IL-10 Gene Expression Research Articles

In vivo anti-inflammatory activity, safety and gene expression profiles of Carissa edulis, Withania somnifera, Prunus africana and Rhamnus prinoides for potential management of rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is a chronic, inflammatory and systemic autoimmune disease. Treatment for RA is aimed at eliminating symptoms, slowing disease progression, and optimizing quality of life. However, drugs currently in use are associated with adverse side effects. Search for alternative treatment for rheumatoid arthritis involves traditional herbal plants owing to the fewer side effects and more compatibility with long-term usage compared to the conventional drugs. The use of the selected medicinal plants to manage RA among local communities in Kenya is rife. This study sought to establish the safety and effectiveness of Carissa edulis, Withania somnifera, Prunus africana and Rhamnus prinoides aqueous extracts in the management and treatment of RA. MethodLambda IV Carrageenan was used to induce inflammation and the percentage inhibition calculated, gene expression of IL-6, TNF-α and IL-4 was evaluated using Real Time Polymerase Chain Reaction and acute oral and sub-acute toxicity was assessed in Swiss albino mice. ResultsC. edulis, W. somnifera, P. africana and R. prinoides showed a dose dependent anti-inflammatory activity, there was also a downregulation of TNF-α and IL-6 and upregulation expression of IL-4. Acute toxicity showed no mortality or significant changes in body weight and behavioral parameters at a cut-off dosage of 2000 mg/kg of the plant's extracts. The sub-acute toxicity also confirmed no toxic effects as evidenced by the hematological parameters and weekly change in body weights of mice. ConclusionThis study confirms potential application of these medicinal plants in RA management and act as a lead in drug development.

Three-Dimensional Printed Poly (Lactic-co-Glycolic Acid)-Magnesium Composite Scaffolds for the Promotion of Osteogenesis Through Immunoregulation.

Scaffolds play an important role in bone tissue engineering. The ideal engineered scaffold needs to be biocompatible, bioactive, and able to regulate immune cells to enhance bone regeneration. In this study, magnesium (Mg)-contained poly(lactic-co-glycolic acid) (PLGA) scaffolds (hereinafter, referred to as PLGA-2Mg) were fabricated by 3-dimensional printing using a mixture of PLGA and MgSO 4 powder. Poly(lactic-co-glycolic acid) scaffolds (hereinafter, referred to as PLGA) were also fabricated by 3-dimensional printing and were used as control. The biocompatibility, immunoregulatory ability, and osteogenic properties of PLGA-2Mg were analyzed and compared with those of PLGA. The results indicate that the incorporation of Mg increased the Young modulus and surface roughness of the scaffold, but did not affect its degradation. The PLGA-2Mg further promoted the adhesion and proliferation of MC3T3-E1 cells compared with PLGA, which indicates its improved biocompatibility and bioactivity. In addition, PLGA-2Mg inhibited the polarization of RAW 264.7 cells toward the M1 phenotype by down-regulating the IL-1β , IL-6 , and iNOs gene expression when challenged with lipopolysaccharide stimulation. In contrast, it promoted the polarization of RAW 264.7 cells toward the M2 phenotype by up-regulating the TGF-β , IL-10 , and Arg-1 gene expression without lipopolysaccharide stimulation. Finally, MC3T3-E1 cells were cocultured with RAW 264.7 cells and scaffolds using a transwell system. It was found that the expression level of osteogenic-related genes ( ALP , COL-1 , BMP2 , and BSP ) was significantly upregulated in the PLGA-2Mg group compared with that in the PLGA group. Consequently, PLGA-2Mg with increased biocompatibility and bioactivity can promote osteogenesis through immunoregulation and has the potential to be used as a novel scaffold in bone tissue engineering.

