Tumor Necrosis Factor-α Gene Research Articles

The Association of TNF-α Promoter Polymorphisms with Genetic Susceptibility to Cervical Cancer in a Chinese Han Population

BackgroundThe tumour necrosis factor-α (TNF-α) gene plays an important role in the host immune response, which will influence the development and clearance of cancer. Polymorphism of the TNF-α promoter region is considered to influence its transcription and be a risk factor for tumorigenesis. In the current study, we evaluated the role of TNF-α promoter region polymorphisms in susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer (CC).MethodsA total of 2732 subjects, including 1173 healthy controls, 579 patients with CIN and 980 patients with CC in a Chinese Han population, were selected for the current study. Five SNPs in the TNF-α promoter, rs1799964 (−1031 C>T), rs1800630 (−863 A>C), rs1799724 (−857 C>T), rs1800629 (−308 A>G) and rs361525 (−238 A>G), were selected and genotyped using TaqMan Assays. The association of these SNPs with CIN and cervical cancer was evaluated among healthy controls, CIN and CC patients.ResultsThe frequency distribution of rs1800629 and rs361525 alleles was significantly different between the CC group and the control group (P=0.009 and P=0.002). The rs1800629 A allele was found to be a protective factor for CC (OR=0.72; 95% CI=0.56–0.92). The rs361525 A allele was found to be a risk factor for CC (OR=1.69; 95% CI=1.21–2.38). After pathological subtyping of CC, the allele distribution of rs1800629 and rs361525 were both significantly different between the cervical squamous cell carcinoma and control groups (P=0.002 and P<0.001). The rs1800629 A allele was protective factor for cervical squamous cell carcinoma (OR=0.66; 95% CI=0.50–0.86). The rs361525 A allele was a risk factor for cervical squamous cell carcinoma (OR=1.87; 95% CI=1.32–2.65). Moreover, the genotypic frequency of rs361525 was significantly different between cervical cancer stage I and stage II (P=0.003).ConclusionThe rs1800629 and rs361525 in the TNF-α promoter are associated with susceptibility to CC in the Chinese Han population.

Association of Tumor Necrosis Factor-α Gene Promoter Polymorphisms with Periodontitisin Type II Diabetic Syrian Population

Association of Tumor Necrosis Factor-α Gene Promoter Polymorphisms with Periodontitisin Type II Diabetic Syrian Population

Dietary supplementation of Solanum aethiopicum and Solanecio biafrae leaves alters stress and immune responses, antioxidant status, and meat quality in broilers raised in a hot-dry environment

ABSTRACT 1. This study investigated the influence of dietary supplementation of Solanum aethiopicum and Solanecio biafrae leaves, which have nutraceutical properties, on stress response, cytokine expression, antioxidant status, blood chemistry, abdominal fat and meat quality in broilers reared in a hot, dry environment. 2. One day old, Ross 308 chicks (n = 350) were randomly allotted to basal diets containing either no supplement (D1); 2.5 g/kg Solanum aethiopicum leaf (SAL; D2); 5 g/kg SAL (D3); 2.5 g/kg Solanecio biafrae leaf (SBL; D4); or 5 g/kg SBL (D5) for 42 d. Birds were reared at 34 ± 2°C and 40–50% relative humidity for 6 h/d from 22–42 d. Each dietary group was replicated in seven pens containing 10 chicks. 3. In the period 1–21 d, body weight gain, feed efficiency and feed intake were not influenced by diet. At 22–42 and 1–42 d, birds supplemented with SAL and SBL had higher (P < 0.05) body weight gain and feed efficiency than the D1 birds. Cloaca temperature, carcase cuts and relative organ weight did not differ between diets. The D3 birds had higher (P < 0.05) erythrocytes and haemoglobin compared with other birds. Dietary supplements reduced (P < 0.05) mortality, abdominal fat, serum total cholesterol, corticosterone, glucose and blood aspartate aminotransferase levels. 4. The treatments up-regulated (P < 0.05) splenic intelukin-10, and down-regulated (P < 0.05) tumour necrosis factor-α and interleukin-1β genes. A dose-dependent improvement (P < 0.05) in antioxidant enzyme activities and total antioxidant capacity of serum and breast muscle were found in the supplemented birds. The breast meat of the supplemented birds had lower (P < 0.05) carbonyl and malondialdehyde contents, and higher (P < 0.05) water holding capacity and redness compared with the non-supplemented meat. 5. These results illustrated that supplementation with either 5 g/kg SAL or 5 g/kg SBL attenuated the deleterious effects of heat stress in broiler chickens.

