IL-10 Gene Expression Research Articles

P1257: MOLECULAR CHARACTERIZATION AND CLONAL EVOLUTION OF MYCOSIS FUNGOIDES

Background: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma with a frequency of over 50% of all cases. MF has an indolent progression over several years through different stages. Symptoms evolve from a non-aggressive “low-risk” (LR) clinical form to an aggressive and treatment-resistant “high-risk” (HR) form. Approximately 20% of patients with MF evolve to a HR MF with transformed cells (tMF), which is associated with a poor prognosis. Aims: At the molecular level, the genomic landscape of MF remains poorly studied. Furthermore, the mechanisms that determine the progression to HR and tMF are still unknown. Methods: We performed whole exome sequencing (WES) of 70 samples from 48 patients at the University Hospital Center (CHU) of Lille, France, between 2007 and 2018. Some patients have multiple sequential samples over several years, with or without progression from LR to HR. Sequencing was performed on the Illumina NovaSeq 6000 system at the Broad Institute (BI) Genomics Platform. The bioinformatics analysis was performed on the Terra platform (BI), which includes tools for the analysis of genomic data. Copy number variations (CNVs) are detected with ModelSegments software in Tumor-Only mode and common large and focal CNVs in the cohort are highlighted by GISTIC2.0. Single nucleotide variants (SNVs) were detected with the CGA WES Characterization Pipeline (Getz lab, BI). Significantly mutated genes were determined by MutSig2CV. The mutational signature was performed with SignatureAnalyzer software. Subsequently ABSOLUTE software is used to calculate the cancer cells fraction of each variant and CNVs in order to follow the clonal evolution of sequential samples. Results: Somatic mutation analysis at the time of diagnosis detected genes involved in T-cell oncogenesis, by order of frequency: the transcription factor JUNB, the MAP kinase member MAPK1, the JAK/STAT member STAT5A and the epigenetic regulators of DNA SUZ12 and TET2. Mutational signatures were represented by the COSMIC SBS1, SBS7, and SBS15, characterized by aging, ultraviolet (UV) exposure, and defective DNA mismatch repair and microsatellite instability, respectively, suggesting their role in the mutational process of MF oncogenesis. The analysis of the CNVs revealed focal deletions affecting genes involved in ER stress TMEM259 (cytoband 19p13.3), the tumor suppressor gene TP53 (17p13.1), the transcriptional repressor gene ZEB1 (10p11.22) which inhibits interleukin 2 IL-2 gene expression, the TNFAIP3 gene (6q16.3) which inhibits nuclear factor kappa B (NF-kB), and the CDKN2A and MTAP genes (9p21.3) which are frequently co-deleted in cancers. The single focal amplification identified a small cytoband in 10p15.1 that carries the genes encoding the interleukin 2 receptor alpha (IL2RA) and interleukin 15 receptor alpha (IL15RA) which have a central role in T cell survival and proliferation. Clonal evolution analysis established that del10p11.22, amp10p15.1 and triplication of chromosome 7 are present only in HR stage, suggesting their role in the tumor progression. Overall survival analysis shows that amp10p15.1 and del10p11.22 – both associated with IL2 pathway - are significantly associated with reduced survival. Summary/Conclusion: WES data from MF identified key CNVs events of oncogenesis and clonal evolution of MF that could serve as predictive markers in clinical practice. Our findings clarify MF genetics and provide novel insights into the disease progression.

Transcription Factor AhR, Cytokines IL-6 and IL-22 in Subjects with and without Peri-Implantitis: A Case Control-Study.

Peri-implantitis is a plaque-associated condition characterized by mucosal inflammation and subsequent progressive loss of supporting bone; it is caused by bacterial biofilm, but the host response triggered by bacterial stimulation promotes the release of cells and mediators that culminate in tissue destruction. The Aryl-hydrocarbon Receptor (AhR) is associated with IL-22 production by Th22 and Th17 CD4+ Th cells. The presence of IL-6 may promote the Th22 phenotype. The present case-control study evaluated the gene expression of AhR, IL-22, and IL-6 in the peri-implant tissues of healthy and peri-implantitis patients. Tissue biopsies were collected from thirty-five volunteers (15 healthy and 20 with peri-implantitis). A real-time PCR reaction was utilized to assess the AhR, IL-22, and IL-6 gene expression levels relative to the reference gene (GAPDH). The results were analyzed using the Mann–Whitney test with a significance level of 5%. Higher levels of gene expression of AhR and IL-6 were detected in peri-implantitis tissues. The IL-22 gene expression levels did not differ between groups. In conclusion, higher gene expression levels for AhR and IL-6 were detected in the soft tissues of peri-implantitis patients. IL-22 did not vary between conditions, which may indicate the loss of the immunomodulatory role of IL-22 in periimplantitis.

