جستجوی مقالات مرتبط با کلیدواژه « cytokine » در نشریات گروه « پزشکی »

The endometriosis treatment was critical due to complications associated with current drug delivery system. The present study was conducted with aim to compare the curative effect of Vitamin D3 (VTD3) and Omega–3 (OG3) with Diphereline during the treatment of endometriosis.

In this study, endometriosis was induced in different groups containing 60 adult female rats. The rat model was categorized into 6 groups untreated and treated (Olive Oil (solvent), VTD3 (42 mcg/kg/day), OG3 (450 mg/kg/day), VTD3+OG3, Diphereline (3 mg/kg/day)). The suspension containing combination of Diphereline and supplements was injected and treated for 4 weeks to analyze the effect of supplements. The interleukin -6 (IL-6) and Tumor necrosis factor – alpha (TNFα) inflammatory responses were measured from the serum samples while endometrial implants was dissected and histopathological investigation was done.

At the end of four weeks, pathologic score decreased significantly with simultaneous measurement of inflammation score of endometriotic lesion, size of implant area, IL-6, TNFα response and compared with untreated female rat. No significant different was observed in groups undergoing treatment of VTD3, OG3 and Diphereline. The combined effect of VTD3+OG3 has similar responses with Diphereline treated endometrial implants.

treatment of VTD3 deficiency and making a change in dietary habits of high-risk population for endometriosis from adolescence may also play a preventative role in adulthood.

Besides the clinical and laboratory research on the COVID-19 virus, the bioinformatics study in the field of genetics of immunity to COVID-19 is of particular importance. In this account, studies show that in patients with COVID-19, the level of tumor necrosis alpha (TNFα) and interleukin-6 (IL-6) is high and in severe cases of COVID-19, the production of IL-6, TNF-α, and other cytokines increases profoundly. On the other hand, investigating the molecular structure and receptors of IL-6 and TNFα and the structural analysis of the receptor proteins may potentially help to develop new therapeutic plans for COVID-19 infection.

To identify genes with significant and different expressions in patients with COVID-19 in a microarray data set containing transcriptional profiles from GEO as a functional genomic database the GEO query package version 2.64.2 in a programming language R version 4.2.1 was downloaded. In this way, functional enrichment analysis for DEGs, WikiPathways, REGO, gene ontology, and STRING database was also investigated and employed.

The structure and function of pro-inflammatory cytokines TNFα and IL-6 involved in the pathogenesis of COVID-19 were investigated, and in general, after performing various analyses in this study and extracting A series of genes with different expressions from the KEGG database, the final 5 DEGs include CXCL14, CXCL6, CCL8, CXCR1, TNFRSF10, and the relationship and expression effects of them were observed in different pathways.

IL-6 and TNFα were involved in immunological processes that had a direct and indirect relationship with the activation of cytokines, including IL6 and TNF-a, and cytokine storm, and this indicates their role in the formation of problems and complications, including ARDS, in COVID-19 patients. Of course, determining the effectiveness of each of these genes requires more specialized and clinical studies.

Ulcerative colitis (UC) is an inflammatory bowel disease that leads to gastrointestinal ulcers. An overactive immune response against the intestinal microbiota has been suggested as one of the pathogenic factors. Some evidence indicates the immunomodulatory effects of Bifidobacterium lactis. sugarcane molasses, rich in vitamins and nutrients, can be used to compensate for the related nutrient deficiencies.

This study aims to evaluate the effects of sugar-free sugarcane (SFS)-molasses on the immune system of UC patients.

Bifidobacterium lactis was cultivated in MRS broth and killed by UV de-sugarization of sugarcane molasses. It was prepared using the Steffen method. Peripheral blood mononuclear cells (PBMCs) of 12 UC patients were separated by Ficoll-Hypaque centrifugation. Peripheral blood mononuclear cells, SFS-molasses, and B. lactis were co-cultured. After 18h, the expression level of the FOXP3 gene was assessed by RT-qPCR (real-time PCR). The interferon gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured in the supernatant of PBMCs by ELISA.

Transforming growth factor beta in the SFS-molasses group was significantly increased compared to the controls (P = 0.032). The TGF-β in SFS-molasses + bacteria and the bacteria-alone groups increased compared to the control group (P = 0.039 and P = 0.049, respectively). The level of IFN-γ in the SFS-molasses group was significantly decreased compared to the controls (P = 0.004). Interferon gamma increased in the SFS-molasses + B. lactis group compared to the controls, but this was not significant. Expression of FOXP3 wasn’t affected after SFS-molasses treatment.