Human adrenomedullin and its binding protein attenuate tissue injury and inflammation following hepatic ischemia reperfusion in rabbits

BackgroundLiver injury caused by ischemia reperfusion (I/R) during surgical procedures, such as liver resection or liver transplantation, is a major cause of liver damage and graft failure. The current method of treatment is mostly preventative (i.e., ischemic preconditioning). While a number of pharmacological modalities have been studied to reduce hepatic I/R injury, none have been entirely successful. It has been demonstrated that the administration of adrenomedullin (AM) in combination with AM-binding protein (AM/AMBP-1) exerts significant protective effects in various pathological conditions. In an effort to develop AM/AMBP-1 as a novel therapeutic for hepatic I/R injury, the present study examined the effect of a low dose of human AM, which does not induce hypotension, in combination with human AMBP-1 in a rabbit model of hepatic I/R (i.e., non-rodent species). MethodsIschemia of 70% of the liver was induced by placing a microvascular clip across the hilum of the left and median lobes for 60 min. The clip was then removed to commence reperfusion. At 15 min following clip removal (i.e., reperfusion), human AM/AMBP-1 was administered intravenously via the ear marginal vein continuously for 30 min. At 20 h, blood and tissue samples were collected for various measurements. ResultsThe serum levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and lactate dehydrogenase, were elevated following hepatic I/R. The administration of AM/AMBP-1 significantly decreased these levels by 58, 44, 41%, respectively. Hepatic I/R increased the direct and total bilirubin levels, whereas treatment with human AM/AMBP-1 decreased these levels by 60% and 69%, respectively. Treatment with AM/AMBP-1 also inhibited interleukin-6 gene expression by 95%. There were no changes in tumor necrosis factor-α (TNF-α) gene expression and myeloperoxidase activity (MPO), lactate and Suzuki scores after treatment. The treatment, however, reduced apoptosis post-hepatic I/R in the ischemic portion of the liver. ConclusionAdditional experiments with AM and AMBP-1 alone are needed to completely interpret the experimental results in this non-rodent species of hepatic I/R injury. The present study suggests that human AM/AMBP-1 may be developed as a novel therapeutic to attenuate hepatic I/R associated inflammation and liver injury.

Molecular Analysis of rs2910164 Polymorphism and its Association with TNF-α Gene Expression in Colorectal Cancer

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world, which has been introduced as the third most common cancer and the third leading cause of death. This cancer is uncommon before the age of 50. Its prognosis is controversial, and many studies report a poor prognosis in older patients, and the others show no difference. In addition to the factors, such as diet, environmental factors, somatic, and hereditary mutations, genetic factors, including altered expression of some microRNAs and mutations in tumor necrosis factor-α (TNF-α) gene, may be involved in CRC. Objectives: This study aimed to investigate the rs2910164 polymorphism from the miRNA146a gene and its association with the expression of TNF-α gene in CRC before and after the age of 50 for early diagnosis and treatment. Methods: In this study, 65 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with cancerous lesions of colorectal tissue (37 cases over 50 years were considered as the case group and 28 cases under 50 years were considered as the control group). DNA was extracted from the samples, and rs2910164 polymorphism of the miRNA146a gene was investigated by PCR. Moreover, RNA was extracted from the samples, and the expression of the miRNA146a and TNF-α genes were evaluated. Finally, Epi Info software version 7.1.3.10 and MedCalc Version 19.2.0 were used for data analysis. Results: The frequency of GG, GC, and CC genotypes from rs2910164 polymorphism of miRNA146a gene in the control group was 0.29, 0.46, and 0.25, respectively, but in the case group, it was 0.54, 0.38, and 0.08, respectively. The results also showed that the expression of miRNA146a (P = 0.00006) and TNF-α (P = 0.009) genes was higher in the case group than in the control group. Conclusions: Based on the results of this study, a significant correlation was found between GG genotype and rs2910164 polymorphism of miRNA146a gene and TNF-α gene expression in the CRC samples. Therefore, investigation of these factors may be helpful in patients with CRC over 50 years.