Role of IL-23 gene expression in development of psoriatic arthritis among psoriasis patients

Background: Psoriasis (PS) is an inflammatory skin disorder that lasts for a long time. About 30% of peoples with psoriatic arthritis and characterized as inflammatory arthritis that affects joints or entheses. Although there is growing evidence that interleukin-23 is a kind of interleukin that is produced by (IL-23) Signaling is important in the pathophysiology of both PS and PsA, it is unclear whether IL-23-induced skin inflammation causes joint disease. The goal of this research is to determine the expression of genes (IL-23) in PsA patients in Basrah. Material and Methods: The current study included 88 participants, 59 of whom had Poraisis (Ps), 29 of whom had Psoriatic arthritis, and 40 healthy controls (HC). From August 2020 to February 2022, samples were collected from patients at Al-Sadar Teaching Hospital and Basrah Teaching Hospital's Rheumatology Unite and Biological Therapy Center. Total RNA was collected from peripheral blood and used to evaluate the expression of the genes of interest using qRT-PCR. Results: The binding of the SYBR green dye was unique to the target genes through one peak in the melting curve data and amplification curve for the genes of interest, which included IL-23.

Molecular phenotypes of colorectal cancer.

e15506 Background: Despite the positive results of colorectal cancer treatment, there is a group of patients that progresses despite successful treatment for I–II stage of the disease. it may be that modern predictors in do not fully cover the entire spectrum of molecular genetic traits, especially the tumor microenvironment. Perhaps expression analysis is not only tumor tissue, but resection margin could also reach a consensus on the molecular gene phenotypes of colorectal cancer with the achievement of the goal of prognostic efficiency and therapeutic and prophylactic diagnostic tactics. Methods: The expression level of 64 genes in tumor tissue in samples obtained from 172 patients with stage I–III CRC was analyzed by real-time Polymerase chain reaction (PCR). The mean follow-up time was 28.15±14.7 months. Data analysis and predictive modeling arrays using the R 3.6.3 Computation Evaluation Framework (R Foundation for statistical computing, Vienna, Austria) using additional packages rms 5.1-4, survival 3.2-7 and pROC 1.16.2. Results: As a result of statistical analysis, data were obtained on the presence of predictors of the studied unfavorable source code among the selected sets of genes carcinogenesis in colorectal cancer. The next step revealed progression status with BIRC5, IL2, SCUBE2, MYC and P16INK4A gene expression as in tissues tumors, and in resection margin. 2 regression models were built to predict survival without progression in patients with the inclusion of the level of expression in the tumor tissue- nor, the inclusion of the level of gene expression in tumor and resection margin. Model with inclusion only tumor transcripts statistics did not differ from models without predictors. Conclusions: In this study, it was possible to identify a group of genes associated with certain favorable prognosis and responsible in one way or another for proliferation, angiogenesis, immune status of the tumor. It can be concluded that the study of the level of expression of numerical genes in tumor tissue can become a promising direction for the selection of patients in the group of poor prognosis in colorectal cancer.

The Efficacy of Encapsulated Gamma-Cyclodextrin/Tributyrin on Growth and Inflammation in a Dextran Sodium Sulfate-Challenge Piglet Model

