Systematic levels of IL-29 and microRNA185-5p were not associated with severe COVID-19 in the Iranian population.

BACKGROUND: Increased systematic pro-inflammatory cytokines is the main cause of the inflammatory conditions of the hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. In this project, serum levels of IL-29 and whole blood levels of microRNA-185-5p (miR-185-5p) were evaluated in the hospitalized SARS-CoV-2 infected patients. METHODS: This project was performed on the 60 hospitalized SARS-CoV-2 infected patients and 60 healthy controls to evaluate IL-29 and miR185-5p expression levels. IL-29 expression was explored using enzyme linked immunoassay (ELISA), while miR185-5p was evaluated using Real-Time PCR techniques. RESULTS: The results demonstrated that neither IL-29 serum levels nor relative expressions of miR-185-5p were significantly different between patients and healthy controls. CONCLUSION: Due to the results that are presented here, systematic levels of IL-29 and miR-185-5p cannot be considered as the main risk factors for induction of inflammation in the hospitalized SARS-CoV-2 infected patients.

Expression of toll like receptors before and after coronary angiography with isomolar contrast among those with and without coronary atherosclerosis.

Angiography is a safe technique for the detection of and treatment of cardiovascular diseases. However, the effects of the technique on the molecular response of the immune system are yet to be clarified. Toll like receptors (TLRs) are the important molecule participate in the innate immunity responses and induction of inflammation. This project was designed to explore the effects of angiography on the expression of TLR1, TLR2, TLR3 and TLR4. Fifty-five participants, including three separate groups (without artery stenosis, with one artery stenosis and more than one artery stenosis), were assessed in this project. TLR1, TLR2, TLR3 and TLR4 expression levels were evaluated in peripheral blood immune cells by measuring mRNA before and after angiography using Real-Time PCR techniques. mRNA levels of TLR1, TLR2 and TLR3 were significantly increased following angiography. Expression of TLR4 did not change after angiography. Other criteria also showed no correlation on TLR expression after angiography. TLR4 mRNA levels had a positive correlation with age in the participants without artery stenosis. Angiography may induce inflammation in subjects without artery stenosis via up-regulation of TLR1, 2 and 3 which may lead to cardiovascular diseases related complications.

Depression Is Associated with Downregulation of IPS-1 in Chronic HBV-Infected Patients in a Sex-Dependent Manner.

BACKGROUND: Depression and anxiety can modulate immune-related molecule expressions. The chronic HBV-infected (CHB) patients suffer from inappropriate immune responses. Additionally, psychological disorders are prevalent among the patients. Thus, depression and anxiety may alter immune-related molecule expression. This study aimed to examine IPS-1 and RIP1 mRNA levels in CHB patients suffering from various degrees of anxiety and depression. METHODS: Sixty patients with CHB participated in this research and completed standard questionnaires to evaluate depression and anxiety. The expression levels of IPS-1 and RIP1 were examined using real-time PCR techniques. RESULTS: The result revealed that although the expression of IPS-1 and RIP1 did not change in the CHB patients with various ranges of depression and anxiety, IPS-1 was significantly decreased in the male CHB patients who suffered from mild, moderate, and severe depression when compared to the patients with no depression. CONCLUSION: So, it was hypothesized that depression may be associated with alteration in the expression of IPS-1 in a sex-dependent manner. In other words, it appears that the male CHB patients are at risk of depression-related alteration in immune-related gene expression.

The effect of IFN-ß 1a on expression of MDA5 and RIG-1 in multiple sclerosis patients.

The aims of this study were to compare mRNA levels of melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene 1 (RIG-1) in multiple sclerosis (MS) patients in comparison to the healthy controls as well as investigating the effects of IFN-ß 1a on the expression of these molecules. In this study, mRNA levels of MDA5 and RIG-1 in peripheral leukocytes of 30 new cases of MS patients and 35 healthy controls were evaluated using the real-time-PCR method. mRNA levels of MDA5 and RIG-1 were determined in the MS patients 6 months after treatment with standard doses of IFN-ß 1a. mRNA levels of MDA5 and RIG-1 were significantly decreased in the MS patients in comparison to the healthy controls. The analysis also revealed that IFN-ß 1a therapy leads to the upregulation of RIG-1, but not MDA5, in the total MS patients and the female group. MS patients suffer from insufficient expression of MDA5 and RIG-1, and IFN-ß 1a therapy results in the upregulation of RIG-1 in the patients, especially in the female patients. Thus, it seems that IFN-ß 1a not only decreased pathogenic inflammatory responses but also modulated the expression of RIG-1 to protect the patients from infectious diseases and upregulation of IFN-I in a positive feedback.

