Potential roles of NLRP3 inflammasome in the pathogenesis of Kawasaki disease.

There is a heterogeneous group of rare illnesses that fall into the vasculitis category and are characterized mostly by blood vessel inflammation. Ischemia and disrupted blood flow will cause harm to the organs whose blood arteries become inflamed. Kawasaki disease (KD) is the most prevalent kind of vasculitis in children aged 5 years or younger. Because KD's cardiovascular problems might persist into adulthood, it is no longer thought of as a self-limiting disease. KD is a systemic vasculitis with unknown initiating factors. Numerous factors, such as genetic predisposition and infectious pathogens, are implicated in the etiology of KD. As endothelial cell damage and inflammation can lead to coronary endothelial dysfunction in KD, some studies hypothesized the crucial role of pyroptosis in the pathogenesis of KD. Additionally, pyroptosis-related proteins like caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), proinflammatory cytokines like IL-1 and IL-18, lactic dehydrogenase, and Gasdermin D (GSDMD) have been found to be overexpressed in KD patients when compared to healthy controls. These occurrences may point to an involvement of inflammasomes and pyroptotic cell death in the etiology of KD and suggest potential treatment targets. Based on these shreds of evidence, in this review, we aim to focus on one of the well-defined inflammasomes, NLRP3, and its role in the pathophysiology of KD.

The potential roles of Th17 cells in the pathogenesis of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated chronic autoimmune disease, whose pathogenesis and etiology are not entirely understood. OLP is characterized by subepithelial lymphocyte infiltration and elevated intra-epithelial lymphocytes. The majority of lamina propria lymphocytes are CD4+ T cells. CD4+ helper T (Th) cells play a crucial role in activating CD8+ cytotoxic T cells (CTLs) through interactions and cytokine production. Th1 and Th2 cells are well-accepted to be associated with OLP pathogenesis. However, OLP treatment is challenging yet, the more information we have about the pathology of OLP, the easier it will be treated. With the discovery of Th17 cells in recent years and the demonstration of their role in autoimmune disease, many researchers started to investigate the role of Th17 in the pathogenesis of OLP. METHODS: To make up this review, studies covering the role of TH17 in different types of lichen planus were selected from major databases. RESULTS: As we review in this article, Th17 cells and their signature cytokines play an important role in OLP pathogenesis. As well, utilizing some anti-IL-17 antibodies showed promising results in improving the disease; however, more studies are still needed to better understand and treat OLP.

Anticancer traits of chimeric antigen receptors (CARs)-Natural Killer (NK) cells as novel approaches for melanoma treatment.

Owing to non-responsiveness of a high number of patients to the common melanoma therapies, seeking novel approaches seem as an unmet requirement. Chimeric antigen receptor (CAR) T cells were initially employed against recurrent or refractory B cell malignancies. However, advanced stages or pretreated patients have insufficient T cells (lymphopenia) amount for collection and clinical application. Additionally, this process is time-consuming and logistically cumbersome. Another limitation of this approach is toxicity and cytokine release syndrome (CRS) progress and neurotoxicity syndrome (NS). Natural killer (NK) cells are a versatile component of the innate immunity and have several advantages over T cells in the application for therapies such as availability, unique biological features, safety profile, cost effectiveness and higher tissue residence. Additionally, CAR NK cells do not develop Graft-versus-host disease (GvHD) and are independent of host HLA genotype. Notably, the NK cells number and activity is affected in the tumor microenvironment (TME), paving the way for developing novel approaches by enhancing their maturation and functionality. The CAR NK cells short lifespan is a double edge sword declining toxicity and reducing their persistence. Bispecific and Trispecific Killer Cell Engagers (BiKE and Trike, respectively) are emerging and promising immunotherapies for efficient antibody dependent cell cytotoxicity (ADCC). CAR NK cells have some limitations in terms of expanding and transducing NK cells from donors to achieve clinical response. Clinical trials are in scarcity regarding the CAR NK cell-based cancer therapies. The CAR NK cells short life span following irradiation before infusion limits their efficiency inhibiting their in vivo expansion. The CAR NK cells efficacy enhancement in terms of lifespan TME preparation and stability is a goal for melanoma treatment. Combination therapies using CAR NK cells and chemotherapy can also overcome therapy limitations.

