IL-1β Gene Research Articles

Design of a prognostic model for assessing the risk of developing asbestosis based on the results of molecular genetic studies

Introduction. Preventive measures, including the development of a system for diagnosing early signs of changes in the health status of employees and predicting individual risks of developing the disease, aimed at preserving labor resources, reducing disability and extending working life expectancy, are an absolute priority in the field of occupational safety.
 The aim of the study to develop a prognostic model of the risk of developing asbestosis based on molecular genetic studies in employees of enterprises for the extraction and enrichment of chrysotile asbestos.
 Materials and methods. Based on studies previously conducted in the Laboratory of Biomedical Research at the Izmerov Research Institute of Occupational Health, scientists have identified a set of informative and significant single-nucleotide polymorphic gene variants for use as predictors in the construction of a prognostic model in the development of asbestos in workers of enterprises for the extraction and enrichment of chrysotile asbestos. We examined 136 people who worked at the enterprise for the extraction and enrichment of chrysotile asbestos. The researchers formed two groups comparable in terms of work experience, dustiness, age and gender: 68 former employees of the main production specialties with an established diagnosis of asbestos and 68 workers without bronchopulmonary pathology.
 The authors calculated the exposure dose of chrysotile-containing dust and calculated it taking into account the percentage of time spent at the workplace, and also performed a molecular genetic study of single-nucleotide polymorphic variants of the genes IL-1β rs16944, IL-4 rs2243250, TGF-β1 rs1800471, SOD-2 rs4880 and MMP-9 rs17576.
 Results. A predictive model has been developed to determine the probability of developing asbestosis in workers of an enterprise for the extraction and enrichment of chrysotile asbestos based on the determination of single nucleotide polymorphisms IL-1β rs16944, SOD-2 rs4880 and MMP-9 rs17576. The results of genetic tests are entered into the formula and if the resulting probability of developing asbestosis is equal to or higher than the threshold (0.582), the employee is included in the high-risk group. The sensitivity and specificity of the developed model were 70.1% and 70.6%, respectively.
 Conclusion. Molecular genetic indicators can act as predictors in the development of asbestosis in workers of the chrysotile extraction and enrichment industry and can be used to form high-risk groups during preventive measures.
 Ethics. The study was conducted in compliance with ethical standards that guarantee respect for all research subjects and the protection of their health and rights in accordance with the requirements of the Helsinki Declaration of the World Medical Association. All persons included in the study gave informed voluntary consent to the examination in accordance with Federal Law No. 323-FZ dated 11/21/2011 "On the Basics of Public Health Protection in the Russian Federation". The study was approved by the conclusion of the local Ethics committee of Izmerov Research Institute of Occupational Health (minutes of the meeting of the Ethics committee of Izmerov Research Institute of Occupational Health No. 9 dated 11/29/2016).

Promotion of Colitis in B Cell-Deficient C57BL/6 Mice Infected with Enterotoxigenic Bacteroides fragilis.

Enterotoxigenic Bacteroides fragilis (ETBF) causes colitis and is implicated in inflammatory bowel diseases and colorectal cancer. The ETBF-secreted B. fragilis toxin (BFT) causes cleavage of the adherence junction, the E-cadherin, resulting in the large intestine showing IL-17A inflammation in wild-type (WT) mice. However, intestinal pathology by ETBF infection is not fully understood in B-cell-deficient mice. In this study, ETBF-mediated inflammation was characterized in B-cell-deficient mice (muMT). WT or muMT C57BL/6J mice were orally inoculated with ETBF and examined for intestinal inflammation. The indirect indicators for colitis (loss of body weight and cecum weight, as well as mortality) were increased in muMT mice compared to WT mice. Histopathology and inflammatory genes (Nos2, Il-1β, Tnf-α, and Cxcl1) were elevated and persisted in the large intestine of muMT mice compared with WT mice during chronic ETBF infection. However, intestinal IL-17A expression was comparable between WT and muMT mice during infection. Consistently, flow cytometry analysis applied to the mesenteric lymph nodes showed a similar Th17 immune response in both WT and muMT mice. Despite elevated ETBF colonization, the ETBF-infected muMT mice showed no histopathology or inflammation in the small intestine. In conclusion, B cells play a protective role in ETBF-induced colitis, and IL-17A inflammation is not attributed to prompted colitis in B-cell-deficient mice. Our data support the fact that B cells are required to ameliorate ETBF infection-induced colitis in the host.

