Interleukin-2 Gene Research Articles

Influence of spleen meal and hydrolyzed yeast on growth performance, blood cells, antibody titres and IL-2 gene expression in broiler chickens

ABSTRACT Two experiments were conducted to evaluate spleen meal (SPM) nutritional value and compare its effects and hydrolyzed yeast (HY) in broiler chickens. In experiment 1, nutrient composition and metabolizable energy content of SPM were determined using male broilers. In experiment 2, 600 broiler chicks were assigned to 5 groups. Dietary treatments were control group, HY1: hydrolyzed yeast (1 g/kg), HY2: hydrolyzed yeast (2 g/kg), SPM1: (30 g/kg diet) and SPM2: (60 g/kg diet). Interleukin-2 (IL-2) gene expression and antibody titre against Newcastle and infectious bursal diseases were evaluated on day 21. apparent metabolizable energy (AME) and AMEn content of SPM were 3496 and 3296 kcal/kg, respectively. Supplementation with SPM improved (P < 0.001) body weight gain and feed conversion ratio compared to control and HY1 groups. Antibody titre against IBV was improved in SPM1, SPM2 and HY2 groups compared to HY1 and control groups. WBC was increased and heterophile was reduced in groups fed with SPM compared to control and HY groups. The highest gene expression for IL-2 was observed in broilers which received SPM1 and SPM2 compared to control and HY groups. It was concluded that dietary supplementation of HY and SPM has potential to improve broiler performance and immune response.

Interleukin-2 gene expression and its relation to red blood cell indices and T lymphocytes in anemic Egyptian children

Context Iron-deficiency anemia (IDA) is a health problem affecting children, females, and the aged. Increased knowledge about the etiology and cytokines of IDA can aid early detection and management. Aims The objectives of this research to assess interleukin-2 (IL-2) gene expression by real-time PCR and examine its relation to red blood cell indices and T lymphocytes in IDA in children. Settings and design This was a case–control study. A total of 60 children was included, and two groups were identified: group 1 (latent iron-deficiency anemia) and group 2 (IDA). Moreover, 30 healthy children were included as a control group. Patients and methods Complete blood count, serum ferritin, and immunophenotyping of the T lymphocyte subtypes were performed. Statistical analysis used Statistical Package for Social Science (SPSS) for Windows (version 16.0) software program was used for statistical analysis. Results A total of 21 (70%) patients of IDA group showed a low IL-2 gene expression. There is a significant positive correlation between IL-2 gene expression and T lymphocyte cell count (CD3+), cytotoxic T lymphocyte cells count (CD3+CD8+), and mean fluorescence intensity of CD3+CD8+ cells. Conclusions There was a significant positive correlation between IL-2 gene expression and red blood cell count, mean corpuscular hemoglobin concentration, serum ferritin level, serum iron level, T lymphocyte cells count (CD3+), cytotoxic T lymphocyte cells count (CD3+CD8+), and mean fluorescence intensity of CD3+CD8+ cells.

Assessment of Interleukin-12 Gene Polymorphism in Vitiligo Patients

Vitiligo is an obtained pigmentary turmoil of the skin and mucous films. Interleukin-12 has a positive synergistic proliferative impact on pre-initiated NK and T cells, improves freely and additionally synergistically the cytolytic capacity of both NK and CD8+ T cells by upregulation of qualities that encode cytotoxic cell granule-related proteins. The point of the work is to uncover the relationship between IL-12 quality polymorphism and vitiligo pathogenesis among contemplated gathering of Egyptian populace. This case-control study included 50 patients experiencing vitiligo (Group A) and 50 obviously solid people of coordinated age and sex as a benchmark (Group B). All patients were exposed to the followings: Full history taking, Clinical assessment, and Laboratory examinations for the genotypes of interleukin-12 (1188 A/C) SNP. Results and Conclusion: The IL12B rs3212227 CC genotype and C allele indicated fundamentally lower recurrence in situations when contrasted with control bunches with defensive impact to create vitiligo cases. Negative family ancestry, non-smokers and CC genotype were viewed as defensive indicators against vitiligo powerlessness. More seasoned period of beginning, more limited illness term, CA and CC genotypes were viewed as free indicators of less extreme vitiligo patients. By and by, bigger examinations are as yet expected to affirm our discoveries and to research the function of - 12 hereditary polymorphism in sickness seriousness.