Opportunities and obstacles for the melanoma immunotherapy using T cell and chimeric antigen receptor T (CAR-T) applications: a literature review.

Chimeric antigen receptor T (CAR-T) cell therapy procedure includes taking personal T cells and processing or genetic engineering using specific antigens and in vitro expanding and eventually infusing into the patient's body to unleash immune responses. Adoptive cell therapy (ACT) includes lymphocytes taking, in vitro selection and expansion and processing for stimulation or activation and infusion into the patient's body. Immune checkpoint inhibitors (ICIs), ACT and CAR-T cell therapies have demonstrated acceptable results. However, rare CAR-T cells tissue infiltration, off-target toxicity and resistance development include main disadvantages of CAR-T cell based therapy. Selection of suitable target antigens and novel engineered immune cells are warranted in future studies using "surfaceome" analysis. Employment of cytokines (IL-2, IL-7) for T cells activation has been also associated with specific anti-melanoma function which overcome telomeres shortening and further T cells differentiation. In resistant cases, rapidly accelerated fibrosarcoma B-type and mitogen-activated extracellular signal-regulated kinase inhibitors have been mostly applied. The aim of this study was evaluation of CAR-T cell and adoptive cell therapies efficiency for the treatment of melanoma.

Upregulation of hsa_circ_0004812 promotes COVID-19 cytokine storm via hsa-miR-1287-5p/IL6R, RIG-I axis.

BACKGROUND: SARS-CoV-2 is one of the most contagious viruses in the Coronaviridae (CoV) family, which has become a pandemic. The aim of this study is to understand more about the role of hsa_circ_0004812 in the SARS-CoV-2 related cytokine storm and its associated molecular mechanisms. MATERIALS AND METHODS: cDNA synthesis was performed after total RNA was extracted from the peripheral blood mononuclear cells (PBMC) of 46 patients with symptomatic COVID-19, 46 patients with asymptomatic COVID-19, and 46 healthy controls. The expression levels of hsa_circ_0004812, hsa-miR-1287-5p, IL6R, and RIG-I were determined using qRT-PCR, and the potential interaction between these molecules was confirmed by bioinformatics tools and correlation analysis. RESULTS: hsa_circ_0004812, IL6R, and RIG-I are expressed higher in the severe symptom group compared with the negative control group. Also, the relative expression of these genes in the asymptomatic group is lower than in the severe symptom group. The expression level of hsa-miR-1287-5p was positively correlated with symptoms in patients. The results of the bioinformatics analysis predicted the sponging effect of hsa_circ_0004812 as a competing endogenous RNA on hsa-miR-1287-5p. Moreover, there was a significant positive correlation between hsa_circ_0004812, RIG-I, and IL-6R expressions, and also a negative expression correlation between hsa_circ_0004812 and hsa-miR-1287-5p and between hsa-miR-1287-5p, RIG-I, and IL-6R. CONCLUSION: The results of this in-vitro and in silico study show that hsa_circ_0004812/hsa-miR-1287-5p/IL6R, RIG-I can play an important role in the outcome of COVID-19.

Dynamic alterations and durability of T helper 22 and its corresponding cytokines following treatment in pediatric visceral leishmaniasis.

Considering the collaboration between immune responses and medications for the improvement of visceral leishmaniasis (VL), this study investigated the levels of T helper (Th) 22 and the corresponding cytokines in the acute phase of VL and their alterations following treatment. The study was conducted on 18 patients with confirmed VL and 20 healthy sex and age matched children as the controls. The levels of Th22 cells and the cytokines driving their differentiations and functions in the blood and peripheral blood mononuclear cells (PBMC) cultured supernatants, were assessed using flow cytometry method. The results revealed significantly higher levels of Th22, IL-21 and IL-6 in the patients' blood than those in the controls. Additionally, higher levels of IL-21 and IL-22 were observed in the cultured supernatants of VL patients' PBMCs, compared to the controls. Upon treatment, Th22 and IL-6 were down-regulated and conversely, IL-21, IL-22, IL-23 and IL-33 were significantly up-regulated in the patients' blood at different time points. Receiver operating characteristic (ROC) curve analysis indicated that for the differential diagnosis of VL, plasma IL-21 is more sensitive and specific than Th22 and the above mentioned cytokines. The higher proportions of Th22 and IL-21 in the VL patients and their alterations post treatment confer their roles in the immunopathogenesis of VL. So, Th22 and IL-21 in the patients' blood can be considered as biomarkers to be used for the differential diagnosis of VL. Nevertheless, further studies are warranted to clarify their particular mechanisms in this process.