ObjectivesInflammatory bowel diseases are common in adults, and their incidence is increasing in children. Butyrate, a short chain fatty acid, can improve gut health, but its bitterness limits incorporation into foods. Herein, the efficacy of tributyrin (TB), a butyrate analog, encapsulated with ɣ-cyclodextrin (ɣ-CD) on growth and intestinal inflammation in a piglet model of dextran-sodium sulfate (DSS)-induced colitis was investigated. MethodsTwo-day-old piglets were randomized to three diets: control (formula alone, CON, N = 41), CD (CON + 9.0 mM ɣ-CD, N = 41), or CDTB (CON + 9.0 mM ɣ-CD/TB, N = 43). Half of the piglets in each group received DSS (1.25 g/kg body weight) from postnatal day (PND) 14 to 18. Blood and intestinal samples were collected on PND 19 and 27. IL-6 and TNF-α concentration in serum and colon mucosa were assessed by ELISA and IL-6, TNF-α, IL-10 and IFN-γ gene expression in colonic tissue were measured by qPCR. A quantitative histological grading system was used to assess 4 independent parameters: epithelial lining, cell infiltration, crypt damage and extent of the intestinal section affected. ResultsAverage daily weight gain (WG) between PND2-10 and 10–19 were affected by diet (P < 0.05), while colitis led to lower WG from PND19-27. A diet and colitis interaction indicated that after PND22 CDTB-COL piglets weighed less than CON and CD (P = 0.051). Diet had no impact on the descending colon (DC) morphology in the colitis animals, but the severity of the DC inflammation increased from PND19 and 27 (P < 0.0001). TNF-α and IL-6 concentrations were elevated in the ascending colon (AC) at PND19, but by PND27 concentrations were similar to non-colitis levels. A similar pattern was found in the DC, except that IL-6 remained elevated on PND27. IL-6, TNF-α and IFN-γ gene expression were significantly higher in the DC of colitis vs. non-colitis animals on PND27. Diet and colitis had no effect on serum TNF-α and IL-6. ConclusionsThe piglet as a model of DSS colitis is a feasible alternative to rodents. Dietary ɣ-CD/TB reduced growth rate and did not ameliorate the inflammatory process of DSS-induced colitis in neonatal pigs. Herein, oral administration of encapsulated TB did not reduce DSS-induced tissue damage or inflammation, however, additional studies are needed to confirm these observations. Funding SourcesNIFA, ISDA 2017–67,017-26,519.

Wheatgerm Supplementation Reduces Gut Inflammation and Epithelial Barrier Dysfunction in IL-10 KO Mice Fed Atherogenic Diet

Abstract Objectives Wheat germ (WG) contains many bioactive compounds with the potential to maintain an anti-inflammatory gut environment. This study investigated the effects of WG supplementation on gut inflammation and integrity in high-fat fed interleukin (IL)-10 KO mice. Methods Eight-wk-old female B6.129P2-Il10tm1Cgn/J (IL-10KO) and C57BL/6 (WT) mice (n = 10/group) were randomly assigned to diets: WT fed a control diet (WTCO; AIN93-M) and IL-10 KO mice fed control (KOCO), high-fat with high-cholesterol (HFHC; 45% fat kcal, 1% cholesterol), or HFHC + 10% WG (HFWG) for 3 m. Disease activity indices (fecal blood, ruffled fur, stool softness, and rectal prolapse) were monitored twice a week. Fecal indole and short chain fatty acids (SCFAs) concentration were assessed at the beginning and end of study. Proinflammatory cytokines were assessed in the serum and ileum. Ileal and colonic protein expression of transcription factors (STAT3, p-STAT3, PPARg, FoxP3, and AhR), tight junction proteins (ZO-1, occludin), and tryptophan catabolizing enzyme (IDO-1) were assessed by immunoblotting. Relative ileal and colonic gene expression of IL-22 and antimicrobial peptides (Reg3b and Reg3g) were assessed using qRT-PCR. P &amp;lt; 0.05 was considered statistically significant. Results WG increased (P = 0.003) colon length compared to the HFHC group. Weight loss (12.2% in HFHC vs WTCO) was not prevented by WG, but disease activity indices were significantly reduced in the WG vs HFHC group. WG also increased fecal indole, total SCFAs and acetate accompanied by an increase in colonic protein expression of PPARg (P &amp;lt; 0.0001) and FoxP3 (P = 0.001). Ileal STAT3 phosphorylation was reduced (P = 0.0076) due to WG supplementation. An increased colon and ileal protein expression of IDO-1 in the HFHS group was reduced by WG, while also increasing the expression of AhR, ZO-1, and occludin. The relative gene expression of the antimicrobial peptides (Reg3b and Reg3g) was increased (P &amp;lt; 0.05) while serum and ileal tissue concentration of the proinflammatory cytokine, IL-17 was reduced (P = 0.0165 and p = 0.0248 respectively) by WG. Conclusions WG modulated changes that are associated with HF-feeding in IL-10 KO mice, and might be a promising regimen for ameliorating the effects of gut inflammation. Funding Sources Oklahoma Agriculture Experiment Station, Jim and Lynn Williams Professorship, and Barbara K. Pass Grant.