Alterations in <I>IL</I>-17 expression in pediatric patients with psoriatic arthritis

Introduction. Psoriatic arthritis is a common inflammatory disease affecting the joints and it is usually accompanied by plaque psoriasis. The pathogenetic link between psoriasis and psoriatic arthritis well reflects the mechanistic hypotheses of disease pathogenesis. Psoriatic arthritis is characterized by chronic inflammation which results in bone erosion and bone loss, as well as new bone formation around the affected joints. The exaggerated inflammatory response leads to enthesitis with the crucial contribution of IL-17 producing T cells and entheseal resident cells, expressing IL-23R. Studying the IL-17 gene expression patterns can help choose a therapy for patients with psoriatic arthritis.Aim. To study alterations in IL-17 gene expression in immune cells of paediatric patients with psoriatic arthritis.Materials and methods. Mono nuclear cells were isolated from the peripheral blood of 45 patients with psoriatic arthritis and 20 healthy controls. The IL-17 gene expression was analysed using a real-time PCR.Results and discussion. Mononuclear cells were isolated from whole peripheral blood for subsequent analysis of IL-17 gene expression by quantitative RT-PCR. The comparative analysis of the expression levels of patients with psoriatic arthritis and healthy volunteers showed that the expression level of IL-17 gene in patients with psoriatic arthritis was 345 times higher than the expression level in healthy volunteers.Conclusion. Patients with psoriatic arthritis are characterized by a very high level of IL-17 gene expression in immune blood cells. The high IL-17 gene expression level confirms its significant role in the inflammatory process in patients with psoriatic arthritis.

Transcriptional landscape of Kaposi sarcoma tumors identifies unique immunologic signatures and key determinants of angiogenesis

BackgroundKaposi sarcoma (KS) is a multicentric tumor caused by Kaposi sarcoma herpesvirus (KSHV) that leads to morbidity and mortality among people with HIV worldwide. KS commonly involves the skin but can occur in the gastrointestinal tract (GI) in severe cases.MethodsRNA sequencing was used to compare the cellular and KSHV gene expression signatures of skin and GI KS lesions in 44 paired samples from 19 participants with KS alone or with concurrent KSHV-associated diseases. Analyses of KSHV expression from KS lesions identified transcriptionally active areas of the viral genome.ResultsThe transcript of an essential viral lytic gene, ORF75, was detected in 91% of KS lesions. Analyses of host genes identified 370 differentially expressed genes (DEGs) unique to skin KS and 58 DEGs unique to GI KS lesions as compared to normal tissue. Interleukin (IL)-6 and IL-10 gene expression were higher in skin lesions as compared to normal skin but not in GI KS lesions. Twenty-six cellular genes were differentially expressed in both skin and GI KS tissues: these included Fms-related tyrosine kinase 4 (FLT4), encoding an angiogenic receptor, and Stanniocalcin 1 (STC1), a secreted glycoprotein. FLT4 and STC1 were further investigated in functional studies using primary lymphatic endothelial cells (LECs). In these models, KSHV infection of LECs led to increased tubule formation that was impaired upon knock-down of STC1 or FLT4.ConclusionsThis study of transcriptional profiling of KS tissue provides novel insights into the characteristics and pathogenesis of this unique virus-driven neoplasm.

MTORC1 inhibition may improve T lymphocytes affected by aging

BackgroundDue to the increase of the elderly’s population and related social and economic problems, it is very important to provide strategies on health. In this regard, induction of T lymphocytes responses, the most important cells of the immune system, may be a good approach. Among different agents considered as antiaging factors, mTORC1 pathway inhibitors are significant. So, the purpose of this study was to evaluate the effect of two mTORC1 inhibitors, Everolimus and Metformin, on age-related features of activated T cells.Materials and methodsOptimum doses of drugs was determined with evaluating the effect of treatments on IL-2 gene expression. T cells isolated from old and young mice were treated with drugs and PHA. IL-2 production was evaluated by ELISA. Also, the expression of CD28, PD-1, and KLRG-1, proliferation, and intracellular oxidative stress were assessed by flow cytometry-based assays, phenotyping, CFSE, and DCF-DA assay respectively.ResultsBoth drugs increased IL-2 production in the T cells of old mice. Also, using drugs especially Metformin could improve age-related phenotypical markers and increase the proliferation of T cells of old mice significantly. In addition, Metformin and Everolimus reduced intracellular oxidative stress in aged cells. However, the effect of both drugs on the T cells of young mice wasn’t significant or was in opposite to the results of old mice T cells.DiscussionIn line with studies noting mTOR inhibitors as antiaging drugs, Metformin and Everolimus may improve T cells affected from aging in vitro, and a decrease in intracellular oxidative stress may be one of their mechanism of function.