Interleukine-22 gene variants are associated with susceptibility to visceral leishmaniasis.

Visceral leishmaniasis (VL) is an infectious disease caused by an intracellular protozoan belonging to Leishmania species. Interleukin (IL)-22 plays an important role in inflammatory response, chemotaxis, regulation of cellular proliferation and tissue repair. Considering the role of IL-22 in control of leishmaniasis and the effect of its single nucleotide polymorphisms (SNPs) on respective function and production, this study aimed to investigate the probable association of IL-22 SNPs with VL. The study was carried out on 110 patients with VL, 102 healthy individuals with negative leishmanin skin test (negative control group (NCG)), and 144 healthy individuals with positive leishmanin skin test (LSTPG). Four SNPs in IL-22 including rs2227501, rs2227503, rs2227513 and rs1026786 were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR- RFLP) in the study groups. The frequency of A allele and AA genotype at rs1026786 were significantly higher in the LSTPG group than in the patients (P = 0.013 and P = 0.001, respectively). Conversely, the frequency of AG genotype was significantly higher in the patients and the NCG than in the LSTPG group (P = 0.0001 and P = 0.002, respectively). For rs2227503, the frequency of AG genotype was significantly higher in the LSTPG group than in the NCG (P = 0.025). The haplotype TGAA frequency was significantly higher in the NCG, compared to patients and LSTPG group (P = 0.004 and P = 0.023, respectively). The frequencies of haplotypes TAAG and TGAG were significantly higher in the patients than in the LSTPG group (P = 0.046 and P = 0.014, respectively). The TAAA/TAAG frequency was significantly higher in the patients than in the LSTPG group (P = 0.013). Inheritance of rs1026786 A allele and AA genotype of IL-22 could be a possible protective factor against VL, whereas the inheritance of the haplotypes TAAG and TGAG may predispose Iranian population to the disease.

Treatment effects on IL-9+CD4+ T cells and the cytokines influencing IL-9 production in paediatric visceral leishmaniasis.

AIMS: Given the involvement of IL-9 in the immune responses to parasitic infections, we aimed to determine alterations in the levels of IL-9+CD4+ T cells and the cytokines influencing their differentiations and functions following treatment in paediatric visceral leishmaniasis (VL). METHODS AND RESULTS: Eighteen VL and 20 healthy children were included. The levels of IL-9+CD4+ T cells and cytokines influencing their differentiations and functions were measured in the blood and PBMC culture supernatant at the onset of diagnosis and 1 and 2 weeks and 2 months after treatment, using flow cytometer. IL-9+CD4+ T cells, IL-2 and TNF-α were significantly higher in the blood of VL patients than those in the controls; however, following treatment, IL-9+CD4+ T cells down-regulated and IL-33 and IFN-γ significantly up-regulated. After ex vivo stimulation, although the released cytokines were not significantly different between the study groups, the levels of IL-2, IL-9 and IFN-γ significantly decreased. CONCLUSIONS: The higher frequency of IL-9+CD4+ T cells and its decline following treatment implies their roles in the immunopathogenesis of VL; however, at the diagnosis onset, lower levels of serum IL-9 and its higher level in the culture supernatant may confer in vivo dysfunction of IL-9+CD4+ T cells in the acute phase of human VL.

Effect of Prolonged Infusion of Alamandine on Cardiovascular Parameters and Cardiac ACE2 Expression in a Rat Model of Renovascular Hypertension.

