Search results for: cytokines

Authors: Jie Ding, Yingying Pan, Shammy Raj, Lindy Schaffrick, Jolene Wong, Antoinette Nguyen, Sharada Manchikanti, Larry Unsworth, Peter Kwan, Edward E. Tredget

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Background: Exosomes (EXOs) have been considered a new target that is thought to be involved in and treat wound healing. More research is needed to fully understand the EXO characteristics and mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. Methods: Total EXOs were isolated from 85 serum samples of 29 burn patients and 13 healthy individuals. We characterized the EXOs for morphology and density, serum concentration, protein level, marker expression, size distribution, and cytokine content. After confirmation of EXO uptake by dermal fibroblasts, we also explored functional regulation of primary human normal skin and hypertrophic scar fibroblast cell lines by the EXOs in vitro, including cell proliferation and apoptosis. Results: EXOs dynamically changed their morphology, density, size, and cytokine level during wound healing in burn patients, which were correlated with burn severity and the stages of wound healing. EXOs from both burn patients and healthy individuals stimulated dermal fibroblast proliferation and apoptosis. Conclusion: EXO features may be important signals that influence wound healing after burn injury; however, to understand the mechanisms by which EXOs regulated the fibroblasts in healing wounds, further studies will be required in the future.

Keywords: exosome, burn, wound healing, hypertrophic scarring, cytokines

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Authors: Saleh N. Maodaa

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Perinatal exposure to nicotine imbalances the redox status in newborns. This study investigated the effect of Anethum graveolens (dill) extract on oxidative stress and tissue injury in the liver and kidney of mice newborns exposed to nicotine perinatally. Pregnant mice received nicotine (0.25 mg/kg) on gestational day 12 to day 5 after birth and/or A. graveolens extract on a gestational day 1 to day 15 after birth. Newborn mice exposed to nicotine showed multiple histopathological alterations in the kidney and liver, including inflammatory cell infiltration and degenerative changes. Nicotine exposure increased hepatic and renal reactive oxygen species (ROS), lipid peroxidation, tumor necrosis factor (TNF-_), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) (p < 0.001), and decreased antioxidant defenses (p < 0.001). A. graveolens supplementation significantly prevented liver and kidney injury, suppressed ROS generation (p < 0.001), lipid peroxidation (p < 0.001), and inflammatory response (p < 0.001), and enhanced antioxidant defenses. In addition, A. graveolens upregulated hepatic and renal Nrf2 and HO-1 mRNA and increased HO-1 activity in normal and nicotine-exposed mice. In conclusion, A. graveolens protects against perinatal nicotine-induced oxidative stress, inflammation, and tissue injury in the liver and kidney of newborn mice. A. graveolens upregulated hepatic and renal Nrf2/HO-1 signaling and enhanced antioxidant defenses in mice.

Keywords: dill, oxidative stress, cytokines, nicotine

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Authors: Ghaleb Bin Huraib

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Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin disease characterized by severe itching and recurrent, relapsing eczema-like skin lesions, affecting up to 20% of children and 10% of adults in industrialized countries. AD is a complex multifactorial disease, and its exact etiology and pathogenesis have not been fully elucidated. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-β1on AD susceptibility in a Saudi cohort. One hundred four unrelated patients with AD and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms using ARMS-PCR and PCR-RFLP technique. The frequency of genotypes AA and AT of IFN-γ (874A/T) differed significantly among patients and controls (P 0.001). The genotype AT was increased while genotype AA was decreased in AD patients as compared to controls. AD patients also had a higher frequency of T-containing genotypes (AT+TT) than controls (P = 0.001). The frequencies of alleles T and A were statistically different in patients and controls (P = 0.04). The frequencies of genotype GG and allele G of IL-6 (174G/C) were significantly higher, while genotype GC and allele C were lower in AD patients than in controls. There was no significant difference in the frequencies of alleles and genotypes of TGF-β1 (509C/T) polymorphism between the patient and control groups. These results showed that susceptibility to AD is influenced by the presence or absence of genotypes of IFN-γ (874A/T) and IL-6 (174G/C) polymorphisms. It is concluded T-allele and T-containing genotypes (AT+TT) of IFN-γ (874A/T) and G-allele and GG genotype ofIL-6 (174G/C) polymorphisms are susceptible to AD in Saudis. On the other hand, the TGF-β1 (509C/T) polymorphism may not be associated with AD risk in our population; however, further studies with large sample sizes are required to confirm these results.