Treatment Response to Oral Antivirals in Chronic Hepatitis B Patients: Assessment of Polymorphism in the IL-28B Gene (rs809991)

Treatment Response to Oral Antivirals in Chronic Hepatitis B Patients: Assessment of Polymorphism in the IL-28B Gene (rs809991)

Genetic predictors of abdominal complications after cardiac surgery: a prospective study

Introduction: The prediction of postoperative abdominal complications is a continuing concern in the cardiac surgery. Identifying genetic predictors will allow a better understanding of the pathophysiological mechanisms underlying postoperative disorders and their prevention.Objective: To identify genetic predictors of abdominal complications after heart surgery.Methods: A prospective study was carried out at the Federal Center for Cardiovascular Surgery (Chelyabinsk) involving 72 patients with abdominal complications and 102 controls without such complications. The distribution of genotypes was assessed for adherence to the Hardy-Weinberg distribution using the exact method according to the SNP-HWE algorithm in the PLINK package (version 1.9). To identify marker genes associated with the risk of abdominal complications, 6 models were evaluated for each polymorphic gene: allelic, codominant, dominant, recessive, overdominant, and log-additive. To analyze the SNPs of the IL6 (rs1800795), TNF (rs1800629), and SERPINE1 (rs1799768) genes, real-time polymerase chain reaction (PCR) was performed on a Rotor-Gene 6000 detecting cycler (Corbett Research Pty Ltd., Mortlake, Australia) using primers and probes manufactured by Syntol CJSC (Moscow, Russia) according to the manufacturer's instructions. To analyze the SNPs of the IL1B (rs1143634), CXCL8 (rs4073), IL10 (rs1800872), APOE (rs429358), FABP2 (rs1799883), NOS3 (rs1799983), VEGFA (rs699947) genes, real-time PCR was performed on a DTprime 4 analyzer (DNA-Technology, Moscow, Russia) using primers and probes manufactured by TestGene LLC (Ulyanovsk, Russia) according to the manufacturer's instructions. The determination of the SNP of the TLR3 gene (rs3775291) relied on real-time PCR according to melting curves using TestGene LLC reagent kits on a DTprime 4 device.Results: Two genes, IL1B rs1143634 and FABP2 rs1799883, were found to be associated with the risk of abdominal complications. Following the adjustment for multiple comparisons, only FABP2 rs1799883 remained statistically significant. The rs1799883 polymorphism of the FABP2 gene can be considered a predictor of the risk of abdominal complications and can be evaluated within the codominant and dominant models, which exhibit similar p-values (0.003 and 0.002, respectively). Overall, the analysis of the obtained data suggests that the risk of abdominal complications is associated with the presence of the mutant allele C in the genome, likely due to its dominance. Specifically, in the dominant model, the odds ratio was 3.53 (95% CI 1.62 to 7.70).Conclusion: The most significant markers of the risk of abdominal complications were the IL1B (rs1143634) and FABP2 (rs1799883) genes, of which FABP2 (rs1799883) remained statistically significant after adjusting for multiple comparisons. Its polymorphism as a predictor of abdominal complications can be evaluated within the codominant and dominant models. Received 13 June 2023. Revised 28 November 2023. Accepted 29 November 2023. Funding: The study was supported by the Russian Science Foundation, project No. 22-25-20016, https://rscf.ru/project/22-25-20016/ Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: O.S. Abramovskikh, A.A. Fokin, D.V. BelovData collection and analysis: Yu.V. LoginovaStatistical analysis: M.A. ZotovaDrafting the article: D.V. BelovCritical revision of the article: Yu.V. LoginovaFinal approval of the version to be published: D.V. Belov, O.S. Abramovskikh, M.A. Zotova, Yu.V. Loginova, A.A. Fokin