Enhanced H3K4 Trimethylation in TNF-α Promoter Gene Locus with Cell Apoptosis in the Ventral-Medial Striatum following Opioid Withdrawal of Neonatal Rat Offspring from Morphine-Addicted Mothers.

Prenatal opioid exposure might disturb epigenetic programming in the brain of neonatal offspring with various consequences for gene expressions and behaviors. This study determined whether altered trimethylation of histone 3 at lysine 4 (H3K4me3) in the promoter of the tumor necrosis factor-α (tnf-α) gene with neural cell apoptosis was involved in the ventral-medial striatum, an important brain region for withdrawal symptoms, of neonatal rat offspring from morphine-addicted mothers. Female adult rats were injected with morphine before gestation and until 14 days after giving birth. On postnatal day 14 (P14), rat offspring from morphine-addicted mothers were subjected to an opioid-withdrawal protocol and were analyzed 2 or 8 h after administration of that protocol. Expressions of the TNF-α protein, H3K4me3 in the tnf-α promoter gene, and neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring were evaluated. In the absence of significant opioid withdrawal (2 h after initiation of the opioid-withdrawal protocol on P14), prenatal morphine exposure led to increased levels of H3K4me3 in the tnf-α promoter gene, of the TNF-α protein, and of neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring. Following opioid withdrawal (8 h after initiation of the opioid-withdrawal protocol on P14), differential expression of H3K4me3 in the tnf-α promoter gene locus and upregulation of the level of TNF-α protein expression were further enhanced in these offspring. In addition, increased levels of caspase-3 and neural cell apoptosis were also observed. Taken together, this study revealed that prenatal opioid exposure can activate an epigenetic histone mechanism which regulates proinflammatory factor generation, which hence, led to cell apoptotic damage within the ventral-medial striatum of neonatal rat offspring from morphine-addicted mothers. More importantly, the opioid-withdrawal episode may provide augmented effects for the abovementioned alterations and could lead to deleterious effects in the neonatal brain of such offspring.

Tumor necrosis factor-α gene promoter −308 and −238 polymorphisms and its serum level in psoriasis

BackgroundPsoriasis is a chronic, immune-mediated, inflammatory skin disease affecting genetically predisposed individuals and requiring long-term treatment. The etiology of psoriasis is not fully understood. This article aimed to determine association between genetic polymorphisms in tumor necrosis factor-α (TNF -α) promoter −308 (rs1800629) and −238 (rs 361,525) and its serum level in psoriasis patients. MethodsThe study was conducted on 70 patients with psoriasis and 70 age and sex-matched, healthy individuals. All patients were subjected to history taking and complete medical examination. The polymorphisms of TNF -α promoter gene −308 (rs1800629) and −238 (rs 361,525) were detected by real time PCR and Serum levels of TNF -α were measured by ELISA technique. ResultsAG polymorphism and A allele of TNF-α −238 G/A (rs 361,525) were significantly more in patients than controls, whereas AG polymorphism and A allele of TNF-α −308 G/A (rs1800629) were significantly more in controls than patients. There were significant high levels of TNF-α in serum of patients in comparison to controls. ConclusionsThe AG polymorphism and A allele of TNF-α −238G/A (rs 361,525) may act as a risk factor for occurrence of psoriasis, whereas AG polymorphism and A allele of TNF-α −308G/A (rs1800629) may have protective role. There is pivotal role of TNF-α as a pro-inflammatory mediator in pathogenesis of psoriasis.