Assessment of tissue levels of miR-146a and proinflammatory cytokines in experimental cerebral toxoplasmosis following atovaquone and clindamycin treatment: An in vivo study

BackgroundDespite recent advances for treating cerebral toxoplasmosis (CT), monitoring the parasite burden and treatment response is still challenging. miRNAs are small non-coding RNAs with regulatory functions that can be used in diagnosis and treatment monitoring. We investigated the changes in miR-146a, BAG-1 gene, IL-6, and IL-10 tissue levels in the brain of BALB/c mice with chronic CT caused by the PRU strain of T. gondii following anti-parasitic and antibiotic treatment. MethodFifty-three 6-to 8-week-old BALB/c mice were infected using intraperitoneal inoculation of cerebral cysts of T. gondii PRU strain and then divided into five groups as follows: group 1 included mice treated with 100 mg/kg/d Atovaquone (AT), group 2 included mice treated with 400 mg/kg/d clindamycin (CL), group 3 included mice treated with combination therapy (AT + CL), group 4 included infected untreated mice as a positive control (PC), and; group 5 included uninfected untreated mice as negative control (NC). After the completion of the treatment course, tissue level of mir-146a, miR-155, BAG-1 gene, IL-6, and IL-10 was investigated with real-time polymerase chain reaction. The IL-6/IL-10 ratio was calculated as an indicator of immune response. Moreover, brain cyst numbers were counted on autopsy samples. ResultsmiR-146a, IL-6, IL-10, and BAG-1 genes were expressed in PC, but not in the NC group; miR-146a, IL-6, IL-10, and BAG-1 gene expression were significantly lower in AT, CL, and AT + CL compared with PC. MiR-146a and BAG-1 levels in AT and CL were not different statistically, however, they both had lower levels compared to AT + CL (P < 0.01). There was no difference in the expression of IL-6 and IL-10 between treatment groups. BAG-1 expression was significantly lower in AT, than in CL and AT + CL (P < 0.0089 and < 0.002, respectively). The PC group showed a higher ratio of IL-6/IL-10, although this increase was not statistically significant. It is noteworthy that the treatment with AT reduced this ratio; in the inter-group comparison, this ratio showed a decrease in the AT and AT + CL compared to the PC. The number of brain tissue cysts was significantly lower in AT, CL, and AT + CL, than in PC (p < 0.0001). AT had significantly lower brain cysts than CL and AT + CL (P < 0.0001). ConclusionIt seems that the factors studied in the current research (microRNA and cytokines) are a suitable index for evaluating the response to antiparasitic and antibiotic treatment. However, more studies should be conducted in the future to confirm our findings.

Hyperbaric Oxygen in Combination with Epigallocatechin-3-Gallate Synergistically Enhance Recovery from Spinal Cord Injury in Rats.

Spinal cord injury (SCI) following trauma is a devastating neurological event that can lead to loss of sensory and motor functions. However, the most effective measures to prevent the spread of damage are treatment measures in the early stages. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with epigallocatechin-3-gallate (EGCG) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley rats were randomly planned into five equal groups (n=18). In addition to sham group that only underwent laminectomy, SCI rats were allocated into 4 groups as follows: control group; HBO group; EGCG group; and HBO+EGCG group. Tissue samples at the lesion site were obtained for stereological, immunohistochemical, biochemical, and molecular evaluation. In addition, behavioral tests were performed to assess of neurological functions. The finding indicated that the stereological parameters, antioxidant factors (CAT, GSH, and SOD), IL-10 gene expression levels and neurological functions were considerably increased in the treatment groups in comparison with control group, and these changes were more obvious in the HBO+EGCG group (P<0.05). On the other hand, we observed that the density of apoptotic cells and gliosis, the biochemical levels of MDA and the expression levels of inflammatory genes (TNF-α and IL-1β) in the treatment groups, especially the HBO+EGCG group, were considerably reduced in comparison with control group (P<0.05). We conclude that co-administration of HBO and EGCG has a synergistic neuroprotective effects in animals undergoing SCI.

