate in maintaining immunological tolerance between mother and semi-allograft fetus through various mechanisms. They further seem to play critical roles in placentation and fetus growth process. The absence or dysregulation of MDSCs during pregnancy have been reported in several pregnancy complications. These cells are also abundant in the cord blood of neonates so as to balance the immune responses and prevent aggressive inflammatory responses. The current review summarizes and organizes detailed data on MDSCs and their roles during pregnancy. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells seem to be the most common innate lymphocyte subtypes, and they're known for their ability to guide anti-tumor and anti-viral responses, making them potentially therapeutic. Since NK cells lack polymorphic clonotypic receptors, they must rely on inhibitory receptors to develop, mature, and distinguish between "self" and "non-self." In the clinic, genetically engineered immune cells expressing a chimeric antigen receptor (CAR) that consists of an extracellular antigen recognizing domain connected to an intracellular signaling domain have gained interest. The U.S. food and drug administration (FDA) approved two CAR-T cells, anti-CD19 CARs, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). Nevertheless, CAR-T cell therapy is linked to a series of negative side effects, including fatal cytokine release syndrome (CRS) and tumor lysis syndrome (TLS), as well as a lack of regulatory control. CAR-transduced NK cells (CAR-NK) are thought to have many benefits, including clinical safety, the mechanisms by which they identify cancerous cells, and their abundance in clinical specimens, according to a growing number of studies. In pre-clinical and clinical trials, human primary NK cells and the NK-92 cell line were effectively transduced to express CARs against hematological cancers and solid tumors. Here, it is tried to summarize the development of CAR-NK cells, challenges and coping strategies, as well as managing the challenges and obstacles related to its protection, which promises to eliminate the shortcomings of conventional CARs. • Immune cells expressing a chimeric antigen receptor (CAR) connected to an intracellular signaling domain have gained interest. • CAR-transduced NK cells (CAR-NK) are thought to have many benefits, including clinical safety, the mechanisms by which they identify cancerous cells. • The practical implementation of CAR-NK cell treatments is linked to significant challenges that must be overcome for them to realize their greatest capacity. [ABSTRACT FROM AUTHOR]

Human Leukocyte Antigen-G (HLA-G), a polymorphic non-classical HLA (HLA-Ib) with immune-regulatory properties in cancers and infectious diseases, presents both membrane-bound and soluble (sHLA-G) isoforms. Polymorphism has implications in host responses to pathogen infections and in pathogenesis. Differential expression patterns of HLA-G/sHLA-G or its polymorphism seem to be related to different pathological conditions, potentially acting as a disease progression biomarker. Pathogen antigens might be involved in the regulation of both membrane-bound and sHLA-G levels and impact immune responses during co-infections. The upregulation of HLA-G in viral and bacterial infections induce tolerance to infection. Recently, sHLA-G was found useful to identify the prognosis of Coronavirus disease 2019 (COVID-19) among patients and it was observed that the high levels of sHLA-G are associated with worse prognosis. The use of pathogens, such as Plasmodium falciparum, as immune modulators for other infections could be extended for the modulation of membrane-bound HLA-G in COVID-19-infected tissues. Overall, such information might open new avenues concerning the effect of some pathogens such as parasites in decreasing the expression level of HLA-G to restrict pathogenesis in some infections or to influence the immune responses after vaccination among others. [ABSTRACT FROM AUTHOR]

There are important challenges when investigating individual post-translational modifications (PTMs) or protein interaction network and delineating if PTMs or their changes and cross-talks are involved during infection, disease initiation or as a result of disease progression. Proteomics and in silico approaches now offer the possibility to complement each other to further understand the regulatory involvement of these modifications in parasites and infection biology. Accordingly, the current review highlights key expressed or altered proteins and PTMs are invisible switches that turn on and off the function of most of the proteins. PTMs include phosphorylation, glycosylation, ubiquitylation, palmitoylation, myristoylation, prenylation, acetylation, methylation, and epigenetic PTMs in P. falciparum which have been recently identified. But also other low-abundant or overlooked PTMs that might be important for the parasite's survival, infectivity, antigenicity, immunomodulation and pathogenesis. We here emphasize the PTMs as regulatory pathways playing major roles in the biology, pathogenicity, metabolic pathways, survival, host-parasite interactions and the life cycle of P. falciparum. Further validations and functional characterizations of such proteins might confirm the discovery of therapeutic targets and might most likely provide valuable data for the treatment of P. falciparum , the main cause of severe malaria in human. [Display omitted] • Multidrug-resistant P. falciparum is a major health problem that need investment in proteomics research based advances. • PTMs play critical roles in the biology, pathogenicity, metabolic pathways, survival, and life cycle of Plasmodium parasites. • Key proteins relevant to PTMs in P. falciparum are critically involved during infection, pathogenicity and survival. • Novel research directions involving and targeting PTMs have the potential to provide insights and tools to manage malaria. [ABSTRACT FROM AUTHOR]