Correlation between TNF-α- serum level and TNF-α -308 gene polymorphism in Iraqi patients with type 2 diabetes mellitus

Type II diabetes mellitus -T2DM- is a metabolizing disease resulted when insulin deficiency. Mutations of tumour necrosis factor-α gene (TNF-α gene) is reminiscent of intervention with type of insulin-sensitive glucose utilization and cause resistance to insulin that leads to T2DM. Our work was aimed to evaluate the impact of TNF-α-308 G/A mutations and their relation to the establishment of T2DM in Iraqi people. In this study, DNA extraction and sequencing were carried out by using conventional polymerase chain reaction (PCR). A TNF-α-serum level with T2DM was evaluated by using ELISA technique. In this study, it seems that whatever A or G allele of TNF-α-308 mutation in the Iraqi people is related with the increasing of TNF-α productivity stills to be decided. It is noted that making of this cytokine (TNF-α) might be impacted by several mutations occurred in their gene as well as other immune-associated factors. In conclusion, TNF-α-308 G/A SNP in Iraqi people might be involved in genetic susceptibleness to T2DM.

Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS-induced acute lung injury.

Muscle may contribute to the systemic inflammatory environment during critical illness, but leukocyte interaction and cytokine influence on muscle and its response has not been fully explored in this context. Using an in vivo model of intratracheal lipopolysaccharide (IT LPS)-induced acute lung injury, we show that skeletal muscle rapidly responds with expression of proinflammatory genes, which may be explained by migration of LPS into the circulation. Treatment of mature C2C12 myotubes with LPS at a level achieved in the circulation following IT LPS elicited a proinflammatory cytokine expression profile similar to that of in vivo murine muscle following IT LPS. Stimulation with toll-like receptor (TLR) 2 and 3 agonists provoked comparable responses in C2C12 myotubes. Additionally, co-cultures of C2C12 myotubes and bone marrow-derived macrophages (BMDM) identified the capacity of macrophages to increase myotube proinflammatory gene expression, with tumor necrosis factor-α (TNFα) gene and protein expression largely attributable to BMDM. To investigate the contribution of TNFα in the synergy of the co-culture environment, C2C12 myotubes were treated with recombinant TNFα, co-cultures were established using TNF-deficient BMDM, and co-cultures were also depleted of TNFα using antibodies. To determine whether the in vitro observations were relevant in vivo, mice received intramuscular administration of LPS±TNFα or TNFα-neutralizing antibodies and showed that TNFα is both sufficient and necessary to induce synergistic cytokine release from muscle. Taken together, these data demonstrate how skeletal muscle tissue may contribute proinflammatory cytokines following acute endotoxin injury and the potential of leukocytes to augment this response via TNFα secretion.

Assessment of IL-10, IL-1ß and TNF-α gene polymorphisms in patients with peri-implantitis and healthy controls.

Peri-implantitis (PI) is a multifactorial condition caused by the interactions of pathogens and the host immune response. Previous studies have demonstrated a relationship between PI and specific gene polymorphisms, particularly cytokine genes involved in the pathogenesis of PI. This study aimed to evaluate the frequency of single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) genes in PI patients and healthy controls. A total of 50 patients with PI and 89 periodontally healthy controls were recruited for this study. Venous blood samples (5cc) were collected, and DNA was extracted. After DNA purification, the relevant gene segments were amplified by polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) and electrophoresis were performed to assess the polymorphisms of the related genes. The analysis revealed that allele and genotype frequencies of IL-10 ─ 819 C/T, IL-10 ─ 592 C/A, and IL-1ß + 3954 C/T significantly differed between PI patients and healthy controls. The analysis revealed no significant association between TNF-α ─ 857 G/A and TNF-α ─ 308 G/A polymorphisms and PI. Our results indicated that specific gene polymorphisms of IL-10 ─ 819 C/T, IL-10 ─ 592 C/A, and IL-1ß + 3954 C/T may play a role in the pathogenesis of PI, and increase its risk of occurrence.