The Effect of Rehabilitation with Selected Concurrent Training on the Expression of Thrombospondin-1 and Interleukin-1 Beta in Blood Mononuclear Cells in Male Patients After Coronary Artery Bypass Graft Surgery

Introduction and purpose: Coronary artery bypass graft (CABG) is a common therapeutic intervention that is performed in patients suffering from coronary heart diseases. The aim of this study was to determine the effect of selected combined rehabilitation exercises on the expression of thrombospondin-1 (TSP-1) and interleukin-1 beta (IL-1β) genes in patients after coronary artery bypass surgery. Method: In this semi-experimental study, 20 male patients from Afshar Hospital (Yazd city) after coronary artery surgery were purposefully selected and available and randomly divided into two groups of combined exercise and control. Combined exercise program group performed aerobic (15-20 minutes with an intensity of 50-60% of the maximum heart rate) and resistance exercise (10-20 minutes, including three movements of the upper limbs and two movements of the lower limbs, each movement includes three sets and each set with 10 repetitions and 30 to 60 percent of a maximum repetition) for 10 weeks (30 sessions) and three sessions per week. Gene expression was measured by Real Time PCR method.. The data were analyzed using the Paired t-test and One-Way ANOVA at the P<0.05. Results: After the intervention period, a significant decrease in the expression of IL-1β was observed, but no significant difference was observed in the expression of TSP-1. Conclusion: Combined exercises as a non-pharmacological rehabilitation intervention can be useful in patients who have undergone CABG by reducing systemic inflammation.

Diet Supplementation with Prinsepiae Nux Extract in Broiler Chickens: Its Effect on Growth Performance and Expression of Antioxidant, Pro-Inflammatory, and Heat Shock Protein Genes.

Heat stress significantly undermines the poultry industry by escalating rates of morbidity and mortality and impairing growth performance. Our recent findings indicate that Prinsepiae Nux extract (PNE) effectively stimulates the Nrf2 signaling pathway, a vital element in cellular antioxidant stress responses. This study further explores the prospective benefits of supplementing PNE into poultry feed to enhance broiler growth in heat-stressed conditions. An Nrf2-luciferase reporter assay was developed in a chicken fibroblast cell line, demonstrating that PNE induces Nrf2 activity in a concentration-dependent manner. Real-time RT-PCR results showed that PNE intensifies the expression of Nrf2-responsive targets such as Ho1 and Nqo1 in chicken fibroblasts. A total of 160 one-day-old Arbor Acres broiler chicks were randomly assigned into four groups, each receiving a basal diet supplemented with either 0% (control), 0.1% PNE, 1% PNE, or commercial electrolyte for 35 days. Broilers were raised in an environment where the ambient temperature exceeded 30 °C for approximately seven hours each day, fluctuating between 26 and 34 °C, which is known to induce mild heat stress. The findings reveal that a 1% PNE supplement led to a significant decrease in the feed conversion ratio (FCR) compared to the control group. Moreover, chickens supplemented with 1% PNE exhibited a substantial increase in hepatic mRNA expression of antioxidant genes, such as Nqo1, Gclc, Sod2, Cat, and heat shock protein-related genes including Hsp90 and Hsf1, and a decrease in pro-inflammatory cytokine genes Il-6 and Il-1β. Consequently, PNE holds potential as a feed supplement to strengthen the antioxidant defenses of broilers and build heat stress resilience in the poultry industry.

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.

THE STUDY OF ASSOCIATIONS BETWEEN IL1Β C3953T GENE POLYMORPHISM AND CLINICAL-NEUROLOGICAL, NEUROIMAGING, HEMODYNAMIC CHARACTERISTICS AND COGNITIVE DYSFUNCTION IN PATIENTS WITH POST-INFECTIOUS ENCEPHALOPATHY