These data showed that SFS molasses increases the levels of anti-inflammatory cytokine TGF-β and decreases the pro-inflammatory cytokine IFN-γ levels. These results may encourage researchers to continue studying the possible application of molasses as a nutritious food for patients with UC.

Pancreatic cancer commonly refers to Pancreatic Ductal Adenocarcinoma (PDAC) which accounts for more than 90% of pancreatic cancers (1). The substantial burden of disease is characterized by the approximate deaths of as many as cases annually. PDAC as the seventh leading cause of cancer-induced mortalities globally, has been a focal point of research in the field of oncology (2).Despite the vast research and significant effort devoted to the treatment of PDAC, the 5-year survival rate for this cancer remained less than 5%. This scant survival rate is a consequence of late-onset diagnosis, accelerated tumor growth, and limited extant treatments. Hence, innovative strategies, such as immunotherapy, seek to enhance antitumor immune reactions, offering a more precise and targeted therapeutic alternative (1).Immunotherapy is categorically segmented into four primary subtypes: vaccines, cellular therapies, cytokines, and antibodies, with Immune Checkpoint Inhibitors (ICIs) falling under the latter classification (3).Cancer vaccines stimulate immune responses by leveraging tumor-associated antigens to activate cytotoxic T-lymphocytes. These antigens can be sourced from whole-cell tumor lysates, recombinant tumor peptides, or recombinant viruses (1). Regarding vaccines, messenger RNA (mRNA) vaccines have been more promising than conventional vaccines, which present various challenges, for a personalized therapeutic approach in pancreatic cancer. These vaccines utilize the genetic profile of an individual’s tumors, particularly those with mutant Kras, and custom proteins can be encoded (3). KRAS as a proto-oncogene has been recognized as mutated among 90% of patients diagnosed with PDAC, making it a valid target. They enhance antitumor immunity against oncogenic KRAS by presenting oncogenic KRAS neoantigens to major histocompatibility complex molecules, leading to the generation of cancer-specific memory T cells with long-term efficacy. In terms of other vaccines that are under investigation regarding their efficacy in PDAC, telomerase vaccines, gastrin vaccines, survivin-targeting vaccines, heat-shock protein peptide complex-based vaccines, MUC-1 targeting vaccines, listeria-based vaccines, dendritic cell-based vaccines, Granulocyte-Macrophage Colony-Stimulating Factor (GMCSF)-allogeneic pancreatic tumor cells (GVAX) vaccines, and Hyper-Acute-Pancreas algenpantucel-L (HAPa), Mucin-1 (MUC-1) vaccines can be mentioned (4–6).Adoptive cell therapy is a rapidly growing technology consisting of NK cells or T cells that are either allogeneic or autologous. and have been genetically modified to target specific proteins using chimeric antigen receptors and T-cell receptors. These engineered cells are designed to recognize a peptide/MHC complex to effectively eliminate cancer cells. Numerous Chimeric Antigen Receptor (CAR) T-cell therapies have been approved for the treatment of different hematological malignancies. In PDAC, mesothelin CAR-T therapy has shown promise in preclinical mouse models by extending survival. However, the translation of this strategy to clinical settings for solid tumors faces various obstacles. To address these challenges, the development of next-generation CAR-T cells is underway to enhance the effectiveness of this therapy (3,7).Cytokine therapies, including the use of Interleukin-2 (IL-2) and Interferon alpha (IFN-α), have been utilized as an early form of immunotherapy in the management of malignant conditions, establishing them as foundational components of this treatment approach. Cytokines with immune stimulatory properties, including IL-2, IL-15, GM-CSF, and IFN-α, have been incorporated as adjunctive elements in comprehensive immunotherapy strategies for PDAC. While monotherapy with cytokines showed promise during the peri-operative period, no recent studies have been published on this subject in the last ten years (3,8).ICIs are monoclonal antibodies that target specific extracellular proteins expressed by tumor cells or tumor-associated lymphocytes, leading to the suppression of the body’s immune response against the cancer (1). To address some of the main ICIs, Anti-PD-1/Anti-PD-L1, Anti-CTLA-4, Anti-TIM-3, Anti-TIGIT, and Anti-LAG-3 can be mentioned. Anti-PD-1/Anti-PD-L1 blocks the PD-1 pathway in which PD-1 ligation induces self-tolerance by preventing the activation of T cells as well as their proliferation. In PDAC, despite other solid tumors, the efficacy of Anti-PD-1/Anti-PD-L1 as monotherapy was not as promising as its effectiveness in combination with chemotherapy. The inhibitory CTLA-4 receptor on T cells competes with the co-stimulatory receptor CD28 for binding to the CD80 and CD86 ligands on antigen-presenting cells (APCs). CTLA-4 has a higher affinity for these ligands. Lower levels of CTLA-4 and higher expression of CD80 in PDAC are associated with increased survival rates. Binding of CTLA-4 primarily inhibits the activation of naïve T cells in lymphoid organs, but may also hinder the direct anti-tumor activity of T cells in the effector phase, potentially by reducing the presence of suppressive regulatory T cells. Based on a previous study, the co-administration of GVAX with anti-CTLA-4 appears to stimulate a T cell-mediated immune reaction and could potentially enhance the survival rate of patients with advanced PDAC. Numerous clinical trials are currently underway to assess the efficacy of the combination of anti-CTLA-4 therapy with other immunotherapeutic agents and/or radiotherapy in the treatment of PDAC (8). Both PD-L1 and CTLA-4 are often overexpressed in a subgroup of PDAC and are associated with poorer survival outcomes, making them potential targets for therapeutic intervention (1).In conclusion, despite the aforementioned substantial investigations regarding therapeutic approaches for PDAC, treatment of this highly impacting disease is hampered by so many obstacles. Further research is necessary to overcome the remission-disrupting factors such as immunity evasions, altered tumor microenvironment, immunosuppressive activities, etc.Conflict of InterestThe authors had no competing interests.

