Interleukin-1β Gene Research Articles

Effects of Alkalinity Stress on Amino Acid Metabolism Profiles and Oxidative-Stress-Mediated Apoptosis/Ferroptosis in Hybrid Sturgeon (Huso dauricus ♀ × Acipenser schrenckii ♂) Livers

Alkaline water is toxic to cultured aquatic animals that frequently live in pH-neutral freshwater. Overfishing and habitat destruction have contributed to the decline in the wild sturgeon population; consequently, the domestic hybrid sturgeon has become an increasingly important commercial species in China. Hybrid sturgeons are widely cultured in alkaline water, but little is known about the effects of alkalinity stress on hybrid sturgeon liver tissues. We exposed hybrid sturgeons to four alkaline concentrations (3.14 ± 0.02 mmol/L, 7.57 ± 0.08 mmol/L, 11.78 ± 0.24 mmol/L and 15.46 ± 0.48 mmol/L). Histopathology, biochemical index assessment, gene expression level detection and metabolomics analysis were used to investigate the negative effects on liver functions following exposure to NaHCO3. Livers exposed to alkaline stress exhibited severe tissue injury and clear apoptotic characteristics. With increased exposure concentrations, the hepatic superoxide dismutase, catalase, glutathione peroxidase and alkaline phosphatase activities significantly decreased in a dose-dependent manner. NaHCO3 exposure up-regulated the transcriptional levels of apoptosis/ferroptosis-related genes in livers. Similarly, the expression trends of interleukin-1β and heat shock protein genes also increased in high-alkalinity environments. However, the expression levels of complement protein 3 significantly decreased (p < 0.05). Hepatic untargeted metabolomics revealed the alteration conditions of various metabolites associated with the antioxidant response, the ferroptosis process and amino acid metabolism (such as beta-alanine metabolism; alanine, aspartate and glutamate metabolism; and glycine, serine and threonine metabolism). These data provided evidence that NaHCO3 impaired immune functions and the integrity of hybrid sturgeon liver tissues by mediating oxidative-stress-mediated apoptosis and ferroptosis. Our results shed light on the breeding welfare of domestic hybrid sturgeons and promote the economic development of fisheries in China.

Impacts of microRNA-155 on the Expression of Interleukin-1β and Tumor Suppressor Gene JADE-1 in Iraqi Women with Cervical Cancer

Background: Cervical cancer poses a significant health challenge globally, with an increase in nations with poor or medium incomes, including Iraq. Objective: This study investigates the molecular interaction between microRNA-155 (miR-155-5p), interleukin-1β (IL-1β), and the tumor suppressor gene JADE-1, exploring their roles in the pathogenesis of cervical cancer among Iraqi women. Methods: By analyzing samples from 40 cervical cancer patients and 40 healthy controls, the study investigated the expression levels of miR-155-5p and its impact on IL-1β and JADE-1 through qRT-PCR and ELISA techniques. Results: The study reveals a significant upregulation of miR-155-5p in patients compared to controls, alongside a notable downregulation of JADE-1. While slightly elevating the serum level of IL-1β (p>0.05). These changes at the molecular level point to miR-155-5p possibly playing a role in cancer by creating an inflammatory environment around the tumor and decreasing the activity of pathways that stop tumors from growing through JADE-1. Conclusions: The study paves the way for further exploration into the mechanistic pathways of these molecules, offering potential biomarkers for early detection, prognosis, and the development of targeted therapies, thus aiming to improve the management and outcomes for women afflicted with cervical cancer in Iraq.

Efficacy of doxorubicin and lipiodol therapy by trans-arterial chemoembolization in hepatocellular carcinoma Egyptian patients and relation to genetic polymorphisms