Mannan-Binding Lectin Promotes Murine Graft-versus-Host Disease by Amplifying Lipopolysaccharide-Initiated Inflammation

Conditioning regimens used for hematopoietic stem cell transplantation (HCT) can escalate the severity of acute T cell-mediated graft-versus-host disease (GVHD) by disrupting gastrointestinal integrity and initiating lipopolysaccharide (LPS)-dependent innate immune cell activation. Activation of the complement cascade has been associated with murine GVHD, and previous work has shown that alternative pathway complement activation can amplify T cell immunity. Whether and how mannan-binding lectin (MBL), a component of the complement system that binds mannose as well as oligosaccharide components of LPS and lipoteichoic acid, affects GVHD is unknown. In this study, we tested the hypothesis that MBL modulates murine GVHD and examined the mechanisms by which it does so. We adoptively transferred C3.SW bone marrow (BM) cells ± T cells into irradiated wild type (WT) or MBL-deficient C57Bl/6 (B6) recipients with or without inhibiting MBL-initiated complement activation using C1-esterase inhibitor (C1-INH). We analyzed the clinical severity of disease expression and analyzed intestinal gene and cell infiltration. In vitro studies assessed MBL expression on antigen-presenting cells (APCs) and compared LPS-induced responses of WT and MBL-deficient APCs. MBL-deficient recipients of donor BM ± T cells exhibited significantly less weight loss over the first 2 weeks post-transplantation weeks compared with B6 controls (P < .05), with similar donor engraftment in the 2 groups. In recipients of C3.SW BM+T cells, the clinical expression of GVHD was less severe (P < .05) and overall survival was better (P < .05) in MBL-deficient mice compared with WT mice. On day-7 post-transplantation, analyses showed that the MBL-deficient recipients exhibited less intestinal IL1b, IL17, and IL12 p40 gene expression (P < .05 for each) and fewer infiltrating intestinal CD11c+, CD11b+, and F4/80+ cells and TCRβ+, CD4+, CD4+IL17+, and CD8+ T cells (P < .05 for each). Ovalbumin or allogeneic cell immunizations induced equivalent T cell responses in MBL-deficient and WT mice, demonstrating that MBL-deficiency does not directly impact T cell immunity in the absence of irradiation conditioning. Administration of C1-INH did not alter the clinical expression of GVHD in preconditioned WT B6 recipients, suggesting that MBL amplifies clinical expression of GVHD via a complement-independent mechanism. WT, but not MBL-deficient, APCs express MBL on their surfaces. LPS-stimulated APCs from MBL-deficient mice produced less proinflammatory cytokines (P < .05) and induced weaker alloreactive T cell responses (P < .05) compared with WT APCs. Together, our data show that MBL modulates murine GVHD, likely by amplifying complement-independent, LPS-initiated gastrointestinal inflammation. The results suggest that devising strategies to block LPS/MBL ligation on APCs has the potential to reduce the clinical expression of GVHD.

The in vitro effects of vitamin 1, 25(OH) 2 D3 on expression of cytokines: In new-onset systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a variety of factors in the immune system. Awareness of the role of cytokines in SLE has led to new clinical perspectives in its pathogenesis; therefore, the aim of this study was to investigate the effect of vitamin 1, 25(OH) 2 D3 (D3) on the expression of IL-2, IL-4, IL-5, IL-10, and IFN-γ cytokines in patients with lupus. A total of 65 new-onset SLE patients were enrolled in the study. After peripheral blood mononuclear cell isolation, the lymphocytes of each patient were divided into two groups, one treated with a concentration of 50μmol vitamin D3 (test) and the other untreated with vitamin D3 (control), were cultured. After 24hours, the cultured cells were collected and the expressions of IL-2, IL-4, IL-5, IL-10, and IFN-γ genes were analyzed by RT-qPCR. It was observed that vitamin D3 reduced expression of IFN-γ, IL-4, IL-5, and IL-10 genes by 73, 50, 37, and 29%, respectively, and increased IL-2 gene expression by 31% (p ≤ 0.05). With different patterns of cytokine changes in patients with lupus in different studies, it seems that the pattern of cytokine changes is largely dependent on the phase of the disease and with this study it can be concluded that vitamin D3 administration at the time of diagnosis and in the early stages and before starting treatment have different effects from its administration in the acute stage of the disease, which requires further studies to prove. It seems that in patients with systemic lupus erythematosus, vitamin D should be administered taking into account the phase of the disease.

TNF-alpha, IL-6, IL-10 and fatty acids in rheumatoid arthritis patients receiving cDMARD and bDMARD therapy.