Investigating the ameliorative effects of melatonin on cytokine levels, apoptosis, and NF-κB immunoreactivity in rats with cerulein-induced acute pancreatitis. Thirthy-two Wistar Albino rats were divided into four groups: Control group which didn’t undergo acute pancreatitis induction and was left without treatment, pancreatitis group in which the acute pancreatitis was induced by 2 successive intraperitoneal doses of cerulein at a 2-hour interval (50 µg/kg and then 25 µg/kg), melatonin-treated pancreatitis group which was intraperitoneally administrated with 50 mg/kg of melatonin, 30 min before each cerulein injection, and melatonin group which was intraperitoneally administrated with 2 successive doses of melatonin (50 mg/kg each) at a 2-hour interval. Pancreatic tissue and blood samples were taken from animals of all groups. IL-1β, TNF-α, and IL-10 levels were determined in blood samples. Apoptosis was determined by the TUNEL assay and the NF-κB was detected immunohistochemically in acinar cells of the exocrine pancreatic portion. IL-1β, TNF-α, and IL-10 levels in the acute pancreatitis group were significantly increased when compared to the control negative group. IL-1β and TNF-α levels in the melatonin-treated pancreatitis group were significantly lower than those of the acute pancreatitis group. While number of apoptotic cells and percentage of NF-κB immunopositive cells in the acute pancreatitis group were significantly increased compared to other groups and it was observed that these parameters were significantly reduced in the melatonin-treated pancreatitis group compared to the acute pancreatitis group. These findings suggest that melatonin administration can significantly reduce the severity of acute pancreatitis in rats.

Antiretroviral therapy (ART) should significantly improve the recovery of the immune system in Human immunodeficiency virus (HIV) infected patients. In some patients under ART, it was not possible to increase CD4+ cells reasonably in spite of effective virological control, which is known as discordant immune response (DIR). The aim of this study is the evaluation of the expression of C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 5 (CCR5), interleukin 12B (IL12B), cluster of differentiation 3(CD3), tumor necrosis factor alpha (TNFα), protein tyrosine kinase 2 beta (PTK2B), and t-cell receptor beta TCR β genes in patients with DIR.

In this case-control study, peripheral blood mononuclear cell (PBMC) specimens from patients of the two groups were isolated, RNA was extracted: patients of the control group who were immunologic responders and patients of the case group, which were non-immunologic responders. Real-time relative quantitative polymerase chain reaction (PCR) was performed in duplicate using One Step PrimeScript™ RT-PCR Kit and data analyzed by using GraphPad prism software version 8.0.2.