ABSTRACT Background Genetic polymorphisms play a crucial role in predicting treatment efficacy in patients with hepatocellular carcinoma (HCC). This study aims to evaluate the response to Transarterial Chemoembolization (TACE) in relation to the genetic polymorphisms of interleukin 28B (IL28B) and angiopoietin-2 (ANGPT2) in HCC patients. Research design and methods Prospective cohort study conducted on 104 eligible HCC Egyptian patients who underwent TACE using doxorubicin and lipiodol. Genotyping of the IL28B and ANGPT2 genes was performed with laboratory data analysis. Results At baseline IL28B rs12979860 genotypes C/T, C/C and T/T appeared in 43.9%, 34.6% and 21.5% while ANGPT2 rs55633437 genotypes C/C, C/A and A/A found in 71.03%, 28.04% and 0.93% of patients respectively. After one month of therapy, 51.4% of patients achieved a complete response. There was a significant difference in relation to IL28B rs12979860 genotypes (p = 0.017) whereas ANGPT2 rs55633437 genotypes (p = 0.432) showed no significant difference in patient response after one month of TACE Conclusion This study demonstrates the effectiveness of TACE in Egyptian HCC patients, as evidenced by low recurrence rates. Furthermore, the IL28B rs12979860 (C/T) gene may be associated with the efficacy and prognosis of TACE treatment in HCC Egyptian patients. Trial Registration The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05291338)

NLRP3 inflammasome pathway involved in the pathogenesis of metabolic associated fatty liver disease

The prevalence of Metabolic-associated fatty liver disease (MAFLD) has been steadily increasing worldwide, paralleling the global epidemic of obesity and diabetes. It is estimated that approximately one-quarter of the global population is affected by MAFLD. Despite its high prevalence, MAFLD often goes undiagnosed due to the lack of specific symptoms in its early stages. However, as the disease progresses, it can lead to more severe liver-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, we aimed to investigate the expression levels of the nucleotide-binding oligomerization domain, leucine-rich repeat (LRR)—containing proteins (NLR) family pyrin domain-containing protein 3 [NLRP3] inflammasome pathway components, NLRP3 and interleukin 1β (IL-1β) genes in patients with MAFLD with various degrees of steatosis and fibrosis. Participants were classified into two equal groups; MAFLD group: consisted of 120 patients with different degrees of hepatic fibrosis and steatosis based on fibro scan results. The non-MAFLD group was comprised of 107 participants. Molecular analysis of pyrin domain-containing protein 3 and IL-1β relative gene expressions was performed in the blood of all participants, using Real-time quantitative polymerase chain reaction (RT-qPCR). Patients with post-MAFLD hepatic fibrosis had significantly higher relative gene expression levels of IL-1β and NLRP3; with IL-1β > 1.1 had AUC of 0.919, sensitivity of 88.33, specificity of 96.26, PPV of 96.4, and NPV of 88 and 92.3 accuracy (p value < 0.001). NLRP3 > 1.33 had a sensitivity of 97.5, specificity of 99.07, PPV of 99.2, NPV of 97.2, and 98.3 accuracy with an AUC of 0.991 (p value < 0.001) as predictors of post-MAFLD hepatic fibrosis.. A significant increase in the mean relative gene expression levels of both IL-1β and NLRP3 found in patients with early fibrosis (F0-F1-2); 31.97 ± 11.8 and 6.76 ± 2.18, respectively; compared with patients with advanced hepatic fibrosis stages (F2-F3); 2.62 ± 3.71 and 4.27 ± 2.99 (p < 0.001 each). The present study provides novel evidence for the possible involvement of IL-1β and NLRP3 inflammasome in metabolic-associated fatty liver disease pathogenesis and could be valid markers for the early detection of post-MAFLD hepatic fibrosis.

Interleukin-6 (-174G/C), Interleukin-1β (-511 C/T), and Apolipoprotein B-100 (2488 C/T) Gene Polymorphism in Pre-Eclampsia.

Background and objectives: Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1β, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods: This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1β, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy-Weinberg equation and chi-square test to evaluate the results. Results: There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1β-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy-Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions: The polymorphisms of the IL-6, IL-1β, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy-Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied.

Macleaya cordata extract exhibits some potential as a surrogate antibiotic by improving gastrointestinal epithelial status and humoral response in goats