Brain magnetic resonance imaging without contrast significantly increased serum levels of IL-6, but not IL-10, IL-17A and TGF-ß.

Introduction: Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality. However, the effects of MRI on the immune system in the in vivo conditions are yet to be clarified. In this study we explored the effects of routine brain MRI on the protein and mRNA peripheral blood levels of interleukin-6 (IL-6), IL-10, IL-17A and transforming growth factor-beta (TGF-ß).Material and methods: 40 subjects, who referred for brain MRI, were entered for evaluating effects of routine brain MRI on the protein and mRNA peripheral blood levels of IL-6, IL-10, IL-17A and TGF-ß. Accordingly, peripheral blood were collected before and 3 hours after MRI from the participants. Protein levels of the cytokines were evaluated using ELISA. Also, mRNA levels were analyzed using Real-Time PCR techniques.Results: Brain MRI without contrast led to an increase in protein levels of IL-6 in the peripheral serum, but did not change protein and mRNA levels of IL-10, IL-17A and TGF-ß. IL-6 mRNA levels after MRI were higher in the participants with mild anxiety compared to those without anxiety.Conclusion: brain MRI without contrast can induce secretion of IL-6 and may be associated with its functions, such as development of plasma cells or induction of inflammation.

The immune response against Toxoplasma gondii in BALB/c mice induced by mannose-modified nanoliposome of excreted/secreted antigens.

This study aimed to compare the immune response against Toxoplasma gondii (T. gondii) in BALB/c mice induced by excreted/secreted (E/S) antigens and mannose-modified nanoliposome of E/S antigens. Here, E/S antigens and mannose-modified nanoliposome of E/S antigens were firstly prepared, and then BALB/c female inbred mice were separately immunized. In the next step, anti-E/S antigen antibodies and the relative expression levels of IL-10 and IL-12 mRNA were detected by ELISA and real-time PCR, respectively. After immunization, mice were intraperitoneally challenged with 102 tachyzoites of T. gondii, and the survival rate was recorded. The ELISA analysis showed significant differences between the levels of anti-E/S antigen antibodies in the mice immunized by E/S antigens and those immunized by mannose-modified nanoliposome of E/S antigens at days 7, 10, 20, 25, and 30 (P < 0.05). Real-time PCR analysis showed that the relative expression of IL-10 was significantly decreased during 20 days. Yet, the relative expression of IL-12 was significantly increased during 20 days (P < 0.05). In T. gondii challenge test, significant differences were found between the survival rates of mice immunized by E/S antigens and mice immunized by mannose-modified nanoliposome with E/S antigens. This project evidenced that mannose-modified nanoliposome of E/S antigens induced a more powerful immune response against T. gondii in BALB/c mice when compared with excreted/secreted antigens alone.

Mesenchymal Stem Cells: The Potential Therapeutic Cell Therapy to Reduce Brain Stroke Side Effects.