Liraglutide Increases the Catabolism of Apolipoprotein B100-Containing Lipoproteins in Patients With Type 2 Diabetes and Reduces Proprotein Convertase Subtilisin/Kexin Type 9 Expression.

Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect of the GLP-1 agonist liraglutide on the metabolism of apoB100-containing lipoproteins. We performed an in vivo kinetic study with stable isotopes (L-[1-13C]leucine) in 10 patients with T2D before and after 6 months of treatment with liraglutide (1.2 mg/day). We also evaluated in mice the effect of liraglutide on the expression of genes involved in apoB100-containing lipoprotein clearance. In patients with T2D, liraglutide treatment significantly reduced plasma apoB100 (0.93 ± 0.13 vs. 1.09 ± 0.11 g/L, P = 0.011) and fasting triglycerides (1.76 ± 0.37 vs. 2.48 ± 0.69 mmol/L, P = 0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL1-apoB100 (4.11 ± 1.91 vs. 2.96 ± 1.61 pools/day, P = 0.005), VLDL2-apoB100 (5.17 ± 2.53 vs. 2.84 ± 1.65 pools/day, P = 0.008), and IDL-apoB100 (5.27 ± 2.77 vs. 3.74 ± 1.85 pools/day, P = 0.017) and in catabolism of LDL-apoB100 (0.72 ± 0.22 vs. 0.56 ± 0.22 pools/day, P = 0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced proprotein convertase subtilisin/kexin type 9 (PCSK9), retinol-binding protein 4 (RBP4), and tumor necrosis factor-α (TNF-α) gene expression in adipose tissue and decreased PCSK9 mRNA and increased LDL receptor protein expression in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver. Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL1, VLDL2, IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100-containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2D.

Bioactivities of Lentinus polychrous and Ganoderma lucidum (Agaricomycetes) Polysaccharide Extracts.

This study aimed to compare the bioactivities of Lentinus polychrous polysaccharide extracts with Ganoderma lucidum. Three hot water-extracted polysaccharide fractions of L. polychrous (LPE), including immature fruiting bodies (im-LPE), mature fruiting bodies (ma-LPE), and mycelium (my-LPE), were analyzed for their phytochemical contents and bioactivities (e.g., anticancer, antiviral, anti-inflammatory, and immunomodulatory effects) compared with G. lucidum extract (GLE). Although GLE had the highest total phenolic and protein contents and lower carbohydrate content than LPE, im-LPE showed strong inhibition on HepG2 cell proliferation as did GLE. GLE and LPE showed antiviral effects on herpes simplex virus-1 and the relative antiproliferative activity was from im-LPE > my-LPE > ma-LPE. However, im-LPE showed the best protective activity on the viral attachment step with some virucidal effects. Moreover, all LPE showed selective and stronger inhibitory effects on LPS-induced RAW264.7 macrophages than those of GLE on genetic expression. Considering the 50% inhibitory concentration values, my-LPE possessed the strongest inhibitory activity on the expression of cyclooxygenase-2 and inducible nitric oxide synthase. However, ma-LPE had the strongest inhibitory effects on interleukin-1β and tumor necrosis factor-α gene expression. The extracts increased splenocyte proliferation under mycohaemagglutinin induction with a relative order of my-LPE > GLE > ma-LPE = im-LPE. In conclusion, LPE showed positive effects and stronger activity than G. lucidum. L. polychrous may have potential for use as an ingredient in functional foods.

Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model.