Correlation between p16 and Interleukin-2 Gene Expression and Oral and Maxillofacial Wound Healing

To analyze the relationship between p16 and interleukin-2 protein and messenger RNA levels and wound healing in patients with oral and maxillofacial trauma. 86 patients with oral and maxillofacial trauma were selected in our hospital from June 2018 to June 2020 and divided into good and poor trauma healing group. All patients were treated with vacuum sealing drainage and given empirical antibacterial antiinfective medication, nutritional support and correction of fluid-electrolyte disturbances for 7 d. Serum levels of inflammatory factors were measured before and after 7 d of treatment. The levels of interleukin-2, p16 and messenger RNA were measured by western blot and polymerase chain reaction. White blood cells, tumor necrosis factor alpha, interleukin-6, C-reactive protein and procalcitonin were lower in both groups than before treatment while the phosphorylated form of p16/p16, phosphorylated form of interleukin-2/ interleukin-2 proteins and messenger RNA levels were lower immediately after extubation (p<0.05). Pearson correlation analysis revealed that phosphorylated form of p16/p16 and phosphorylated form of interleukin-2/ interleukin-2 were significantly lower in the group immediately after extubation (p<0.05). Phosphorylated form of p16/p16 and phosphorylated form of interleukin-2/interleukin-2 were positively correlated with white blood cells, tumor necrosis factor alpha, interleukin-6, C-reactive protein and procalcitonin after treatment (p<0.001). It is concluded that p16 and interleukin-2 in the drainage fluid of patients with oral and maxillofacial trauma can promote the process of wound healing by promoting the release of serum inflammatory factors.

Gazella bennetti (indian gazelle or chinkara) of Pakistan: genetic profiling and conservation priorities

&lt;p&gt;La gacela india es oriunda de la zona silvestre del norte de Pendjab (Pakistán). De acuerdo a las categorías de la lista roja de la Unión Internacional de Conservación de la Naturaleza y los Recursos Naturales, constituye una especie en peligro. El entendimiento de la genética de la respuesta inmune en esta especie puede ser útil para diseñar efectivas estrategias de conservación. El objetivo del estudio fue evaluar la diversidad genética molecular en la interleukina 2 (IL-2), secuencias de genes que ponen en peligro a G. bennetti como un gen que codifica una citokina involucrada en algunas actividades vitales de regulación de la respuesta inmune. El gen IL-2 (492 bp) fue amplificado y secuenciado en muestras de ADN colectadas de la naturaleza, así como de ejemplares cautivos de gacela india, seguidos por la alineación y el análisis filogenético. Los vecinos que unen el árbol construido de MEGA6 mostraron que G. bennetti es distinto de otros y forma un clado diferente. El análisis de los resultados del estudio mostró que las gacelas indias constituyen una única población aislada encontrada en Pakistán, la cual es endémica y está expuesta al peligro. Por consiguiente, las técnicas de conservación in-situ y ex-situ para G. bennetti constituyen una buena alternativa para evitar el peligro de extinción de la especie.&lt;/p&gt;

Interleukin-4 and Interleukin-5 Map to Human Chromosome 5 in a Region Encoding Growth Factors and Receptors and Are Deleted in Myeloid Leukemias With a del(5q)

Interleukin-4 (IL-4) is a potent mediator of growth and differentiation of cells of several hematopoietic lineages. Interleukin-5 (IL-5) is a lineage-specific hematopoietic growth factor that stimulates the production of eosinophils and eosinophil colonies from normal human bone marrow cells. By using somatic cell hybrids and in situ chromosomal hybridization, we localized the IL-4 and IL-5 genes to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the IL-4 and IL-5 genes were found to be deleted in the 5q- chromosome of four patients with refractory anemia (RA) or therapy-related acute nonlymphocytic leukemia (t-ANLL), who had a del(5q). Thus a small segment of chromosome 5 contains IL-4, IL-5, IL-3, and GM-CSF as well as other genes such as CD14 and EGR1. Our findings that each of these genes was deleted in the 5q- chromosome suggest that loss of function of one or more of these genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).