The present study aimed to examine the effects of cDMARD and bDMARD therapy on both gene expressions and protein levels of TNF-α, IL-6, IL-10 and fatty acid levels in patients with RA. Plasma TNF-α, IL-6, and IL-10 levels were examined by the ELISA method, while TNF-α, IL-6, and IL-10 gene expression levels were examined by RT-qPCR, and fatty acid levels were examined by GC/MS. IL-10 gene expression levels significantly increased in RA patients receiving cDMARD treatment compared to those of the control group. Also, eicosadienoic acid, myristoleic acid and capric acid levels were significantly lower in the patient groups compared to those in the control group. The drugs used in the treatment of RA had no effect on the fatty acid levels whereas had effects on the mRNA and protein levels of the target cytokines.

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection.

One of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice. Two months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-β gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2. This study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.

Immunomodulatory Effect of SINA 1.2 Therapy Protocol in Asthmatic Mice Model: A Combination of Oxymel and Sauna.

Alternative medicine, has become popular in asthmatic patients. We evaluated the immunomodulatory effects of SINA 1.2 therapy protocol derived from Persian medicine in an asthmatic mice model. Forty-two male BALB/c mice divided into six groups: one control (sham) and five sensitized groups (by parenteral injection of 20 μg ovalbumin in 100 μL normal saline plus 50 μL alum on days 1 and 14). Sensitized groups were as: untreated, budesonide (1 mg nebulized budesonide: 200 μg/puff every 5 min for 25 min), dry sauna (30 min, 37°C), oral oxymel (gavaged: 0.2 mL of the syrup plus 0.8 mL of water), and SINA protocol No.1.2 (oxymel followed by sauna) groups. Treatments were given for 10 days from day 23 to 33 then sacrificed. Significant gene expression reduction of interleukin(IL)-4, IL-5, and MUC5AC and increase of interferon(IFN)-γ and IFN-γ/IL-4 ratio and decreased perivascular and peribronchial inflammation, goblet cell hyperplasia, and subsequent mucus hypersecretion in SINA group were seen compared to untreated group. SINA lowered IL-5 and MUC5AC gene expression levels similar to the budesonide and acted better than budesonide in increasing IFN-γ gene expression up to normal level. Compared with the asthma group, sauna alone only affected MUC5AC and IFN-γ gene expressions and oxymel alone, only reduced IL-4 gene expression, perivascular and peribronchial inflammation, and mucus hypersecretion. It seems that SINA therapy alleviates asthma via immune modulation of pro-inflammatory cytokines and improvement of pathological changes in ovalbumin-induced asthma in mice, supporting the notion of innate healing power mentioned in Persian medicine literature.

Peripheral blood mononuclear cell gene expression and cytokine profiling in patients with intermittent claudication who exhibit exercise induced acute renal injury.

BackgroundIntermittent claudication (IC) is a common manifestation of peripheral arterial disease. Some patients with IC experience a rise in Urinary N-acetyl-β-D-Glucosaminidase (NAG)/ Creatinine (Cr) ratio, a marker of renal injury, following exercise. In this study, we aim to investigate whether peripheral blood mononuclear cells (PBMC) from patients with IC who exhibit a rise in urinary NAG/ Cr ratio following exercise exhibit differential IL-10/ IL-12 ratio and gene expression compared to those who do not have a rise in NAG/ Cr ratio.MethodsWe conducted a single center observational cohort study of patients diagnosed with IC. Blood and urine samples were collected at rest and following a standardised treadmill exercise protocol. For comparative analysis patients were separated into those with any rise in NAG/Cr ratio (Group 1) and those with no rise in NAG/Cr ratio (Group 2) post exercise. Isolated PBMC from pre- and post-exercise blood samples were analysed using flow cytometry. PBMC were also cultured for 20 hours to perform further analysis of IL-10 and IL-12 cytokine levels. RNA-sequencing analysis was performed to identify differentially expressed genes between the groups.Results20 patients were recruited (Group 1, n = 8; Group 2, n = 12). We observed a significantly higher IL-10/IL-12 ratio in cell supernatant from participants in Group 1, as compared to Group 2, on exercise at 20 hours incubation; 47.24 (IQR 9.70–65.83) vs 6.13 (4.88–12.24), p = 0.04. 328 genes were significantly differentially expressed between Group 1 and 2. The modulated genes had signatures encompassing hypoxia, metabolic adaptation to starvation, inflammatory activation, renal protection, and oxidative stress.DiscussionOur results suggest that some patients with IC have an altered immune status making them ‘vulnerable’ to systemic inflammation and renal injury following exercise. We have identified a panel of genes which are differentially expressed in this group of patients.