Alamandine is a new member of the angiotensin family. Here, we studied the mRNA and protein expression of cardiac angiotensin-converting enzyme 2 (ACE2) in the chronic phase of a rat model of 2-kidney, 1-clip hypertension (2K1C), and the effects of 2-week alamandine infusion on blood pressure, cardiac indices, and ACE2 mRNA and protein expression in the hearts. The rats were subjected to to sham-operation or placement of plexiglass clips around the left renal artery. Alamandine, at a dose of 600 µg/kg/d, was administered for 2 weeks via an osmotic mini-pump. At 18 weeks, after induction of hypertension, blood pressure and cardiac indices of contractility were measured using a Powerlab Physiograph system. The ACE2 mRNA and protein levels were determined using real time-PCR and Western blotting, respectively. In the hypertensive rats, alamandine caused a significant decrease in systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), left ventricular end-diastolic pressure (p < 0.001) and, left ventricular systolic pressure (p < 0.001) and increase in the maximum rate of pressure change in the left ventricle (dP/dt(max)) (p < 0.05). Also, the ACE2 mRNA expression in the heart increased in the hypertensive rats compared to the normotensive rats (p < 0.05), and alamandine restored this to normal values, although these changes were only seen at the mRNA and not the protein level. Histological analysis of cardiac tissue confirmed that alamandine decreased cardiac fibrosis and hypertrophy in 2K1C hypertensive rats. Our results indicate that alamandine, which acts as a depressor arm of the renin-angiotensin system, could be developed for treating hypertension.

Mesenchymal Stem Cells Upregulate the Expression of PD-L1 But Not VDR in Dendritic Cells.

OBJECTIVE: Mesenchymal stem cells (MSCs) show immunomodulatory functions. But the exact mechanism underlying these activities of MSCs is still not completely understood. There have been a few studies which have assessed the effects of these cells on dendritic cells (DCs) function. Given the importance of programmed cell death receptor-1 (PD-L1) and vitamin D receptor (VDR) expression in induction of tolerance in DCs, we were encouraged to investigate if one of the immunomodulatory functions of MSCs could be inducing upregulation of PD-L1 and VDR on DCs or not. METHODS: DCs were co-cultured with MSCs or treated with them in transwell plates in the presence or absence of Lipopolysaccharide (LPS). Expression of PD-L1 and VDR mRNA and proteins in treated DCs were assessed by Real-time PCR and Western blot techniques. Furthermore, treated DCs were co-cultured with allogeneic T-cells, and T-cell proliferation and cytokine secretions in co-culture supernatants were assessed. RESULTS: The results showed that PD-L1 but not VDR expression is significantly upregulated in the DCs co-cultured with MSCs. Furthermore, cell-to-cell contact and also presence of maturation inducers like LPS is necessary for this function. Moreover, our results indicated that MSCs could induce tolerogenic DCs (TolDCs) which could decrease the secretion of IL-2 by T-cells and inhibit T-cell proliferation as well as increase secretion of IL-10. CONCLUSIONS: Overall, our results show that MSCs may have several suppressive effects on immune responses by induction of TolDCs expressing more PD-L1 immunomodulatory molecule and change the cytokines profile of DCs and T-cells.

Evaluation of Immunomodulatory Effects of Mesenchymal Stem Cells Soluble Factors on miR-155 and miR-23b Expression in Mice Dendritic Cells.

Mesenchymal stem cells (MSCs) can modulate dendritic cells (DCs) activation and induce tolerogenic characteristics in DCs. All mechanisms involved in MSCs-induced tolerogenic DCs are not fully understood. MicroRNAs (miRs) play important role in maturation and function of DCs. In this study, we investigated the effects of MSCs culture supernatant (C.S.) on expression of miR-155 and miR-23b in mice DCs. BALB/c mice spleens were used for DCs isolation. MSCs were isolated from the mice bone marrow and cultured in DMEM media. When MSCs expanded to sixth passage, C.S. was collected after 12, 24 and 48 h. Quantitative polymerase chain reaction (QPCR) was used to determine the expression of miR-155 and miR-23b in DCs treated with C.S. after 6 and 12 h. Secretion of IL-23 and TGF- ß were detected in DCs treated with C.S. by ELISA after 24 h. miR-23b expression was significantly increased in DCs treated with 12 h C.S. for 12 h compared to negative controls. miR-155 expression did not change in DCs treated with C.S. after 6 and 12 h. miR-23b expression was significantly increased in DCs treated with 12 h C.S. for 12 h, compared to those treated with C.S. for 6 h. Similarly, miR-23b expression was increased in DCs treated with 24 h C.S. for 12 h when compared to those treated for 6 h. Production of TGF-ß and IL-23 were not influenced by C.S. In conclusion, miR-23b is considered to be one of the mechanisms involved in tolerogenic DCs induction by C.S. in a time-dependent manner.