The aim: To investigate potential associations between the C3953T polymorphic variant of the interleukin-one beta (IL1β) gene and clinical-neurological, neuroimaging, hemodynamic characteristics, as well as cognitive dysfunction in patients with post-infectious encephalopathy (PIE).
 Materials and methods: A total of 128 patients with post-infectious encephalopathy (PIE) who were receiving inpatient treatment in the neurological departments of the Communal Non-commercial Enterprise “Ternopil Regional Clinical Psychoneurological Hospital” of Ternopil Regional Council,” Ternopil, Ukraine, were examined and included in the retrospective analysis in 2021–2022. The molecular-genetic testing was performed for 26 patients in the molecular genetics laboratory of the State Institution “Reference Centre for Molecular Diagnostics of the Ministry of Health of Ukraine,” Kyiv. The control group consisted of 12 people, who were representative in age and gender. Statistical processing of the results was performed using the STATISTICA 10.0 software.
 Results: Analysis of the dependence of neuroimaging changes on the frequency of genotypes of the C3953T polymorphic variant of the IL1β gene in patients with PIE showed a significant relationship between their frequency distribution and the presence/absence of gliosis phenomena (p=0.009). Thus, gliosis was detected in all carriers of the T/T genotype C3953T polymorphic variant of the IL1β gene. Analyzing the dependence of changes obtained during the transcranial Doppler ultrasound scanning of cerebral vessels on the polymorphic variant C3953T of the IL1β gene in patients with PIE, all carriers of the T/T genotype were diagnosed with angiospasm (p=0.038) and vertebrobasilar insufficiency (p=0.010).
 Conclusions: Results suggest the reasonability of further researching the interaction between IL1β and glial cells and changes in the cognitive functioning of cytokine genotypes with larger sample sizes that may help explain the pathophysiological mechanisms leading to cognitive impairment in patients with PIE.

Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification

BackgroundInnate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PurposeThis study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). Study designAfter co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. MethodsWe observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. ResultsACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1β, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. ConclusionThis study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

Promoter polymorphisms of neuropeptide Y, interleukin-1B and increased IL-1β levels are associated with rheumatoid arthritis susceptibility in South Gujarat population

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction. Interleukin-1B(IL-1β) has been implicated in RA, and neuropeptide Y (NPY) induces the release of pro-inflammatory cytokines including IL1-β, TNF-α and IL-6. Single nucleotide polymorphisms (SNPs) in NPY and IL1B gene may lead to their altered levels leading to RA pathogenesis. Therefore, we aimed to investigate association of NPY rs16147(T > C) SNP, and genotype–phenotype correlation of the IL1B rs16944(C > T) SNP in 302 RA patients and 337 controls by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Both the genotype and allele frequencies for NPY rs16147(T > C)(p = 0.0019 &p = 0.012) and IL1B rs16944(C > T)(p = 0.0024 &p = 0.0014) SNPs differed significantly between RA patients and controls. The odds ratios of 1.23 and 1.47 for NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs respectively, suggest that these SNPs may be genetic risk factor for RA in South Gujarat population. The plasma IL-1β levels(p = 0.0332) and genotype-phenotype correlation of IL1B rs16944(C > T) SNP suggested increased IL-1β levels, particularly in patients with susceptible ‘TT' genotypes(p < 0.0001). Additionally, plasma IL-1β level was significantly increased in severe RA patients (p = 0.0025) and positively correlated with Rheumatoid factor(RF) (r = 0.9240, p < 0.0001), suggesting the role of IL-1β in disease severity. Overall, the study for the first time suggests that NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs may be associated with RA susceptibility in South Gujarat population. Additionally, the IL1B rs16944 susceptible ‘TT' genotype may lead to increased IL-1β levels, thereby contributing to RA pathogenesis and severity.

Pulsed electromagnetic field stimulation enhances neurite outgrowth in neural cells and modulates inflammation in macrophages