Tissue plasminogen activator (tPA) is the gold standard treatment for ischemic stroke in the time window of 3-4.5 hours after the onset of symptoms. However, tPA administration is associated with inflammation and neurotoxic effects. Mesenchymal stem cells (MSC)-based therapy is emerging as a promising therapeutic strategy to control different inflammatory conditions. This project was designed to examine the protective role of MSC administration alone or in combination with royal jelly (RJ) five hours after stroke onset. The mice model of middle cerebral artery occlusion (MCAO) was established and put to six groups, including intact (healthy mice without stroke), control (untreated stroke), treated with mouse MSC (mMSC), Sup (conditioned medium), RJ and combination of mMSC and RJ (mMSC/RJ). Thereafter, behavioral functions, serum and brain (in both infarcted and non-infarcted tissues) levels of interleukin (IL)-1ß, IL-4, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) the sizes of brain infarction have been determined in the groups. Administration of mMSC and mMSC/RJ significantly improved the behavioral functions when compared to the controls. mMSC, RJ and mMSC/RJ significantly decreased the infarcted volumes. RJ and mMSC/RJ, but not mMSC, significantly decreased the brain edema. The infarction increased the serum levels of the cytokines, except TNF-α, and treatment with mMSC, Sup and RJ reduced serum levels of the pro-inflammatory cytokines. mMSC reduced IL-1ß in the non-infarcted brain tissue. To conclude, data revealed that using mMSC/RJ combination significantly reduced stroke side effects, including brain edema and serum levels of pro-inflammatory cytokines, and suggested that combination therapy of MSCs with RJ may be considered as an effective stroke therapeutic strategy.

The study of the serum level of IL-4, TGF-ß, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension.

BACKGROUND: Obesity increases the risk of diabetes mellitus (DM) and hypertension. We aimed to analyze the serum levels of cytokines that have relevance to the pathologies including, interleukin-4 (IL-4), transforming growth factor-ß (TGF-ß), interferon-γ (IFN-γ), and IL-6 cytokines of overweight men with DM and/or hypertension. METHODS: The study collected serum from 164 men. The sample population contained, 54 overweight men without DM or hypertension (control [CTL] group), 36 men with both DM and hypertension (DH group), 20 men with DM but no hypertension (D group), and 54 had hypertension without DM (H). RESULTS: The main results showed that the concentration of IFN-γ in the DH group was significantly higher than the D, H, and CTL groups, IL-6 in DH and D groups was significantly lower than the CTL group. The serum level of TGF-ß and IL-4 cytokines did not show any significant differences across the four groups. Serum levels of IL-6 were also significantly lower in untreated patients in D group than controls and in DH when compared with H groups. CONCLUSION: In conclusion, it appears that the proinflammatory and anti-inflammatory cytokines either play a significant role in the pathogenesis of hypertension and DM or serve as markers for these pathologies. Accordingly, increased serum levels of IFN-γ may participate in the pathogenesis of hypertension in the diabetic patients and decreased IL-6 is associated with type 2 DM.

Up-regulation of RIP1 and IPS-1 in chronic HBV infected patients.

IPS-1 and RIP1 are the main downstream molecules of RIG1 and MDA5, as intracytoplasmic receptors, which are the main receptors involved in recognition of internal and external viral double-stranded RNA. In this project, mRNA levels of IPS-1 and RIP1 were investigated in the peripheral blood immune cells of chronic hepatitis B (CHB) patients. IPS-1 and RIP1 mRNA levels were measured in 60 CHB patients and 120 healthy subjects, using RT-qPCR technique. A significant increase in expression levels of IPS-1 and RIP1 was found in patients when compared to healthy individuals. There was no correlation between IPS-1 and RIP1expression levels with the serum levels of hepatitis B e-Antigen (HBeAg) and liver enzymes in patients. Based on the results, it seems that IPS-1 and RIP1 can participate in the induction of low chronic inflammation, which is a main cause of liver cirrhosis and hepatocellular carcinoma.

Downregulation of IL-22 can be considered as a risk factor for onset of type 2 diabetes.

There is some controversy as for the roles played by tumor growth factor-ß (TGF-ß), interleukin-1ß (IL-1ß), and IL-22 in the onset process of type 2 diabetes (T2D). The main aim of this project was to examine serum levels of TGF-ß, IL-1ß, and IL-22 in the new cases and long period T2D patients as well as healthy controls. In this study, 115 new T2D patient cases (group 1), 434 T2D patients who have suffered from the disease more than 2 years (group 2), and 104 healthy controls have been selected from 6240 (3619 females) patients who were under study population from Kerman Coronary Artery Disease Risk Factor Study. Serum levels of TGF-ß, IL-1ß, and IL-22 have been evaluated using commercial kits. Serum levels of TGF-ß and IL-1ß significantly increased, while IL-22 decreased in 2 groups in comparison to healthy controls. Serum levels of IL-22, but not TGF-ß and IL-1ß, were significantly decreased in group 1 in comparison to healthy controls. There were no significant differences between groups 1 and 2 as for the cytokine levels. Serum levels of IL-22 increased in the females in group 2 when compared to females in group 1. It appears that TGF-ß and IL-1ß participate in the induction of inflammation after establishment of T2D, while decrease in IL-22 may be considered as a key factor for onset of the disease. Gender can also be considered as the main risk factor for variation in cytokine levels.