Astaxanthin Attenuates D-Galactosamine-Induced Pancreatic Injury by Activating Antioxidant Enzymes and Inhibiting VEGF-C Gene Expression.

&lt;b&gt;Background and Objective:&lt;/b&gt; Astaxanthin (3,3'-dihydroxy-β-β-carotene-4,4'-dione) is a carotenoid, commonly found in marine environments has been reported to possess versatile biological properties including anti-inflammatory and antioxidant. In this study, the pancreatic protective effect of astaxanthin was investigated in D-Galactosamine-induced pancreas injury in rats. &lt;b&gt;Materials and Methods:&lt;/b&gt; In this experimental study, MTT assay was used to determine cytotoxic effects of the Astaxanthin on pnc1 cells. A total of 30 adult albino rats divided into 5 groups, six rats in each. Group I was given an equal amount of distilled water, group II was received 400 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. D-galactosamine on 15th day, groups III-V were treated with astaxanthin (50 and 100 mg kg&lt;sup&gt;1&lt;/sup&gt;) and/or silymarin (50 mg kg&lt;sup&gt;1&lt;/sup&gt;) for 14 days + 400 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt. D-galactosamine on the 15th day, respectively. &lt;b&gt;Results:&lt;/b&gt; IC&lt;sub&gt;50 &lt;/sub&gt;of Astaxanthin against the pnc1 cell line was 92.9 μg mL&lt;sup&gt;1&lt;/sup&gt;. The daily oral administration of astaxanthin (50 and 100 mg kg&lt;sup&gt;1&lt;/sup&gt;) as well as silymarin (50 mg kg&lt;sup&gt;1&lt;/sup&gt;) for 14 days to rats treated with D-galactosamine resulted in a significant improvement in plasma AST, ALT, ALP as well as pancreatic TNF-α, IL-1β, IL-10, NO and VEGF-C gene expression. On the other hand, inducible oral administration of astaxanthin increased the activity of pancreatic GSH, SOD, GPx, GR, CAT and the level of TBARs in D-galactosamine-treated pancreatic of rats. Furthermore, Astaxanthin almost normalized these effects in pancreatic tissue histoarchitecture and MRI examination. &lt;b&gt;Conclusion:&lt;/b&gt; The obtained results showed that Astaxanthin protected experimental animals against D-galactosamine-induced pancreatic injury through activation of antioxidant enzymes and IL-10 and inhibition of VEGF-C activation.

Extremely low frequency electromagnetic fields exposure during the prenatal and postnatal periods alters pro-inflammatory cytokines levels by gender

ABSTRACT Maternal exposure to the excessive electromagnetic fields is considered harmful to infants and associated with several health problems in life, such as neurological or immune diseases. In this present study we aimed to investigate the potential effects of extremely low-frequency electromagnetic field (ELF-EMF) exposure during the gestational and lactational period of dams on immune system parameters. The development of white blood cells (WBC), lymphocyte subpopulations (CD4+ T cells, CD8+ T cells, Natural Killer (NK) cells, and B cells) and production of T cell related cytokines were explored in the offsprings. Significant changes were found in WBC and lymphocyte counts. Although no changes in lymphocyte subunits were observed among groups, CD4+ cells were significantly increased in the female group exposed to ELF-EMF. Also, IL-17A and IFN-γ levels increased in plasma and spleen. The mean IL-4 level and the expression level of the IL-4 gene were not changed, in the experimental groups. But the expression of the IL-17A gene was also upregulated, which supports cytokine quantification analyses. In conclusion, ELF-EMF exposure in the prenatal and postnatal period increases the level of IL-17A in the spleen and blood of young female rats, and it upregulates IL-17 gene expression in the spleen, resulting in CD4+ cell proliferation and inflammation.

ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses.

CD8+ T cells are critical for the immune response to pathogens and tumors, and CD8+ T cell memory protects against repeat infections. In this study, we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of CD8+ T cell immune responses. Mice with a T cell-specific deletion of ATF7ip have a CD8+ T cell-intrinsic enhancement of Il7r expression and Il2 expression leading to enhanced effector and memory responses. Chromatin immunoprecipitation sequencing studies identified ATF7ip as a repressor of Il7r and Il2 gene expression through the deposition of the repressive histone mark H3K9me3 at the Il7r gene and Il2-Il21 intergenic region. Interestingly, ATF7ip targeted transposable elements for H3K9me3 deposition at both the IL7r locus and the Il2-Il21 intergenic region, indicating that ATF7ip silencing of transposable elements is important for regulating CD8+ T cell function. These results demonstrate a new epigenetic pathway by which IL-7R and IL-2 production are constrained in CD8+ T cells, and this may open up new avenues for modulating their production.