Single Nucleotide Polymorphism of IL-2 Gene at Position +166 in Type 1 Diabetes of Iraqi Patients

The present study aimed at investigating of frequency of polymorphism of interleukin-2 gene (IL2) at position+166 SNP) in Type 1 Diabetes and in healthy controls subjects 39 of Iraqi patients, (12 males &amp; 27 females;1 5.65 ± 1.79 years) and 21 controls.(7 mail &amp; 14 female ; 14.66 ± 3.43 years) attended the hospital in Baghdad for diagnosis and treatment during the period February 2015 – January 2016 were enrolled in this study, the polymorphism of IL2+166 was data waved by polymerase chain reaction-specific sequence primer (PCR-SSP) assay. The results showed a comparison IL2+166 genotypes &amp; alleles between T1D patients &amp; controls frequencies of TT genotype &amp; T allele (71.69vs. 68.95%;P =0.589 respectively) There was a significant increase in patients contrast to controls, (51.38vs. 48.08%; P =0.312) and associated RR rates were 19.2% &amp; 27.0%, respectively. And the related EF values were 1.56 &amp; 1.60 .Similar observations were made in GG genotype. In contrast TG genotype &amp; G allele (23.93 vs. 28.55%,P =1.000 respectively) Low frequency was observed in patients compared to healthy subjects (43.28 vs. 43.22%; P =0.312), and the related PF values were 0.56 &amp; 0.62 , respectively. The results of the study indicate that IL2+166 SNP may have a role in the mechanism of etiopathogenic of T1D in the samples of Iraqi patients

Phase I trial of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for the treatment of metastatic pancreatic cancer

The safety of oncolytic adenovirus-mediated suicide and interleukin-12 (IL12) gene therapy was evaluated in metastatic pancreatic cancer patients. In this phase I study, a replication-competent adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) expressing yCD/mutTKSR39 (yeast cytidine deaminase/mutant S39R HSV-1 thymidine kinase) and human IL-12 (IL12) was injected into tumors of 12 subjects with metastatic pancreatic cancer (T2N0M1-T4N1M1) at escalating doses (1 × 1011, 3 × 1011, or 1 × 1012 viral particles). Subjects received 5-fluorocytosine (5-FC) therapy for 7 days followed by chemotherapy (FOLFIRINOX or gemcitabine/albumin-bound paclitaxel) starting 21 days after adenovirus injection. The study endpoint was toxicity through day 21. Experimental endpoints included measurements of serum IL12, interferon gamma (IFNG), and CXCL10 to assess immune system activation. Peripheral blood mononuclear cells and proliferation markers were analyzed by flow cytometry. Twelve patients received Ad5-yCD/mutTKSR39rep-hIL-12 and oral 5-FC. Approximately 94% of the 121 adverse events observed were grade 1/2 requiring no medical intervention. Ad5-yCD/mutTKSR39rep-hIL-12 DNA was detected in the blood of two patients. Elevated serum IL12, IFNG, and CXCL10 levels were detected in 42%, 75%, and 92% of subjects, respectively. Analysis of immune cell populations indicated activation after Ad5-yCD/mutTKSR39rep-hIL-12 administration. The median survival of patients in the third cohort is 18.1 (range, 3.5–20.0) months. The study maximum tolerated dose (MTD) was not reached.

Tumor-Associated Macrophage and Tumor-Cell Dually Transfecting Polyplexes for Efficient Interleukin-12 Cancer Gene Therapy.