The expression levels in the patients of the case group in comparison with the patients of the control group were measured for CXCR4, CCR5, IL12B, TNF-α, CD3, PTK2B and TCR-β. The Fold change ratio for CCR5, TCR-β, and CD3 were (0.225), (0.12), (0.09), respectively, and in all three of them, a significant decrease was observed with confidence values. p <0.05, p <0.02 and p <0.01, respectively. None of the CXCR4, IL12B, TNF-α, and PTK2B was statistically significantly different and their fold change ratio was (1.01), (0.6), (1.04), and (0.718) respectively.

we showed significant decrease in the expression of CCR5, TCR-β, and CD3 genes in the patients of the case group in comparison with the patients of the control group, but we could not verify this low expression of these genes are the reason of the low CD4+ T-cell count. Further investigation is necessary, if the suppression of these genes can influence the proliferation or development of CD4 T cells, in-vitro.

Combined training play important role in improving body composition, but less is known about its anti-inflammatory mechanism in obesity. Researcher in the present study investigated the effect of three-month combined exercise training on the serum levels of interleukin-6 and C-reactive protein in sedentary obese women.

The 24 obese women age ranging 20-35 years old with average body mass index (BMI) 32.02±1.03 kg/m2 randomly allocated in 2 groups (12 participants in each group) including control and combined training (endurance-resistance) groups. Exercise training program conducted for 12 weeks and three session per week. Endurance training intensity was 60 percent of reserve heart rate and resistance training intensity was 75 percent of 1RM. Blood samples collected before and after 12 weeks training program and IL-6 and CRP levels were measured by Elisa method. Data were analyzed by means of SPSS software version 24 with analysis of covariance test.

Present study findings indicated that serum levels of IL-6 in combined training group significantly decreased compared to control group (P < 0.001). In addition, significant decrease in CRP levels were observed in combined training group compared to control group (P = 0.0188), which decrease in inflammatory mediators was associated with significant decrease in percent body fat in combined training group (P < 0.001).

According to present study, combined training plays an important role in down-regulation of inflammatory mediators and the anti-inflammatory effect may be related to decrease in body fat mass as a main source for secreting the inflammatory mediators including CRP and IL-6.

Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes. To investigate ginger extract’s effect on reducing inflammation and improving the symptoms in the EAE model. The EAE was induced by injecting MOG35-55 and pertussis toxin into eight-week-old female C57BL6 mice. The mice were treated with an intraperitoneal injection of 300 mg/kg/day of hydroalcoholic extract of ginger for 21 days. The disease severity and weight changes were measured daily. Then, the mice spleens were removed; the gene expressions of interleukin (IL)-17, transforming growth factor beta (TGF-β), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) were analyzed by Real-time PCR and the percentage of regulatory T lymphocytes (Treg cells) was determined by flow cytometry. Serum nitric oxide and antioxidant capacity were measured, and brain tissue sections were prepared to investigate the leukocyte infiltration and plaque formation. The severity of symptoms in the intervention group was lower than in the control. The gene expression levels of inflammatory cytokines, including IL-17 (P=0.04) and IFN-γ (P=0.01), were reduced. The Treg cells increased significantly, and the serum nitric oxide level was lower in the ginger-treated group. There was no significant difference in lymphocyte infiltration in the brain between the two groups. The present study indicated that ginger extract could effectively reduce inflammatory mediators and modulate immune responses in EAE.

NK cells are defined as the major components of the immunological network which exerts defense against tumors and viral infections as well as regulation of innate and adaptive immunity, shaped through interaction with other cells like T cells. According to the surface markers, NK cells can be divided into CD56dim NK and CD56bright NK subsets. CD56bright NK cells usually are known as regulatory NK cells. Once the immune system loses its self-tolerance, autoimmune diseases develop. NK cells and their subsets can be altered during autoimmune diseases, indicative of their prominent regulatory roles and even pathological and protective functions in autoimmune disorders. In this regard, activation of CD56bright NK cells can suppress activated autologous CD4+ T cells and subsequently prevent the initiation of autoimmunity. In this review article, we summarize the roles of regulatory NK cells in autoimmune disease occurrence which needs more research to uncover their exact related mechanism. It seems that targeting NK cells can be a promising therapeutic platform against autoimmune diseases.