Keywords: atopic dermatitis, Polymorphism, Interferon, IL-6

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Authors: Sara Mohammad Atef Sabaika

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Background: The development of factor VIII (FVIII) inhibitor and hemophilic arthropathy in patients with hemophilia A (PWHA) are a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. Aim: Study the association between tumor necrosis alpha level and genotypes in pediatric patients with hemophilia A and its relation to inhibitor development and joint status. Methods: A cross-sectional study was conducted among a sufficient number of PWHA attending the Pediatric Hematology and Oncology Unit, Pediatric department in Menoufia University hospital. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of −380G > A TNF-α gene polymorphism was performed using real time polymerase chain reaction. Results: Among the 50 PWHA, 28 (56%) were identified as severe PWHA. The FVIII inhibitor was identified in 6/28 (21.5%) of severe PWHA. There was a significant correlation between serum TNF-α level and the development of inhibitor (p = 0:043). There was significant correlation between polymorphisms of −380G > A TNF-α gene and hemophilic arthropathy development (p = 0:645). Conclusion: The prevalence of FVIII inhibitor in severe PWHA in Menoufia was 21.5%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level and its gene polymorphism might be used to predict inhibitor development and joint status in pediatric patients with hemophilia A.

Keywords: hemophilic arthropathy, TNF alpha., patients witb hemophilia A PWHA, inhibitor

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Wissem Abdaoui, Nizar M. Mhaidat, Ilhem Mokhtari, Adel Gouri

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Colorectal cancer (CRC) is one of the most common tumors all over the world. Obesity, considered a risk factor of CRC, is characterized by a high level of secreted cytokines from adipose tissue. Among these inflammatory molecules, leptin is considered the key mediator for CRC cancer development and progression by activation of mitogenic and anti apoptotic signaling pathways. Gene expression can be significantly modulated by alterations in DNA methylation patterns. The aim of this study is to investigate the impact of leptin gene methylation on CRC prognosis and sensitivity to chemotherapy. The study involved 70 CRC tissue samples collected from King Abdullah University Hospital (KAUH) from which only 53 was analyzed because of bisulfate fragmentation and low yield of DNA extracted from FFPE tissues. A total of 22 blood samples were collected from healthy volunteers and enrolled as a control group. Leptin promoter methylation was analyzed by methylation specific PCR after bisulfate conversion. Results revealed that the incidence of leptin gene methylation was significantly higher in CRC patients in comparison to that of controls (P < 0.05). The correlation between patient’s demographics and leptin gene methylation was not significant (P < 0.05). However, a significant correlation between leptin gene methylation status and early cancer stages (I, II and III) was found in male but not in female (p < 0.05). Moreover, a significant correlation was found between leptin promoter methylation and early tumor localization T1-2 (p < 0.05). The correlation between epigenetic regulation of leptin and chemosensitivity was not significant. Taken together, these results suggest the possibility to use leptin gene methylation as a biomarker for the evaluation of CRC prognosis and metastasis.

Keywords: colorectal cancer, obesity, leptin, DNA methylation, disease prognosis, bisulfate conversion, chemoresistance

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Authors: Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O Saleh, Manal Badawi

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Background: Diabetes is a metabolic disease that affects a wide range of people worldwide and results in serious complications. Streptozotocin (STZ) causes selective cytotoxicity in the pancreatic β-cell, and it has been extensively used to induce diabetes mellitus in rats. The present study investigated the effects of diosmin and chrysin alone or in combination with each other on glucose level and on liver in STZ diabetic rats. Methods: In this study, rats were divided into six experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with glycazide (10 mg/kg B.W, oral), treated STZ-diabetic with diosmin (100 mg/kg B. W., oral), treated STZ-diabetic with chrysin (80 mg/kg B.W., oral), treated STZ-diabetic with diosmin (50 mg/kg B.W, oral) + chrysin (40 mg/kg B.W., oral). After 2 weeks blood samples were withdrawn and glucose was measured. Animals were anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for dissecting liver. Results: Throughout the experimental period, all treatments significantly (P<0.05) lowered serum glucose, AST, ALT, triglyceride, cholesterol, IL-6, TNF-α and IL-1β. Moreover, the treated diabetic rats showed higher levels of reduced glutathione (P<0.05) in the liver compared to the diabetic control rats and inhibited diabetes-induced elevation in the levels of malondialdehyde in liver. The results of this study clearly demonstrated that diosmin and chrysin possess several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects and anti-inflammatory effects. Conclusion: Considering these observations, it appears that diosmin and chrysin may be a useful supplement to delay the developmentof diabetes and its complications.