Interleukin 12 (IL12) is a potent pro-inflammatory chemokine with multifunction, including promoting cytotoxic T-cell-mediated killing of cancer cells. IL12-based cancer gene therapy can overcome IL12's life-threatening adverse effects, but its clinical translation has been limited by the lack of systemic gene-delivery vectors capable of efficiently transfecting tumors to produce sufficient local IL12. Macrophages inherently excrete IL12, and tumor-associated macrophages (TAMs) are the major tumor component taking up a large fraction of the vectors arriving in the tumor. It is thus hypothesized that a gene vector efficiently transfecting both cancer cells and TAMs would make the tumor to produce sufficient IL12; however, gene transfection of TAMs is challenging due to their inherent strong degradation ability. Herein, an IL12 gene-delivery vector is designed that efficiently transfects both cancer cells and TAMs to make them as a factory for IL12 production, which efficiently activates anticancer immune responses and remodels the tumor microenvironment, for instance, increasing the M1/M2 ratio by more than fourfold. Therefore, the intravenously administered vector retards tumor growth and doubles survival in three animal models' with negligible systemic toxicities. This work reports the first nonviral IL12 gene delivery system that effectively makes use of both macrophages and tumor cells.

Decrease in naïve T cell production due to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development

Human T-lymphocytic virus 1 (HTLV-1) is mainly associated with adult T-cell leukemia/lymphoma (ATLL) and HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP exhibit significant changes in their immune response, and HTLV-1 infection can interfere in cytokine production and perhaps in T cell production. The aims of this study were to evaluate thymic function in HAM/TSP patients and HTLV-1 healthy carriers (HCs) and correlate it to age and interleukin 7 (IL-7) gene expression. Thymic function in 21 HAM/TSP patients and 12 HCs was evaluated by quantifying T cell receptor rearrangement excision circle (TREC) particles and IL-7 gene expression, both measured by quantitative polymerase chain reaction. HAM/TSP patients presented lower TREC particle counts (p = 0.0112) and lower IL-7 expression (p = 0.0102) than HCs. Both TREC particles and IL-7 gene expression were separately analyzed in two age groups: ≤ 59 years and ≥60 years, The ≤59-year-old HAM/TSP patients had a lower TREC count compared with the ≤59-year-old HCs (p = 0.0476). In conclusion, HAM/TSP development could interfere with thymic function because the results showed TREC particle reduction in HAM/TSP patients in relation to HCs, and it could be associated with a concomitant reduction in IL-7 expression.

Single Nucleotide Polymorphism of IL-2 Gene at Position +166 in Type 1 Diabetes of Iraqi Patients

The present study aimed at investigating of frequency of polymorphism of interleukin-2 gene (IL2) at position+166 SNP) in Type 1 Diabetes and in healthy controls subjects 39 of Iraqi patients, (12 males &amp; 27 females;1 5.65 ± 1.79 years) and 21 controls.(7 mail &amp; 14 female ; 14.66 ± 3.43 years) attended the hospital in Baghdad for diagnosis and treatment during the period February 2015 – January 2016 were enrolled in this study, the polymorphism of IL2+166 was data waved by polymerase chain reaction-specific sequence primer (PCR-SSP) assay. The results showed a comparison IL2+166 genotypes &amp; alleles between T1D patients &amp; controls frequencies of TT genotype &amp; T allele (71.69vs. 68.95%;P =0.589 respectively) There was a significant increase in patients contrast to controls, (51.38vs. 48.08%; P =0.312) and associated RR rates were 19.2% &amp; 27.0%, respectively. And the related EF values were 1.56 &amp; 1.60 .Similar observations were made in GG genotype. In contrast TG genotype &amp; G allele (23.93 vs. 28.55%,P =1.000 respectively) Low frequency was observed in patients compared to healthy subjects (43.28 vs. 43.22%; P =0.312), and the related PF values were 0.56 &amp; 0.62 , respectively. The results of the study indicate that IL2+166 SNP may have a role in the mechanism of etiopathogenic of T1D in the samples of Iraqi patients