Knowledge on Human Papillomavirus Infections, Cancer Biology, Immune Interactions, Vaccination Coverage and Common Treatments: A Comprehensive Review.

Human papillomavirus (HPV) is a circular, double-stranded DNA virus and recognized as the most prevalent sexually transmitted infectious agent worldwide. The HPV life cycle encompasses three primary stages. First, the virus infiltrates the basal cells of the stratified epidermis. Second, there is a low-level expression of viral genes and preservation of the viral genome in the basal layer. Lastly, productive replication of HPV occurs in differentiated cells. An effective immune response, involving various immune cells, including innate immunity, keratinocytes, dendritic cells, and natural killer T cells, is instrumental in clearing HPV infection and thwarting the development of HPV-associated tumors. Vaccines have demonstrated their efficacy in preventing genital warts, high-grade precancerous lesions, and cancers in females. In males, the vaccines can also aid in preventing genital warts, anal precancerous lesions, and cancer. This comprehensive review aims to provide a thorough and detailed exploration of HPV infections, delving into its genetic characteristics, life cycle, pathogenesis, and the role of high-risk and low-risk HPV strains. In addition, this review seeks to elucidate the intricate immune interactions that govern HPV infections, spanning from innate immunity to adaptive immune responses, as well as examining the evasion mechanisms used by the virus. Furthermore, the article discusses the current landscape of HPV vaccines and common treatments, contributing to a holistic understanding of HPV and its associated diseases.

Interleukin-17A genetic variants can confer resistance to brucellosis in Iranian population.

On the subject of brucellosis, it seems that Th1/Th2 cytokines balance may be involved in the resistance or susceptibility to Brucella infection. In this respect, Th1 cytokines confer resistance, while Th2 cytokines predispose brucellosis. It is also clarified that IL-17 is required for the induction of IFN-γ and IL-12 in macrophages and dendritic cells. Then, it seems that IL-17 can affect the induction of Th1 immunity which is necessary for controlling Brucella. In the present study, we tried to investigate probable relationship between IL-17A genetic variants and susceptibility to the human brucellosis. One hundred and seventy six patients with brucellosis and 84 healthy animal husbandmen, who consumed contaminated raw milk and dairy products from animals with brucellosis, were included in this study. All individuals were genotyped for 9 single nucleotide polymorphisms (SNPs) (rs4711998AG, rs8193036CT, rs3819024AG, rs2275913AG, rs3819025AG, rs8193038AG, rs3804513AT, rs1974226AG and rs3748067AG) being selected by using NCBI SNP database and literature using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The distribution of IL-17 rs4711998, rs8193038, rs3748067 AA genotypes and AAGAA haplotype were significantly more frequent in the patients than in the controls (P=0.008, 0.0019, 0.003 and 0.002, respectively) while IL-17 genotypes rs3819024GG and rs3819025AA were more frequent in the controls than the patients (P=0.001 and 0.0035, respectively). Based on the results, IL-17 rs4711998, rs8193038, rs3748067 AA genotypes and AAGAA haplotype could be considered as susceptibility factors for brucellosis while the inheritance of IL-17 rs3819024GG and rs3819025AA genotypes might be resistance factors against the disease.

Association of interleukin-18 gene variants with susceptibility to visceral leishmaniasis in Iranian population.