Nerve regeneration following traumas remains an unmet challenge. The application of pulsed electromagnetic field (PEMF) stimulation has gained traction for a minimally invasive regeneration of nerves. However, a systematic exploration of different PEMF parameters influencing neuron function at a cellular level is not available. In this study, we exposed neuroblastoma F11 cells to PEMF to trigger beneficial effects on neurite outgrowth. Different carrier frequencies, pulse repetition frequencies, and duty cycles were screened with a custom ad hoc setup to find the most influential parameters values. A carrier frequency of 13.5 MHz, a pulse repetition frequency of 20 Hz, and a duty cycle of 10% allowed maximal neurite outgrowth, with unaltered viability with respect to non-stimulated controls. Furthermore, in a longer-term analysis, such optimal conditions were also able to increase the gene expression of neuronal expression markers NeuN and Tuj-1 and transcription factor Ngn1. Finally, the same optimal stimulation conditions were also applied to THP-1 macrophages, and both pro-inflammatory (TNF-α, IL-1β, IL-6, IL-8) and anti-inflammatory cytokines (IL-10, CD206) were analyzed. The optimal PEMF stimulation parameters did not induce differentiation towards an M1 macrophage phenotype, decreased IL-1β and IL-8 gene expression, decreased TNF-α and IL-8 cytokine release in M1-differentiated cells, increased IL-10 and CD206 gene expression, as well as IL-10 cytokine release in M0 cells. The specific PEMF stimulation regime, which is optimal in vitro, might have a high potential for a future in vivo translation targeting neural regeneration and anti-inflammatory action for treating peripheral nerve injuries.

The Effect of Secretome Hypoxia Mesenchymal Stem Cells on PDGF and IL-1b Gene Expression (Experimental Study on Wistar Rats Hyperglycemic Wound Models)

Hyperglycemic wounds take longer to heal, and high glucose results in an increase in inflammatory cells, a decrease in the angiogenesis process, and the production of growth factors. Antibiotic treatment, surgery, or debridement can increase the risk of amputation. This study aimed to determine the effect of administering gel secretome hypoxia mesenchymal stem cells (SH-MSCs) on the expression of PDGF and IL-1b in Wistar rats with a hyperglycemic wound model. In vivo laboratory experimental research with a Post Test Only Control Group Design. The samples consisted of 30 Wistar rats, divided into 5 groups, namely healthy rats (P1), negative control (P2), positive control with gentamicin (P3), gel secretome dose of 20 μL/rat (P4), and gel secretome dose of 40 μL/rat (P5). MSC secretome hypoxia gel treatment for 10 days, then skin tissue samples were examined using the RTq-PCR method to analyze PDGF and IL-1b gene expression. Analysis of PDGF gene expression showed significant differences between treatment groups using the Kruskal-Wallis test with a result of 0.018 (p&lt;0.05), but there were no significant differences between groups using the Mann-Whitney test (p&lt;0.05). Analysis of IL-1b gene expression showed significant differences between treatment groups using the Kruskal Wallis test with a result of 0.001 (p&lt;0.05), various doses of secretome gel affected reducing IL-1b gene expression using the Mann Whitney test with a result of 0.004 (p&lt;0, 05). The most significant decrease was at a secretome dose of 40 μL/mouse. MSC secretome hypoxia gel at a dose of 40 μL/rat effectively reduces IL-1b gene expression in Wistar rats with a hyperglycemic wound model. However, various doses of MSC secretome hypoxia gel do not significantly increase PDGF gene expression.

Impact of IL-6 and IL-1β Gene Variants on Non-small-cell Lung Cancer Risk in Egyptian Patients

Lung cancer is a serious health and life issue, with the fastest-growing incidence and fatality rates worldwide. It is now clear that inflammation is a key factor involved in all aspects of carcinogenesis, notably lung cancer development. Genetic changes, including polymorphisms in inflammatory genes, are supposed to be a significant cause of increased lung cancer risk. The main idea of this research was to disclose the linkage between both IL-6 rs1800795 and IL-1β rs16944 variants and susceptibility to non-small-cell lung cancer (NSCLC) in Egyptians. This case–control design was composed of 127 cases and 138 controls, which were genotyped using the ARMS-PCR technique. To examine the NSCLC susceptibility under various genetic models, the odds ratio (OR) and 95% confidence intervals (CIs) were determined by logistic regression. Rs1800795 of the IL-6 gene was linked to higher odds of NSCLC under the allele model (adjusted, OR 2.28; 95% CI 1.2–4.33; p = 0.011). In the genetic models, IL-6 rs1800795 elevated the odds of NSCLC, while IL-1β rs16944 decreased the odds of NSCLC. Stratification analysis showed that IL-6 rs1800795 greatly increased the NSCLC risk in females and adenocarcinoma subtypes, whereas IL-1β rs16944 largely decreased the NSCLC risk for males, patients aged < 55, and nonsmokers. Regarding clinical data, the IL-6 variant was remarkably correlated with tumor size. This work primarily established that IL-6 and IL-1β variants have a great impact on NSCLC development in the Egyptian population; thus, it may be a supportive guide for earlier NSCLC prevention.