Immunosuppressive role of Benzo[a]pyrene in induction of lung cancer in mice

AimBenzo[a]pyrene [BP] is one of the major carcinogenic precursors of cigarette smoke that primary affects the lung at its first proximity. The goal of the current research was to elucidate new mechanisms underlying the tumorigenic impact of oral BP in the lung of mice, with focus on immunosuppressive effects and cancer stemming properties. MethodsFemale albino mice (n = 44) were divided into 2 groups: normal control and BP group. BP was administered orally to mice (50 mg/kg body weight), twice a week for four weeks in succession. At the end of experiment (22 weeks), gene expression were measured for transforming growth factor-β (TGF-β), cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death ligand 1(PD-L1), forkhead box protein P3 (FOXP3) and interleukin 12 (IL-12) and CD83+, CD8+ and CD166+ cell percentage were measured in lung tissue. ResultsThe results indicated the tumorigenic role of BP in the lung which was evidenced by histopathological examination. BP group also showed immunosuppressive role which evidenced by increased expression of lung TGF-β, CTLA-4, PD-L1, FOXP3 genes and decreased expression of lung IL-12 gene compared with normal control group. BP group also showed decreased CD83+ cells, CD8+ cells and increased number of CD166+ cells. ConclusionOur findings indicated that BP has immunosuppressive role in lung cancer besides increasing the percentage of cancer stem like cells.

CTIM-05. COMBINATION OF CONTROLLED INTERLEUKIN-12 GENE THERAPY WITH IMMUNE CHECKPOINT BLOCKADE IN RECURRENT GLIOBLASTOMA: UPDATED RESULTS OF A MULTI-INSTITUTIONAL, OPEN LABEL PHASE 1 TRIAL

Abstract A published clinical trial of veledimex (V)-regulatable interleukin-12 (IL-12) gene therapy (“Controlled IL-12”) under the control of a transcriptional switch (RheoSwitch Therapeutic Systemâ, RTSâ) as monotherapy in recurrent glioblastoma (rGBM) showed sustained infiltration of activated T cells within the tumor months after treatment (Sci Transl Med. 2019;11(505)). These T cells demonstrated up-regulation of immune checkpoint signaling, providing a rationale for combination therapy with the PD-1 inhibitor, nivolumab (nivo). We report interim findings following completion of enrollment (with follow-up ongoing) for a multi-institutional, open label, dose-escalation phase 1 trial (NCT03636477) evaluating safety and tolerability of loco-regional Controlled IL-12 in combination with nivo in adults with rGBM. Replication-incompetent adenovirus coding for RTS-IL-12 (Ad) was administered during surgery by free-hand injection into the tumor and periphery (2 x 1011 viral particles, Day 0) accompanied by V (10 or 20 mg) PO QD x 15 (Days 0 to 14) in combination with nivo (1 or 3 mg/kg) IV on Days -7, 15, then Q2W. Twenty-one subjects were treated (Cohort 1: V 10 mg, nivo 1 mg/kg, n=3; Cohort 2: V 10 mg, nivo 3 mg/kg, n=3; and Cohort 3: V 20 mg, nivo 3 mg/kg, n=3 &amp; 12 in expansion). Safety data were comparable to Ad+V monotherapy. Adverse reactions (ARs) during follow-on nivo dosing were consistent with nivo labeling. ARs were manageable and generally reversible with no synergistic toxicities. Updated overall survival findings will be presented. Baseline and post-treatment histochemical staining and multiplex immunofluorescence analyses for a subgroup of subjects will be discussed. The safety of this combination immunotherapy has been established, leading to a currently accruing phase 2 clinical trial of loco-regional Controlled IL-12 gene therapy in combination with the PD-1 inhibitor cemiplimab-rwlc (NCT 04006119).