Macleaya cordata extract (MCE) is a potential replacement for antibiotics. In the current study, effects of MCE on the gastrointestinal health and humoral responses of host animals were explored. A total of 30 weanling goats with similar body weight of 9.15 ± 1.36 kg were randomly allocated into three groups (n = 10 per group): control group (CON group, fed with a basal diet), antibiotic group (Abx group, fed with the basal diet supplemented with 0.18 g/d vancomycin and 0.36 g/d neomycin), and MCE group (fed with the basal diet supplemented with 5 g/d MCE), for three weeks. Results showed that antibiotic addition decreased the height and area of rumen papillae, ruminal mucosa Toll-like receptor 8 (TLR8), interleukin-8 (IL-8) and interleukin-1β (IL-1β) gene relative expression levels and microbial diversity, altered the volatile fatty acid (VFA) profile in the rumen, and increased monocytes amount and CD4+ T cells percentage in the peripheral blood (P < 0.05) compared to CON group. MCE addition increased the average daily gain, ileal villus height, villus height/crypt depth, and immunoglobulin M (IgM) content in the peripheral blood (P < 0.05) compared to the CON. Additionally, MCE addition decreased the proportion of isobutyric acid in the chyme of the ileum (P = 0.005) compared to the CON group. These results suggest that antibiotic supplementation may suppress the epithelial state and microbial diversity and fermentation in goats, but stimulate cellular response to maintain the growth performance of goats. MCE administration improved the epithelial state and humoral response to promote the growth performance in goats.

Mechanism of Biejiajian Pills against non-alcoholic steatohepatitis based on lipidomics

This study aims to explore the potential mechanism of Biejiajian Pills in the treatment of non-alcoholic steatohepatitis(NASH) based on lipidomics. A mouse model of NASH was induced by high-fat/high cholesterol diet, and the mice of the normal group were fed with a normal diet. The therapeutic efficacy of Biejiajian Pills against NASH was evaluated through biochemical indexes in both of serum and liver, as well as the hepatic histopathology. Lipid metabolites in the liver were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)-based lipidomics. Then the partial least-squares discriminant analysis, t-test and receiver operating characteristic curve analysis were performed to screen the differential lipid metabolites and the main biomarkers. The proteins and genes involved in the lipid metabolism and inflammatory response were detected by Western blot and qPCR. The results demonstrated that Biejiajian Pills notably lowered the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) in the serum and the levels of triglyceride(TG) and total cholesterol(TC) in the liver tissue. In addition, Biejiajian Pills alleviated the lipid accumulation, hepatocyte ballooning, and liver fibrosis. Lipidomics revealed that Biejiajian Pills regulated the content of 11 biomarkers including phosphatidyl choline(PC), phosphatidyl ethanolamine(PE), sphingomyelin(SM), and ceramide(Cer). The results of Western blot and qPCR demonstrated that Biejiajian Pills regulated the expression of sterol regulatory element-binding protein 1(SREBP1), peroxisome proliferator-activated receptor gamma(PPARγ) and phospho-AMP-activated protein kinase(p-AMPK), and the mRNA level of fatty acid translocase 36 gene(Cd36), Pparγ, cardiolipin synthase 1 gene(Crls1), and phospholipase Cβ2 gene(Plcβ2). Furthermore, Biejiajian Pills displayed inhibitory effects on phospho-p38 MAPK(p-p38 MAPK) and phospho-ERK1/2(p-ERK1/2) and the mRNA levels of interleukin-6 gene(Il-6), interleukin-1β gene(Il-1β) and tumor necrosis factor-α gene(Tnf-α). In conclusion, Biejiajian Pills could alleviate the lipid metabolism disorders and regulate the expression of SREBP1, PPARγ, and p-AMPK and the mRNA levels of pro-inflammatory cytokines.

Dietary multi-strains Bacillus spp. enhanced growth performance, blood metabolites, digestive tissues histology, gene expression of Oreochromis niloticus, and resistance to Aspergillus flavus infection