The aim of the study was to investigate traditionally used Royal Jelly (RJ) for treating an ethanol-induced gastric ulcer model in rats. A total of 32 Wistar albino male rats were divided into 4 groups of 8: group I = Control, group II = Ethanol, group III = RJ + Ethanol, and group IV = Lansoprazole + Ethanol. In groups II, III, and IV, animals were administered 1ml of absolute ethanol orally after a 24-h fast to induce ulcer formation. The histopathological changes in the gastric mucosa were determined using hematoxylin-eosin (H&E) staining. Immunohistochemically, inducible nitric oxide (iNOS) and nuclear factor kappa beta (Nf-κβ) markings were evaluated in gastric tissue. Cell death in the gastric mucosa was determined by the TUNEL method. Oxidative status markers, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and myeloperoxidase (MPO) levels were determined spectrophotometrically. Expression of the interleukin - 1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) genes in gastric tissues was determined by real-time PCR; and TNF-α, IL-10, and IL-1β levels were determined. RJ was found to inhibit iNOS and Nf-κβ activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-α and IL-1β levels were significantly decreased in the RJ + Ethanol group compared to the Ethanol group. In addition, a decrease in the MPO level indicated that RJ prevented tissue damage, especially by preventing inflammatory cell infiltration. The study demonstrated a possible gastroprotective effect of RJ in a rat ethanol-induced gastric ulcer model.

Association of genetic polymorphism at tumor necrosis factor-α gene promoter - 1031T/C and parasitic infections among children in Northern South Africa

Intestinal parasitic diseases are common in developing countries including South Africa and have been documented to be the most common in children under the age of five. The present study aimed to identify any potential association that may exist between TNF-α promoter gene polymorphism and parasitic infections. A total of 199 blood samples were evaluated from children who were part of the MAL-ED study cohort. The DNA was used to investigate polymorphism in the promoter region of the TNF-α gene at position -1031T/C. The polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. The TC genotype at position -1031 was significantly higher in healthy controls children than in children who were infected with Entamoeba species (59.9% vs 29.4%, P = 0.015) and Entamoeba coli (59.1% vs 30.8%, P = 0.046), indicating that TC genotype may be protective against Entamoeba infections and Entamoeba coli infections. The CC genotype at position -1031 was more common among children with parasite and diarrhea and the results was statistically significant (P = 0.04). This study has revealed that the CC genotype may be is a risk factor for symptomatic parasitic infections while the TC genotype might be protective of Entamoeba infections among children in Dzimauli community.

Effects of immunopotentiators on biochemical parameters, proinflammatory cytokine, and nonspecific immune responses in Shaoxing ducklings

Antibiotics are one of the most important medical discoveries of the 20th century and will remain an essential tool for treating animal and human diseases in the 21st century. However, misuse of antibiotics imperils the development of animal husbandry and human health all over the world, and it is important to find reliable alternatives to antibiotics to reduce the use of antibiotics. In this study, 22 potential immunopotentiators were screened on the levels of apoptosis and inflammatory factor in duck embryo fibroblast cells (DEFs). The results indicated that interferon (IFN)-β and tumor necrosis factor-α gene transcriptions were significantly upregulated, while interleukin (IL)-2 and Bcl2 mRNA levels were significantly decreased during 22 immunopotentiators treatment. Besides, the expression level of IL-1β mRNA showed significant increase during dihydromyricetin, chlorogenic acid, naringin, imiquimod, thymopentin, β-D-Glucan, astragalus polysacharin, astragalus saponin I, astragalus flavone, curcumin, CpG-DNA-2, and LPS treatment. And the level of caspase 3 protein was significantly upregulated with treating chlorogenic acid, β-D-Glucan, astragalus polysacharin, astragalus flavone, curcumin, CpG-DNA-2, chicken IgG, LPS, and poly(I:C). These results indicated that chlorogenic acid, β-D-Glucan, astragalus flavone, CpG-DNA-2, and chicken IgG have the positive immune regulation effects on duck DEFs. Thus, the 5 immunopotentiators were chosen to further verify their immunomodulatory function in vivo. The results showed that the activity of serum AST was significantly downregulated during all immunopotentiators treatments excepting for β-D-Glucan, and the activities of serum IL12p40, IL-1β, IFN-α, and IFN-β were significantly increased compared with the control group. Five immunopotentiators also induced the duck's pattern recognition receptors and inflammatory factor gene expression. In addition, 5 immunopotentiators could facilitate the contents of serum caspase 3, iNOSm and COX2 and reduce the Bcl2. These results suggested that these 5 immunopotentiators could enhance duck innate immune responses. Taken together, our study not only screened out 5 kinds of duck innate immune immunopotentiators but also initially clarified their underlying mechanism of action, which provide a new insight for the development of efficient approaches to prevent the duck disease from pathogen infections.

