Inflammatory bowel disease, colitis, and cancer: unmasking the chronic inflammation link.

BACKGROUND: Chronic inflammation is a significant driver in the development of various diseases, including cancer. Colitis-associated colorectal cancer (CA-CRC) refers to the increased risk of colorectal cancer in individuals with chronic inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. METHODS: This narrative review examines the link between chronic inflammation and CA-CRC. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2000 and 2024. Studies were selected based on relevance to the role of inflammation in CA-CRC, specifically targeting molecular pathways and clinical implications. Both clinical and mechanistic studies were reviewed. CONCLUSION: Sustained inflammation in the colon fosters a pro-tumorigenic environment, leading to the initiation and progression of CA-CRC. Prevention strategies must focus on controlling chronic inflammation, optimizing IBD management, and implementing regular screenings. Emerging therapies targeting key inflammatory pathways and immune responses, along with microbiome modulation, hold promise for reducing CA-CRC risk. Understanding these molecular mechanisms provides a path toward personalized treatment and better outcomes for patients with IBD at risk of colorectal cancer.

Correction: Mansoori et al. HMGA2 Supports Cancer Hallmarks in Triple-Negative Breast Cancer. Cancers 2021, 13, 5197.

In the original publication [...].

Triple-negative breast cancer-derived exosomes change the immunological features of human monocyte-derived dendritic cells and influence T-cell responses.

BACKGROUND: Triple-negative breast cancer (TNBC) exhibits a lower survival rate in comparison to other BC subtypes. Utilizing dendritic cell (DC) vaccines as a form of immunotherapy is becoming a promising new approach to cancer treatment. However, inadequate immunogenicity of tumor antigens leads to unsatisfactory effectiveness of the DC vaccines. Exosomes are the basis for the latest improvements in tumor immunotherapy. This study examined whether TNBC-derived exosomes elicit immunogenicity on the maturation and function of monocyte-derived DCs and the impact of the exosome-treated monocyte-derived DCs (moDCs) on T cell differentiation. METHODS: exosomes were isolated from MDA-MB-231 TNBC cancer cells and characterized. Monocytes were separated from peripheral blood mononuclear cells and differentiated into DCs. Then, monocyte-derived DCs were treated with TNBC-derived exosomes. Furthermore, the mRNA levels of the genes and cytokines involved in DC maturation and function were examined using qRT-PCR and ELISA assays. We also cocultured TNBC-derived exosome-treated moDCs with T cells and investigated the role of the treatment in T cell differentiation by evaluating the expression of some related genes by qRT-PCR. The concentration of the cytokines secreted from T cells cocultured with exosome-treated moDCs was quantified by the ELISA assays. RESULTS: Our findings showed that TNBC-derived exosomes induce immunogenicity by enhancing moDCs' maturation and function. In addition, exosome-treated moDCs promote cocultured T-cell expansion by inducing TH1 differentiation through increasing cytokine production. CONCLUSION: TNBC-derived exosomes could improve vaccine-elicited immunotherapy by inducing an immunogenic response and enhancing the effectiveness of the DC vaccines. However, this needs to be investigated further in future studies.

VSIG-3/IGSF11 silencing in A2058 melanoma cells simultaneously suppresses melanoma progression and induces anti-tumoral cytokine profile in human T cells: In silico and in vitro study.

VISTA is a newly discovered immune checkpoint whose functional mechanisms have become increasingly important to study due to its brilliant results in cancer immunotherapy. Despite VSIG-3/IGSF11 being identified as an inhibitory ligand for VISTA with potential as a target for cancer immunotherapy, very little is known of its functions. This study aimed to conduct a detailed analysis of VSIG-3/IGSF11 in melanoma, as well as to study the effects of its silencing on melanoma cell line progression and human T cell functions. Online databases were used to investigate VSIG-3/IGSF11 expression, its relationships, and prognostic value in melanoma. Then, the effects of VSIG-3/IGSF11 silencing on proliferation, migration, cell cycle arrest, and apoptosis in A2058 melanoma cells were assessed using MTT, colony formation, wound healing, cell cycle, and Annexin-V FITC/PI assays, respectively. Finally, A2058 cells transfected with VSIG-3/IGSF11 siRNA were co-cultured with human T cells, and the expression levels of T cell cytokines were evaluated using qRT-PCR. VSIG-3/IGSF11 expression was significantly increased in melanoma patients and cell lines; however, no correlation was found between VSIG-3/IGSF11 expression levels and clinicopathological characteristics, survival, or immune cell infiltration. Following VSIG-3/IGSF11 silencing in A2058 cells, viability, proliferation, and migration rates were decreased, while apoptosis was increased. T cells co-cultured with VSIG-3/IGSF11 siRNA-transfected A2058 cells exhibited increased expression levels of IFN-γ and IL-12 and decreased expression levels of IL-10, TGF-ß, and TNF-α. The inhibitory effect of VSIG-3/IGSF11 silencing on A2058 melanoma cell progression, along with the alteration of T cell cytokines towards a pro-inflammatory phenotype, suggests that VSIG-3/IGSF11 is primarily involved in melanoma progression and modulating immune responses. Therefore, it may be a valuable target for immunotherapy in melanoma patients.