Keywords: diabetes, streptozocin, chrysin, rat, diosmin, cytokines

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Authors: Emily Schlebes, Christian Hundhausen, Jens W. Fischer

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The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix, typically produced by fibroblasts of the connective tissue but also by immune cells. Here, we investigated the capacity of human peripheral blood CD8 T cells from healthy donors to produce HA and to express HA receptors as well as HA degrading enzymes. Further, we evaluated the effect of pharmacological HA inhibition on CD8 T cell function. Using immunocytochemistry together with quantitative PCR analysis, we found that HA synthesis is rapidly induced upon antibody-induced T cell receptor (TCR) activation and almost exclusively mediated by HA synthase 3 (HAS3). TCR activation also resulted in the upregulation of HA receptors CD44, hyaluronan-mediated motility receptor (HMMR), and layilin (LAYN), although kinetics and strength of expression varied greatly between subjects. The HA-degrading enzymes HYAL1 and HYAL2 were detected at low levels and induced by cell activation in some individuals. Interestingly, expression of HAS3, HA receptors, and hyaluronidases were modulated by the proinflammatory cytokines IL-6 and IL-1bβ in most subjects. To assess the functional role of HA in CD8 T cells, we performed carboxyfluorescein succinimidyl ester (CFSE) based proliferation assays and cytokine analysis in the presence of the HA inhibitor 4- Methylumbelliferone (4-MU). Despite significant inter-individual variation with regard to the effective dose, 4-MU resulted in the inhibition of CD8 T cell proliferation and reduced release of TNF-α and IFN-γ. Collectively, these data demonstrate that human CD8 T cells respond to TCR stimulation with a synthesis of HA and expression of HA-related genes. They further suggest that HA inhibition may be helpful in interfering with pathogenic T cell activation in human disease.

Keywords: CD8 T cells, extracellular matrix, hyaluronan, hyaluronan synthase 3

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Authors: Banaeifar Abdolali, Rahmanimoghadam Neda, Sohyli Shahram

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Obesity is an increase in body fat , in addition it has been introduced as a risk factor for the progress of lipid disorders, hypertension, cardiovascular disease and type 2 diabetes (1,2). In recent years, Adipose tissue is now recognized as an endocrine organ that secretes many cytokines such as: interleukin 6, leptin, and visfatin (3). Visfatin is an adipocytokine that release from adiposities. It is unidentified whether training also influences concentrations of visfatin. Purpose: The purpose of this study was to examine the effects of 12 weeks of aerobic training on visfatin levels and lipid profile in obese women. Method: Thirty two obese women (age = 37.8 ± 13.2 years, body mass index = of 39.4 ± 6.4 kg/m2 .) volunteered to participate in a 12-wk exercise program. They were randomly assigned to either a training (n = 16) or control (n = 14) group. The training group exercised for 70 minutes per session, 3 days per week during the 12 week training program. The control group was asked to maintain their normal daily activities. Samples were obtained before and at the end of training program. We use t.paire and independent,test for data analyzes. Results: Exercise training resulted in a decrease in body weight (p < 0.05), percent body fat (% fat) and BMI (p < 0.05), fasting glucose level and visfatin concentration decreased but wasn’t significant (p > 0.05). Also the levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol did not change significantly. Conclution: In conclusion, three month aerobic training program used in this study was very effective for producing significant benefits to body composition and HDL.c but didn’t significant chenging visfatin levels and lipid profile in these obese women.

Keywords: aerobic training, visfatin, lipid profile, women

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Authors: Sahar Essa, Hussain A. Safar, Raj Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications in immunologically immature and immunocompromised hosts. Effective CMV vaccines that help diminish CMV disease in transplant patients and avoid congenital infection are of great importance. Though the exact roles of defense mechanisms are unidentified, viral-specific antibodies and cytokine responses are known to be involved in controlling CMV infections. CMV envelope glycoprotein B (UL55/gB), matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. We immunized mice intraperitoneally with these five CMV-related proteins (commercial) for their ability to induce specific antibody responses (in-house immunoassay) and cytokine production (commercial assay) in a mouse model. We observed a significant CMV-antigen-specific antibody response to pp38 and pp65 (E/C ˃2.0, p˂0.001). Mice immunized with pp38 had significantly higher concentrations of GM-CSF, IFN-α, IL-2 IL-4, IL-5, and IL-17A (p˂0.05). Mice immunized with pp65 showed significantly higher concentrations of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF-α. Th1 to Th2 cytokines ratios revealed a Th1 cytokine bias in mice immunized with pp38, pp65, pp150, and gB. We suggest that stimulation with multiple CMV-related proteins, which include pp38, pp65, and gB antigens, will allow both humoral and cellular immune responses to be efficiently activated, thus serving as appropriate CMV antigens for future vaccines.