A Study on IFN-γ and IL-10 Gene Expression Changes in Gallus gallus Embryo Infected with Pseudomonas aeruginosa and Its Possible Restoration by Bakreshwar Hot Spring Water

Bakreswar hot spring is a naturally occurring hot spring located at Birbhum district in West Bengal, India. The surface temperatures of the hot springs varies between 35°C to 66°C. The water of hot spring is alkaline with pH 9 and has curative properties. Pseudomonas aeruginosa is an important pathogen causing hospital acquired infections and in this study we used multi-drug resistance (MDR) isolate. The motive of the study is to compare the IL-10 and IFN-γ gene expression changes in Gallus gallus domesticus embryo infected with Pseudomonas aeruginosa by using the Bakreswar hot spring water.The curative properties of the hot spring water collected from Agnikund (65°C) was studied on 14thdays old chick eggs infected with Pseudomonas aeruginosa. After harvesting and allantoic fluid collection, RNA extraction was done and cDNA synthesis and RT-PCR were performed. After infection of the chick embryo with MDR Pseudomonas aeruginosa, both IL-10 and IFN-Ƴ gene expressions were increased, but in the curative sets those were challenged with Bakreswar hot spring water IL-10 and IFN- γ both gene expressions were decreased. From this study we may conclude that hot spring water of Bakreswar has antimicrobial activity against Pseudomonas aeruginosa due to which it decreses the cytokine gene expressions.

Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes.

Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (P ≤ 0.001), plasma cells (P ≤ 0.001) and regulatory B cells (P < 0.05), and an elevation in switched memory B cells (P ≤ 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (P < 0.05 and P ≤ 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (r = -0.51, P < 0.05) and a moderate positive correlation with plasma cell ratios (r = 0.46, P < 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r = 0.54, P < 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.

The effect of risperidone on behavioral reactions and gene expression of pro- and anti-inflammatory cytokines in neuropathic pain model induced by chronic constriction injury of the sciatic nerve in rat.

Neuropathic pain results from lesions or diseases affecting the somatosensory system. The management of a patient with chronic neuropathic pain remains a challenge several studies report the analgesic effect of serotonin receptor antagonists in different models of experimental pain. The present study was designed to study the effect of systemic administration of risperidone, on behavioral scores of neuropathic pains in chronic constriction (CCI) model in rats. Inducing neuropathic pain with the CCI model which causes heat hyperalgesia, heat, and mechanical allodynia was performed on rats, and then, in two phases, risperidone effect was determined. In the acute phase, risperidone 1, 2, 4mg was administered for three groups half an hour before behavioral tests on the 7th, 14th, and 21st day after surgery, and in the chronic phase, risperidone 1, 2, and 4mg was administered for three different groups from the 1st to 14th days after surgery than on 14th-day behavioral scores were performed. For gene expression analysis, samples are taken from spinal cord tissues in lumbar segments. This study shows chronic administration of risperidone as an antipsychotic drug was effective on heat hyperalgesia and allodynia. However, only the max dosage (4mg) of risperidone showed meaningful improvement in increasing mechanical allodynia. However, acute administering of risperidone did not show any meaningful changes in behavioral tests on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. In addition, gene expression results showed an increase in IL-4 and IL-10 gene expression in the risperidone group compared to the sham group. This study suggests the helpful preventive effects of risperidone in developing and increasing neuropathic pain, but it does not have any instant effect.

