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.

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68.

The molecular mechanisms of opium action with regard to coronary artery disease (CAD) have not yet been determined. The aim of this study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in CAD patients with and without opium addiction. This case-control study was conducted on three groups: (1) opium-addicted CAD patients (CAD + OA, n = 30); (2) CAD patients with no opium addiction (CAD, n = 30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n = 17). The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by the flow cytometry and quantitative polymerase chain reaction (RT-qPCR) methods, respectively. The consumption of atorvastatin, aspirin, and glyceryl trinitrate was found be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD + OA group than in the CAD and Ctrl groups (p = 0.001 and p = 0.005, respectively). MDA levels significantly increased in CAD and CAD + OA patients in comparison with the Ctrl group (p = 0.010 and p = 0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Down-regulation of transforming growth factor-beta and interleukin-6 serum levels in the idiopathic chronic obstructive pulmonary disease.

BACKGROUND: Idiopathic chronic obstructive pulmonary disease (ICOPD) is a prevalent human disease. The etiology of the disease is yet to be clarified. The main aim of this project was to explore serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) in the ICOPD patients in comparison to healthy controls. METHODS: In this cross-sectional study, serum levels of IL-6, TNF-α and TGF-ß were evaluated in the 70 non-smoker ICOPD patients and 70 sex and age matched controls, using ELISA technique by the commercial kits from Karmania Pars Gene Company. Analysis of data was performed by parametric independent and Pearson correlation test. RESULTS: Serum levels of IL-6 and TGF-ß, but not TNF-α, were significantly decreased in the ICOPD patients in comparison to controls. Serum levels of IL-6, TNF-α and TGF-ß were not altered in the ICOPD male in comparison to female and also in mild when compared to moderate ICOPD patients. CONCLUSIONS: Down-regulation of TGF-ß may be the main risk factor for deterioration of inflammation in the ICOPD patients. Decreased IL-6 may be related to the idiopathic type of COPD.

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68.

The molecular mechanisms of opium with regard to coronary artery disease (CAD) have not yet been determined. The aim of the present study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in patients with CAD with and without opium addiction. This case-control study was conducted in three groups: (1) opium-addicted patients with CAD (CAD+OA, n=30); (2) patients with CAD with no opium addiction (CAD, n=30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n=17). Protein and messenger RNA (mRNA) levels of CD9, CD36, and CD68 were evaluated by flow cytometry and reverse transcription-quantitative PCR methods, respectively. Consumption of atorvastatin, aspirin, and glyceryl trinitrate was found to be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD+OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). MDA levels significantly increased in the CAD and CAD+OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Aqueous extract of Achillea millefolium significantly affects mesenchymal stem cell renewal and differentiation in a dose dependent manner.

Introduction: Achillea millefolium is an Iranian herbal medicine with various effects on the human cells. The aim of this study was to investigate the effects of the aqueous extract of Achillea millefolium (AEAM) on the proliferation and differentiation of mesenchymal stem cells (MSCs). Methods: In this study, bone marrow-MSCs (BM-MSCs) were obtained from Wister rat bone morrow and then cultured in Dulbecco's modified Eagle's medium /Nutrient Ham's Mixture F-12 (DMEM/F12) media. Then, the isolated MSCs were cultured in either osteocyte or adipocyte differentiation media containing 0.2 or 2 mg/mL AEAM and assessed using specific staining method. Results: The isolated BM-MSCs exhibited fibroblast-like morphology and were positive for CD73, and CD90, while negative for CD34 and CD45. AEAM significantly increased self-renewal of BM-MSCs at low dose (0.2 mg/ml, P= 0.001) and increased the pool stem cells in both osteocyte and adipocyte differentiation media. Conclusion: AEAM at low doses may be used in cases where there is a need for large number of stem cells, via increased numbers of MSCs, and help tissue repair and immunomodulation.

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.

Severe Acute Respiratory Syndrome Coronavirus 2: The Role of the Main Components of the Innate Immune System.

At the end of December 2019, the COVID-19 pandemic began in Wuhan of China. COVID-19 affects different people with a wide spectrum of clinical manifestations, ranging from asymptomatic with recovery without hospitalization up to a severe acute respiratory syndrome (SARS). The innate and adaptive immunity appears responsible for the defense against the virus and recovery from the disease. The innate immune system, as the first line of defense, is essential for the detection of virus and subsequent activation of acquired immunity. The innate immune response is carried out by sentinel cells such as monocytes/macrophages and dendritic cells and by receptors known as pattern recognition receptors (PRR). These receptors can recognize various components of the virus, which lead to intracellular signaling and subsequently the synthesis of various cytokines. These cytokines then recruit other immune cells, activate adaptive immune responses, and inhibit viral spreading. The most common receptors include Toll-like receptors, C-type lectin receptors, and RIG-I like receptors. This review describes the current knowledge about the interplay between innate immune responses and SARS-CoV-2 with a focus on the innate immune cells and the role of their receptors in viral RNA recognition, as well as their mechanisms for recognizing SARS-CoV-2.

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.

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.

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.

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 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.

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.

APLN/APJ pathway: The key regulator of macrophage functions.

Macrophages play key roles during cardiovascular diseases (CVD) and their related complications. Apelin (APLN) is a key molecule, whose roles during CVD have been documented previously. Therefore, it has been hypothesized that APLN may perform its roles via modulation of macrophages. Additionally, due to the widespread distribution of the CVD, more effective therapeutic strategies need to be developed to overcome the related complications. This review article collected recent information regarding the roles of APLN on the macrophages and discusses its potential chance to be a target for molecular/cellular therapy of APLN and the APLN treated macrophages for CVD.

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.

Toll-like receptor 4 and breast cancer: an updated systematic review.

Toll-like receptors (TLRs) may play dual roles in human cancers. TLR4 is a key molecule which may participate in both friend and foe roles against breast cancer. This review article collected recent data regarding the mechanisms used by TLR4 in the eradication of breast cancer cells and induction of the tumor cells, and discussed the mechanisms involved in the various functions of TLR4. The literature searches revealed that TLR4 is a key molecule that participates in breast cancer cell eradication or induction of breast cancer development and also transformation of the normal cells. TLR4 eradicates breast cancer cells via recognition of their DAMPs and then induces immune responses. Over-expression of TLR4 and also alterations in its signaling, including association of some intrinsic pathways such as TGF-ß signaling and TP53, are the crucial factors to alter TLR4 functions against breast cancer.

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.

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.

Interleukin-6 and Tumor Growth Factor-ß are Risk Factors for Idiopathic Epistaxis.

OBJECTIVE: To evaluate the serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, tumor growth factor (TGF)-ß, endothelin, and immunoglobulin (Ig)E in patients with idiopathic epistaxis, compared with healthy control individuals. METHODS: Serum levels of IL-6, IL-8, TNF-α, TGF-ß, endothelin, and IgE were evaluated in 110 patients with idiopathic epistaxis and 100 healthy controls using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Serum levels of IL-6 (P <.001) and TGF-ß (P = .001) were significantly increased in patients with idiopathic epistaxis, compared with controls. TNF-α serum levels were significantly increased in male patients, compared with female patients (P = .053). We observed decreased antihistamine levels and increased expression of TGF-ß (P = .02) and TNF-α (P = .02), respectively. CONCLUSIONS: IL-6 and TGF-ß appear to participate in the pathogenesis of idiopathic epistaxis. TNF-α may be considered a risk factor for male patients in developing epistaxis. Antihistamines may inhibit angiogenesis by decreasing expression of TGF-ß and increasing expression of TNF-α.