IL-2 and IL-2R gene polymorphisms and immune function in people residing in areas with high background radiation, Yangjiang, China

Purpose Long-term exposure to low dose radiation may trigger immune response and stimulate hormesis. Interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R) play a crucial role in immune function. We aimed to explore the possible association of IL-2 and IL-2R gene polymorphisms with low dose radiation exposure, as well as the relationship with IL-2 gene expression in people residing in areas with a high background radiation in Yangjiang, China. Materials and methods We recruited and assigned 54 native men residing in Yangxi County, Yangjiang city to the high natural background radiation (HNBR) group, and 53 native men residing in Hengpi County, Enping city to the control area (CA) group. All the participants wore a thermoluminescent dosimeter (TLD) for 90 days, and answered questionnaires. The serum levels of IL2, IL4, IL5, sIL2R, and tumor growth factor (TGF), and expression levels of IL2RA, IL2RB, IL2RG, and IL2 were also analyzed. Additionally, we tested 10 polymorphic loci associated with the IL-2 gene. Results The annual effective radiation doses in the HNBR and CA groups were 6.24 mSv y–1 and 1.95 mSv y–1, respectively. After adjusting for potential confounding factors, the serum levels of IL-2 and IL-5 were higher in the HNBR group than the CA group (p < .05), while the serum level of TGFβ was lower in the HNBR group (p < .05). The IL-2 gene mRNA expression level was higher in the HNBR group than the CA group (p < .05). The IL-2RB rs76206423 AA allele showed significant variations in the HNBR group (p = .0381). Conclusions Long-term exposure to low dose radiation may enhance immune function, and IL-2RB rs76206423 may be related to the expression of IL-2 by other coding variants. Moreover, our data provide a better understanding of the molecular mechanism of the immune response to low dose radiation.

Immune Response in Young Thoroughbred Racehorses under Training.

Simple SummaryStressful stimuli, both infectious and non-infectious, can modify and trigger an innate immune response and inflammation, via an attempt to restore a homeostatic state. Coping with stressors can be measured by different procedures, including the evaluation of immunological parameters. These are also modulated by exercise, which can be considered stress prototypic in the Thoroughbred racehorse. To evaluate the complex of physiological regulations during the training period, twenty-nine clinically healthy, two-year-old Thoroughbred racehorses were followed during their first 3 months of sprint training. Blood collection was performed at rest, three times until 90 days of training, for testing immunological parameters during incremental sprint training to evaluate its effect on the immunological status of the animals. During the training period, we observed the following: (A) an increase in red blood cell parameters that are crucial for exercise performance adaptation, improving O2 transport and muscle cell respiration; (B) variations of blood granulocytes; and (C) changes in inflammatory cytokine gene expression. On the basis of clinical and laboratory findings, training exercise probably played a major role in the modulation of the above parameters. These latter changes could be seen as a preparation of the innate immune system to respond quickly and adequately to environmental conditions.Training has a great impact on the physiology of an athlete and, like all stressful stimuli, can trigger an innate immune response and inflammation, which is part of a wider coping strategy of the host to restore homeostasis. The Thoroughbred racehorse is a valid animal model to investigate these changes thanks to its homogeneous training and highly selected genetic background. The aim of this study was to investigate modifications of the innate immune response and inflammation in young untrained Thoroughbred racehorses during the first training season through haematological and molecular investigations. Twenty-nine Thoroughbred racehorses were followed during their incremental 3-month sprint exercise schedule. Blood collection was performed at time 0 (T0; before starting the intense training period), 30 days after T0 (T30), and 90 days after T0 (T90). Haematological parameters (red and white blood cells, haemoglobin, and platelets) were evaluated and haematocrit (HCT), mean corpuscular haemoglobin concentration (MCHC), and red cells width distribution + standard deviation (RDW-SD) were calculated. Moreover, via RT-qPCR, we investigated the expression of, Interleukin 1β (IL-1β), Interleukin 4 (IL-4) Interleukin 6 (IL-6), Interleukin 2 (IL-2), Interleukin 3 (IL-3), Interleukin 5 (IL-5) Interleukin 8 (IL-8), Trasformig Growth Factor β and α (TGF-β), Tumor necrosis factor α (TNF-α), and Interferon γ (IFN-γ)genes. Main corpuscular volume (MCV) showed a significant (p = 0.008) increase at T90. Main corpuscular haemoglobin (MCH) and haemoglobin concentration (MCHC) values were significantly augmented at both T30 (p < 0.001) and T90 (p < 0.001). Basophils were significant increased at T30 (p = 0.02) and eosinophils were significantly increased at T90 (p = 0.03). Significant differences in gene expression were found for all the genes under study, with the exception of IFN-γ and TNF-α. In particular, IL-2 (T30, p = 0.011; T90, p = 0.015), IL-4 (T30, p = 0.009; T90, p < 0.001), and IL-8 (T30, p < 0.001; T90, p < 0.001) genes were significantly upregulated at both T30 and T90 with respect to T0, TGF-β was intensely downregulated at T30 (p < 0.001), IL-5 gene expression was significantly decreased at T90 (p = 0.001), while IL-1β (p = 0.005) and IL-3 (p = 0.001) expression was strongly augmented at the same time. This study highlighted long-term adjustments of O2 transport capability that can be reasonably traced back to exercise adaptation. Moreover, the observed changes of granulocyte numbers and functions and inflammatory cytokine gene expression confirm a major role of the innate immune system in the response to the complex of stressful stimuli experienced during the training period.