Hyperbaric oxygen therapy and coenzyme Q10 synergistically attenuates damage progression in spinal cord injury in a rat model

BackgroundIdentifying effective spinal cord injury (SCI) treatments remains a major challenge, and current approaches are still unable to effectively improve its. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with coenzyme Q10 (CoQ10) in the recovery of SCI in rats. Material and methodsNinety female mature Sprague-Dawley rats were allocated into five equal groups, including; sham group, SCI group, HBO group (underwent SCI and received HBO), CoQ10 group (underwent SCI and received CoQ10), and HBO+CoQ10 group (underwent SCI and received HBO plus CoQ10). Tissue samples at the lesion site were obtained for evaluation of stereological, immunohistochemical, biochemical, molecular. Also, functional tests were performed to evaluate of behavioral properties. ResultsWe found that a significant increase in stereological parameters, biochemical factors (GSH, SOD and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells, as well as expression of inflammatory genes (TNF-α and IL-1β) were considerably reduced in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. ConclusionWe conclude that co-administration of HBO and HBO+CoQ10 has a synergistic neuroprotective effects in animals undergoing SCI.

A Study on IFN-γ and IL-10 Gene Expression Changes in Gallus gallus domesticus Embryo Infected with E. coli and its Possible Alteration by Bakreshwar Hot Spring Water

In search of effective treatment against E. coli there are some conventional medicinal treatments available but it becomes difficult to fight against MDR strains as they are resistant to most of the antibiotics. It was found that Bakreshwar hot spring water has some therapeutic properties against various infections, mostly against skin infections. Bakreshwar hot spring having a pH range of 8.1-8.5 and temperature which varies from 35°-71°C, contains several chemical compounds. Our aim of this work was to study whether Bakreshwar hot spring water can cure infections caused by E. coli in Gallus gallus embryo in relation to their gross appearances and IFN- γ and IL-10 gene expression changes. The sample water was collected around March, 2023. To study the therapeutic activity of Bakreshwar hot spring water, different experimental sets were set up with 14days embryonated eggs. Freshly prepared 0.5Mcfarland E. coli culture was inoculated into the eggs and in curative set, 100µl hot spring water was injected to check any alterations. Allantoic fluid was collected and mRNA was extracted the very next day. cDNA was synthesized from the extracted mRNA. Along with master mixture (primers, nuclease free water, Syber green) the cDNA was run at RT-PCR and CT value was obtained. The mean gene expression shows that IL-10 and IFN- γ both gene expression was decreased in curative set after treatment with water as compared to control sets. These finding suggests that Bakreshwar hotspring water treatment can be a potential method to control E. coli caused infections.

The Effect of secretome-hypoxia mesenchymal-stem-cells and vitamin-d3 in type-2 diabetes-mellitus induced periodontitis rats

Background: A systemic metabolic disorder by insulin resistance, type-2 diabetes mellitus (T2DM), is characterised by an increased level of reactive oxygen species (ROS) and decreased superoxide dismutase (SOD), which is associated with the activation of proinflammatory cytokine pathways such as tumor necrosis (TNF)-α. This condition usually stimulates inflammation of the periodontal tissue (periodontitis). Vitamin-D3 can inhibit the release of inflammatory mediator and reduce the risk of chronic periodontitis. Purpose this study to determine the effect of the secretome-hypoxia mesenchymal-stem-cells (SH-MSCs)-Vitamin-D3 combination on the expression of SOD, IL-10, and TNF-α genes in T2DM periodontitis-induced rats.&#x0D; Method: 30 rats were randomly divided into five groups; normal sham condition, positive control, SH-MSCs group, vitamin-D3 group, and combination of SH-MSCs and vitamin D3 group. SH-MSCs were injected at doses of 150 uL in the gingival. In addition, vitamin D3 5000 IU 2.25 mcg were administrated orally. After 35 days, all rats were sacrificed, and qRT-PCR from gingival tissue was performed to identify the expression of SOD, IL-10 and TNF-α genes &#x0D; Results: The results a significant increase in SOD and IL-10 gene expression (p

Preclinical immunological characterization of rademikibart (CBP-201), a next-generation human monoclonal antibody targeting IL-4Rα, for the treatment of Th2 inflammatory diseases