IL-17A and IL-23: plausible risk factors to induce age-associated inflammation in Alzheimer's disease.

Background: Aging and its complications such as Alzheimer's disease (AD) are associated with chronic low-grade inflammation entitled age-associated inflammation. However, the main mechanisms whichinduce age-associated inflammation in aging and AD are yet to beclarified. L-23/IL-17A axis plays important roles in the induction of inflammation and consequently autoimmune disease. This review evaluates the main roles played by IL-17A, IL-23, and IL-17A/IL-23 axis in the pathogenesis of age-associated inflammation in AD patients. Result: IL-23/IL-17A axis, is an important factor participate in the pathogenesis of age-associated inflammation. The genetic variations and microbial infection can be considered as the most important candidates to induce AD via upregulation of IL-17A. IL-17A also deteriorates AD via induction by amyloid-ß. IL-17A participates in the induction of AD by increasing neutrophils infiltration to brain, induction of neuroinflammation, increase in FASL, and amyloid-ßdeposition as well as activation of microglia. Conclusions: Due to the important roles played by IL-23/IL-17A axis in AD pathogenesis, it can be considered as a target for immunotherapy against AD. Abbreviations: Aß: ß-Amyloid; AD: Alzheimer's disease; CD: cluster of differentiation; DAMPs: Damage-associated molecular patterns; DCs: dendritic cells; HLA: human leukocyte antigen; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; RAR: retinoic-acid receptor; RORγt: RAR-related orphan receptor gamma t; SAMP8: senescence-accelerated mouse prone 8 strain; TGF-ß: tumor growth factor-ß; TLRs: toll-like receptors.

TGF-ß in Toxoplasmosis: Friend or foe?

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan causing several forms of toxoplasmosis in humans. The main mechanisms that allow the development of the prolonged forms of the disease and its subsequent pathology are yet to be clarified. However, many researchers have hypothesized that immunological and genetic parameters may play crucial roles in the etiology of the disease. Transforming growth factor beta (TGF-ß) is a cytokine with a dual role in the regulation of immune responses including those against parasites. However, the relationship between TGF-ß and immune responses against T .gondii are not fully understood. The important roles played by TGF-ß in the development of Th17 and T regulatory lymphocytes, mucosal immunity and regulation of immune responses have been documented and this provides insights into TGF-ß function during parasitic infections such as toxoplasmosis. Therefore, the aim of this review is to collate the current information regarding the status and association of TGF-ß with T. gondii infection.

Important roles played by TGF-ß in hepatitis B infection.

Hepatitis B virus (HBV) which includes, fulminant, acute, chronic, asymptomatic, and occult HBV infection is the most prevalent virus that leads to human liver diseases. Chronic, asymptomatic, and occult infection can induce further sever diseases such as hepatocellular carcinoma (HCC) and cirrhosis of the liver. The underlying mechanisms that allow progression of the prolonged forms of the infection and subsequent HCC or cirrhosis of the liver are yet to be clarified. However, many researchers have suggested that immunological and genetic parameters may play important roles in the etiology of hepatitis B. Transforming growth factor beta (TGF-ß) is an important cytokine with dual regulatory functions in the immune system and in the responses against viral infections. However, the pathways and mechanisms controlling these are not fully understood. The crucial roles of TGF-ß in the development of Th17 and T regulatory lymphocytes, the main cell types involved in autoimmunity and destructive immune related diseases, have been documented and this provides insights into TGF-ß function during hepatitis infection and subsequent HCC and cirrhosis of the liver. Recent findings also confirm that TGF-ß directly alters hepatocyte function during hepatitis B, hence, the aim of this review is to address the current data regarding the association and status of TGF-ß with hepatitis B infection and its related disorders including HCC and cirrhosis of the liver.