The present study tested the symbiotic effects of dietary multi-strain Bacillus probiotics (MSB) (Bacillus licheniformis, B. pumilus, and B. subtilis) in Nile tilapia (Oreochromis niloticus) exposed to Aspergillus flavus infection. Furthermore, this study investigated water quality, growth performance, blood metabolites, histological morphology, immune regulatory genes, and resistance to A. flavus infection. For 70 days, fish (n = 240) were divided into four groups in triplicate: T0 (control group; MSB0), T1 (1 g/kg, MSB1), T2 (2 g/kg, MSB2), and T3 (3 g/kg, MSB3). The immune response was then assessed by challenging all fish groups with the A. flavus pathogen. The results showed that the rearing water quality, fish growth, and blood parameters, as well as total proteins, albumin, globulins, and amylase activity were significantly (P < 0.05) increased in all MSB-treated groups with the best results in MSB2 and MSB3 groups. Meanwhile, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and glucose levels were significantly (P < 0.05) modulated, particularly at higher concentrations of the probiotic mixture (MSB3 group). Fish fed with various levels of MSB showed a maintained histological structure of the hepatopancreas, intestine, and spleen tissues. The mRNA expression of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor receptor-1 (IGF-1R), and interleukin-8 (IL-8) were increased in a dose-dependent manner due to MSB dietary inclusion (P < 0.05). Conversely, the mRNA expression of interleukin-1β (IL-1β) gene was significantly decreased in MSB groups compared to untreated group (P < 0.05). Surprisingly, supplemented groups in Bacillus spp. probiotics exhibited significant modulations in all computed parameters. MSB supplementation improved the pathogenic tolerance of tilapia after change with A. flavus. The integration of growth performance, biochemical, and transcriptomic results confirms that the dietary intervention of multi-strain Bacillus spp. is symbiotic and enhances the benefits for the maintenance of O. niloticus’ health, growth, and digestion. This is achieved by supporting growth genes, reducing inflammatory genes, and enhancing immune-antioxidant resistance to combat A. flavus infection.

Mentha piperita powder enhances the biological response, growth performance, disease resistance, and survival of Oreochromis niloticus infected with Vibrio alginolyticus

Recently, medical plants have been widely used as replacements for antibiotics in disease treatment. Because of its multiple medicinal uses, peppermint (Mentha piperita, MP) is a common herbal remedy. In the present study, MP powder was used as a feed additive to assess growth performance; hematological; biochemical and immune parameters; intestinal histology; and interleukin 1β (IL-1β) gene expression, as well as protection against Vibrio alginolyticus infection in Oreochromis niloticus. O. niloticus (n = 120, 25.66 ± 0.16 g) were fed diets containing 0 (CTR), 2, 3, or 4% MP for 60 days. The results revealed that the inclusion of 2% MP significantly improved the growth indices, intestinal morphological parameters, and reduced the feed conversion ratio. The 2% MP treatment significantly (P < 0.05) increased hematological parameters (red blood cell (RBC) count, white blood cell (WBC) count, packed cell volume% (PCV%), hemoglobin) compared with those of the CTR (P < 0.05). Additionally, feeding fish 2% MP diets decreased the levels of cholesterol and LDL (low-density lipoprotein). There were significant increases in immune responses (serum protein and phagocytic activity and index) and non-significant increases in the expression of IL-1β in the 2% MP group comparing with the other groups and the CTR group (P < 0.05). At the end of the feeding trial (60 days), fish were challenged with a virulent strain of Vibrio alginolyticus and the results showed that the mortality rate decreased in the 2% MP treatment group, followed by the 3% and 4% MP groups. Overall, the results revealed that the dietary inclusion of 2% MP can exhibit growth-promoting and immunostimulant effects for sustainable aquaculture.

Ameliorative Effect of Macadamia Nut Protein Peptides on Acetaminophen-Induced Acute Liver Injury in Mice.

This study aims to examine the ameliorative effect of macadamia nut protein peptides (MPP) on acetaminophen (APAP)-induced liver injury (AILI) in mice, and develop a new strategy for identifying hepatoprotective functional foods. The molecular weight distribution and amino acid composition of MPP were first studied. Forty mice were then randomized into four groups: control group (CON), APAP model group, APAP+MPP low-dose group (APAP+L-MPP), and APAP+MPP high-dose group (APAP+H-MPP). The APAP+L-MPP (320 mg/kg per day) and APAP+H-MPP (640 mg/kg per day) groups received continuous MPP gavage for 2 weeks. A 12 h of APAP (200 mg/kg) gavage resulted in liver damage. Pathological alterations, antioxidant index levels, expression of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB), and associated inflammatory factors were determined for each treatment group. The results revealed that the total amino acid content of MPP was 39.58 g/100 g, with Glu, Arg, Asp, Leu, Tyr, and Gly being the major amino acids. The molecular weight range of 0-1000 Da accounted for 73.54%, and 0-500 Da accounted for 62.84% of MPP. MPP ameliorated the pathological morphology and reduced the serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase of AILI in mice. MPP significantly increased the activities of superoxide dismutase and glutathione peroxidase in the liver compared with the APAP group. MPP inhibited the expression of TLR4, NF-κB, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) genes in AILI mice. MPP also inhibited the expression levels of inflammatory factors (TNF-α and IL-6). Our study concludes that MPP alleviates AILI in mice by enhancing antioxidant capacity and inhibiting TLR4/NF-κB pathway-related gene activation.