Immersion prime and oral boost vaccination with an inactivated Vibrio harveyi vaccine confers a specific immune response and protection in Asian seabass (Lates calcarifer)

Asian seabass (Lates calcarifer) holds significant economic value in fish farming in the Asia-Pacific region. Vibriosis caused by Vibrio harveyi (Vh) is a severe infectious disease affecting intensive farming of this species, for which prevention strategies by vaccination have been developed. This study investigated an alternative approach to injectable vaccination to prevent vibriosis in Asian seabass juveniles. The strategy begins with an immersion prime vaccination with a heat-inactivated Vh vaccine, followed by two oral booster doses administered at 14- and 28-days post-vaccination (dpv). Expression of five immune genes TNFα, IL1β, CD4, CD8, and IgM in the head kidney and spleen, along with investigation of anti-Vh antibody response (IgM) in both systemic and mucosal systems, was conducted on a weekly basis. The efficacy of the vaccines was assessed by a laboratory challenge test at 43 dpv. The results showed that the immunized fish displayed higher levels of mRNA transcripts of the immune genes after the immersion prime and the first oral booster dose compared to the control group. The expression levels peaked at 14 and 28 dpv and then declined to baseline at 35 and 42 dpv. Serum specific IgM antibodies were detected as early as 7 dpv (the first time point investigated) and exhibited a steady increase, reaching the first peak at 21 dpv, and a second peak at 35 dpv. Although the antibody levels gradually declined over subsequent weeks, they remained significantly higher than the control group throughout the experiment. A similar antibody response pattern was also observed in the mucosal compartment. The laboratory challenge test demonstrated high protection by injection with 1.65 × 104 CFU/fish, with a relative percent of survival (RPS) of 72.22 ± 7.86 %. In conclusion, our findings highlight the potential of an immersion prime-oral booster vaccination strategy as a promising approach for preventing vibriosis in Asian seabass.

Ferulic acid via attenuation of oxidative stress and neuro-immune response utilizes antinociceptive effect in mouse model of formalin test

IntroductionPlenty evidences suggests that neuroinflammation and oxidative stress augmented the neural sensitivity specifying that neuro-immune response is involved in the pathophysiology of pain. Ferulic acid (FA), a natural antioxidant found in various fruits, has various pharmacological properties. The purpose of the current study was to assess the antinociceptive effect of FA in a mouse model of formalin test with focus on its anti-neuroinflammatory and antioxidative stress effects. MethodsThe injection of FA (40 mg/kg), piroxicam (2 mg/kg), and saline (0.9% NaCl) (1 ml/kg) was done intraperitoneally and after one hour, formalin injected into the plantar surface of the hind paw of mice. Then pain behavior was documented during 60 min. Then mice were euthanized and prefrontal cortex (PFC) samples were taken. Malondialdehyde (MDA) level, antioxidant capacity and expression of inflammatory genes, counting tumor necrosis factor (TNF-) and interleukine 1 (IL-1) evaluated in the PFC. Resultsexhibited that FA declined the pain behavior following injection of formalin. Besides, FA significantly diminished the MDA level and increased the antioxidant capacity in the PFC. We revealed that FA diminished the expression of TNF-α and IL-1β genes in the PFC. ConclusionWe conclude that FA exerted antinociceptive effects in the formalin test in mice, at least partially, by reducing oxidative stress and neuroimmune response in the PFC.