The Symbiotic Effect of a New Nutraceutical with Yeast β-Glucan, Prebiotics, Minerals, and Silybum marianum (Silymarin) for Recovering Metabolic Homeostasis via Pgc-1α, Il-6, and Il-10 Gene Expression in a Type-2 Diabetes Obesity Model.

The use of natural products and derivatives for the prevention and control of non-communicable chronic diseases, such as type-2 diabetes (T2D), obesity, and hepatic steatosis is a way to achieve homeostasis through different metabolic pathways. Thus, male C57BL/6 mice were divided into the following groups: high-fat diet (HFD) vehicle, HFD + Supplemented, HFD + Supplemented_S, and isolated compounds. The vehicle and experimental formulations were administered orally by gavage once a day over the four weeks of the diet (28 consecutive days). We evaluated the energy homeostasis, cytokines, and mitochondrial gene expression in these groups of mice. After four weeks of supplementation, only the new nutraceutical group (HFD + Supplemented) experienced reduced fasting glycemia, insulin, HOMA index, HOMA-β, dyslipidemia, ectopic fat deposition, and hepatic fibrosis levels. Additionally, the PPARγ coactivator 1 α (Pgc-1α), interleukin-6 (Il-6), and interleukin-10 (Il-10) gene expression were augmented, while hepatic steatosis decreased and liver parenchyma was recovered. The glutathione-S-transferase activity status was found to be modulated by the supplement. We discovered that the new nutraceutical was able to improve insulin resistance and hepatic steatosis mainly by regulating IL-6, IL-10, and Pgc-1α gene expression.

Indigodole E from Strobilanthes cusia exhibits anti-IL-17A effect

One new indazole alkaloid, indigodole E (1), was isolated from a traditional Chinese medicine Qing Dai prepared from the aerial parts of Strobilanthes cusia. The structure of 1 was elucidated by NMR, MS, UV, and IR spectra as well as optical rotation. Additionally, compound 1 could obviously inhibit not only IL-17A protein production at concentrations from 1.25 to 2.5 μg/mL, but also IL-17 gene expression at concentrations from 5.0 to 10.0 μg/mL without cytotoxicity toward Th17 and Jukat cells, respectively. Overall, indazole analogue 1 could be the anti-IL 17 A contributor of Qing Dai in this investigation.

Toll-Like Receptor- and Protein Kinase R-Induced Type I Interferon Sustains Infection of Leishmania donovani in Macrophages.

Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis, provoking liver and spleen tissue destruction that is lethal unless treated. The parasite replicates in macrophages and modulates host microbicidal responses. We have previously reported that neutrophil elastase (NE) is required to sustain L. donovani intracellular growth in macrophages through the induction of interferon beta (IFN-β). Here, we show that the gene expression of IFN-β by infected macrophages was reduced by half when TLR4 was blocked by pre-treatment with neutralizing antibodies or in macrophages from tlr2 -/- mice, while the levels in macrophages from myd88-/- mice were comparable to those from wild-type C57BL/6 mice. The neutralization of TLR4 in tlr2 -/- macrophages completely abolished induction of IFN-β gene expression upon parasite infection, indicating an additive role for both TLRs. Induction of type I interferon (IFN-I), OASL2, SOD1, and IL10 gene expression by L. donovani was completely abolished in macrophages from NE knock-out mice (ela2 -/-) or from protein kinase R (PKR) knock-out mice (pkr -/-), and in C57BL/6 macrophages infected with transgenic L. donovani expressing the inhibitor of serine peptidase 2 (ISP2). Parasite intracellular growth was impaired in pkr -/- macrophages but was fully restored by the addition of exogenous IFN-β, and parasite burdens were reduced in the spleen of pkr -/- mice at 7 days, as compared to the 129Sv/Ev background mice. Furthermore, parasites were unable to grow in macrophages lacking TLR3, which correlated with lack of IFN-I gene expression. Thus, L. donovani engages innate responses in infected macrophages via TLR2, TLR4, and TLR3, via downstream PKR, to induce the expression of pro-survival genes in the host cell, and guarantee parasite intracellular development.