SNPs in the interleukin-12 signaling pathway are associated with breast cancer risk in Puerto Rican women.

Interleukin-12 (IL-12) is a proinflammatory cytokine that links innate and adaptive immune responses against tumor cells. Single Nucleotide Polymorphisms (SNPs) in IL-12 genes have been associated with cancer risk. However, limited studies have assessed the role of IL-12 in breast cancer (BC) risk comprehensively, and these were done in European and Asian populations. Here, we evaluated the association of the IL-12 signaling pathway and BC risk in Puerto Rican women. A genetic association study was completed with 461 BC cases and 463 non-BC controls. By logistic regression, IL-12 signaling SNPs were associated with an increased BC risk, including rs2243123 (IL12A), rs3761041, rs401502 and rs404733 (IL12RB1), rs7849191 (JAK2), rs280500 (TYK2) and rs4274624 (STAT4). Conversely, other SNPs were associated with reduced BC risk including rs438421 (IL12RB1), rs6693065 (IL12RB2), rs10974947, and rs2274471 (JAK2), rs10168266 and rs925847 (STAT4), and rs2069718 (IFNG). Analyses based in hormone receptors such as estrogen (ER) and progesterone (PR) receptors also revealed protective (for SNPs rs3212227-IL12B; rs3024896 and rs3821236-STAT4) and predisposing (for rs2069705-IFNG SNP) BC associations. Haplotype analysis showed a decreased BC risk for IL12B and STAT4 SNPs, whereas increased risk for IL12RB1 SNPs. This study suggests a role of the IL-12 signaling axis and BC risk. SNPs in this pathway may alter IL-12 induced anti-tumor responses and modulate BC predisposition in a population-specific context. Functional studies will be necessary to confirm these findings, which potentially may benefit IL-12 related immunotherapeutic approaches towards BC.

Investigations of antioxidant potential and protective effect of Acanthophora algae on DNA damage: An electrochemical approach

In this paper, the electrochemical method was used as a rapid and sensitive method to measure the antioxidant activity of Acanthophora red macro-algae (collected from the Persian Gulf coast of Bushehr-Iran). The algae extract was obtained by a combination of maceration and microwave methods, and then the important volatile and bioactive compounds were identified by GC-Mass analysis. To prepare the sensor and improve the electrochemical signal, gold nanoparticles synthesized by the green method were used to modify the electrode surface. Differential pulse voltammetry method (DPV) was used to investigate the inhibitory effect of the extract on ABTS and DPPH radicals.To investigate the ability of the Acanthophora algae extract to prevent DNA damage induced by Fenton reaction, an electrochemical biosensor was designed based on the immobilization of human interleukin-2 (IL-2) gene probe on the surface of gold nanoparticle-modified carbon screen-printed electrode. Then, the protective effect of the algae extract was investigated by electrochemical impedance spectroscopy. Finally, the toxicity effect of Acanthophora algae extract on the HT-29, SKOV3, MCF-7, and SKMES-1 cancer cell lines was evaluated by MTT assay.

Anti-Relapse effects of donor natural killer cells and IL-2 gene modification on allogeneic hematopoietic stem cell transplantation in acute leukemia.