Neuroprotective effect of resveratrol against radiation after surgically induced brain injury by reducing oxidative stress, inflammation, and apoptosis through NRf2/HO-1/NF-κB signaling pathway.

The impact of resveratrol (RSV) on radiation (RAD)-induced brain injury in rats' brains was investigated. A total of 40 male Wistar Albino rats were randomly divided into four groups (control, RAD, RAD + RSV, and RSV groups, with 10 rats in each group). The results revealed a significant decrease in catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, as well as glutathione (GSH) content. Further, a significant elevation in malondialdehyde, nitric oxide, interleukin-1-beta (IL-1β), IL-6, and transforming growth factor-β1 levels were observed. Furthermore, decreased B-cell lymphoma 2 (Bcl-2), increased Bcl-2-associated X, and tumor necrosis factor-α genes expression, decreased nuclear factor erythroid-related factor 2, heme oxygenase-1, and increased nuclear factor-κB protein levels were noticed. Also, an apoptosis marker, caspase-3-positive cells, was seen in the hippocampus. Those effects were observed in the RAD group of rats. The treatment of RSV displayed a significant amendment of the studied parameters in the brain tissues of the RAD group of animals. This effect is interrelated to the ability of RSV to scavenge the free radicals, enhance the activity of the antioxidant enzymes, increase GSH contents, and downregulate the inflammatory responses and apoptosis markers in the brain tissues of RAD animals. In conclusion, this study demonstrated that the potent antioxidant, anti-inflammatory, and antiapoptotic activities of RSV can improve the antioxidant status and suppress the inflammatory responses and apoptosis in the brain tissues of RAD animals.

Взаимосвязь полиморфизма гена фактора некроза опухоли-альфа с острым панкреатитом: систематический обзор

Взаимосвязь полиморфизма гена фактора некроза опухоли-альфа с острым панкреатитом: систематический обзор

Effect of dietary differences on changes of intestinal microbiota and immune-related gene expression in juvenile olive flounder (Paralichthys olivaceus)

This study was carried out to investigate the effect of dietary differences on intestinal microbial population alteration and its relationship to immune-related gene expression in juvenile olive flounder (Paralichthys olivaceus). Initially, flounder were divided into three groups and supplemented with fishmeal diet (FM), fishmeal replaced by plant protein (termed low-fishmeal (LFM)), and Bacillus sp. SJ-10 probiotic-inoculated LFM (Pro) for 4 weeks. At the start (Initial group) and after completing the feeding trial, intestines were subjected to microbiota analysis and immune-related gene expression. The results of the intestinal microbiota analysis demonstrated that the FM and LFM groups' microbial richness (Chao1, ACE, and Jackknife) and diversity (Shannon and Simpson) did not differ significantly (P > .05) compared to the Initial group. However, the Pro group exhibited increased (P < .05) richness compared to all other groups, but its diversity was lower than that of the Initial group. A similar alteration phenomenon was also found in community composition between these two groups. At the phylum level, the most abundant phylum was Proteobacteria for all groups, but the second most abundant phylum in the Initial and Pro groups was Bacteroidetes, whereas in the FM and LFM groups, it was Firmicutes. An additional analysis of genus-level community composition and prediction of functional composition analysis showed differences among the groups. In the intestine, the transcription of interleukin (IL)-10 and IL-1β was increased more in the LFM and Pro groups compared to the FM group. IL-6 was increased only in the Pro group, and tumor necrosis factor-α (TNF-α) gene expression did not differ significantly among the groups. Therefore, we concluded that dietary changes affect intestinal microbiota composition and immune-related gene expression; in particular, diets containing probiotics can lead to greater change during the same feeding period.

Hyssopus officinalis exerts hypoglycemic effects on streptozotocin-induced diabetic rats via modulating GSK-3β, C-fos, NF-κB, ABCA1 and ABGA1 gene expression.