Efficacy of nutritional selenium nanoparticles on growth performance, immune response, antioxidant capacity, expression of growth and immune-related genes, and post-stress recovery in juvenile Sobaity seabream (Sparidentex hasta)

This study evaluated the impacts of nano-Se on the growth, immunity, antioxidant capacity, physiological parameters, gene expression, and stress resistance of fingerling Sobaity seabream (Sparidentex hasta). The fish with an average weight of 21.5 ± 0.1 g were divided into four treatment groups in triplicates that received one of the test diets supplemented with varying levels of nano-Se: 0 (control), 0.5 (Se-0.5), 1 (Se-1), and 2 (Se-2) mg/Kg for 60 days. The results showed that final weight, weight gain rate, specific growth rate, feed intake, and feed conversion ratio improved with significant linear and quadratic trends (P < 0.05) in response to nano-Se-supplemented diets, and the best values were measured in the Se-2 group. Superoxide dismutase activity level remained unaffected among the four groups (P > 0.05). Catalase activity increased in nano-Se-supplemented groups, with the highest level measured in fish fed the Se-0.5 diet. Glutathione peroxidase activity levels were not significantly different between the control and nano-Se groups, but the lowest malondialdehyde concentration was detected in the Se-2 group. Nano-Se had no marked effect on total plasma Ig levels; however, the highest lysozyme activity and alternative complement activity (ACH50) were observed in the Se-0.5 and Se-2 groups, respectively. No significant differences (P > 0.05) were observed in plasma total protein, albumin, globulin, triglyceride, and thyroid hormone (T3 and T4) contents among the groups. However, the lowest cholesterol and low-density lipoprotein values and the highest high-density lipoprotein concentration were measured in the Se-2 group. The Se-0.5 and Se-1 groups exhibited significantly lower levels of aspartate aminotransferase activity, and the lowest alkaline phosphatase activity level was detected in the Se-1 group. The expression level of insulin-like growth factor I gene in all nano-Se-fed groups was significantly higher than the control. Also, the expression of interleukin-1β and lysozyme genes was significantly upregulated in nano-Se-supplemented groups, with the highest values in the Se-2 group. Following acute crowding stress, plasma cortisol and lactate levels at all post-stress time intervals were not significantly different among the experimental groups. Fish fed the Se-0.5 and Se-2 diets tended to have lower plasma glucose concentrations than other groups. In conclusion, dietary nano-Se at 2 mg/kg is recommended to promote growth performance and enhance antioxidant and immune parameters in Sobaity juveniles.

Phenolic-rich fraction of green tea attenuates histamine-mediated cardiopulmonary toxicity by inhibiting Cox-2/NF-κB signaling pathway and regulating oxidant/antioxidant balance

BackgroundHistamine (HIS) has a substantial impact on the development of numerous allergic disorders including asthma. Antihistamines mostly target histamine receptor-1 alone, so it is not entirely effective in the treatment of allergic diseases. In the current investigation, we examine the growing evidence for novel therapeutic strategies that aim to treat histamine-mediated cardiopulmonary toxicity with the phenolic-rich fraction of green tea (PRFGT).ResultsOur findings demonstrated that weekly ingestion of HIS to rats induced oxidant/antioxidant imbalance in both lung and heart homogenates. The histopathological examination demonstrated extensive interstitial pneumonia with progressive alveolar and bronchial damage in HIS receiving groups. Heart sections showed severe myocardial necrosis and hemorrhage. All lesions were confirmed by the immunohistochemical staining that demonstrated strong caspase-3, cyclooxygenase-2 (Cox-2), and tumor necrosis factor-α (TNF-α) protein expressions along with upregulation of the pulmonary m-RNA expression of TNF-α, nuclear factor kappa-B (NF-κB), and interleukin-1β (IL-1β) genes and cardiac levels of many apoptotic genes. Otherwise, the pretreatment of rats with PRFGT had the ability to alleviate all the aforementioned toxicological parameters and return the microscopic picture of both lung and heart sections to normal histology.ConclusionsWe concluded that PRFGT’s powerful antioxidant, anti-inflammatory, and anti-apoptotic properties can reduce cardiopulmonary toxicity caused by HIS. We recommended daily intake of green tea as a beverage or adding it to foods containing elevated levels of HIS to prevent its possible toxicity.