Keywords: cytomegalovirus, UL99/pp28, UL80a/pp38, UL83/pp65, UL32/pp150, UL55/gB, CMV-antigen-specific antibody, CMV antigen-specific cytokine responses

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

Procedia PDF Downloads 176

Authors: Kathy Stein, Mariola Lysson, Anja Schmidt, Beatrix Schumak, Sabine Specht, Hicham Bouabe, Jürgen Heesemann, Axel Roers, Joerg C. Kalff, Sven Wehner

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Objective: Postoperative ileus (POI) is a common complication of abdominal surgery. Monocyte infiltration is a hallmark of POI. The polarization of macrophages/monocytes in this process is not well understood. We aimed to investigate if and how M2 macrophage/monocyte differentiation is involved in POI pathogenesis. Design: POI was induced by intestinal manipulation (IM). C57Bl/6, CCR2-/-, IL-10 reporter (ITIB), IL-10-/- and LysMcre/IL-10fl/fl mice underwent IM. At various points in time leukocyte influx, gene and protein expression of cytokines, chemokines and M2 differentiation markers and intestinal motility were analyzed. Results: IM induced the postoperative expression of the M2 markers Arginase-1 and YM-1, predominantly in F4/80+Ly6C+ monocytes. Gene expression analyses indicated an IL-10-dependent, IL-4-independent M2 polarization of these monocytes. IL-10 dependency of M2 differentiation was confirmed in IL-10 deficient mice. Leukocytes, in the order of infiltrating monocytes, neutrophils, and resident macrophages were the main IL-10 producers during POI. IL-10 producing monocytes as well as M2 marker expression were almost absent in CCR2-deficient mice. However, postoperative IL-10 expression was not altered in CCR2-/- mice. The loss of M2 polarized monocytes neither protected CCR2-/- mice from nor affected resolution of POI. In contrast, IL-10 deficiency reduced postoperative neutrophil numbers and ameliorated POI. IL-10Ra expression was strongly induced in neutrophils but not in monocytes. Conclusion: We conclude that IL-10 counteracts POI resolution by activating IL-10Ra-expressing neutrophils in the late phase of disease while IL-10-dependent M2 differentiation is not pivotal to POI manifestation and resolution.

Keywords: interleukin-10, macrophages, neutrophils, postoperative ileus

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Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

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Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: Mohammed Flaih Alotaibi, Rasheed Ahemad Shaik, Mohammed Z. Nasrullah

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Diabetic foot ulcers are the foremost global healthcare burden. Hyperglycemia in diabetics is incriminating in impeding wound healing and it can allow for more severe medical issues. The study was intended to establish a nanoconjugate of cordycepin-melittin (COR-MEL) and evaluate its healing effects in wounded diabetic rats. Diabetes induced by injecting streptozotocin intraperitoneally (50 mg/kg, body weight). Therefore, animals were classified into various groups; diabetic untreated, vehicle-treated, COR alone, MEL alone, and COR-MEL nanoconjugate treated, respectively. Animals with diabetes were exposed to excision and treated with Vehicle, COR, MEL, or COR-MEL nanoconjugate topically. After 14 days, the wounded skin was sliced and subjected to histological and biochemical assessments. The formulated nanoconjugate has a particle size of 253.5± 17.4 nm by a polydispersity index of 0.36 ± 0.05, and a zeta potential of 1.72 ± 0.3 mV. The study demonstrated an accelerated wound contraction in COR-MEL-treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde and exhaustion of superoxide dismutase and glutathione peroxidase enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of proinflammatory cytokines (IL-6 and TNF-α). Additionally, the nanoconjugate exhibits a strong expression of growth factors (TGF-β1, VEGF-A, and PDGFR-β), indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1. Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Keywords: diabetic wounds, cordycepin, melittin, nanoconjugate, wound healing

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Authors: Kamyar Moradi

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Background: Acute mesenteric ischemia is known as a life-threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury, which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. Methods: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg, and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 minutes followed by 120 minutes of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also, protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. Results: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. Conclusion: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. Still, more studies would clarify existing causality in this phenomenon.