Co-targeting NRF2 potentially enhances the in vitro anticancer effects of paclitaxel in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a highly chemoresistant malignancy with a poor prognosis. Paclitaxel's low response rate as second-line chemotherapy for advanced GC has prompted intensive research into its molecular basis and prospective targeted therapies to enhance its therapeutic efficacy. The objective of this study was to investigate the synergistic effects of NRF2 silencing in combination with paclitaxel treatment on GC cell viability, apoptosis, proliferation, autophagy, and migration. METHODS: \After the siRNA-mediated silencing of NRF2 in AGS cells, the transfection efficacy was evaluated by qRT-PCR. The MTT assay was then applied to assess cell viability, followed by flow cytometry analysis for apoptosis, proliferation, and autophagy in AGS cells treated with NRF2 siRNA, paclitaxel, or their combination. Thereafter, the migration of cells was measured using a wound-healing assay. Ultimately, the relative gene expression levels of apoptotic (Bax, Caspase-3, and Caspase-9), anti-apoptotic (Bcl-2), metastatic (MMP-2), and cell cycle (P53) genes were measured by qRT-PCR in all experiment groups to further assess the molecular basis for the combination therapy. RESULTS: NRF2 siRNA transfection significantly enhanced paclitaxel-induced apoptosis and sensitized AGS cells to paclitaxel via modulating the expression of apoptosis-related genes including Bcl-2, Bax, Caspase-3, and Caspase-9. Besides, NRF2 siRNA and paclitaxel synergistically induced cell cycle arrest at the G2 phase, promoted autophagy activation, and inhibited AGS cell migration via MMP-2 downregulation. Additionally, P53, a key regulator of cell growth, was significantly upregulated in the treated groups compared to the control group. CONCLUSIONS: Our findings suggest that paclitaxel combined with siRNA-mediated silencing of NRF2 might represent a promising therapeutic strategy for GC, however further translational and clinical research are warranted.

Boosting immunotherapy efficacy: Empowering the Potency of Dendritic cells loaded with breast cancer lysates through CTLA-4 suppression.

Anticancer immunotherapies with a dendritic Cell (DC) basis are becoming more popular. However, it has been suggested that the tumor's immunosuppressive mechanisms, such as inhibitory immunological checkpoint molecules, reduce the effectiveness of anticancer immunogenicity mediated by DC. Thus, overcoming immune checkpoints and inducing effective antigen-specific T-cell responses uniquely produced with malignant cells represent the key challenges. Among the inhibitory immune checkpoints, DCs' ability to mature and present antigens is decreased by CTLA-4 expression. Consequently, we hypothesized that by expressing CTLA-4 cells on DCs, the T cells' activation against tumor antigens would be suppressed when confronted with these antigens presented by DCs. In this research, by loading cell lysate of breast cancer (BC) on DCs and the other hand by inhibiting the induction of CTLA-4 using small interfering RNA (siRNA), we assessed the functional activities and phenotypes of DCs, and also the responses associated with T-cells following co-culture DC/T cell. Our research has shown that the suppression of CTLA-4 enhanced the stimulating capabilities of DCs. Additionally, CTLA-4-suppressed BC cell lysate-loaded DCs produced more IL-4 and IFN-ϒ and increased T cell induction in contrast to DCs without CTLA-4 suppression. Together, our data point to CTLA-4-suppressed DCs loaded with BC cell lysate as a potentially effective treatment method. However, further research is required before employing this method in therapeutic contexts.