Predictive Potential Of Il28b Gene In Hcv Patients, Resistant To Daclatasvir And Sofosbuvir In KPK Population.

Recently various combinations of direct acting antivirals (DAAs) have been tried successfully. The Sofosbuvir + Daclatasvir combination has been used with promising results. Recently, resistance has been noticed against DAAs. Therefore, polymorphism at particular sites in the interleukin 28B gene are under study to find possible association with resistance. This study was aimed at finding out any association of SNPs rs8099917 and rs12979860 (IL28B gene) with response and resistance to treatment in HCV genotype 3 patients in Khyber Pakhtunkhwa. This cross sectional, Analytical study was conducted at Gastroenterology/hepatology OPD of Prime Teaching Hospital, Peshawar Medical College. Collected Samples were stored at -20o C in PCR Lab of the College. DNA extraction and genotyping was carried out at BJ Molecular Biology Lab in Rawalpindi. Data was analyzed by using SPSS version 21. Chi-Square Test was used to see the statistically significant differences between rs8099917 T/G and rs12979860 T/C model. In the IL28-B gene, single nucleotide polymorphism at rs12979860 T/C model, we observed that there are 37.5% CC homozygous, 12.5% TT homozygous and 50% CT heterozygous genotypes in resistant patients and 42.85% CC homozygous, 28.57% TT and 28.57% CT genotype in responder group. In rs12979860 T/C model, genotype of IL28-B in the responder and resistant group significantly varies at p-value =0.00572. We conclude that in SNP at rs12979860, CC genotype is associated with clearance of HCV, while CT genotype was more prevalent in the resistant group and associated with chronicity.

Interleukin-1β gene rs1143634 polymorphism and cardiovascular complications in patients with coronary artery atherosclerosis

The course of heart failure, regardless of its etiology, is associated with local and systemic activation of inflammatory signaling cascades. Identification of the association of candidate cytokine genes with the risk of developing coronary heart disease and chronic heart failure remains a subject of interest for many researchers. The review presents an analysis of studies of the rs1143634 polymorphism of the IL-β gene in relation to the risk of atherosclerotic cardiovascular complications. The presence of the minor allele T is associated with an increase in the concentration of IL-1β in the blood serum. Data on the role of the rs1143634 polymorphism of the IL-β gene in atherosclerotic coronary heart disease, including in combination with chronic heart failure syndrome, are presented, taking into account ethnic characteristics and gender of patients. The carriage of the T allele was associated with the risk of developing atherosclerosis and myocardial infarction. At the same time, it is reported that the C allele and the CC genotype of the rs1143634 polymorphism of the IL-1β gene were a genetic risk factor for the development and progression of heart failure. In a number of studies and meta-analyses, the association of this polymorphism with diseases of the cardiovascular system was not confirmed, but certain trajectories of the risk of complications were identified due to differences in the rs1143634 polymorphism of the IL-β gene in heart failure.

Association between interleukin-12B gene polymorphisms and multiple sclerosis in turkish population

Elevated levels of IL-12p40 have been observed in the cerebrospinal fluid and serum of MS patients, and it has been suggested that genetic variants in the IL-12B gene may contribute to MS susceptibility and/or pathogenesis. In this study, we investigated the association between MS and IL-12B gene rs17860508 and rs3212227 polymorphisms in the Turkish population. We identified two polymorphic regions in the IL-12B gene using bioinformatics tools and genotyped 351 MS patients and 221 healthy controls for these variants. Our results showed a significant association between the IL-12B rs17860508 polymorphism and MS, but no significant relationship between rs17860508 genotype distribution and allele frequency and MS age onset or subtypes. Genotype distribution and allele frequency of IL-12B rs3212227 polymorphism did not show any significant association with MS directly. However, AC genotype of IL-12B rs3212227 polymorphism in early-onset multiple sclerosis (EOMS) was a risk factor according to age of onset. Additionally, we observed a higher risk for the relapsing-remitting multiple sclerosis (RRMS) subtype in females. This is the first study to investigate the association between IL-12B polymorphisms and MS in the Turkish population.