Host resistance to Leishmania infection is mediated by cellular immune responses leading to macrophage activation and parasite killing. Interleukin-18 (IL-18) known as interferon-γ (IFN-γ) inducing factor, stimulates IFN-γ production by T cells. Taking into account the important role of IL-18 in the defense against visceral leishmaniasis (VL) and the known effect of IL-18 gene polymorphisms on its production, the aim of this study was to investigate the probable relationship between IL-18 gene polymorphisms and the susceptibility to VL. The study groups included 118 pediatric patients who suffered from VL and 156 non-relative healthy people as the controls from the same endemic area. IL-18 gene polymorphisms at the positions -656 G/T, -137 G/C and +105A/C (codon 35/3) were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). The results showed that the frequency of T allele at the position -656 was significantly higher in the controls, compared with that in the patients (P = 0.047), but it couldn't tolerate Bonferroni correction. Regarding the IL-18 genotypes, there was no significant difference between the patients and controls. Although the frequencies of ATG single haplotype and AGG/ATG double haplotype were significantly higher in the controls (P = 0.043) and the patients (P = 0.044), respectively, the two P values couldn't tolerate Bonferroni correction. Furthermore, a strong linkage disequilibrium was observed among the -656, -137 and +105 single nucleotide polymorphisms of IL-18 gene (all Ps < 0.001). In conclusion, this study suggests that the inheritance of T allele at the position -656 may be considered as a genetic factor for resistance to VL.

Toll-like receptor 4 (TLR4) polymorphisms in Iranian patients with visceral leishmaniasis.

The role of Toll-like receptor (TLR) 4 in visceral leishmaniasis (VL), a disease caused by an obligate intracellular protozoan parasites belonging to the genus Leishmania, has been shown in the recent leishmaniasis experimental studies. As genetic host factors play an important role in the susceptibility and/or resistance to VL, the association between TLR4 gene mutations [A896G and C1196T single nucleotide polymorphisms (SNPs)] and VL was investigated. Genotyping of A896G (Asp299Gly) and C1196T (Thr399Ile) SNPs was performed in the patients with VL (N = 122) and ethnically matched controls (N = 155) using polymerase chain reaction-restriction fragment length polymorphism method. When VL patients and the controls were compared, no statistically significant differences were observed in A896G and C1196T alleles and genotypes (P > 0.05). The TLR4 A896G and C1196T were in moderate linkage disequilibrium in the controls and patients (r (2) = 0.497, 0.548 and D' = 0.705, 0.808, respectively), and haplotypes reconstructed from these SNPs were not significantly different between the aforementioned study groups. In conclusion, based on the results, TLR4 gene polymorphisms at the positions 896 and 1196 cannot be regarded as the major contributors to VL susceptibility among the Iranian population.

IL-1ß (-511T/C) gene polymorphism not IL-1ß (+3953T/C) and LT-α (+252A/G) gene variants confers susceptibility to visceral leishmaniasis.

Lymphotoxin-α (LT-α) and interleukin-1beta (IL-1ß) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-α (+252A/G) and IL-1ß (+3953T/C and -511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was not found any significant differences in allele and genotype frequencies of LT-α (+252A/G) and IL-1ß (+3953) among the study groups. However, the frequency of IL-1ß -511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1ß -511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1ß CC (-511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1ß -511C allele, CC genotype and CC (-511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1ß -511TT genotype, T allele and TT haplotype (-511/+3953) might be counted as the influential factors for resistance to the disease.

Interleukin-18 single nucleotide polymorphisms contribute to the susceptibility to brucellosis in Iranian patients.

It seems that IL-18 has a crucial role in immunity against Brucella infection. Since the expression of IL-18 can be affected by polymorphisms in its gene, we decided to investigate any probable relationship between the six different IL-18 gene polymorphisms and brucellosis. A total of 193 patients with brucellosis and 83 healthy farmers who consumed contaminated raw milk and dairy products from the animals with brucellosis, were included in this study. All the individuals were genotyped for six IL-18 polymorphisms at positions -656, -607, -137, +113, +127 and codon 35/3, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The distributions of alleles for IL-18 polymorphisms at positions -137G/+113T/+127C/codon 35/3A (correlated with higher production of IL-18) were significantly higher in healthy controls than in patients (P=0.012, 0.012, 0.012 and 0.0018, respectively). It could be suggested that individuals who inherited the aforementioned genotypes/alleles are able to produce higher levels of IL-18 at the onset of infection, and it leads to more IFN-gamma production and control Brucella infection before the emerging brucellosis.

Reporting of substance use treatment quality in United States adult drug courts.