Rademikibart (CBP-201) is a next-generation human monoclonal antibody targeting IL-4Rα, undergoing evaluation in Phase 2 clinical trials for the treatment of moderate-to-severe Th2 inflammatory diseases. We report the immunological characterization of rademikibart. Rademikibart and dupilumab were associated with KD of 20.7 pM and 45.8 pM, respectively, when binding to distinct human IL-4Rα epitopes. Rademikibart did not bind to IL-4Rα from other species. Rademikibart inhibited IL-4 and IL-13-mediated STAT6 signaling (mean ± SD IC50: 7.0 ± 2.5 and 6.6 ± 1.5 ng/mL, respectively), TF-1 cell proliferation (IC50: 8.0 ± 1.6 and 9.7 ± 0.8 ng/mL, respectively) and TARC production in PBMCs (IC50: 59.2 ± 3.9 and 13.5 ± 0.2 ng/mL, respectively). Rademikibart versus dupilumab was more potent in the STAT6 assays (IL-4, p < 0.01; IL-13, p = 0.03), with non-significant trends towards greater potency in the TF-1 cell assays (IL-4, p = 0.09; IL-13, p = 0.20), and similar potency in the TARC assays. In experiments with mice expressing human IL-4Rα and IL-4, rademikibart and dupilumab demonstrated similar potency; both monoclonal antibodies eliminated IL-4 (p < 0.0001) and IL-13 (p < 0.05) mediated B cell activation in vitro and ovalbumin-induced IgE (p < 0.01) and eosinophilic lung infiltration (p < 0.0001) in vivo. In Th2-stimulated human skin explants, rademikibart rapidly downregulated IL-4, IL-13, and TARC gene expression, with greater effectiveness than dupilumab for IL-4 (p < 0.01) and a non-significant trend towards superiority for IL-13. In summary, rademikibart bound to a distinct IL-4Rα epitope with high affinity and demonstrated reductions in Th2 inflammatory biomarkers with at least similar and potentially superior potency to dupilumab.

Distribution of Body Mass Index and Abdominal Obesity in Bayelsa State with Associated Interleukin-2 Gene Expression

Aims: The aim of the present study was to evaluate the distribution, prevalence and determinants of obesity, overweight and abdominal obesity in Bayelsa State, Nigeria as well as associated IL-2 gene expression.&#x0D; Study Design: A community based cross sectional study design was employed to randomly select 420 participants (aged 18 – 65 years) for the study.&#x0D; Methodology: The study participants were grouped into normal, overweight and general obesity based on their body mass index (BMI) and sub-grouped into normal and abdominal obesity based on their waist circumference. Weighing scale, metre rule and measuring tape were used to measure weight, height and waist circumference respectively. Real time PCR was used to quantify IL-2 gene expression.&#x0D; Results: The BMI distribution of adults in Bayelsa State was symmetrical around the mean (27.25 ± 4.12). Mean waist circumference was 95.27 ± 15.92 (men 97.51 ± 12.38; women 93.41 ± 18.15 cm). The prevalence of obesity, overweight and abdominal obesity were 26.2% (male, 10.7%; females, 15.5%), 35.2% (males, 16.4%; female, 18.8%), and 62.9% (males, 28.1% females, 34.8%) respectively. Compared with the normal group, a significant upregulation of IL-2 gene expression was found in the overweight, general obesity and abdominal obesity groups (p &lt; 0.05). Significant association of the following determinants with obesity was found: both sexes, age group 36 - 55 years, working as small and medium scale business entrepreneurs and civil servants. Age group 56 – 65 years and female sex were associated with abdominal obesity.&#x0D; Conclusion: The present study found a high prevalence of overweight, general obesity and abdominal obesity in Bayelsa State and associated over expression of IL-2 gene. Findings may have implication for IL-2 based biomarker and drug development. Interventions to reduce BMI and waist circumference in Bayelsa State is emphasized in the present study.