Feasibility evaluation of fermented peanut meal to replace soybean meal in the diet of common carp (Cyprinus carpio): Growth performance, serum biochemistry, intestinal health and microflora composition

The effectiveness of soybean meal (SBM) substitution with fermented peanut meal (FPM) were appraised in common carp juveniles. A diet containing 30 % SBM was perceived as the control diet, then 25 %, 50 %, 75 % and 100 % of SBM was replaced by the FPM (FPM0, FPM25, FPM50, FPM75, FPM100 groups). Each group was fed to three replicate groups of common carp (4.83 ± 0.02 g) for 56 days. Results exhibited that FPM50 group attained the significantly higher mass gain rate and specific growth rate than those of the other groups except for FPM25, higher protein efficiency ratio and lower feed conversion rate than those of the FPM75 and FPM100 groups. The FPM50 group significantly increased the contents of serum total protein and albumin and decreased the content of serum urea nitrogen. The activity of hindgut protease was significantly enhanced in the FPM50 group. Significantly higher and lower intestinal villi height was, respectively, observed in the FPM50 and FPM100 group. The FPM50 group significantly enhanced the gene expression and activities of antioxidant enzymes in the intestine, reversely decreased the content of malonaldehyde. Significant increments in the occludin, myosin light chain kinase and claudin3 gene expressions in the FPM50 group improved the increase of intestinal permeability induced by pro-inflammatory factor related genes interleukin 1β, interleukin 6 and tumor necrosis factor α. Staphylococcus and Enterococcus in the intestine abundances were effectively suppressed in the FPM50 group, and Lactococcus became the dominant intestinal bacteria genera. The optimum substitution level was estimated to be 50.93 % and 49.89 % using broken-line regression analyses based on MGR and FCR. Overall, the soybean meal in common carp feed could be substituted up to 50 % by FBM without negative influence on growth, feed utilization and intestinal health.

Selection and evaluation of stable reference genes for quantitative real-time PCR in the head kidney leukocyte of Oreochromis niloticus

To investigate the antibacterial mechanisms of Nile tilapia, it is necessary to understand the responses of immune-related genes in infected lymphocytes. Usually, quantitative real-time polymerase chain reaction (qRT-PCR) is applied to investigate transcriptional profiling. However, few studies have evaluated stable reference genes for qRT-PCR in Nile tilapia head kidney lymphocytes (HKLs). In this research, we assessed the stability of seven common reference genes, which include 18 S ribosomal RNA (18 s rRNA), beta actin (β-actin), beta-2-microglobulin-like (β-MG), elongation factor 1a (EF1A), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Tubulin alpha chain-like (TUBA), and Ubiquitin-conjugating enzyme (UBE)，in both resting state and several responding states of Nile tilapia HKLs. Results showed that β-MG was the optimum reference gene in both resting state and LTA stimulation state, while GAPDH was the optimum for LPS stimulation. However, no single candidate gene could be employed as the universal reference under all situations. Next, the geNorm and RefFinder tools was applied to access the adequacy of the union of two reference genes, and the results suggested that the combination of β-MG and GAPDH was the best candidate. Finally, the expression profiles of three typical immune-related genes interleukin-1β (IL-1β), transcription factor p65(P65), and tumor necrosis factor α (TNFα) under LPS/LTA situations in HKLs were evaluated via multiple reference genes and single reference gene difference analysis. The findings revealed that TUBA and UBE were incapable of working as reference genes, and the union of two reference genes was better than any sole reference gene. The single-cell RNA-Seq (scRNA-Seq) data of Nile tilapia HKLs confirmed the above results. In conclusion, our data suggest that the combination of β-MG and GAPDH may be the best criterion for qRT-PCR calculation in tilapia HKLs.

Prediction of response to sofosbuvir-based therapy using serum interleukin-12 and single nucleotide polymorphism of the interleukin 28B gene as predictive factors in HCV positive genotype-4 patients.