TLR4 in Toxoplasmosis; friends or foe?

Toxoplasma species are obligate intracellular protozoan which are responsible for induction of several forms of Toxoplasmosis in humans. The mechanisms responsible for the progression of the prolonged forms of Toxoplasmosis and associated pathologies are yet to be identified. However, previous studies proposed that immunological and genetic parameters may play important roles in the etiology and complexity of Toxoplasmosis. Pathogen recognition receptors (PRRs) recognize microbial antigens and induce immune responses against parasites, including toxoplasma species. Toll like receptors (TLRs) are PRRs which recognize toxoplasma as a pathogenic parasite and activate immune cells. It has been reported that the TLR4 is a critical innate immune cell receptor in toxoplasma detection and subsequently activates immune responses using either MYD88 or TRIF pathways. This review collates recent information regarding the role of TLR4 and its related signaling molecules with Toxoplasmosis.

Altered expression of apoptotic genes in response to OCT4B1 suppression in human tumor cell lines.

OCT4B1 is a newly discovered spliced variant of OCT4 which is primarily expressed in pluripotent and tumor cells. Based on our previous studies, OCT4B1 is significantly overexpressed in tumors, where it endows an anti-apoptotic property to tumor cells. However, the mechanism by which OCT4B1 regulates the apoptotic pathway is not yet elucidated. Here, we investigated the effects of OCT4B1 suppression on the expression alteration of 84 genes involved in apoptotic pathway. The AGS (gastric adenocarcinoma), 5637 (bladder tumor), and U-87MG (brain tumor) cell lines were transfected with OCT4B1 or irrelevant siRNAs. The expression level of apoptotic genes was then quantified using a human apoptosis panel-PCR kit. Our data revealed an almost similar pattern of alteration in the expression profile of apoptotic genes in all three studied cell lines, following OCT4B1 suppression. In general, the expression of more than 54 apoptotic genes (64 % of arrayed genes) showed significant changes. Among these, some up-regulated (CIDEA, CIDEB, TNFRSF1A, TNFRSF21, TNFRSF11B, TNFRSF10B, and CASP7) and down-regulated (BCL2, BCL2L11, TP73, TP53, BAD, TRAF3, TRAF2, BRAF, BNIP3L, BFAR, and BAX) genes had on average more than tenfold gene expression alteration in all three examined cell lines. With some minor exceptions, suppression of OCT4B1 caused upregulation of pro-apoptotic and down-regulation of anti-apoptotic genes in transfected tumor cells. Uncovering OCT4B1 down-stream targets could further elucidate its part in tumorigenesis, and could lead to finding a new approach to combat cancer, based on targeting OCT4B1.

IL-17A in hepatitis B infection: friend or foe?

Hepatitis B virus (HBV) is one of the most prevalent and infectious agents that leads to liver disease in humans. Five clinical forms of HBV infection exist, including fulminant, acute, chronic, asymptomatic and occult. The chronic, asymptomatic and occult forms are long-term infections that can lead to hepatocellular carcinoma (HCC) and liver cirrhosis. The mechanisms responsible for progression of these forms of the infection to HCC and liver cirrhosis are not yet clearly understood or characterised. However, genetic and immunological parameters may play important roles in the disease. IL-17A is an important cytokine involved in early immune responses against fungal and bacterial infections, but its role in the response against viral infections is yet to be fully clarified. The crucial roles of IL-17A in the pathogenesis of autoimmune and destructive immune-related diseases have been documented and may provide insights into its functions during hepatitis infection. Therefore, the aim of this review was to address the recent information regarding the status and association of IL-17A during hepatitis B infection and its related disorders, including HCC and liver cirrhosis.

NK cells in hepatitis B virus infection: a potent target for immunotherapy.