Effects of ginger extract and/or propolis extract on immune system parameters of vaccinated broilers

Newcastle disease (ND), avian influenza (AI, H5N8), and infectious bronchitis (IB) are important diseases in the poultry industry and cause significant losses. Vaccination isthe most practical method for controlling infectious diseases. To reduce vaccination costs and several disorders in poultry farms, using herbal water supplements for immunomodulation with vaccination is critical to improving or preventing some conditions in the poultry industry. However, drinking water supplementation of ginger extract (GE)/propolis extract (PE) alone/in combination may increase broilers' humoral and cellular immunity due to the immunomodulatory effects of ginger and propolis. This protocol aimed to see how GE/PE alone or in combination improved the immunity, immune organ gene expression, and histology of the immune organs of broilers for 35 d after vaccination against NDV, H5N8, IBV, and IBDV. The chicks were dispensed into 5 groups according to GE and/or PE with vaccination. The control group was offered normal drinking water without any supplements or vaccinations. The GE group was supplemented with ginger extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The GE+PE group was supplemented with GE (0.5 mL/L drinking water) and PE (0.5 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The PE group was supplemented with propolis extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The fifth group was the vaccinated untreated group. This experiment showed the immunomodulatory properties of GE and/or PE against 3 common diseases, NDV, AI, and IB, in broiler chicken farms for 35 d applied to a vaccination program. Thus, ginger extract and propolis extract supplementation in drinking water increased antibody titer, INF, IL10, and IL2 and TLR3 gene expression in the bursa of Fabricius, thymus, and spleen, respectively, as well as cellular immunity as indicated by increased CD3, CD4, and CD8 in the bursa of Fabricius, thymus, and spleen, respectively, with normal lymphocytes in the medulla of the bursa, thymus, and spleen. In conclusion, propolis extracts alone or with GE improved all of the metrics mentioned above without harming the histology of the immune organs.

Evaluation of IL-4, MIP-1α, and MMP-9 gene expression levels in peri-implant tissues in peri-implantitis.

This case-control study evaluated the gene expression levels of interleukin (IL)-4, macrophage inflammatory protein type 1 alpha (MIP-1α), and metalloproteinase (MMP)-9, factors involved in the formation of giant cells in healthy peri-implant tissue and peri-implantitis. Thirty-five subjects (15 healthy and 20 with peri-implantitis), who met the inclusion and exclusion criteria, were included in this study. The peri-implant tissue biopsies were subjected to total RNA extraction, DNAse treatment, and cDNA synthesis. Subsequently, the reaction of real-time PCR was performed to evaluate the gene expression levels of IL-4, MIP-1α, and MMP-9 concerning the reference gene. IL-4 gene expression showed higher (18-fold) values in the Peri-Implantitis Group of Patients when compared with the Healthy (Control) Group (p<0.0001). Although MIP- 1α and MMP-9 gene expression levels were higher in diseased implants, they showed no significant differences (p=0.06 and p=0.2337), respectively. Within the limitations of this study, the results showed that in tissues affected by peri-implantitis, only levels of Il-4 were increased when compared with tissues in the control group.

Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a critical medical condition during which sensorimotor function is lost. Current treatments are still unable to effectively improve these conditions, so it is important to pay attention to other effective approaches. Currently, we investigated the combined effects of human placenta mesenchymal stem cells (hPMSCs)-derived exosomes along with hyperbaric oxygen (HBO) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley (SD) rats were allocated into five equal groups, including; sham group, SCI group, Exo group (underwent SCI and received hPMSCs-derived exosomes), HBO group (underwent SCI and received HBO), and Exo+HBO group (underwent SCI and received hPMSCs-derived exosomes plus HBO). Tissue samples at the lesion site were obtained for the evaluation of stereological, immunohistochemical, biochemical, molecular, and behavioral characteristics. Findings showed a significant increase in stereological parameters, biochemical factors (GSH, SOD, and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in treatment groups, especially Exo+HBO group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells and gliosis, as well as expression of inflammatory genes (TNF-α and IL-1β) were considerably reduced in treatment groups, especially Exo+HBO group, compared to SCI group. We conclude that co-administration of hPMSCs-derived exosomes and HBO has synergistic neuroprotective effects in animals undergoing SCI.