Some hepatitis-C virus patients have resistance to direct-acting-antivirals (DAAs). Genetic polymorphisms have been associated with drug resistance. This study aimed to evaluate the role of interleukin (IL)-28B gene polymorphism and IL-12 levels as predictors for a response to sofosbuvir/ribavirin (SOF/RBV) with (triple-therapy) or without (dual-therapy) Peg-alpha-interferon. 92 hepatitis C virus (HCV)/RNA (+)-patients treated with dual (n = 72) or triple (n = 20) therapy. IL28B genetic polymorphism and IL-12 level assessments. 30.4% of the patients were IL28B C/C genotype, 56.5% C/T-genotype, and 13% T/T-genotype. Mean baseline IL-12 levels were 27.5 ± 3.0 pg/mL. Rapid viral response was achieved in 86/92 patients. All patients achieved end-of-treatment virologic response. The 12- and 24-week sustained virologic responses (SVR) were achieved in 76 patients (82.6%), that is, a relapse was found in 16 patients (17.4%). 8 and 12-weeks after antiviral therapy, IL-12 levels decreased significantly, and became comparable to those of the control-group. That drop in IL-12 levels was similar across the dual- and triple-therapy patients. Finally, logistic regression analysis showed that the increase in baseline aspartate aminotransferase (AST) and T/T genotyping had an independent effect on increasing the probability a SVR failing in both dual- and triple-therapy groups (P = .0007 and P = .02, respectively). Single-nucleotide polymorphism (SNP) in IL-28B and IL-12 levels play roles as predictors in DAAs resistance.

Role of interleukin 1β and interleukin 10 variants on ocular toxoplasmosis in Brazilian individuals.

Ocular toxoplasmosis (OT) is an intraocular inflammation caused by Toxoplasma gondii infection that affects the retina and choroid, giving rise to posterior uveitis. Genetic polymorphisms in cytokine genes may exert influence in the expression of these molecules and play a significant role in inflammatory responses and susceptibility to OT. The aim of this study was to evaluate the role of polymorphisms rs16944 (-511 C>T) of the interleukin (IL) 1β gene and rs1800896 (-1082 G>A) of the IL10 gene on OT in Brazilian individuals with a serologic diagnosis of T. gondii and after conducting fundoscopic exams. Participants with a positive serology were classified into two distinct groups according to the presence (G1; n=110) or absence (G2; n=104) of OT. The control group (G3) consisted of individuals without the infection (n=108). It was observed that the C/C genotype of the IL1β gene polymorphism was a protective factor for OT (p=0.02, OR=0.28, 95% CI 0.08-0.78 for G1 vs. G2; p=0.03; OR=0.29, 95% CI 0.09-0.82 for G1 vs. G3), according to the recessive inheritance model. The -511C.T polymorphisms of the IL1β gene seems to play an important role in the pathogenesis of OT in Brazilian individuals.

Distinct hypoxic molecular mechanisms differentially regulate human vs.mouse Interleukin 1β gene expression in monocytes/macrophages

Abstract Interleukin 1β (IL-1β) is an important cytokine, whose regulation is distinct from that of Tumor Necrosis Factor (TNF). We previously reported that LPS/TLR4 initiates hypoxia in mice, with HIF-1α binding the murine Il1b gene, suggesting that TLR4 directly activates Trained Innate Immune Memory (TIIM). To address whether human monocyte IL1B gene regulation parallels that of mouse, mRNA and chromatin immunoprecipitation (ChIP) kinetics, with small molecule inhibitors under either normoxia or hypoxia, were evaluated. IL1B transcription kinetics in Lipopolysaccharide (LPS)-treated human THP-1 monocytes revealed an Immediate-Early (IE) phase of IL1B gene induction, requiring Spi1/PU.1, NF-κB and C/EBPβ transcription factors (TF), followed by a late-phase of lower-level continuous non-tolerized TIIM expression that depends upon hypoxia-inducible TFs. We observed that Spi1/PU.1 is required for IL1B gene transcription, performing a critical role in inducing the promoter for IE expression via a TAF1-independent mechanism. Late HIF-2α-dependent IL1B expression is due to LPS pseudo-hypoxic stabilization of the labile HIF factor. In contrast to IE activation, late-phase transcription revealed minimal dependence on NF-κB due to human-specific competition for an overlapping NF-κB/HIF enhancer element. Our studies reveal that IL1B in naïve THP-1 human monocytes binds HIF-2α, not HIF-1α, while PMA treatment morphologically polarizes THP-1 macrophages to bind both HIF isoforms at IL1B. Additionally, bioinformatic screening revealed other immunologically important genes regulated by similar mechanisms, providing insight for novel therapeutic targeting of transcription factors other than NF-κB. Interleukin Foundation, Denver Colorado