Effect of dietary Spirulina ( Arthrospira platensis ) on the growth performance, immune‐related gene expression and resistance to Vibrio anguillarum in European seabass ( Dicentrarchus labrax )

This research was conducted to reveal the effects of dietary Spirulina (Arthrospira platensis) meal on the growth performance, immune responses and resistance against Vibrio anguillarum in European seabass (Dicentrarchus labrax). In the study, the fish (5.74 ± 0.02 g) were fed with control (C) and three different levels (1%, 2.5% and 5%) of Spirulina meal-containing diets (SP1, SP2.5 and SP5) for 60 days. The adaptive and innate immune responses of fish were determined every 30th day of the study. The results showed that respiratory burst activity (RBA) was significantly elevated on the SP2.5 and SP5 groups on the 30th day of the study. Lysozyme activity (LYS) was increased on the SP1 group on the 30th day and the SP5 group on the 60th day (p < 0.05). Myeloperoxidase activity (MPO) was raised on the 60th day of the SP2.5 and SP5 groups compared with the C (p < 0.05). IL-1β gene expression increased in the kidney and intestine of fish on the 30th day and in the spleen on the 60th day. IL-10 gene expression in the intestine of fish fed the Spirulina-containing diet was elevated at each sampling time relative to the C group (p < 0.05). Elevated IL-6 activity was determined in the kidney and the intestine on all Spirulina-fed groups compared with control at both sampling times. Similar to IL-6, IL-8 gene expressions were elevated in all Spirulina-fed groups (p < 0.05). TNF-α was up-regulated in the kidney and intestine of all Spirulina-fed groups compared with the C group on the 30th day of the study (p < 0.05). TGF-β gene expression was increased in the kidney and intestine of all Spirulina groups compared with the C group on all sampling times. COX-2 gene expression in the kidneys and intestines of fish fed with Spirulina diets was significantly elevated compared with the C diet at days 60th and 30th respectively. Hepcidin gene expression of all groups was elevated in all tissue samples on the 30th day of the study. The survival rate of fish infected with V. anguillarum was higher in all Spirulina-fed groups than in the C group. The feed conversion rate and protein efficiency ratio of fish fed with a 1% Spirulina diet was found to be better than those fed with other diets. These results show that up to the 5% inclusion of Spirulina meal in European seabass diets promotes some growth parameters and supports immunity in fish.

Folic acid supplementation during pregnancy alters behavior in male rat offspring: nitrative stress and neuroinflammatory implications.

Pregnancy diet can impact offspring's neurodevelopment, metabolism, redox homeostasis, and inflammatory status. In pregnancy, folate demand is increased due to the requirement for one-carbon transfer reactions. The present study was proposed to investigate the effect of folic acid supplementation throughout pregnancy on a battery of behavior tests (olfactory preference, motor activity, exploratory capacity, habituation, memory, anxiety- and depression-like behavior). Redox homeostasis and neuroinflammatory status in cerebral cortex were also investigated. After pregnancy confirmation, the pregnant rats were randomly divided into two groups, according to the diet: group 1, (control) standard diet (2mg/kg diet of folic acid) and group 2, supplemented diet with 4mg/kg diet of folic acid. Throughout the gestational period, the pregnant rats received experimental diets. Results show that the supplemented diet with 4mg/kg diet of folic acid throughout pregnancy impaired memory and motricity of the offspring when compared with control (standard diet). It was also observed an increase in anxiety- and depression-like behavior in this group. Nitrite levels increased in cerebral cortex of the offspring, when compared to control group. In contrast, iNOS expression and immunocontent were not altered. Moreover, we identify an increase in TNF-α, IL-1β, IL-6, IL-10, and MCP-1 gene expression in the cerebral cortex. In conclusion, our study showed that the supplemented diet with 4mg/kg diet of folic acid throughout pregnancy may cause behavioral and biochemical changes in the male offspringGraphical abstract After pregnancy confirmation, the pregnant rats were randomly divided into two groups, according to the diet: group 1, (control) standard diet (2mg/kg diet of folic acid) and group 2, supplemented diet with 4mg/kg diet of folic acid. Throughout the gestational period, the pregnant rats received experimental diets. Results show that folic acid supplementation did not impair the mother-pup relationship. We showed that supplemented diet with 4mg/kg diet of folic acid during pregnancy impairs memory and motricity of the offspring when compared with standard diet. It was also observed an increase in anxiety- and depression-like behavior in this group. Nitrative stress and neuroinflammation parameters were increased in the cerebral cortex of the offspring. ROS, reactive oxygen species.