Viruses, including hepatitis B virus (HBV), are the most prevalent and infectious agents that lead to liver disease in humans. Hepatocellular carcinoma (HCC) and cirrhosis of the liver are the most serious complications arising from prolonged forms of hepatitis B. Previous studies demonstrated that patients suffering from long-term HBV infections are unable to eradicate HBV from hepatocytes completely. The mechanisms responsible for progression of these forms of infection have not yet been clarified. However, it seems that there are differences in genetic and immunological parameters when comparing patients to subjects who successfully clear HBV infections, and these may represent the causes of long-term infection. Natural killer (NK) cells, the main innate immune cells that target viral infections, play important roles in the eradication of HBV from hepatocytes. NK cells carry several stimulatory and inhibitor receptors, and binding of receptors with their ligands results in activation and suppression of NK cells, respectively. The aim of this review is to address the recent information regarding NK cell phenotype, functions and modifications in hepatitis B. This review addresses the recent data regarding the roles of NK cells as novel targets for immunotherapies that target hepatitis B infection. It also discusses the potential to reduce the risk of HCC or cirrhosis of the liver by targeting NK cells.

TLR3 plays significant roles against hepatitis B virus.

Hepatitis B virus (HBV) as the main prevalent infectious agent, play important roles in inducing severe liver diseases. Previous studies demonstrated that during prolonged forms of hepatitis B infection including chronic, asymptomatic and occult forms, patients are unable to eradicate HBV from hepatocytes completely. The main mechanisms responsible for development of the forms of hepatitis B are yet to be identified. Investigators suggested that the various genetic and immunological parameters of the patients may are responsible for resulting in the prolonged infection forms. It has been evidenced that TLRs play key roles in inducing appropriate immune responses, against viral infections. Therefore, these molecules can be considered as crucial sensors for HBV detection to induce immune responses against this virus. It has also been documented that the TLR3 detects intracellular viral dsRNA and subsequently activates NF-κB via the TRIF pathway. Therefore, impaired TLR3 expression may result in inappropriate immune responses against HBV which is reported in prolonged forms of hepatitis B. This review collected the recent information regarding the important roles of TLR3 in immune responses against HBV and also the status of TLR3 expression and its genetic variations in prolonged forms of HBV infections.

Ectopic expression of micro-RNA-1, 21 and 125a in peripheral blood immune cells is associated with chronic HBV infection.

Micro-RNAs (miRNAs) play key roles in regulating genes of the immune system. The aim of this study was to examine the expression of miR-1, 21 and 125a in the immune cells taken from the peripheral blood of patients suffering from chronic HBV infection (CHB). This cross-sectional study was performed on 60 CHB patients and 60 healthy controls and expression of miR-1, 21 and 125a was evaluated using quantitative Real-Time PCR. The results showed that expression of miR-1, 21 and 125a was significantly increased in CHB patients in comparison to healthy controls. Based on our results it may be concluded that increased expression of miR-1, 21 and 125a is significantly associated with CHB and may play key roles in the induction of impaired immune responses in CHB patients.

Current information concerning association of IL-12 and hepatitis B infection.

BACKGROUND: Hepatitis B is one of the most prevalent infectious diseases and is induced by hepatitis B virus (HBV). The chronic, asymptomatic, and occult forms of hepatitis B are long-term infections that can lead to various hepatic cancers and cirrhosis in the carrier. IL-12 is one of the main cytokines involved in inducing appropriate immune responses against viral infections, especially HBV. Therefore, the aim of the present review was to address the most recent information within the database regarding the status and association between IL-12 and hepatitis B infection and its complications including cirrhosis and hepatocellular carcinoma. METHODS: The data presented was collected by searching the following keywords in the Pubmed and Scopous databases: Hepatitis B, occult HBV infection, chronic HBV infection, asymptomathic HBV infection, acute HBV infection, fulminant HBV infection, IL-12, and all the papers regarding the relation between IL-12 and hepatitis B were used. These data were presented in the current review article. RESULTS: Results showed that IL-12 plays important roles in Hepatitis B infection and patients infected with the long-term form of hepatitis B are unable to produce sufficient amount of this cytokine. CONCLUSIONS: Our research provided mechanistic insights into the immunoprotective roles of IL-12 and proposed that it can be considered as an important molecule for immunotherapy of HBV infected infection.