Keywords: albendazole, ischemia reperfusion injury, inflammation, mesenteric ischemia

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Authors: Ekin Ece Gürer, Tarık Onur Tiryaki, Sevgi Kalayoğlu Beşışık, Fatma Savran Oğuz, Uğur Sezerman, Fatma Erdem, Gülşen Günel, Dürdane Serap Kuruca, Zerrin Aktaş, Oral Öncül

Abstract:

Aim: Chemotherapytreatment in HodgkinLymphomaandNon-HodgkinLymphoma (NHL) diseasescausesgastrointestinalepithelialdamage, disruptstheintestinalmicrobiotabalanceandcausesdysbiosis. Inourstudy, it wasaimedtoshowtheeffect of thedamagecausedbychemotherapy on themicrobiotaandtheeffect of thechangingmicrobiota flora on thecourse of thedisease. Materials And Methods: Seven adult HL and seven adult HL patients to be treatedwithchemotherapywereincluded in the study. Stoolsamplesweretakentwice, beforechemotherapytreatmentandafterthe 3th course of treatment. SamplesweresequencedusingNextGenerationSequencing (NGS) methodafternucleicacidisolation. OTU tableswerepreparedusing NCBI blastnversion 2.0.12 accordingtothe NCBI general 16S bacterialtaxonomyreferencedated 10.08.2021. Thegenerated OTU tableswerecalculatedwith R Statistical Computer Language version 4.04 (readr, phyloseq, microbiome, vegan, descrand ggplot2 packages) to calculate Alpha diversityandtheirgraphicswerecreated. Statistical analyzeswerealsoperformedusing R Statistical Computer Language version 4.0.4 and studio IDE 1.4 (tidyverse, readr, xlsxand ggplot2 packages). Expression of IL-12 and IL-17 cytokineswasperformedbyrtPCRtwice, beforeandaftertreatment. Results: InHL patients, a significantdecreasewasobserved in themicrobiota flora of Ruminococcaceae_UCG-014 genus (p:0.036) andUndefined Ruminococcaceae_UCG-014 species (p:0.036) comparedtopre-treatment. When the post-treatment of HL patientswerecomparedwithhealthycontrols, a significantdecreasewasfound in themicrobiota of Prevotella_7 genus (p:0.049) andButyricimonas (p:0.006) in the post-treatmentmicrobiota of HL patients. InNHL patients, a significantdecreasewasobserved in themicrobiota flora of Coprococccus_3 genus (p:0.015) andUndefined Ruminoclostridium_5 (p:0.046) speciescomparedtopre-treatment. When post-treatment of NHL patientswerecomparedwithhealthycontrols, a significantabundance in theBacilliclass (p:0.029) and a significantdecrease in theUndefinedAlistipesspecies (p:0.047) wereobserved in the post-treatmentmicrobiota of NHL patients. While a decreasewasobserved in IL-12 cytokineexpressionuntilbeforetreatment, an increase in IL-17 cytokineexpressionwasdetected. Discussion: Intestinal flora monitoringafterchemotherapytreatmentshowsthat it can be a guide in thetreatment of thedisease. It is thoughtthatincreasingthediversity of commensalbacteria can alsopositivelyaffecttheprognosis of thedisease.

Keywords: hodgkin lymphoma, non-hodgkin, microbiota, cytokines

Procedia PDF Downloads 108

Authors: Kebret Kebede, Anthony Scinta

Abstract:

Obesity is the most prevalent global problem that continues to rise at alarming rates both in the industrialized and developing countries. Adipose tissue is an endocrine tissue that secretes numerous chemical signals, hormones, lipids, cytokines and coagulation factors as well as prompting insulin resistance which is a primary contributor to Type II Diabetes- one of its most common adverse effects on health. Other hormones whose levels are linked to obesity and nutritional state are leptin, IGF-1, and adiponectin. Several studies indicate that obesity is the leading cause of high levels of cholesterol that leads to fatty liver disease, gallstones, hypertension, increased risk for cancer and degenerative joint disease that primarily affects the weight bearing joints of the lower extremities. The activation of inflammatory pathways promotes synovial pathology that results in accelerated degeneration of the joints. The study examines the prevalence of obesity in the US female population in comparison to that of the developing world and its emergence as a significant and potentially modifiable risk factor in degenerative disease of the hip and knee joints that has resulted in staggering healthcare cost. Studies have shown that as the prevalence of obesity rises, we continue to see a rise in degenerative joint disease. The percentage of arthritis cases linked directly to obesity has risen from 3 percent in 1971 to 18 percent in 2002. A person with obesity is around 60 percent more likely to develop arthritis than someone of normal body weight. In women, obesity is associated with increased mortality from breast, cervical, endometrial and ovarian cancer that may accompany debilitating joint diseases and restricted mobility.