Microbial natural compounds and secondary metabolites as Immunomodulators: A review.

Immunomodulatory therapies are beneficial strategies for the improvement of immune system function. Today, due to the increasing prevalence of immune disorders, cancer, and new viral diseases, there is a greater need to introduce immunomodulatory compounds with more efficiency and fewer side effects. Microbial derivatives are fertile and attractive grounds for discovering lots of novel compounds with various medical properties. The discovery of many natural compounds derived from bacterial sources, such as secondary metabolites with promising immunomodulating activities, represents the importance of this topic in drug discovery and emphasizes the necessity for a coherent source of study in this area. Considering this need, in this review, we aim to focus on the current information about the immunomodulatory effects of bacterial secondary metabolites and natural immunomodulators derived from microorganisms.

Enhancing Chemotherapy Efficacy: Investigating the Synergistic Impact of Paclitaxel and cd73 Gene Suppression on Breast Cancer Cell Proliferation and Migration.

Background Enhancing chemotherapy efficacy is crucial in breast cancer treatment. This study examines the synergistic effects of paclitaxel, a common chemotherapeutic drug, and Cluster of differentiation 73 (cd73) gene suppression via siRNA on MDA-MB-231 breast cancer cells. Methods MDA-MB-231 cells were transfected with CD73 siRNA and treated with paclitaxel. Cell viability, apoptosis, and migration were assessed by using MTT assays, Annexin V-FITC/PI staining, and wound healing assays, respectively, with flow cytometry analyzing cell cycle distribution. Results The combination of CD73 siRNA and paclitaxel significantly reduced cell viability, lowering paclitaxel's IC50 from 14.73 µg/mL to 8.471 µg/mL, indicating enhanced drug sensitivity. Apoptosis rates increased with the combination treatment, while cell migration was significantly inhibited. Flow cytometry revealed cell cycle arrest in the Sub-G1 and G2-M phases. Conclusion These findings suggest that cd73 gene suppression enhances paclitaxel's cytotoxic effects, promoting apoptosis and inhibiting cell migration in MDA-MB-231 breast cancer cell line. This combined strategy shows promise for improving breast cancer treatment outcomes by increasing the efficacy of existing chemotherapeutic regimens, warranting further research to explore its potential clinical applications and effectiveness in other breast cancer cell lines and models.

Bicalutamide reveals immunomodulatory effects in prostate cancer by regulating immunogenic dendritic cell maturation.

Prostate cancer poses a significant global health challenge, ranking as the second most prevalent and fifth most lethal malignancy among males. The intricate interplay between androgen signaling and the immune microenvironment underscores the complexity of prostate cancer progression. Notably, androgen receptor (AR) signaling has been shown to affect immune response mediated by tumor antigen-presenting dendritic cells (DCs). Therefore, this study aimed to explore the potential of Bicalutamide, a nonsteroidal anti-androgen, in modulating DCs-mediated immune responses. Peripheral blood mononuclear cells (PBMCs) were isolated, and monocytes were extracted, followed by their differentiation into immature dendritic cells (iDCs) using GM-CSF and IL-4. Harvested tumor cell lysates from human prostate cancer cells were then utilized to induce the transformation of iDCs into mature dendritic cells (mDCs). Then, mDCs were treated with non-toxic concentration of Bicalutamide determined by annexin V/PI assay. The morphological characteristics of mDCs were investigated using an inverted light microscope. Flow cytometry was used to determine the cell surface expression of molecular markers of DC maturation, and qRT-PCR was employed to evaluate expression levels of proinflammatory genes involved in DC maturation. The obtained results indicated that Bicalutamide treatment of monocyte-derived mDCs induces an immunogenic and matured phenotype, marked by increased expression of CD86 and HLA-DR. Besides, qRT-PCR results evidenced that Bicalutamide decreased the expression of anti-inflammatory genes, including Interleukin-10 (IL-10) and TGF-beta, as an indication of immunogenic DCs. These findings suggest that beyond its established anti-androgen role, Bicalutamide may exert anti-tumor effects through the modulation of DCs-mediated immune responses. This novel immunomodulatory feature holds promise for the development of novel therapies, including combination therapies, in prostate cancer treatment.

Linoleic Acid Modulates the Expression of Metastatic and Angiogenic Markers MMP-2 and Talin-2 in Gastric Cancer Cell Line MKN-45.