Chemokine CCL19 promotes type 2 helper T cell differentiation and allergic airway inflammation

Abstract Allergic asthma is largely driven by the actions of allergen-specific CD4 +type 2 T helper (Th2) cells. Following allergen inhalation, these cells are induced by the interaction of naïve CD4 +T cells with antigen-bearing dendritic cells (DCs) in lung-draining lymph nodes (LNs). The molecular mechanisms underlying the induction of T helper cells have been well studied and include the migration of allergen-bearing DCs from the lung to regional LNs in a manner dependent on the chemokine receptor, CCR7. Previous studies have demonstrated that CCL21, a CCR7 ligand, is required for the accumulation of naïve T cells and activated DCs in the LNs, but the function of another ligand, CCL19, has been unknown. In the present study, we investigated the role of CCL19 in allergic airway inflammation using CCL19-deficient mice. In a mouse model of asthma, eosinophils and lymphocytes were significantly reduced in airways of CCL19-deficient mice compared with those of wildtype (WT) animals, and production of IL-4 and IL-13 in the lung was significantly diminished, suggesting that CCL19 is required for type 2 immune responses. Co-cultures of naïve WT CD4 +T cells with CCL19-deficient DCs produced less type 2 cytokines than did T cells co-cultured with WT DCs. Further, fibroblastic reticular cells (FRCs) from CCL19-deficient mouse LNs produced less Th2 cytokine production compared with WT FRCs. Addition of recombinant CCL19 to the culture of naïve CD4 +T cells increased phosphorylation of STAT5 and gene expression of Il2, Il2ra, Il2rb, Il2rg, Sta5a, Stat5b and Stat6. Together, our findings suggest that CCL19 produced by DCs and FRCs promotes Th2 differentiation through the activation of STAT5-signaling, and that this promotes allergic airway inflammation. This work was supported by Intramural Research Program of NIEHS, NIH (ZIA ES102025-09).

Prohibitin is Upregulated on Donor T cells in Murine Acute Graft-versus-Host Disease and Promotes Th17 Response

Abstract Introduction: Acute graft-versus-host disease (GVHD) is a T cell-mediated disorder and the main cause of non-relapse mortality in allogeneic hematopoietic cell transplantation recipients. Here, we investigate PHB in Th17-mediated inflammation and as a therapeutic target for acute GVHD. Methods: Irradiated mice received T cell depleted bone marrow cells and allogeneic or syngeneic splenocytes. At day 25 post-transplant, blood, spleen, liver, and colon were harvested and analyzed for surface PHB, IFNγ, and IL-17 on donor T cells by flow cytometry. Splenocytes were cultured in the presence of PHB pharmacological inhibitor rocaglamide (RocA) and analyzed for PHB and IL-17 expression in donor T cells. Naïve murine CD4 T cells were cultured in Th17 polarizing conditions with RocA. CRISPR/Cas9-mediated knockout of PHB was performed followed by evaluation of Il17a, Il17f, and Il22 gene expression by quantitative PCR. Results: Surface expression of PHB is increased in murine allogeneic donor T cells in liver, spleen, colon, and peripheral blood in acute GVHD. PHB-expressing splenic T cells secrete IL-17, which is reduced with treatment with a PHB inhibitor in ex vivo experiments. PHB inhibition of murine CD4 T cells in vitro impairs differentiation into the Th17 subtype resulting in reduced IL-17 secretion and downregulation of Il17a, Il17f, and Il22 genes. Knockout of PHB reduces transcription of Il17 and Il22 genes. Conclusions: These findings show relevancy of PHB in Th17-mediated inflammation and suggest a potential role for PHB in acute GVHD. To our knowledge, this study is the first to investigate PHB in acute GVHD, and our findings will offer greater support for clinical use of PHB inhibition to treat this fatal disease. Supported by grants from AAI (KS, PR), ACS (PR; RSG-22-053-01-IBCD), and NIH NCI (PR; R01 CA252469).