Keywords: obesity, endocrine, degenerative, mortality, joint diseases, cancer, debilitating, mobility

Procedia PDF Downloads 449

Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das

Abstract:

Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.

Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death

Procedia PDF Downloads 103

Authors: Sasan Khademnematolahi, Kevine Kamga Silihe, Katarína Pružinská, Martina Chrastina, Elisabeth Louise Ndjengue Mindang, František Dráfi, Katarína Bauerová

Abstract:

Background: In ethnomedicine, plant parts and compounds are traditionally utilized to treat many disorders. Azadirachta indica, known as Neem, has been traditionally used in medicinal practices. Due to the presence of bioactive substances such as nimbolide, azadirachtin, and gedunin, Neem offers a variety of medicinal properties, including anti-inflammatory and antioxidant properties. Through its effect on pathological inflammatory processes, supplementation with it could alleviate the symptoms of rheumatoid arthritis (RA). Methods: This research aimed to assess Neem seed oil's impact on rats with adjuvant arthritis. Three doses in monotherapy and two in combination with methotrexate (MTX) have been studied, and their effect was compared. Neem p.o. doses of 100, 200, and 300 mg/kg and MTX p.o. doses of 0.3 mg/kg were examined. After clinical parameters assessment, biochemical analysis was performed in plasma. Results: During the acute phase of the experimental arthritis (Day21), levels of MMP-9, MCP-1, and cytokines IL-1beta and IL-17A were measured. The positive results of inflammatory mediators evaluation in plasma encourage additional analysis also in related tissues to prove if Neem seed oil can be used as an adjuvant therapy for RA. Conclusion: In this study, the combination therapy of Neem with MTX was the most effective of all therapies investigated. Acknowledgement: SAIA PROJECT of Kevine Kamga Silihe, Slovakia-Cameroon 2023: “The effect of Crocus sativus L (Saffron), Azadirachta indica (Neem) and their main bioactives compounds in combinatory treatment with methotrexate on experimental arthritis”, VEGA 2/0079/24, VEGA 2/0136/20, VEGA 2/0126/23 and VEGA 2/0091/23.

Keywords: adjuvant, Neem, methotrexate, arthritis

Procedia PDF Downloads 44

Authors: Leila Karshenas, Hamidreza Khodaei, Behnaz Mahdavi

Abstract:

Ovulation is a physiologic process with an inflammatory response that depends on a coordinated activity of gonadotropins and steroid hormones, as well as inflammatory mediators such as cytokines, prostaglandins, leptin, nitric oxide (NO), etc. Conjugated linoleic acid (CLA) is composed of polyunsaturated fatty acids (PUFA) found in dairy products, beef and lamb. There is strong evidence that dietary CLA affects mediators involved in ovulation. The aim of this study was to determine the effects of different doses of dietary CLA on systemic and local hormones and factors involved in ovulation. In this case-control study, 80 (50±2-day old) female mice were randomly divided into four groups (C as the controls and T1, T2 and T3 as the treatment groups). There were four replicates in each group and there were five mice in every replicate (20 mice, in total). The mice in the control group were fed with no CLA in their diet but the ones in the treatment group received 0.1, 0.3 and 0.5g/kg of CLA (replacing corn oil in the diet), respectively for 120 days. Later on, blood samples were obtained from the tails of animals that displayed estrus signs and estradiol (E2), progesterone (P4), LH, FSH, NO, leptin and TNFα were measured. Furthermore, the effects of CLA on the ovarian production of prostaglandins (PGs) and NO were investigated. The data were analyzed by SAS software.CLA significantly decreased serum levels of FSH (p<0.05), LH, estradiol, NO, leptin and TNFα (p<0.01). In addition, CLA decreased progesterone levels but this effect was statistically insignificant. The significantly negative effects of CLA were seen on the ovarian production of PGE2 and PGF2α (p<0.01).It seems that CLA may play an effective role in reducing the ovulation rate in mice as CLA adversely affected female reproduction and it had negative effects on systemic and local hormones involved in ovulation.

Keywords: conjugated linoleic acid, nitric oxide, ovary, ovulation, prostaglandin, gonadotropin

Procedia PDF Downloads 301

Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis

Abstract:

Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.

Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds

Procedia PDF Downloads 135

Authors: S. Essa, H. Safar, R. Raghupathy

Abstract:

Human cytomegalovirus (CMV) continues to be a source of severe complications to immunologically immature and immune-compromised hosts. Effective CMV vaccine that diminishes CMV disease in transplant patients and avoids congenital infection remains of high importance as no approved vaccines exist. Though the exact links of defense mechanisms are unidentified, viral-specific antibodies and Th1/Th2 cytokine responses have been involved in controlling viral infections. CMV envelope glycoprotein B (UL55/gB), the matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and the assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. In this study, mice were immunized with five HCMV antigens (UL32/pp150, UL80a/pp38, UL99/pp28, and UL83/pp65), and serum samples were collected and evaluated for eliciting viral-specific antibody responses. Moreover, Splenocytes were collected, stimulated, and assessed for cytokine responses. The results demonstrated a CMV-antigen-specific antibody response to pp38 and pp65 (E/C >2.0). The highest titers were detected with pp38 (average E/C 16.275) followed by pp65 (average E/C 7.72). Compared to control cells, splenocytes from PP38 antigen immunized mice gave a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-5, and IL-17A (P<0.05). Also, splenocytes from pp65 antigen immunized mice resulted in a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF- α. The designation of target CMV peptides by identifying viral-specific antibodies and cytokine responses is vital for understanding the protective immune mechanisms during CMV infection and identifying appropriate viral antigens to develop novel vaccines.

Keywords: hepatitis C virus, peripheral blood mononuclear cells, neutrophils, cytokines

Procedia PDF Downloads 139

Authors: A. Watson, G. Telford, D. I. Pritchard

Abstract:

Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

Procedia PDF Downloads 121

Authors: Ying Sun, Biao Cheng, Qing Lu, Xuefei Tao, Xiaoyu Lai, Cheng Guo, Dan Wang

Abstract:

Fibrinogen-like protein 2 (FGL2) has recently been identified to play an important role in inflammatory diseases such as atherosclerosis through a thrombin-dependent manner. Here, a murine monoclonal antibody was raised against the critical residue Ser(89) of FGL2, and the effects of the anti-FGL2 mAb (SPF89) were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Firstly, it was proved that SPF89, which belongs to the IgG1 subtype with a KD value of 44.5 pM, could specifically show the expression levels of protein FGL2 in different cell lines of known target gene status. The lipopolysaccharide (LPS)-mediated endothelial cell proliferation was significantly inhibited with a decline of phosphorylation nuclear factor-κB (NF-κB) in a dose-dependent manner after SPF89 treatment. Furthermore, SPF89 reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1, tumor necrosis factor-α, Matrix metalloproteinase MMP-2, Integrin αvβ3, and interleukin-6 in HUVECs. In macrophage-like THP-1 cells, SPF89 effectively inhibited LPS and low-density lipoprotein-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of anti-FGL2 mAb in HUVECs and THP-1 cells were significantly reduced after treatment with an NF-κB inhibitor PDTC. All the above suggest, by efficiently inhibiting LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB dependent pathway, the new anti-FGL2 mAb SPF89 could to be a potential therapeutic candidate for protecting the vascular endothelium against inflammatory diseases such as atherosclerosis. This work was supported by the Program of Sichuan Science and Technology Department (2017FZ0069) and Collaborative Innovation Program of Sichuan for Elderly Care and Health(YLZBZ1511).

Keywords: monoclonal antibody, fibrinogen like protein 2, inflammation, endothelial cells

Procedia PDF Downloads 271

Authors: Hamidreza Khodaei, Ali Daryabeigi Zand

Abstract:

Ovulation is a physiologic process with an inflammatory response that depends on a coordinated activity of gonadotropins and steroid hormones, and inflammatory mediators such as cytokines, prostaglandins, leptin, nitric oxide (NO), etc. Conjugated linoleic acid (CLA) is composed of polyunsaturated fatty acids (PUFA) found in dairy products, beef, and lamb. There is strong evidence that dietary CLA affects mediators involved in ovulation. The objective of this study is to evaluate the impacts of various doses of dietary CLA on systemic and local hormones and parameters involved in ovulation. In this case-control research, 80 (50 ± 2-day old) female mice were randomly divided into 4 groups (C as control treatment and T1, T2 and T3 are considered as the treatment groups). There were four replicates in each group, and there were five mice in every replicate (20 mice, in total). The mice in the control group were fed with no CLA in their diet, but the ones in the treatment group received 0.1, 0.3 and 0.5g/kg of CLA (replacing corn oil in the diet), respectively for four months. After that, blood samples were obtained from the tails of animals that displayed estrus signs and estradiol (E2), progesterone (P4), LH, FSH, NO, leptin and TNFα were measured. In addition, the impacts of CLA on the ovarian production of prostaglandins (PGs) and NO were studied. The data were analyzed by SAS software. CLA considerably decreased serum levels of FSH (p < 0.05), LH, estradiol, NO, leptin and TNFα (p < 0.01). In addition, CLA decreased progesterone levels, but this effect was statistically not significant. The significantly adverse effects of CLA were observed in the ovarian production of PGE2 and PGF2α (p < 0.01). It seems that CLA may play an important role in reducing the ovulation rate in mice as CLA negatively affected female reproduction and it had adverse effects on systemic and local hormones involved in ovulation.