Background: Linoleic acid (LA) has modulatory effects on gastric cancer cell lines. This study aimed to investigate the effects of linoleic acid on the expression of metastatic and angiogenic molecular markers in gastric cancer cell line MKN-45. Methods: In this study performed in Tabriz, Iran in 2021, MKN-45 cells were treated with LA in the presence or absence of docetaxel. Total RNA was extracted, and cDNA synthesized from the cells before and after treatment. The expression levels of Talin-2 and MMP-2 genes and mir-20, mir-30, mir-126, and mir-194, were determined by quantitative real-time PCR. Results: LA treatment reduced the expression levels of mir-126, mir-194, mir-30, and MMP-2, while increased the expression levels of Talin-2 mRNA. Docetaxel treatment could decrease the expression levels of mir-20, Talin-2, and MMP-2 mRNA levels while increasing the expression levels of mir-126, mir-194, and mir-30. Additionally, the combined treatment of MKN-45 cells with LA and docetaxel could reduce the expression levels of mir-20 and mir-126 and increased the expression levels of mir-194, mir-30, Talin-2, and MMP-2 mRNAs. Conclusion: Modulation of the expression levels of gastric cancer involved microRNAs, Talin-2, and MMP-2 may be a mechanism through which LA may exert its biological effects on GC cell line MKN-45. LA may have an antimetastatic effect by reducing the MMP-2 expression and pro-angiogenic effect through increasing Talin-2 expression levels.

A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection.

Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.

BRD4 expression and its regulatory interaction with miR-26a-3p, DLG5-AS1, and JMJD1C-AS1 lncRNAs in gastric cancer progression.

Gastric cancer remains a significant health challenge despite advancements in diagnosis and treatment. Early detection is critical to reducing mortality, necessitating the investigation of molecular mechanisms underlying gastric cancer progression. This study focuses on BRD4 expression and its correlation with miR-26a-3p, DLG5-AS1, and JMJD1C-AS1 lncRNAs in gastric cancer. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed significant upregulation of BRD4 in gastric cancer tissues compared to normal tissues, correlating negatively with miR-26a-3p and positively with DLG5-AS1 and JMJD1C-AS1 lncRNAs. Quantitative RT-PCR confirmed these findings in 25 gastric cancer tissue samples and 25 normal samples. BRD4's overexpression was associated with reduced survival rates and older patient age. MiR-26a-3p, a known tumor suppressor, showed decreased expression in gastric cancer tissues, with ROC analysis suggesting it, alongside BRD4, as a potential diagnostic biomarker. Additionally, bioinformatics predicted miR-26a-3p's interaction with BRD4 mRNA. Upregulated lncRNAs DLG5-AS1 and JMJD1C-AS1 likely act as competing endogenous RNAs, sponging miR-26a-3p, thus promoting BRD4 dysregulation. These lncRNAs have not been previously studied in gastric cancer. The findings propose a novel BRD4/lncRNA/miRNA regulatory axis in gastric cancer, highlighting the potential of BRD4, DLG5-AS1, and JMJD1C-AS1 as biomarkers for early diagnosis. Further studies with larger sample sizes and in vivo and in vitro experiments are needed to elucidate this regulatory mechanism's role in gastric cancer progression.

The chimeric UreB, FliD and Omp18 proteins for a sensitive and specific diagnosis of Helicobacter pylori infections.

Background and Objectives: Helicobacter pylori is known as the main cause of gastrointestinal diseases including gastritis, gastric ulcer and stomach cancer. Serodiagnosis of H. pylori infection is a noninvasive and rapid method but the efficiency of this method is highly dependent to the antigens used. This study evaluated the efficacy of recombinant UreB-Omp18 and FliD for serodiagnosis of H. pylori infection. Materials and Methods: The genes encoding for fliD, ureB, and omp18 was amplified by PCR and cloned into pET-22b and pET-28a vectors. The constructs were expressed in E. coli BL21 and purified by affinity chromatography. The antigenic properties and diagnostic potential of the recombinant proteins were analysed by immunoblotting and ELISA, respectively. Results: The recombinant UreB-Omp18 and FliD with molecular weights of 48 kDa and 25 kDa were observed on SDS-PAGE and purified by the Ni-NTA column. The ELISA results showed that the sensitivity and specificity of recombinant UreB-Omp18 protein in serodiagnosis of H. pylori infection were 89% and 83%, respectively. Also, the sensitivity and specificity of the recombinant FliD protein were calculated to be 91% and 76%, respectively. Conclusion: The results indicated that the recombinant UreB-Omp18 and FliD could diagnose H. pylori infection with high sensitivity and specificity.