Type 2 diabetes mellitus (DMT2) is contributed to dual interactions between environmental factors and certain genetic factors. This impressed a great need for novel treatment strategy. Nevertheless, Hyssopus officinalis (H. officinalis) as a terrestrial herb is considered to be an important source of natural antioxidants, it could be assessed as an anti-hyperglycemic agent. In the current study, HPLC identified the active constitutes of H. officinalis, including total polyphenols, and flavonoids. Type 2 diabetes mellitus was induced in male Wistar albino rats via a single ip dose of streptozotocin (STZ) (35 mg/kg BW). One week post diabetes induction, rats were administrated H. officinalis (500 mg/ kg BW) orally for one month. Molecular analysis was assessed to investigate the efficiency of H. officinalis on modulating ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) genes, in addition to apoptotic biomarkers, glycogen synthase kinase-3β (GSK-3β) and cellular oncogene-fos (C-fos) genes. Furthermore, inflammatory biomarkers, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) gene expression were also assessed. H. officinalis alcoholic extract declared the presence of polyphenols as gallic acid and flavonoids as quercetin in addition to many active constituents. Apigenin-7-glucoside and Chlorgenic acid were the most common constituents in the extract. RT-PCR results declared a significant up-regulation in mRNA gene expression of ABCA1 and ABCG1 upon H. officinalis treatment. Meanwhile, C-fos gene expression recorded a slight down-regulation. Gene expression of apoptotic biomarker GSK-3β demonstrated a significant down regulation as well as inflammatory biomarkers NF-κB and TNF-α. From the data recorded, it could be concluded that H. officinalis exerts a great hypoglycemic potential via modulating C-fos, GSK-3β, NF-κB, TNF-α, ABCA1 and ABCG1 gene expression and signaling pathways and could be considered as an effective candidate for DMT2 treatment.

Preconditioning of Adipose-Derived Mesenchymal Stem-Like Cells with Eugenol Potentiates Their Migration and Proliferation In Vitro and Therapeutic Abilities in Rat Hepatic Fibrosis.

Mesenchymal stem cells (MSCs) have considerable therapeutic abilities in various disorders, including hepatic fibrosis. They may be affected with different culture conditions. This study investigated, on molecular basics, the effect of pretreatment with eugenol on the characteristics of adipose tissue-derived MSCs (ASCs) in vitro and the implication of eugenol preconditioning on the in vivo therapeutic abilities of ASCs against CCl4-induced hepatic fibrosis in rats. The effect of eugenol on ASCs was assessed using viability, scratch migration and sphere formation assays. Expressions of genes and proteins were estimated by immunofluorescence or qRT-PCR. For the in vivo investigations, rats were divided into four groups: the normal control group, fibrotic (CCl4) group, CCl4+ASCs group and CCl4 + eugenol-preconditioned ASCs (CCl4+E-ASCs) group. Eugenol affected the viability of ASCs in a concentration- and time-dependent manner. Eugenol improved their self-renewal, proliferation and migration abilities and significantly increased their expression of c-Met, reduced expression 1 (Rex1), octamer-binding transcription factor 4 (Oct4) and nanog genes. Furthermore, E-ASCs showed more of a homing ability than ASCs and improved the serum levels of ALT, AST, albumin, total bilirubin and hyaluronic acid more efficient than ASCs in treating CCl4-induced hepatic fibrosis, which was confirmed with histopathology. More interestingly, compared to the CCl4+ASCs group, CCl4+E-ASCs group showed a lower expression of inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), cluster of differentiation 163 (CD163) and tumor necrosis factor-α (TNF-α) genes and higher expression of matrix metalloproteinase (MMP)-9 and MMP-13 genes. This study, for the first time, revealed that eugenol significantly improved the self-renewal, migration and proliferation characteristics of ASCs, in vitro. In addition, we demonstrated that eugenol-preconditioning significantly enhanced the therapeutic abilities of the injected ASCs against CCl4-induced hepatic fibrosis.