Keywords: conjugated linoleic acid, nitric oxide, ovary, ovulation, prostaglandin, gonadotropin

Procedia PDF Downloads 212

Authors: Goodarzvand Fatemeh, Soori Rahman, Effatpanah Mohammad, Ajbarnejad Ali

Abstract:

Attention deficit hyperactivity disorder (ADHD) is characterized by a pervasive pattern of developmentally inappropriate inattentive, impulsive and hyperactive behaviors that typically begin during the preschool ages and often persist into adulthood. This disorder is related to autism and schizophrenia and other psychological disorders and clinical conditions such as insulin resistance and they may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others. While ADHD is not fully understood as developmental disorder with an etiopathogeny, but studies show that core symptom of disorder was associated with and increased by the interleukins IL-13, where relation of IL-13 with inattention was notable. Regular exercise improves functions associated with attention deficit hyperactivity disorder (ADHD). However, the impact of exercise on cytokines associated with the disease activity remains relatively unexplored. The aim of this study was to examine the effects of 6 weeks high intensity by intervals training (HIIT) on IL-13 levels and insulin resistance in boys with ADHD. Twenty eight boys with ADHD disease in a range of 12-18 year of old participated in this study as the subject. Subjects were divided into control group (n=10) and training group (n=18) randomly. The training group performed progressive HIIT program, 3 days a week for 6 weeks. The control group was in absolute rest at the same time. The results showed that after six weeks of HIIT, IL-13 decreased in the exercise group and these changes achieved (p= 0.002) statistical significance (p < 0.005). The results suggest HIIT with specific intensity and duration utilized in this study had not significant effect on insulin resistance levels in female patients with ADHD (p=0.39), while the difference in the average control and case group was decreased.

Keywords: attention deficit hyperactivity disorder, interleukin 13, insulin resistance, high intensity by intervals training

Procedia PDF Downloads 511

Authors: Shahira El Shafie, Hanaa Eldash, Engy Ghabbour, Mohamed Eid

Abstract:

Several immunologic defects can be found in patients with beta-thalassemia, among which the impairment of neutrophil phagocytic function is of utmost importance. Attention has been directed to the role of proinflammatory cytokines in neutrophil chemotaxis and phagocytosis. Interleukin-8 (IL-8) is an important chemotactic and activation peptide for neutrophils; changes in IL-8 level and potential correlation with neutrophil function can be relevant to immunomodulation pathophysiology in beta-thalassemia patients. This case-control study aimed to evaluate IL-8 level and to assess granulocyte recruitment, as markers of immunomodulation, in poly-transfused thalassemia patients attending Fayoum University Hospitals. The study was conducted on 50 patients with ß thalassemia and 32 age-matched controls. 21/50 patients were transfused more than ten times, and 29/50 were transfused in a lower frequency. Patients and controls were subjected to thorough history taking and clinical examination, measurement of IL-8 level using human IL-8 ELISA kit, and Rebuck skin window technique (RSWT) to assess granulocyte recruitment. Our data showed statistically significant higher levels of IL-8 in ß thalassemia patients compared to control with a much higher difference in patients transfused more than ten times. Neutrophil recruitment was significantly lower in ß thalassemia patients compared to control at 4 hours and 24 hours test time. Although IL-8, the main chemotactic pro-inflammatory cytokine showed a higher level in thalassemia patients, neutrophils recruitment was significantly lower, especially in those receiving more than ten transfusion times. Our findings suggest a possible role of other neutrophil chemotactic factors, defective neutrophil response, or increased IL-8 as compensation of abnormal function. We recommend the use of IL-8 and Rebuck skin window technique as useful markers of immunomodulation in thalassemia and further study for these biomarkers to assess their clinical implications and impact on the management of thalassemia patients.

Keywords: beta-thalassemia, Interleukin-8, Rebuck skin window technique, immunomodulation

Procedia PDF Downloads 187