MicroRNA-143 overexpression enhances the chemosensitivity of A172 glioblastoma cells to carmustine.

As an aggressive malignancy, glioblastoma multiforme (GBM) is the most common type of brain tumor. The existing treatments have shown limited achievement in increasing the overall survival of patients. Therefore, identifying the key molecules involved in GBM will provide new potential therapeutic targets. Carmustine is an alkylating agent used as a supplementary therapeutic option for GBM. However, the extensive use of carmustine has been limited by uncertainty about its efficacy. MicroRNAs (miRNAs) are essential in post-transcriptional gene regulation. Many aberrantly expressed miRNAs have been detected in various types of human cancer, including GBM. In this study, we evaluated the potential therapeutic effect of miR-143 in combination with carmustine on GBM cells. A172 cells were transfected with miR-143 mimics and then treated with carmustine. To assess the cell viability, apoptosis induction, and cell cycle progression, the MTT assay, Annexin V/PI apoptosis assay, and flow cytometry were used, respectively. Furthermore, qRT-PCR assay was applied to evaluate the expression level of genes related to apoptosis. The obtained results evidenced that miR-143 transfection could promote the sensitivity of A172 cells to carmustine and enhance carmustine-induced apoptosis via modulating the expression levels of Caspase-3, Caspase-9, Bax, and Bcl-2. Also, our results revealed that combination therapy could effectively diminish cell cycle progression in A172 cells. In conclusion, these results confirmed that miR-143 could enhance carmustine-mediated suppression of cell proliferation and improve the chemosensitivity of A172 cells to this chemotherapeutic agent. Therefore, miR-143 combination therapy may be a promising GBM treatment approach.

Interaction of noncoding RNAs with hippo signaling pathway in cancer cells and cancer stem cells.

The Hippo signaling pathway has a regulatory function in the organogenesis process and cellular homeostasis, switching the cascade reactions of crucial kinases acts to turn off/on the Hippo pathway, altering the downstream gene expression and thereby regulating proliferation, apoptosis, or stemness. Disruption of this pathway can lead to the occurrence of various disorders and different types of cancer. Recent findings highlight the importance of ncRNAs, such as microRNA, circular RNA, and lncRNAs, in modulating the Hippo pathway. Defects in ncRNAs can disrupt Hippo pathway balance, increasing tumor cells, tumorigenesis, and chemotherapeutic resistance. This review summarizes ncRNAs' inhibitory or stimulatory role in - Hippo pathway regulation in cancer and stem cells. Identifying the relation between ncRNAs and the components of this pathway could pave the way for developing new biomarkers in the treatment and diagnosis of cancers.

Advancements in Melanoma Therapies: From Surgery to Immunotherapy.

OPINION STATEMENT: Melanoma is defined as the most aggressive and deadly form of skin cancer. The treatment of melanoma depends on the disease stage, tumor location, and extent of its spread from its point of origin. Melanoma treatment has made significant advances, notably in the context of targeted and immunotherapies. Surgical resection is the main therapeutic option for earlystage melanoma, and it provides favourable outcomes. With disease metastasis, systemic treatments such as immunotherapy and targeted therapy become increasingly important. The identification of mutations that lead to melanoma has influenced treatment strategies. Targeted therapies focusing on these mutations offer improved response rates and fewer toxicities than conventional chemotherapy. Furthermore, developing immunotherapies, including checkpoint inhibitors and tumor-infiltrating lymphocyte (TIL) therapies, has demonstrated encouraging outcomes in effectively combating cancer cells. These therapeutic agents demonstrate superior effectiveness and a more tolerable side-effect profile, improving the quality of life for patients receiving treatment. The future of melanoma treatment may involve a multimodal approach consisting of a combination of surgery, targeted therapy, and immunotherapy adapted to each patient's profile. This approach may improve survival rates and health outcomes.

CTLA-4 silencing could promote anti-tumor effects in hepatocellular.