The effects of Leishmania RNA virus 2 (LRV2) on the virulence factors of L. major and pro-inflammatory biomarkers: an in vitro study on human monocyte cell line (THP-1)

BackgroundCutaneous Leishmaniasis (CL) is a parasitic disease with diverse outcomes. Clinical diversity is influenced by various factors such as Leishmania species and host genetic background. The role of Leishmania RNA virus (LRV), as an endosymbiont, is suggested to not only affect the pathogenesis of Leishmania, but also impact host immune responses. This study aimed to investigate the influence of LRV2 on the expression of a number of virulence factors (VFs) of Leishmania and pro-inflammatory biomarkers.Materials and methodsSample were obtained from CL patients from Golestan province. Leishmania species were identified by PCR (LIN 4, 17), and the presence of LRV2 was checked using the semi-nested PCR (RdRp gene). Human monocyte cell line (THP-1) was treated with three isolates of L. major with LRV2 and one isolate of L. major without LRV2. The treatments with four isolates were administered for the time points: zero, 12, 24, 36, and 48 h after co-infection. The expression levels of Leishmania VFs genes including GP63, HSP83, and MPI, as well as pro-inflammatory biomarkers genes including NLRP3, IL18, and IL1β, were measured using quantitative real-time PCR.ResultsThe expression of GP63, HSP83, and MPI revealed up-regulation in LRV2 + isolates compared to LRV2- isolates. The expression of the pro-inflammatory biomarkers including NLRP3, IL1β, and IL18 genes in LRV2- were higher than LRV2 + isolates.ConclusionThis finding suggests that LRV2 + may have a probable effect on the Leishmania VFs and pro-inflammatory biomarkers in the human macrophage model.

Effects of dietary baobab, Adansonia digitata on growth, haemato-immunological status, antioxidant biomarkers, intestinal histomorphometry, gene expression responses, and disease resistance in Nile tilapia, Oreochromis niloticus

This study explored the influences of baobab fruit extract powder (BP) on growth, oxidant-antioxidant balance, immunity, intestinal histology, expression of growth and immune genes, and disease resistance in Nile tilapia. Fish were fed on five test diets supplied with different BP levels as BP0 (control; 0 g kg−1), BP1 (1 g kg−1), BP2 (2 g kg−1), BP3 (3 g kg−1), and BP4 (4 g kg−1) for two months. Results revealed that dietary BP improved the growth in all BP groups compared with the BP0 group, with the best values apparent in the BP4 group. However, dietary BP did not affect the whole-body chemical composition and survival rates in all groups. Serum immunity biomarkers (lysozyme, myeloperoxidase, and bactericidal activities) were enhanced in all BP groups compared to the BP0 group. Hepatic antioxidant status significantly improved, as manifested by increases in the hepatic CAT, SOD, and T-AOC and decreases in MDA concentrations in BP groups compared to the controls. Of interest, dietary BP supplementation significantly increased the expression of growth-related genes (ghr1, ghr2, igf-1, and igf-2) in the liver and immunity-associated genes (inf-γ1, lyz, il-1β, il-10, and hepcidin) in the spleen of BP-treated fish in comparison with the controls. The intestinal histological sections revealed no significant variations among all groups with normal histoarchitecture and goblet cells. After experimental infection with Aeromonas hydrophila, the survival rates (%) in the BP0, BP1, BP2, BP3, and BP4 groups were 23.33, 43.33, 56.67, 63.33, and 70.00, respectively, suggesting the positive roles of BP in increasing the fish disease resistance. To conclude, dietary BP could improve growth (particularly in the BP4), serum immunity, antioxidant capacity, and transcription of growth and immune genes in O. niloticus. In addition, the highest disease resistance was also found in the BP4 group. All in all, BP at a dose rate (4 g kg−1 diet) could be regarded as a functional feed supplement for tilapia farming.

Fucoxanthin Abrogates Ionizing Radiation-Induced Inflammatory Responses by Modulating Sirtuin 1 in Macrophages.