Patients with acute leukemia (AL) refractory to induction or reinduction chemotherapy show poor prognoses if they do not undergo allogeneic hematopoietic stem-cell transplantation (AHSCT). The present study aims to investigate whether donor natural killer (NK) cells and interleukin-2 (IL-2) gene modification exert anti-relapse effects on AHSCT after establishing a mouse model of AL. C57BL/6 (H-2b) mice were selected as donor mice to obtain NK cells and hematopoietic stem cells, while BALB/c (H-2d) mice were selected as the recipient mice for AHSCT. The AHSCT-treated mice were then injected with the donor NK cells, recombinant adenovirus expressing IL-2 (AdIL-2), or the NK cells infected by AdIL-2. Flow cytometry was performed to detect the cell transplantation rate, immune cell number, and cell immunogenicity. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the secretion of IL-2 in spleen cells, and the level of peripheral blood factors, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-35, transforming growth factor β (TGF-β), and IL-10. In our experiments, promotional effects of NK cells and AdIL-2 were found on cell transplantation rate, immune reconstitution ability, cell immunogenicity, IL-2 secretion, as well as increased peripheral blood factor levels in the recipient mice treated with AHSCT, with improved pathological changes observed. Moreover, the aforementioned changes were further promoted in the AHSCT-treated recipient mice injected with the AdIL-2-infected NK cells. These results uncover that the donor NK cells and IL-2 gene modification could inhibit the relapse of AL mice underwent AHSCT, hereby providing a new target for leukemia treatment.

Auto-lysed yeast and yeast extract effects on dry matter intake, blood cells counts, IgG titer and gene expression of IL-2 in lactating dairy cows under heat stress

The objective of this study was to assess the effects of auto-lysed yeast and yeast extract on performance and immune responses of cows in hot climate in the early lactation period. Twenty five lactating dairy cows randomly assigned to 5 groups and 5 replicates. Cows received basal diet with or without auto-lysed yeast (20 or 40 g/d/head) or yeast extract (20 or 40 g/d/head) as on top-dressed. There were no differences for daily dry matter intake, milk production milk fat and the counts of red blood cells and white blood cells among treatments (p &gt; 0.05). There were significant differences among treatments for immunoglobulin G (IgG) level, lymphocyte and neutrophil percentages. Yeast extract had no effect on IgG level, but auto-lysed yeast increased IgG level and neutrophil percentage and decreased lymphocyte percentage (p &lt; 0.05). The highest relative interleukin-2 gene expression was for cows received auto-lysed yeast at the level of 40 g/d/head. Yeast extract had no significant effect on interleukin-2 gene expression as compared to the control group. It was concluded that auto-lysed yeast at the level of 40 g/d/head had no effect on performance, but it could positively influence on immune response of lactating dairy cows in hot climate during early period of lactation.

Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant.

Tumor cell-based vaccines use tumor cells as a source of tumor-associated antigens. In our study, we aimed to develop and test a tumor vaccine composed of tumor cells killed by irradiation combined with in vivo interleukin-12 gene electrotransfer as an adjuvant. Vaccination was performed in the skin of B16-F10 malignant melanoma or CT26 colorectal carcinoma tumor-bearing mice, distant from the tumor site and combined with concurrent tumor irradiation. Vaccination was also performed before tumor inoculation in both tumor models and tumor outgrowth was followed. The antitumor efficacy of vaccination in combination with tumor irradiation or preventative vaccination varied between the tumor models. A synergistic effect between vaccination and irradiation was observed in the B16-F10, but not in the CT26 tumor model. In contrast, up to 56% of mice were protected from tumor outgrowth in the CT26 tumor model and none were protected in the B16-F10 tumor model. The results suggest a greater contribution of the therapeutic vaccination to tumor irradiation in a less immunogenic B16-F10 tumor model, in contrast to preventative vaccination, which has shown greater efficacy in a more immunogenic CT26 tumor model. Upon further optimization of the vaccination and irradiation regimen, our vaccine could present an alternative tumor cell-based vaccine.