Preclinical and clinical research showed that immune checkpoint blockade provides beneficial effects for many patients with liver cancer. This study aimed to assess the effect of CTLA-4-specific siRNA on the proliferation, cell cycle, migration, and apoptosis of HePG2 cells. Transfection of siRNA was performed by electroporation. The viability of cells was determined through MTT assay. Flow cytometry was performed to investigate the cell cycle and apoptosis rate, and the wound-healing assay was used to determine HepG2 cells migration. The expression levels of CTLA-4, c-Myc, Ki-67, BCL-2, BAX, caspase-9 (CAS9), and MMP-2,9,13 were measured by qRT-PCR. Transfection of specific CTLA-4-siRNA significantly inhibited the expression of the CTLA-4 gene. Also, our results revealed that CTLA-4 silencing diminished the proliferation and migration as well as induced the apoptosis of HePG2 cells. CTLA-4-siRNA transfection induced the cell cycle arrest in G2 phase. Moreover, CTLA-4-siRNA transfection reduced the expression levels of c-Myc, Ki-67, BCL-2, MMP-2,9,13, and elevated the expression levels of BAX and caspase-9. Our results suggest that silencing CTLA-4 through specific siRNA may be a promising strategy for future therapeutic interventions for treating liver cancer.

Altered gene expression of miR-155 in peripheral blood mononuclear cells of Multiple sclerosis patients: Correlation with TH17 frequency, inflammatory cytokine profile and autoimmunity.

In the chronic, organ-specific autoimmune disorder known as multiple sclerosis (MS), the myelin sheath is attacked by immune cells, leading to damage to the central nervous system (CNS). It has been discovered that miRNAs are important in the etiology of MS, since deregulation of miRNAs can lead to defects in immune tolerance. In this study, we sought to investigate the involvement of miR-155 in MS disorder through examination of its altered expression in peripheral blood mononuclear cells (PBMCs) of patients with MS in compare with healthy controls. Furthermore, we investigated the frequency of T helper 17 cells (Th17) in MS patients and analyzed not only the expression of inflammatory cytokines including IL-6, IL-17 and IL-21 in patients' PBMCs, but also their secreted levels in serum of patients suffering from MS. Subsequently, we assessed the correlation between miR-155 expression with Th17 frequency and levels of released cytokines in serum. Upregulated expression of miR-155 was detected in PBMCs of MS patients and the positive correlation between its expression with increased frequency of Th17 cells and their related inflammatory cytokine profile augmented secretion in serum were identified. In conclusion, our study revealed the significant association between Th17 frequency, increased level of cytokines related to Th17 differentiation and function with miR-155 augmented expression in PBMCs. So, our findings suggested that miR-155 and especially its expression in immune cells including effector T cells can be the target of future therapeutic strategies for the management and prevention of MS progression, however, further research is requisite before this approach can be utilized in clinical practice.

Dopamine receptor agonist cabergoline promotes immunogenic phenotype in human monocyte-derived dendritic cells.

Dendritic cells (DCs) are known as antigen-presenting cells that are capable of regulating immune responses. DCs and T cells can interact mutually to induce antigen-specific T-cell responses. Cabergoline, which is a dopamine (DA) receptor agonist, seems to implement anti-inflammatory properties in the immune system, and therefore in the present study the impact of a DA receptor agonist cabergoline on the monocyte-derived DCs (moDCs) was assessed. Immature moDCs were treated with lipopolysaccharide to produce mature DCs (mDCs). The expression of DCs' related surface markers namely: CD11c, HLA-DR, and CD86 was measured by utilizing of flow cytometry. Real-time PCR was the technique of choice to determine the levels at which diverse inflammatory and anti-inflammatory factors in cabergoline-treated and control mDC groups were expressed. DCs treated with cabergoline displayed a significant decrease in CD86 and HLA-DR expression, markers linked to maturation and antigen presentation, respectively. In addition, the cabergoline-mDC group showed a considerable decline in terms of the levels at which IL-10, TGF-ß, and IDO genes were expressed, and an increase in the expression of TNF-α and IL-12 in comparison to the mDC control group. Our findings revealed that cabergoline as an immunomodulatory agent can relatively shift DCs into an immunogenic state, and there is a requirement for further investigations to evaluate the effects of cabergoline-treated DCs on the T cell responses in vitro, and also in various diseases including cancer in animal models.