Ionizing radiation (IR) triggers an overproduction of reactive oxygen species (ROS), disrupting the normal function of both immune and metabolic systems, leading to inflammation and metabolic disturbances. To address the pressing requirement for protection against IR, fucoxanthin (FX), a naturally occurring compound extracted from algae, was utilized as an efficient radioprotective agent in macrophages. In this study, we cultured murine RAW 264.7 macrophages and treated them with FX, along with agents influencing the activity of sirtuin 1 (SIRT1) and estrogen receptor α (ERα), to investigate their impact on IR-induced cellular responses. FX significantly attenuated IR-induced upregulation of pro-inflammatory genes (Il1b, Tnf, and Ccl2) and inhibited macrophage polarization toward the pro-inflammatory M1 phenotype. Additionally, FX regulated IR-induced metabolic genes mediating glycolysis and mitochondrial biogenesis. The ability of FX to mitigate IR-induced inflammation and glycolysis was ascribed to the expression and activity of SIRT1 and ERα in macrophages. This study not only uncovers the underlying mechanisms of FX's radioprotective properties but also highlights its potential as a protective agent against the detrimental effects of IR, thus offering new opportunities for enhancing radiation protection in the future.

Influence of polymorphisms in TNF-α and IL1β on susceptibility to alcohol induced liver diseases and therapeutic potential of miR-124-3p impeding TNF-α/IL1β mediated multi-cellular signaling in liver microenvironment.

Alcoholic liver disease (ALD) is the leading cause of the liver cirrhosis related death worldwide. Excessive alcohol consumption resulting enhanced gut permeability which trigger sensitization of inflammatory cells to bacterial endotoxins and induces secretion of cytokines, chemokines leading to activation of stellate cells, neutrophil infiltration and hepatocyte injury followed by steatohepatitis, fibrosis and cirrhosis. But all chronic alcoholics are not susceptible to ALD. This study investigated the causes of differential immune responses among ALD patients and alcoholic controls (ALC) to identify genetic risk factors and assessed the therapeutic potential of a microRNA, miR-124-3p. Bio-Plex Pro™ Human Chemokine analysis/qRT-PCR array was used for identification of deregulated immune genes. Sequencing/luciferase assay/ELISA detected and confirmed the polymorphisms. THP1 co-cultured with HepG2/LX2/HUVEC and apoptosis assay/qRT-PCR/neutrophil migration assay were employed as required. The combined data analysis of the GSE143318/Bio-Plex Pro™ Human Chemokine array and qRT-PCR array revealed that six genes (TNFα/IL1β/IL8/MCP1/IL6/TGFβ) were commonly overexpressed in both serum/liver tissue of ALD-patients compared to ALC. The promoter sequence analysis of these 6 genes among ALD (n=322)/ALC (n=168) samples revealed that only two SNPs, rs361525(G/A) at -238 in TNF-α/rs1143627(C/T) at -31 in IL1β were independently associated with ALD respectively. To evaluate the functional implication of these SNPs on ALD development, the serum level of TNF-α/IL1β was verified and observed significantly higher in ALD patients with risk genotypes TNF-α-238GA/IL1β-31CT+TT than TNF-α-238GG/IL1β-31CC. The TNF-α/IL1β promoter Luciferase-reporter assays showed significantly elevated level of luciferase activities with risk genotypes -238AA/-31TT than -238GG/-31CC respectively. Furthermore, treatment of conditioned medium of TNF-α/IL1β over-expressed THP1 cells to HepG2/LX2/HUVEC cells independently showed enhanced level of ER stress and apoptosis in HepG2/increased TGFβ and collagen-I production by LX2/huge neutrophil infiltration through endothelial layer. However, restoration of miR-124-3p in THP1 attenuated such inter-cellular communications and hepatocyte damage/collagen production/neutrophil infiltration were prohibited. Target analysis/luciferase-reporter assays revealed that both TNF-α/IL1β were inhibited by miR-124-3p along with multiple genes from TLR4 signaling/apoptosis/fibrogenesis pathways including MYD88, TRAF3/TRADD, Caspase8/PDGFRA, TGFβR2/MCP1, and ICAM1 respectively. Thus, rs361525(G/A) in TNF-α and rs1143627(C/T) in IL1β gene may be used as early predictors of ALD susceptibility among East Indian population. Impeding overexpressed TNF-α/IL1β and various genes from associated immune response pathways, miR-124-3p exhibits robust therapeutic potential for ALD patients.

Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.