BACKGROUND: Adult drug courts are growing in popularity within the Unites States, but the quality of substance use treatment within drug court programs and the impact of drug courts on health and substance use treatment outcomes is largely unknown. We appraised the quality of United States adult drug court process evaluations and the inclusion of measures of substance use treatment quality. METHODS: We systematically reviewed the adult drug court evaluations between 2008 and 2018 in accordance with recommended strategies for systematic gray literature search. We appraised evaluation quality using the Evidence for Policy and Practice Information and Coordination Center tool for process evaluations. We extracted recommended measures of substance use treatment quality, including measures related to screening and monitoring, diagnosis, service availability, service utilization, and outcomes. RESULTS: Our search identified 112 evaluations. Process measures were included within 68 evaluations, 45% of which had poor data reliability. We found that less than 10% of evaluations reported substance use treatment quality measures related to service utilization, overdose, and mortality, while more than 75% contained criminal justice measures, including program graduation (completion of criminal justice proceedings) and participant recidivism. CONCLUSIONS: We found low uptake of measures of substance use treatment quality. The absence of data call into question the ability of drug courts to stem harmful substance use related health outcomes.

Improved Function and Maturation of Dendritic Cells Stimulated by Recombinant pp65 Protein: An in-vitro Design.

BACKGROUND: Stimulated dendritic cells (DCs) have been shown to be effective in the induction of specific immune cells. Also, the CMV pp65 plays an important role in CMV life cycle and immune recognition. OBJECTIVE: To assess the effect of CMV pp65 on the maturity and function of dendritic cells. METHODS: Splenic DCs were treated with non-cytotoxic concentrations of the pp65 and analyzed for MHC II, CD86, and CD40 expression by flow cytometry. Then, ROR-γ, GATA3, T-bet, and FOXP3 gene expression levels were evaluated in T cells co-cultured with DCs using Real time-PCR. Finally, the effects of pp65 on allogenic T-cell responses in mixed lymphocyte culture (MLR), and the release of cytokines were investigated by ELISA and flow cytometry. RESULTS: The phagocytosis rate was significantly lower in the pp65-treated DCs than the non-stimulated DCs. There were significant differences in the raised level of CD40, CD86, and CCR7 in DCs as maturation markers. Furthermore, ROR-γ, and T-bet overexpression in T cells of the pp65-treated group compared with the non-stimulated group was observed. Significant differences were observed in the levels of IL-2, IL-6, IL-17, IL-22, TNF-α, and IFN-γ in pp65-stimulated groups compared with the non-stimulated DCs. CONCLUSIONS: The pp65-treated DCs can induce differentiation and functional activity of the cellular immune system, including Th17, and Th1, but not other major T-cell subsets such as Tregs, and Th2 population.

The Effect of Mesenchymal Stem Cells on the Expression of IDO and Qa2 Molecules in Dendritic Cells.

Purpose: Mesenchymal stem cells (MSCs) have been shown to reduce the activity of immune cells, including dendritic cells (DCs). But the exact mechanism of mesenchymal inhibition of DCs is still unknown. In this study, the effect of mesenchymal cells on the expression of indoleamine dioxygenase (IDO) and Qa2 molecules in DCs was evaluated. Methods: MSCs and DCs were respectively isolated from the bone marrow and spleen of BALB/c mice. Then DCs were co-cultured with MSCs in the present and absence of lipopolysaccharides (LPS). Then the expression of mRNA and protein of IDO and Qa2 molecules were investigated in DCs that were treated with MSCs. Results: The expression of IDO and Qa2 mRNA in DCs that were treated with MSCs did not significantly differ from the control group. The expression of IDO protein in DCs that were cocultured with MSCs (in 1:10 and 1:50 ratios) in absence of LPS was increased, although they were not statistically significant (P values: 0.24 and 0.18, respectively). The expression of Qa2 protein in DCs that were co-cultured with MSCs (in 1:10 and 1:50 ratios) in presence of LPS was increased, although they were not statistically significant (P-values: 0.09 and 0.33, respectively). Conclusion: Our results denied the possibility that MSCs led to the induction of tolerogenic DCs by increasing the expression of the IDO and Qa2 immunomodulatory molecules.