Scorpion venom contains various biological compounds. Clinical symptoms in individuals and laboratory animals exposed to scorpion venom depend on the response of the host immune system. The secretion of inflammatory cytokines is one of the most critical factors involved in the pathogenesis of scorpion venom. This comparative study aimed to evaluate the expression of inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 in rats treated with Hottentotta saulsyi scorpion venom. The venom was obtained from the Razi Vaccine and Serum Research Institute of Ahvaz branch. After determining the H. saulsyi venom LD50, the rats were divided in two groups of test and control (n-12). The test group received 1/3 LD50 dose in 0.5 ml of physiological serum by subcutaneous injection per rat. The exact amount of physiological serum was injected into the control group. After that, cardiac blood samples were taken from rats at 0, 4, 24, and 72 hours after anesthesia. After serum preparation, the levels of IL-10 and IL-6 cytokines were measured in both groups using ELISA assays. The obtained LD50 equaled 1.01 mg/kg of the rat’s body weight. Four hours after experimentally envenomation, the serum levels of IL-6 and IL-10 were significantly increased compared to the control group (P <0.05); but in the taken samples 24 hours after the treatment, there was no significant difference compared to the control group. During 72 hours, the level of these cytokines decreased in the treatment group compared to the control group. Changes in inflammatory and anti-inflammatory cytokines levels during scorpion stings can be used as a novel clinical finding to assess patients' status and perform appropriate therapeutic interventions to reduce scorpion sting complications.

The coronavirus disease 2019 (COVID-19) pandemic has prompted researchers to look for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenicity in depth. Immune system dysregulation was one of the major mechanisms in its pathogenesis. The evidence regarding the levels of interferons (IFNs) and pro- and anti-inflammatory cytokines in COVID-19 patients is not well-established.

This study evaluated the expression level of type-I, II, III IFNs, along with interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), and FOXP3 genes in patients with severe COVID-19 to provide additional insights regarding the regulation of these cytokines during COVID-19 infection.

Peripheral blood mononuclear cells were isolated from two groups, including severe COVID-19 patients and healthy controls. Ribonucleic acid was extracted to evaluate the expression level of IFN-a, IFN-b, IFN-g, IFN-la, IL-1, IL-6, IL-10, and FOXP3 genes using real-time polymerase chain reaction. The correlations between the expression levels of these genes were also assessed.

A total of 40 samples were divided into two groups, with each group consisting of 20 samples. When comparing the severe COVID-19 group to the controls, the expression levels of IFN-g, tumor necrosis factor-alpha (TNF-), IL-6, and IL-10 genes were significantly higher in the severe COVID-19 group. The two groups had no significant differences in IFN-a, IFN-b, IFN-la, IL-1, and FOXP3 expression. The correlation analysis revealed a negative correlation between type I and type III IFNs (i.e., IFN-a and IFN-la) and proinflammatory cytokines (i.e., IL-1 and IL-10).

This study suggests the possible upregulation of IFN-g, IL-6, IL-10, and TNF-during SARS-CoV-2 pathogenicity. The preliminary findings of this study and those reported previously show that the levels of IFNs and pro- and anti-inflammatory cytokines are not uniformly expressed among all COVID-19 patients and might differ as the disease progresses to the severe stage.

Sesamol is a phenolic lignan extracted from sesame seeds, and it possesses anti-inflammatory and antioxidant activities. Lipopolysaccharide (LPS) is known to produce neuroinflammatory responses and memory impairment. The current study aimed to investigate the protective influence of sesamol against LPS-mediated neuroinflammation and memory impairment. Sesamol (10 and 50 mg/kg) was injected to Wistar rats for two weeks. Then, animals received LPS injection (1 mg/kg) for five days, while treatment with sesamol was performed 30 min before LPS injection. Spatial learning and memory were assessed by the Morris water maze (MWM), two hours after LPS injection on days 15-19. Biochemical assessments were performed after the end of behavioral experiments. LPS-administered rats showed spatial learning and memory deficits, since they spent more time in the MWM to find the hidden platform and less time in the target quadrant. Besides these behavioral changes, tumor necrosis factor-α (TNF-α) and lipid peroxidation levels were increased, while total thiol level was decreased in the hippocampus and/or cerebral cortex. In addition, sesamol treatment (50 mg/kg) for three weeks decreased the escape latency and increased the time on probe trial. Sesamol also reduced lipid peroxidation and TNF-α level, while enhanced total thiol level in the brain of LPS-exposed rats. Supplementation of sesamol attenuated learning and memory impairments in LPS-treated rats via antioxidative and anti-inflammatory activities in the rat brain.